Stroke in patients with heparin-induced thrombocytopenia and the effect of argatroban therapy

Objective. To investigate the frequency, mortality rate, and characteristics of stroke in heparin-induced thrombocytopenia and the effect of argatroban therapy in that setting. Design: Retrospective analysis of two prospective studies of argatroban therapy in heparin-induced thrombocytopenia. Setting: Hospitalized care. Patients. Patients were 960 patients with heparin-induced thrombocytopenia (767 argatroban-treated patients, 193 historical controls). Interventions. Argatroban 2 mug-kg(-1.)min(-1), adjusted to achieve activated partial thromboplastin times 1.5-3 times baseline. Measurements and Main Results: Case records were reviewed to identify patients with stroke present at or within 37 days of study entry and to assess 37-day outcomes. Stroke occurred in 30 (3.1%) patients (stroke at entry, n = 9; new stroke during follow-up, n = 24; more than one stroke, n = 4). By logistic regression with treatment, protocol, age, and gender as covariates, females were significantly more likely to suffer stroke (odds ratio, 2.48; 95% confidence interval, 1.11-5.53; p = .026) and stroke-associated mortality (odds ratio, 4.10; 95% CI, 1.12-15.01; p = .033), and argatroban-treated patients had significantly reduced odds, vs. control, of new stroke (odds ratio, 0.31; 95% confidence interval, 0.10-0.96; p = .041) and stroke-associated mortality (odds ratio, 0.18; 95% confidence interval, 0.03-0.92; p = .039). Stroke (odds ratio, 3.66; 95% confidence interval, 1.73-7.73; p < .001) and age (odds ratio per year, 1.017; 95% confidence interval, 1.004-1.029; p = .008) were significant predictors of all-cause death. In the argatroban group, baseline platelet counts were significantly less in patients with, vs. without, stroke (medians, 42 x 10(9)/L vs. 72 x 10(9)/L; p = .006). Of 35 stroke events, 33 (94%) were ischemic and two (6%) were hemorrhagic (one per group, none during argatroban infusion); 30 (86%) were present at or within 13 days of entry. Conclusions. Stroke, particularly ischemic stroke, is common in heparin-induced thrombocytopenia and significantly increases mortality risk, Stroke in heparin-induced thrombocytopenia occurs most often in females, in patients with more severe thrombocytopenia, and within 2 wks of heparin-induced thrombocytopenia presentation. Argatroban therapy vs. control significantly reduces the likelihood of new stroke and stroke-associated mortality in heparin-induced thrombocytopenia without increasing intracranial hemorrhage.