Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
vials containing 500 IU or 1000 IU as powder for reconstitution
Approved indication: congenital protein C deficiency
Australian Medicines Handbook section 7.4
Protein C is a circulating glycoprotein. When it is activated, protein C has an anticoagulant effect on the clotting system. Patients who have a deficiency of protein C are therefore prone to thrombosis. These patients may need to take warfarin for life.
Starting warfarin in a patient with a severe congenital deficiency of protein C can result in skin necrosis. This is thought to be caused by an imbalance of coagulant and anticoagulant activity which results in capillary thrombosis.
Another presentation of severe protein C deficiency is purpura fulminans. This occurs in babies who are homozygous for the deficient gene. Capillary thrombosis within a few hours of birth results in ecchymoses and skin necrosis. The child may die or require an amputation if gangrene sets in.
It is hoped that concentrates of protein C will help to manage purpura fulminans and coumarin-induced skin necrosis. This product is manufactured from pooled human plasma. One international unit contains the same protein C activity as 1 mL of plasma. An initial dose of 60–80 IU/kg is recommended to restore protein C activity. The half-life is variable and may be shortened in patients with purpura fulminans or skin necrosis so several doses may be needed to maintain the activity of protein C. In acute cases the protein C activity should be checked every six hours.
Although concentrates have been used to treat patients with protein C deficiency due to severe sepsis, a recombinant product (drotrecogin alfa) is already available. As the severe congenital cases of protein C deficiency are rare, clinical trial data are limited. Intravenous injection of the concentrate will help some patients, but it may not prevent death.
As the product is a protein patients can develop hypersensitivity reactions. Its anticoagulant action can also cause bleeding.