Human thrombi contain an abundance of active thrombin

This study assessed the abundance and activity of thrombin in human thrombi , removed at autopsy or during surgery. Arterial and venous thrombus sectio ns showed thrombin activity by in situ zymography, based on conversion of f ibrinogen to fibrin. Hirudin or antibodies to thrombin abolished the activi ty. Thrombin activity in extracts of 40 thrombi was quantified by cleavage of fibrinogen or small peptide substrates; the results correlated well (r = 0.87, p <0.0001) with a median activity of about 4.5 IU/g of thrombus (wet weight). Activity correlated poorly with total prothrombin (median 27 mug/ g) and was inversely related to antithrombin, but not to PAI-1. Zymography showed two major active bands, thrombin at 37 kDa, and a 50 kDa form that p robably corresponds to meizothrombin desF1. The abundant local thrombin dem onstrated here has implications for thrombus lysis and extension: incomplet e lysis and exposure of active thrombin may lead to re-occlusion of vessels .