Modulation of fibrin clot formation by human serum amyloid P component (SAP) and heparin.
Serum amyloid P-component (SAP) is a normal plasma constituent in man with a circulating concentration of approximately 40 micrograms/ml. Supraphysiological amounts of SAP (150-300 micrograms/ml) have been reported to affect coagulation. We have investigated this further by studying the effect of SAP upon clot times in both the absence and presence of heparin, a suggested ligand for SAP and itself a modulator of coagulation processes. In the absence of heparin, SAP (5-125 micrograms/ml) had no effect on clot times generated by Activated Thrombofax Reagent, brain thromboplastin, Russell's Viper Venom or thrombin when assessed in normal citrated plasma. However, in the presence of amounts of heparin that had only a minor effect upon clot times, SAP (5-40 micrograms/ml) greatly prolonged clot formation, with the thrombin time the most sensitive to SAP. This suggested that the primary effect of SAP was at this distal level of the coagulation pathway. Evaluation by radioimmunoassay revealed that supraphysiological concentrations of SAP (150-300 micrograms/ml) alone reduced by approximately 25% the release of fibrinopeptide A (FPA) from fibrinogen. In the presence of heparin, substantial synergism was observed with maximal reductions of approximately 70% in FPA production requiring only 25-50 micrograms/ml SAP. This inhibition correlated with increased thrombin clot time but was unrelated to any direct modulation in either the activities of anti-thrombin III or activated Factor XIII, and was independent of an alteration in the rate of fibrinolysis. Further, while SAP itself did not interfere with the process of spontaneous fibrin polymerization, in the presence of heparin a prolonged polymerization time (greater than 145%) was observed. We believe that these data reflect the primary mechanisms by which serum amyloid P component influences blood coagulation.
D000682:Amyloid / Q000502:physiology*; D001777:Blood Coagulation; D005337:Fibrin / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D005340:Fibrinogen / Q000378:metabolism; D006493:Heparin / Q000502:physiology*; D006801:Humans; D046911:Macromolecular Substances; D010314:Partial Thromboplastin Time; D011108:Polymers / Q000032:analysis; D000685:Serum Amyloid A Protein / Q000502:physiology*; D013918:Thrombin Time
D000682:Amyloid; D046911:Macromolecular Substances; D011108:Polymers; D000685:Serum Amyloid A Protein; D005337:Fibrin; D005340:Fibrinogen; D006493:Heparin