Cryoprecipitate Transfusion

Abstract

Fibrinogen is a critical coagulation protein involved in both primary and secondary hemostasis. Cryoprecipitate preparation was first described Dr. Judith Graham Pool in 1964 at Stanford University as a product for factor VIII replacement in patients with hemophilia A. Its use for hemophilia A has been superseded by safer, virally inactivated or recombinant products. At the present time cryoprecipitate is only used for fibrinogen replacement for patients with serious bleeding (or at risk for serious bleeding) and hypofibrinogenemia. The product also contains factors VIII, von Willebrand factor, fibronectin, factor XIII, and platelet microparticles, in addition to fibrinogen. The hemostatic contribution of these other components in the management of the trauma patient is unknown. Each 10 unit pool must contain at least 1.5 g (150 mg per unit) of fibrinogen by regulatory requirements, although contains substantially more (approximately 5 g per 10 pool or median 500 mg per unit). Hypofibrinogenemia is common in trauma patients on arrival (less than <1.5 g/L in 14 %, <1.0 g/L in 5 % and <0.5 g/L in 3 % in adult trauma patients) and may be more common in pediatric trauma patients (52 % <2.0 g/L, 20 % <1.0 g/L, and 11 % undetectable). A preserved fibrinogen level on arrival to hospital is associated with substantially better outcomes (odds of death reduced by 0.22 during the first 28 days for every 1 g/L rise in baseline fibrinogen). The fibrinogen is depleted by a combination of factors including: consumption at sites of injury, hemodilution from intravenous fluids, and depletion from hyperfibrinolysis due to activation of protein C and uncontrolled release of tissue plasminogen activator (tPA). Worldwide, approximately 10 % of cryoprecipitate distributed to hospitals is transfused to trauma patients. Adult patients on average receive a dose of approximately 10 units of cryoprecipitate at about 3 h after arrival to hospital (at about the eighth unit of red cells), and with a rise in fibrinogen level of 0.5–0.9 g/L post-transfusion. Several retrospective studies in adult and pediatric, civilian and military, trauma settings suggest that more aggressive use of fibrinogen replacement may improve outcomes, although the data quality is poor due to the retrospective design in all trials. It is unclear what should be the appropriate dose, threshold for administration, or hemostatic target level. Studies from the settings of cardiac surgery and postpartum hemorrhage suggest that the target of 1.0 g/L in some guidelines may be inadequate for some patients and that a higher target may be necessary (>1.5–2.0 g/L). While we await better evidence on when and how cryoprecipitate should be used, it is reasonable to administer cryoprecipitate if the fibrinogen is under 2 g/L and the patient has serious ongoing hemorrhage where immediate surgical control is not possible. A dose of 10 units (or 50 mg/kg of fibrinogen in pediatrics) is a reasonable starting dose as such patients will also be receiving some fibrinogen replacement with each bag of plasma and platelets.