A pilot study of subcutaneous recombinant hirudin (HBW 023) in the treatment of deep vein thrombosis.

BACKGROUND: Recombinant hirudin, a pure, specific antithrombin could be more effective than heparin in the treatment of deep vein thrombosis, but its short half-life requires constant intravenous infusion, whereas subcutaneous administration of recombinant hirudin can ensure stable and prolonged plasma levels. The aim of our study was to assess the pharmacokinetics, the results on the coagulation variables, and the safety of a recombinant hirudin (HBW 023) administered subcutaneously in patients suffering from deep vein thrombosis. METHODS: Recombinant hirudin (HBW 023) was administered subcutaneously to 10 patients with recent deep vein thrombosis, at a dose of 0.75 mg/kg of body weight twice daily for 5 days, after which standard heparin and acenocoumarol were introduced. Bilateral lower limb venography, and pulmonary angiography, 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 1st and the 10th injections. Prothrombin fragments 1 + 2, thrombin-antithrombin III complexes, fibrin degradation products were collected on days 1 and 5. RESULTS: Clinical evolution was uneventful in all but one patient who had a probable recurrence of pulmonary embolism on day 4. No 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 injection. 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 antithrombin complexes non-significantly decreased from day 1 to day 5. CONCLUSIONS: Subcutaneous administration of recombinant hirudin ensures prolonged stable plasma levels of recombinant hirudin which results in efficient anticoagulation. A dose-ranging study conducted with subcutaneous recombinant hirudin in comparison to conventional heparin therapy may answer the question as to efficacy.

Dose effect relationship of reviparin in chronic hemodialysis: a crossover study versus nadroparin.

Low molecular weight heparins (LMWHs) are used for prevention of clotting in the dialysis circuit. The aim of this trial was to define the optimal dose of a new LMWH and to test the efficiency of a single dose at the start of the session. Fifteen patients were treated according to a double blind and crossover design during 4 blocks of 5 consecutive reviparin doses assigned randomly as 50, 60, 70, 85, and 100 IU anti-Xa/kg. Assessment was carried out on screening of fibrin rings or clots in the arterial and venous air traps and on visual detection of fiber in the dialyzer after rinsing. These clinical results were compared to plasmatic anti-Xa activity and thrombin-antithrombin (TAT) complex generation. A standard dose of 70 IU anti-Xa/kg of nadroparin was used as the control. After a bolus of 50 to 100 IU anti-Xa/kg, the occurrence of fibrin rings and clots in the air traps was dependent on three factors: dose of LMWH, time of the session, and patient status. A bolus of 85 IU anti-Xa/kg of reviparin was effective and safe for sessions of 4 h. For this dose, plasmatic anti-Xa activity was 0.96 +/- 0.28 IU/ml at Hour 2 and 0.82 +/- 0.22 IU/ml at Hour 4. TAT complexes are good markers of the activation of the coagulation. They did not increase during a 4 h session after a reviparin bolus of 100 IU/kg. For the same LMWH dose, the trial shows a great variability of the clinical effect and anti-Xa activities from one patient to another. A single dose of 85 IU anti-Xa/kg of reviparin can be used at the start of the dialysis session as a loading dose. We advise adapting the dose during the subsequent sessions according to the appearance of the blood circuit. The benefit of monitoring anti-Xa activity and TAT complexes could be tested in a further trial.

Plasma factor VII, triglyceride concentration and fibrin degradation products in primary hyperlipidemia: a clinical and laboratory study.

There is evidence that the increase in coagulation factor VII (FVII) represents a predictive risk factor of arterial thrombosis in coronary heart disease. Its relative contribution to this multifactorial process and its relationship to other risk factors, namely cholesterol and triglycerides, is yet a matter of investigation. In this study we aimed to clarify whether FVII synthesis or activation correlated with plasma lipid concentrations. For this, we assayed the plasma levels of FVII antigen (FVII:ag) and FVII coagulant activity (FVIIc) in types IIa, IIb and IV hyperlipidemic individuals, together with the levels of cholesterol, triglycerides, high-density lipoproteins and apolipoprotein B. FVII activation state (FVIIa) was then assessed by FVIIc/FVII:ag. In order to assess the possible correlation of FVII levels with the generation of thrombin and formation of fibrin, we also assayed the plasma concentration of fibrin degradation products (D-dimers) in these patients. Considering all the patients studied, there was a fair correlation between FVIIc and FVII:ag (r = 0.704; p less than 0.01). The mean levels of FVIIc and FVII:ag were significantly higher in type IV hyperlipidemia than in controls (t = 4.260; p less than 0.001 and t = 3.015; p less than 0.01, respectively) and other types of hyperlipidemia. We also found that FVIIc and FVII:ag significantly correlated to triglyceride concentration. We could not detect an evident activation of FVII in these patients since FVIIc/FVII:ag was not elevated in comparison with controls, nor did it correlate with any of the lipid determinations in any of the types of hyperlipidemia studied.(ABSTRACT TRUNCATED AT 250 WORDS)