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

Chest. 2006 Jun;129(6):1407-16. doi: 10.1378/chest.129.6.1407.

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 mug/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.

MeSH terms

  • Aged
  • Amputation
  • Anticoagulants / therapeutic use*
  • Arginine / analogs & derivatives
  • Cohort Studies
  • Controlled Clinical Trials as Topic
  • Female
  • Heparin / adverse effects*
  • Humans
  • Male
  • Middle Aged
  • Pipecolic Acids / therapeutic use*
  • Platelet Count
  • Retrospective Studies
  • Sulfonamides
  • Thrombocytopenia / blood
  • Thrombocytopenia / chemically induced*
  • Thrombocytopenia / drug therapy*
  • Thrombosis / etiology*
  • Thrombosis / surgery
  • Treatment Outcome

Substances

  • Anticoagulants
  • Pipecolic Acids
  • Sulfonamides
  • Heparin
  • Arginine
  • argatroban