ORIGINAL ARTICLE Protein C deficiency

activity <1 IU dL)1) is a rare autosomal recessive disorder that usually presents in the neonatal period with purpura fulminans (PF) and severe disseminated intravascular coagulation (DIC), often with concom-itant venous thromboembolism (VTE). Recurrent thrombotic episodes (PF, DIC, or VTE) are common. Homozygotes and compound heterozygotes often possess a similar phenotype of severe protein C deficiency. Mild (i.e. simple heterozygous) protein C deficiency, by contrast, is often asymptomatic but may involve recurrent VTE episodes, most often triggered by clinical risk factors. The coagulopathy in protein C deficiency is caused by impaired inactiva-tion of factors Va and VIIIa by activated protein C after the propagation phase of coagulation activa-tion. Mutational analysis of symptomatic patients shows a wide range of genetic mutations. Manage-ment of acute thrombotic events in severe protein C deficiency typically requires replacement with pro-tein C concentrate while maintaining therapeutic anticoagulation; protein C replacement is also used for prevention of these complications around sur-gery. Long-term management in severe protein C deficiency involves anticoagulation with or without a protein C replacement regimen. Although many patients with severe protein C deficiency are born with evidence of in utero thrombosis and experience multiple further events, intensive treatment and monitoring can enable these individuals to thrive. Further research is needed to better delineate optimal preventive and therapeutic strategies