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Elevated serum homocysteine
4%
11/270
Thrombin inhibitor deficiency
9%
24/270
Deficiency in protein C
41%
112/270
Auto-antibodies directed against phospholipids
11%
29/270
Resistance to clotting factor degradation
33%
89/270
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The most likely diagnosis in this patient is an unprovoked deep venous thrombosis (DVT) due to inherited factor V Leiden mutation. The factor V Leiden mutation creates a hypercoagulable state by producing a mutant factor V that is resistant to degradation by activated protein C. Factor V Leiden is the most common inherited thrombophilia among Caucasians. It classically presents with recurrent unprovoked DVTs in otherwise healthy caucasian individuals in their 20s and 30s. Normally, protein C degrades activated factors V and VIII to slow the coagulation cascade. The factor V Leiden mutation is a point mutation (Arg506Gln) that impairs inactivation of factor V by protein C. This subsequently leads to excess activated factor V, unregulated prothrombin activation, and a hypercoagulable state. Incorrect Answers: Answer 1: Hyperhomocysteinemia is associated with an increased risk of thrombotic events. Multiple mechanisms have been proposed for the association between homocysteine and thrombosis including elevated tissue factor expression, impaired anticoagulant activity, and enhanced platelet activation. Answer 2: Antithrombin III is an endogenous anticoagulant that regulates the coagulation cascade by inactivating multiple clotting factors including Xa and IIa. Antithrombin III deficiency is a rare inherited cause of recurrent venous thrombosis, pulmonary embolism, and intrauterine fetal death. Answer 3: Proteins C and S are endogenous anticoagulants that regulate the coagulation cascade by degrading factors V and VIII. Deficiencies in either protein will lead to a prothrombotic state. Answer 4: Antiphospholipid antibody syndrome (APLS) is an autoimmune condition characterized by recurrent arterial and venous thrombi as well as recurrent miscarriages. It occurs due to the presence of antibodies directed against phospholipids on plasma membranes. Bullet Summary: Factor V Leiden thrombophilia is the most common inherited cause of hypercoagulability. It is caused by a point mutation in factor V which renders it resistant to degradation by protein C.
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