A New Type of Congenital Dysfibrinogen, Fibrinogen Bremen, with an Aα Gly-17 to Val Substitution Associated with Hemorrhagic Diathesis and Delayed Wound Healing

Yasuo Wada; Kazuki Niwa; Hisato Meakawa; Shinji Asakura; Teruko Sugo; Makoto Nakanishi; Günter Auerswald; Manfred Popp; Michio Matsuda

doi:10.1055/s-0038-1649593

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1993; 70(03): 397-403
DOI: 10.1055/s-0038-1649593

Original Article

Clinical Studies

Schattauer GmbH Stuttgart

A New Type of Congenital Dysfibrinogen, Fibrinogen Bremen, with an Aα Gly-17 to Val Substitution Associated with Hemorrhagic Diathesis and Delayed Wound Healing

Yasuo Wada

¹The Division of Hemostasis and Thrombosis Research, Institute of Hematology, Tochigi, Japan

,

Kazuki Niwa

¹The Division of Hemostasis and Thrombosis Research, Institute of Hematology, Tochigi, Japan

,

Hisato Meakawa

¹The Division of Hemostasis and Thrombosis Research, Institute of Hematology, Tochigi, Japan

,

Shinji Asakura

¹The Division of Hemostasis and Thrombosis Research, Institute of Hematology, Tochigi, Japan

,

Teruko Sugo

¹The Division of Hemostasis and Thrombosis Research, Institute of Hematology, Tochigi, Japan

,

Makoto Nakanishi

²The Department of Biochemistry, Jichi Medical School, Tochigi, Japan

,

Günter Auerswald

³Prof.-Hess-Kinderklinik, Zentralkrankenhaus, Bremen, Germany

,

Manfred Popp

³Prof.-Hess-Kinderklinik, Zentralkrankenhaus, Bremen, Germany

,

Michio Matsuda

¹The Division of Hemostasis and Thrombosis Research, Institute of Hematology, Tochigi, Japan

› Author Affiliations

Abstract

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Summary

We have identified a new type of Aα Gly-17 to Val substitution in a congenital dysfibrinogen, fibrinogen Bremen, derived from a 15-year-old boy having manifested easy bruising and delayed wound healing. The functional abnormality was characterized by altered fibrin monomer polymerization, which became evident by increasing the salt concentration and pH. A synthetic tetrapeptide with a sequence of the amino-terminal segment of normal fibrin α-chain, Gly-Pro-Arg-Val, substantially inhibited polymerization of both normal and the patient-derived fibrin monomers. A synthetic tetrapeptide with the Bremen type sequence of Val-Pro-Arg-Val inhibited polymerization of the patient’s fibrin monomers partially at a peptide: fibrin monomer molar ratio of 4,000:1, and that of normal one at a much higher ratio of 10,000:1. Likewise, a synthetic peptide Ala-Pro-Arg-Val with a replacement of the Gly residue by another aliphatic amino acid Ala inhibited similarly the patient’s fibrin monomer polymerization. Thus, the hypothetical two-pronged socket-like structure consisting of the α-amino group of the amino-terminal Gly and the guanidino group of an Arg at position 3 of the normal fibrin α-chain seems to be restored considerably in the mutant fibrin α-chain at low ionic strengths and pH’s, despite the replacement of the amino-terminal Gly by another aliphatic amino acid Val.

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References

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