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Clotting Problems on the Physician Assistant Exam

The Physician Assistant Exam (PANCE) will ask questions involving too much clotting of the blood. These problems are often associated with a hypercoagulable or thrombophilic state. Medical conditions that predispose someone to a hypercoagulable state are often abnormalities in one or more aspects of Virchow’s triad: venous stasis, hypercoagulable state, and/or endothelial dysfunction.

Here are the key points on evaluating someone with a clotting problem or suspected thrombophilic disorder:

  • Look at the family history for a history of clotting. Family history is important in trying to figure out which particular problem you’re dealing with.

  • The key testing clues for deep venous thrombosis (DVT) are a long plane trip or car trip, ambulatory dysfunction, and a history of immobilization. These issues are related to the problems of venous stasis that increase the risk of developing a deep venous thrombosis.

  • Many causes of hypercoagulable state can cause deep venous thrombosis. A few can also cause arterial thromboses, including antiphospholipid antibody syndrome and Factor V Leiden mutation (homozygous).

Hereditary causes

Here are several hereditary causes of a hypercoagulable state:

  • Factor V Leiden mutation is the most common hereditary cause of thrombophilia in the world. It can be homozygous or heterozygous. It’s caused by a genetic mutation that prevents Factor V from being broken down by Protein C.

  • Prothrombin G mutation is a gene defect for prothrombin. It increases the risk of clots.

Other causes of a hypercoagulable state include deficiencies in antithrombin III, Protein C, and Protein S. You establish the deficiencies by measuring specific factor levels.

When an acute thrombosis develops, the standard treatment is intravenous heparin and then warfarin (Coumadin). This treatment has two caveats:

  • Heparin works by potentiating antithrombin III, so higher levels of heparin may be needed if someone has antithrombin III deficiency

  • In patients with Protein C and S deficiencies, the use of warfarin may actually raise the pro-clotting effect. Before you initiate warfarin, the affected person should be fully anticoagulated on heparin.

For many hereditary causes, after a deep venous thrombosis has been diagnosed, the treatment for thrombophilia is lifelong anticoagulation.

Causes of thrombophilia

You should be aware of two acquired causes of thrombophilia: malignancy and the anti-phospholipid antibody syndrome.

Malignancies related to solid organ cancers, particularly pancreatic cancer, can increase the risk of forming a deep venous thrombosis. The treatment is usually lifelong anticoagulation and treatment of the underlying cancer.

Antiphospholipid antibody syndrome (APS) is an acquired coagulation disorder that can present with thrombocytopenia, venous (or arterial) thromboses, and spontaneous abortions, usually in the second trimester. In addition to the clinical history, lab tests that can confirm antiphospholipid antibody syndrome include a lupus anticoagulant and anticardiolipin antibody. The treatment is anticoagulation.

Which of the following statements concerning the use of warfarin (Coumadin) is true?

(A) It works by increasing the activity of vitamin K.
(B) It is used for chronic anticoagulation for medical conditions such as deep venous thrombosis and atrial fibrillation.
(C) A rare side effect is bone necrosis.
(D) It is used for anticoagulation acutely in the setting of a myocardial infarction.
(E) It can be given during pregnancy.

The answer is Choice (B). Warfarin antagonizes the activity of vitamin K. It causes warfarin-induced skin necrosis, not bone necrosis. Because warfarin does not inhibit platelet aggregation, warfarin isn’t used in the acute treatment of a myocardial infarction. Heparin and other antiplatelet agents are used. And it can’t be given during pregnancy.

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