Summary
Previous studies showed that α-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, α-profibrin lacking only
one of the two FPA are produced in the course of conversion of human fibrinogen to
fibrin. Since clearance of the α-fibrin monomer is saturable and receptor mediated,
the extent to which α-profibrin or other fibrin(ogen) derivatives might compete for
monomer uptake was deemed important. We compared plasma decay of injected human α-fibrin,
fibrinogen, and α-profibrin in rabbits using rabbit anti-human fibrinogen for assays.
The circulatory half-life of human α-fibrin monomer was short (t1/2 = 2.3 h) and followed a simple exponential decay curve, as anticipated from clearance
of rabbit α-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 α-profibrin had an intermediary half-life (t1/2 = 11 h) determined from double exponential decay curves. Since redistribution accompanied
the slow clearance of α-profibrin, its binding by the fibrin receptor(s) must be weak,
probably too weak to compete with the clearance of α-fibrin monomer. The initial production
of α-fibrin monomer is only partially dependent on prior formation of α-profibrin,
as recently shown. Thus, it is the slow clearance and the weak competition from α-profibrin
that underlie the occurrence of substantial levels of α-profibrin unaccompanied by
detectable levels of α-fibrin monomer in many subjects with vascular disease.
Keywords
Fibrinogen - α-profibrin - α-fibrin - clearance
