A 64-year-old man admitted to a rehabilitation facility after right total knee replacement develops sudden-onset chest pain and shortness of breath on postoperative day 5. He has been receiving heparin for prophylaxis of deep vein thrombosis. Two months ago, he was hospitalized for pneumonia and improved with 1 week of antibiotics. Examination shows clear lungs and normal heart sounds. Cardiac enzymes are normal. ECG shows sinus tachycardia. CT angiogram reveals pulmonary embolism. Complete blood count shows platelets of 45,000/mm³. Prior to the knee surgery, his platelet count was 170,000/mm³. Heparin is discontinued and argatroban is started. Which of the following is the best approach for this patient?

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Explanation: 11ec2b69_bf60_1c3b_8f63_5177cbc7e7ef_MD0005_00 This patient with a newly diagnosed pulmonary embolism (requiring anticoagulation) has thrombocytopenia in the setting of recent heparin therapy. This presentation suggests type 2 heparin-induced thrombocytopenia (HIT), an immune-mediated disorder resulting in platelet aggregation and thrombosis (eg, pulmonary embolism). HIT should be suspected clinically when platelet counts fall ≥50% from baseline 5-14 days after starting heparin, in new-onset unexplained thrombocytopenia, or with thrombosis in patients recently treated with heparin. The first management step is to immediately stop all heparin products (including low molecular-weight heparin such as enoxaparin) and obtain confirmatory laboratory testing (eg, serotonin release assay). Alternate agents such as direct thrombin inhibitors (eg, argatroban, bivalirudin) or fondaparinux (synthetic pentasaccharide) should be given due to the high risk of thrombosis in type 2 HIT. These agents are not administered orally; therefore, the patient with a pulmonary embolism would need to be transitioned to an oral anticoagulant. Initial treatment with warfarin by itself is contraindicated, as rapidly dropping protein C levels cause a prothrombotic state (Choices B, C, and D). Therefore, patients are continued on a non-heparin anticoagualnt, and warfarin is usually started after the patient recovers a platelet count to ≥150,000/mm³ (with the non-heparin anticoagulant continued until the INR is therapeutic). Direct oral anticoagulants (eg, apixaban) can also be considered. (with the non-heparin anticoagulant continued until the INR is therapeutic) Educational objective: Suspected heparin-induced thrombocytopenia requires immediate cessation of all forms of heparin, laboratory testing to confirm the diagnosis, and starting alternate anticoagulants (eg, direct thrombin inhibitors) even if thrombosis has not occurred. Warfarin is usually started after treatment with a non-heparin anticoagulant and platelet count recovery to ≥150,000/mm³. References: Antithrombotic drugs for the treatment of heparin-induced thrombocytopenia. (http://www.ncbi.nlm.nih.gov/pubmed/12211410) Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). (http://www.ncbi.nlm.nih.gov/pubmed/18574270)

A 64-Year-Old Man Admitted to a Rehabilitation Facility After Right