Fresh frozen plasma hemostatic effect pdf. Fresh frozen plasma as a cause of severe allergic complications, according to an expert assessment of the quality of medical care. Defrosting and storing thawed food
Fresh frozen plasma (FFP)
In medical practice, mainly two types of plasma are used for transfusions - native (isolated from a dose of canned blood or obtained by plasmapheresis) and more often - fresh frozen plasma. FFP contains the entire complex of labile and stable components of the coagulation system, fibrinolysis and complement system; proteins of various activities (including enzymes), fats, carbohydrates and salts. It consists of 90% water.
The recommendations of the British Committee for Standardization and the decisions of a number of consensus conferences on the use of FFP allowed Krenkel D (1990) to formulate reasonable, conditional and unconfirmed indications for the use of FFP in pediatric practice, which, according to some researchers, are also acceptable for adult patients.
Reasonable testimony:
Laboratory confirmed isolated deficiency of blood coagulation factors or inhibitors (AT-III, proteins C, S);
Overdose of oral anticoagulant;
Vitamin K deficiency;
Acute DIC syndrome;
Thrombotic thrombocytopenic purpura (TTP)
Sepsis
Together with red blood cells (“modified blood”) in patients after open heart surgery with extracorporeal circulation.
Conditional indications(only in the presence of bleeding and laboratory confirmed coagulopathy):
Massive transfusion (replacement);
Severe liver damage;
Cardiopulmonary surgery with extracorporeal circulation (for consumption coagulopathy).
In all other conditions, FFP transfusion is not justified. These include:
1. Correction of hypovolemia.
For the purpose of restoring blood volume, transfusion of FFP is not indicated. In reality, the volemic effect of plasma is very small and short-lived. It is inferior even to the volemic effect of albumin solution and is significantly lower volume of replacement colloidal effect plasma substitutes.
2. Protein parenteral nutrition for hypoproteinemic conditions.
The introduction of plasma, on the contrary, stimulates protein catabolism. For the purpose of nutritional support, it is necessary to use special preparations for parenteral or enteral nutrition, which are available on the modern market in sufficient quantities.
3. Stimulation of immunity. Human immunoglobulins have been developed for these purposes (with the exception of antistaphylococcal plasma, which includes the corresponding antibodies).
It's interesting that:
The effectiveness of FFP in patients with active bleeding and severe liver disease is uncertain. One dose of plasma for the treatment of an adult patient is homeopathic and inappropriate. If used, large volumes of FFP are apparently required, exceeding 5 doses.
AT-III replacement may be useful in severe disseminated intravascular coagulation associated with low AT-III levels, but there are no controlled studies to demonstrate its effectiveness.
The main coagulogram indicators, which allow a more or less objective assessment of the hemostatic system, and which we use in our clinic, include:
APTT (activated partial thromboplastin time). Its norm is 25-35 seconds. A prolonged APTT indicates a tendency toward hypocoagulation, which is observed with a deficiency of coagulation factors, as well as with excessive heparinization. A shortening of the aPTT indicates, accordingly, hypercoagulability blood from this patient.
PI (prothrombin index). Normal values for this indicator are 70-100% and its decrease is also a sign of a deficiency of coagulation factors or an overdose of indirect anticoagulants. It must be taken into account that the site of prothrombin synthesis is the liver, so its pathology can significantly affect this indicator.
Thawed plasma cannot be stored and should be used no later than 1-2 hours after thawing (24 hours according to other sources), in order to avoid loss of activity of coagulation factors.
It must be emphasized that when transfusing FFP, there is always a danger of transfusion transmission of infections and viruses, as well as allergic reactions, including anaphylaxis.
41. The transfused fresh frozen plasma of the donor must be of the same ABO group as that of the recipient. Diversity according to the Rh system is not taken into account. When transfusing large volumes of fresh frozen plasma (more than 1 liter), the matching of the donor and recipient for antigen D must be taken into account.
42. In emergency cases, in the absence of single-group fresh frozen plasma, transfusion of fresh frozen plasma of group AB(IV) to a recipient with any blood group is allowed.
43. Medical indications for prescribing transfusions of fresh frozen plasma are:
a) acute disseminated intravascular coagulation syndrome, complicating the course of shocks of various origins (septic, hemorrhagic, hemolytic) or caused by other causes (amniotic fluid embolism, crash syndrome, severe trauma with crushing tissue, extensive surgical operations, especially on the lungs, blood vessels, brain , prostate), massive transfusion syndrome;
b) acute massive blood loss (more than 30% of the circulating blood volume) with the development of hemorrhagic shock and disseminated intravascular coagulation syndrome;
c) 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);
d) overdose of indirect anticoagulants (dicoumarin and others);
e) therapeutic plasmapheresis in patients with thrombotic thrombocytopenic purpura (Moschkowitz disease), severe poisoning, sepsis, acute disseminated intravascular coagulation syndrome;
f) coagulopathy caused by a deficiency of plasma physiological anticoagulants.
44. Transfusion (transfusion) of fresh frozen plasma is performed by stream or drip. In acute DIC with severe hemorrhagic syndrome, transfusion (transfusion) of fresh frozen plasma is performed only as a stream. When transfusion (transfusion) of fresh frozen plasma, it is necessary to perform a biological test (similar to that carried out during transfusion (transfusion) of donor blood and erythrocyte-containing components).
45. For bleeding associated with DIC, at least 1000 ml of fresh frozen plasma is administered, while hemodynamic parameters and central venous pressure are monitored.
In case of acute massive blood loss (more than 30% of the circulating blood volume, 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 transfused blood and (or) its components, prescribed to replenish blood loss (at least 800-1000 ml).
In severe liver diseases, accompanied by a sharp decrease in the level of plasma coagulation factors and bleeding or bleeding during surgery, transfusion of fresh frozen plasma is carried out at the rate of 15 ml/kg of body weight of the recipient, followed (after 4-8 hours by repeated transfusion of fresh frozen plasma into smaller volume (5-10 ml/kg).
46. Immediately before transfusion (transfusion), fresh frozen plasma is thawed at a temperature of 37 C using specially designed thawing equipment.
47. Transfusion (transfusion) of fresh frozen plasma should begin within 1 hour after it is thawed and last no more than 4 hours. If there is no need to use thawed plasma, it is stored in refrigeration equipment at a temperature of 2-6 C for 24 hours.
48. To increase the safety of blood transfusions, reduce the risk of transferring viruses that cause infectious diseases, prevent the development of reactions and complications arising in connection with the transfusion (transfusion) of donor blood and (or) its components, use fresh frozen plasma, quarantined (or) fresh frozen plasma virus ( pathogen) inactivated.
8.2. Indications and contraindications for transfusion of fresh frozen plasma
Indications for prescribing fresh frozen plasma transfusions are:
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.
It is not recommended to transfuse fresh frozen plasma for the purpose of replenishing circulating blood volume (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.
8.3. 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.
The volume of fresh frozen plasma transfused depends on clinical indications. For bleeding associated with DIC, 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 circulating blood volume, 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. .e. at least 800 - 1000 ml.
In chronic disseminated intravascular coagulation syndrome, as a rule, a transfusion of fresh frozen plasma is combined with the prescription of direct anticoagulants and antiplatelet agents (coagulological monitoring 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.
In 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 of body weight is indicated, followed, after 4 - 8 hours, by repeated transfusion of plasma in a smaller volume ( 5 - 10 ml/kg).
Immediately before transfusion, fresh frozen plasma is thawed in a water bath at a temperature of 37°C. Thawed plasma may contain fibrin flakes, but this does not prevent its use with standard intravenous transfusion devices with a filter.
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.
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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 group 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
RecommendationIf 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 titres of anti-T plasma 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 as 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.
Links
American Association of Blood Banks (2002) In: Blood Transfusion Therapy: A Physician’s Handbook, 7th edn (ed. by D. J. Triulzi). American Association of Blood Banks, Bethesda, MD.Atance, R., Pereira, A. & Ramirez, B. (2001) Transfusing methylene blue – photoinactivated plasma instead of FFP is associated with an increased demand for plasma and cryoprecipitate. Transfusion, 41, 1548–1552.
Baglin, T. (1998) Management of warfarin (coumarin) overdose. Blood Review, 12, 91–98.
BCSH (1988) Guidelines for transfusion for massive blood loss. Clinical Laboratory Hematology, 10, 265–273.
BCSH (1990a) Guidelines on hospital blood bank documentations and procedures. Journal of Clinical Laboratory and Hematology, 12, 209–220.
BCSH (1990b) Guidelines on oral anticoagulation: second edition. Journal of Clinical Pathology, 43, 177–183.
BCSH (1992) Guidelines for the use of fresh frozen plasma. Transfusion Medicine, 2, 57–63.
BCSH (1994) Guidelines for administration of blood products, transfusion of infants and neonates. Transfusion Medicine, 4, 63–69.
BCSH (1998) Guidelines on oral anticoagulation: third edition. British Journal of Haematology, 101, 374–385.
BCSH (1999) Guidelines for administration of blood products, and management of transfused patients. Transfusion Medicine, 9, 227–238.
BCSH (2003) Guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anemias. British Journal of Haematology, 120, 556–573.
BCSH (2004) Guidelines on the transfusion of neonates and older children. British Journal of Haematology, 124, 433–453.
Bjerrum, O.S. & Jersild, C. (1971) Class specific anti-IgA associated with severe anaphylactic transfusion reactions in a patient with pernicious anemia. Vox Sanguinis, 21, 411–424.
Bull, B.S., Huse, W.M., Brauer, F.S. & Korpman, R.A. (1975) Heparin therapy during extracorporeal circulation: II. The use of a dose-response curve to individualize heparin and protamine dosage. Journal of Thoracic and Cardiovascular Surgery, 69, 686–689.
Carson, J.L., Poses, R.M., Spence, R.K. & Bonavita, G. (1988) Severity of anemia and operative mortality and morbidity. Lancet, 331, 727–729.
Ciavarella, D., Reed, R.L., Counts, R.B., Pavlin, E., Baron, L., Heimbach, D.M. & Carrico, J. (1987) Clotting factor levels and the risk of diffuse microvascular bleeding in the massively transfused patient. British Journal of Haematology, 67, 365–368.
Cohen, H. (1993) Avoiding the use of FFP. British Medical Journal, 307, 395–396.
College of American Pathologists Practice Guidelines Development Task Force (1994) Practice parameters for the usage of FFP, cryo and platelets. Journal of the American Medical Association, 271, 777–781.
Council of Europe (2004) Guide to the Preparation, Use and Quality Assurance of Blood Components, 10th edn. Council of Europe Publishing, Strasbourg.
De la Rubia, J., Arriaga, F., Linares, D., Larrea, L., Carpio, N., Marty, M.L. & Sanz, M.A. (2001) Role of methylene blue treated of fresh frozen plasma in the response to plasma exchange in patients with thrombotic thrombocytopic purpura. British Journal of Haematology, 114, 721–723.
Department of Health (1998) Vitamin K for New Born Babies. PL/CMO/98/3, PL/CMO/98/4. Department of Health, London.
Det Norske Veritas (1999) Assessment of the Risk of Exposure to vCJD Infectivity in Blood and Blood Products. A Report to Spongiform Encephalopathy Advisory Committee. Det Norske Veritas, London.
Dyer, C. (2003) Second vCJD patient to receive experimental treatment. British Medical Journal, 273, 886.
Eagleton, H., Benjamin, S. & Murphy, M.F. (2000) Audits of appropriate use of FFP. Bloods Matters, 4, 5–8.
Eder, A.F. & Manno, C.S. (2001) Does red cell activation matter? British Journal of Haematology, 114, 25–30.
vans, G., Llewelyn, C., Luddington, R., Baglin, T.P. & Williamson, L.M. (1999) Solvent/detergent fresh frozen plasma as primary treatment of acute thrombotic thrombocytopenic purpura. Clinical and Laboratory Hematology, 21, 119–123.
Food Standards Agency (2003) OTM Rule Review: Core Stakeholder Group Report. WWW document. URL: http://www.foodstandards.gov.uk.
Furlan, M., Robles, R., Galbusera, M., Remuzzi, G., Kyrle, P. A., Brenner, B., Krause, M., Scharrer, I., Aumann, V., Mittler, U., Solenthaler , M. & Lammle, B. (1998) Von Willebrand factor cleaving protease in thrombotic thrombocytopenic purpura and the haemolytic uraemic syndrome. New England Journal of Medicine, 339, 1578.
Garwood, M., Cardigan, R.A., Drummond, O., Hornsey, V., Turner, C.P., Young, D., Williamson, L.M. & Prowse, C.V. (2003) The effect of methylene blue photoinactivation and methylene blue removal on the quality of fresh-frozen plasma. Transfusion, 43, 1238–1247.
Goodnough, L.T. (1999) Transfusion Medicine 2nd of 2 parts. New England Journal of Medicine, 340, 525–533.
Green, G., Dymock, I.W., Poller, L. & Thomson, J.M. (1975) Use of factor VII-rich prothromin complex concentrate in liver disease. Lancet, 1, 1311–1314.
Harke, H. & Rahman, S. (1980) Haemostatic disorders in massive transfusion. Biblioteca Haematologica, 46, 179–188.
Harrison, C.N. Lawrie, A.S., Iqbal, A., Hunter, A. & Machin, S.J. (1996) Plasma exchange with solvent/detergent plasma of resistant thrombotic thrombocytopenic purpura. British Journal of Haematology, 94, 756–758.
Hellstern, P. & Haubelt, H. (2002) Indications for plasma in massive transfusion. Thrombosis Research, 107(Suppl. 1), S19–S22.
Hett, D.A., Walker, D., Pilkington, S.N. & Smith, D.C. (1995) Sonoclot analysis. British Journal of Anaesthesia, 75, 771–776.
Hewitt, P.E. & Machin, S.J. (1990) Massive blood transfusion. British Medical Journal, 300, 107–109.
Hiippala, S.T., Myllyla, G. & Vahtera, E.M. (1995) Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates. Anesthesia and Analgesia, 81, 360–365.
Hilton, D.A., Ghani, A.C., Conyers, L., Edwards, P., McCardle, L., Penney, M., Ritchie, D. & Ironside, J.W. (2002) Accumulation of prion protein in tonsil and appendix: review of tissue samples. British Medical Journal, 325, 633–634.
Horrow, J.C., Hlavecek, J., Strong, M.D., Collier, W., Brodsky, I., Goldman, S.M. & Goel, I.P. (1990) Prophylactic tranexamic acid decreases bleeding after cardiac operations. Journal of Thoracic and Cardiovascular Surgery, 99, 70–74.
Houston, F., Foster, J.D., Chong, A., Hunter, N. & Bostock, C.J. (2000) Transmission of BSE by blood transfusion in sheep. Lancet, 356, 999–1000.
Hunt, B.J. (1991) Modifying periperative blood loss. Blood Reviews, 5, 168–176.
Hunter, N., Foster, J., Chong, A., McCutcheon, S., Parnham, D., Eaton, S., MacKenzie, C. & Houston, F. (2002) Transmission of prion diseases by blood transfusion. Journal of General Virology, 83, 2897–2905.
Jain, N., Kirschbaum, N., Gaines, A., Coignard, B., Jarvis, W. & Silverman, T. (2003) Pulmonary embolism in liver transplant setting associated with the use of solvent detergent plasma. Journal of Thrombosis and Haemostasis, 1(Suppl. 1), abstract no. OC159.
Kopto, P.M. & Holland, P.V. (1999) Transfusion related acute lung injury. British Journal of Haematology, 105, 322–329.
Lakkis, N.M., George, S., Thomas, E., Ali, M., Guyer, K. & Carville, D. (2001) Use of ICHOR-platelet works to assess platelet function in patients treated with GP IIb/IIIa inhibitors . Catheterization and Cardiovascular Interventions, 53, 346–351.
Laupacis, A. & Fergusson, D. for the International Study of PeriOperative Transfusion (ISPOT) Investigators (1997) Drugs to minimize perioperative blood loss in cardiac surgery: meta-analyses using perioperative blood transfusion as the outcome. Anaesthesia and Analgesia, 85, 1258–1267.
Levi, M. & ten Cate, H. (1999) Disseminated intravascular coagulation. New England Journal of Medicine, 341, 586–592.
MacGregor, I., Hope, J., Barnard, G., Kirby, L., Drummond, O., Pepper, D., Hornsey, V., Barclay, R., Bessos, H., Turner, M. & Prowse, C. (1999) Application of a time-resolved fluoroimmunoassay for the analysis of normal prion protein in human blood and its components. Vox Sanguinis, 77, 88–96.
Machin, S.J. (1984) Thrombotic thrombocytopenia purpura. British Journal of Haematology, 56, 191–197.
Makris, M. & Watson, H.G. (2001) The management of coumarin induced over anticoagulation. British Journal of Haematology, 114, 271–280.
Makris, M., Greaves, M., Phillips, W.S., Kitchen, S., Rosendaal, F.R. & Preston, F.E. (1997) Emergency oral anticoagulant reversal: the relative efficacy of infusions of fresh frozen plasma and clotting factor concentrate on correction of the coagulopathy. Thrombosis and Haemostasis, 77, 477–480.
Male, C., Johnston, M., Sparling, C., Brooker, L., Andrew, M. & Massicotte, P. (1999) The influence of developmental haemostasis on the laboratory diagnosis and management of haemostatic disorders during infancy and childhood . Clinics in Laboratory Medicine, 19, 39–69.
Mannucci, P.M., Franchi, F. & Diaguardi, N. (1976) Correction of abnormal coagulation in chronic liver disease by combined use of fresh frozen plasma and prothrombin complex concentrates. Lancet, 2, 542–545.
Mannucci, P.M., Federici, A.B. & Sirchia, G. (1982) Haemostasis testing during massive blood replacement. A study of 127 cases. Vox Sanguinis, 42, 113–123.
Mansouri, A. & Lurie, A.A. (1993) Consise review: metaemoglobinaemia. American Journal of Haematology, 42, 7–12.
McClelland, D.B.L. (ed.) (2001) The Handbook of Transfusion Medicine, 3rd edn. HMSO, London. http://www.thestationeryoffice.co.uk/nbs/handbook2001/index.htm.
Mollison, P. L. (1972) Blood Transfusion in Clinical Medicine, 5th edn. Blackwell Scientific Publications, Oxford, p. 188.
Murphy, M.F. (1999) NV CJD, the risk of transmission by blood transfusion and potential benefit of leucocyte reduction of blood components. Transfusion Medicine Reviews, 13, 75–83.
Murphy, M.E. (2001) Febrile reactions and TRALI. In: Practical Transfusion Medicine (ed. by Murphy, M.F. & Pamphilon, D.H.), pp. 157–163. Blackwell Science, Oxford.
Northern Neonatal Nursing Initiative Trial Group (1996) Randomized trial of prophylactic early fresh-frozen plasma or gelatin or glucose in preterm babies: outcome at 2 years. Lancet, 348, 229–232.
O'Shaughnessy, D.F. (2000) Communication theory in the setting of blood transfusion in a DGH, MBA thesis. Oxford Brookes University.
Osborn, D.A., Lui, K., Pussell, P., Jana, A.K., Desai, A.S. & Cole, M. (1999) T and Tk antigen activation in necrotizing enterocolitis: manifestations, severity of illness and effectiveness of testing. Archives of Diseases in Childhood, Fetal and Neonatal Edition, 80, 192F–197F.
Palfi, M., Berg, S., Ernerudh, J. & Berlin, G. (2001) A randomized controlled trial of transfusion-related acute lung injury: is plasma from multiparous blood donors dangerous? Transfusion, 41, 317–322.
Pamphilon, D.H. (2000) Viral inactivation of FFP. British Journal of Haematology, 109, 680–693.
Peters, D.C. & Noble, S. (1998) Aprotinin: an update of its pharmacology of therapeutic use in open heart surgery and coronary artery bypass surgery. Drugs, 57, 233–260.
Pincock, S. (2004) Patient's death from vCJD may be linked to blood transfusion. Lancet, 363, 43.
Popovsky, M.A., Chaplin, Jr, H.C. & Moore, S.B. (1992) Transfusion related acute lung injury a neglected, serious complication of haemotherapy. Transfusion, 32, 589–592.
Rock, G., Shumak, K.H., Sutton, D.M.C., Buskard, N.A., Nair, R.C., Michelson, A.D. & Members of the Canadian Apheresis Group (1996) Cryosupernatant as repalcement fluid for plasma exchange in the thrombotic thrombocytopenic purpura. British Journal of Haematology, 39, 1227–1234.
Sandler, G.S., Mallory, D., Malamui, D. & Eckrich, R. (1995) IgA anaphylactic transfusion reactions. Transfusion Medicine Reviews, 9, 1–8.
Sazama, K. (1994) Bacteria in blood for transfusion: a review. Archives of Pathology Laboratory Medicine, 118, 350–365.
Serious Hazards of Transfusion (2001) Annual Report 1999–2000. ISBN 0 9532 789 3 X.
Serious Hazards of Transfusion (2002) Annual Report 2000–2001. ISBN 0 9532 789 4 8.
Serious Hazards of Transfusion (2003) Annual Report 2001–2002. ISBN 0 9532 789 5 6.
Shehata, N., Blajchman, M. & Heddle, N. (2001) Coagulation factors in FFP and cryosupernatant. Transfusion Medicine, 11, 391–401.
Shore-Lesserson, L., Manspeizer, H.E., DePerio, M., Francis, S., Vela-Cantos, F. & Ergin, M.A. (1999) Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. Anaesthesia and Analgesia, 88, 312–319.
Silliman, C.C., Boshkov, L.K., Mehdizadehkashi, Z. Elzi, D.J., Dickey, W.O., Podlosky, L. Clarke, G. & Ambruso, D.R. (2003) Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors. Blood, 101, 454–462.
Solheim, B.G. & Hellstern, P. (2003) Composition, efficacy, and safety of S/D-treated plasma (letter). Transfusion, 43, 1176–1178.
Solheim, B.G., Rollag, H., Svennevig, J., Arafa, O., Fosse, E. & Bergerud, U. (2000) Viral Safety of solvent/detergent treated plasma. Transfusion, 40, 84–90.
Stainsby, D. & Burrowes-King, V. (2001) A National Audit of the Use of Fresh Frozen Plasma. NBS. WWW document. URL: http://www.nbsweb/med/ca/pf/ffprep.pdf
Stainsby, D., MacLennan, S. & Hamilton, P.J. (2000) Commentary. Management of massive blood loss: a template guideline. British Journal of Anaesthesia, 85, 487–491.
Stanworth, S.J., Brunskill, S.J., Hyde, C.J., McClelland, D.B.L. & Murphy, M.F. (2004) Is FFP clinically effective? A systematic review of randomized controlled trials. British Journal of Haematology, in press.
Turner, M. L. & Ironside, J.W. (1998) New variant CJD: the risk of transmission via blood products. Blood Reviews, 12, 255–268.
United Kingdom Blood Transfusion Services/National Institute for Biological Standards and Control (2002) Guidelines for the Blood Transfusion Services in the United Kingdom, 6th edn. TSO. WWW document. URL: http://www.thestationeryoffice.com.nbs/rdbk2001/guidelines.htm and http://www.transfusionguidelines.org.uk.
United Kingdom Haemophilia Center Directors’ Organization (1997) Guidelines on therapeutic products to treat haemophilia and other hereditary coagulation disorders. Haemophilia, 3, 63–77.
United Kingdom Haemophilia Center Directors’ Organization (2003) Guidelines on the selection and use of therapeutic products to treat haemophilia and other hereditary bleeding disorders. Haemophilia, 9, 1–23.
Will, R.G., Ironside, J.W., Zeider, M., Cousens, S.N., Estiberio, K., Alperovitch, A., Poser, S., Pocchiari, M., Hofman, A. & Smith, P.G. (1996) A new variant of Creutzfeldt–Jakob disease in the UK. Lancet, 347, 921–925.
Williamson, L.M. (2001) Storage of blood components. In: Practical Transfusion Medicine (ed. by M.F. Murphy & D.H. Pamphilon), pp. 231–243. Blackwell Science, Oxford.
Williamson, L.M., Llewelyn, C.A., Fisher, N.F., Allain, J.-P., Bellamy, M.C., Baglin, T.P., Freeman, J., Klinck, J.K., Ala, F.A., Smith, N., Neuberger, J. & Wreghitt, T.G. (1999) A randomized trial of solvent/detergent and standard fresh frozen plasma in the coagulopathy of liver disease and liver transplantation. Transfusion, 39, 1227–1234.
Wuillemin, W.A., Gasser, K.M., Zeerleder, S.S. & Lammle, B. (2002) Evaluation of a platelet function analyzer (PFA 100) in patients with a bleeding tendency. Swiss Medical Weekly, 132, 443–448.
Yarranton, H., Cohen, H., Pavord, S.R., Benjamin, S., Hagger, D. & Machin, S.J. (2003) Venous thromboembolism associated with the management of acute thrombotic thrombocytopenic purpura. British Journal of Haematology, 121, 778–785.
Zeigler, Z.R., Shadduck, R.K., Gryn, J.F., Rintels, P.B., George, J.N., Besa, E.C., Bodensteiner, D., Silver, B., Kramer, B.E. & The North American TTP Group (2001) Cryoprecipitate poor plasma does not improve early response in primary adult thrombotic thrombocytopenic purpura. Journal of Clinical Apheresis, 16, 19–22. Zipursky, A. (1998) Prevention of vitamin K deficiency. Bleeding in newborns. British Journal of Haematology, 104, 430–437.
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 -
The procedure of blood transfusion (blood or plasma transfusion) cannot be taken carelessly. In order for the manipulation to bring the expected therapeutic benefit, it is important to correctly select the donor material and prepare the recipient.
The success of this manipulation depends on a number of irreplaceable factors. A significant role is played by the thoroughness of the preliminary assessment of indications for blood transfusion and the correct phasing of the operation. Despite the development of modern transfusiology, it is impossible to exclude with 100% probability the risk of such a consequence of blood plasma transfusion as death.
Briefly about the history of manipulation
In Moscow, since 1926, the National Medical Research Center of Hematology has been operating - the leading scientific center in Russia. It turns out that the first attempts at blood transfusion were recorded in the Middle Ages. The majority of them were not successful. The reason for this can be attributed to the almost complete lack of scientific knowledge in the field of transfusiology and the impossibility of establishing group and Rh affiliation.
Transfusion of blood plasma in the event of antigen incompatibility is doomed to the death of the recipient, so today doctors have abandoned the practice of administering whole blood in favor of implanting its individual components. This method is considered safer and more effective.
Risks for the recipient
Even though a blood transfusion is somewhat similar to administering saline or medication by drip, the procedure is more complex. Blood transfusion is a manipulation equivalent to the transplantation of biological living tissue. Implanted materials, including blood, contain many different cellular components that carry foreign antigens, proteins, and molecules. Ideally selected tissue will never be identical to the patient's tissue, so the risk of rejection is always present. And in this sense, responsibility for the consequences of blood plasma transfusion lies solely on the shoulders of a specialist.
Any intervention carries risks that do not depend on the qualifications of the doctor or on preliminary preparation for the procedure. At the same time, at any stage of plasma transfusion (sample or direct infusion), a superficial attitude of medical staff towards work, haste or lack of a sufficient level of qualifications is unacceptable. First of all, the doctor must make sure that this manipulation cannot be avoided. If there are indications for plasma transfusion, the doctor must be sure that all alternative methods of therapy have been exhausted.
Who is blood transfusion indicated for?
This manipulation has clear goals. In most cases, the infusion of donor material is due to the need to replenish lost blood during extensive bleeding. Also, blood transfusion may be the only way to increase platelet levels to improve coagulation parameters. Based on this, the indications for blood plasma transfusion are:
- deadly blood loss;
- state of shock;
- severe anemia;
- preparation for planned surgical intervention, presumably accompanied by significant blood loss and carried out using devices for artificial circulation (surgery on the heart, blood vessels).
These readings are absolute. In addition to these, sepsis, blood diseases, and chemical poisoning of the body can serve as a reason for blood transfusion.
Transfusion for children
There are no age restrictions for blood transfusion. If there is an objective need, manipulation can also be prescribed for a newborn. Blood plasma transfusion at an early age has similar indications. In addition, when choosing a treatment method, a decision in favor of blood transfusion is made in case of rapid progression of the disease. In children of the first year of life, blood transfusion may be caused by jaundice, an increase in the size of the liver or spleen, and an increase in the level of red blood cells.
The main argument in favor of this manipulation is considered to be the bilirubin indicator. For example, if in a newborn it exceeds 50 µmol/l (material for research is taken from the baby’s condition, they begin to closely monitor it, since this violation signals the need to administer donor blood in the near future. Doctors monitor not only bilirubin levels, but also the rate its accumulation.If it significantly exceeds the norm, the child is prescribed a blood transfusion.
Contraindications
Determining contraindications is an equally important step in the process of preparing for the procedure. According to the rules for blood plasma transfusion, the main obstacles to this manipulation include:
- heart failure;
- recent myocardial infarction;
- cardiac ischemia;
- congenital heart defects;
- bacterial endocarditis;
- hypertensive crisis;
- acute cerebrovascular accident;
- thromboembolic syndrome;
- pulmonary edema;
- glomerulonephritis at the acute stage;
- liver and kidney failure;
- tendency to allergies to many irritants;
- bronchial asthma.
In some cases, when transfusion is the only way to save the patient’s life, certain contraindications may be ignored. In this case, the tissues of the recipient and the donor must undergo many tests to confirm compatibility. Plasma transfusion should also be preceded by a comprehensive diagnosis.
Donor blood for allergy sufferers
For a person suffering from allergic reactions, different rules apply for plasma transfusion. Immediately before the manipulation, the patient must undergo a course of desensitizing therapy. To do this, Calcium Chloride is administered intravenously, as well as antihistamines Suprastin, Pipolfen, and hormonal drugs. To reduce the risk of an allergic reaction to foreign biomaterial, the recipient is injected with the minimum required amount of blood. Here the emphasis is not on quantitative, but on its qualitative indicators. Only those components that the patient lacks are left in the plasma for transfusion. In this case, the volume of fluid is replenished with blood substitutes.
Biomaterial for transfusion
The following liquids can be used for transfusion:
- whole donor blood, which is used extremely rarely;
- red blood cell mass containing a tiny amount of leukocytes and platelets;
- platelet mass, which can be stored for no more than three days;
- fresh frozen plasma (transfusion is used in case of complicated staphylococcal, tetanus infections, burns);
- components to improve coagulation parameters.
The introduction of whole blood is often impractical due to the high consumption of biomaterial and the high risk of rejection. In addition, the patient, as a rule, needs specifically missing components; there is no point in “loading” him with additional foreign cells. Whole blood is transfused mainly during open-heart surgery, as well as in emergency cases of life-threatening blood loss. The introduction of the transfusion medium can be carried out in several ways:
- Intravenous replenishment of missing blood components.
- Exchange transfusion - part of the recipient's blood is replaced with donor fluid tissue. This method is relevant for intoxication, diseases accompanied by hemolysis, acute renal failure. The most common transfusion is fresh frozen plasma.
- Autohemotransfusion. This involves infusing the patient's own blood. This liquid is collected during bleeding, after which the material is cleaned and preserved. This type of blood transfusion is relevant for patients with a rare group in which difficulties arise in finding a donor.
About compatibility
Transfusion of plasma or whole blood involves the use of materials of the same group that match the Rh group. But, as you know, every rule has an exception. If there is no suitable donor tissue, in an emergency situation, patients with group IV are allowed to receive blood (plasma) of any group. In this case, it is important to observe only the compatibility of Rh factors. Another interesting feature concerns group I blood: for patients who need to replenish the volume of red blood cells, 0.5 liters of this liquid tissue can replace 1 liter of washed red blood cells.
Before starting the procedure, personnel must ensure the suitability of the transfusion medium, check the expiration date of the material, its storage conditions, and the tightness of the container. It is also important to evaluate the appearance of the blood (plasma). If the liquid contains flakes, strange impurities, convolutions, or a film on the surface, it should not be administered to the recipient. Before performing the actual manipulation, the specialist must once again clarify the blood group and Rh factor of the donor and the patient.
Preparing for a transfusion
The procedure begins with formalities. First of all, the patient must familiarize himself with the likely risks of this manipulation and sign all the necessary documents.
The next stage is to conduct an initial study of blood group and Rh factor according to the ABO system using zoliclones. The information received is recorded in a special registration journal of the medical institution. Then the removed tissue sample is sent to the laboratory to clarify blood phenotypes by antigens. The results of the study are indicated on the title page of the medical history. For patients with a history of complications from transfusion of plasma or other blood components, as well as pregnant women and newborns, the transfusion medium is selected individually in the laboratory.
On the day of the procedure, blood is taken from a vein (10 ml) from the recipient. Half is placed in a tube with an anticoagulant, and the rest is sent to a container for a series of tests and biological samples. When transfusion of plasma or any other blood components, in addition to testing according to the ABO system, the material is tested for individual compatibility using one of the methods:
- conglutination with polyglucin;
- conglutination with gelatin;
- indirect Coombs reaction;
- reactions on planes at room temperature.
These are the main types of tests that are carried out during the transfusion of plasma, whole blood or its individual components. Other tests are prescribed to the patient at the discretion of the doctor.
In the morning, both participants in the procedure should not eat anything. Blood and plasma transfusions are performed in the first half of the day. The recipient is advised to cleanse the bladder and bowels.
How does the procedure work?
The operation itself is not a complex intervention requiring serious technical equipment. For exchange blood transfusion, the subcutaneous vessels on the arms are punctured. If there is a long transfusion ahead, large arteries are used - the jugular or subclavian.
Before starting a direct blood infusion, the doctor should not have the slightest doubt about the quality and suitability of the components being introduced. A detailed inspection of the container, its tightness, and the correctness of the accompanying documents must be carried out.
The first step in blood plasma transfusion is a single injection of 10 ml of transfusion medium. The liquid is introduced into the recipient’s bloodstream slowly, at an optimal speed of 40-60 drops per minute. After infusion of a test 10 ml of donor blood, the patient’s condition is observed for 5-10 minutes. repeat twice.
Dangerous signs that indicate incompatibility of donor and recipient biomaterials are sudden shortness of breath, increased heart rate, severe redness of the facial skin, decreased blood pressure, and suffocation. If such symptoms appear, the manipulation is stopped and the patient is immediately provided with the necessary medical assistance.
If no negative changes have occurred, proceed to the main part of the blood transfusion. Simultaneously with the intake of blood components into the human body, it is necessary to monitor his body temperature, carry out dynamic cardiorespiratory monitoring, and control diuresis. The rate of administration of blood or its individual components depends on the indications. In principle, jet and drip administration is allowed at a rate of about 60 drops every minute.
During a blood transfusion, the needle may become blocked by a blood clot. In this case, you cannot push the clot into the vein. The procedure is suspended, the thrombosed needle is removed from the blood vessel and replaced with a new one, which is already inserted into another vein and the supply of liquid tissue is restored.
After transfusion
When all the required amount of donor blood has entered the patient’s body, a little blood (plasma) is left in the container and stored for two to three days in the refrigerator. This is necessary in case the patient suddenly develops post-transfusion complications. The drug will help identify their cause.
Basic information about the manipulation is recorded in the medical history. The documents indicate the volume of injected blood (its components), composition, results of preliminary tests, the exact time of manipulation, and a description of the patient’s well-being.
After the procedure, the patient should not get up immediately. You will have to spend the next few hours lying down. During this time, medical staff must carefully monitor heartbeat and temperature readings. A day after the infusion, the recipient undergoes urine and blood tests.
The slightest deviation in well-being may indicate unforeseen negative reactions of the body, rejection of donor tissue. If the heart rate increases, there is a sharp decrease in blood pressure and pain in the chest, the patient is transferred to the intensive care unit or intensive care unit. If over the next four hours after the transfusion of plasma or other blood components, the recipient’s body temperature does not increase, and the blood pressure and pulse are within normal limits, we can speak of a successful manipulation.
What complications can there be?
If the correct algorithm and rules for blood transfusion are followed, the procedure is absolutely safe for humans. The slightest mistake can cost a person's life. For example, when air enters through the lumen of blood vessels, embolism or thrombosis may develop, which are manifested by breathing problems, cyanosis of the skin, and a sharp drop in blood pressure. Such conditions require emergency resuscitation measures, as they are fatal to the patient.
Post-transfusion complications, as mentioned above, are extremely rarely life-threatening and often represent an allergic reaction to components of the donor tissue. Antihistamines help cope with these.
A more dangerous complication, which has fatal consequences, is incompatibility of blood group and Rh, which results in the destruction of red blood cells, multiple organ failure and death of the patient.
Bacterial or viral infection during the procedure is a relatively rare complication, but its likelihood cannot be completely excluded. If the transfusion medium was not stored under quarantine conditions, and all sterility rules were not observed during its preparation, there is still a minimal risk of contracting hepatitis or HIV.