A 64-year-old woman is hospitalized for elective hip replacement surgery. She has osteoarthritis and is experiencing progressive right hip pain that limits her daily activities. The patient also has a history of hypertension and hypothyroidism. Her blood pressure is 130/80 mm Hg and pulse is 90/min. BMI is 31.5 kg/m². Her serum creatinine is 0.9 mg/dL. She undergoes surgery without complications and is postoperatively started on a medication that is a low molecular weight fraction of a negatively charged chemical stored in mast cell granules. Which of the following is the most likely mechanism of action of the medication used?

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11ec160b_3bd7_9c13_9249_979a9ee583e1_MD0001_00 Nonambulatory hospitalized patients are at increased risk for developing lower extremity deep venous thrombosis (DVT), which can lead to pulmonary embolism. In patients undergoing elective surgery without prophylaxis against DVT, the risk can be even higher, particularly with certain orthopedic procedures such as hip and knee replacement. In such cases, DVT prophylaxis is usually initiated within hours of wound closure. Unfractionated and low molecular weight heparins (LMWHs) are commonly used for DVT prevention in inpatient settings. Administration of heparin (a negatively charged chemical naturally present in mast cells) increases the effect of the naturally occurring anticoagulant antithrombin III (AT III). Unfractionated heparin binds to AT III via a pentasaccharide in the heparin chain. This results in a conformational change of AT III, which subsequently inhibits factor Xa and neutralizes thrombin, promoting anticoagulation. AT III activated by LMWH (which has better bioavailability and does not need laboratory monitoring when given therapeutically) acts predominantly on factor Xa, not thrombin. (Choice B) Direct thrombin inhibitors directly inhibit thrombin-mediated fibrin formation. Lepirudin and argatroban (parenteral) are primarily used for management of heparin-induced thrombocytopenia. Dabigatran (oral) is used for DVT prevention and treatment and for stroke prevention in atrial fibrillation. (Choice C) Clopidogrel and ticlopidine inhibit ADP-mediated platelet aggregation. They are useful following percutaneous coronary intervention and for treatment of unstable angina and non-ST segment elevation myocardial infarction. (Choice D) Use of drugs that convert inactive plasminogen to plasmin leads to fibrinolysis and clot lysis; such medications are given for clot lysis in acute myocardial infarction, pulmonary embolism, and arterial thrombosis. (Choice E) 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 stroke. Educational objective: Heparin is commonly used for the prevention of deep venous thrombosis in nonambulatory patients or those undergoing elective surgery, especially hip and knee surgery. Heparin increases the effect of the naturally occurring anticoagulant antithrombin III. __________ References: New Antithrombotic Drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Page(s): PMC3278067 (http://www.ncbi.nlm.nih.gov/pubmed/3278067) New anticoagulants. (http://www.ncbi.nlm.nih.gov/pubmed/20368532)

A 64-Year-Old Woman Is Hospitalized for Elective Hip Replacement Surgery