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Heparin-Associated Thrombocytopenia 2 - HAT 2
Description:
The goal of the study was to evaluate treatment with lepirudin compared with historical controls among patients with heparin-induced thrombocytopenia (HIT).
Study Design
Study Design:
Patients Enrolled: 112
Mean Patient Age: Range 11-82 years
Female: 53
Patient Populations:
Diagnostic decrease in platelet count by ≥50% or to values <100 g/L and/or new TECs during prestudy heparin administration.
Exclusions:
Overt signs of bleeding, pregnancy, alcohol or drug abuse, and anticipated poor compliance.
Primary Endpoints:
Proportion of laboratory responders, defined as 1) maintenance of on-treatment aPTT ratio >1.5 in ≥80% of measurements with ≤2 dose increases and 2) increase in platelet count by ≥30% from the lowest value and to a value >100 g/L by day 10 of lepirudin treatment in thrombocytopenic patients, or maintenance of a normal baseline platelet count on both days 3 and 10.
Drug/Procedures Used:
Patients with HIT were treated with lepirudin for 2 to 10 days dosed in one of the following 3 groups: a) lepirudin 0.4 mg/kg IV bolus, followed by 0.15 mg/kg/h intravenous infusion (n=65); b) thrombolysis plus lepirudin 0.2 mg/kg, followed by 0.10 mg/kg/h (n=4); or c) lepirudin 0.10 mg/kg/h (n=43). Data were compared to historical controls with HIT (n=120).
Principal Findings:
Treatment was completed in 83% of patients, with a median duration of treatment of 11 days. Platelet response was achieved in 92.6% of patients, and anticoagulant response was achieved in 72.3%. The primary endpoint of complete laboratory response (both aPTT and platelet count) was achieved in 69.1% of lepirudin-treated patients. There was no difference between the lepirudin treatment regimens in median aPTT. Among the clinical events in the 2 weeks after lepirudin discontinuation, new thromboembolic complication occurred in 17.9% of lepirudin-treated patients, limb amputation in 8.9%, and death in 9.8% for a combined event rate of 29.5%. At 35 days after HIT confirmation, the composite event rates for lepirudin-treated patients trended lower compared with historical controls (30.9% vs 52.1%, p=0.12 by log-rank). Bleeding by 35 days occurred more frequently in the lepirudin-treated patients compared with historical controls (44.6% vs 27.2%, p=0.0001).
Interpretation:
Among patients with heparin-induced thrombocytopenia, treatment with lepirudin was associated with a substantial portion of patients achieving complete laboratory response and a trend toward lower rates of the composite of death, limb amputations, and new thromboembolic complications compared with historical controls, although bleeding was increased in lepirudin-treated patients.
Platelet count was increased and aPTT was prolonged in the majority of patients treated with lepirudin. While the difference in the composite of death, limb amputations, and new thromboembolic complications in lepirudin-treated patients did not reach statistical significance compared with historical controls, it was directionally in favor of lepirudin, an important finding given the few treatment options in these patients. It should be noted that the rate of bleeding was higher in lepirudin-treated patients compared with historical controls, although there was no difference in bleeding requiring transfusion.
References:
Greinacher A, et al. Lepirudin (Recombinant Hirudin) for Parenteral Anticoagulation in Patients With Heparin-Induced Thrombocytopenia. Circulation. 1999;100:587-593.
Keywords: Platelet Count, Heparin, Recombinant Proteins, Hirudins, Thrombocytopenia
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