背景:原发性免疫性血小板减少症(ITP)患者血栓形成的风险增加,这可能是由于纤维蛋白溶解改变。
目的:阐明ITP患者延迟纤溶的临床影响。
方法:进行了比浊法凝块形成和溶解测定以及荧光纤溶酶生成(PG)测定,纤溶酶原激活物抑制剂-1(PAI-1)的水平,组织纤溶酶原激活剂(tPA),tPA-PAI-1复合物,α2-抗纤溶酶,在86例成人原发性ITP患者和78例健康对照(HC)中评估了TAFI和D-二聚体。
结果:ITP患者显示明显延迟凝块形成,凝块密度增加,与HC相比,凝块溶解时间(CLT)延长,患者的中位(IQR)CLT为28.0(13.7-34.7)分钟,HC为17.3(12.0-28.0)分钟,而在PG中,仅滞后时间延长。在ITP患者与对照组相比,PAI-1较高(1.2(0.8-2.6)比1.1(0.6-2.1)U/mL),tPA抗原和活性较低(tPA抗原:2.6(1.1-4.4)vs3.7(3.2-4.7)ng/mL;tPA活性≤0U/mL:26%vs7%)。多元线性回归分析中TPA-PAI-1复合物水平与CLT呈正相关(β=0.241,p=0.019),而PG参数与CLT无关。六个病人,在随访期间出现血栓形成的人,具有较高水平的tPA-PAI-1复合物。
结论:长期的CLT和PG的延迟发作可能表明ITP患者存在纤溶降低倾向,高PAI-1和低tPA水平也表明了这一点。未发现纤溶潜能与出血表型之间存在关联,而较高的tPA-PAI-1复合物水平与CLT延长相关,并且在有未来血栓形成的患者中增加.
BACKGROUND: Patients with primary immune thrombocytopenia (ITP) have an increased risk of thrombosis, which may be due to altered fibrinolysis.
OBJECTIVE: To elucidate the clinical impact of delayed fibrinolysis in ITP patients.
METHODS: A turbidimetric clot formation and lysis assay and a fluorometric plasmin generation (PG) assay were performed and levels of plasminogen-activator-inhibitor-1 (PAI-1), tissue-plasminogen-activator (tPA), tPA-PAI-1 complexes, α2-antiplasmin, TAFI and D-Dimer were assessed in 86 adult primary ITP patients and 78 healthy controls (HC).
RESULTS: ITP patients showed significantly delayed clot formation, increased clot density, and prolonged clot lysis time (CLT) compared to HC with a median (IQR) CLT of 28.0 (13.7-34.7) minutes in patients and 17.3 (12.0-28.0) minutes in HC, while in PG only the lag time was prolonged. In ITP patients compared to controls, PAI-1 was higher (1.2 (0.8-2.6) vs 1.1 (0.6-2.1) U/mL), and tPA antigen and activity were lower (tPA antigen: 2.6 (1.1-4.4) vs 3.7 (3.2-4.7) ng/mL; tPA activity ≤0 U/mL: 26% vs 7%). TPA-PAI-1 complex levels were positively associated with CLT in multiple linear regression analysis (β=0.241, p=0.019), whereas PG parameters were not associated with CLT. Six patients, who developed thrombosis during follow-up, had higher levels of tPA-PAI-1 complexes.
CONCLUSIONS: Prolonged CLT and delayed onset of PG may indicate a hypofibrinolytic tendency in ITP patients, as also indicated by high PAI-1 and low tPA levels. No association was found between fibrinolytic potential and the bleeding phenotype, whereas higher tPA-PAI-1 complex levels were associated with prolonged CLT and increased in patients with future thrombosis.