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 Transfusion Medicine Advisory Group of BC describes appropriate use of frozen plasma, fresh-frozen plasma, and cryosupernatant. 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 blood 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- cryoprecipitate, 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, Blood Transfusion 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 bleeding 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 warfarin 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 hypovolemia, 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- VOL. 49 NO. 6, JULY/ AUGUST 2007 BC MEDICAL JOURNAL 311 Guidelines for frozen plasma transfusion Table. Characteristics of four frozen plasma products. Frozen plasma Fresh-frozen plasma Cryoprecipitate plasma Cryosupernatant plasma (from whole blood collection) (from apheresis 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 proteins 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 (platelets, 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 coagulation 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 fibrinogen 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. 312 BC MEDICAL JOURNAL VOL. 49 NO. 6, JULY/ AUGUST 2007 Guidelines for frozen plasma transfusion 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.