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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
1   Department of Biomedical Engineering, University of Applied Sciences, Jena, Germany
,
Kathrin Franke
1   Department of Biomedical Engineering, University of Applied Sciences, Jena, Germany
,
Walter Richter
2   Institute of Ultrastructural Research, Friedrich Schiller University Jena, Germany
,
Frank Steiniger
2   Institute of Ultrastructural Research, Friedrich Schiller University Jena, Germany
,
Ulrich T. Seyfert
3   Department of Clinical Haemostaseology and Blood Transfusion, University Saarland, Homburg, Germany
,
Joachim Schenk
3   Department of Clinical Haemostaseology and Blood Transfusion, University Saarland, Homburg, Germany
,
Jörn Treuner
4   Department of Pediatrics, Olga Hospital, Stuttgart, Germany
,
Werner Haberbosch
1   Department of Biomedical Engineering, University of Applied Sciences, Jena, Germany
,
Roswit Eisert
1   Department of Biomedical Engineering, University of Applied Sciences, Jena, Germany
,
Monika Barthels
1   Department of Biomedical Engineering, University of Applied Sciences, Jena, Germany
› Author Affiliations
Further Information

Publication History

Received 26 September 2002

Accepted after revision 07 January 2003

Publication Date:
07 December 2017 (online)

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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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