Ernofsson M, Strekerud F, Toss H, Abildgaard U, Wallentin L, Siegbahn A
Department of Clinical Laboratory Sciences, Clinical Chemistry, University Hospital Uppsala, Sweden.
Thromb Haemost. 1998 Mar;79(3):491-4.
Unstable coronary artery disease (UCAD) is associated with an increased risk of further coronary events. In the FRISC study, the risk was decreased during treatment with a high, twice-daily, dose of dalteparin, a low-molecular-weight heparin. However, lowering the dose resulted in raised risk of recurrences. To investigate the underlying pathophysiology, the thrombin generation and activity in patients with UCAD randomized to a 6-week placebo-controlled treatment with dalteparin were evaluated. Plasma prothrombin fragment 1+2 (F1+2) (n = 342), thrombin-antithrombin complex (TAT) (n = 186) and soluble fibrin (SF) (n = 298) were analyzed before and during treatment with dalteparin/placebo administered subcutaneously, 120 IU/kg bw twice daily for 5-8 days and 7.500 IU once daily the following 35-40 days. High-dose treatment with dalteparin resulted in significantly reduced levels of all coagulation markers, demonstrating diminished thrombin generation and activity. When reducing the dalteparin dose, plasma TAT and SF remained low, indicating minimal fibrin formation. However, F1+2 increased during this period. though the level at day 45 was still lower than in the placebo group. In the placebo group elevated thrombin generation and activity persisted during the entire period. In conclusion, high-dose treatment with dalteparin twice daily resulted in significantly reduced thrombin generation and activity. However, after changing to a lower, once-daily dose, the treatment was not sufficient in preventing a return to a procoagulable state. These changes of the coagulation activity might explain the changes in event rate observed during dalteparin treatment.
不稳定型冠状动脉疾病（UCAD）与进一步发生冠状动脉事件的风险增加相关。在FRISC研究中，高剂量、每日两次的达肝素（一种低分子量肝素）治疗期间风险降低。然而，降低剂量会导致复发风险升高。为了研究潜在的病理生理学，对随机接受达肝素6周安慰剂对照治疗的UCAD患者的凝血酶生成和活性进行了评估。在皮下注射达肝素/安慰剂治疗前及治疗期间，分析血浆凝血酶原片段1+2（F1+2）（n = 342）、凝血酶 - 抗凝血酶复合物（TAT）（n = 186）和可溶性纤维蛋白（SF）（n = 298），前5 - 8天每日两次，120 IU/kg体重，之后35 - 40天每日一次，7500 IU。高剂量达肝素治疗导致所有凝血标志物水平显著降低，表明凝血酶生成和活性减弱。当降低达肝素剂量时，血浆TAT和SF仍保持低水平，表明纤维蛋白形成极少。然而，在此期间F1+2升高，尽管第45天时的水平仍低于安慰剂组。在安慰剂组中，整个期间凝血酶生成和活性持续升高。总之，每日两次高剂量达肝素治疗导致凝血酶生成和活性显著降低。然而，改为较低的每日一次剂量后，该治疗在预防恢复到促凝状态方面并不充分。凝血活性的这些变化可能解释了达肝素治疗期间观察到的事件发生率变化。
