Abstract
Congenital fibrinogen disorders are rare pathologies of the hemostasis, comprising quantitative (afibrinogenemia, hypofibrinogenemia) and qualitative (dysfibrinogenemia and hypodysfibrinogenemia) disorders. The clinical phenotype is highly heterogeneous, being associated with bleeding, thrombosis, or absence of symptoms. Afibrinogenemia and hypofibrinogenemia are the consequence of mutations in the homozygous, heterozygous, or compound heterozygous state in one of three genes encoding the fibrinogen chains, which can affect the synthesis, assembly, intracellular processing, stability, or secretion of fibrinogen. In addition to standard coagulation tests depending on the formation of fibrin, diagnostics also includes global coagulation assays, which are effective in monitoring the management of replacement therapy. Genetic testing is a key point for confirming the clinical diagnosis. The identification of the precise genetic mutations of congenital fibrinogen disorders is of value to permit early testing of other at risk persons and better understand the correlation between clinical phenotype and genotype. Management of patients with afibrinogenemia is particularly challenging since there are no data from evidence-based medicine studies. Fibrinogen concentrate is used to treat bleeding, whereas for the treatment of thrombotic complications, administered low-molecular-weight heparin is most often. This review deals with updated information about afibrinogenemia and hypofibrinogenemia, contributing to the early diagnosis and effective treatment of these disorders.
Highlights
Biomedical Center Martin, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Molecular Biology and Genomics, Comenius University in Bratislava, Jessenius Faculty of Afibrinogenemia and
The first remark on afibrinogenemia was made by Rabe and Salomon in 1920, when the authors discussed an unusual case of 9-year-old boy suffering from repeated bleeding episodes by gastrointestinal bleeding starting shortly after his birthday [4]
In patients with hypofibrinogenemia, diagnosed arterial thrombolow fibrinogen activity have higher occurrence of unprovoked major bleeding events, sis were documented, confirming that thrombosis frequently develops at younger age, while patients with sufficient fibrinogen activity were asymptomatic [37]
Summary
Congenital fibrinogen disorders are a heterogeneous group of rare, inherited abnormalities of blood coagulation [1]. Type I disorders (afibrinogenemia and hypofibrinogenemia) influence the amount of fibrinogen in human blood (fibrinogen level decreased to less than 1.8 g/L), whereas type II (dysfibrinogenemia and hypodysfibrinogenemia) impact primarily the quality of fibrinogen in the circulation [1,2]. Following the laboratory parameters needed for definition of disease seriousness, suggested by the European Network of Rare Bleeding Disorders (EN-RBD) with the support of the International Society of Thrombosis and Hemostasis, quantitative fibrinogen deficiency may be classified into mild hypofibrinogenemia (lower limit of normal level—1.0 g/L), moderate hypofibrinogenemia (0.9–0.5 g/L), severe hypofibrinogenemia (0.5–0.1 g/L), and afibrinogenemia (unmeasurable fibrinogen level
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