Argatroban Anticoagulation in Intensive Care Patients: Effects of Heart Failure and Multiple Organ System Failure

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We retrospectively evaluated argatroban dosing patterns, clinical outcomes, and the effects of heart failure and multiple organ system failure on dosing requirements in 65 adult, intensive care patients administered arga-troban anticoagulation for clinically suspected heparin-induced thrombocytopenia (n = 56) or history of heparin-induced thrombocytopenia (n = 9). Argatroban was initiated then titrated to achieve target activated partial thromboplastin times 1.5 to 3 times normal control (ie, 42–84 seconds). Overall, argatroban was initiated at 1.14 ± 0.62 μg/kg/min (mean ± SD) and administered for 11.4 ± 9.5 days, with comparable dosing patterns between patients with suspected, versus previous, heparin-induced thrombocytopenia. Sixty-four (98.5%) patients achieved target activated partial throm-boplastin times, typically following no or one dose adjustment. Therapeutic doses were lower in patients with, versus without, heart failure (0.58 ± 0.28 vs 0.97 ± 0.6 μg/kg/min, P = .042) and decreased as the number of failed organ systems increased from 1 to 2 to =3 (1.10 ± 0.67 vs 0.87 ± 0.47 vs 0.58 ± 0.47 μg/kg/min, P = .008). From argatroban initiation until patient discharge or death, 11 (16.9%) patients (3 off argatroban) developed thromboembolic complications; 14 (21.5%) died (11 off argatroban, 7 from multiple organ system failure); and 1 (1.5%) required amputation. Nine patients (13.8%) experienced bleeding, none fatal. This experience suggests that argatroban administered at approximately 1 μg/kg/min provides adequate levels of anticoagulation in many intensive care unit patients with suspected or previous heparin-induced thrombocytopenia. Reduced doses are needed when heart failure or multiple organ system failure is present.

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