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

作者：Marchi Rita^*; Rojas Hector; Meyer Michael; Castillo Oscar; De Saez Ruiz Arlette; Weisel John W

来源：Thrombosis and Haemostasis, 2011, 105(4): 627-634.

DOI：10.1160/TH10-03-0179

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

A novel dysfibrinogenaemia with a replacement of Tyr by Asn at B beta 41 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 x 10(-9) cm(2) compared to 6 +/- 0.5 x 10(-9) cm(2) 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 beta chain of fibrin in the polymerisation process and its consequences on the clot organisation on the surface of endothelial cells.

• 出版日期2011-4