Lepirudin for prophylaxis of thrombosis in patients with acute isolated heparin-induced thrombocytopenia: an analysis of 3 prospective studies.
This analysis of 3 prospective multicenter trials in patients with laboratory-confirmed acute heparin-induced thrombocytopenia (HIT) without clinically evident thromboembolic complications (TECs), isolated HIT, assessed the combined individual end points of death, new TECs, and limb amputation. Patients with the same inclusion criteria who did not receive lepirudin or danaparoid served as a contemporaneous control group. Ninety-one patients were treated with lepirudin (intravenous infusion 0.10 mg/kg/h, no bolus, activated partial thromboplastin time [aPTT]-adjusted to 1.5-2.5 times baseline) for a median of 11.0 days (range, 1-68 days). During the observation period (median 24 days), 13 (14.3%) deaths, 4 (4.4%) new TECs, 3 (3.3%) limb amputations (combined 18 [19.8%]), and 13 (14.3%) major bleeding events occurred. In comparison to the control group (N = 47), the combined end point (P = .0281) and new TECs (P = .02) were reduced, and major bleeding was not significantly different between groups (P = .5419). In renal impairment, lepirudin did not reach its steady state within 4 hours, and additional monitoring every 4 hours after start of lepirudin until steady state is reached is recommended. Lepirudin seems to be effective in patients with isolated HIT. Dose reductions in renal impairment are important. Keeping the aPTT in the range corresponding to 600 to 700 microg/L lepirudin during treatment may minimize bleeding complications.
Dept of Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University Greifswald, Germany.
Norbert
N
Lubenow
Petra
P
Eichler
Theresia
T
Lietz
Beate
B
Farner
Andreas
A
Greinacher
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D000990:Antithrombin III; D005260:Female; D006493:Heparin / Q000009:adverse effects; D006629:Hirudins / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010447:Peptide Hydrolases / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D013921:Thrombocytopenia / Q000139:chemically induced*; D013927:Thrombosis / Q000517:prevention & control*; D016896:Treatment Outcome
D000925:Anticoagulants; D006629:Hirudins; D011994:Recombinant Proteins; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D006493:Heparin; D010447:Peptide Hydrolases; C083544:lepirudin