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

Rita Marchi; Ulf Lundberg; Jos Grimbergen; Jaap Koopman; Argimiro Torres; Norma B. de Bosch; Frits Haverkate; Carmen Luisa Arocha Piñango

doi:10.1055/s-0037-1614006

Thrombosis and Haemostasis, Inhaltsverzeichnis

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

Authors

Rita Marchi

¹From Centro de Medicina Experimental, Laboratorio de Fisiopatología, Instituto Venezolano de Investigaciones Científicas, IVIC, Caracas, Venezuela, The Netherlands
Ulf Lundberg

¹From Centro de Medicina Experimental, Laboratorio de Fisiopatología, Instituto Venezolano de Investigaciones Científicas, IVIC, Caracas, Venezuela, The Netherlands
Jos Grimbergen

²Gaubius Laboratory TNO, Leiden, The Netherlands
Jaap Koopman

³Pharming, Leiden, The Netherlands
Argimiro Torres

⁴Banco Municipal de Sangre del Distrito Federal, Caracas, Venezuela, The Netherlands
Norma B. de Bosch

⁴Banco Municipal de Sangre del Distrito Federal, Caracas, Venezuela, The Netherlands
Frits Haverkate

¹From Centro de Medicina Experimental, Laboratorio de Fisiopatología, Instituto Venezolano de Investigaciones Científicas, IVIC, Caracas, Venezuela, The Netherlands

²Gaubius Laboratory TNO, Leiden, The Netherlands
Carmen Luisa Arocha Piñango

¹From Centro de Medicina Experimental, Laboratorio de Fisiopatología, Instituto Venezolano de Investigaciones Científicas, IVIC, Caracas, Venezuela, The Netherlands

Abstract

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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Referenzen

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