Leurs P B, van Oerle R, Wolffenbuttel B H, Hamulyak K
Department of Internal Medicine, University Hospital, Maastricht, The Netherlands.
Thromb Haemost. 1997 Mar;77(3):472-6.
Recently, we found an increase in tissue factor pathway inhibitor (TFPI) activity in patients with insulin-dependent diabetes mellitus (IDDM). This increase in TFPI activity could be the result of increased thrombin formation and/or altered binding of TFPI to glycosaminoglycans. We studied TFPI activity (chromogenic assay) in relation to prothrombin F1 + 2 fragments and endogenous thrombin potential (ETP), in 46 IDDM patients, and 18 age and sex-matched healthy controls. Prothrombin, antithrombin and thrombomodulin were also determined. In IDDM patients, TFPI activity and F1 + 2 levels were significantly higher, while ETP, prothrombin antigen levels, and antithrombin activity were lower as compared to the controls. In IDDM patients with microalbuminuria, a manifestation of generalized angiopathy, TFPI activity, F1 + 2 and thrombomodulin levels were higher than in patients with only retinopathy or patients without complications. No correlation between TFPI activity, F1 + 2 levels and thrombomodulin was found, while TFPI activity was negatively correlated with ETP (r = -0.27). Microalbuminuria was significantly correlated with TFPI activity (r = 0.46), F1 + 2 (r = 0.56), and thrombomodulin (r = 0.52). In TFPI-depleted plasma, ETP increased, indicating that ETP is affected by TFPI. In conclusion, the increase in TFPI activity in IDDM patients may not be considered to be a reaction on a procoagulant state. It is hypothesized that vascular damage, leading to alterations in glycosaminoglycans, is in part responsible for the changes in TFPI activity, F1 + 2 levels and ETP.
最近，我们发现胰岛素依赖型糖尿病（IDDM）患者的组织因子途径抑制物（TFPI）活性增加。TFPI活性的这种增加可能是凝血酶生成增加和/或TFPI与糖胺聚糖结合改变的结果。我们研究了46例IDDM患者以及18例年龄和性别匹配的健康对照者中TFPI活性（发色底物法）与凝血酶原F1 + 2片段及内源性凝血酶潜力（ETP）的关系。同时还测定了凝血酶原、抗凝血酶和血栓调节蛋白。与对照组相比，IDDM患者的TFPI活性和F1 + 2水平显著更高，而ETP、凝血酶原抗原水平和抗凝血酶活性则更低。在患有微量白蛋白尿（全身性血管病变的一种表现）的IDDM患者中，TFPI活性、F1 + 2和血栓调节蛋白水平高于仅患有视网膜病变或无并发症的患者。未发现TFPI活性、F1 + 2水平与血栓调节蛋白之间存在相关性，而TFPI活性与ETP呈负相关（r = -0.27）。微量白蛋白尿与TFPI活性（r = 0.46）、F1 + 2（r = 0.56）和血栓调节蛋白（r = 0.52）显著相关。在去除TFPI的血浆中，ETP增加，表明ETP受TFPI影响。总之，IDDM患者TFPI活性的增加可能不应被视为对促凝状态的一种反应。据推测，血管损伤导致糖胺聚糖改变，部分导致了TFPI活性、F1 + 2水平和ETP的变化。
