A 42-year-old mildly overweight man is being evaluated for his second episode of deep vein thrombosis in 2 years. Both episodes appear to have been unprovoked. He has no recent prolonged immobility, long-distance travel, or lower-extremity trauma. The patient has no past medical history of diabetes, cancer, or liver disease. A thrombophilia workup is ordered. Use of which of the following drugs is most likely to lead to low protein S levels?

Question

A 42-year-old mildly overweight man is being evaluated for his second episode of deep vein thrombosis in 2 years.  Both episodes appear to have been unprovoked.  He has no recent prolonged immobility, long-distance travel, or lower-extremity trauma.  The patient has no past medical history of diabetes, cancer, or liver disease.  A thrombophilia workup is ordered.  Use of which of the following drugs is most likely to lead to low protein S levels?

Quizplus · Accepted Answer

11ec25c8_d40b_25e0_bc81_a3669748341b_MD0003_00 Warfarin is a coumarin anticoagulant most commonly used in the setting of thrombophilia and cardiac conditions that predispose to intracardiac thrombus formation. Warfarin functions by inhibiting synthesis of the vitamin K-dependent clotting factors II, VII, IX, and X, as well as the vitamin K-dependent anticoagulant proteins C and S. As a result, it can cause a decrease in measured levels of protein S. This may lead to an incorrect diagnosis of inherited protein S deficiency. If possible, vitamin K antagonists such as warfarin should be discontinued for 2 weeks prior to evaluating protein S levels. (Choice A) Aspirin is an antiplatelet agent that inhibits cyclooxygenase-1, thereby inhibiting thromboxane A₂ synthesis. (Choice B) Clopidogrel is an antiplatelet agent that prevents platelet activation by blocking adenosine diphosphate receptors on the surface of platelets. (Choice C) Heparin activates antithrombin III, which in turn inactivates factor IIa (thrombin), factor IXa, and factor Xa. (Choice D) Simvastatin is a lipid-lowering agent that functions by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme reductase. Educational objective: Warfarin is an anticoagulant agent that functions by inhibiting the synthesis of vitamin K-dependent factors II, VII, IX, and X, protein C, and protein S. References: Pitfalls in special coagulation testing: three illustrative case studies. (http://www.ncbi.nlm.nih.gov/pubmed/23480842) Protein S abnormalities: a diagnostic nightmare. (http://www.ncbi.nlm.nih.gov/pubmed/21523802)

A 42-Year-Old Mildly Overweight Man Is Being Evaluated for His