Bara L, Planes A, Samama M M
Laboratoires de Thrombose Expérimentale, Université Pierre et Marie Curie, Paris, France.
Br J Haematol. 1999 Feb;104(2):230-40. doi: 10.1046/j.1365-2141.1999.01153.x.
Studies in experimental animal models and in patients receiving low molecular weight heparin (LMWH) to prevent thromboembolic events after surgery have not demonstrated a clear relationship between anti-Xa and anti-IIa activities in plasma and either bleeding or prevention of thrombosis. The relationship between these clinical outcomes and ex vivo anti-Xa and anti-IIa activities, activated partial thromboplastin time (APTT) and D-dimers were evaluated in 440 patients undergoing total hip replacement and given prophylaxis once daily with a LMWH (tinzaparin or enoxaparin) in a multicentre double-blind randomized study. 221 patients received 4500 anti-Xa IU of tinzaparin; 219 patients received 40 mg (4000 anti-Xa IU) of enoxaparin. Both regimens were administered subcutaneously once daily. Blood samples for anti-IIa, anti-Xa, D-dimers levels and APTT were taken at baseline, on day 1, day 5 and on the day of discharge (days 8-14) and clinical assessments were performed dafly until day 14. All patients had bilateral venography between days 8 and 14. All coagulation tests were performed in central laboratories. A significant correlation was observed between anti-IIa activity and anti-Xa activity and the dose of each LMWH injected. The anti-Xa activity was significantly higher with enoxaparin and the anti-IIa activity was significantly higher with tinzaparin. No clear relationship between these two activities and the clinical outcomes was observed. This was also true with regards to APTT. Before and after surgery, D-dimers were significantly higher in patients with deep vein thrombosis (DVT) than in those without DVT but had no predictive value. Interestingly, a significant post-operative increase of D-dimers persisted in both groups of patients during the whole observation period, possibly suggesting that a longer duration of prophylactic treatment may be appropriate.
在实验动物模型以及接受低分子量肝素（LMWH）以预防术后血栓栓塞事件的患者中开展的研究，尚未证实血浆中抗Xa和抗IIa活性与出血或血栓形成预防之间存在明确关系。在一项多中心双盲随机研究中，对440例行全髋关节置换术且每日接受一次LMWH（替扎肝素或依诺肝素）预防的患者，评估了这些临床结局与体外抗Xa和抗IIa活性、活化部分凝血活酶时间（APTT）及D - 二聚体之间的关系。221例患者接受4500抗Xa国际单位的替扎肝素；219例患者接受40毫克（4000抗Xa国际单位）的依诺肝素。两种方案均每日皮下注射一次。在基线、第1天、第5天和出院日（第8 - 14天）采集血样检测抗IIa、抗Xa、D - 二聚体水平及APTT，并每日进行临床评估直至第14天。所有患者在第8至14天之间进行双侧静脉造影。所有凝血检测均在中心实验室进行。观察到抗IIa活性和抗Xa活性与所注射的每种LMWH剂量之间存在显著相关性。依诺肝素的抗Xa活性显著更高，而替扎肝素的抗IIa活性显著更高。未观察到这两种活性与临床结局之间存在明确关系。APTT情况也是如此。手术前后，深静脉血栓形成（DVT）患者的D - 二聚体显著高于无DVT患者，但无预测价值。有趣的是，两组患者在整个观察期内术后D - 二聚体均持续显著升高，这可能提示或许需要更长疗程的预防性治疗。
