Deficiencies in plasma coagulation factors can cause bleeding (Table 34–3). Spontaneous bleeding occurs when factor activity is less than 5–10% of normal. Factor VIII deficiency (classic hemophilia, or hemophilia A) and factor IX deficiency (Christmas disease, or hemophilia B) account for most of the heritable coagulation defects. Concentrated plasma fractions and recombinant protein preparations are available for the treatment of these deficiencies. Administration of plasma-derived, heator detergent-treated factor concentrates and recombinant factor concentrates are the standard treatments for prevention and treatment of bleeding associated with hemophilia. Lyophilized factor VIII concentrates are prepared from large pools of plasma. Transmission of viral diseases such as hepatitis B and C and HIV is reduced or eliminated by pasteurization and by extraction of plasma with solvents and detergents. However, this treatment does not remove other potential causes of transmissible diseases such as prions. For this reason, recombinant clotting factor preparations are recommended whenever possible for factor replacement. The best use of these therapeutic materials requires diagnostic specificity of the deficient factor and quantitation of its activity in plasma. Recently, several longer-acting factor VIII and IX preparations have been developed. Eloctate is a factor VIII-Fc domain conjugate that prolongs the factor VIII half-life and allows twice-weekly dosing in many cases. Idelvion is a factor IX-albumin conjugate with a half-life of 100 hours (native factor IX has a half-life of 16 hours) and is FDA-approved for prophylaxis or treatment of bleeding in hemophilia B patients, offering the possibility of once-weekly
TABLE 34–3 Therapeutic products for the treatment of coagulation disorders.1
FFP, fresh frozen plasma; DDAVP, 1-deamino-8-D-arginine vasopressin.
1For warfarin overdose or coumarin rodenticide poisoning, a four-factor concentrate (II, VII, IX, X) is available. Antithrombin concentrates are available for patients with thrombosis in the setting of antithrombin deficiency. Activated protein C concentrates were approved for treatment of sepsis but withdrawn from the market in 2011 following publication of a study demonstrating no benefit in sepsis and increased bleeding risk.
2Cryoprecipitate should be used to treat bleeding in the setting of factor VIII deficiency and von Willebrand disease only in an emergency in which pathogen-inactivated products are not available.
dosing in the case of Idelvion. Intermediate purity factor VIII concentrates (as opposed to recombinant or high purity concentrates) contain significant amounts of von Willebrand factor. Humate-P is a factor VIII concentrate that is approved by the FDA for the treatment of bleeding associated with von Willebrand disease. Vonicog alfa is a recombinant von Willebrand factor product approved for treatment and control of bleeding in adults with von Willebrand disease. Fresh frozen plasma is used for factor deficiencies for which no recombinant form of the protein is available. A four-factor plasma replacement preparation containing vitamin K–dependent factors II VII, IX, and X (4F PCC, Kcentra) is available for rapid reversal of warfarin in bleeding patients.
Hemophilia A and B patients are given factor VIII and IX replacement, respectively, as prophylaxis to prevent bleeding, and in higher doses to treat bleeding events or to prepare for surgery.
Desmopressin acetate increases the factor VIII activity of patients with mild hemophilia A or von Willebrand disease. It can be used in preparation for minor surgery such as tooth extraction without any requirement for infusion of clotting factors if the patient has a documented adequate response. High-dose intranasal desmopressin (see Chapter 17) is available and has been shown to be efficacious and well tolerated by patients.