Human protein C concentrates for replacement therapy in congenital and acquired protein C deficiency

The protein C pathway has an important function in regulating and modulating blood coagulation and ensuring patency of the microcirculation. Protein C deficiency leads to macro- or microvascular thrombosis. Hereditary severe protein C deficiency is a life-threatening state with neonatal purpura fulminans. Patients with heterozygous protein C deficiency have an increased risk for thromboembolic events or coumarin-induced skin necrosis. Secondary protein C deficiency occurs during disseminated intravascular coagulation (DIC), sepsis (especially meningococcal sepsis with purpura fulminans), liver failure and vitamin K deficiency. Replacement with protein C concentrates is an established treatment for congenital protein C deficiency. The high-purity, plasma-derived protein C concentrate Ceprotin (Baxter AG, Vienna, Austria) is approved for this indication, but its use in acquired deficiency states is not approved. Several case series demonstrated beneficial effects in infectious purpura fulminans and DIC, but no controlled studies for these indications exist. Protein C concentrate may therefore be given off-label in such cases. Protein C concentrate has an excellent safety profile: no drug interactions, overdose or bloodborne infections, bleeding or prothrombotic complications have been observed. As with all protein preparations, a potential risk of hypersensitivity reactions exists.