Thrombosis in patients with hereditary fibrinogen deficiency

Abstract

Introduction. In most cases, in patients with hereditary fibrinogen deficiency, clinical manifestations are represented by bleeding of varying intensity and localization. However, the clinical picture of hereditary fibrinogen deficiency can also be represented by thrombosis.Aim — to characterize the detected mutations in fibrinogen genes and to analyze prothrombotic factors in patients with hereditary hypofibrinogenemia and thrombosis.Materials and methods. Forty-nine patients with hereditary hypofibrinogenemia were observed, of which 46 patients had no history of thrombosis and 3 patients had a confirmed history of thrombosis. These 3 patients made up the study group.Results. Heterozygous mutations were found in all 3 patients in the fibrinogen gamma chain gene (FGG), one of them had a previously undescribed deletion g.2653_2684+211del, p.(Asp167Glufs*2), which removes 32 terminal nucleotides of the fifth exon of the FGG gene and leads to the formation of a stop codon in place of amino acid 168. In two other patients, there were missense mutations c.1140T>A, p.(Cys365Ser) and c.1114A>T, p.(Asp356Val), which can determine the thrombogenic properties of the altered protein structure of fibrinogen. Other prothrombotic factors were also identified: genetic polymorphisms of low thrombotic risk, surgery, taking combined oral contraceptives.Conclusion. Hereditary fibrinogen deficiency does not play a protective role in relation to the development of thrombosis and may cause the development of thrombosis, which is associated with its multifunctional role in the hemostasis system. The pathogenesis of thrombosis in patients with hereditary hypofibrinogenemia is multifactorial and may be associated with the characteristics of the main protein defect and the coexistence of hereditary and acquired thrombotic risk factors (surgical interventions, taking combined oral contraceptives, etc.).