摘要：

Congenital combined deficiency of factor V (FV) and factor VIII (FVIII; F5F8D, OMIM 227300) is a rare hereditary coagulopathy and accounts for approximately 3% of cases of rare coagulation disorders. The prevalence of this disease in the general population is estimated to be 1:1,000,000 and is significantly higher in regions where consanguineous marriages are permitted, such as the Mideast and South Asia. The disease has an autosomal recessive mode of inheritance and therefore occurs with an equal incidence among males and females. Heterozygous mutation carriers usually do not have clinical manifestations. The molecular basis of this disease differs from that of stand-alone congenital deficiencies of FVIII and FV. F5F8D is caused by mutations in either LMAN1 or MCFD2, which encode components of a cargo receptor complex for endoplasmic reticulum to Golgi transport of FV and FVIII, leading to defects in an intracellular transport pathway shared by these two coagulation factors. Congenital combined deficiency of FV and FVIII is characterized by decreased activities of both FV and FVIII in plasma, usually to 5 to 30% of normal. Clinical manifestations in most cases are represented by mild or moderate hemorrhagic syndrome. The simultaneous decreases of two coagulation factors present complications in the diagnosis and management of the disease. In female patients, the disease requires a special approach for family planning, pregnancy management, and parturition. This review summarizes recent progress in clinical, laboratory, and molecular understanding of this disorder.

收起

展开 