Argatroban Anticoagulation in Patients With Heparin-Induced Thrombocytopenia

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Résumé

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an intensely prothrombotic syndrome managed by discontinuation of heparin therapy and substitution of an alternative inhibitor of thrombin. We describe our experience with argatroban, a direct thrombin inhibitor, in patients with HIT or HIT with thrombosis (HITTS). METHODS: In this multicenter, nonrandomized prospective study, 418 patients with HIT were administered intravenous argatroban, 2 micro g/kg per minute, adjusted to maintain the activated partial thromboplastin time at 1.5 to 3 times the baseline value for a mean of 5 to 7 days. Comparisons were made with a historical control cohort (n = 185). The prospectively defined, primary efficacy end point was a composite of all-cause death, all-cause amputation, or new thrombosis in 37 days. Other end points included the components of the composite, death due to thrombosis, increased platelet count, and bleeding. RESULTS: In the HIT arm, the composite end point was significantly reduced in argatroban-treated patients vs controls (28.0% vs 38.8%; P =.04). In the HITTS arm, the composite end point occurred in 41.5% of argatroban-treated patients vs 56.5% of controls (P =.07). By time-to-event analysis of the composite end point, argatroban therapy was significantly better than historical control therapy in HIT (P =.02) and HITTS (P =.008). Argatroban therapy also significantly reduced new thrombosis in HIT and HITTS and death due to thrombosis in HITTS. There were no significant between-group differences in all-cause death or amputation. Platelet counts recovered more rapidly in argatroban-treated patients than in controls. Bleeding rates were similar between groups. CONCLUSION: Argatroban therapy, compared with historical control, improves outcomes, particularly new thrombosis and death due to thrombosis, in patients with heparin-induced thrombocytopenia.

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La notice

Revue

Archives of Internal Medicine

Thématique

Heparin-Induced Thrombocytopenia and Thrombosis

Domaine

Medicine

Établissements canadiens

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Organismes subventionnaires

Medical Center, University of RochesterClaude Pepper Older Americans Independence Center, Wake Forest School of MedicineUniversity of California, San FranciscoCollege of Engineering, Michigan State UniversityNational Institutes of HealthUniversity of AlbertaUniversity of RochesterBrigham and Women's HospitalCleveland Clinic FoundationMichigan State UniversityCleveland ClinicGeorge Washington UniversityHeart and Stroke Foundation of CanadaNorthwestern UniversityUniversity of Nebraska Medical CenterYale UniversitySchool of Medicine, University of North Carolina at Chapel HillOchsner HealthGlaxoSmithKlineMassachusetts General Hospital

Mots-clés

ArgatrobanMedicineDirect thrombin inhibitorHeparin-induced thrombocytopeniaThrombosisDiscontinuationDiscovery and development of direct thrombin inhibitorsHeparinInternal medicineSurgeryWarfarinAnesthesiaPlateletThrombinAtrial fibrillation

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