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Home , Blood product, Cryosupernatant, Fresh frozen plasma, Volume expander, Whole blood

Michelle P. Wong, MD, Nadejda Droubatchevskaia, MD, Kate M. Chipperfield, MD, FRCPC, Louis D. Wadsworth, MB, ChB, FRCPC, FRCPath, David J. Ferguson, MD, FRCPC

Guidelines for frozen plasma transfusion

A new document from the Advisory Group of BC describes appropriate use of frozen plasma, fresh-frozen plasma, and .

ABSTRACT: Guidelines based on a he Transfusion Medicine veloped by the British Committee for systematic literature review have Advisory Group (TMAG) Standards in Haematology (BCSH)1 been developed by the Transfusion of BC has prepared guide- and the systematic review by Stan- Medicine Advisory Group of BC to Tlines to assist physicians in worth and colleagues.2 The grading of provide physicians with evidence- their clinical decision-making regard- evidence and strength of recommen- based indications for transfusion of ing the appropriate use of frozen plas- dations were based on those devel- frozen plasma. Practices outlined in ma products in adults and neonates. oped by the US Agency for Health- these guidelines are preferred to These guidelines are available elec- care Research and Quality (formerly practices for product use tronically on the British Columbia the US Agency for Health Care Policy based on anecdotal reports or per- Provincial Coordinating Office web and Research) (seeAppendix A ) and sonal experience, which may lead to site (www.bloodlink.bc.ca) and will those referenced in the BCSH guide- unjustified exposure of patients to be updated periodically. Prescribing lines for the use of fresh-frozen plasma, biological products as well as to physicians are responsible for refer- , and cryosupernatant.1 overuse of scarce resources. The ring to the most recent guidelines, recommendations in the guidelines which are intended to guide therapy Dr Wong is a hematopathology resident in prepared by the Transfusion Medi- but are not intended to replace the clin- the Department of Pathology and Labora- cine Advisory Group were graded ical judgment of the attending physi- tory Medicine at the University of British according to the US Agency for Health- cian and appropriate consultation with Columbia. Dr Droubatchevskaia is a hema- care Research and Quality (formerly an expert in transfusion medicine. topathology resident in the Department of the US Agency for Health Care Poli- Pathology and Laboratory Medicine at cy and Research). At present, trans- How the guidelines were UBC. Dr Chipperfield is regional medical fusion of frozen plasma is indicated developed leader, Medicine, Van- for correction of known factor defi- Acomprehensive literature search was couver Coastal Health, and a clinical assis- ciencies for which no factor-specif- undertaken on PubMed using combi- tant professor in the Department of Pathol- ic concentrate is available, multiple- nations of keywords, including the ogy and Laboratory Medicine at UBC. Dr factor deficiencies associated with following: plasma, fresh-frozen plas- Wadsworth is a hematopathologist at Chil- severe and/or disseminated ma, guidelines, transfusion, trial, ran- dren’s and Women’s Health Centre of BC, a intravascular coagulopathy, urgent domized, liver, cardiac surgery, surgi- clinical professor in the Department of reversal of effect, and for cal bleeding, thawing, storage, massive Pathology and Laboratory Medicine at UBC massive transfusion to maintain INR transfusion, thrombotic thrombocy- and is chair of the Transfusion Medicine and PTT at less than 1.5 times the topenic purpura (TTP), disseminated Advisory Group of BC. Dr Ferguson is the reference range. Frozen plasma is intravascular coagulopathy (DIC), and medical director of BC Biomedical Labora- not indicated for a number of clinical neonate. Particular attention was paid tories Ltd., and an assistant clinical profes- situations, including , to the recently published guidelines sor in the Department of Pathology and wound healing, and treatment of im- for the use of fresh-frozen plasma, cry- Laboratory Medicine at UBC. munodeficiency states. oprecipitate, and cryosupernatant de-

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Table. Characteristics of four frozen plasma products.

Frozen plasma Fresh-frozen plasma Cryoprecipitate plasma Cryosupernatant plasma (from collection) (from collection) (cryo) (cryo-poor plasma)

Whole blood is centrifuged at Whole blood is processed Plasma is frozen for 24 hours, Plasma is frozen for 24 hours, high speed, allowing separa- through a cell separator to and then thawed at 1°– 6°C and then thawed at 1°– 6°C tion of plasma, red blood cells obtain plasma. Plasma is until insoluble precip- until insoluble proteins precip- (RBCs), and the buffy coat frozen within 8 hours of col- itate. The pack is centrifuged itate. The pack is centrifuged layer (, white blood lection and is designated as to obtain the cryoprecipitate. to obtain the supernatant. cells, some RBCs and plasma). fresh-frozen plasma (FFP). In The cryoprecipitate is then The supernatant, or cryo-poor Plasma is frozen within 24 general, 1 unit of FFP from refrozen for storage. plasma, is then refrozen for hours of collection and is des- apheresis collection is equiva- storage. ignated as frozen plasma (FP). lent to approximately 2 units Once thawed, the product It is prepared for use by thaw- of FP from whole blood collec- should be transfused immedi- Once thawed, the product Preparation ing at 37°C, a process that can tion. The two products can be ately, with completion of should be transfused immedi- take up to 30 minutes. used interchangeably. transfusion within 4 hours of ately, with completion of issuing product. transfusion within 4 hours of Once thawed, the product Once thawed, the product issuing product. should be transfused immedi- should be transfused immedi- ately, with completion of ately, with completion of transfusion within 4 hours of transfusion within 4 hours of issuing product. issuing product.

Contains all of the Contains all of the coagulation Contains FVIII:C, von Is deficient in high molecular factors, including the labile factors, including the labile Willebrand factor (vWF), fib- weight vWF multimers and factors (FV and FVIII:C). For factors (FV and FVIII:C). rinogen, FXIII, and fibronectin. FVIII:C. product prepared within 24 Cryoprecipitate has the fol- hours of collection, FVIII:C lev- lowing factor activities: els are less than those found 91 IU of FVIII: C per bag, in fresh-frozen plasma pre- 113 IU of vWF per bag, and Factors pared within 8 hours of collec- 150 mg of per bag. tion, but levels are still at or above 0.50 IU/mL. FP can be used for coagulation factor replacement except for isolat- ed or severe FVIII deficiency.

Each bag = 1 unit Each bag = 1 unit Each bag = 1 unit (5–15 mL) Each bag = 1 unit (>100 mL) Volume (200 – 250 mL) (100 – 600 mL)

Typical adult dose of plasma is Typical adult dose of plasma is Typical adult dose of cryo is Typically 1.0–1.5 times plasma 10–15 mL/kg body weight. 10–15 mL/kg body weight. 1 unit/5 kg body weight, up to volume exchange is a total dose of 10 units (bags). performed per plasma The pediatric dose of plasma The pediatric dose of plasma exchange (PLEX) run. is 10–15 mL/kg body weight. is 10–15 mL/kg body weight. The pediatric dose is 1 unit/5–10 kg body weight or Indicated as replacement fluid Infusion rate is over 2–3 Infusion rate is over 2–3 5–10 mL/kg. in PLEX for thrombotic throm- Dose hours, or as required. hours, or as required. bocytopenic purpura. Will raise fibrinogen by Will raise factor levels by Will raise factor levels by 0.5 g/L, assuming there is no 25%, assuming there is no 25%, assuming there is no ongoing consumption/loss of ongoing consumption/loss of ongoing consumption/loss of fibrinogen. factors. factors.

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The resulting guidelines were peer- lished and the underlying condition • The typical adult dose of plasma is reviewed by hematopathologists and should be treated, even if frozen plas- 10 mL to 15 mL per kilogram of clinicians, including hematologists ma must be given immediately. body weight. Each unit, or bag, con- and critical care physicians, and were • Once the cause of coagulopathy has tains approximately 100 mL to 600 subsequently approved by the Trans- been established, the transfusion of mL of anticoagulated plasma. It is fusion Medicine Advisory Group (see plasma should not be based solely therefore strongly recommended Appendix B ). on the patient’s abnormal INR and/ that plasma be ordered by required or PTT. Only a subset of patients with volume rather than number of units. General considerations abnormal coagulation test results will The volume of plasma administered Although most plasma products are demonstrate clinical bleeding. The should be sufficient to improve prepared from whole blood, a small decision to transfuse should be based hemostasis. proportion are prepared with plasma on the patient’s clinical condition • Prothrombin complex concentrate collected by apheresis. Physicians and, more specifically, the risk and (Prothromplex/Bebulin) containing contemplating the use of a frozen plas- consequences of bleeding. FII, FVII, FIX, and FX, is only avail- ma product (seeTable ), should keep • Before transfusing a frozen plasma able through the Canadian Blood in mind the following general consid- product, a clinician should be aware Services (CBS) Special Access Pro- erations: that: gram of Health Canada. There may • In British Columbia, informed con- - Satisfactory hemostasis may be be a role for its use in patients with sent is required prior to the transfu- achieved when coagulation fac- the effects of excessive warfarin1,6 sion of frozen plasma. tor levels are at least 20% to 30% and for reversal of anticoagulation • All routine coagulation parameters of normal, and when the fibrino- in patients who have had an intrac- should be checked before a product gen level is above 1 g/L.3 erebral hemorrhage.7 However, avail- is ordered. This includes complete - The of coagulation ability of this product is limited. To blood count (CBC), count, factors after plasma exchange seek approval for the product, please international normalized ratio (INR), (PLEX) of 1 blood volume is ap- contact your local Transfusion Med- partial thromboplastin time (PTT), proximately 30% of normal levels.4 icine Laboratory Service. and fibrinogen. - There is no direct relationship • Ideally, transfused plasma should be • The Transfusion Medicine Labora- between bleeding and abnormal the same ABO group as the patient. tory Service should be made aware results of coagulation tests. How- If this is not possible, then the local of the clinical diagnosis on the re- ever, bleeding more often occurs Transfusion Medicine Laboratory quest form used to order frozen plas- in patients when the INR or the Service will issue compatible plas- ma. The reason for the transfusion PTT is greater than 1.5 times the ma of a different group according to should also be clearly and accurate- upper limit of the reference policies of acceptable transfusion ly recorded in the patient’s chart. range.5 substitutions. With respect to Rh • Frozen plasma should be given only • Patients who have received plasma blood group compatibility, plasma after risks associated with transfu- should have their clinical status and that is derived from either Rh-posi- sion of allogeneic blood products coagulation tests monitored to as- tive or Rh-negative donors may be have been considered and only when sess response to treatment and to transfused to any recipient irrespec- the benefits outweigh the risks. guide assessment of ongoing trans- tive of their Rh status. There is a • Most laboratories in British Colum- fusion needs. small risk of Rh immunization for bia convert the prothrombin time (PT) • Prophylactic transfusions should not Rh-negative patients receiving Rh- to the international normalized ratio be given in the absence of clinically positive plasma because of potential to facilitate comparison of results abnormal bleeding. However, trans- small amounts of intact red cells between laboratories. (Throughout fusion of blood components may be or red cell stromal contamination. the document, we have tried to use indicated for patients with severely However, this risk is very low, which the INR where possible, as this is abnormal INR and/or PTT results or means that no Rh immunoglobulin typically what is reported by British platelet counts prior to a planned is required if an Rh-negative patient Columbia laboratories.) invasive bedside procedure, or when receives Rh-positive plasma.1 • If possible, the cause of abnormal urgent reversal of warfarin therapy coagulation results should be estab- is warranted.

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Clinical indications for use transfusion policies to manage DIC.11 which product should be used as the of frozen plasma in adults Platelets, FP, FPP, and cryoprecipitate treatment of choice. Any patient with The literature and clinical experience should be transfused only when there a presumed diagnosis of TTP must be support the use of frozen plasma in the is active bleeding and coagulation referred emergently to a centre staffed following situations. abnormalities.1,10 Transfusion of blood with a or nephrology con- components is not indicated to nor- sultant and capable of undertaking Single-factor deficiencies. Current- malize laboratory coagulation results plasma exchange therapy. As an inter- ly, specific concentrates are available in chronic or acute DIC without hem- im measure, a slow infusion of frozen for FXIII, FXI, FIX, FVIII:C, FVIII:C orrhage. Response to transfusion of plasma may be initiated at a rate of 1 complexed with von Willebrand fac- components and assessment of ongo- unit every 2 hours. However, this tor (Humate P), FVII, FVIIa, fibrino- ing needs should be based primarily should be done only after consultation gen, , C, and C1 on the clinical response supplemented with the accepting consultant. (Grade esterase inhibitor. A Health Canada by the results of laboratory tests. Addi- B recommendation, level Ib evidence Special Access Program application tion of therapy (e.g., for daily plasma exchange at presen- may be required for some of the prod- tranexamic acid or aprotinin) may be tation.) ucts and consultation with the local useful to control hyperfibrinolysis- Transfusion Medicine Laboratory induced bleeding. (Grade C recom- Need for urgent reversal of warfar- Service is recommended. Frozen plas- mendation, level IV evidence.) in effect. Frozen plasma should only ma is indicated for replacement of sin- be used to reverse the warfarin effect gle congenital factor deficiencies for Thrombotic thrombocytopenic when there is severe bleeding or which no specific fractionated prod- purpura. Most patients who develop hemostasis is required for emergent uct is available in Canada.8-10 This is thrombotic thrombocytopenic purpu- surgery or an invasive procedure. mainly applicable to FV replacement. ra are deficient in an active metal- Frozen plasma should not be used as Occasionally, frozen plasma may be loproteinase plasma enzyme due to the first-line therapy for reversal of used in emergency situations if spe- the presence of a transient antibody the warfarin effect except in severe cific concentrates are unavailable or directed against the enzyme. The re- urgent clinical situations, such as unattainable, but the patient should be sulting enzyme deficiency allows the limb- or life-threatening hemorrhage transferred as soon as possible to fa- accumulation of high molecular weight (e.g., intracranial hemorrhage) and cilities where the appropriate factor (HMW-vWF) when prothrombin complex concen- concentrates are available or, alterna- multimers, leading to excess platelet trate is not available. Depending on tively, factor concentrate should be activation, aggregation, and consump- the degree of anticoagulation, the war- brought in for the patient. (Grade C tion. The syndrome is characterized farin effect may be reversed more recommendation, level IV evidence.) by microangiopathic and effectively by a number of measures, thrombocytopenia, usually with neu- such as withholding medication and Multiple-factor deficiencies, hypo/ rologic and/or thrombotic complica- monitoring the INR or the administra- , and/or dissemi- tions. Previously, the acute treatment tion of K. Studies have shown nated intravascular coagulopathy. of TTP was daily plasma exchange that reversal of anticoagulation with Frozen plasma is indicated for use in using frozen plasma for replacement, is achieved more rapidly patients with multiple-factor deficien- which results in removal of the an- with intravenous administration than cies associated with severe bleeding tibody and the HMW-vWF, and re- oral administration.16 and/or disseminated intravascular co- placement of the deficient protease.12 In addition to vitamin K, a factor agulopathy. DIC can occur as a result Currently, many hospitals use cryo- concentrate (e.g., prothrombin com- of , septicemia, massive blood supernatant or cryo-poor plasma plex concentrate) or frozen plasma loss, severe vessel injury, tumor lysis (plasma from which cryoprecipitate will help to immediately reverse the syndrome, or obstetrical complica- has been removed) instead of FP or warfarin effect. However, one study tions such as amniotic fluid embolism. FPP for replacement as it lacks the has shown that frozen plasma does not Treating the underlying cause of DIC HMW-vWF.13 The choice of cryosu- contain sufficient of is paramount. Transfusion therapy pernatant plasma versus frozen plas- vitamin K factors, particularly FIX, to may be useful and necessary, although ma is controversial14,15 and further ran- completely reverse the warfarin ef- there is no defined consensus for domized studies are needed to establish fect.17 A factor concentrate rather than

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frozen plasma may more readily patients should be established by each testing fails to predict bleeding out- achieve complete and rapid reversal clinical unit. In the presence of nor- come.23-25 There is little evidence to of over-anticoagulation and decrease mal liver function, the coagulation support the routine use of pre-proce- the incidence of hematoma enlarge- factors return to hemostatic levels ap- dure frozen plasma and platelet trans- ment.17,18 However, as prothrombin proximately 12 hours after vitamin K fusions prior to liver biopsies for complex concentrate is available in administration.5 (Grade B recommen- patients with mild to moderate abnor- British Columbia only through the dation, Level IIa evidence.) mal results of hemostasis (INR and CBS special access program, frozen plasma is an acceptable alternative for urgent reversal of the warfarin effect. In such instances, frozen plasma (15 Before transfusing a frozen plasma mL/kg) is recommended with simul- taneous administration of intravenous product, a clinician should be aware that vitamin K16 for longer term correction there is no direct relationship between of hemostasis.19 Response to therapy and the need for additional therapy bleeding and abnormal results of should be guided by the clinical hemo- coagulation tests. However, bleeding more static response. Monitoring of the INR is also essential. Of note, clinical tri- often occurs in patients when the INR or als are being conducted with recom- the PTT is greater than 1.5 times the binant FVIIa in the setting of intra- cranial hemorrhage and, pending the upper limit of the reference range. results, this may be an acceptable al- ternate or preferred product for use in this setting. (Preference of a factor concentrate to frozen plasma—grade Liver disease, especially in the set- PTT less than 1.5 times the upper limit B recommendation, level III evi- ting of liver biopsy. Patients with of the reference range, platelet count dence. Administration of intravenous liver disease often have coagulation greater than 50 ϫ 109/L) as the risk of versus oral vitamin K—grade B rec- abnormalities that parallel the degree hemorrhagic complications is not reli- ommendation, level IIa evidence.) of parenchymal liver damage. Throm- ably reduced by transfusion of frozen bocytopenia secondary to spleno- plasma. If the patient has a marked Vitamin K deficiency. Many hospi- megaly and dysfibrinogenemia may abnormality of coagulation parame- talized or ill patients have inadequate further increase the risk of bleeding. ters (i.e., outside the parameters listed vitamin K intake, especially if they However, spontaneous bleeding sel- above) then the prophylactic use of are on a low-lipid diet and/or antibi- dom occurs without a precipitating frozen plasma may be undertaken pri- otics. Body stores of vitamin K last event such as surgery, liver biopsy, or or to a procedure, based upon the clin- only 2 weeks, so these patients are par- vessel rupture. The response to frozen ician’s judgment. However, there are ticularly susceptible to developing a plasma in liver disease is unpredictable no randomized trials to support this deficiency. These patients may have a and seldom corrects coagulation ab- practice. Given the nature and risks prolonged INR20 (and often a prolong- normalities;22 therefore, routine pro- involved in the procedure, all patients ed PTT) and administration of oral or phylactic administration of FP is of who undergo the procedure, including intravenous vitamin K will correct de- questionable utility. Of the small per- those with normal coagulation labora- ficits in vitamin K-dependent coagu- centage of patients who bleed follow- tory values, should be monitored for lation factors.21 Frozen plasma should ing the procedure, some may require signs and symptoms of bleeding. not be used to correct inadequate vit- surgical intervention. The risk of (Grade B recommendation, level IIa amin K intake even if clotting times bleeding is more likely related to vas- evidence.) are prolonged, unless urgent invasive cular lesions, including malignant procedures are required or the patient tumors, or other patient factors such Preparation for invasive bedside is bleeding. Protocols and policies for as poor nutrition. Several authors con- procedures. Invasive bedside proce- the administration of vitamin K to clude that pre-procedure coagulation dures are commonly performed in

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hospitals and they typically include fusion requirements during CPB have event of intractable bleeding follow- the following: decreased in the last 2 decades be- ing transfusion of large volumes of • insertion cause of improved surgical techniques , PRBC, and platelets, frozen • Thoracocentesis/paracentesis and the availability of “near-patient” plasma and cryoprecipitate may be • Gastrointestinal endoscopy and coagulation tests. Furthermore, the transfused to maintain the INR and biopsy use of either prophy- PTT values at less than 1.5 times the • Bronchoscopy, transbronchial lung lactically or in response to excessive upper limit of the reference range5 and biopsy, and pulmonary procedures hemorrhage has also decreased blood to increase fibrinogen concentration • Renal biopsy component use. Current evidence does to a minimum of 1.0 g/L.27 (Grade B • Epidural anesthesia, diagnostic lum- not support the routine use of frozen recommendation, level IIb evidence.) bar puncture, and neurosurgical pro- plasma in CPB surgery.26 (Grade B cedures recommendation, level IIb evidence.) Clinical indications for use • Angiography of frozen plasma in neonates Prior to performing invasive bed- For massive transfusion. A massive In addition to the clinical circum- side procedures, coagulation tests transfusion is defined as the replace- stances already described, it may be are commonly ordered with the in- ment of a patient’s whole blood appropriate to use frozen plasma in tention to assess the risk of bleeding volume with stored blood within a the following situations. complications. However, there is little 24-hour period. Other definitions of evidence in the current literature to massive hemorrhage necessitating Inherited deficiencies of clotting suggest that mild to moderate ab- massive transfusion are more predic- factors. Refer to the section above on normalities of the INR and PTT are tive and are defined as 50% blood vol- single-factor deficiencies. If no fac- predictive of hemorrhagic risk, or that ume loss within 3 hours or a rate of tor-specific concentrate is available, these patients will benefit from pre- loss of 150 mL/min.27 There are many then frozen plasma may be indicated. procedure frozen plasma transfusion.25 causes of massive hemorrhage, includ- Mild to moderate abnormal coagula- ing trauma, surgery (cardiac, trans- Hemorrhagic disease of the newborn. tion results do not imply clinically ab- plantation), gastrointestinal bleeding, Although the incidence of hemorrha- normal bleeding because of the basic disseminated intravascular coagulo- gic disease of the newborn (HDN) has design of the INR and PTT assays and pathy, and obstetrical complications. decreased since the introduction of the normal physiological reserve of In all of the above situations, massive routine vitamin K prophylaxis, some hemostasis. Baseline coagulation fac- transfusion may become necessary infants are still at high risk. This group tor activity of 40% or higher is re- and a coagulopathy may ensue that is includes those who are born prema- quired to maintain hemostasis. These traditionally ascribed to dilution of turely, those with liver disease, or are general guidelines and more con- platelets and clotting factors as pa- those born to mothers on medications servative practices may be justified tients lose whole blood while receiving such as anticonvulsants, warfarin, or for higher-risk procedures (e.g., lum- replacement with packed red blood isoniazid. Frozen plasma may also be bar disc space insertions, neurosurgi- cells (PRBC) and colloid fluids. It is considered for treatment of severe cal procedures, and pulmonary biop- now recognized that the coagulopathy HDN. Currently, there are no studies sies and procedures). The decision to is multifactorial due to the prolonged to guide the dosage,1 but a dose of 10 transfuse blood products can usually effects of hypothermia, hypotension, mL to 15 mL per kilogram of body be justified when treating hemorrhag- shock, and the development of DIC. weight is usually well tolerated. (Grade ic complications. (Grade B recom- Overall, the decision to transfuse C recommendation, level IV evidence.) mendation, level IIa evidence.) frozen plasma or other blood compo- nents should be based on clinical judg- Coagulopathy and bleeding, or co- During intraoperative cardio- ment and timely coagulation tests. agulopathy with planned procedure. pulmonary bypass. The etiology of There is no role for the use of replace- Frozen plasma is indicated for neo- coagulopathy during intraoperative ment “formulae” to guide transfu- nates with , hypotension, hypo- cardiopulmondary bypass (CPB) is sions3 except in the rare situation xia (respiratory distress syndrome), or multifactorial and relates to platelet where the rate of blood loss outstrips liver disease if they have significant dysfunction, heparinization, and pos- the clinician’s ability to repeat assess- coagulopathy and bleeding or if they sible dilutional coagulopathy. Trans- ments and coagulation testing. In the are at risk of bleeding from an inva-

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sive procedure. They should receive Response to transfusion of approximately 15 mL of frozen plas- ma per kilogram of body weight and a components and assessment of dose of vitamin K.1 The response ongoing needs should be based should be monitored clinically and by coagulation studies.28 (Grade C rec- primarily on the clinical response ommendation, level IV evidence.) supplemented by the results Possible use for of laboratory tests. frozen plasma The use of frozen plasma may be con- sidered in the following situation.

Prevention of hemol- not indicated in the following situa- polycythemia; crystalloid is consid- ysis related to red cell Tantigen acti- tions. ered an effective partial-exchange vation. Red blood cells carry cryptic transfusion fluid.31 Infants who are antigens that can be exposed when a Hypovolemia. Frozen plasma should clinically well or with only minor neonate is infected with neuraminidase- not be used as a simple intravascular symptoms do not necessarily benefit producing bacteria such as clostridia, in adults or children. from partial-. streptococcus, or pneumococcus in Crystalloids and/or volume expanders, conditions such as necrotizing entero- such as pentastarch, are indicated; Wound healing. Frozen plasma is not colitis (NEC). This is known as red they are safer, less expensive, and indicated to enhance or promote cell T antigen activation. Donor plas- readily available. wound healing. ma contains naturally occurring “anti- T” antibodies. Theoretically, when a Plasma exchange. Frozen plasma is Treatment of immunodeficiency plasma product containing anti-Tanti- not routinely indicated for replace- states. Frozen plasma is not indicated bodies is administered, the antibodies ment volume in PLEX, except for pa- for treatment of immunodeficiency can damage the patient’s T-activated tients with TTP. states. Purified intravenous immuno- red cells causing hemolysis. Current- globulin preparations are available for ly, there are no randomized controlled Reversal of prolonged INR in the these conditions. trials to support the use of specially absence of bleeding. Frozen plasma prepared plasma products (i.e., low- is not indicated for prolonged INR in Other inappropriate uses. In addi- titre anti-T plasma) for infants with the absence of bleeding. If the prolon- tion, frozen plasma should not be used NEC.29 For management of patients gation is due to an oral , for nutritional support, protein-losing with NEC and suspected red cell then the medication should be with- states, Guillain-Barré syndrome,2 acute T antigen activation, the physician held. Depending on the extent of INR pancreatitis,2 or .2 should consult the transfusion medi- elevation and the severity of the pa- cine director for product selection as tient’s clinical condition, vitamin K Competing interests this is a controversial topic and opti- administration may be helpful. None declared. mal management has not been clearly defined. (Grade B recommendation, Prevention of intraventricularhem- References level IIa evidence.) orrhage in preterm infants. Routine 1. O’Shaughnessy DF, Atterbury C, Bolton administration of frozen plasma is not Maggs P, et al.; British Committee for Inappropriate uses for indicated for prevention of intraven- Standards in Haematology, Blood Trans- frozen plasma tricular hemorrhage in infants born fusion Task Force. Guidelines for the use Because there are many alternatives before 32 weeks gestation.30 of fresh-frozen plasma, cryoprecipitate available for the treatment of the clin- and cryosupernatant. Br J Haematol ical conditions listed below, and be- Treatment of neonates with poly- 2004;126:11-28. cause of the risks involved in transfu- cythemia. Frozen plasma is not indi- 2. Stanworth SJ, Brunskill SJ, Hyde CJ, sion, use of frozen plasma products is cated in the treatment of neonates with et al. Is clinically

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Appendix A US Agency for Healthcare Policy and Research guidelines for defining the types of evidence and the grading rec- ommendations. Levels of evidence Grades of recommendations Ia Evidence obtained from the meta-analysis of ran- A Required at least one randomized controlled trial as domized controlled trials. part of a body literature of overall good quality and Ib Evidence obtained from at least one randomized consistency addressing the specific recommenda- controlled trial. tions (evidence levels Ia, Ib). IIa Evidence obtained from at least one well-designed B Requires availability of well conducted clinical controlled study without randomization. studies but no randomized clinical trials on the topic IIb Evidence obtained from at least one other type of of recommendations (evidence levels IIa, IIb, III). well-designed quasi-experimental study. C Requires evidence obtained from expert committee III Evidence obtained from well-designed non-exper- reports or opinions and/or clinical experiences of imental descriptive studies, such as comparative respected authorities. Indicates an absence of studies, correlation studies and case studies. directly applicable clinical studies of good quality IV Evidence obtained from expert committee reports (evidence level IV). or opinions and/or clinical experiences of respect- ed authorities.

Appendix B The Transfusion Medical Advisory Group advises the BC Ministry of Health. It is composed of transfusion medi- cine experts who meet regularly to discuss pertinent transfusion-related issues and to endorse transfusion initiatives that will improve the Canadian health care system.

Members Ms Sheila Armstrong, Administrator, Provincial Dr Randell Moore, Anesthesiologist, St. Paul’s Laboratory Coordinating Office Hospital, Vancouver, BC Dr Brian Berry, Director Hematopathology and Dr Doug Morrison, Director, Transfusion Medicine, Transfusion Medicine, Vancouver Island Health— Royal Columbian Hospital, New Westminster, BC South Island, Victoria, BC Dr David Pi, Director, Provincial Blood Coordinating Dr Mark Bigham, Medical Officer, Canadian Blood Office, Vancouver, BC Services—BC and Yukon Centre Ms Pam Quibell, Charge Technologist—Transfusion Dr Kate M. Chipperfield, Regional Medical Leader, Services, Northern Health, Prince George, BC Blood Transfusion Medicine, Vancouver Coastal Mr Lyle Unrau, Customer Service Rep, Canadian Health, Vancouver, BC Blood Services—BC and Yukon Centre Dr Jason Doyle, Director, Transfusion Services— Dr Louis D. Wadsworth, Executive Medical Director, Interior Health, Kelowna, BC Provincial Health Services Authority (PHSA) Ms Shelley Feenstra, Regional Blood Transfusion Corporate—Lab Services, Vancouver, BC (Chair) Clinician—Vancouver Coastal Health, Vancouver, Ms Maureen Wyatt, Assistant Charge Technologist, BC Interior Health, Kelowna, BC Dr David Ferguson, Medical Director, BC Biomedical Mr Ed Yee, Regional Director, Canadian Blood Laboratories Ltd., Surrey, BC Services—BC and Yukon Centre Dr Gershon Growe, Canadian Blood Services—BC Dr Wilson Yeung, Hematopathologist, St. Paul’s and Yukon Centre Hospital, Vancouver, BC Ms Donna Miller, Chair, Nursing Resource Group, Royal Jubilee Hospital, Victoria, BC

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