Cryoprecipitate therapy

The authors review the evolving usage of cryoprecipitate, noting the uncertainty of appropriate dosing and optimal administration.† They call for randomized controlled trials to help guide the use of cryoprecipitate and current, alternative therapeutic options.Cryoprecipitate, originally developed as a therapy for patients with antihaemophilic factor deficiency, or haemophilia A, has been in use for almost 50 yr.However, cryoprecipitate is no longer administered according to its original purpose, and is now most commonly used to replenish fibrinogen levels in patients with acquired coagulopathy, such as in clinical settings with haemorrhage including cardiac surgery, trauma, liver transplantation (LT), or obstetric haemorrhage.Cryoprecipitate is a pooled product that does not undergo pathogen inactivation, and its administration has been associated with a number of adverse events, particularly transmission of blood-borne pathogens and transfusion-related acute lung injury.As a result of these safety concerns, along with emerging availability of alternative fibrinogen preparations, cryoprecipitate has been withdrawn from use in a number of European countries.Compared with the plasma from which it is prepared, cryoprecipitate contains a high concentration of coagulation factor VIII, coagulation factor XIII, and fibrinogen.Cryoprecipitate is usually licensed by regulatory authorities for the treatment of hypofibrinogenaemia, and recommended for supplementation when plasma fibrinogen levels decrease below 1 g litre 21 ; however, this threshold is empiric and is not based on solid clinical evidence.Consequently, there is uncertainty over the appropriate dosing and optimal administration of cryoprecipitate, with some guidelines from professional societies to guide clinical practice.Randomized, controlled trials are needed to determine the clinical efficacy of cryoprecipitate, compared with the efficacy of alternative preparations.These trials will allow the development of evidence-based guidelines in order to inform physicians and guide clinical practice.Keywords: blood; blood coagulation factors; coagulation protein disorders; cryoprecipitate coagulum; fibrinogen; transfusion Concentrated antihaemophilic factor (AHF), or factor VIII (FVIII), was first produced in the 1940s by Edwin J. Cohn, via the fractionation of plasma with ethanol. 1 Modest amounts of this product were used as a treatment for haemophilia throughout the 1950s, 2 and in the early 1960s attempts were made to create an improved FVIII concentrate, which led to the discovery that cryoprecipitate, which forms when frozen plasma is allowed to thaw slowly at 1-108C, is rich in fibrinogen, AHF, and factor XIII. 3 This product was first discovered and introduced by Pool and colleagues nearly 50 years ago, as a therapy for patients with AHF deficiency or haemophilia A; 4 5 however, its major use today is far removed from that for which it was originally intended.As a labile blood product derived from plasma, cryoprecipitate is enriched with fibrinogen and also high concentrations of FVIII, von Willebrand factor, and factor XIII.Its main use today is to replenish fibrinogen levels during coagulopathies associated with massive haemorrhage, in which fibrinogen decreases to a critical level 6 7 because of processes such as consumption through clotting, dilution, blood loss, or all.Cryoprecipitate has been withdrawn from many European countries because of safety concerns such as the transmission of pathogens.8 9 Instead, commercial fibrinogen preparations are available for fibrinogen replacement therapy.10 Nevertheless, cryoprecipitate remains available for haemostatic therapy in several countries, including the USA and Canada, but Level 1 evidence in the form of prospective, randomized, controlled trials to support its efficacy is lacking.Here, we examine the clinical evidence and current guidelines for the use of cryoprecipitate to treat patients with acquired coagulopathy. PreparationEach unit (U) of cryoprecipitate is commonly prepared from 1 unit of fresh frozen plasma (FFP; plasma which is frozen