Conditions and shelf life of fresh frozen plasma. Features of FFP transfusion Plasma transfusion


British Committee for Standards in Haematology, Blood Transfusion Task Force (J. Duguid, Chairman): D. F. O'Shaughnessy (Convenor, Task Force nominee),1,* C. Atterbury (RCN nominee),2 P. Bolton Maggs (RCPCH nominee ),3 M. Murphy (Task Force nominee),4 D. Thomas (RCA nominee),5 S. Yates (representing Biomedical Scientists)6 and L. M. Williamson (Task Force nominee)7

1Southampton University Hospitals, Southampton, 2Queen Elizabeth Hospital, Kings Lynn, 3Central Manchester and Manchester Children’s University Hospitals, Manchester, 4NBS Oxford, Oxford, 5Morriston Hospital, Swansea, 6Blood Transfusion Laboratories, Southampton University Hospitals, Southampton, and 7NBS Cambridge, Cambridge, UK

  Indications for transfusion of fresh frozen plasma (FFP), cryoprecipitate and cryosupernatant plasma are very limited. They may cause unpredictable adverse effects. The risk of transmission of infection is approximately the same as with transfusion of other blood components unless pathogen-reduced plasma (PRP) is used. Specific adverse reactions include allergic reactions and anaphylaxis, transfusion-related acute lung injury, and hemolysis due to the administration of antibodies to blood group antigens, especially A and B. FFP is not indicated for disseminated intravascular coagulation without bleeding and is recommended as a plasma exchange medium only in thrombotic thrombocytopenic purpura (cryosupernatant is a possible alternative in this case), should never be used to treat warfarin overdose in the absence of serious bleeding, and is only of very limited value as prophylaxis before liver biopsy. The use of FFP and cryoprecipitate for surgical or traumatic bleeding should be based on data from coagulation studies, which may include bedside tests. FFP is not indicated for the treatment of vitamin K deficiency in neonates or patients in intensive care units. PRP can be used as an alternative to FFP. In the UK, PRP from countries where BSE is rare is recommended by the Department of Health for transfusion in children born after 1 January 1996. A commercial preparation of PRP from US donors (Octaplas) is licensed and available in the UK. FFP should be thawed using a technique that does not pose the risk of bacterial contamination. Plastic bags containing any of the plasma products are frozen and must be handled with care.

Key words: fresh frozen plasma, clinical use, guideline.

Clinical indications for the use of fresh frozen plasma (FFP), cryoprecipitate and cryosupernatant (see Section 10),

Single coagulation factor deficiency (Section 10.1)

  Fresh frozen plasma should be used to compensate for hereditary clotting factor deficiencies only in cases where a fractionated virus-safe product is not available. Currently this mainly refers to factor (F)V.

Multiple clotting factor deficiencies (Section 10.2); disseminated intravascular coagulation (DIC) (Sections 10.3 and 10.4)

  Fresh frozen plasma and platelets are indicated when there is a confirmed multifactorial coagulation deficiency associated with severe bleeding and/or disseminated intravascular coagulation.
  Cryoprecipitate may be indicated if plasma fibrinogen levels are less than 1 g/L, although there is no established threshold for clinically significant hypofibrinogenemia. Fresh frozen plasma is not indicated for DIC without signs of bleeding. There is no evidence that a prophylactic replacement regimen prevents DIC or reduces the need for further transfusion.

Thrombotic thrombocytopenic purpura (TTP) (Section 10.5)

  Daily replacement of one volume of plasma should be started at the onset of signs (grade of recommendation A, level of evidence Ib), and ideally within 24 hours (grade of recommendation C, level of evidence IV). Daily plasma replacement should continue for at least 2 days after remission is achieved (grade of recommendation C, level of evidence IV).

Reversing the effects of warfarin (Section 10.6)

  Excessive anticoagulation caused by warfarin should be managed according to the British Committee for Standards in Hematology guidelines (BCSH, 1998). FFP is only partially effective and is not an optimal treatment and should never be used to reverse excessive anticoagulation caused by warfarin in the absence of severe bleeding (grade of recommendation B, level of evidence IIa).

Vitamin K deficiency in the intensive care unit (ICU) (Section 10.7)

  Fresh frozen plasma should not be used to correct elevated clotting times in ICU patients; it should be corrected with vitamin K (grade of recommendation B, level of evidence IIa).

Liver diseases (Section 10.8)

  There are supporters of prescribing fresh frozen plasma to prevent bleeding in patients with liver disease and a long prothrombin time (PTT), although the response may be unpredictable and complete normalization of the hemostatic defect does not always occur.
  If FFP is prescribed, coagulation tests should be repeated after infusion to guide further decisions.
There is no evidence to support the practice, in many tertiary units, of performing liver biopsy only if the PTT is within 4 s of control (grade of recommendation C, level of evidence IV).

Surgical bleeding and massive transfusion (Section 10.9)

  Whether and how much FFP to prescribe for massive blood loss should be based on data from temporary coagulation tests, including bedside tests. FFP should never be used for volume replacement in adults or children (grade of recommendation B, level of evidence IIb).

Use of FFP in pediatrics (Section 11.0) (see BCSH, 2004)

  Children born after January 1, 1996 should receive only pathogen-reduced FFP (PRFFP) (see Section 3).
  In case of bleeding associated with hemorrhagic disease of the newborn (HDN), administration of FFP 10-20 ml/kg is indicated, as well as intravenous administration of vitamin K. Prothrombin complex concentrate (PCC) could also fill the deficiency in this case, but in this case situation there are no data to indicate dosage (grade of recommendation, level of evidence IV).
  Neonates with coagulopathy who have bleeding or who require invasive procedures should receive FFP and vitamin K (grade of recommendation C, level of evidence IV). Normalization of increased clotting time is difficult to predict and should be monitored after drug administration.
Routine administration of FFP to prevent periventricular hemorrhage (PVH) in preterm infants is not indicated (grade of recommendation A, level of evidence IIb).
  Fresh frozen plasma is not indicated for polycythemia in children. There are no definitive data to support clinical decisions regarding the use of FFP with low anti-T activity in neonates with T activation.

Selection of SWP

  Fresh frozen plasma is made from portions of whole blood (reconstituted FFP) and by plasmapheresis. Both methods are equivalent in terms of therapeutic effect on hemostasis and side effects (grade of recommendation A, level of evidence I).
  The risk of transmission of infection is quite low (see Section 9.5); The clinical benefit expected from the use of FFP must be weighed against the potential for complications and possible transmission of infection (grade of recommendation B, level of evidence II/III).
  Patients who are likely to be transfused with significant amounts of FFP should consider vaccination against hepatitis A and B (grade of recommendation C, level of evidence IV). In addition, in patients likely to be prescribed larger volumes or repeated prescriptions of FFP, it may be appropriate to prescribe products with a reduced risk of transmission, such as pathogen-reduced plasma (PRP). These patients include those with congenital clotting factor deficiencies when no pathogen-reduced concentrates are available and patients undergoing extensive plasma turnover, such as in TTP (grade of recommendation C, level of evidence IV).
  There are two types of PRP available – methylene blue and light treated FFP (MBFFP) and solvent detergent treated FFP (SDFFP). Each type has certain potential disadvantages that may influence clinical decisions regarding their use (see Section 3). In addition, transmission of hepatitis A virus (HAV) or parvovirus B19 is possible even through PRP.
  Blood group status (see Table I). Patients with group 0 can only be transfused with FFP of group 0. The first choice for transfusion in patients in groups A, B, or AB should be FFP of the same group AB0. If this is not possible, transfusion of FFP from other groups is possible if it does not have a high titer of anti-A or anti-B antibodies (grade of recommendation B, level of evidence III).
  Non-Group 0 infants or newborns are more likely to develop hemolysis when transfused with Group 0 FFP due to the relatively large volumes transfused (grade of recommendation B, level of evidence III).

Table I. Principles for selecting fresh frozen plasma according to the blood type of the donor and recipient (AB0).

Recipient group 0 A B AB
    (a) positive test for high titer (HT) or portions not tested for HT*    
1st choice 0 A B AB
2nd choice A AB AB A**
3rd choice B B A** B**
4th choice AB - - -
    (b) VT negative portions***
1st choice 0 A B AB
2nd choice A B A A
3rd choice B AB AB B
4th choice AB - - -

*Group 0 plasma should only be received by group 0 recipients. Group AB plasma does not contain hemolysins, but is often in limited supply.
**For emergency use in adults only.
***Group 0 plasma should only be received by group 0 recipients.

Use of FFP, cryoprecipitate and cryosupernatant

  The thawing procedure for any of these products must be adjusted in such a way as to avoid bacterial contamination.
  After thawing, in which case the patient does not require replacement of factor FVIII, FFP and cryosupernatant can be stored at a temperature of 4 ° C in a special refrigerator for storing blood before administration to the patient for up to 24 hours (grade of recommendation B, level of evidence III).

The purpose of this guideline

  The purpose of this guideline is to help clinicians make decisions about FFP transfusion. Many of the commonly accepted and frequently taught indications for FFP transfusion are not supported by compelling evidence of clinical benefit. The surest way to avoid risk to patients associated with FFP transfusion is to avoid inappropriate use or unproven clinical indications (Cohen, 1993). This guideline is aimed at all clinical staff involved in the management of emergency patients, including clinical haematologists, pediatricians, surgeons, anaesthesiologists, transfusion physicians, researchers and nurses.

Methods

  This guide is based on a MedLine literature search using relevant keywords (including: plasma, plasma + randomized, plasma + trial, plasma + therapy, plasma + liver, plasma + cardiac surgery, plasma + surgical bleeding, plasma + thawing, and plasma + storage). All these searches were repeated with the word plasma replaced by cryoprecipitate or cryosupernatant. A systematic review project (Stanworth et al, 2004) was also consulted. This guideline has been reviewed, among others, by the College of American Pathologists (1994) and reprinted several times by the BCSH (1988, 1990a, b, 1992, 1994, 1998, 1999, 2003, 2004). The gradation of evidence and levels of recommendation occurred using the criteria of the American Agency for Health Care Policy and Research (see Appendix A).

1. Introduction

1.1. Historical and current use of NWS

  Fresh frozen plasma has been available since 1941 and was initially often used as volume replacement. With the advent of albumin and hydroxyethyl starch, and a better understanding that FFP is not indicated for volume replacement, it is now commonly used in cases of ongoing bleeding or bleeding prophylaxis in patients with coagulopathy who require aggressive procedures. Its use has been expanded to patients with coagulopathy without bleeding (eg, in the ICU).
  The use of FFP in hospital practices has increased by more than 20% over the past few years, and by 5-9% in the past year alone. The question has been raised about the appropriateness of its clinical use. The UK Transfusion Service issued 365,547 units of FFP and 94,114 units of cryoprecipitate in 1999–2000; 374,760 units of FFP and 95,456 units of cryoprecipitate for 2000–2001; and 385,236 units of FFP and 88,253 units of cryoprecipitate for 2001–2002 [Serious Hazards of Transfusion (SHOT), 2001, 2002, 2003]. According to the UK census in 2001 the total population was 58,789,194.
  Previous indications for the use of FFP were published by the BCSH in 1992. Three audits in London and Oxford between 1993 and 2000 showed that 34% of transfusions were for indications not specified in the guideline (Eagleton et al, 2000). A similar unpublished audit, with comparable results, was carried out in the Wessex Region in 1998, and Stainsby and Burrowes-King (2001) described the first phase of the national audit in England as disappointing regarding the policy and strategy for the use of plasma components. Despite restrictive policies for the production of FFP in blood and plasma banks, inappropriate use (19% in Oxford, and 15% in Southampton in 2000) is a concern (O'Shaughnessy, 2000).

1.2. Issues with variant Creutzfeldt-Jakob disease (vCJD) and the use of non-UK plasma (see vCJD position in the UK Transfusion Service document library; http://www.transfusionguidelines.org.uk)

  In 1996, the first cases of vCJD, a new and rapidly progressive spongiform encephalopathy, were described (Will et al, 1996). At that time, the disease was only reported in the UK and followed an epidemic of bovine spongiform encephalopathy (BSE), which affected 200,000 cattle and led to the slaughter of 750,000 animals. By December 1, 2003, 143 cases of definite or probable vCJD had been reported. It is incurable and fatal within a few months of the onset of symptoms, although of interest are two cases in which patients were treated with pentosan polysulfate (Dyer, 2003). The vCJD prion shows affinity for lymphatic tissue and is found in the tonsillar tissue of infected individuals and in the appendix of asymptomatic patients several months before the apparent onset of disease (Hilton et al., 2002). Animal experiments have shown the possibility of transmission of the prion infectious agent through plasma and the clear layer of the blood clot as well as through whole blood (Houston et al., 2000; Hunter et al., 2002). This evidence, along with others, showed that it was likely that prion transfer from the periphery to the brain was due to B lymphocytes, leading to the widespread introduction of leukocyte blood purification in the UK, completed by November 1999 (Det Norske Veritas, 1999; Murphy, 1999) .
  Subsequent analysis of the distribution of normal cellular prion (PrPc) showed that plasma is the main source (68%) and only 26% is present on platelets, with trace amounts on erythrocytes and leukocytes (MacGregor et al, 1999). Since the mechanism of infection appears to involve alteration of normal cellular PrPc into PrPsc, and since excluding British donors from the production process of all blood products was neither feasible nor acceptable, it seemed prudent not to use British plasma for the fractionation process, in the meantime, using UK donors to provide cell products and individual portions of FFP (Turner & Ironside, 1998). For the same reasons, plasma has been mainly imported into the UK from the USA and Germany since 1998.
  The risk of transmission of vCJD through blood or blood products could be significant. Fifteen people who later developed vCJD may have donated blood in the UK. In December 2003, the UK Department of Health reported the first case of possible transmission of vCJD through transfusion (Pincock, 2004). In 2002, the UK Department of Health issued a recommendation that FFP for neonates and children born after 1 January 1996 should be obtained from areas where BSE and vCJD are of low endemicity. The risk of infection through transfusion may be even higher than through consumption of contaminated meat. Some donors, while in the incubation period, may not show any signs of vCJD for some time. This situation will remain until there is more accurate data showing the extent of the vCJD epidemic among UK adults.
  Although the source of material for FFP production is obtained from donors living in areas where BSE and vCJD have low endemicity, there is a risk of transmission of other infections (for example, if the prevalence of vector-borne diseases caused by known organisms is relatively high). However, most of these pathogens can be effectively inactivated in plasma during pathogen reduction procedures. Although these procedures do not inactivate prions, when applied to imported plasma, the overall risk of transmission of infection (including vCJD) through these products will be reduced. There are currently two licensed procedures for inactivating pathogens in FFP; MBFFP (currently used in UKBTS), and SDFFP (commercially available – 'Octaplas'). Since the Methylene Blue + Light process was developed at UKBTS, limited supplies of UK origin FFP processed by this process are already available. UKBTS plans to soon manufacture MBFFP from male donors in the United States. Since 1998, Octaplas has been manufactured for use in the UK by Octapharma from donors in the United States.
  It is possible that PRFFP obtained from non-UK donors who have not previously been transfused should be used wherever possible (see Sections 1.3 and 9.2 regarding selection of non-transfused male donors). There are obvious difficulties in establishing a patient's year of birth after which only microbiologically safe available FFP can be used, especially if many patients (eg adults) are excluded. Although extending the use of non-UK donor PRP to all recipients merits careful consideration, the main limitation at present is the cost of the product. This guideline does not prohibit the use of pathogen-free FFP from UK donors, nor the use of PRP in older patients, although no specific conditions are set for this position. To date, the risk of transmission of the pathogen through FFP from UK donors is quite low (see Section 9.4).
  These problems once again emphasize that any blood products must be used strictly for specific indications.

1.3. The problem of transfusion-associated acute lung injury (TRALI) and the use of plasma from male donors (see Section 9.2),

  Transfusion-related acute lung injury is largely, but not exclusively, associated with the presence of leukocyte alloantibodies in the donor plasma. Such antibodies are most often found in women after pregnancy, and are not present in the plasma of men unless they have previously undergone blood transfusion. Even with a history of blood transfusions, such antibodies appear to be less active in men than in women who have been pregnant. Using male plasma as a source for FFP production appears to reduce the incidence of TRALI.

2. Specifications, preparation, storage and handling of FFP and cryoprecipitate

2.1. SZP

  In the UK, FFP is produced either by centrifugation of whole blood or by apheresis from material donated by pre-screened donors. Current guidelines (United Kingdom Blood Transfusion Services/National Institute for Biological Standards and Control, 2002) specify requirements for quality monitoring, including platelet and white blood cell levels, and indicate that FFP should be rapidly frozen to a temperature that maintains the activity of unstable coagulation factors. . Material from donors donating blood for the first time cannot be used for the production of FFP.
  FFP prepared from portions of whole blood and using plasmapheresis can differ only in the amount of plasma in the package. The volume can vary from 180 to 400 ml. Procedures for thawing FFP should be designed to avoid bacterial contamination (see Section 6.1).

  These values ​​were determined in the pathology laboratories of the University Hospital of Southampton. High levels of sodium, glucose, citrate and phosphate are associated with the use of a preservative anticoagulant mixture, and low levels of ionized calcium are also associated with this.
  The prepared plasma is quickly frozen to -30 degrees C, the recommended temperature for storage. The interval between collection and freezing is not specified in current guidelines (United Kingdom Blood Transfusion Services/National Institute for Biological Standards and Control, 2002).
  Frozen plastic bags containing FFP become relatively brittle and must be handled with care.
  Immediately after thawing, standard FFP should contain at least 70 IU/ml FVIII in at least 75% of the packages. This requirement has been relaxed for the PDP (see Section 3, and Table III).
  Packages should be inspected immediately before infusion. If any unexpected changes are observed in them, such as flaking, discoloration or obvious packaging defects, it is necessary to refrain from transfusion or observe these bags for a while to make a decision further. Other details of quality control requirements are also specified in the guidelines (United Kingdom Blood Transfusion Services/National Institute for Biological Standards and Control, 2002).

Recommendation
  Fresh frozen plasma produced by centrifugation of whole blood units and plasmapheresis is therapeutically equivalent in its effect on hemostasis and side effect profile (grade of recommendation A, level of evidence I).

2.2. Cryoprecipitate and cryosupernatant (‘cryo-depleted plasma’)

  Current guidelines (United Kingdom Blood Transfusion Services/National Institute for Biological Standards and Control, 2002) define cryoprecipitate as the cryoglobulin fraction of plasma obtained by thawing one portion of FFP at 4 ± 2 ° C; while the plasma remaining after cryoprecipitate preparation (also called cryo-depleted plasma or cryosupernatant) is the supernatant plasma removed during cryoprecipitate preparation. The precipitated cryoproteins are rich in FVIII, von Willebrand factor (VWF), FXIII, fibronectin and fibrinogen. After centrifugation, the cryoproteins are separated and resuspended in a smaller volume of plasma. Although the guidelines do not set any limits, most UK blood centers prepare cryoprecipitate in volumes of 20-40 ml. The cryoprecipitate specification requires that 75% of the bags contain at least 140 mg fibrinogen and 70 IU/mL FVIII. It should be noted that using two or three packets of FFP can replace more fibrinogen than using a smaller amount of cryoprecipitate.
  Plasma cryosupernatant is depleted of FVIII and fibrinogen. The concentration of FVIII can be about 0.11 IU/ml. Only a smaller portion of fibrinogen is removed from the cryosupernatant, while up to 70% is retained (Shehata et al., 2001). The cryosupernatant has a reduced content of high molecular weight (HMW) VWF multimers, but contains VWF metalloproteinases.

3. Pathogen-reduced plasma (PRFFP and PRP)

The British Department of Health has recommended that FFP prescribed to newborns and children born after 1 January 1996 should be obtained from areas where no cases of BSE have been reported and be subject to pathogen reduction procedures. Older patients who have previously received blood components and who require a significant volume of FFP transfusion (eg in the case of plasma replacement in TTP) may also benefit if PRP is used. However, in such cases it is difficult to predict the likely scale of the need. To reduce the risk of the recipient developing TRALI, donors should be predominantly male (see Section 9.3).

3.1. PRP manufacturing methods: quality control

  There are two methods for inactivating pathogens in plasma for clinical use: methylene blue and light treatment (MBFFP); and solvent detergent (SDFFP). The principal features of these products are shown in Table III (modified from Williamson, 2001).

3.1.1. MBFFP. Blood transfusions in the UK

  The National Institute of Biological Standards and Control (2002) defines MBFFP in which the pathogen-reducing methylene blue methylene is not removed (product contains approximately 1.0 µmol methylene blue), and FFP treated with methylene blue, which is then removed (product contains no more than 0.30 µmol methylene blue). The latter drug is usually preferable. MBFFP from UK group AB donors is available for children and newborns.
Table III. Comparison of standard fresh frozen plasma (FFP) with methylene blue-treated FFP and solvent detergent-treated FFP.
  Standard FFP MBFFP* SDFFP
Source British donors pre-tested for viruses. Single serving format. Donors are volunteers from the USA, only men. Single serving format. Non-British donors; batches up to 380 l (600–1500 identical AB0 portions)

Donor tests
Serology
HIV, HBV, HCV, HTLV

HIV, HBV, HCV, HTLV

HIV, HBV, HCV, HTLV
Genomic HCV HCV, HIV HAV, HCV, B19, HIV, HBV

Risk of virus transmission
HIV 1+2 1:10 million There have been no proven cases reported to date for HIV, HBV, HCV (one possible HCV transmission) To date, there have been no reports of transmission of HIV, HBV, HCV through SDFFP or solvent detergent treated plasma products
Hepatitis C 1:50 million
Hepatitis B 1:1.2 million
Hepatitis A Rare cases Neither reported
Parvovirus B19 Rare cases No more than for a standard FFP. Not a single message to date. Consignment seizures due to possible Containment B19. Seroconversion in patients is no greater than for untreated FFP.
Volume 180-300 ml + 50 ml pediatric portion. 235-305 ml + 50 ml pediatric portion. 200 ml; no pediatric portion.
Content of coagulation factors Varies between servings. 75% of doses > 0.7 IU/ml FVIII Varies between servings. 75% of doses > 0.5 IU/ml FVIII; all other factors > 0.5 IU/ml; there is no decrease in the content of AT III, protein C, protein S. There is no activation of coagulation factors and complement activation. Constant within the party. All factors > 0.5 IU/ml.
Cryoprecipitate/cryosupernatant Available May be available Not available
Residual additives No Do not contain more than 0.3 µmol/l methylene blue. At this level, no toxicity was observed or predicted, even in preterm neonates.

Allergic reactions

Can be reduced by removing white blood cells

Cell-related responses are likely reduced.

Probably less frequent than with FFP.
Moderate 1% No data
Heavy 0,1% No data

Antibody-related adverse reactions
 
Same as when using standard FFP

Forming parties reduces risk.
red blood cells Tested for high titer anti-A, B Not tested for high titer anti-A, B A high titer of anti-A, B is not a problem when forming batches of the product.
TRALI >20 cases per year (SHOT) Not reported to date. Only one possible case of TRALI has been reported
Thrombocytopenia Very rarely
Cell content Reduced leukocyte count Reduced content Contains no cells or cell fragments
Product Licensing Not required Medical product; CE marking Licensed, Bulk Product
Indications   Same as for SZP Same as for SZP
Usage to date 300,000 units per year in UK > 1,000,000 units in Europe 3,000,000 units in Europe

TRALI, transfusion-related acute lung injury; SDFFP, solvent detergent treated FFP; AT III, antithrombin III.
*See also Garwood et al (2003).
** TNBP, tri-(N-butyl)-phosphate.

  At the time of writing (December 2003) the supply of various types of MBFFP was being done in various regions of the UK and no non-UK plasma was available. Although harvesting FFP from male donors may reduce the risk of developing TRALI, such separation is not universally available. MBFFP obtained from AB male donors is sometimes available in packets containing 50-75 ml. During 2004, the supply of plasma obtained from donors from regions with a low incidence of BSE and pathogen-reduced using the MB process will be established for children born after 1996.

3.1.2. SDFFP.

  Earlier materials such as ‘Octaplas’ used by Solheim et al (2000) were manufactured in batches of 400 - 1200 doses. More recent batches are from 2,500 pooled units of thawed FFP. SDFFP contains reduced HMW-VWF content and reduced S protein activity. "Octaplas", licensed and available for order. The product must be compatible with the patient under group AB0.

3.1.3. Pathogen-reduced cryoprecipitate and cryosupernatant

  not currently available in the UK.

3.1.4. Quality control.

  Current guidelines (United Kingdom Blood Transfusion Services/National Institute for Biological Standards and Control, 2002) specify that, in addition to the features described in Section 2.1, MBFFP must contain at least 0.50 IU/mL FVIII. In contrast to standard FFP (0.70 IU/ml FVIII).

3.2. Efficiency and safety

  Each type of FFP has a spectrum of potential adverse effects; the decision regarding the use of one type or another may depend on specific clinical circumstances and drug availability.

3.2.1. MBFFP and SDFFP.

  Both pathogen reduction methods cause some loss of clotting factors. MBFFP has relatively low FVIII and fibrinogen activity (Atance et al., 2001). These authors also believe that the product has less clinical efficacy. In SDFFP, VWF and FVIII activity is reduced. It also has decreased functional activity of protein S (Jain et al., 2003; Yarranton et al., 2003).

3.2.2. MBFFP

  Virus safety. There has been one possible but unproven case of HCV transmission via an MBFFP package from a single donor (Pamphilon, 2000). However, the product from a single donor does not carry the same risk as when pooled into a batch, in which 1 portion contaminated with HCV or other non-inactivated organisms can cause infection in many recipients.
  Toxicological safety. Doses of methylene blue much higher than those present in MBFFP are well known as a treatment for methemoglobinemia (Mansouri and Lurie, 1993). There is no reason for special caution in patients with glucose-6-phosphate dehydrogenase deficiency (grade of recommendation A, level of evidence I).

3.2.3. SDFFP.

  Materials from different manufacturers may differ in detail and have different efficacy and safety profiles (Solheim and Hellstern, 2003). Reduced protein S activity is associated with the possibility of developing venous thromboembolism (VTE). Yarranton et al (2003) reported eight episodes in seven of 68 patients with TTP treated with plasma replacement. Jain et al (2003) reported the association of SDFFP with thromboembolic complications in patients undergoing liver transplantation. Also of concern is the possibility of transmission of non-lipid coated viruses through PRFFP. In the United States, shipments have been seized due to possible parvovirus B19 content. Suppliers now measure levels of HAV and B19 antibodies when making the drug, and can also perform genomic tests for the presence of B19. Studies of patients treated with SDFFP compared with conventional FFP have not shown an increase in transmission of non-lipid-coated viruses, but the number of patients studied is still small.

Recommendation
  Any patient prescribed PRP must weigh the risk of HAV and parvovirus B19 transmission and their possible complications against the likely clinical benefit (grade of recommendation, B evidence level II/III).

4. Selection of FFP based on blood type

The following recommendations have been updated from previous guidelines.

4.1. Blood compatibility according to AB0 group (see Table I),

 Group 0 plasma is more likely to contain high titers of AB0 antibodies than plasma from group A or B donors, although activity varies widely between donors. The British Blood Service tests all donors for high titre antibodies. Low titer doses are noted to have a low risk of developing ABO-associated hemolysis. Although there were no reports of ABO-associated hemolysis in the first 5 years of the SHOT regimen, in 2000, three patients with blood type A who received reconstituted, pooled platelets diluted in plasma had hemolytic reactions; for one of them, platelets were obtained by apheresis, and the plasma did not contain a high titer of hemolysins according to the test criteria.
  If fresh frozen plasma of the same AB0 group as that of the recipient is not available, plasma of another group should be used only if it does not contain a high titer of anti-A and anti-B antibodies; It is preferable to use Group A FFP for Group B patients and vice versa if ABO-identical plasma is not available. However, even with a negative in vitro test, hemolysis can always occur in the body, especially if large volumes are used. Clinicians and hospital blood and plasma bank staff should be aware that hemolysis can occur when transfusion of A0-incompatible FFP is given. This also applies to group A plasma administered to group B patients and vice versa, even if the material has been tested and labeled as not containing high titer antibodies, according to the protocol.
  Group AB FFP can be used in a critical situation if the patient's AB0 blood type is not known, but it is likely to be available only in limited quantities.

Recommendation
  Regarding AB0 blood groups, the first choice for prescription is FFP of the same group as the patient. If this is not available, an FFP of another A0 group can also be used if it is not tested to have anti-A or anti-B activity above the “high titer” threshold. Group 0 FFP should only be given to group 0 donors (grade of recommendation B, level of evidence III).

  Plasma prescribed to infants and newborns should not contain a clinically significant amount of irregular blood group antibodies. FFP from group AB donors contains neither anti-A nor anti-B antibodies and is often preferred.

Recommendation
  Group 0 FFP should not be used in non-group 0 infants or newborns because the relatively large volumes required may result in passive immune hemolysis (grade of recommendation B, level of evidence III).

4.2. Rh blood group compatibility

  Although FFP and MBFFP may contain some red blood cell stroma, sensitization following administration of Rh D positive FFP to Rh D negative patients is unlikely because stroma is less immunogenic than intact red blood cells (Mollison, 1972). The 10th edition of the Council of Europe Guideline does not require packages of FFP to be marked according to their Rh group (Council of Europe, 2004).

Recommendation
  Fresh frozen plasma, MBFFP and SDFFP of any Rh group can be administered regardless of the recipient's Rh group. No anti-D prophylaxis is required if Rh D negative patients receive Rh D positive FFP (grade of recommendation B, level of evidence IIa).

5. Dosage

  The volume of FFP in each package is indicated on the label and can vary from 180 to 400 ml. The traditional dosage of 10–15 ml plasma per kg body weight is likely to be exceeded in cases of massive bleeding (Hellstern and Haubelt, 2002). Therefore, the dosage depends on the clinical situation and monitoring data.

6. Defrosting and storing melted product

  Frozen plastic containers are brittle and vulnerable, especially along seams and exit lines, which can be easily damaged.

6.1. Thawing FFP, cryoprecipitate and cryosupernatant

  Frozen plasma products must be thawed at 37°C (if thawed at 4°C, cryoprecipitate will form).
  There are several ways this can be achieved, the most common being a recirculating water bath. The process carries a risk of bacterial contamination and must be carried out according to a sterility control protocol. Dry heating systems that prevent denaturation of plasma proteins are preferred.

6.1.1. Dry ovens (incubator with temperature control and fan).

  They may have a lower potential for contamination of FFP bags with microorganisms, although they usually have a limited capacity. The time for thawing FFP is usually 10 minutes for 2 bags.

6.1.2. Microwaves.

  Although they defrost in 2-3 minutes, they have several disadvantages such as high cost and limited capacity. There are also problems associated with the formation of "hot spots" in the bags and the potential for air pockets in the bag causing expansion when heated.

6.1.3. Water baths.

  When thawing, it is important to place the FFP package in a sealed plastic bag to protect against bacterial contamination. After thawing, the outer bag should be removed from the first and the packaging should be inspected for leaks or damage. Damaged packages should not be used. Water baths for thawing FFP should be used for this purpose only. They must be washed regularly (at least once a day) and filled with clean, laboratory-grade water. The use and maintenance of bathtubs must be described in specific standard operating instructions. The entire service process must be recorded. The average thawing time for 2 packages is 20 minutes.

6.2. Storage after defrosting

  Thawed plasma and cryosupernatant should be stored at 4°C if there is any delay in transfusion. Current UK guidelines (United Kingdom Blood Transfusion Services/National Institute for Biological Standards and Control, 2002) require transfusion within 4 hours; at the same time, the American Association of Blood and Plasma Banks (2002) allows a delay of transfusion up to 24 hours. FVIII activity in FFP decreases by 28% after 24 hours of storage at 4°C, but all other factors remain stable over 5 days (see Table IV). Shehata et al (2001) showed that storing FFP for 72 hours after thawing resulted in a decrease in FVIII activity by approximately 40%, although FVIII activity and fibrinogen content still remained significantly higher than in the cryosupernatant. The activity of FII and FV in FFP persists for 72 hours after thawing. These authors recommended that FFP stored 72 hours after thawing can be used as cryosuppernatant plasma if FVIII replacement is not required. Another safety concern is the microbial contamination that can occur during defrosting, especially if a water bath is used. The use of proper protocols and documentation, as well as defrosting methods that do not involve immersion in water, reduce this risk. Therefore, further research is needed to recommend storage beyond 24 hours after thawing.

Recommendation
  After thawing, if replacement is not required, FVIII, FFP and cryosupernatant can be stored at 4° C in a special blood storage refrigerator until administered to the patient within 24 hours (grade of recommendation B, level of evidence III).

Table IV. Content of hemostasis factors in thawed fresh frozen plasma (FFP), and after storage at 4° C. Content in a typical unit of 300 ml (IU/ml), except fibrinogen (g/l).
  Levels immediately after thawing Levels at 24 hours Levels by day 5
Fibrinogen 2,67 2,25 2,25
FII 80 80 80
F.V. 80 75 66
FVII 90 80 72
FVIII 92 51 41
FIX 100
FX 85 85 80
FXI 100
FXII 83
Antithrombin III 100
VWF 80*

These values ​​were determined at the Diagnostic Pathology Laboratories of the University of Southampton. Protein C and antithrombin levels are in the normal range.
*With a slight decrease in the content of HMW multimers, especially if processed with SD.

7. Control of receipt and transfusion

  The BCSH guidelines for the administration of blood and blood components and the management of patients undergoing transfusion should be followed (BCSH, 1990b, 1994, 1999). Like all blood components, FFP should be administered to adults and children, only through a 170–200 lm filter, as provided in the standard kits provided.
  Fresh frozen plasma and cryoprecipitate must be issued from the hospital blood and plasma bank, according to the same criteria as red blood cells and platelets. Care must also be taken to ensure that blood samples are obtained from the correct patient, to the completion of the request or order form, and to the administration and documentation of the transfusion. Hospitals should have a policy for handling FFP that is consistent with this guideline.

8. Response to FFP transfusion

  The response must be monitored, since further treatment will depend on it. If FFP is given for bleeding, clinical response may well be the best indication of the effectiveness of the transfusion. If FFP is prescribed to correct coagulation parameters, the degree of correction should be recorded. Monitoring may consist of measuring coagulation activity using traditional laboratory techniques or using various bedside tests; the methods chosen must be timely and appropriate to the clinical situation.

9. Adverse effects

9.1. Allergy

  Allergy, manifested by urticaria, is reported in 1-3% of transfusion cases, but anaphylaxis is rare (Bjerrum and Jersild, 1971; Sandler et al, 1995). In the first 6 years of the SHOT regimen, 23 allergic and 25 anaphylactic reactions to FFP, and one acute reaction involving IgA antibodies, were reported. For patients with proven sensitivity to IgA, IgA-deficient plasma is available upon request. Patients who experience severe side effects after transfusion should be managed according to McClelland (2001).

9.2. TRALI

Transfusion-related acute lung injury manifests clinically as severe respiratory distress, with hypoxia, pulmonary edema, infiltrates or opacities on the chest radiograph, and sometimes fever and hypotension, which usually develops within 4 hours of transfusion (Kopto and Holland, 1999) . It cannot be clinically distinguished from adult respiratory distress syndrome or other forms of acute lung injury (Popovsky et al., 1992; Murphy, 2001; Palfi et al., 2001). Symptoms usually improve after a few days, although signs of illness may persist for at least 7 days.
  Since 1996, the SHOT regimen has received reports of TRALI in 109 transfusion recipients, of whom 30% died—mostly due to complex causes. During the 15-month period 2001–2002, FFP was a component in 12 of 22 TRALI cases. Of these patients, one (who received FFP only) died.
  According to some authors, TRALI develops in two stages (Silliman et al., 2003). First, predisposing conditions such as surgery or active infection cause the release of cytokines and stimulate neutrophil tropism towards the vascular endothelium, especially in the pulmonary capillaries. The second step is that lipids and cytokines, as well as human leukocyte antigens or granulocyte alloantibodies (found in 80% of donors in some series, most of whom were women who were pregnant), cause further neutrophil activation and pulmonary damage.
  If leukocyte alloantibodies are important in TRALI, its incidence could be reduced by using FFP from male donors. Plans to speed up such separation in areas of the UK may be supported by further research, but this is as yet an unproven hypothesis. There have been no proven cases of TRALI reported using SDFFP. This may be due to the fact that the pooling process dilutes any unit with a high titer of alloantibodies.

9.3. Complications associated with white blood cell depletion

  There are few reports of complications. There have been reports from the USA of the development of red eye syndrome (a form of allergic conjunctivitis) after transfusion of red blood cells through a certain type of leukemia filter from one specific batch. Hypotension occurs after bedside filtration of cell products in patients receiving angiotensin-converting enzyme antagonists, but does not occur with prefiltration because bradykinin is rapidly degraded in normal plasma. Although bedside filtration is no longer available in the UK, it is a reminder to report any complication, including red eye syndrome, to the SHOT scheme (Williamson, 2001).

9.4. Infection

  The freezing process inactivates bacteria. Bacterial contamination and growth with endotoxin production prior to freezing is unlikely and has not been reported in the UK in the past 5 years (Sazama, 1994; SHOT, 2001, 2002, 2003). Removal of cellular components also removes intracellular bacteria, most protozoa (except Tryponasoma cruzi), and cell-associated viruses. In summary, transmission of malaria, cytomegalovirus, and human T-lymphotropic virus has not been reported with the use of FFP. However, freezing does not inactivate free viruses, such as hepatitis A, B and C viruses, human immunodeficiency virus (HIV) 1+2, and parvovirus B19 (Pamphilon, 2000). Taking into account the exclusion of new donors for FFP production and HCV genome testing (Garwood et al, 2003; R. Eglin and K. Davison, personal communication), the estimated residual risk that a unit of FFP would contain the following viruses is: 1.0 per 10 million for HIV 1+2; 0.2 per 10 million for hepatitis C, and 0.83 per 10 million for hepatitis B. However, hepatitis A and B vaccination should be considered in patients who are frequently transfused. It should be noted that the hepatitis A vaccine is not licensed for children under 2 years of age.

Recommendation
  For patients likely to receive multiple doses of FFP units, such as those with congenital coagulopathy, vaccination against hepatitis A and B should be considered (grade of recommendation C, level of evidence IV).

9.5. Graft versus host disease (GvHD)

  There have been no reported cases of FFP-associated GvHD. FFP does not need to be irradiated.

9.6. VTE

  See Section 3.2.3 (VTE associated with the use of SDFFP during plasma exchange for TTP).

9.7. Reports of Adverse Reactions

  As both SDFFP and MBFFP are new products in the UK, it is important to report unexpected issues. For SDFFP, the Medicines Control Agency's "Yellow Card" system for drug reactions applies. Adverse reactions to MBFFP should be discussed immediately with the blood supply center. Adverse reactions to MBFFP or SDFFP, as well as to cryoprecipitate and cryosupernatant, should be reported to the SHOT office (details in Appendix B).

10. Clinical indications for the use of FFP, cryoprecipitate and cryosupernatant

10.1. Single factor deficiency

  Fresh frozen plasma should be used to correct single clotting factor deficiency only in cases where no fractionated virus-safe product is available. Currently, this mainly applies to FV. FFP should also be used rather than FXI concentrate in patients with congenital FXI deficiency if there is concern about the potential thrombogenicity of FXI, for example during the peripartum period (see recommendation in Section 3.2.3). More information about individual clotting factor concentrates and their use can be found in the British Haemophilia Centers (1997, 2003). PRP is recommended for children born after January 1, 1996, and there are cases where PRP (Section 3) is considered for patients of all ages.

10.2. Multiple coagulation factor deficiencies

  Fresh frozen plasma is indicated when there is a multifactorial deficiency associated with severe bleeding and/or disseminated intravascular coagulation, as discussed in the following paragraphs.

10.3. Hypofibrinogenemia

  The most common indication for the use of cryoprecipitate is to increase fibrinogen levels in dysfibrinogenemia and acquired hypofibrinogenemia, which develops with massive transfusion and disseminated intravascular coagulation. Prescription is usually indicated if plasma fibrinogen levels are less than 1 g/L, although there is no absolute threshold value for diagnosing clinically significant hypofibrinogenemia. Fibrinogen measurement results vary depending on the method used. A pathogen-reduced fibrinogen concentrate of higher purity is in development but is still available. 10.4. Disseminated intravascular coagulation (see Section 10.9.2),   Disseminated intravascular coagulation occurs when septicemia, massive blood loss, severe vascular injury, or toxins (such as snake venom, amniotic fluid, pancreatic enzymes) trigger hemostasis mechanisms. It can be clinically compensated and manifested only according to laboratory tests. However, the trigger can cause decompensation, leading to significant capillary bleeding as well as microangiopathic thrombosis. All coagulation factors are exhaustible, but especially fibrinogen and FV, FVIII and FXIII. Addressing the underlying cause is the cornerstone of treatment for DIC. Although transfusion support may be necessary, there is no consensus regarding optimal treatment. If the patient is bleeding, a combination of FFP, platelets, and cryoprecipitate is indicated. However, if there is no bleeding, blood products are not indicated, regardless of laboratory test data, and there is no evidence for prophylactic management of platelets or plasma (Levi and ten Cate, 1999).

10.5. TTP (Machin, 1984; BCSH, 2003)

Most patients with TTP have normal or near-normal coagulation test values, although in some patients they may be similar to those seen in DIC - low platelet counts, changes in PT and activated partial thromboplastin time (APTT). Neurological abnormalities develop late and indicate serious deterioration requiring immediate intervention. Furlan et al (1998) demonstrated that most patients have a deficiency of the active metalloproteinase enzyme, resulting in the accumulation of HMW-VWF, which leads to excessive platelet activation and consumption.
  The mainstay of management of acute TTP is daily plasma replacement (Evans et al, 1999). Before the introduction of this method, the mortality rate was over 90%. With the introduction of plasma transfusion for treatment, the mortality rate dropped to 37%, and with the introduction of plasma replacement, the mortality rate dropped further to 22%. All forms of FFP contain the missing enzyme, but FFP deficient in HMW-VWF, namely SDFFP (Harrison et al., 1996) or cryosupernatant (cryo-depleted FFP) may be preferred. This statement is based on a study that used historical controls (Rock et al., 1996). This issue is currently the subject of a Canadian randomized trial comparing cryosupernatant versus SDFFP. The findings of Zeigler et al (2001) are somewhat different.
FFP treated with methylene blue and light is also effective in this situation, but may require more plasma replacement procedures (De la Rubia et al, 2001). Although no randomized trials have been conducted comparing SD- and MB-treated foods, in this case, De la Rubia et al (2001) suggested that MBFFP was less effective than SD FFP (grade of recommendation C, level of evidence III). SDFFP has been associated with the development of VTE when used as a plasma replacement medium in TTP. MB cryosupernatant may be more effective than standard FFP for the treatment of TTP (grade of recommendation C, level of evidence III), but at the time of writing was not yet available for routine use in the UK.
  Although plasma replacement with FFP is clearly effective, the optimal regimen has not yet been determined, but the current recommendation is to use at least 1.0 volume of plasma replacement every day until at least 2 days after achieving remission (criteria - normal neurological status, platelet count more than 150 x 10^9/l, normal level of lactate dehydrogenase and increased hemoglobin concentration).

Recommendation
  Daily single plasma volume replacement procedures should ideally be started immediately upon presentation (grade of recommendation A, level of evidence Ib), and preferably within 24 hours of presentation (grade of recommendation C, level of evidence IV). Daily plasma replacement should be continued for at least 2 days after remission is achieved (grade of recommendation C, level of evidence IV).

10.6. Reversing the effect of warfarin (see BCSH, 1990b; BCSH, 1998; Baglin, 1998; Makris and Watson, 2001)

  Warfarin achieves its anticoagulant effect by inhibiting vitamin K-dependent carboxylation of FII, FVII, FIX and FX. Thus, there is a functional deficiency of these procoagulants as well as the anticoagulants proteins C and S. The anticoagulant effects of warfarin can be demonstrated by an increase in the duration of PT and the international normalized ratio (INR). Target INRs for various thrombotic indications are given in BCSH (1998).
  Hyperanticoagulation due to excessive effects of warfarin may completely disappear within a few measurements. In mild to severe circumstances, they are treated by: stopping warfarin, administering oral or parenteral vitamin K (eg, 5 mg slow intravenous injection; grade of recommendation B, level of evidence III); transfusion of FFP, or transfusion of PCC (FII, FVII, FIX and FX, or separate administration of FII, FIX, FX concentrate and FVII concentrate). PCC (50 units/kg) is preferred over FFP. Details have been published previously (BCSH, 1998; Makris and Watson, 2001). Makris et al (1997) showed that FFP contains insufficient concentrations of vitamin K-related factors (especially FIX) to completely reverse the effects of warfarin. This supports the view that FFP is not the optimal treatment in such cases. The BCSH Oral Anticoagulant Guideline (BCSH, 1998) recommends FFP (15 ml/kg) only if there is overt bleeding in patients on warfarin if PCC is not available. Concomitant intravenous vitamin K (5 mg) is also recommended, although they note that individual factor levels are likely to remain below 20%.

Recommendation
  Fresh frozen plasma should not be used to reverse the anticoagulant effects of warfarin unless there is evidence of severe bleeding (grade of recommendation B, level of evidence IIa).

10.7. Policy for the use of vitamin K in the ICU

  Many patients in the ICU have vitamin K deficiency, especially if they are prescribed parenteral nutrition, which has a limited lipid component. This may lead to an increase in the duration of PTT, which is usually corrected by oral or parenteral vitamin K; Vitamin K intake should be maintained. FFP is not a treatment option to correct inadequate vitamin K intake, even if there is an increase in clotting time, and aggressive procedures such as liver biopsy are possible.

Recommendation
  Intensive care unit patients should receive vitamin K routinely; 10 mg three times a week for adults and 0.3 mg per kg for children (grade of recommendation B, level of evidence IIa).

10.8. Liver diseases

  Patients with liver diseases experience various abnormalities of the coagulation system. The level of deviation in hemostasis parameters correlates with the degree of parenchymal damage. Decreased synthesis of clotting factors, reflected in increased duration of PTT, may predispose to bleeding, which may be exacerbated by dysfibrinogenemia, thrombocytopenia, and activation of fibrinolysis. However, bleeding rarely occurs without a trigger such as surgery, liver biopsy, or rupture of varicose veins.
  There are still advocates for the use of fresh frozen plasma to prevent bleeding in patients with liver disease and increased PTT, although complete normalization of hemostasis does not always occur (Williamson et al, 1999). The routine use of FFP in these circumstances is therefore questionable. Platelet count and functional activity, as well as vascular integrity, may be more important in this situation. Although it has been shown that PCCs can significantly correct abnormalities in hemostatic factors in liver disease (Green et al, 1975; Mannucci et al, 1976), its use, even a less thrombogenic drug available later, is not recommended due to the high risk of developing disseminated intravascular coagulation. For similar reasons, it is also advisable, if possible, to avoid administering SDFFP in this situation due to the relative depletion of protein S.
  Many specialist units perform a liver biopsy only if the PTT is no more than 4 seconds above the upper limit of the normal range. There is no evidence to support this approach. Other tests, such as APTT and thrombin time, are not usually helpful in decision making. The response to FFP in liver disease is unpredictable. If FFP is prescribed, coagulation tests should be repeated once the infusion is completed to aid further decision making. The merits of different infusion regimens, such as 5 mL/kg/hour versus intermittent boluses, have not been studied. Further research is needed in this area. Further work is needed to examine the role, if any, of FFP in patients with liver disease to correct bleeding tendencies prior to biopsy.

Recommendation
  Available data indicate that patients with liver disease and an increase in PTW of more than 4 seconds compared with controls are unlikely to benefit from FFP (grade of recommendation C, level of evidence IV).

10.9. Surgical bleeding

  There has been much debate about the management of major bleeding that occurs during or after surgery. Goodnough (1999) described many uses of blood components, including FFP. Recent advances in the understanding of coagulation mechanisms have also led to a reconsideration of the value of traditional coagulation tests (PTT, APTT, TT) and bedside tests such as thromboelastogram (TEG) (Shore-Lesserson et al, 1999).

10.9.1. Coronary artery bypass graft (CABG) surgeries.

  Patients undergoing CABG operations are heavily heparinized to prevent thrombosis of the shunt. They receive 25,000 – 30,000 units of heparin. Their hemostasis is usually monitored by activated clotting time (ACT), and at the end of the operation the heparin is completely inactivated by protamine. Continued bleeding after surgery may require more protamine to be given (Bull et al, 1975). In the past, the need for blood transfusions was high, but with improvements in facilities and technology, the use of blood products has decreased and many patients undergoing surgery now do not require transfusions. Recently developed bedside coagulation tests have enabled surgeons and anesthesiologists to treat non-surgical causes without transfusion of blood products. These methods include TEG, which is used in several UK heart centers; Sonoclot (Hett et al., 1995); Plateletworks (Lakkis et al., 2001); and Platelet Function Analyzer 100 (Wuillemin et al., 2002). The use of pharmacological agents (such as tranexamic acid and aprotinin), used prophylactically or to treat established bleeding when excessive activation of fibrinolysis is suspected, is accompanied by an even greater reduction in the use of blood products (Horrow et al, 1990; Hunt, 1991; Laupacis et al, 1997 ; Peters and Noble, 1998).

10.9.2. Massive transfusion.

  Can be defined as the complete replacement of a patient's blood volume with conserved blood in less than 24 hours, although alternative definitions exist, with other time intervals (such as 50% blood volume loss over 3 hours, or a loss of 150 ml/minute) and may be more useful for clinical use (Stainsby et al, 2000). Earlier guidelines and reports suggested that early adequate management of shock is key to preventing coagulopathy, but prophylactic plasma replacement regimens neither prevent the process nor reduce transfusion requirements (Harke and Rahman, 1980; Mannucci et al, 1982; Ciavarella et al, 1987; Carson et al., 1988; Hewitt and Machin, 1990). Like most of these reports, the latest BCSH guidelines for the management of major haemorrhage (BCSH, 1988) were issued when the most commonly transfused red blood cell preparations were 'packed cells' or whole blood. They contained 150-300 ml of donor plasma, whereas currently, preparations in the UK, with the exception of red blood cells for exchange transfusion, are resuspended in the added solution and contain only residual amounts of plasma, approximately 30 ml. The BCSH (1988) states that coagulation factor depletion is not a common finding in massive blood loss in the absence of disseminated intravascular coagulation, which, if it occurs, is likely to be a delayed consequence of shock. In this situation, they are reticent to prescribe FFP, stating that although in theory a deviation in PTT or APTT should be an indication for prescribing FFP, there is still insufficient objective clinical evidence that it has a clinical benefit. This situation has not changed significantly. Ciavarella et al (1987) found that the use of a reimbursement policy for the use of blood products, including FFP, for major bleeding was no more effective than a reimbursement policy based on timely coagulation tests and clinical signs. They also found that platelet count significantly correlated with the development of capillary bleeding and recommended platelet transfusion if platelet levels dropped below 50 x 109/L. More recently, Hiippala et al (1995) found that clinically significant fibrinogen deficiency develops after a loss of approximately 150% of blood volume—earlier than any other hemostatic abnormality—when plasma-poor red cell concentrates are used to replace blood loss; and Stainsby and Burrowes-King (2001) stated that the use of FFP in major transfusion (and cardiac surgery) should be based on data from coagulation tests, and if rapid benefit cannot be achieved, the use of bedside tests merits consideration. In their comments on massive blood loss (which provide a template guideline), Stainsby et al (2000) recommended that if bleeding continues after the transfusion of large volumes of (crystalloid-suspended) red cells and platelets, FFP and cryoprecipitate can be administered so that the ratios of PTT and APTT are reduced up to 1.5, and fibrinogen concentration to at least 1.0 g/l in the resulting plasma.

Recommendation
  Whether and how much FFP should be used to treat a patient with apparent blood loss should be based on data from timely coagulation tests (including bedside tests). The prophylactic regimen should not be used (grade of recommendation B, level of evidence IIb).

11. Use of FFP in pediatrics (see BCSH, 2004),

  Children born after January 1, 1996 should receive only PRP (see Section 3). MBFFP is available in small packages. SDFFP has been used in neonates and infants and no short-term toxicity has been reported, but clinical experience is limited. Since early 2004, MBFFP from North America used for children must be available. The most common causes of bleeding in newborns are vitamin K deficiency and inherited clotting factor deficiencies. Prematurity may predispose to longer clotting times but is not itself an indication for FFP. It should be noted that the normal clotting time of infants is longer than that of adults. In premature infants (due to decreased protein synthesis in the liver), it can be even longer, even in the absence of any pathology (Male et al., 1999).

11.1. Hereditary deficiency of clotting factors

  See Section 10.1.

11.2. Hemorrhagic disease of the newborn (HDN)

  Prevention of HDN with vitamin K has become routine practice in many countries since the 1960s. Without such prevention, one in 200 to 400 live newborns will develop HDN (Zipursky, 1998). Defined as high-risk infants are those who are premature, have liver disease, or are born to mothers taking anticonvulsants, isoniazid, or warfarin (Department of Health, 1998). Early HDN (within 24 hours) and classic HDN (2–5 days) are usually severe, while late HDN (2–12 weeks) is often less severe.

11.2.1. Management of acute bleeding. SZP

Recommendation
  If bleeding associated with HDN occurs, FFP (10-20 ml/kg) is indicated, as is intravenous vitamin K (grade of recommendation C, level of evidence IV).

PCC (see Section 10.6).

  Currently, these drugs are available for use only in centers with large pediatric ICUs and are not available to most pediatricians. There are no data yet to establish the dosage for their use, but they should be kept in mind when treating severe HDN because of the possible rapid resolution of coagulopathy. All acute care hospitals should have access to PCCs.

Recommendation
  Although the coagulation defect in HDN can be completely corrected by PCC, there are no data to guide the dosage in this situation (grade of recommendation C, level of evidence IV).

11.3. Neonates with coagulopathy and bleeding, or risk of bleeding due to the use of aggressive procedures

  Fresh frozen plasma is indicated for sick infants with hypoxia (respiratory distress), hypotension, sepsis, or liver abnormalities associated with significant coagulopathy and bleeding, or those at risk of bleeding due to aggressive procedures and significant coagulopathy.

Recommendation
Neonates with significant coagulopathy and risk of bleeding, or those about to undergo aggressive procedures, should receive approximately 15 ml/kg FFP as well as vitamin K (grade of recommendation C, level of evidence IV). The reduction in clotting time is unpredictable and should be monitored after administration.

11.4. Prevention of intraventricular hemorrhage in premature infants

  The Neonatal Nursing Initiative Trial Group (1996) found that there is no evidence that routine early administration of FFP or any other form of intravascular volume expansion affects the risk of death or neurological impairment in infants born more than 8 weeks before term.

11.5. Polycythemia in infants

  There are no indications for the use of FFP in this situation.

11.6. T antigen activation by red cells

T activation can occur through exposure to latent 'T' antigen on the cell wall of newborn red blood cells if the patient is infected with clostridia, streptococcus, or pneumococcus in conditions such as necrotizing enterocolitis (NEC). Anti-T antibodies are found in virtually all donor plasma, but the clinical significance of T activation in relation to transfusion policy is unclear. There is debate among transfusion centers as to whether plasma transfusion actually causes hemolysis (Eder and Manno, 2001). If clinically significant hemolysis were to occur in this situation, the logical approach would be to limit plasma transfusion to only that containing a low titer of anti-T, which is not usual. This approach has advocates, but requires identification of low titer anti-T antibodies.
T activation is associated with significant morbidity and mortality, and occurs in approximately 27% of selected infants with NEC requiring surgery, compared with 11% in cases where surgery was not indicated and only up to 1% in otherwise normal infants. There are subtypes (T, Th, Tk, Tx, etc.) that may or may not be associated with different infections; but Eder and Manno (2001) argue that differentiating between T-activated cell types may not be of practical importance or clinical benefit, and Osborn et al (1999) found that the clinical course of NEC in infants with T-activated cells was no different from those with who developed Tk-activated cells. In addition, hemolysis rarely follows transfusion even in critically ill children with NEC and T activation, and if hemolysis occurs, it may not be immune. There is insufficient definitive evidence to support clinical decisions in these circumstances.
Randomized controlled trials to screen for T activation in at-risk patients and ensure low titre plasma anti-T components may provide some evidence on which to base recommendations (Eder and Manno, 2001), but such products may not be widely available. , and delaying transfusion of standard blood products may be more dangerous for the patient.

Recommendations
  In the absence of specific data, each clinical department should formulate its own policies and protocols for investigating any unexpected hemolysis associated with plasma transfusion in a child with NEC or similar infection. A selective testing strategy and transfusion protocol may also be required in such cases (grade of recommendation C, level of evidence IV).
  If there is a high suspicion of T-activated hemolysis, exchange transfusion using plasma products and red blood cells with a low titer of anti-T may be indicated. In this situation, (washed/resuspended) low titer anti-T platelet concentrate may also be indicated (grade of recommendation C, level of evidence IV). It should be taken into account that avoiding transfusion of plasma-containing blood components in infants with T-activated red cells may be an inappropriate policy for patients who require correction of hemostasis (grade of recommendation B, level of evidence II/III).

12. Additional instructions for patients who, for various reasons, refuse transfusion

  This applies, among other things, to Jehovah's Witnesses, who usually refuse plasma (FFP) but sometimes accept the administration of blood fractions (such as clotting factor concentrate, even if they are not recombinant and contain donor albumin as a vehicle ). Each hospital should have additional consent (optional) protocols that all such patients admitted to the hospital must sign before a decision is made about the use of certain products.

13. No indications for the use of FFP

13.1. Hypovolemia

  Fresh frozen plasma should never be used for simple volume replacement in adults or children. Crystalloids are safer, cheaper and more widely available.

13.2. Plasma exchange (except TTP)

  Although the use of replacement fluids without plasma results in a progressive decrease in coagulation factors, immunoglobulins, complement and fibronectin; Bleeding and/or infection usually does not develop. In rare cases, if bleeding occurs, it is advisable to check the platelet count before prescribing FFP. Low pseudocholinesterase levels may be a problem as a result of repeated plasma replacement using saline/albumin if the patient requires further anesthesia. This can be corrected with FFP, although alternative drugs that can be used are available and known.

13.3. Correction of increased INR in the absence of bleeding

  There are no data to justify the use of FFP to correct an elevated INR in the absence of bleeding.

Legal Disclaimer
  While the recommendations and information in this guide are believed to be true and accurate at the time of publication, neither the authors nor the publishers can accept any legal liability or responsibility for any omissions or errors that may be made.

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Appendix A

 The definitions of levels of evidence and grades of recommendation used in this guideline are taken from the US Agency for Healthcare Policy and Research and are listed below.

Points of evidence

Ia Evidence obtained from meita analysis of randomized controlled trials.
Ib Evidence from at least one randomized controlled trial.
IIa Evidence from at least one well-designed controlled trial without randomization.
IIb Evidence from at least one other type of well-designed quasi-experimental study.
III Evidence obtained from well-designed non-experimental descriptive studies such as comparative, correlational, and case studies.
IV Evidence obtained from expert committee reports and the opinions and/or clinical observations of reputable experts. A Requires at least one randomized controlled trial of good quality and consistency addressing specific recommendations (levels of evidence Ia, Ib).
B Requires available well-performed clinical trials, but there are no randomized clinical trials regarding recommendations (levels of evidence IIa, IIb, III).
C Requires evidence from expert committee reports and the opinions and/or clinical observations of reputable experts. Indicates that there are no good quality clinical studies directly applicable to this recommendation (Level IV evidence).

Translation and web design -

Exam questions on professional retraining

"Transfusiology"

1. Bacteriological study of the air environment of boxed premises involves determining:

b) the total content of microbes and the amount of Staphylococcus aureus and streptococcus;

c) the amount of Staphylococcus aureus, mold and yeast fungi

The most dangerous biological fluids for HIV

c) blood

d) sperm

3. Blood substitutes with hemodynamic action are:

A ). Reopoliglyukin

b). Acesol

V). Polidez

G). Glucose

Human blood antigens include:

A. Erythrocyte and leukocyte

B. Erythrocyte, leukocyte, platelet

B. Simple and complex

G. Erythrocyte, leukocyte, platelet, serum

The instructions on the drug packaging “store in a cool place” correspond to the parameters

A). 2 to 8 °C;

b). 8 to 15 °C;

V). 18 to 20 °C;

G). 15 to 25 °C.

Time the tourniquet is on the limb

A). in summer no more than 30 minutes, in winter 40 minutes

b). in summer no more than 60 minutes, in winter 90 minutes

V). in summer no more than 15 minutes, in winter 30 minutes

G). can stay indefinitely

What class of waste do expired medicines belong to?

a) Class A

b) Class B

c) Class G

d) Class B

A specialist in the field of nursing organization must have a certificate in the specialty

a) "Nursing"

b) "Medicine"

c) "Midwifery"

d) "Organization of nursing"

d) "Medical and preventive care"

Which of the following methods is aimed at preventing HIV infection, hepatitis B and C?

a) Deratization

b) Pest control

V) Disinfection

d) All of the above

Founder of nursing development

A). Ekaterina Mikhailovna Bakunina

b). Dasha Sevastopolskaya

V). Florence Nightingale

G). Virginia Henderson

11. National Donor Day is celebrated in Russia every year:

12. Responsibility for the state of labor protection in the institution lies with:

a) Chairman of the occupational safety commission;

b) Manager;

V ) OSH Commissioner.

13. Disinfection of boxes in which material is tested for sterility is carried out:

a) when mold fungi are detected in the air or on the surface;

b) daily before the start of work;

c) at least once a week

Control of sterilization regimes by biological method is carried out:

a) 2 times a month;

b) 2 times a week;

c) 2 times a year

Incubation period for HIV infection

a) up to 7 days

b) up to 30 days

V) from 3 weeks to 3 months, sometimes up to a year

Duration of virus carriage

a) no more than 20-30 days

b) up to several months

c) for life

Causes of immunodeficiency in HIV

a) damage to B cells

b) damage to T cells

c) damage to erythrocytes

The most common opportunistic infections in HIV

a) flatulence

b) Kaposi's sarcoma

c) pneumocystosis

Incubation period for viral hepatitis B

b) 6 months

c) 2 months

Routes of transmission of viral hepatitis B

a) parenteral

b) sexual

c) fecal-oral

Storage conditions for sera for ELISA

a) at t 0ºC – up to 2 days

b) at t 4ºC – up to 7 days

c) at t 6ºC – up to 3 days

Laboratory research methods for diagnosing HIV infection

a) complement fixation reaction

c) immunoblot

What does ELISA detect when testing for HIV?

a) antigen

b) antibodies

c) p24 antigen and total HIV antibodies 1,2

24. Preparations for parenteral nutrition are:

A). Gelatinol

b). Amino acid mixtures

V). Perftoran

G). Lactosol

25. Blood products with complex action are:

A ). Albumin solution and fresh frozen plasma

b). Protein and red blood cell mass

V). Cryoprecytpitate

G). Albumin and protein solution

26. Conditions and shelf life of red blood cells prepared with the preservative “CPDA-1”:

A). At a temperature of 4±2 °C, 21 days

b). At a temperature of 4±2 °C, 35 days

V). At a temperature of 4±2 °C, 42 days

G). At a temperature of 4±2 °C, 50 days

Conditions and shelf life of platelet concentrate

A). At a temperature of 4±2 °C, 2 hours if continuous stirring is not possible

b). At a temperature of 20±2 °C, 5 days with continuous stirring

V). At a temperature of 20±2.2 days if continuous stirring is impossible

G). At a temperature of 20±2.6 hours if continuous stirring is impossible

28. Blood components include:

A). Erythrocyte mass, fresh frozen plasma, immunoglobulins, antistaphylococcal human plasma

b). Erythrocyte suspension, albumin, platelet concentrate

V). Red blood cell mass, filtered, fresh frozen plasma, cryoprecipitate

G). Washed erythrocytes, thrombin, erythrocyte suspension thawed and washed

Conditions and shelf life of fresh frozen plasma

A). At a temperature of minus 18 °C, 3 years

b). At a temperature of minus 25 °C, 3 years

V). At a temperature of minus 30 °C, 5 years

G). At a temperature of minus 20 °C, 1 year

30. Quarantine of fresh frozen plasma is carried out:

A). For a period of no more than 180 days from the date of study at a temperature of minus 25 °C

b). For a period of at least 180 days from the moment of freezing at a temperature of minus 25 ° C

V). For a period of no more than 90 days from the moment of fractionation at a temperature of minus 30 °C

G). For a period of no more than 90 days from the moment of inactivation at a temperature of minus 30 ° C

31. After quarantine of fresh frozen plasma, the following is carried out:

A). Use for the production of blood components and preparations

b). Use for transfusion to recipients

V). Repeated examination of the donor’s health status and laboratory testing of his blood for blood-borne infections

G ). Repeated laboratory testing of donor blood for blood-borne infections and norms for the composition of biochemical parameters of peripheral blood

32. Regulatory documents regulating the quarantine method:

A). Order of the Ministry of Health of the Russian Federation No. 193 dated 05/07/2003

b). Order of the Ministry of Health of the Russian Federation No. 363 dated November 25, 2002.

V). Decree of the Government of the Russian Federation dated January 26, 2010. No. 29

G). SANPIN 2.1.7.2790-10

33. The main sections of transfusiology are:

A). General transfusiology, blood service organization, clinical transfusiology,

b). Blood service, transfusion immunology, clinical transfusiology, industrial transfusiology

V). Theoretical transfusiology, practical transfusiology

G). Industrial transfusiology, theoretical transfusiology, clinical transfusiology

34. The main tasks of the SEC are:

A). Acquisition, registration and medical examination of donors, procurement and storage of donor blood and its components, organization of donated blood testing, control over the organization of transfusion therapy in medical organizations

b). Procurement, processing, storage, transportation and ensuring the safety of donor blood and its components in order to meet the needs of medical organizations for blood components

V). Planning, recruitment and medical examination of donors, control of the process of plasma procurement using plasmapheresis, ensuring the safety of collected plasma at all stages of the production process

G). Organization of provision of medical departments with blood components for the provision of transfusion assistance, storage of blood components, participation in the investigation of post-transfusion reactions and complications

35. The staffing levels of blood service institutions should be determined in accordance with the order:

A). Ministry of Health of the USSR No. 155 (1990)

b). Ministry of Health of the Russian Federation No. 278n (2012)

V). Ministry of Health of the USSR No. 1055 (1985)

G). Ministry of Health of the Russian Federation No. 183n (2013)

36. Documents required for the effective organization of production of blood components:

A). External (laws, orders, instructions, etc.)

b). Standard Operating Procedures

V). Records (quality data)

G). All listed

37. Resources of the quality management system in a blood service institution:

a) - Occupational health and safety, information resources

b) - Personnel, donors, premises

c) – Equipment, production environment

d) - All of the above

Clinically significant antigens of the Rhesus system:

b. Rh(D), rhC, rhE

V. Rh(D), rhC, rhc, rhE, rhe

G . Rh(D), rhC, rhc, rhE, rhe, Kell

The ABO antigenic system includes:

A. Antigens A and B

b. Antigens A and B, antibodies α and β

V. Antigens A and antibodies α

G. Antibodies α and β

Before donation, blood donors are determined:

A . Blood type and hemoglobin content

b. ALT activity and blood group

V. Hemoglobin content, number of leukocytes, platelets, ESR

G. Blood type, hemoglobin content, anti-erythrocyte antibodies

Normal ALT activity is:

A. no more than 40 U/l

b. no more than 31 U/l

V. Men no more than 40 U/l, Women no more than 31 U/l

G. Men no more than 31 U/l, Women no more than 40 U/l

After plasma donation, plasma donors are examined for:

A. ALT activity, total protein content, blood group, Rhesus affiliation, anti-erythrocyte antibodies

b. ALT activity, total protein content, blood group, Rhesus affiliation, anti-erythrocyte antibodies, microprecipitation reaction to Lues

V. ALT activity, blood group, Rhesus affiliation, anti-erythrocyte antibodies, microprecipitation reaction to Lues

G. ALT activity, total protein content, protein fractions (after 5 plasma doses), blood group, Rhesus affiliation, anti-erythrocyte antibodies, microprecipitation reaction to Lues

Immunohematological studies of donor blood include:

A. – determination of blood group according to the ABO system

- definition of rhesus - belonging

- determination of the phenotype of erythrocyte antigens using the Rhesus and Kell systems

- screening of anti-erythrocyte antibodies

b.– determination of blood group

Definition of Rhesus - belonging

V.– determination of hemoglobin

Blood group determination

Definition of Rhesus - belonging

Equipment required to determine blood group according to the ABO system using the cross method:

A .

- 0.9% NaCl solution

- tablets

- pipettes

- stirring sticks

b.– Coliclones anti-A, anti-B, anti-AB

Standard red blood cells O(I), A(II), B(III)

0.9% NaCl solution

V.– Coliclones anti-A, anti-B, anti-AB

0.9% NaCl solution

Tablets

Pipettes

Stirring sticks

Hourglass at 3 and 5 minutes

G.– Coliclones anti-A, anti-B, anti-AB

Standard red blood cells O(I), A(II), B(III)

Tablets

Pipettes

Stirring sticks

Hourglass at 3 and 5 minutes

How long does it take to monitor the progress of the reaction when determining Rhesus status?

A. 3 minutes

b. 5 minutes

V. 2 minutes

Causes of errors when determining blood group:

A.– incorrect labeling of tubes

Incorrect order of applying reagents to the plate

Individual characteristics of blood

b . - incorrect labeling of tubes

- incorrect order of applying reagents to the tablet

- incorrect ratio of reagents and test blood

- reduction of reaction observation time

- temperature violation

- individual characteristics of the blood being tested

V.– presence of an anticoagulant in the blood being tested

Low ambient temperature

Use of capillary blood

The main document regulating the conduct of immunohematological studies of donor blood:

A. Decree of the Government of the Russian Federation of December 31, 2010 No. 1230 “On approval of the rules and methods of research and rules for the selection of donor blood samples necessary for the application and implementation of technical regulations on the safety requirements of blood, its products, blood replacement solutions and technical means used in transfusion and infusion therapy "

b . Order of the Ministry of Health of the Russian Federation dated January 09, 1998 No. 2 “On approval of instructions for immunoserology.”

V. Order of the Ministry of Health of the Russian Federation No. 364 of September 14, 2001. “On approval of the procedure for medical examination of blood donors and its components.”

First aid for frostbite

A. remove the impact of the damaging factor

b . apply an aseptic bandage and wrap the affected part of the body

V. Give a hot drink

d. administer anesthesia

d. immobilize injured limbs

i.e. all of the above

Principles of cardiopulmonary resuscitation

A. restoration of airway patency

b. emergency mechanical ventilation and oxygenation

V. Maintaining circulation

G . all of the above

Classification of burns by degree

b. 1,2,3a,3b,4

First aid for acute coronary syndrome

A . provide the patient with rest, give him an aspirin tablet to chew, 1-2 tablets of nitroglycerin under the tongue, heparin 10,000-15,000 units subcutaneously, call an ambulance.

b. call an ambulance and try to distract the sick person by talking, give a validol tablet

V. Invite the patient to walk to improve blood circulation.

Plasma, frozen no later than two hours after taking blood from donors, has the working name antihemophilic plasma, since it contains clotting factor VIII - antihemophilic globulin in higher concentrations than FFP obtained at a later date (there is no blood product under this name in OK KKChiK ). In clinical practice it can be replaced by cryoprecipitate.

SZP can be stored at a temperature of -30 °C for 12 months from the date of vein puncture, provided that the packaging is sealed. In accordance with Order No. 193 of the Ministry of Health of the Russian Federation dated 05/07/2003, quarantined fresh frozen plasma is allowed storage mode 24 months at temperatures below -30 °C. Then order N 170 of March 19, 2010 was issued, in which the storage period for plasma was extended up to 36 months and a temperature not lower than -25 °C.

Selection donor-recipient pairs produced according to the AB0 system. Plasma of group AB(FV) in emergency cases can be transfused to a patient with any blood group.
Directly before transfusion of FFP thaw at a temperature of +37-38 °C. In the absence of special equipment for defrosting FFP, you can use water baths (with strict control over the water temperature - overheating is not allowed). After thawing, plasma is allowed to be stored for a short time before transfusion (no more than 1 hour at +1-6). The content of fibrin flakes in thawed plasma does not prevent transfusion through standard plastic systems with filters. Re-freezing and use of thawed plasma is not permitted.

If canned blood has not been deleukocyted before separation into components, it is recommended to transfuse FFP through special filters that retain leukocytes.
Thawed FFP is usually administered intravenously. According to certain indications, in case of massive surgical bleeding - intraarterially. Plasma can be injected into the bone marrow, subcutaneously.

SZP used primarily to replenish coagulation factors. For replacement purposes, FFP is injected in large volumes, usually in combination with polyglucin.
FFP dosages depend on the clinical situation and course of the disease and can range from 250-300 ml to 1000 ml per day. Administration is by drip or jet, depending on the indications for use. For the treatment of most diseases, a standard dose of FFP is recommended - 15 ml/kg. In cases where FFP transfusions are combined with platelet concentrate transfusions, it should be taken into account that with every 5-6 doses of platelet concentrate the patient receives a volume of plasma equivalent to 1 dose of FFP.

For achievement hemodynamic effect the total dose of infused FFP should ensure a sustained increase in blood pressure above the critical level (90 mm Hg).
In order to dehydration in patients with signs of cerebral edema, pulmonary edema in the absence of albumin, administration of native plasma concentrate is indicated.

Indications for FFP transfusion are steadily expanding without sufficient reason. There are two main reasons contributing to this: high cost and the lack of sufficient quantity and assortment (at least for domestic clinics) of specific concentrates of coagulation factors that could replace FFP, and, very importantly, the current lack of unified recommendations and clear indications for FFP transfusions.

Application of FFP indicated for the following clinical conditions:
lack of a specific drug for the treatment of isolated deficiency of blood coagulation factors (II, V, VII, IX, X, XI and XIII) or inhibitors (antithrombin III, proteins C and S, C1-esterase);
acute DIC syndrome;
thrombotic thrombocytopenic purpura;
sepsis (including neonatal sepsis);
patients after open heart surgery;
extracorporeal circulation;

The need for urgent neutralization of an oral anticoagulant in cases of overdose (in the absence of appropriate antidotes or their ineffectiveness);
vitamin K deficiency (in newborns);
hemophilia A and B, accompanied by bleeding;
correction of blood volume in case of massive blood loss, external and internal bleeding;
burn disease - plasma volume replacement;
purulent-septic processes of various etiologies - replacement of plasma volume and as a detoxification agent;
cerebral edema - for the purpose of dehydration. Plasma should be used to replace plasma volume, as a detoxification agent and for the purpose of dehydration only in the absence of appropriate blood substitutes.

Pre- and post-transfusion assessment patient's coagulation state- the most important component of transfusiological tactics when using FFP. It should be carried out on the basis of a set of clinical and laboratory data.

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PLASMA

Plasma is the liquid part of the blood, devoid of cellular elements. Normal plasma volume is about 4% of total body weight (40-45 ml/kg). Plasma components maintain normal circulating blood volume and its fluid state. Plasma proteins determine its colloid-oncotic pressure and balance with hydrostatic pressure; They also maintain a balanced state of the blood coagulation and fibrinolysis systems. In addition, plasma ensures the balance of electrolytes and the acid-base balance of the blood.

In medical practice, fresh frozen plasma, native plasma, cryoprecipitate and plasma preparations are used: albumin, gamma globulins, blood coagulation factors, physiological anticoagulants (antithrombin III, protein C and S), components of the fibrinolytic system.

PLASMA FRESH FROZEN

Under fresh frozen plasma refers to plasma that, within 4-6 hours after blood exfusion, is separated from red blood cells by centrifugation or apheresis and placed in a low-temperature refrigerator, ensuring complete freezing to a temperature of -30°C in an hour. This mode of plasma procurement ensures its long-term (up to a year) storage. In fresh frozen plasma, labile (V and VIII) and stable (I, II, VII, IX) coagulation factors are preserved in an optimal ratio.

It is desirable that fresh frozen plasma meets the following standard quality criteria: protein amount not less than 60 g/l, hemoglobin amount less than 0.05 g/l, potassium level less than 5 mmol/l. Transaminase levels should be within normal limits. The results of tests for markers of syphilis, hepatitis B and C, and HIV are negative.

Fresh frozen plasma volume, obtained by centrifugation from one dose of blood, is 200-250 ml. When performing double donor plasmapheresis, the plasma yield can be 400-500 ml, while hardware plasmapheresis can be no more than 600 ml.

Xhurt at a temperature - 20°WITH. At this temperature, PSZ can be stored up to 1 year. During this time, labile factors of the hemostatic system remain in it. Immediately before transfusion, the PSZ is thawed in water at a temperature +37 - +38°WITH. Fibrin flakes may appear in thawed plasma, which does not prevent transfusion through standard plastic systems with filters. The appearance of significant turbidity and massive clots indicate poor quality plasma, and it cannot be transfused.

Thawed plasma can be stored prior to transfusion no more than 1 hour. Re-freezing it is unacceptable.

The transfused fresh frozen plasma must be of the same group as the recipient according to the AB 0 system. Compatibility according to the Rh system is not mandatory, since fresh frozen plasma is a cell-free medium, however, with volume transfusions of fresh frozen plasma (more than 1 liter), Rh compatibility is required. Compatibility for minor erythrocyte antigens is not required. When transfusing PSZ, a group compatibility test is not performed. (?)

In emergency cases, in the absence of single-group fresh frozen plasma, transfusion of group AB(IV) plasma is allowed to a recipient with any blood group.

Indications and contraindications for transfusion of fresh frozen plasma:

Acute disseminated intravascular coagulation (DIC), complicating the course of shocks of various origins (septic, hemorrhagic, hemolytic) or caused by other causes (amniotic fluid embolism, crash syndrome, severe injuries with crushing tissue, extensive surgical operations, especially on the lungs, blood vessels, brain brain, prostate), massive transfusion syndrome;

Acute massive blood loss (more than 30% of circulating blood volume) with the development of hemorrhagic shock and disseminated intravascular coagulation syndrome;

Liver diseases accompanied by a decrease in the production of plasma coagulation factors and, accordingly, their deficiency in the circulation (acute fulminant hepatitis, cirrhosis of the liver);

Overdose of indirect anticoagulants (dicoumarin and others);

When performing therapeutic plasmapheresis in patients with thrombotic thrombocytopenic purpura (Moschkowitz disease), severe poisoning, sepsis, acute disseminated intravascular coagulation syndrome;

Coagulopathies caused by a deficiency of plasma physiological anticoagulants.

For burn disease in all clinical phases;

With purulent-septic processes;

Not recommended transfuse fresh frozen plasma to replenish the volume of circulating blood (there are safer and more economical means for this) or for parenteral nutrition purposes. Caution should be exercised in prescribing fresh frozen plasma transfusions in persons with a significant transfusion history or in the presence of congestive heart failure.

Features of fresh frozen plasma transfusion. Transfusion of fresh frozen plasma is carried out through a standard blood transfusion system with a filter, depending on clinical indications - in a stream or drip; in acute DIC with severe hemorrhagic syndrome - in a stream. It is prohibited to transfuse fresh frozen plasma to several patients from the same container or bottle.

When transfusing fresh frozen plasma, it is necessary to perform a biological test (similar to transfusion of blood gas carriers). The first few minutes after the start of the infusion of fresh frozen plasma, when a small amount of the transfused volume has entered the recipient's circulation, are decisive for the occurrence of possible anaphylactic, allergic and other reactions. fresh frozen plasma native cryoprecipitate

Transfused volumeSZP depends on clinical indications. For bleeding associated with DIC syndrome administration of at least 1000 ml of fresh frozen plasma at a time under the control of hemodynamic parameters and central venous pressure is indicated. It is often necessary to re-administer the same volumes of fresh frozen plasma under dynamic monitoring of the coagulogram and clinical picture. In this condition, the administration of small amounts (300-400 ml) of plasma is ineffective.

In case of acute massive blood loss(more than 30% of the volume of circulating blood, for adults - more than 1500 ml), accompanied by the development of acute disseminated intravascular coagulation syndrome, the amount of transfused fresh frozen plasma should be at least 25-30% of the total volume of transfusion media prescribed to replenish blood loss, i.e. at least 800-1000 ml.

For chronic DIC syndrome, as a rule, they combine transfusion of fresh frozen plasma with the prescription of direct anticoagulants and antiplatelet agents (coagulological control is required, which is a criterion for the adequacy of the therapy). In this clinical situation, the volume of fresh frozen plasma transfused once is at least 600 ml.

For severe liver diseases accompanied by a sharp decrease in the level of plasma coagulation factors and the development of bleeding or the threat of bleeding during surgery, transfusion of fresh frozen plasma at the rate of 15 ml/kg body weight is indicated, followed, after 4-8 hours, by repeated transfusion of plasma in a smaller volume (5-10 ml /kg).

The possibility of long-term storage of fresh frozen plasma allows it to be accumulated from one donor in order to implement the “one donor - one recipient” principle, which allows to sharply reduce the antigenic load on the recipient.

Reactions during transfusion of fresh frozen plasma. The most serious risk when transfusing fresh frozen plasma is the possibility transmission of viral and bacterial infections. That is why today much attention is paid to methods of viral inactivation of fresh frozen plasma (plasma quarantine for 3-6 months, detergent treatment, etc.).

In addition, it is potentially possible immunological reactions associated with the presence of antibodies in the plasma of the donor and recipient. The most severe of them is anaphylactic shock, clinically manifested by chills, hypotension, bronchospasm, and chest pain. As a rule, such a reaction is caused by IgA deficiency in the recipient. In these cases, it is necessary to stop the plasma transfusion and administer adrenaline and prednisolone. If there is a vital need to continue therapy using fresh frozen plasma transfusion, it is possible to prescribe antihistamines and corticosteroids 1 hour before the start of the infusion and re-administer them during the transfusion.

Absolute contraindications to FFP transfusions:

* hypercoagulation;

* sensitization to parenteral administration of protein. It must be remembered that plasma is the main carrier of markers of infectious diseases.

Technology for obtaining and preparing plasma. Plasma can be collected using several methods:

· centrifugation of a dose of preserved blood and isolation of native plasma from it;

· plasmapheresis method - repeated taking of a dose of blood from one donor, centrifugation of it, isolation of plasma and return of red blood cells to the donor;

· method of automatic plasmapheresis - separation of plasma from a continuous flow of donor blood entering an automatic separator

Currently, blood service institutions can stock several types of plasma:

· native plasma - isolated from donor canned blood within the permissible storage period;

· fresh frozen plasma (FFP);

· factor VIII-depleted plasma (plasma remaining after cryoprecipitate is isolated);

· cell-depleted plasma (remaining after harvesting QDs and CLs from LTS).

From 500 ml. 250-300 ml of canned blood is obtained. native plasma. Containers containing red blood cells and plasma are aseptically separated, sealed and labeled. Plasma is sent: for processing into medicines; frozen or used for transfusion to patients.

Obtaining blood components using plasmacytopheresis methods by qualified, specially trained personnel is a safe procedure. The plasmapheresis operation consists of a number of stages: preparation of equipment, equipment and polymer double containers; taking blood from a donor into a polymer container; centrifuging a polymer container with blood; plasma separation; reinfusion of autologous red blood cells to the donor. After the donor returns his own red blood cells, the single plasmapheresis procedure is stopped. The collected plasma must be transferred to the clinic for transfusion within the first 3 hours after the end of plasmapheresis or no later than 4 hours, after which the plasma must be frozen.

Automatic hardware plasmapheresis is carried out by a plasma production system of a Gemanetic device, which is fully automated and computerized. She receives whole blood from a donor; mixes it with an anticoagulant, separates the plasma from the globular mass and returns the unused cellular elements to the donor.

The prepared plasma is collected in plastic containers. A larger amount is frozen, and some is sent for clinical use.

NATIVE PLASMA

Native plasma is obtained under sterile conditions from whole donor blood after centrifugation.

After separation of water from plasma, the concentration of total protein and plasma coagulation factors, in particular IX, increases significantly - such plasma is called plAzma native concentrated.

Concentrated native plasma (NCP) contains all the main components of freshly prepared plasma (except for the reduced content of factor VIII), but in a 2.5-4 times smaller volume (80 ± 20 ml). The concentration of total protein is higher than in native plasma and should be at least 10% (100 g/l). Possesses increased hemostatic and oncotic properties due to an increase in plasma proteins and coagulation factors (except factor VIII).

Indications for use. PNK is intended for the treatment of patients with severe deficiency of various procoagulants, hypo- and afibrinogenemia; as a dehydrating and detoxifying agent; for the treatment of diseases accompanied by protein deficiency, the development of edematous-ascitic and hemorrhagic syndromes.

Directions for use and doses. For bleeding caused by congenital or acquired deficiency of procoagulants, PNA is administered at a dose of 5-10 ml/kg per day until the bleeding stops completely.

In case of protein deficiency with the development of ascitic syndrome, it is possible to use the drug in a dose of 125-150 ml per day at intervals of 2-3 days, on average 5-6 transfusions per course.

Contraindications. PNC should not be used in severe renal impairment with anuria. After administration of the drug, allergic reactions may develop, which can be controlled by the administration of antihistamines.

Storage conditions. The drug is stored frozen. Shelf life - 3 months at a temperature of -30 °C.

CRYOPRECIPITATE

If cryoprecipitate is removed from plasma during fractionation, the remaining part of the plasma is the supernatant fraction of plasma (cryosupernatant), which has its own indications for use.

Last time cryoprecipitate, being a medicinal product obtained from donor blood, it is considered not so much as a transfusion medium for the treatment of patients with hemophilia A, von Willebrand disease, but as a starting material for further fractionation in order to obtain purified factor VIII concentrates.

For hemostasis, it is necessary to maintain factor VIII levels up to 50% during operations and up to 30% in the postoperative period. One unit of factor VIII corresponds to 1 ml of fresh frozen plasma. Cryoprecipitate obtained from one unit of blood must contain at least 100 units of factor VIII.

Requirement calculation in transfusion of cryoprecipitate is carried out as follows:

Body weight (kg) x 70 ml/kg = blood volume (ml).

Blood volume (ml) x (1.0 - hematocrit) = plasma volume (ml)

Plasma volume (ml) x (required factor VIII level - available factor VIII level) = required amount of factor VIII for transfusion (units).

Required amount of factor VIII (units): 100 units = number of doses of cryoprecipitate required for a single transfusion.

The half-life of transfused factor VIII in the recipient's circulation is 8–12 hours, so repeat transfusions of cryoprecipitate are usually necessary to maintain therapeutic levels.

In general, the amount of cryoprecipitate transfused depends on the severity of hemophilia A and the severity of bleeding. Hemophilia is regarded as severe when the level of factor VIII is less than 1%, moderate - when the level is in the range of 1-5%, mild - when the level is 6-30%.

The therapeutic effect of cryoprecipitate transfusions depends on the degree of distribution of the factor between the intravascular and extravascular spaces. On average, one fourth of the transfused factor VIII contained in the cryoprecipitate passes into the extravascular space during therapy.

The duration of therapy with cryoprecipitate transfusions depends on the severity and location of bleeding and the patient's clinical response. For major surgeries or dental extractions, it is necessary to maintain factor VIII levels of at least 30% for 10-14 days.

If, due to some circumstances, it is not possible to determine the level of factor VIII in the recipient, then the adequacy of therapy can be indirectly judged by the activated partial thromboplastin time. If it is within the normal range (30-40 s), then factor VIII is usually above 10%.

Another indication for the use of cryoprecipitate is hypofibrinogenemia, which is extremely rarely observed in isolation, more often as a sign of acute disseminated intravascular coagulation. One dose of cryoprecipitate contains, on average, 250 mg of fibrinogen. However, large doses of cryoprecipitate can cause hyperfibrinogenemia, which is fraught with thrombotic complications and increased sedimentation of erythrocytes.

Cryoprecipitate must be compatible according to the AB 0 system. The volume of each dose is small, but transfusion of many doses at once is fraught with volemic disturbances, which is especially important to consider in children who have a smaller blood volume than adults. Anaphylaxis, allergic reactions to plasma proteins, and volume overload may occur with cryoprecipitate transfusion. The transfusiologist must constantly remember the risk of their development and, if they appear, carry out appropriate therapy (stop transfusion, prescribe prednisolone, antihistamines, adrenaline).

PLASMA PREPARATIONS

Antihemophilic plasma- plasma from freshly citrated donor blood, obtained 30 minutes after its collection. Contains unchanged antihemophilic globulin and other easily inactivated blood clotting factors. Dried antihemophilic plasma can be stored at room temperature for a year.

Fibrinogen-specific plasma protein takes part in blood clotting. It is obtained from plasma (1 g from 1 liter of plasma). Used to stop bleeding caused by afibrinogenemia and fibrinolysis. Antihemophilic globulin - factor VIII concentrate (dry or cryoprecipitate); 20 ml of cryoprecipitate corresponds to 250 ml of antihemophilic plasma. Used for hemophilia (hemophilia A) as a hemostatic agent. Can be stored for 6 months at a temperature of -30°C.

Clotting factor concentrate (PPSB)- prothrombin, proconvertin, Stewart factor and antihemophilic factor B. Used for hemorrhagic diathesis caused by a lack of these factors.

Fibrinolysin- a plasma enzyme preparation with high thrombolytic activity. Before use, the dry powder is dissolved in an isotonic sodium chloride solution and administered intravenously in combination with heparin for several hours. Used for vascular thrombosis and embolism. Streptase, cabinase, streptodecase are more effective.

Protein- a protein preparation obtained from hemolyzed blood, containing 75-80% albumin and 20-25% globulins. The protein concentration in the preparation is about 4.5-6%. It has a hemodynamic and detoxification effect due to the rapid increase in blood volume, dilution and binding of toxins. Used for traumatic, hemorrhagic, dehydration and other types of shock, as well as sepsis, hypoproteinemia of various origins. Administered intravenously (from 250 to 1000 ml). It is stored for about 3 years at a temperature of 4 "C.

Albumen 5, 10, 20% is obtained by ethanol fractionation of donor plasma. Shelf life - 3 years at a temperature of 4-8 °C. It has a pronounced therapeutic effect in cases of shock, blood loss, hypoproteinemia, cerebral edema, hepatic-renal failure, etc. It quickly increases blood pressure. Administered by drip. A single dose of a 10% solution is about 100-300 ml.

IMMUNE PLASMA

The most in demand at present is PI of the following specificity: antistaphylococcal plasma, antipseudomonal plasma, antiprotean plasma. At the same time, using modern diagnostic kits, it is possible to obtain PIs of a different specificity (anti-escherichiosis, etc.).

The main stages of obtaining (production) of IP are:

* selection and recruitment of immune plasma donors;

* examination of donor blood samples for the presence of antibodies to opportunistic microorganisms and determination of their titer;

* documenting research results in the Laboratory Research Registration Book? and ?Donor card? ;

* selection of plasma samples containing antibacterial antibodies (ABA) in therapeutic titers and suitable for transfusion;

* applying markings to the labels of selected donor plasma samples that correspond to the established specificity of AAA with an indication of the titer;

* registration (documentation) of receiving IP in the “Register of the procurement of blood and its components”? and transfer for storage;

* release of IP suitable for transfusion.

To study natural AAA, labeled samples of donor serum are used, remaining after the completion of immunohematological studies, stored at a temperature of +2 °C ... +6 °C in the absence of signs of poor quality (infection, hemolysis, etc.). The timing of screening should not exceed 3 days after taking blood from donors. If long-term storage is necessary, donor serum can be frozen at -20°C and below in special sealed plastic tubes.

Antistaphylococcal human plasma and antipseudomonas human plasma. Transfusions ASP or ASGP are indicated for the treatment or prevention of purulent-septic complications caused by the corresponding bacterial agent (sepsis, wound infection, burn disease, abscess pneumonia, hemoblastosis, etc.).

Plasma administered intravenously daily or every other day - depending on the severity of the disease - 200-300 ml or 3-5 ml/kg body weight (at least 18 IU). Course: 3-5 times or more in accordance with the severity of the disease and therapeutic effect. Children of the period newborns, including premature infants, transfusion of antistaphylococcal plasma is carried out at the rate of 10 ml/kg body weight (at least 60 IU). For each type of plasma, the indications for transfusion will be different.

Antistaphylococcal hyperimmune plasma. Currently, anti-staphylococcal plasma is obtained at blood transfusion stations from donors immunized with staphylococcal toxoid. After immunization (1.0-1.0-2 ml) and the appearance of specific antibodies in the blood at a titer of 6.0-10 IU/l, donors undergo plasmapheresis. It should be emphasized that one of the conditions for obtaining immune plasma is the use of plasmapheresis.

When carrying out treatment with this immune drug, it is necessary to take into account that a significantly greater clinical effect is achieved not with its single administration, but with a course of treatment, which consists of 3-5 intravenous infusions of anti-staphylococcal hyperimmune plasma of 150-200 ml per day.

Sources

1. http://ksmu.org.ru/library/surgery/536.html.

2. http://arenmed.org/ob10006.php.

3. http://spbgspk.ru/index.php?option=com_content&view=article&id=178&Itemid=21.

4. Production and clinical use of immune plasma in military medical institutions. Guidelines.

5. http://www.medskop.ru/antistafilokokkovaya_plazma/.

6. http://meduniver.com/Medical/Xirurgia/1024.html.

7. http://www.vrachebnye-manipulyacii.ru/vm/18.html.

8. http://www.transfusion.ru/doc/3638.htm.

9. Instructions for the use of blood components (approved by order of the Ministry of Health of the Russian Federation dated November 25, 2002 N 363).

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Magazine issue: August 2012

O.V.Vozgoment
Department of Anesthesiology and Reanimatology, Perm State Medical Academy named after. acad. E.A. Wagner

The results of an expert assessment of the quality of medical care for 3 patients who, during treatment, experienced blood transfusion complications due to the administration of fresh frozen plasma, which led to an unfavorable outcome, are presented. Based on the clinical analysis, a conclusion was made about the allergic nature of these complications, and the possibility of their development as anaphylactic shock or acute lung injury was shown. The problems of preventing and treating such complications are discussed.
Key words: transfusion, fresh frozen plasma, complication, allergy, diagnosis, examination, prevention, treatment.

Fresh frozen plasma as a cause of severe allergic complications, according to medicine care quality expert survey
O.V.Vozgoment
Anesthesiology and Reanimatology Department, E.A.Vagner Perm State Medicine Academy

The article presents the expert survey of 3 cases, in which hemotransfusion complication followed by unfavorable outcome after fresh frozen plasma injections have developed. Clinical analysis shows an allergic origin of these complications, as well as their developing in anaphylactic shock or acute lung lesion way. Problems of such complications prevention and treatment are discussed.
Keywords: transfusion, fresh frozen plasma, complication, allergy, diagnostics, expert survey, prevention, treatment.

Fresh frozen plasma (FFP) transfusions are widely used in clinical practice, especially in critically ill patients. FFP serves as a source of missing coagulation factors that are released during blood loss and consumed during the rapid and significant formation of blood clots in other pathological conditions. Deficiency of platelets and plasma coagulation factors can lead to the development of disseminated intravascular coagulation (DIC), which is characterized by the consumption of coagulation factors, the occurrence of consumption coagulopathy and activation of fibrinolysis, the clinical manifestation of which is increased bleeding and hemorrhagic syndrome. Thus, conceptually, FFP transfusions are only indicated to replenish plasma coagulation factors, i.e. for the purpose of correcting hemostasis disorders. However, the use of FFP, like other components of donor blood, is associated with the risk of infectious complications, allergic reactions, immunosuppression, etc., some of which can be potentially life-threatening. This report presents the results of an examination of clinical cases associated with the development of severe allergic reactions to the infusion of FFP and erythromass.
Clinical case 1. Patient B., 18 years old, was delivered to the gynecological department of the city hospital by an ambulance team on December 16. V
9 hours 31 minutes with a diagnosis: ovarian apoplexy? uterine bleeding. Blood pressure – 140/90 mm Hg. Art. Heart rate –
120 beats/min. From the anamnesis: from 13.12. I'm bothered by a runny nose and cough. At the same time, heavy bleeding appeared (last menstruation at the end of November). Upon admission, the patient was in a moderate state, consciousness was clear, the skin was pale. Heart rate – 108 beats/min, blood pressure – 80/50 mmHg. Art. A diagnosis was made: Menstrual irregularities due to
ARVI? Posthemorrhagic anemia, severe.
In OAK from 16.12: Red blood cells – 1.42¥1012/l, Hb –
51 g/l, Ht – 12%, L – 15¥109/l, p/i – 7%, s/i – 67%, lymphocytes – 29%, monocytes – 6%, ESR – 13 mm/h, time coagulation – 6 min 45 s.
Conservative hemostatic therapy was started, 400.0 ml of 5% glucose solution was administered intravenously. Due to ongoing bleeding on 16.12. at 12 o'clock
The uterine cavity was curetted for 30 minutes under IV ketamine anesthesia. Oxytocin was introduced. The bleeding stopped. For replacement purposes, 250.0 ml of refortan and 400.0 ml of gelatinol were administered intravenously. At 13:00: moderate condition, heart rate – 106 beats/min, blood pressure – 110/60 mm Hg. Art., no discharge from the genital tract. After determining the blood group (Rh factor is doubtful), at 13:20 a transfusion of FFP A(II) gr., Rh(+) – 200.0 ml was started. Biological test is negative. The patient's Rh factor also turned out to be negative. At 14:00, towards the end of the transfusion of the first bottle of FFP, the patient experienced difficulty breathing and coughing. On auscultation, wheezing appeared in the lungs. At 2 p.m.
She was examined by a resuscitator for 35 minutes. The condition is extremely serious, consciousness is clear. Sharp cough, severe pallor of the skin with a jaundiced tint. Heart rate – 120 beats/min, blood pressure – 110/80 mm Hg, respiratory rate – 24/min. There are wet rales across all fields.
At 15:00 the patient was transferred to the intensive care unit. Preliminary diagnosis: PE? Air embolism? X-ray shows pulmonary edema. At 15:30 a blood transfusion of 300.0 er was started. mass A(II) gr., Rh(-). At 15:55, tracheal intubation was performed, transfer to mechanical ventilation with positive expiratory pressure, and alcohol inhalation. The condition is extremely serious. Pulmonary edema, which is classified as non-cardiogenic, progresses. Foamy sputum mixed with blood is released through the endotracheal tube. At 16.12: heart rate – from 116 to 145 beats/min, blood pressure – 100/60–140/80 mm Hg, Sa02 – from 50 to 99%, CVP – 210–120 mm H2O. Art. Diuresis – 3400 ml. Diagnosis. Hemorrhagic shock. Posthemorrhagic anemia. Pulmonary edema. RDSV?
Inotropes, morphine, diuretics, antibiotics were prescribed: cefazolin + gentamicin, glucocorticoids and (?!) massive infusion-transfusion therapy. Over 17 hours, 1770 ml of air was administered. mass, 1850 ml FFP. The total amount of fluid administered was 5340 ml.
17.12. at 6 o'clock: the condition is extremely serious. He is on a ventilator. The clinical picture of pulmonary edema is growing. 1500 ml (!) of fluid was released from the trachea. The R-gram shows negative dynamics. SaO2 – 56%. There is no consciousness. The volume of infusion therapy is reduced to 1100.0 ml. Changing antibiotics. Instead of gentamicin, abactal and metragil are prescribed. The administration of inotropes, vasodilators, and hormones continues. A counterman has been appointed. During 17.12. the condition is extremely serious. Unconscious. A large amount of mucous-viscous sputum is aspirated. Single moist rales. Heart rate – 96–124 beats/min, blood pressure – 90/60–140/80 mm Hg. Art. CVP – 140–210 mm water. Art. Sa02 – up to 85%. Daily diuresis – 2850 ml. In OAK there is a sharp neutrophil shift (p/i – 47%), leukocytosis – up to 18.8¥109/l. The R-gram (December 18) shows pulmonary edema in the resolution stage. Body temperature – 38–38.2°C. Tube feeding started. Positive neurological symptoms. Stable hemodynamics. The skin is pink. Biochemical blood test: hypoproteinemia, hypernatremia up to 223 mmol/l, hypokalemia. Subsequently, the condition stabilizes and hyperthermia persists. In OAK: Ht – 44–35%, leukocytosis – up to 16.1¥109/l, neutrophil shift – up to melocytes, lymphopenia progresses – up to 2%. In OAM – moderate proteinuria, hematuria, leukocyturia. Biochemical analysis showed hypoproteinemia. By 12/24. – normalization of sodium and potassium levels. The patient consults a therapist, pulmonologist, neurologist, and ophthalmologist.
21.12. The patient is conscious, breathing spontaneously through the endotracheal tube. Extubated. 22.12. due to increasing respiratory failure, she was again intubated and transferred to mechanical ventilation. 23.12. extubated again. 24.12. again an increase in respiratory failure and again intubation and transfer to mechanical ventilation. Pastyness of the lower extremities and swelling of the feet are noted, more so on the right. 28.12. due to grade 3–4 anemia. (OAK 27.12.: air – 3.6¥1012/l, Нb –
76 g/l, Ht – 29%) blood transfusion is performed
640.0 ml of single-group erythromass without reactions or complications. 29.12. purulent hemorrhagic sputum is released in large quantities. A tracheostomy was performed. Due to the diagnosed DIC syndrome, 550.0 ml of FFP was transfused. The condition is extremely serious. There are a large number of dry and moist rales in the lungs. Infusion therapy continues: 2100.0 ml intravenously and 600.0 ml via tube per day. Inotropic support with dopamine and adrenaline. 30.12. against the background of mechanical ventilation, circulatory arrest occurred. Resuscitation measures are ineffective.
Final diagnosis. Main: dysfunctional uterine bleeding.
Complication: severe posthemorrhagic anemia. Hypovolemic and anemic shock. Respiratory distress syndrome. Pulmonary edema. Bilateral pneumonia. DIC syndrome. Sepsis. Multiple organ failure. Associated: Chronic pyelonephritis. P/a main diagnosis: Dysfunctional uterine bleeding against the background of sclerocystic changes in the ovaries. Complications: Hemorrhagic shock. Severe posthemorrhagic anemia. Foci of damage in the myocardium of the left ventricle of the heart and the papillary muscles of the mitral valve with the development of minor necrosis and myocytolysis; severe degeneration of cardiomyocytes and minor hemorrhages. Membranogenic pulmonary edema grade 4. Acute purulent-obstructive tracheobronchitis, bronchiolitis with the development of acute 2-sided focal purulent-destructive bronchopneumonia. Sepsis. Septicopyemia. Metastatic kidney abscesses. DIC syndrome. Hemorrhages in the serous and mucous membranes, the adrenal medulla. Thrombosis of the right subclavian vein at the site of catheterization. Hemorrhagic erosions of the stomach. Swelling of internal organs. Dropsy of the serous cavities (pleural - 1000 ml, abdominal - 1500 ml, pericardial - 100 ml). Brain swelling. Parenchymal dystrophy and venous congestion of internal organs. Operations: 12/16/01 - curettage, uterine cavity, 12/29/tracheostomy. Associated: 1. Diffuse fibrocystic disease of the mammary glands with a predominance of fibrosis. 2. Cholesterosis of the gallbladder. 3. Atherosclerosis of the ascending aorta, stage of lipoidosis.
A comment. It is clear that the cause of death in this case was severe sepsis and multiple organ failure. But this is the final reason. Of course, hemorrhagic shock could also initiate the pathological process. But the patient did not experience any serious circulatory disorders upon admission to the gynecology department. The level of Hb and red blood cells is not an indicator of a state of shock, especially since the blood loss occurred within three days and the history indicates that the patient has had hyperpolymenorrhea for the last three years. In addition, the high central venous pressure and polyuria noted in the patient are not characteristic of hypovolemic shock. The condition worsened due to the infusion of 200 ml of FFP. The patient developed symptoms reminiscent of an allergic reaction (cough, difficulty breathing, pulmonary edema). It could have been anaphylactic shock. According to
P. Marino the most common anaphylactogens are drugs,
R-contrast agents and preparations of plasma and its proteins. Allergic reactions to donor plasma proteins occur in 1–3% of recipients. Moreover, in patients with immunoglobulin A deficiency, allergic reactions can occur without prior sensitization. But anaphylactic shock is primarily a circulatory disorder. Nothing about this was noted in the gynecologist’s note, except for disturbances in the respiratory system. The resuscitator's note, made after 35 minutes, shows satisfactory indicators of central hemodynamics and notes pronounced pallor of the skin, shortness of breath, as well as a sharp cough and moist rales in the lungs, which fits into the picture of anaphylactic shock according to the asphyxial variant, the possibility of which is in 20% patients are indicated by A.S. Lopatin. Perhaps this is precisely how the pathological process developed in our patient. A type of allergic reaction can also be acute lung injury, which is a fairly rare complication of blood transfusion. The pathogenesis of ARF is associated with the ability of anti-leukocyte antibodies from donor blood to interact with granulocytes of the recipient. The complexes enter the lungs, the released mediators of the inflammatory cascade damage the capillary wall, and pulmonary edema develops. The picture is reminiscent of the RDSV.
Unfortunately, the post-transfusion complication was not diagnosed. The diagnosis emphasizes the role of hemorrhagic shock and the patient is given ultra-vigorous intensive therapy: respiratory support, inotropes, peripheral vasodilators, hormones, diuretics, combination antibacterial therapy and excessive infusion-transfusion therapy. This is evidenced by CVP indicators, forced diuresis, and progressive pulmonary edema. 1.5 liters of fluid was released in 17 hours through the endotracheal tube(!). Polyuria, despite the limited infusion, persisted on the second day. Severe, dangerous dyselectrolythemia developed (Na - up to 240 mmol/l). Limiting the infusion and carrying out complex therapy, including adequate antibacterial therapy, led to some stabilization of the condition. But 21.12. the patient is prematurely transferred to spontaneous breathing and 22.12. Due to increasing respiratory failure, he is again transferred to mechanical ventilation. A similar precedent occurs on December 23–24. The patient has swelling. Hypoproteinemia in the blood. However, the volume of hydration is not corrected. Every day, starting from 19.12. more than three liters of fluid are introduced, which clearly exceeds the volume of fluid released. It lingers, aggravating hemodilution and overhydration. 28.12. in connection with grade 3–4 anemia, with blood levels generally acceptable for this condition, a blood transfusion of 640 ml of red blood cell mass is performed. Respiratory failure worsens. A tracheostomy is performed and 550 ml of FFP is infused. Again the picture of wet lungs and a fatal outcome.
Thus, in this case we are dealing with a severe post-transfusion complication that arose after the infusion of FFP against the background of severe posthemorrhagic anemia and respiratory viral infection, and not entirely adequate, although vigorous, intensive care.

Clinical case 2. Patient G., 24 years old, had a second pregnancy (the first 2 years ago ended in a miscarriage at 4 weeks). The pregnancy, which occurred against the background of grade I anemia, was complicated by placental insufficiency. At 23–24 weeks she suffered from pneumonia, was treated in the therapeutic department, at 33–34 weeks, 22.02. hospitalized in the pregnancy pathology department due to severe placental insufficiency (up to stage IV), chronic intrauterine hypoxia of the newborn to moderate severity. Appropriate examination and treatment were prescribed. 05.03. the woman left the department without permission and returned on 03/06. When examined at 1:15 p.m., pale skin and weakness were noted. The pregnant woman complained of deterioration in health, dizziness, and pain in the lower abdomen. As a result of the examination, antenatal fetal death due to total placental abruption and stage I hemorrhagic shock were diagnosed. According to emergency indications, a lower-median laparotomy was performed, a caesarean section in the lower segment according to Gusakov, followed by extirpation of the uterus with tubes (Kuveler's uterus), and drainage of the abdominal cavity. During the operation, for replacement purposes, the following was administered: infucol - 500 ml, saline. solution – 1200 ml and FFP – 850 ml. 08.03. due to severe anemia (er. - 2.5 × 1012/l, Hb - 68 g/l, Ht - 20%) a blood transfusion (erythromass) was performed in a volume of 213.0; 213.0 and 213 ml. According to the records in the medical documentation, before the blood transfusion, the patient’s blood type and Rh factor, as well as the erythromass in the hemacons, were determined, group and Rh compatibility tests were carried out, a biological test was carried out, and then post-transfusion observation was carried out in order to prevent post-transfusion complications.
08.03. clinical signs of post-transfusion complications appeared (yellowness of the sclera, hemoglobinemia, hemoglobinuria). ABO incompatibility is suspected. Therapy was prescribed to correct homeostasis during transfusion of incompatible blood - infusion therapy, including sodium bicarbonate 4% - 200 ml, stimulation of diuresis, glucocorticoids, etc. 9.03. the condition was classified as moderate. It worsened sharply during fractional plasmapheresis on March 9. at 10 p.m. Replacement of exfused blood was carried out by FFP. After the second blood draw and administration of FFP, difficulty breathing, acrocyanosis, bradycardia, and then tachycardia - up to 160 beats/min, and arterial hypertension appeared. Transferred to mechanical ventilation. Subsequently, the condition remained serious. The phenomena of renal and multiple organ failure increased. 11.03. Due to the negative dynamics of purification indicators for hemodialysis, it was decided to transport the patient to the regional hospital. The patient's condition was regarded as conditionally transportable. She was brought to the emergency department in terminal condition. The resuscitation measures taken were ineffective.
The diagnosis is clinical. Main: late postpartum period (5th day after the first urgent surgical birth). Total detachment of a normally located placenta, antenatal fetal asphyxia. Cuveler's uterus. Complication: hemorrhagic shock. Post-transfusion hemolytic complication. Multiple organ failure. Brain swelling. Coma. Operations and benefits: laparotomy, midline laparotomy. Caesarean section in the lower segment. Extirpation of the uterus with tubes. Drainage of the abdominal cavity (06.03.). Blood transfusion – 08.03. Plasmapheresis. Ventilation KPV – 08.03. Cardiopulmonary resuscitation. The diagnosis is forensic. Main: red blood cell transfusion (03/08–03/09). Complication: acute renal failure: glomerular anemia, necronephrosis. Bilateral hypostatic purulent pneumonia. Catarrhal laryngotracheobronchitis. Background: pregnancy II. First premature operative birth (35–
36 weeks). Fetoplacental insufficiency. Chronic intrauterine fetal hypoxia. Cervicitis. Hypertensive angiopathy. Community-acquired pneumonia on the left in segments 8, 9, 10 on the left and 5–8 on the right of moderate severity. Premature total abruption of a normally located placenta. Hemorrhagic shock. Intrauterine fetal death. Cuveler's uterus. Operation: laparotomy, midline laparotomy. Caesarean section in the lower segment. Extirpation of the uterus with tubes. Drainage of the abdominal cavity – 06.03. Blood transfusion – 08.03. Plasmapheresis. Ventilation KPV – 08.03. Cardiopulmonary resuscitation – 11.03.
A comment. Thus, the leading factor in thanatogenesis can be considered a hemolytic post-transfusion reaction, which served as a trigger for all subsequent complications leading to death. The mechanism of this post-transfusion reaction is not entirely clear. It is unlikely that this is the result of blood incompatibility for ABO or Rh factor, since all the necessary tests before blood transfusion, according to the documentation provided, were performed. At the same time, during a control check of the contents of the hemacons by the laboratory doctor and the head. The SPK revealed that the erythromass in one of the hemacons was hemolyzed and the blood group and Rh affiliation could not be determined. So, the nature of hemolysis in the patient is probably due to the administration of hemolyzed blood. If we exclude dishonesty in performing blood compatibility tests, which would necessarily have revealed initial hemolysis, then we can assume that hemolysis occurred after all compatibility tests were performed. The cause of hemolysis could be overheating of the erythromass before blood transfusion. The possibility of thermal hemolysis is indicated by Yu.L. Shevchenko, V.N. Shabalin and others. Hemolysis, however, was not accompanied by severe systemic disorders, and diuresis was maintained. A sharp deterioration in the patient's condition occurred during plasmapheresis. The clinical situation described was very reminiscent of an anaphylactic reaction, apparently to the protein of the transfused plasma. The patient received blood components from 10 donors over 3 days, so the likelihood of cross-anaphylaxis is very high. Subsequently, the condition remained serious, the patient was on mechanical ventilation, hyperthermia, hypoxemia (SaO2 - 86%), clinical signs of cerebral edema remained, and the R-gram showed interstitial pulmonary edema, that is, acute lung injury syndrome. Infusion therapy, inotropic support, stimulation of diuresis were carried out, and antibacterial drugs were prescribed - claforan and metrogil. The patient's diuresis was sufficient at 10.03. it amounted to 1440 ml. At the same time, the clearance rates increased, which forced the decision to transfer the patient to a regional hospital, which, unfortunately, turned out to be fatal.
In this case, it should be noted that the forensic medical diagnosis was formulated incorrectly. Transfusion of red blood cells is not a pathology. The diagnosis of community-acquired pneumonia in a patient who was hospitalized for 5 days and on mechanical ventilation for 2 days also raises doubts.
Clinical case 3. Patient U., 31 years old, was delivered to the obstetric department by an ambulance team on May 10. at 20:26 with a diagnosis: Pregnancy 40–41 weeks. Complicated obstetric history. Harbingers of childbirth. Chronic IUI. Vegetative-vascular dystonia, compensated. Large fruit. To prevent fetal hypoxia, Actovegin was administered intravenously. Oxytocin was administered to induce labor. At 16:25 a full-term boy was born with Apgar scores of 5–6. Immediately after birth, short-term chills and headache were noted, which resolved on their own. Blood loss was 200 ml (BP – 120/80 mm Hg,
Heart rate – 78 beats/min, respiratory rate – 18/min). Diagnosis: Childbirth
3 urgent giant fruit. OAA. Low water. Chronic IUI. Vegetovascular dystonia. ARVI. The umbilical cord is entwined around the fetal neck. 11.05. V
At 18:00 a simultaneous bleeding from the birth canal with a volume of 500 ml was recorded, the blood did not clot. The mother's condition is satisfactory. Blood pressure –120/70–130/70 mm Hg. Art. Heart rate – 88 beats/min. NPV – 18/min. Catheter diuresis – 200 ml. (urine is light). A manual examination of the uterine cavity was performed, and the remaining placental tissue was removed. The uterus has shrunk and moderate bleeding continues. 400.0 ml of saline was injected intravenously. solution, then 400.0 ml saline. solution +1.0 ml oxytocin, then 200.0 ml saline. solution + 10.0 ml tranexam and ceftriaxone. To stop bleeding, clamps are applied to the uterine vessels. The recorded blood loss was 1500 ml. At 18:40, transfusion of 1 liter of FFP was started, after which the bleeding stopped at 19:00. At 19:40 a control blood test was performed: er. –3.07¥1012/l, Нb – 86 g/l, Нt – 28%, Тg. – 160¥109/l. At 20:00 after transfusion of 150 ml of erythromass, the patient’s condition sharply worsened, weakness, headache, coughing, and a drop in A/D to 70/30 mm Hg were noted. Art. Moist rales are heard in the lungs. Diagnosis: Early postpartum period after the third birth with a giant fetus. Early postpartum hemorrhage grade 1–2. Early blood transfusion reaction to FFP transfusion. Blood transfusion shock. Amniotic fluid embolism? Alveolar pulmonary edema. Manual examination of the uterine cavity, isolation of remnants of placental tissue, additional placenta. At 20:15 she was examined by the resuscitator on duty. The patient is conscious, but lethargic. Complaints of weakness, difficulty breathing. Cyanosis of the nasolabial triangle. Tachypnea - up to 30 per minute, wheezing in the lungs on both sides. Blood pressure – 90/50 mm Hg. Art., tachycardia up to 100 beats/min. Dexamethasone - 16 mg, aminophylline - 240 mg and 1.0 adrenaline s.c. were administered intravenously. At 20:40, the postpartum woman was transferred to the ICU, against the background of oxygen insufflation through a nasal catheter, the patient’s condition continued to deteriorate: tachypnea - up to 40 beats/min, SaO2 - 70%. At 21:05 she was intubated and transferred to mechanical ventilation. After 1 hour 20 minutes, the patient’s condition showed negative dynamics: a critical decrease in blood pressure - up to 40/0 mm Hg. Art., progressive clinical picture of pulmonary edema (hard breathing, moist bilateral rales, copious serous sputum), diuresis after drug stimulation was 100 ml. 12.05. at 02:10 a.m. she was examined by a resuscitator from the air ambulance service. Diagnosis: Amniotic fluid embolism? Shock. Multiple organ dysfunction. Then, over the course of two days, against the background of the therapy, the patient’s condition continued to deteriorate: coma, constant hyperthermia (up to 41.2°C), tachycardia (up to 160–170 beats/min), clinical signs of acute respiratory distress syndrome (ARDS) were increasing. Clinic of multiple organ failure.
In the UAC: an increase in leukocytosis - from 11¥109/l (11.05) to 40.9¥109/l (14.05), p/i shift - from 8 to 34%. On 05/14/2011 at 06:25, cardiac arrest was recorded against the background of unstable hemodynamics, mechanical ventilation, and resuscitation measures were without effect. Biological death was declared.
Treatment measures included mechanical ventilation in the SIMV mode, corrective infusion therapy, then in the dehydration mode, inotropic support, antibacterial therapy, hormone therapy, diuretics, and morphine. The clinical diagnosis is final. Main: 3 urgent births, large fetus. Complication: Amniotic fluid embolism. Early blood transfusion reaction to fresh frozen plasma transfusion? Transfusion shock? Incipient fetal asphyxia. Early postpartum hemorrhage, grade 2. DIC syndrome. Alveolar pulmonary edema. Multiple organ dysfunction. Accompanying: VJO 2–3 tbsp. Chronic intrauterine infections without exacerbation.
The diagnosis is pathological. Main: Early postpartum hemorrhage after 3 term deliveries of a large fetus. DIC syndrome. Manual examination of the uterine cavity. Massage of the uterus on a fist. Application of clamps to the parametrium according to Baksheev, clamping of the abdominal aorta, transfusion of FFP. Labor enhancement with oxytocin. Anaphylactoid reaction. Complication: Shock of combined origin: shock lungs with the development of alveolar pulmonary edema, tubular necrosis in the kidneys, centrilobular necrosis of hepatocytes in the liver, severe cerebral edema, cerebral coma. Multiple organ failure. Associated: Interstitial fibroids of the uterus (subserous nodes in the fundus, submucous in the right corner of the uterus with a diameter of 3.5 cm, intramural on the side wall on the left and right with a diameter of up to 1 cm).



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