Argatroban Anticoagulation for Heparin-Induced Thrombocytopenia in Obese, Versus Non-Obese, Patients.

Argatroban, a parenteral direct thrombin inhibitor used for prophylaxis or treatment of thrombosis in heparin-induced thrombocytopenia (HIT), is routinely administered in accordance with patient body weight and activated partial thromboplastin time (aPTT) response. The effect of obesity (BMI >30) on argatroban therapy in HIT however is not well described. In this retrospective analysis of a 118-patient, multicenter HIT registry database, we evaluated argatroban doses, aPTTs, and clinical outcomes in obese, vs. non-obese, argatroban-treated adults with clinically diagnosed HIT or history of HIT. Patients lacking sufficient data to calculate BMI, administered argatroban at doses required during angioplasty, or with a baseline (pre-argatroban) platelet count >150x10⁹/L were excluded. Argatroban was infused and adjusted to achieve aPTTs 1.5–3 times baseline, at the treating physician’s discretion. We identified 41 patients for analysis: 21 non-obese (BMI 17.3–28.9, median 22.9; 52% female) and 20 obese (BMI 30.1–50.8, median 34.8; 55% female). Two patients (1 per group) had history of HIT requiring acute anticoagulation; 39 patients had HIT (median baseline platelet count of 85 and 92x10⁹/L, respectively, in non-obese and obese patients), including 9 (5 obese) with baseline HIT-related thrombosis. Indications for heparin therapy, typically cardiac- or surgery-related, were similar between the non-obese and obese groups. Median argatroban doses were 1.0 μg/kg/min initially in each group, and 1.0 and 1.2 μg/kg/min in the non-obese and obese groups, respectively, during therapy (median 5.4 and 6.3 days, respectively). Therapeutic aPTTs occurred within a median 5.6 and 5.0 h, respectively, with median aPTTs during therapy of 60.5 and 58.7 s. By regression analysis, BMI did not significantly affect argatroban dose. Platelet counts recovered (>100x10⁹/L or 1.5 times baseline) within 4.3 and 2.4 days for the non-obese and obese HIT patients, respectively. Within 37 days of argatroban initiation, death occurred in 7 (33%) non-obese and 5 (25%) obese patients (1 in each group while on argatroban); amputation in 0 (0%) non-obese and 1 (5%) obese patient (off argatroban); new thrombosis in 1 (5%) non-obese and 3 (15%) obese patients (2 while on argatroban); and major bleeding in 1 (5%) non-obese (off argatroban) and 0 (0%) obese patient. Cox regression analysis failed to identify any significant risk factors (BMI, obesity, gender, argatroban dose, baseline platelet count, aPTT) for new thrombosis. We conclude that argatroban dose requirements, aPTT responses, and clinical outcomes are generally comparable between obese vs. non-obese patients with HIT or history of HIT. These findings support the use of body weight-adjusted (and aPTT-adjusted) argatroban dosing for safe, effective anticoagulation, irrespective of patient BMI.