Effects of argatroban therapy, demographic variables, and platelet count on thrombotic risks in heparin-induced thrombocytopenia

Bruce E. Lewis, Diane E. Wallis, Marcie J. Hursting, Robert L. Levine, Fred Leya

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

Study objectives: We investigated the effects of the direct thrombin inhibitor argatroban, patient demographics, and the platelet count on thrombotic risks in heparin-induced thrombocytopenia (HIT), a serious thrombotic condition, to determine if argatroban provides effective antithrombotic therapy in patients with HIT without increasing bleeding. Design: We retrospectively analyzed thrombotic outcomes in 882 HIT patients (697 patients receiving mean argatroban doses of 1.7 to 2.0 μg/kg/min for 5 to 7 days, plus 185 historical control subjects) from previously reported prospective studies. Time-to-event analyses of our primary end point-a thrombotic composite of death due to thrombosis, amputation secondary to HIT-associated thrombosis, or new thrombosis within 37 days-and the individual components were conducted, with hazard ratios estimated for treatment with and without adjustments for patient age, gender, race, weight, and baseline platelet count. Measurements and results: Argatroban, vs control, significantly reduced the thrombotic composite risk (HIT: hazard ratio, 0.33; 95% confidence interval [CI], 0.20 to 0.54, p < 0.001; HIT with thrombosis: hazard ratio, 0.39; 95% CI, 0.25 to 0.62, p < 0.001), regardless of covariate adjustments. More argatroban-treated patients than control subjects remained thrombotic event free during follow-up, regardless of whether baseline thrombosis was absent (91% vs 73%) or present (72% vs 50%). Argatroban significantly reduced new thrombosis (p < 0.001) and death due to thrombosis (p ≤ 0.001). Major bleeding was similar between groups (6 to 7%, p = 0.74). Thrombotic risks were 2 times greater in nonwhite than in white patients, 1.7 times greater in female than male patients with HIT and thrombosis, and increased with decreasing weight or platelet count. Conclusions: Argatroban, vs control, provides effective antithrombotic therapy in patients with HIT, without increasing bleeding. Patients at higher risk for HIT-associated thrombosis include women, nonwhites, and individuals with current HIT-associated thrombosis, lower body weight, or more severe thrombocytopenia.

Original languageEnglish (US)
Pages (from-to)1407-1416
Number of pages10
JournalCHEST
Volume129
Issue number6
DOIs
StatePublished - Jun 2006

Keywords

  • Argatroban
  • Heparin
  • Heparin-induced thrombocytopenia
  • Platelets
  • Thrombocytopenia
  • Thrombosis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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