New molecular defects in the γ subdomain of fibrinogen D-domain in four cases of (hypo)dysfibrinogenemia: fibrinogen variants Hannover VI, Homburg VII, Stuttgart and Suhl

Michael Meyer; Kathrin Franke; Walter Richter; Frank Steiniger; Ulrich T. Seyfert; Joachim Schenk; Jörn Treuner; Werner Haberbosch; Roswit Eisert; Monika Barthels

doi:10.1055/s-0037-1613585

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2003; 89(04): 637-646
DOI: 10.1055/s-0037-1613585

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

New molecular defects in the γ subdomain of fibrinogen D-domain in four cases of (hypo)dysfibrinogenemia: fibrinogen variants Hannover VI, Homburg VII, Stuttgart and Suhl

Michael Meyer

¹Department of Biomedical Engineering, University of Applied Sciences, Jena, Germany

,

Kathrin Franke

¹Department of Biomedical Engineering, University of Applied Sciences, Jena, Germany

,

Walter Richter

²Institute of Ultrastructural Research, Friedrich Schiller University Jena, Germany

,

Frank Steiniger

²Institute of Ultrastructural Research, Friedrich Schiller University Jena, Germany

,

Ulrich T. Seyfert

³Department of Clinical Haemostaseology and Blood Transfusion, University Saarland, Homburg, Germany

,

Joachim Schenk

³Department of Clinical Haemostaseology and Blood Transfusion, University Saarland, Homburg, Germany

,

Jörn Treuner

⁴Department of Pediatrics, Olga Hospital, Stuttgart, Germany

,

Werner Haberbosch

¹Department of Biomedical Engineering, University of Applied Sciences, Jena, Germany

,

Roswit Eisert

¹Department of Biomedical Engineering, University of Applied Sciences, Jena, Germany

,

Monika Barthels

¹Department of Biomedical Engineering, University of Applied Sciences, Jena, Germany

› Institutsangaben

Abstract

Summary

Four new molecular abnormalities in the γ subdomain of the D domain elucidated in three unrelated thrombophilic patients and in one asymptomatic case of hypofibrinogenemia are reported: fibrinogen Suhl, γ 326,Cys →Tyr, fibrinogen Hannover VI, γ 336 Met →Ile, fibrinogen Stuttgart, γ 345, Asn→Asp and fibrinogen Homburg VII, γ354,Tyr→Cys. In all cases, fibrin polymerization in plasma is impaired. In the case of fibrinogen Suhl, there was a normalization of fibrin polymerization in plasma at higher Ca²⁺ concentration. The protective effect of Ca²⁺ on plasmic degradation of fibrinogen was incomplete with all three variants. The fibrinogen molecules in variants Homburg VII and Suhl contain covalently bound albumin. Fibrin clot structure was abnormal in case of variant Homburg VII, with finer and more branched fibers forming a less porous clot. Experimental data indicate possible effects of the molecular abnormalities on Ca²⁺-binding, D-E interaction and lateral association of protofibrils.

Keywords

Dysfibrinogenemia - hypofibrinogenemia - fibrinogen variants - D domain

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Referenzen

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