Guidelines for cryoprecipitate transfusion

1 VOL. 49 NO. 8, OCTOBER2007BC MEDICAL JOURNAL441 ABSTRACT: The literature showsthere is often inappropriate use of blood products, including cryo -precipitate plasma, because of in -adequate education of for cryoprecipitate trans - fusion have been developed by theTransfusion Medicine Advisory Groupof British Columbia to educate clini-cians and address transfusion prac-tices in the province. These guide -lines are based on a MEDLINE search and consultation with hema -to pathologists and clinicians. At pre-sent, transfusion of cryoprecipitateis indicated for hypofibrinogen emia/dysfibrinogenemia, von Willebranddisease, hemophilia A, factor XIII deficiency, and management ofbleeding related to thrombolytictherapy. cryoprecipitate should notbe used to prepare fibrin glue or totreat sepsis. The transfusion Medicine Ad -visory Group (TMAG) of BChas prepared Guidelines to pro-vide physicians with current informa-tion on the appropriate use of cryopre-cipitate plasma.

2 These Guidelines areavailable electronically on the BritishColumbia Provincial CoordinatingOffice web site ( ) and will be updated period-ically. Prescribing physicians areresponsible for referring to the mostrecent Guidelines . How the Guidelines were developedThese Guidelines were developed todirect therapy but are not intended as arigid prescription for cryoprecipitateuse. The Guidelines are based on aMEDLINE search using the keywords cryoprecipitate plus trials or randomized or Guidelines or reviews. The levels of evidence andgrades of recommendations are basedon standards developed by the USAgency for Healthcare Research andQuality (formerly the US Agency forHealth Care Policy and Research)1(seeAppendix A). Because of the limitednumber of clinical trials completed,most of the recommendations are basedon expert opinion level IV evidence,grade C recommendation. These guide -lines were reviewed by hematopathol-ogists and clinicians, including hema-tologists and critical care physicians,and were subsequently approved by theTransfusion Medicine Advisory Group(see Appendix B).

3 General considerationsPhysicians contemplating the use ofcryoprecipitate (see ), shouldkeep in mind the following generalconsiderations: In British Columbia, informed con-sent is required for the transfusion ofcryoprecipitate. All routine coagulation parametersTableGuidelines for cryoprecipitate transfusionA new document from the transfusion Medicine Advisory Groupdescribes appropriate use of cryoprecipitate Droubatchevskaia, MD, Michelle P. Wong, MD, Kate M. Chipperfield, MD, FRCPC, Louis D. Wadsworth, MB, ChB, FRCPC, FRCPath, David J. Ferguson, MD, FRCPCDr Droubatchevskaia is a hema topatholo -gist at St. Paul s Hospital in Vancouver,British Columbia. Dr Wong is a hemato -pathology resident in the Department ofPathology and Laboratory Medicine at theUniversity of British Columbia. Dr Chip -perfield is regional medical leader, blood transfusion Medicine, Vancouver CoastalHealth, and a clinical assistant professor inthe Department of Pathology and Labora-tory Medicine at UBC.

4 Dr Wadsworth is ahematopathologist at Children s and Wo -men s Health Centre of BC, a clinical pro-fessor in the Department of Pathology andLaboratory Medicine at UBC and is chair ofthe transfusion Medicine Advisory Groupof BC. Dr Fer guson is the medical directorof BC Bio medical Laboratories Ltd., and anassistant clinical professor in the Depart-ment of Path ology and Laboratory Medi-cine at MEDICAL JOURNALVOL. 49 NO. 8, OCTOBER2007442py see above)Adult: 10 to 12 units (bags) every 12hoursChild: 1 unit (bag) per 6 kg of bodyweight every 12 hours Hemophilia A (only as a second-linetherapy see above)(Level IV evidence, grade C recom-mendation.)F XIII defi-ciency of factor XIII is an extremelyrare condition. In 2006, the CanadianHemophilia Registry ( ) identified only 41cases. Hemostasis may be achievedwith levels as low as 2% to 3%. Com-pared with the half-life of other coag-ulation factors, the half-life of F XIIIis very long (9 to 10 days).

5 Plasma-derived F XIII concentrate (Fibro -gammin P) is licensed and available inCanada through the Special AccessProgramme for use in patients with FXIII deficiency, but is not stocked inall regional blood centres. Because ofthe rarity of F XIII deficiency, specif-ic factor concentrate is usually notreadily available in emergent situa-tions, and it is in these situations thatcryoprecipitate can and should : 1 unit (bag) per 10 kg of body weightevery 7 to 14 days(Level IV evidence, grade C recom-mendation.)Management of bleeding related tothrombolytic can be used to manage intracranialbleeding in patients during or afteradministration of tissue plasminogenactivator (tPA).8 Randomized con-trolled clinical trials of cyroprecipitateshould be checked before orderingcryoprecipitate. This includes com-plete blood count (CBC), plateletcount, international normalized ratio(INR), partial thromboplastin time(PTT), and fibrinogen.

6 The transfusion Medicine Laborato-ry Service should be made aware ofthe clinical diagnosis on the re questform used to order reason for the transfusion shouldalso be clearly and accurately record-ed in the patient s chart, and in anydocumentation that is used whenadministering cryoprecipitate . cryoprecipitate should be given onlyafter risks associated with transfu-sion of allogeneic blood productshave been considered and only whenthe benefits outweigh the risks. Alternative treatments or adjunctiveagents should be used to minimizeor to avoid the use of cryoprecipi-tate. For example, desmopressin(DDAVP), Humate P, fibrinogenconcentrates, and antifibrinolyticagents may be appropriate in specif-ic situations. Most laboratories in British Colum-bia convert the prothrombin time(PT) to the international normalizedratio to facilitate comparison ofre -sults between laboratories. (Through-out the document, we have tried touse the INR where possible, as thisis typically what is reported by lab-oratories.)

7 Clinical indications for useof cryoprecipitateClinical experience supports the useof cryoprecipitate in the following edlevels of fibrinogen activity can resultfrom either a functional or qualitativedefect (dysfibrinogenemia) or a quanti-tative deficiency, as is seen in massivetransfusion or disseminated intravascu-lar coagulation (DIC). trans fusion ther- Guidelines for cryoprecipitate transfusionapy with either frozen plasma (FP) orcryoprecipitate is usually indicated iffibrinogen levels are less than g/L,and bleeding is present, although clin-ically significant bleeding can occur athigher levels. If fibrinogen levels aregreater than g/L in the setting ofactive bleeding secondary to DIC, thenFP should be given instead of cryo-precipitate in order to address the mul-tiple factor deficiencies typical ofDIC. Cryo precipitate may be consid-ered as a substitute for FP when therequired volume of plasma is relative-ly contraindicated and targeted fibrino-gen replacement in a small volumeis (Level IV evidence, grade C recom-mendation.)

8 Von Willebrand (vWD) disease andhemophilia A (HA).The current prac-tice in patients with mild (type 1)vWD disease or mild HA is to usedesmopressin and/or antifibrinolyticsor virus-inactivated factor VIII (F VIII)concentrate ( , Humate P), whichcontains both F VIII:C and von Wille-brand factor multimers. Most hemo-philia patients with F VIII:C deficien-cy are treated with F VIII:Cconcentrate, which is now a recombi-nant product and no longer derivedfrom human plasma. Cryoprecipitatecan be used by patients with vWD dis-ease that is unresponsive to desmo-pressin and by hemophilia A patientsin those locations where F VIII:C con-centrates are not available. Every effortmust be made to obtain the preferredrecombinant factor concentrate forhemophiliacs before resorting to theuse of : vWD disease (as a second- line thera-number of bags of = [(plasma volume in mL % increase in F VIII: C needed)/100]cryoprecipitate80 VOL.)

9 49 NO. 8, OCTOBER2007BC MEDICAL JOURNAL443 Guidelines for cryoprecipitate transfusionTable. Characteristics of four frozen plasma ppl laassmmaa(from whole blood collection)FFrreesshh--ffrroozzeenn ppl laassmmaa(from apheresis collection)CCrryyoopprreecci ippi ittaat tee ppl laassmmaa(cryo)CCrryyoossuuppeerrnnaat taannt t ppl laassmmaa(cryo-poor plasma) PPrreeppaarraat tiioonnWhole blood is centrifuged athigh speed, allowing separa-tion of plasma, red blood cells(RBCs), and the buffy coatlayer (platelets, white bloodcells, some RBCs and plasma).Plasma is frozen within 24hours of collection and is des-ignated as frozen plasma (FP).It is prepared for use by thaw-ing at 37 C, a process that cantake up to 30 minutes. Once thawed, the productshould be transfused immedi-ately, with completion oftransfusion within 4 hours ofissuing blood is processedthrough a cell separator toobtain plasma. Plasma isfrozen within 8 hours of col-lection and is designated asfresh-frozen plasma (FFP).

10 Ingeneral, 1 unit of FFP fromapheresis collection is equiva-lent to approximately 2 unitsof FP from whole blood collec-tion. The two products can beused thawed, the productshould be transfused immedi-ately, with completion oftransfusion within 4 hours ofissuing is frozen for 24 hours,and then thawed at 1 6 Cuntil insoluble proteins precip-itate. The pack is centrifugedto obtain the cryoprecipitate is thenrefrozen for thawed, the productshould be transfused immedi-ately, with completion oftransfusion within 4 hours ofissuing is frozen for 24 hours,and then thawed at 1 6 Cuntil insoluble proteins precip-itate. The pack is centrifugedto obtain the supernatant, or cryo-poorplasma, is then refrozen thawed, the productshould be transfused immedi-ately, with completion oftransfusion within 4 hours ofissuing toorrssContains all of the coagulationfactors, including the labilefactors (FV and FVIII:C).