A DOSE-RANGING STUDY TO EVALUATE DERMATAN SULFATE IN PREVENTING DEEP-VEIN THROMBOSIS FOLLOWING TOTAL HIP-ARTHROPLASTY

Dermatan sulphate catalyses thrombin inhibition by heparin cofactor II ; it has a lower haemorrhagic to antithrombotic ratio than that of hep arin in animal models. Consecutive patients aged forty years or more, electively undergoing total hip replacement under general anaesthesia, were randomly allocated to one of three dosage regimens of dermatan s ulphate (MF701, Mediolanum Farmaceutici) given intra-muscularly. These were 200 mg once daily (n = 50), 200 mg twice daily (n = 52) and 300 mg twice daily (n = 51), administered from twenty-four hours pre-opera tively until the tenth postoperative day. The overall incidence of DVT assessed by bilateral venography was 53%, 51% and 34% respectively (C hi-square test for trend p = 0.06). The incidence of major proximal DV T was 10.6%, 8.5% and 2.1% respectively. Pulmonary embolism (PE) and b leeding were assessed in all 153 patients. There was one case of PE in each dose group. The incidence of bleeding episodes, volume of blood lost and blood transfusion requirements were low and showed no increas e with increasing dose. The patients were followed up 4-8 weeks after discharge. We conclude that the two lower doses were subtherapeutic in this population, however dermatan sulphate given 300 mg twice daily, proved to be efficacious with an incidence of proximal major DVT of 2. 1% and a low incidence of bleeding complications. A trial of dermatan sulphate 300 mg twice daily compared to standard prophylactic agents i s needed.