Caracterização molecular da hemostasia: um estudo familial

Abstract

Introduction: Hemostasis is defined as a process that is responsible for maintaining the balance between coagulation and blood fluidity. Alterations in this system have been demonstrated to favour both the formation of thrombi and the occurrence of haemorrhages. A multitude of factors have been identified as contributing to this imbalance, with genetic factors being the most significant. Objective: To investigate genetic variants in the Factor V Leiden (F5), Prothrombin (F2), SERPINE1 (PAI-1), THBS1 (Thrombospondin-1), and Methylenetetrahydrofolate reductase (MTHFR) genes through a family study. Materials and Methods: The present study adopted a descriptive and molecular family study model, with 22 participants from a family with a history of thrombosis. Five millilitres of venous blood were collected in EDTA-containing tubes for subsequent hematological and molecular analyses. The genotyping of variants was performed by real-time PCR (qPCR) using TaqMan probes. The results were analysed using SPSS and GraphPad Prism software. A one-way analysis of variance (ANOVA) was employed to compare the means of the haematological data among the variant genotypes, with a significance level of p < 0.05 being applied. Results: The analyses demonstrated the absence of mutations in the F5 and F2 genes in all participants. Only one individual presented heterozygosity in the SERPINE1 gene. Regarding the MTHFR gene, 45.4% presented a heterozygous genotype (CT) and 18.1% a homozygous genotype (TT). For the THBS1 gene, 40.9% were heterozygous (AG) and 22.7% homozygous (GG). Statistically significant associations were observed between some genotypes and hematological parameters, such as MCHC, RDW, and hematocrit. Conclusion: The study demonstrated the absence of the main classic mutations associated with hereditary thrombophilia in the family analyzed. The variants found in MTHFR and THBS1 showed a possible influence on hematological parameters, but without a proven direct association with thrombotic risk. These findings reinforce that thrombosis has a multifactorial character, involving interaction between genetic, metabolic, and environmental factors.