Japanese Journal of Thrombosis and Hemostasis
Online ISSN : 1880-8808
Print ISSN : 0915-7441
ISSN-L : 0915-7441
Fibrinogens Hamasaka and Tokyo III
Impaired Release of Fibrinopeptide A due to Aα Arginine-16 Histidine or Cysteine Substitution
Shinichi MURAMATSUKensuke YAMAZUMIHisato MAEKAWAJun MIMUROYoichi SAKATAYutaka NAKAMURAAkiko ANDOHiroshi HASEGAWAMichio MATSUDA
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1991 Volume 2 Issue 4 Pages 286-292

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Abstract
Two types of congenital dysfibrinogenemias, designated as fbrinogens Hamasaka and Tokyo III, with impaired release of fibrinopeptide A (FPA) were found in a 3-year-old girl and a 63-year-old man, respectively. They were both heterozygotes for abnormality and had been asymptomatic. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), fibrinogen Hamasaka displayed delayed release of FPA by thrombin and defective release by Ancrod, a thrombin-like snake venom enzyme derived from Agkistrodon rhodostoma (Fig. 1). There were two species of FPA, normal and abnormal, and the abnormal FPA was eluted earlier than its normal counterpart in only half the normal amount on reverse phase high-performance liquid chromatography (Fig. 2). From fibrinogen Tokyo III, no aberrant FPA was released by thrombin or Ancrod (Fig. 3). In these abnormal fibrinogens, polymerization of fibrin monomers was not affected (Fig. 4). Reduced and S-carboxymethylated fibrinogen Tokyo III showed the broad Aα chain on SDS-PAGE, suggesting the presence of an excess cysteine residue in the aberrant Aα chain (Fig. 5). Direct amino acid sequencing of the abnormal FPA or Aα chain revealed substitutions of Aα arginine-16 to histidine in fibrinogen Hamasaka and to cysteine in fibrinogen Tokyo III. These rather common mutations are accounted for by a possible single base exchange compatible with the C to T hot spot mutation theory, either in the antisense strand for the former or in the sense strand for the latter.
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© The Japanese Society on Thrombosis and Hemostasis
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