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John R. Shainoff, Patricia M. DiBello
The circulatory half-lives of -profibrin and -fibrin monomer, and comparisons with other fibrin(ogen) derivatives
Previous studies showed that -fibrin monomer (lacking both A-fibrinopeptides, FPA) is normally cleared from the circulation before it assembles into a clot. Recent studies indicate that substantial quantities of an intermediate, -profibrin lacking only one of the two FPA are produced in the course of conversion of human fibrinogen to fibrin. Since clearance of the -fibrin monomer is saturable and receptor mediated, the extent to which -profibrin or other fibrin(ogen) derivatives might compete for monomer uptake was deemed important. We compared plasma decay of injected human -fibrin, fibrinogen, and -profibrin in rabbits using rabbit anti-human fibrinogen for assays. The circulatory half-life of human -fibrin monomer was short (t1/2 = 2.3 h) and followed a simple exponential decay curve, as anticipated from clearance of rabbit -fibrin. It was absorbed as fast as it permeated the extravascular space with no redistribution. Human fibrinogen had a long half-life (t1/2 = 39.5 h), calculated from the double exponential plasma decay curves (redistribution + catabolism) observed over 28 h. The -profibrin had an intermediary half-life (t1/2 = 11 h) determined from double exponential decay curves. Since redistribution accompanied the slow clearance of -profibrin, its binding by the fibrin receptor(s) must be weak, probably too weak to compete with the clearance of -fibrin monomer. The initial production of -fibrin monomer is only partially dependent on prior formation of -profibrin, as recently shown. Thus, it is the slow clearance and the weak competition from -profibrin that underlie the occurrence of substantial levels of -profibrin unaccompanied by detectable levels of -fibrin monomer in many subjects with vascular disease.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 89, 01/2003
Pages: 48 - 52