title: The impact of delayed fibrinopeptide-A release on fibrin structure. Studies of an abnormal fibrinogen.
abstract: The impact of delayed fibrinopeptide-A release on polymerization and structure of fibrin gels was studied utilizing a heterozygously transmitted variant fibrinogen. An arginine to histidine substitution at position 16 of the alpha chain of the abnormal fibrinogen delayed release of an abnormal fibrinopeptide-A (A) by thrombin and completely blocked release of A by reptilase. When clotted with thrombin, patient fibrin formed more slowly than normal fibrin, but clottability was normal and gel fiber mass/length ratios were decreased less than 10%. Gels formed with reptilase clotted slowly, demonstrated reduced clottability, but had normal fiber mass/length ratios. Reptilase clotted the normal but not the variant component of the patient fibrinogen. Thrombin-induced cleavage of fibrinopeptide-B prior to A occurred in these experiments, but polymerization of this species beyond trimers has been reported to be minimal under the conditions used. With time, A is removed by thrombin resulting in the slow production of normal fibrin monomer from the abnormal component. These monomers subsequently polymerize. The minimal change in gel fiber size caused by slow A release implies that fibrin fiber size is primarily a function of ionic environment and not of the sequence of peptide release.
authors: Department of Medicine, Medical College of Virginia, Richmond.
authors: M E
authors: ME
authors: Carr
authors: G D
authors: GD
authors: Qureshi
mesh_terms: D001120:Arginine; D012103:Batroxobin / Q000378:metabolism; D001777:Blood Coagulation; D005337:Fibrin / Q000032:analysis*; D005340:Fibrinogen / Q000235:genetics* / Q000378:metabolism*; D005344:Fibrinopeptide A / Q000378:metabolism*; D006639:Histidine; D006801:Humans; D009391:Nephelometry and Turbidimetry; D009994:Osmolar Concentration; D013917:Thrombin / Q000378:metabolism
chemical_list: D005344:Fibrinopeptide A; D006639:Histidine; D005337:Fibrin; D005340:Fibrinogen; D001120:Arginine; D012103:Batroxobin; D013917:Thrombin