Anticoagulant albumin fragments that bind to fibrinogen/fibrin: possible implications.

The present studies describe an inhibitory effect on fibrin polymerization by albumin fragments. When added to blood or plasma, SCMF or unreduced albumin CNBrF delayed clot formation, in sharp contrast to their acceleration of clotting of fibrinogen solutions. CNBrF inhibition was less marked than that of SCMF. The latter consistently prolonged the lag phase and decreased the opacity of fibrin in plasma, effects that could not be abolished by EDTA or by calcium chloride. Clots formed lacked elasticity in that clotting times were undetectable by mechanical probe in the absence of calcium. Estimated by clot free liquor, PRP clots decreased in size at much slower rates than controls and at complete retraction their volume remained at least threefold higher that of controls (n = 6). When fibrinogen was isolated from plasma or fibrinogen (approximately 5 mg/ml) solutions containing SCMF 1 to 5 mg/ml four SCMF coisolated with fibrinogen (n = 3 and n = 4, respectively), assessed by SDS-PAGE, and these could not be dissociated from fibrinogen by size exclusion chromatography (n = 2). Such fibrinogen isolates displayed prolonged clotting times, decreased clot opacity, and similarly abnormal reaggregation of their solubilized fibrin. In other experiments, limited human neutrophil elastase digestion produced large albumin fragments of which, examined unreduced, several fragments also bound to fibrin(ogen) and displayed this anticoagulant property (n = 2). These and related results suggest that the anticoagulant property is attributable at least in part to the largest SCMF.(ABSTRACT TRUNCATED AT 250 WORDS)