American Society of Hirudotherapy

Lepirudin (recombinant hirudin) for parenteral anticoagulation in patients with heparin-induced thrombocytopenia. Heparin-Associated Thrombocytopenia Study (HAT) investigators.

Research article published in Circulation (1999)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Clinical trialDrug DevelopmentGreinacher et al. · Circulation, 1999

Abstract

BACKGROUND: We prospectively investigated lepirudin for further parenteral anticoagulation in patients with heparin-induced thrombocytopenia (HIT). METHODS AND RESULTS: Patients with confirmed HIT (n=112) received lepirudin according to need for 2 to 10 days (longer if necessary): A1, treatment: 0.4 mg/kg IV bolus, followed by 0.15 mg. kg(-1). h(-1) intravenous infusion, n=65; A2, treatment in conjunction with thrombolysis: 0.2 mg/kg, followed by 0.10 mg. kg(-1). h(-1), n=4; and B, prophylaxis: 0.10 mg. kg(-1). h(-1), n=43. Outcomes from 95 eligible lepirudin-treated patients were compared with those of historical control patients (n=120). Complete laboratory response (activated partial thromboplastin time ratio >1.5 with </=2 dose increases and platelet count normalization by day 10) was achieved in 65 lepirudin-treated patients (69.1%; 95% CI, 59. 3% to 78.3%). At 2 weeks after cessation of lepirudin, 11 patients died (9.8%), 10 underwent limb amputation (8.9%), and 20 suffered a new thromboembolic complication (17.9%). The average combined event rate per patient-day decreased from 5.1% in the pretreatment period to 1.5% in the treatment period. Thirty-five days after HIT confirmation, fewer lepirudin-treated patients than historical control patients had experienced >/=1 outcome (cumulative incidence 30.9% versus 52.1%; relative risk [RR] 0.71; P=0.12, log-rank test). Bleeding events were more frequent in the lepirudin group than the historical control group (cumulative incidence at 35 days, 44.6% versus 27.2%; RR 2.57; P=0.0001, log-rank test). No difference was observed in bleeding events requiring transfusion (cumulative incidence at 35 days, 12.9% versus 9.1%; RR 1.66; P=0.23, log-rank test); no intracranial bleeding was observed in the lepirudin group. CONCLUSIONS: Lepirudin effectively prevents death, limb amputations, and new thromboembolic complications and has an acceptable safety profile in HIT patients. Treatment should be initiated as soon as possible if HIT is suspected.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Publication typeClinical TrialComparative StudyControlled Clinical TrialJournal ArticleMulticenter StudyResearch Support, Non-U.S. Gov't
Indexed MeSH termsAgedAmputation, SurgicalAnticoagulantsAutoimmune DiseasesFemaleHemorrhageHeparinHirudin TherapyHirudinsHumansLife TablesMale

Summary

Lepirudin (recombinant hirudin) for parenteral anticoagulation in patients with heparin-induced thrombocytopenia. Heparin-Associated Thrombocytopenia Study (HAT) investigators.

Why This Matters for Hirudotherapy

This prospective trial evaluated lepirudin (recombinant hirudin) for parenteral anticoagulation in 112 patients with confirmed heparin-induced thrombocytopenia (HIT), compared with 120 historical controls. Lepirudin reduced the combined event rate per patient-day from 5.1% pretreatment to 1.5% during treatment, with fewer cumulative endpoints at 35 days versus controls (30.9% vs. 52.1%), though bleeding events were more frequent in the lepirudin group (44.6% vs. 27.2%) without a significant difference in transfusion-requiring bleeds and no intracranial hemorrhage. This study demonstrates the clinical value of a leech-derived anticoagulant in a life-threatening condition, directly relevant to ASH's interest in therapeutic applications of the leech secretome. However, the study used historical rather than concurrent controls and evaluated pharmaceutical-grade recombinant hirudin, not live leech therapy.

Citation

Lepirudin (recombinant hirudin) for parenteral anticoagulation in patients with heparin-induced thrombocytopenia. Heparin-Associated Thrombocytopenia Study (HAT) investigators.

Greinacher et al. · Circulation, 1999

Added to ASH library: May 28, 2026 · Site last updated: June 18, 2026

This website provides educational information and does not constitute medical advice, diagnosis, or treatment recommendations. Medicinal leech therapy carries clinically meaningful risks and should be performed only by qualified clinicians under institutionally approved protocols. FDA 510(k) clearance for medicinal leeches is limited to specific indications; investigational and off-label discussions are labeled accordingly. For patient-specific guidance, consult a qualified healthcare provider.