Impaired fibrinolytic potential related to elevated ?1-proteinase inhibitor levels in patients with pulmonary thromboembolism

Abstract

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 alpha1-proteinase inhibitor (alpha1-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. alpha1-PI and alpha1-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 alpha1-PI and alpha1-PI-NE complex was carried out. Fibrinolysis is slower in clots prepared from plasma containing elevated levels of alpha1-PI and alpha1-PI-NE complex. The maximal turbidity of the plasma clots shows significant correlation with the alpha1-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 alpha1-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 alpha1-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.

Protease activity in the multi-layered intra-luminal thrombus of abdominal aortic aneurysms

“…Mini-plasminogen is resistant to inhibition compared to plasminogen and also more effective at degrading fibrin. Therefore, NE can degrade fibrin directly or indirectly by activating mini-plasminogen (Gombas, Kolev et al 2004).…”

Role of Cellular Elements in Thrombus Formation and Dissolution

“…Miniplasmin is more efficient on cross-linked fibrin than plasmin and it is ten-times less sensitive to inhibition by α 2 -antiplasmin than plasmin [58]. These effects of elastase on the function of the plasminogen/plasmin system can explain how in vivo elastase increases the global plasma fibrinolytic potential as reported for patients with pulmonary thromboembolism [60].…”

Heritability of Clot Formation, Morphology, and Lysis

“…For the turbidimetric lysis assay, in addition to the lag time (Lag L ), maximum absorbance (MaxAbs L ; the highest absorbance value adjusted for Lag L ), and crude rate of clot formation (CR L ), several lysis time variables were determined (illustrated in Figure 1) based on those analyzed in previous studies reporting turbidimetric lysis assays. [17][18][19][20] Time to 50% lysis was determined in 2 ways: Lys50 t0 (calculated as the time from initiation of clot formation to the time at which a 50% fall in absorbance from MaxAbs L occurred) and Lys50 MA (calculated as the time from MaxAbs L to the time at which a 50% reduction in absorbance occurred). Time to complete lysis, Lys T , was taken as the time from MaxAbs L to the time for the absorbance values to return to baseline, and crude lysis rate (LR) was derived from time and absorbance values for MaxAbs L and the point at which absorbance values returned to baseline.…”