Gebhart J, Laczkovics C, Posch F, Ay C, Reitter-Pfoertner S E, Haslacher H, Muszbek L, Wolberg A S, Pabinger I
Department of Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University Vienna, Vienna, Austria.
Ann Hematol. 2015 Aug;94(8):1301-10. doi: 10.1007/s00277-015-2399-7. Epub 2015 May 15.
In a large proportion of patients with mild bleeding disorders (MBDs) no diagnosis can be established by routine coagulation tests. We investigated whether alterations in plasma clot properties account for MBDs of unknown cause. Ninety-five patients with MBDs of unknown origin and 98 age- and sex-matched healthy controls were investigated. Furthermore, data of 25 patients with a deficiency of factor VIII were analyzed. Plasma clot characteristics in the absence and presence of recombinant tissue plasminogen activator (rtPA) represented by the lag phase, rate of protofibril formation (Vmax), fibrin structure (ΔAbs), time to peak (TTP), half lysis time (t50 and area under the curve (AUC) were measured in turbidometric clot formation and lysis assays. In the fibrinolysis assay, Vmax was lower in patients than in healthy controls. No differences in the other parameters of clot formation and lysis were detected between the groups. There was no clear association of plasma clot properties with the clinical severity of bleeding in patients with MBDs. Patients with known decreased factor VIII levels also showed a lower Vmax. Fibrinogen levels were positively associated with each of the assessed parameters in both groups, with the strongest association with ΔAbs, indicating altered fibrin structure. Factor VIII activity correlated with altered clot characteristics similar to fibrinogen, especially in patients, with the strongest positive correlation to Vmax. This cohort of patients with MBDs of unknown origin showed a lower rate of fibrin formation in the fibrinolysis assay, but otherwise similar plasma clot properties compared to healthy controls.
在很大一部分轻度出血性疾病（MBD）患者中，常规凝血试验无法做出诊断。我们研究了血浆凝块特性的改变是否是不明原因MBD的病因。对95例不明原因的MBD患者和98例年龄及性别匹配的健康对照者进行了研究。此外，还分析了25例因子VIII缺乏患者的数据。在比浊法凝块形成和溶解试验中，测量了在不存在和存在重组组织型纤溶酶原激活剂（rtPA）的情况下血浆凝块的特征，包括延迟期、原纤维形成速率（Vmax）、纤维蛋白结构（ΔAbs）、达到峰值的时间（TTP）、半溶解时间（t50）和曲线下面积（AUC）。在纤维蛋白溶解试验中，患者的Vmax低于健康对照者。两组之间在凝块形成和溶解的其他参数上未检测到差异。MBD患者的血浆凝块特性与出血的临床严重程度之间没有明显关联。已知因子VIII水平降低的患者也表现出较低的Vmax。纤维蛋白原水平与两组中每个评估参数均呈正相关，与ΔAbs的相关性最强，表明纤维蛋白结构改变。因子VIII活性与类似于纤维蛋白原的凝块特征改变相关，尤其是在患者中，与Vmax的正相关性最强。这组不明原因的MBD患者在纤维蛋白溶解试验中显示出较低的纤维蛋白形成速率，但与健康对照者相比，血浆凝块特性在其他方面相似。
