Fibrinogen Maracaibo: Hypo-Dysfibrinogenemia Caused by a Heterozygous Mutation in the Gen that Encodes for the Fibrinogen AÃÂ± Chain (G.1194G>A: P.Gly13>Glu) with Diminished Thrombin GenerationMarchi R1*, Rojas H2, Echenagucia M3, Meyer M4, Acosta M5, Apitz R3 and Ruiz-Sáez A3
- *Corresponding Author:
- Rita Marchi Cappelletti
Centro de Medicina Experimental
Laboratorio de Fisiopatología
Sección Biología del Desarrollo de la Hemostasia
Instituto Venezolano de Investigaciones Científicas, IVIC
Apartado 20632, Caracas 1020-A, República Bolivariana de Venezuela
E-mail: [email protected]
Received date: March 10, 2014; Accepte date:d April 26, 2014; Published date: May 05, 2014
Citation: Marchi R, Rojas H, Echenagucia M, Meyer M, Acosta M, et al. (2014) Fibrinogen Maracaibo: Hypo-Dysfibrinogenemia Caused by a HeterozygousMutation in the Gen that Encodes for the Fibrinogen Aa Chain (G.1194G>A: P.Gly13>Glu) with Diminished Thrombin Generation. J Blood Disord Transfus 5:215. doi: 10.4172/2155-9864.1000215
Copyright: © 2014 Marchi R, et al. This is an open-access article distributed underthe terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Introduction: Hereditary fibrinogen abnormalities can be quantitative and/or qualitative. In hypofibrinogenemia and hypodysfibrinogenemia fibrinogen levels are below 150 mg/dL.
Objectives: The aim of the present work was to characterize the fibrinogen abnormalities in a family where the propositus (an asymptomatic four-year-old male) and his mother had prolonged thrombin time and low fibrinogen levels. Methods: Fibrinogen genes were sequenced. Preliminary studies were performed on fibrin (ogen) function and fibrin network characteristics. Fibrin formation kinetic was done in plasma and purified fibrinogen. Fibrin network porosity was measured and fibrin structure visualized by laser scanning confocal microscopy (LSCM). In addition, global haemostatic tests such as thrombin generation and thromboelastography were performed.
Results: DNA analysis revealed a heterozygous mutation in the fibrinogen gen that encoded for the Aα chain (FGA g.1194G>A: p.Gly13>Glu) in the propositus and his mother. In plasma and purified fibrinogen, the rate of patients´ fibrin formation was approximately two times slower compared to control. Propositus´ fibrin porosity was similar to control, but diminished in his mother (p<0.05). By LSCM patients’ clots morphology were similar to control. Thromboelastographic study was normal in both patients, and thrombin generation diminished in the propositus.
Conclusions: The mutation of fibrinogen at Aα Gly13>Glu impairs fibrin polymerization. The differences found in thrombin generation between the propositus and his mother highlights the utility of global assays for therapy individualization.