A 26-year-old Caucasian female is found to have a single amino acid substitution (glutamine for arginine) near the protein C cleavage site in her coagulation factor V gene product. The patient is at greatest risk for developing which of the following conditions?

Question

A 26-year-old Caucasian female is found to have a single amino acid substitution (glutamine for arginine) near the protein C cleavage site in her coagulation factor V gene product.  The patient is at greatest risk for developing which of the following conditions?

Quizplus · Accepted Answer

The major clinical manifestations of factor V Leiden include deep vein thrombosis (DVT), cerebral vein thrombosis, and recurrent pregnancy loss. Because pulmonary thromboembolism occurs in approximately 50% of all individuals with untreated DVTs, the young woman presented here is at significant risk of developing a pulmonary thromboembolism at some point in her lifetime. Factor V Leiden is the most common cause of inherited thrombophilia, with the heterozygote prevalence of this genetic mutation ranging from 1-9% in Caucasian populations worldwide. Heterozygote carriers of factor V Leiden have five to ten times the risk of developing a thrombosis, while homozygote carriers of factor V Leiden have fifty to one hundred times the risk of developing a thrombosis. Factor V Leiden causes thrombophilia through two pathophysiological mechanisms. In normal hemostasis, activated protein C (APC) restricts clot formation by proteolytically inactivating factors Va and VIIIa. Factor Va Leiden has reduced susceptibility to cleavage by APC, however. Because factor Va is a cofactor in the conversion of prothrombin to thrombin, persistently circulating factor Va Leiden results in increased thrombin production. Additionally, factor V Leiden is unable to support APC anticoagulant activity. This combination of increased coagulation and decreased anticoagulation produces the hypercoagulable state seen in those with factor V Leiden. (Choice A) Petechiae and ecchymoses are more consistent with qualitative or quantitative platelet abnormalities than factor V Leiden. (Choice B) Recurrent hemarthroses are suggestive of hemophilia (factor VIII or IX deficiency), not factor V Leiden. (Choice C) Renal artery stenosis is primarily caused by atherosclerosis and fibromuscular disease, not thrombosis. Moreover, factor V Leiden is associated with an increased risk of deep venous (not arterial) thrombosis. (Choice D) Major causes of splenic infarction include sickle cell anemia, infectious endocarditis, and myeloproliferative disorders. Moreover, the factor V Leiden mutation is associated with deep venous (not arterial) thrombosis. Educational Objective: One to nine percent of Caucasians worldwide are heterozygote carriers of factor V Leiden, which is modified to resist activated protein C. The resulting hypercoagulable state predisposes to deep vein thromboses, which are the source of most pulmonary emboli.

A 26-Year-Old Caucasian Female Is Found to Have a Single