title: The circulatory half-lives of alpha-profibrin and alpha-fibrin monomer, and comparisons with other fibrin(ogen) derivatives.
abstract: Previous studies showed that alpha-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, alpha-profibrin lacking only one of the two FPA are produced in the course of conversion of human fibrinogen to fibrin. Since clearance of the alpha-fibrin monomer is saturable and receptor mediated, the extent to which alpha-profibrin or other fibrin(ogen) derivatives might compete for monomer uptake was deemed important. We compared plasma decay of injected human alpha-fibrin, fibrinogen, and alpha-profibrin in rabbits using rabbit anti-human fibrinogen for assays. The circulatory half-life of human alpha-fibrin monomer was short (t(1/2) = 2.3 h) and followed a simple exponential decay curve, as anticipated from clearance of rabbit alpha-fibrin. It was absorbed as fast as it permeated the extravascular space with no redistribution. Human fibrinogen had a long half-life (t(1/2) = 39.5 h), calculated from the double exponential plasma decay curves (redistribution + catabolism) observed over 28 h. The alpha-profibrin had an intermediary half-life (t(1/2) = 11 h) determined from double exponential decay curves. Since redistribution accompanied the slow clearance of alpha-profibrin, its binding by the fibrin receptor(s) must be weak, probably too weak to compete with the clearance of alpha-fibrin monomer. The initial production of alpha-fibrin monomer is only partially dependent on prior formation of alpha-profibrin, as recently shown. Thus, it is the slow clearance and the weak competition from alpha-profibrin that underlie the occurrence of substantial levels of alpha-profibrin unaccompanied by detectable levels of alpha-fibrin monomer in many subjects with vascular disease.
authors.affiliation: Department of Chemistry, Cleveland State University, Cleveland, OH 44115, USA. j.shainoff@csuohio.edu
authors.forename: John R
authors.initials: JR
authors.lastname: Shainoff
authors.forename: Patricia M
authors.initials: PM
authors.lastname: DiBello
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001775:Blood Circulation; D005337:Fibrin / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D005340:Fibrinogen / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008657:Metabolic Clearance Rate; D011498:Protein Precursors / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D011817:Rabbits; D018000:Receptors, Peptide / Q000378:metabolism
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D011498:Protein Precursors; D018000:Receptors, Peptide; C035637:fibrin receptor; C011468:fibrinmonomer; D005337:Fibrin; D005340:Fibrinogen