Nadejda Droubatchevskaia, MD, Michelle P. Wong, MD, Kate M. Chipperfield, MD, FRCPC, Louis D. Wadsworth, MB, ChB, FRCPC, FRCPath, David J. Ferguson, MD, FRCPC Guidelines for cryoprecipitate transfusion A new document from the Transfusion Medicine Advisory Group describes appropriate use of cryoprecipitate plasma. ABSTRACT: The literature shows he Transfusion Medicine Ad - tologists and critical care physicians, there is often inappropriate use visory Group (TMAG) of BC and were subsequently approved by the of blood products, including cryo - T has prepared guidelines to pro- Transfusion Medicine Advisory Group precipitate plasma, because of in - vide physicians with current informa- (see Appendix B). adequate education of physicians. tion on the appropriate use of cryopre- Guidelines for cryoprecipitate trans- General considerations cipitate plasma. These guidelines are fusion have been developed by the available electronically on the British Physicians contemplating the use of Transfusion Medicine Advisory Group Table Columbia Provincial Coordinating cryoprecipitate (see ), should of British Columbia to educate clini- Office web site (www.blood keep in mind the following general cians and address transfusion prac- link.bc.ca) and will be updated period- considerations: tices in the province. These guide- ically. Prescribing physicians are • In British Columbia, informed con- lines are based on a MEDLINE responsible for referring to the most sent is required for the transfusion of search and consultation with hema- recent guidelines. cryoprecipitate. to pathologists and clinicians. At pre- • All routine coagulation parameters sent, transfusion of cryoprecipitate How the guidelines is indicated for hypofibrinogen emia/ were developed Dr Droubatchevskaia is a hema topatholo - dysfibrinogenemia, von Willebrand gist at St. Paul’s Hospital in Vancouver, These guidelines were developed to disease, hemophilia A, factor XIII British Columbia. Dr Wong is a hemato - direct therapy but are not intended as a deficiency, and management of pathology resident in the Department of rigid prescription for cryoprecipitate bleeding related to thrombolytic Pathology and Laboratory Medicine at the use. The guidelines are based on a therapy. Cryoprecipitate should not University of British Columbia. Dr Chip- MEDLINE search using the key be used to prepare fibrin glue or to perfield is regional medical leader, Blood words “cryoprecipitate” plus “trials” treat sepsis. Transfusion Medicine, Vancouver Coastal or “randomized” or “guidelines” or Health, and a clinical assistant professor in “reviews.” The levels of evidence and the Department of Pathology and Labora- grades of recommendations are based tory Medicine at UBC. Dr Wadsworth is a on standards developed by the US hematopathologist at Children’s and Wo - Agency for Healthcare Research and men’s Health Centre of BC, a clinical pro- Quality (formerly the US Agency for 1 fessor in the Department of Pathology and Health Care Policy and Research) (see Laboratory Medicine at UBC and is chair of Appendix A). Because of the limited the Transfusion Medicine Advisory Group number of clinical trials completed, of BC. Dr Fer guson is the medical director most of the recommendations are based of BC Bio medical Laboratories Ltd., and an on expert opinion—level IV evidence, assistant clinical professor in the Depart- grade C recommendation. These guide- ment of Path ology and Laboratory Medi- lines were reviewed by hematopathol- cine at UBC. ogists and clinicians, including hema- VOL. 49 NO. 8, OCTOBER 2007 BC MEDICAL JOURNAL 441 Guidelines for cryoprecipitate transfusion should be checked before ordering apy with either frozen plasma (FP) or py—see above) cryoprecipitate. This includes com- cryoprecipitate is usually indicated if Adult: 10 to 12 units (bags) every 12 plete blood count (CBC), platelet fibrinogen levels are less than 1.0 g/L, hours count, international normalized ratio and bleeding is present, although clin- Child: 1 unit (bag) per 6 kg of body (INR), partial thromboplastin time ically significant bleeding can occur at weight every 12 hours (PTT), and fibrinogen. higher levels. If fibrinogen levels are • Hemophilia A (only as a second-line • The Transfusion Medicine Laborato- greater than 1.0 g/L in the setting of therapy—see above) ry Service should be made aware of active bleeding secondary to DIC, then (Level IV evidence, grade C recom- the clinical diagnosis on the re quest FP should be given instead of cryo- mendation.) form used to order cryoprecipitate. precipitate in order to address the mul- F XIII deficiency. The reason for the transfusion should tiple factor deficiencies typical of Hereditary defi- also be clearly and accurately record- DIC. Cryo precipitate may be consid- ciency of factor XIII is an extremely ed in the patient’s chart, and in any ered as a substitute for FP when the rare condition. In 2006, the Canadian documentation that is used when required volume of plasma is relative- Hemophilia Registry (www.fhs.mc administering cryoprecipitate. ly contraindicated and targeted fibrino- master.ca/chr/2006) identified only 41 • Cryoprecipitate should be given only gen replacement in a small volume cases. Hemostasis may be achieved 2-4 after risks associated with transfu- is desirable. with levels as low as 2% to 3%. Com- sion of allogeneic blood products (Level IV evidence, grade C recom- pared with the half-life of other coag- have been considered and only when mendation.) ulation factors, the half-life of F XIII the benefits outweigh the risks. is very long (9 to 10 days). Plasma- von Willebrand (vWD) disease and • Alternative treatments or adjunctive derived F XIII concentrate (Fibro - hemophilia A (HA). agents should be used to minimize The current prac- gammin P) is licensed and available in or to avoid the use of cryoprecipi- tice in patients with mild (type 1) Canada through the Special Access tate. For example, desmopressin vWD disease or mild HA is to use Programme for use in patients with F (DDAVP), Humate P, fibrinogen desmopressin and/or antifibrinolytics XIII deficiency, but is not stocked in concentrates, and antifibrinolytic or virus-inactivated factor VIII (F VIII) all regional blood centres. Because of agents may be appropriate in specif- concentrate (e.g., Humate P), which the rarity of F XIII deficiency, specif- ic situations. contains both F VIII:C and von Wille- ic factor concentrate is usually not • Most laboratories in British Colum- brand factor multimers. Most hemo- readily available in emergent situa- bia convert the prothrombin time philia patients with F VIII:C deficien- tions, and it is in these situations that (PT) to the international normalized cy are treated with F VIII:C cryoprecipitate can and should be 7 ratio to facilitate comparison of re - concentrate, which is now a recombi- used. Dosing: sults between laboratories. (Through- nant product and no longer derived out the document, we have tried to from human plasma. Cryoprecipitate • 1 unit (bag) per 10 kg of body weight use the INR where possible, as this can be used by patients with vWD dis- every 7 to 14 days is typically what is reported by lab- ease that is unresponsive to desmo- (Level IV evidence, grade C recom- oratories.) pressin and by hemophilia A patients mendation.) in those locations where F VIII:C con- Clinical indications for use Management of bleeding related to centrates are not available. Every effort of cryoprecipitate thrombolytic therapy. must be made to obtain the preferred Cryoprecipi- Clinical experience supports the use recombinant factor concentrate for tate can be used to manage intracranial of cryoprecipitate in the following sit- hemophiliacs before resorting to the bleeding in patients during or after 2-6 uations. use of cryoprecipitate. administration of tissue plasminogen Hypodysfibrinogenemia. Dosing: 8 Reduc ed activator (tPA). Randomized con- levels of fibrinogen activity can result • vWD disease (as a second-line thera- trolled clinical trials of cyroprecipitate from either a functional or qualitative defect (dysfibrinogenemia) or a quanti- number of bags of = [(plasma volume in mL ϫ % increase in F VIII: C needed)/100] tative deficiency, as is seen in massive cryoprecipitate 80 transfusion or disseminated intravascu- lar coagulation (DIC). Trans fusion ther- 442 BC MEDICAL JOURNAL VOL. 49 NO. 8, OCTOBER 2007 Guidelines for cryoprecipitate 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