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.
OBJECTIVE
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.


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).
Lubenow
N
N
Department of Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.
Eichler
P
P
Lietz
T
T
Greinacher
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000671:Amputation, Surgical / Q000706:statistics & numerical data; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D006493:Heparin / Q000009:adverse effects*; D006629:Hirudins / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D055502:Secondary Prevention; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000150:complications / Q000188:drug therapy* / Q000209:etiology*; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*
D000925:Anticoagulants; D006629:Hirudins; D011994:Recombinant Proteins; D006493:Heparin; C083544:lepirudin