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HIT lepirudin indicated dose 'too high'
The currently recommended dose of the direct thrombin inhibitor lepirudin in patients with heparin-induced thrombocytopenia (HIT) may be excessive, French clinicians believe.
Bernard Tardy, from Hôpital Bellevue in Paris, and colleagues investigated the impact of lepirudin dosage on hemorrhage risk in 181 patients, aged a median of 67 years, who developed HIT a median of 10.7 days after heparin therapy. Almost half (49.2%) of the patients had experienced thrombosis and 6.1% had developed major bleeding.
Lepirudin therapy began with a bolus dose in 59% of patients. The mean total dose during the median duration of 7.7 days was calculated to be 0.06 mg/kg/hour. This varied from 0.04–0.15 mg/kg/hour, with the highest doses given to patients with a history of thrombosis.
This average dose was significantly below the recommended initial lepirudin dosing for HIT patients of 0.15 mg/kg/hour, the researchers observe in the journal Blood.
Overall, 13.8% of patients experienced thrombosis and 20.4% had a major bleeding episode, including seven fatal hemorrhages, during lepirudin therapy.
Multivariate analysis demonstrated that only mean heparin dose predicted risk of thrombosis during lepirudin therapy.
In contrast, the likelihood of major bleeding was significantly foretold by an average lepirudin dose greater than 0.07 mg/kg/hour (odds ratio [OR]=11.01), a long duration of lepirudin therapy (OR=1.10 per extra day), and the presence of moderate-to-severe renal impairment (OR=13.20).
"Current dosing recommendations for lepirudin in patients with HIT may be too high," Tardy et al conclude.
"If this hypothesis is confirmed in prospective trials, the use of lower, but still effective, doses of lepirudin in HIT patients may improve the benefit-to-risk ratio of this drug for the management of this complex syndrome," they postulate.