Coagulation Disorders and Fibrinogen Deficiencies

Coagulation disorders encompass a spectrum of inherited and acquired conditions that disrupt the delicate balance of haemostasis, leading to either excessive bleeding or thrombosis. Among these, fibrinogen deficiencies occupy a central role. Fibrinogen, a soluble plasma glycoprotein synthesised in the liver, is converted by thrombin into insoluble fibrin that stabilises the primary platelet plug. Quantitative deficiencies range from afibrinogenemia, in which fibrinogen is virtually absent, to hypofibrinogenemia, where levels are reduced. Qualitative defects, such as dysfibrinogenemia, involve structurally abnormal fibrinogen molecules that impair polymerisation or interaction with other clotting factors. Clinical manifestations vary widely, from asymptomatic carriers to life-threatening haemorrhage or paradoxical thrombosis. Diagnosis relies on a combination of coagulation assays—measuring antigenic and functional fibrinogen—and genetic testing to identify pathogenic variants in the FGA, FGB and FGG genes. Management strategies include replacement therapy with fibrinogen concentrate, cryoprecipitate or fresh-frozen plasma, tailored to bleeding risk, invasive procedures and individual pharmacogenomic profiles. Globally, the true prevalence of these rare disorders is under-estimated, yet recent population-scale genomic analyses suggest they may be more common than previously thought. Advances in molecular diagnostics, long-term outcome studies and novel therapeutic approaches are reshaping our understanding of fibrinogen-related coagulopathies, with implications for personalised care and public health policy.

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Coagulation Disorders and Fibrinogen Deficiencies publication trend

The graph below shows the total number of articles in coagulation disorders and fibrinogen deficiencies across all publications each year (not limited to Nature Index journals).

Technical terms

Haemostasis: The physiological process that stops bleeding through vascular constriction, platelet aggregation and coagulation cascade activation.

Fibrinogen: A liver-derived plasma glycoprotein that is cleaved by thrombin to form fibrin strands, essential for clot stability.

Afibrinogenemia: A quantitative fibrinogen disorder characterised by undetectable fibrinogen levels and severe bleeding risk.

Hypofibrinogenemia: A condition of reduced plasma fibrinogen concentration leading to variable bleeding or thrombotic tendencies.

Dysfibrinogenemia: A qualitative defect where structurally abnormal fibrinogen impairs polymerisation, fibrinolysis or interaction with coagulation factors.

Fibrinolysis: The enzymatic breakdown of fibrin clots, primarily mediated by plasmin, to restore vessel patency.

References

1. Survival analysis of coagulation disorders: A retrospective study with a 5-year follow-up. Heliyon (2023).
2. Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis. Journal of Clinical Medicine (2022).
3. Treatment of patients with rare bleeding disorders in the Netherlands: Real‐life data from the RBiN study. Journal of Thrombosis and Haemostasis (2022).