Decreased plasmin resistance by clots of a homophenotypic Aalpha R 16H fibrinogen (Kingsport, slower fibrinopeptide A than fibrinopeptide B release).
Reported evidence of a role in fibrinolysis by fibrinopeptide (Fp)B-dependent intermolecular fibrin polymerization contacts and of reversed FpA/FpB release sequence from fibrinogen Kingsport led us to investigate the fibrinolytic properties of Kingsport clots. Clot lysis was induced by either plasmin (pH 7.4) or by a mixture of plasminogen and recombinant tissue plasminogen activator and measured by lysis time and by turbidity (350 nm) time course. Clots were formed by thrombin from plasminogen-free fibrinogen (pH 7.4, 8 mmol/l CaCl2), with or without 40 nmol/l factor XIII or 20% afibrinogenemic plasma. Displaying no differences from corresponding normal controls were (a) lysis of repolymerized fibrin clots, and (b) chromogenic measurements of fibrin-stimulated Glu-plasminogen activation by recombinant tissue plasminogen activator. By contrast, thrombin-induced fine and coarse network clots (n = 7) displayed faster turbidity loss than corresponding normal controls and shorter lysis times ranging 31-55% of controls. Comparison of clots of fibrinogen fractions lacking approximately 90% of their alpha chain carboxyl terminal regions, n = 2, also displayed faster plasmin-induced lysis than corresponding controls. To assess the role of FpB release-dependent intermolecular polymerization contacts, clots were prepared in the presence of three molar excess antibeta 15-42 immunoglobulin G, n = 2, and displayed no differences in plasmin-induced lysis from nonimmune immunoglobulin G controls. The reversed FpA/FpB release sequence from Kingsport fibrinogen resulted in clots with decreased resistance to plasmin. We suggest that both markedly slow polymerization and decreased plasmin resistance played causative roles in the hemorrhagic diathesis associated with this dysfibrinogen.
Galanakis
Dennis K
DK
State University of New York, Stony Brook University, Niccoll's Road, New York, NY 11794-7530, USA. dennis.galanakis@stonybrook.edu
Neerman-Arbez
Marguerite
M
Kudryk
Bohdan
B
Henschen
Agnes
A
D005340:Fibrinogen / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism*; D005342:Fibrinolysis; D005344:Fibrinopeptide A / Q000378:metabolism*; D005345:Fibrinopeptide B / Q000378:metabolism*; D006801:Humans
C464794:fibrinogen Aalpha; D005344:Fibrinopeptide A; D005345:Fibrinopeptide B; D005340:Fibrinogen; D005341:Fibrinolysin