Do we need cryoprecipitate in the era of fibrinogen concentrate and other specific factor replacement options?

Cryoprecipitate was first used in the 1960s as a source of factor VIII (FVIII) for the treatment of bleeding in haemophilia A. Although still used in some countries for this purpose, its main use now is as a concentrated source of fibrinogen, commonly administered as part of major haemorrhage therapy for patients with uncontrolled bleeding. Fibrinogen is recognized as the first clotting protein to fall to clinically significant low levels during major haemorrhage, and there has been a recent explosion of interest around the potential importance of fibrinogen replacement therapy in this setting. This has led many to question the relative benefits of cryoprecipitate as compared to fibrinogen concentrate. This review will explore whether cryoprecipitate, in the era of specific factor concentrates, is an outmoded treatment. Cryoprecipitate is manufactured from frozen plasma after controlled thawing. It is not only a rich source of FVIII and fibrinogen but also contains von Willebrand Factor (VWF), FXIII and fibronectin. In UK, cryoprecipitate is available as single donor units or as pools of 5 units and requires thawing before transfusion. Variability in clotting factor levels in blood donors means that the fibrinogen concentration in cryoprecipitate may vary. With the exception of donor screening and viral testing at the time of donation, no viral reduction steps are taken during manufacture. Fibrinogen concentrate is an alternative concentrated source of fibrinogen but is not licensed in every country for acquired bleeding. It is a plasma‐derived product manufactured from pooled plasma. Many view fibrinogen concentrate as a superior product to cryoprecipitate with reasons including: standardization of production–vials contain a known fibrinogen concentration; lyophilization making it easily portable and not requiring storage or thawing in blood bank; viral inactivation; a consideration for the UK is a likely lower risk for vCJD transmission. Gram for gram, fibrinogen concentrate is four times the cost of cryoprecipitate. The UK haemophilia centre doctors organisation (UKHCDO) recommends the use of single‐factor agents above pooled blood components for replacement therapy in inherited bleeding conditions, where possible, for many of these reasons. But what about cryoprecipitate as therapy for acquired bleeding where patients develop a complex coagulopathy affecting multiple coagulation and fibrinolytic factors? Might cryoprecipitate therapy confer an advantage? Theoretically, higher concentrations of VWF, FVIII and FXIII might promote more rapid primary and secondary haemostasis. Clinical efficacy for the two products in observational studies and one RCT has been reported to be similar, where increases in fibrinogen blood levels are comparable. However, no study has yet been large enough to look at comparative clinical efficacy or indeed safety. In the era of single‐factor concentrates, cryoprecipitate may seem outdated, but at present–in particular in relation to therapy for major haemorrhage–insufficient evidence is available which confirms or refutes it place in major haemorrhage therapy.