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

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.

Viscoelastic Hemostatic Assays: A Primer on Legacy and New Generation Devices

“…ROTEM ® has also been used in the diagnosis of bleeding disorders. Extrinsic thromboelastometry (EXTEM) as a parameter of ROTEM ® delta, modified by the addition of TF to the cup, provides "interim results" much the same as the TF-enhanced rTEG ® produces threshold parameters that trigger action by the clinician prior to the completion of the test in emergency situations [11,29,32,37,53,54].…”

Tranexamic Acid for Shoulder Arthroplasty: A Systematic Review and Meta-Analysis

“…TXA is currently a commonly used perioperative antifibrinolytic agent. The antifibrinolytic is used in surgery but also in various other bleeding manifestations in congenital coagulopathies, such as fibrinogen deficiency [ 25 ]. With the increase in the number of TSAs performed, and the constant expansion of the indications qualifying for the procedure, there is a need to reduce postoperative complications and improve the procedure’s results.…”

Development of Transient Recombinant Expression and Affinity Chromatography Systems for Human Fibrinogen

“…Human fibrinogen (fgn) is a soluble 340 kDa multimeric glycoprotein found in blood plasma. The normal range of circulating fibrinogen levels varies slightly based on gender, age, geographic region, race, and ethnicity, and can also vary slightly among hematology laboratories depending on the measurement techniques utilized [1]. Typically reported values range from 1.5-4.2 g/L [1,2].…”

“…The normal range of circulating fibrinogen levels varies slightly based on gender, age, geographic region, race, and ethnicity, and can also vary slightly among hematology laboratories depending on the measurement techniques utilized [1]. Typically reported values range from 1.5-4.2 g/L [1,2]. Fibrinogen, and its cleavage product fibrin, participate in many important biological functions including hemostasis, angiogenesis, wound healing, and inflammation among others [3][4][5][6].…”