A 44-year-old male is hospitalized with unstable angina. On the fourth day of hospitalization he develops severe foot pain and right toe paleness. His laboratory testing is significant for platelet count of 60,000/mm³. Treatment with argatroban is initiated immediately. The drug (argatroban) used to treat this patient's current condition has which mechanism of action?

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Heparin is the most important cause of thrombocytopenia in hospitalized patients. Occurrence of heparin-induced thrombocytopenia (HIT) is much more common with the use of unfractionated heparin compared to low molecular weight heparin. HIT more commonly leads to paradoxical thrombosis rather than bleeding. HIT is a serious disorder caused by antibodies to heparin and platelet factor IV. Direct thrombin inhibitors (hirudin, lepirudin and argatroban) do not require antithrombin-III for their action and are drugs of choice in the treatment of HIT. Patients with HIT need ongoing anticoagulation due to the presence of, or possibility of thrombosis. Upon clinical suspicion of HIT, the most important initial step in treatment is to stop all forms of heparin. (Choice B) Warfarin inhibits vitamin K dependent γ-carboxylation of glutamic acid residues of clotting factors II, VII, IX and X. (Choices C, D and E) Platelet plug formation involves three critical steps: adhesion, aggregation and release (see diagram). Drugs that inhibit platelet aggregation work by different mechanisms. 11ec160b_3bd8_1144_9249_8d278a8680e2_MD0001_00 Aspirin irreversibly acetylates platelet cyclooxygenase-I leading to decreased formation of thromboxane A2. Aspirin is used for primary and secondary prevention of myocardial infarction and strokes. Ticlopidine and clopidogrel inhibit ADP mediated platelet aggregation. They are useful following percutaneous coronary intervention (PCI), and for treatment of unstable angina and non-Q wave myocardial infarction. Dipyridamole and cilostazol inhibit platelet aggregation by inhibiting phosphodiesterase activity and increasing cAMP. Glycoprotein IIb/IIIa inhibitors inhibit binding of platelet glycoprotein IIb/IIIa with fibrinogen and fibronectin. The glycoprotein IIb/IIIa inhibitors abciximab, eptifibatide and tirofiban are approved for use following percutaneous intervention (PCI) in acute coronary syndrome. Educational objective: Heparin-induced thrombocytopenia (HIT) is treated with direct thrombin inhibitors (DTIs) such as argatroban. Both high molecular weight heparin and LMWH should be avoided in these patients.

A 44-Year-Old Male Is Hospitalized with Unstable Angina