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Review
. 2021 Nov 19;11(11):2140.
doi: 10.3390/diagnostics11112140.

Congenital Afibrinogenemia and Hypofibrinogenemia: Laboratory and Genetic Testing in Rare Bleeding Disorders with Life-Threatening Clinical Manifestations and Challenging Management

Tomas Simurda  1 , Rosanna Asselta  2   3 , Jana Zolkova  1 , Monika Brunclikova  1 , Miroslava Dobrotova  1 , Zuzana Kolkova  4 , Dusan Loderer  4 , Ingrid Skornova  1 , Jan Hudecek  1 , Zora Lasabova  5 , Jan Stasko  1 , Peter Kubisz  1
Affiliations
Review

Congenital Afibrinogenemia and Hypofibrinogenemia: Laboratory and Genetic Testing in Rare Bleeding Disorders with Life-Threatening Clinical Manifestations and Challenging Management

Tomas Simurda et al. Diagnostics (Basel). .

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.

Keywords: afibrinogenemia; bleeding; genetic testing; global coagulation assays; hypofibrinogenemia; thrombosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Worldwide distribution of RBDs derived from the WFH survey 2019.
Figure 2
Figure 2
Characterization of clinical phenotype in patients with quantitative fibrinogen disorders.
Figure 3
Figure 3
Linear correlation (r = 0.9016; p < 0.0001) between PT-derived fibrinogen and fibrinogen Clauss assay in patients with hypofibrinogenemia according to the study published by Skornova et al.
Figure 4
Figure 4
Rotational thromboelastometry (EXTEM, INTEM, FIBTEM) results and fibrinogen activity in the patient with afibrinogenemia from our center. (A) Basal level; (B) 30 min after administration of 24 mg/kg fibrinogen concentrate (Haemocomplettan® P.
See this image and copyright information in PMC

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