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Thromb Haemost 2011; 105(04): 627-634
DOI: 10.1160/TH10-03-0179
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

A novel missense mutation in the FGB g. 3354 T>A (p. Y41N), Fibrinogen Caracas VIII

Rita Marchi
1   Centro de Medicina Experimental, Laboratorio Biología del Desarrollo de la Hemostasia, Instituto Venezolano de Investigaciones Científicas, Caracas, República Bolivariana de Venezuela
,
Héctor Rojas
2   Centro de Biofísica y Bioquímica, Laboratorio de Fisiología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, República Bolivariana de Venezuela
,
Michael Meyer
3   University of Applied Sciences, Department of Medical Engineering and Biotechnology, Jena, Germany
,
Oscar Castillo
1   Centro de Medicina Experimental, Laboratorio Biología del Desarrollo de la Hemostasia, Instituto Venezolano de Investigaciones Científicas, Caracas, República Bolivariana de Venezuela
,
Arlette De Sáez Ruiz
4   Banco Metropolitano de Sangre del Distrito Capital, Caracas, República Bolivariana de Venezuela
,
John W. Weisel
5   Department of Cell & Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
› Author Affiliations Financial support: This work was partially supported by NIH Grant HL 30954 and a fellowship to Oscar Castillo from the Oficina de Planificación del Sector Universitario (OPSU). Received: March 16, 2010 Accepted after major revision: January 16, 2011 Prepublished online: February 8, 2011
Further Information

Publication History

Received: 16 March 2010

Accepted after major revision: 16 January 2011

Publication Date:
28 November 2017 (online)

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Summary

A novel dysfibrinogenaemia with a replacement of Tyr by Asn at Bβ41 has been discovered (fibrinogen Caracas VIII). An asymptomatic 39-year-old male was diagnosed as having dysfibrinogenaemia due to a mildly prolonged thrombin time (+ 5.8 seconds); his fibrinogen concentration was in the low normal range, both by Clauss and gravimetric determination, 1.9 g/l and 2.1 g/l, respectively. The plasma polymerization process was slightly impaired, characterised by a mildly prolonged lag time and a slightly increased final turbidity. Permeation through the patients´ clots was dramatically increased, with the Darcy constant around four times greater than that of the control (22 ± 2 x10–9 cm2 compared to 6 ± 0.5 x10–9 cm2 in controls). The plasma fibrin structure of the patient, by scanning electron microscopy, featured a mesh composed of thick fibres (148 ± 50 nm vs. 120 ± 31 nm in controls, p<0.05) and larger pores than those of the control fibrin clot. The viscoelastic properties of the clot from the patient were also altered, as the storage modulus (G‘, 310 ± 30) was much lower than in the control (831 ± 111) (p ≤0.005). The interaction of the fibrin clot with a monolayer of human microvascular endothelial cells, by confocal laser microscopy, revealed that the patients´ fibrin network had less interaction with the cells. These results demonstrate the significance of the amino terminal end of the β chain of fibrin in the polymerisation process and its consequences on the clot organisation on the surface of endothelial cells.

Keywords

Mutation - abnormal fibrinogen - clots - permeation - viscoelastic properties - scanning electron microscopy - confocal microscopy
 

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