Lau C S, McLaren M, Mackay I, Belch J J
University Department of Medicine, Ninewells Hospital and Medical School, Dundee.
Ann Rheum Dis. 1993 Jun;52(6):443-8. doi: 10.1136/ard.52.6.443.
(1) To assess if patients with various forms of Raynaud's phenomenon (RP) have abnormal plasma fibrinolysis that may contribute to diminished digital blood flow; (2) to assess whether patients with RP with evidence of endothelial damage have abnormal plasma fibrinolysis; (3) to determine the clinical relevance of abnormalities, if any, in plasma fibrinolysis in patients with RP.
One hundred and sixty eight patients with significant RP were studied--46 had primary Raynaud's disease (RD), 32 had suspected Raynaud's syndrome secondary to an undifferentiated connective tissue disorder (undifferentiated CTD), 25 had Raynaud's syndrome associated with atherosclerosis (athero RS), and 65 had an underlying connective tissue disease (CTD RS). All attended in the morning after a low fat light breakfast. After a clinical history was obtained, venous blood samples were collected without stasis for assays of plasma fibrinolysis and factor VIII von Willebrand factor antigen (fVIII vWF Ag). Results were compared with those obtained from normal subjects matched for sex and age. As patients with athero RS were significantly older than the other patients with Raynaud's phenomenon, two groups of control subjects were recruited--namely, 'old' and 'young' control subjects.
Patients with CTD RS and athero RS had higher concentrations of fVIII vWF Ag (CTD RS median 174.5 range (45-370)% v 100 (38-202)%, p < 0.001; athero RS 182-5 (100-240)% v 100 (50-158)%, p < 0.001). Both had raised fibrinogen (CTD RS 3.25 (1.9-6.8) g/l v 2.4 (1.2-4.2) g/l, p < 0.001; athero RS 3.4 (2.2-6.2) g/l v 2.5 (1.8-3.9) g/l, p < 0.001) and both had diminished fibrinolysis with reduced plasminogen activator activity (CTD RS 79.5 (31-72) mm2 v 92 (37-197) mm2, p < 0.04; athero RS 73 (45-125) mm2 v 98 (41-197) mm2, p < 0.03). Patients with CTD RS also had raised plasminogen activity (3.3 (2.3-5.8) cU/ml v 2.9 (1.5-5.4) cU/ml, p < 0.001). On the contrary, patients with primary RD and undifferentiated CTD had normal fibrinogen and plasma fibrinolysis. Within each patient group, no significant differences in any of the measured variables were found between those who had RP all year and those who had RP in the winter only, those with RP of the hands only and of hands and feet, or those with and without digital ulcers.
Diminished plasma fibrinolysis is found in patients likely to have endothelial damage (CTD RS and athero RS). These changes are probably a consequence rather than a cause of the disease.
(1)评估各种形式雷诺现象(RP)患者是否存在异常的血浆纤维蛋白溶解,这可能导致指端血流减少;(2)评估有内皮损伤证据的RP患者是否存在异常的血浆纤维蛋白溶解;(3)确定RP患者血浆纤维蛋白溶解异常(若存在)的临床相关性。
对168例有明显RP的患者进行研究——46例患有原发性雷诺病(RD),32例怀疑继发于未分化结缔组织病(未分化CTD)的雷诺综合征,25例患有与动脉粥样硬化相关的雷诺综合征(动脉粥样硬化性雷诺综合征),65例患有潜在的结缔组织病(结缔组织病相关性雷诺综合征)。所有患者均在低脂清淡早餐后于上午就诊。获取临床病史后,采集静脉血样且不产生淤血,用于检测血浆纤维蛋白溶解及因子VIII血管性血友病因子抗原(fVIII vWF Ag)。将结果与年龄和性别匹配的正常受试者所得结果进行比较。由于动脉粥样硬化性雷诺综合征患者比其他雷诺现象患者年龄明显偏大,因此招募了两组对照受试者——即“老年”和“年轻”对照受试者。
结缔组织病相关性雷诺综合征和动脉粥样硬化性雷诺综合征患者的fVIII vWF Ag浓度较高(结缔组织病相关性雷诺综合征中位数为174.5,范围(45 - 370)% 对比100(38 - 202)%,p < 0.001;动脉粥样硬化性雷诺综合征为182 - 5(100 - 240)% 对比100(50 - 158)%,p < 0.001)。两者的纤维蛋白原均升高(结缔组织病相关性雷诺综合征为3.25(1.9 - 6.8)g/l对比2.4(1.2 - 4.2)g/l,p < 0.001;动脉粥样硬化性雷诺综合征为3.4(2.2 - 6.2)g/l对比2.5(1.8 - 3.9)g/l,p < 0.001),且两者的纤维蛋白溶解均减弱,纤溶酶原激活物活性降低(结缔组织病相关性雷诺综合征为79.5(31 - 72)mm²对比92(37 - 197)mm²,p < 0.04;动脉粥样硬化性雷诺综合征为73(45 - 125)mm²对比98(41 - 197)mm²,p < 0.03)。结缔组织病相关性雷诺综合征患者的纤溶酶原活性也升高(3.3(2.3 - 5.8)cU/ml对比2.9(1.5 - 5.4)cU/ml,p < 0.001)。相反,原发性雷诺病和未分化结缔组织病患者的纤维蛋白原和血浆纤维蛋白溶解正常。在每个患者组中,全年患有RP的患者与仅在冬季患有RP的患者、仅手部患有RP与手部和足部均患有RP的患者,以及有和没有指端溃疡的患者之间,在所测量的任何变量中均未发现显著差异。
在可能存在内皮损伤的患者(结缔组织病相关性雷诺综合征和动脉粥样硬化性雷诺综合征)中发现血浆纤维蛋白溶解减弱。这些变化可能是疾病的结果而非病因。