A PILOT-STUDY OF SUBCUTANEOUS RECOMBINANT HIRUDIN (HBW-023) IN THE TREATMENT OF DEEP-VEIN THROMBOSIS

Background: Recombinant hirudin, a pure, specific antithrombin could b e more effective than heparin in the treatment of deep vein thrombosis , but its short half-life requires constant intravenous infusion, wher eas subcutaneous administration of recombinant hirudin can ensure stab le and prolonged plasma levels. The aim of our study was to assess the pharmacokinetics, the results on the coagulation variables, and the s afety of a recombinant hirudin (HBW 023) administered subcutaneously i n patients suffering from deep vein thrombosis. Methods: Recombinant h irudin (HBW 023) was administered subcutaneously to 10 patients with r ecent deep vein thrombosis, at a dose of 0.75 mg/kg of body weight twi ce daily for 5 days, after which standard heparin and acenocoumarol we re introduced. Bilateral lower limb venography, and pulmonary angiogra phy, and/or ventilation-perfusion lung scan were carried out on day 1 prior to recombinant hirudin injection and repeated on day 5. aPTT and recombinant hirudin plasma levels were serially assessed after the 1s t and the 10th injections. Prothrombin fragments 1 + 2, thrombin-antit hrombin m complexes, fibrin degradation products were collected on day s 1 and 5. Results: Clinical evolution was uneventful in all but one p atient who had a probable recurrence of pulmonary embolism on day 4. N o hemorrhagic complication, no untoward biological event was observed. On days 5, Marder score was unchanged or had decreased. Plasma levels of recombinant hirudin peaked in between 3 and 4 h following the inje ction. aPTT values paralleled, and were significantly correlated with plasma levels of recombinant hirudin on day 1 as well on day 5 (r = 0. 903, r = 0.948 respectively). Fragment 1 + 2, and thrombin antithrombi n complexes non-significantly decreased from day 1 to day 5. Conclusio ns: Subcutaneous administration of recombinant hirudin ensures prolong ed stable plasma levels of recombinant hirudin which results in effici ent anticoagulation. A dose-ranging study conducted with subcutaneous recombinant hirudin in comparison to conventional heparin therapy may answer the question as to efficacy.