Musiał J, Swadźba J, Jankowski M, Grzywacz M, Bazan-Socha S, Szczeklik A
Jagellonian University School of Medicine, Department of Medicine, Cracow, Poland.
Thromb Haemost. 1997 Oct;78(4):1173-7.
Antiphospholipid-protein antibodies (APA) include lupus-type anticoagulant (LA) and antibodies recognizing complexes of anionic phospholipids (e.g. cardiolipin) and proteins (e.g. prothrombin and beta2-glycoprotein I). The presence of APA is associated with an increased risk of both arterial and venous thrombosis. However, the pathogenic mechanism leading to thrombosis in patients with APA remains unclear. We studied 32 patients with systemic lupus erythematosus (SLE) who were divided into two groups depending on the presence (n = 19) or absence (n = 13) of APA. Healthy volunteers (n = 12) matched by age and sex served as controls. In all subjects LA and IgG class anticardiolipin antibodies (ACA) were determined. Thrombin generation was monitored ex vivo measuring fibrinopeptide A (FPA) and prothrombin fragment F1 + 2 (F1 + 2) in blood emerging from a skin microvasculature injury, collected at 30 second intervals. In subjects with antiphospholipid antibodies mean FPA and F1 + 2 concentrations were significantly higher at most blood sampling times than in controls. In some SLE patients with APA the process of thrombin generation was clearly disturbed and very high concentrations of fibrinopeptide A were detected already in the first samples collected. Two minutes after skin incision SLE patients without APA produced slightly more FPA, but not F1 + 2, as compared to healthy subjects. Mathematical model applied to analyze the thrombin generation kinetics revealed that APA patients generated significantly greater amounts of thrombin than healthy controls (p = 0.02 for either marker). In contrast, in the same patients generation of thrombin in recalcified plasma in vitro was delayed pointing to the role of endothelium in the phenomenon studied. In summary, these data show for the first time that in SLE patients with antiphospholipid-protein antibodies thrombin generation after small blood vessel injury is markedly increased. Enhanced thrombin generation might explain thrombotic tendency observed in these patients.
抗磷脂 - 蛋白抗体（APA）包括狼疮样抗凝物（LA）以及识别阴离子磷脂（如心磷脂）与蛋白质（如凝血酶原和β2 - 糖蛋白I）复合物的抗体。APA的存在与动脉和静脉血栓形成风险增加相关。然而，导致APA患者血栓形成的致病机制仍不清楚。我们研究了32例系统性红斑狼疮（SLE）患者，根据是否存在APA将其分为两组（存在组，n = 19；不存在组，n = 13）。年龄和性别匹配的健康志愿者（n = 12）作为对照。测定了所有受试者的LA和IgG类抗心磷脂抗体（ACA）。通过在皮肤微血管损伤后每隔30秒收集血液，测量纤维蛋白肽A（FPA）和凝血酶原片段F1 + 2（F1 + 2），对凝血酶生成进行体外监测。在抗磷脂抗体阳性的受试者中，大多数采血时间点的平均FPA和F1 + 2浓度显著高于对照组。在一些患有APA的SLE患者中，凝血酶生成过程明显紊乱，在采集的首个样本中就检测到非常高浓度的纤维蛋白肽A。与健康受试者相比，皮肤切开两分钟后，无APA的SLE患者产生的FPA略多，但F1 + 2无差异。应用数学模型分析凝血酶生成动力学表明，APA患者产生的凝血酶量显著多于健康对照组（两种标志物的p值均为0.02）。相反，在同一批患者中，体外重新钙化血浆中凝血酶的生成延迟，这表明内皮细胞在该研究现象中起作用。总之，这些数据首次表明，在患有抗磷脂 - 蛋白抗体的SLE患者中，小血管损伤后的凝血酶生成明显增加。凝血酶生成增强可能解释了这些患者中观察到的血栓形成倾向。
