Inheritance of Factor VII and Protein S Deficiency Together with Factor V Leiden Mutation

Homozygous or heterozygous mutations of factor V Leiden (FV Leiden) and the thrombophilic factors like protein S deficiency are associated with venous or arterial thrombosis. In these patients, thrombosis may be seen even in the presence of coexistent congenital disorders of bleeding. Factor VII (FVII) deficiency is a rare autosomal recessive disorder of blood coagulation. When FVII deficiency occurs in combination with thrombophilic mutations, the symptoms of hemorrhagic diathesis are alleviated, like in other inherited hemorrhagic disorders. Herein, a 5-year-old and a 7-year-old, an asymptomatic sister and brother who respectively had 2 (FV Leiden mutation and protein S deficiency) and 1 (FV Leiden mutation) thrombophilic factors coexistent with FVII deficiency, are presented. The levels of FVII were 36% (N: 55%-116%) in the sister and 38% (N: 52%-120%) in the brother. FV Leiden mutation was homozygous and heterozygous in the sister and the brother, respectively. The protein S activity was 47% (N: 54%-118%) in the sister and normal in the brother. Familial work-up revealed FV Leiden mutation (heterozygous) in both parents and protein S deficiency in the mother [51% (N: 55%-160%)]. The paternal grandmother, who had died due to myocardial infarction, was learned to have had FVII deficiency. Neither of the siblings nor the grandmother had hemorrhagic diathesis. Even children with moderately decreased FVII levels may present with bleeding symptoms. Therefore, we think that the absence of hemorrhagic diathesis in our patients can be attributed to coinheritance of thrombophilic factors (protein S deficiency and/or FV Leiden mutation).