Heparin must first bind to _____ to exert its anticoagulant activity.
a. Antithrombin. Heparin must first bind to antithrombin to exert its anticoagulant effect. This complex accelerates antithrombin effect. Heparin potentiates antithrombin’s effect by binding to a glucosamine unit within a pentasaccharide sequence.
J. M. was initiated on heparin and was given a 5,000-unit bolus. Five minutes after the loading dose of heparin, she began to have bloody emesis, and her systolic pressure dropped to 80 mmHg. How much protamine will she require?
b. 50 mg. Every 1 mg of protamine will antagonize approximately 100 units of heparin. Because this patient just received the bolus, she would require 50 mg of protamine. If she had received the dose 30 to 60 minutes ago, then a dose of 0.50 to 0.75 mg of protamine per 100 units of heparin would be required. If she had been on a continuous infusion of heparin, then the dosing would be dependent on the time and dose of the last bolus of heparin and the rate of infusion. In this scenario, most patients require approximately 25 to 50 mg of protamine.
Patients who develop heparin-induced thrombocytopenia have an in vitro cross-reactivity with low-molecular-weight heparin (LMWH) by what percent?
a. 90% to 100%. There have been several reports of patients who have heparin-induced thrombocytopenia being treated with LMWH. However, the cross-reactivity in vitro approaches 100%. The use of LMWH should be considered a contraindication unless there is a documented negative test for antibodies against LMWH.
A patient with a recent history of heparin-associated antibodies presents with new-onset symptomatic AFib and requires anticoagulation. Other significant past medical history includes severe renal failure secondary to long-standing HTN. The patient’s baseline serum creatinine is 4 mg/dL, with an estimated creatinine clearance of 10 mL/min. Which of the following choices is the best initial therapy?
c. Argatroban, 2 µg/kg/min. Argatroban is hepatically cleared and, therefore, does not require dosing adjustment for patients with renal dysfunction and may be a safer alternative for anticoagulation. Lepirudin is reasonable as well; however, patients with significant renal dysfunction require appropriate dosing adjustments. Continuous infusion should not be used in patients with a creatinine clearance <15 mL/min because of accumulation of drug. LMWHs have a high likelihood for in vitro and in vivo crossreactivity of 80% to 100%, and there is a potential for an increase in thrombotic complications.
What is the maximum dose of aspirin that can be concomitantly administered with ticagrelor?
b. 100 mg. The Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes (PLATO) trial evaluated antiplatelet strategies in addition to aspirin post-ACS. The trial did not mandate a specific aspirin maintenance dose which was left to the discretion of the provider. After trial completion, a subset analysis was performed which favored ticagrelor use with low maintenance dose aspirin (≤100 mg) as higher doses resulted in decreased ticagrelor effectiveness. The package insert for ticagrelor recommends the maintenance dose of aspirin to be 75–100 mg daily if being used concomitantly with ticagrelor. An initial 325 mg dose of aspirin should still be given with ticagrelor in the ACS setting.
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