Vitamin K-Dependent Coagulation Factors Deficiency, Diagnosis, and Management

Vitamin K-dependent coagulation factor deficiency (VKCFD), either type I or II, is a rare inherited bleeding disorder caused by mutations in γ-glutamyl carboxylase (GGCX) or vitamin K epoxide reductase complex (VKORC1) gene. The disease is caused by a defective γ-carboxylation of several vitamin K-dependent (VKD) proteins, involved in blood coagulation, calcification, and cell signaling. Patients affected by VKCDF thus experience bleeding symptoms, but they may also develop skin hyper-laxity, skeletal, and cardiac abnormalities. VKCFD is commonly managed with the oral or parenteral administration of vitamin K1, treatment with coagulation factor (prothrombin complex) concentrates may also be needed in case of severe bleeding or surgical procedures. This chapter describes the molecular basis of the disease, its clinical manifestations, and treatment.