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A 19-year-old normal nonsmoking female has a moderately severe pulmonary embolism while on oral contraceptive pills. Which of the following is the most likely predisposing factor?
A. Abnormal factor V
B. Abnormal protein C
C. Diminished protein C level
D. Diminished protein S level
E. Diminished antithrombin III level
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The answer is A.
Many patients who develop pulmonary thromboembolism have an underlying inherited predisposition that remains clinically silent until they are subjected to an additional stress, such as the use of oral contraceptive pills, surgery, or pregnancy.
The most frequently inherited predisposition to thrombosis is so-called activated protein C resistance. The inability of a normal protein C to carry out its anticoagulant function is due to a missense mutation in the gene coding for factor V in the coagulation cascade. This mutation, which results in the substitution of a glutamine for an arginine residue in position 506 of the factor V molecule, is termed the factor V Leiden gene.
Based on the Physicians Health Study, about 3% of healthy male physicians carry this particular missense mutation. Carriers are clearly at an increased risk for deep venous thrombosis and also for recurrence after the discontinuation of warfarin. The allelic frequency of factor V Leiden is higher than that of all other identified inherited hypercoagulable states combined, including deficiencies of protein C, protein S, and antithrombin III and disorders of plasminogen
