title: A dose ranging study to evaluate dermatan sulphate in preventing deep vein thrombosis following total hip arthroplasty.
abstract: Dermatan sulphate catalyses thrombin inhibition by heparin cofactor II; it has a lower haemorrhagic to antithrombotic ratio than that of heparin 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 sulphate (MF701, Mediolanum Farmaceutici) given intramuscularly. 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-operatively until the tenth postoperative day. The overall incidence of DVT assessed by bilateral venography was 53%, 51% and 34% respectively (Chi-square test for trend p = 0.06). The incidence of major proximal DVT was 10.6%, 8.5% and 2.1% respectively. Pulmonary embolism (PE) and bleeding 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 increase 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 is needed.
authors.affiliation: Thrombosis Research Institute, London, UK.
authors.forename: A T
authors.initials: AT
authors.lastname: Cohen
authors.forename: M J
authors.initials: MJ
authors.lastname: Phillips
authors.forename: R A
authors.initials: RA
authors.lastname: Edmondson
authors.forename: J A
authors.initials: JA
authors.lastname: Skinner
authors.forename: S K
authors.initials: SK
authors.lastname: Das
authors.forename: D J
authors.initials: DJ
authors.lastname: Cooper
authors.forename: E M
authors.initials: EM
authors.lastname: Thomas
authors.forename: E
authors.initials: E
authors.lastname: Melissari
authors.forename: V V
authors.initials: VV
authors.lastname: Kakkar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016063:Blood Loss, Surgical; D003871:Dermatan Sulfate / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005069:Evaluation Studies as Topic; D005260:Female; D005500:Follow-Up Studies; D006622:Hip Prosthesis / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010690:Phlebography; D011183:Postoperative Complications / Q000401:mortality; D011655:Pulmonary Embolism / Q000209:etiology; D012016:Reference Values; D012307:Risk Factors; D013924:Thrombophlebitis / Q000209:etiology / Q000517:prevention & control*
chemical_list: D003871:Dermatan Sulfate