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Thromb Haemost 2000; 84(02): 263-270
DOI: 10.1055/s-0037-1614006
Review Article
Schattauer GmbH

Fibrinogen Caracas V, an Abnormal Fibrinogen with an Aα 532 Ser→Cys Substitution Associated with Thrombosis

Rita Marchi
1   From Centro de Medicina Experimental, Laboratorio de Fisiopatología, Instituto Venezolano de Investigaciones Científicas, IVIC, Caracas, Venezuela, The Netherlands
,
Ulf Lundberg
1   From Centro de Medicina Experimental, Laboratorio de Fisiopatología, Instituto Venezolano de Investigaciones Científicas, IVIC, Caracas, Venezuela, The Netherlands
,
Jos Grimbergen
2   Gaubius Laboratory TNO, Leiden, The Netherlands
,
Jaap Koopman
3   Pharming, Leiden, The Netherlands
,
Argimiro Torres
4   Banco Municipal de Sangre del Distrito Federal, Caracas, Venezuela, The Netherlands
,
Norma B. de Bosch
4   Banco Municipal de Sangre del Distrito Federal, Caracas, Venezuela, The Netherlands
,
Frits Haverkate
1   From Centro de Medicina Experimental, Laboratorio de Fisiopatología, Instituto Venezolano de Investigaciones Científicas, IVIC, Caracas, Venezuela, The Netherlands
2   Gaubius Laboratory TNO, Leiden, The Netherlands
,
Carmen Luisa Arocha Piñango
1   From Centro de Medicina Experimental, Laboratorio de Fisiopatología, Instituto Venezolano de Investigaciones Científicas, IVIC, Caracas, Venezuela, The Netherlands
› Author AffiliationsThis work was supported by Grants provided by the Consejo Nacional de Investigationes Cientificas y Tecnologicas CONICIT numbers S1-2697 and S1-2702. We are deeply indebted to the personnel of the Blood Bank of the Federal District of Caracas for their invaluable help in providing the samples. We would also like to thank the Laboratory of Photography at IVIC for photographic work and the department of Graphic Design at IVIC for artwork. We deeply thank Dr. Francisco Gil and Mrs. M. Romano for their expert advice in electron microscopy specimen handling.
Further Information

Publication History

Received 22 November 1999

Accepted after revision 16 March 2000

Publication Date:
14 December 2017 (online)

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Summary

A new dysfibrinogenemia associated with thrombophilia has been identified in a Venezuelan kindred. Thrombin and Reptilase times were prolonged and the accelerating capacity of the patient’s fibrin on the t-PA-induced plasminogen activation was decreased. In addition the affinity of fibrinogen for plasminogen was diminished. Permeability and electron microscopy studies revealed that the abnormal clot was made up of thin and densely packed fibres giving rise to a reduced fibrin gel porosity. This was confirmed by turbidity studies showing a decreased fibre mass/length ratio. Affected members were heterozygous for an Aα 532 Ser→ Cys mutation as demonstrated by genetic analyses. This abnormal fibrinogen has been designated as Fibrinogen Caracas V. The family study showed a convincing association between the mutation and thrombotic manifestations. The thrombotic tendency may be ascribed to lack of accelerating capacity of fibrin to induce fibrinolysis caused by an abnormal clot structure with thin fibres and reduced porosity.

Keywords

Dysfibrinogenemia - thrombophilia - thrombosis
 

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