Lepirudin in patients with heparin-induced thrombocytopenia - results of the third prospective study (HAT-3) and a combined analysis of HAT-1, HAT-2, and HAT-3.

Abstract

OBJECTIVES:

To assess efficacy and safety of lepirudin in patients with heparin-induced thrombocytopenia (HIT) in a prospective study (HAT-3) as well as in a combined analysis of all HAT study data.

PATIENTS/METHODS:

Patients with laboratory-confirmed HIT were treated with lepirudin in three different aPTT-adjusted dose regimen and during cardiopulmonary bypass (CPB). Endpoints were new thromboembolic complications (TEC), limb amputations, and death and major bleeding. A historical control group (n = 120) was used for comparison.

RESULTS:

After start of lepirudin in 205 patients treated in HAT-3, the combined endpoint occurred in 43 (21.0%). Thirty (14.6%) patients died, 10 (4.9%) underwent limb amputation, and 11 (5.4%) new TECs occurred. Major bleeding occurred in 40 patients (19.5%) (seven during CPB surgery). Combining all prospective HAT trials (n = 403), after start of lepirudin treatment, the combined endpoint occurred in 82 patients (20.3%), with 47 deaths (11.7%), 22 limb amputations (5.5%), 30 new TECs (7.4%), and 71 (17.6%) major bleedings. Compared with the historical control group (log-rank test), the combined endpoint after start of treatment was reduced (29.7% vs. 52.1%, P = 0.0473), primarily because of reduction in new thromboses (11.9% vs. 32.1%, P = 0.0008). Mean lepirudin maintenance doses ranged from 0.07 to 0.11 mg kg(-1) h(-1). Major bleeding was more frequent in the lepirudin-treated patients (29.4% vs. 9.1%, P = 0.0148).

CONCLUSIONS:

The rate of new TECs in HIT patients is low after start of lepirudin treatment. The rate of major bleeding of 17.6% might be reduced by reducing the starting dose to 0.1 mg kg(-1) h(-1).

• Authors: N Lubenow, P Eichler, T Lietz, A Greinacher, Hit Investigators Group
• Journal: Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 3 Issue 11 Pg. 2428-36 (Nov 2005) ISSN: 1538-7933 [Print] England
• PMID: 16241940 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Meta-Analysis, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Hirudins
• Recombinant Proteins
• Heparin
• lepirudin

Topics

• Adult
• Aged
• Aged, 80 and over
• Amputation, Surgical (statistics & numerical data)
• Anticoagulants (adverse effects, therapeutic use)
• Female
• Hemorrhage (etiology)
• Heparin (adverse effects)
• Hirudins (adverse effects, immunology)
• Humans
• Male
• Middle Aged
• Prospective Studies
• Recombinant Proteins (adverse effects, immunology, therapeutic use)
• Secondary Prevention
• Survival Analysis
• Thrombocytopenia (complications, drug therapy, etiology)
• Thromboembolism (etiology, prevention & control)