Recombinant hirudin (lepirudin) provides safe and effective anticoagulation in patients with heparin-induced thrombocytopenia: a prospective study.
BACKGROUND
The immunological type of heparin-induced thrombocytopenia (HIT) is the most frequent drug-induced thrombocytopenia. This study evaluated the efficacy of recombinant hirudin (r-hirudin or lepirudin), a potent thrombin inhibitor, for anticoagulation in patients with confirmed HIT.


RESULTS
Eighty-two patients in this prospective, multicenter study received 1 of 4 intravenous r-hirudin regimens: A1, HIT patients with thrombosis (n=51), 0.4-mg/kg bolus and then 0.15 mg. kg-1. h-1; A2, HIT patients with thrombosis receiving thrombolysis (n=5), 0. 2-mg/kg bolus and then 0.1 mg. kg-1. h-1; B, HIT patients without thrombosis (n=18), 0.1 mg. kg-1. h-1; and C, during cardiopulmonary bypass surgery (n=8), 0.25-mg/kg bolus and then 5-mg boluses as needed. Response criteria were increase in platelet count by >/=30% to >10(9)/L and activated partial thromboplastin time (aPTT) values 1.5 to 3.0 times baseline values achieved with a maximum of 2 dose increases. No placebo control was used for ethical reasons. Outcomes of a subset of r-hirudin-treated patients who met predefined inclusion criteria (n=71) were compared with those of a historical control group (n=120) for combined and individual incidences of death, amputations, new thromboembolic complications, and incidences of bleeding. Platelet counts increased rapidly in 88.7% of r-hirudin-treated patients with acute HIT. In regimens A1 and A2, the 25% and 75% quartiles of the aPTT were within the target range at all but 1 time point. The incidence of the combined end point (death, amputation, new thromboembolic complications) was significantly reduced in r-hirudin patients compared with historical control patients (P=0.014). During first selected treatment, the adjusted hazard ratio for r-hirudin patients versus historical control was 0.279 (95% CI, 0.112 to 0.699; P=0.003). Bleeding rates were similar in both groups.


CONCLUSIONS
r-Hirudin treatment is associated with a rapid and sustained recovery of platelet counts, sufficient aPTT prolongations, and true clinical benefits for patients with HIT.
Greinacher
A
A
Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany. greinach@rz.uni-greifswald.de
Völpel
H
H
Janssens
U
U
Hach-Wunderle
V
V
Kemkes-Matthes
B
B
Eichler
P
P
Mueller-Velten
H G
HG
Pötzsch
B
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005858:Germany / Q000453:epidemiology; D006470:Hemorrhage / Q000453:epidemiology; D006493:Heparin / Q000009:adverse effects*; D024764:Hirudin Therapy; D006629:Hirudins / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
D000925:Anticoagulants; D006629:Hirudins; D011994:Recombinant Proteins; D006493:Heparin; C083544:lepirudin