Impaired fibrinolytic potential related to elevated alpha1-proteinase inhibitor levels in patients with pulmonary thromboembolism.
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.
Gombás
Judit
J
Department of Medical Biochemistry, Semmelweis University, Puskin u. 9., 1088 Budapest, Hungary.
Kolev
Krasimir
K
Tarján
Eniko
E
Machovich
Raymund
R
D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D019272:Leukocyte Elastase / Q000097:blood*; D008297:Male; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000097:blood*; D010958:Plasminogen / Q000032:analysis; D010960:Plasminogen Activators / Q000097:blood; D011655:Pulmonary Embolism / Q000097:blood* / Q000473:pathology; D000515:alpha 1-Antitrypsin / Q000032:analysis*
D015415:Biomarkers; D046912:Multiprotein Complexes; D000515:alpha 1-Antitrypsin; D010958:Plasminogen; D010960:Plasminogen Activators; D019272:Leukocyte Elastase