Impaired fibrinolytic potential related to elevated α1-proteinase inhibitor levels in patients with pulmonary thromboembolism
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The contribution of neutrophil leukocyte elastase (NE) to in vivo thrombolysis is still an open question. The present study examines the impact of variable levels of α1-proteinase inhibitor (α1-PI) (the major plasma inhibitor of NE) on fibrinolysis within the setting of thromboembolic diseases. Blood samples were taken from 56 patients with pulmonary thromboembolism prior to treatment. α1-PI and α1-PI-NE complex were measured in the serum and plasma with immunoturbidimetric and enzyme-linked immunosorbent assay (ELISA) methods, respectively. The fibrinolytic potential [spontaneous, tissue-type plasminogen activator (tPA) induced, and plasmin induced] of the plasma was evaluated in vitro with turbidimetric clot lysis assay. Correlation analysis (Pearson product-moment correlation coefficient, r) of the turbidimetric lysis parameters and the blood levels of α1-PI and α1-PI-NE complex was carried out. Fibrinolysis is slower in clots prepared from plasma containing elevated levels of α1-PI and α1-PI-NE complex. The maximal turbidity of the plasma clots shows significant correlation with the α1-PI level (r=0.39, p=0.003) and the correlation of the maximal turbidity and the tPA-induced lysis time is also significant (r=0.77, p<0.001). The lysis time correlates with the plasma level of α1-PI-NE complex, if fibrinolysis is induced with tPA (r=0.37, p=0.02), but not with plasmin (r=0.19, p=0.4). Our study shows that in pulmonary thromboembolism elevated levels of α1-PI are associated with suppressed plasma fibrinolytic potential. This effect can be at least partially explained by the coarse fibrin network structure and retarded plasminogen activator-dependent fibrinolysis.
KeywordsThromboembolism Fibrinolysis Neutrophil leukocyte elastase
This work was supported in part by grants from the Hungarian Scientific Research Fund (T031891), the Hungarian Ministry of Health (ETT 287&288/2000, NFKP-1A/23/2002), and the Wellcome Trust (069520/Z/02/Z). We acknowledge the excellent technical assistance of Györgyi Oravecz.
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