Abstract

The aim of this study was to investigate the proteolytic degradation of fibrin(ogen), with special emphasis on the size of soluble fibrin(ogen) derivatives identified before, during and after intra-arterial catheter-directed thrombolysis with alteplase. Arteriography was performed before thrombolysis and after 0.5, 3, 10 and 24 h in six patients with peripheral native artery or bypass occlusions. Samples collected simultaneously intra-arterially from the thrombus and from venous blood were studied by immunoblotting patterns obtained after polyacrylamide and agarose gel electrophoresis. Supernatant from centrifuged material aspirated from the thrombus before thrombolysis contained soluble fibrin(ogen) derivatives with molecular weights of several thousand kDa. Two types of soluble fibrin(ogen)-related material were visualized during treatment: high molecular weight species (500-1000 kDa) displaying an almost continuous spectrum of molecular weights, suggesting gradual proteolytic degradation of cross-linked fibrin into X-oligomeric material; and X, Y, DD, D and E fragments. The amount and distribution of fragments strongly indicated that preferential fibrinolysis had taken place. The finding of a sustained level of fragments in post-thrombolytic plasma might indicate that insoluble fragments embolize peripherally and subsequently lyse. A close association between angiographical and molecular findings during both successful and failing thrombolysis was demonstrated.

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