Steppich Birgit, Mattisek Christoph, Sobczyk Dean, Kastrati Adnan, Schömig Albert, Ott Ilka
Deutsches Herzzentrum, Lazarettstrasse 36, 80636 München, Germany.
Thromb Haemost. 2005 Jan;93(1):35-9. doi: 10.1160/TH04-06-0393.
In acute myocardial infarction (AMI), increased Tissue Factor (TF) expression on circulating monocytes and microparticles (MP) may contribute to thrombotic events. Because surfacebound Tissue Factor Pathway Inhibitor-1 (TFPI) inhibits TF activity on monocytes and endothelial cells decreased TFPI expression may reinforce the procoagulant activity of circulating MP. Aim of the study was to analyze TFPI expression and TF activity after stenting and thrombolysis inAMI. Thirty-nine patients of a randomized study comparing intravenous thrombolysis (n=19) and stenting (n=20) were included. Before and after therapy blood samples for analysis of MPs, TF antigen and activity, prothrombin fragment F1+2 and D-dimer were obtained. TFPI expression on TF positive MPs was decreased after thrombolysis but not after stenting. In contrast, TF plasma levels and TF positive MP remained unchanged in both treatment groups. After thrombolysis increased D-dimer and F1+2 plasma concentrations indicated activation of fibrinolysis and coagulation. Significance of MPTFPI for inhibition of TF activity was measured using inhibitory TFPI antibodies. Membrane-associated TFPI inhibited TF activity on circulating MPs. After thrombolysis inhibition of TF activity by TFPI was decreased as compared to stenting. Correlation of circulating TF with F1+2 only after thrombolysis, suggests a role for TF-induced activation of coagulation after thrombolysis. Enhanced TF activity on circulating MPs in AMI is inhibited by endogenous surface-boundTFPI. After thrombolysis but not after stenting MPTFPI is degraded and may induce thrombin generation due to unopposed tissue factor activity. Anti-TF therapies during thrombolysis may reduce thrombin generation in AMI.
在急性心肌梗死（AMI）中，循环单核细胞和微粒（MP）上组织因子（TF）表达增加可能导致血栓形成事件。由于表面结合的组织因子途径抑制物-1（TFPI）可抑制单核细胞和内皮细胞上的TF活性，TFPI表达降低可能会增强循环MP的促凝活性。本研究的目的是分析AMI患者支架置入和溶栓治疗后TFPI表达及TF活性。纳入了一项比较静脉溶栓（n = 19）和支架置入（n = 20）的随机研究中的39例患者。在治疗前后采集血样，用于分析MP、TF抗原和活性、凝血酶原片段F1 + 2以及D - 二聚体。溶栓后TF阳性MP上的TFPI表达降低，但支架置入后未降低。相比之下，两个治疗组中TF血浆水平和TF阳性MP均保持不变。溶栓后D - 二聚体和F1 + 2血浆浓度升高表明纤溶和凝血被激活。使用抑制性TFPI抗体测量MP - TFPI对TF活性的抑制作用。膜相关TFPI可抑制循环MP上的TF活性。与支架置入相比，溶栓后TFPI对TF活性的抑制作用降低。仅在溶栓后循环TF与F1 + 2存在相关性，提示溶栓后TF诱导的凝血激活发挥了作用。AMI中循环MP上增强的TF活性受到内源性表面结合TFPI的抑制。溶栓后而非支架置入后，MP - TFPI被降解，由于组织因子活性未受抑制可能导致凝血酶生成。溶栓期间的抗TF治疗可能会减少AMI中的凝血酶生成。
