Cohen A T, Phillips M J, Edmondson R A, Skinner J A, Das S K, Cooper D J, Thomas E M, Melissari E, Kakkar V V
Thrombosis Research Institute, London, UK.
Thromb Haemost. 1994 Dec;72(6):793-8.
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.
硫酸皮肤素可催化肝素辅因子II对凝血酶的抑制作用；在动物模型中，其出血与抗血栓形成的比率低于肝素。连续40岁及以上择期在全身麻醉下进行全髋关节置换的患者，被随机分配至肌肉注射三种剂量方案之一的硫酸皮肤素（MF701，Mediolanum Farmaceutici）组。这三种方案分别为：每日一次200mg（n = 50）、每日两次200mg（n = 52）和每日两次300mg（n = 51），从术前24小时给药至术后第10天。通过双侧静脉造影评估的深静脉血栓形成（DVT）总体发生率分别为53%、51%和34%（趋势卡方检验p = 0.06）。主要近端DVT的发生率分别为10.6%、8.5%和2.1%。对所有153例患者评估了肺栓塞（PE）和出血情况。每个剂量组均有1例PE病例。出血事件的发生率、失血量和输血需求较低，且未随剂量增加而增加。患者在出院后4 - 8周进行随访。我们得出结论，在该人群中，较低的两种剂量未达到治疗效果，然而，每日两次给予300mg硫酸皮肤素被证明是有效的，近端主要DVT的发生率为2.1%，出血并发症的发生率较低。需要进行一项将每日两次给予300mg硫酸皮肤素与标准预防药物进行比较的试验。
