Clinical Features and Management of Congenital Fibrinogen Deficiencies

Abstract

Congenital fibrinogen disorders are rare diseases affecting either the quantity (afibrinogenemia and hypofibrinogenemia) or the quality (dysfibrinogenemia) or both (hypodysfibrinogenemia) of plasmatic fibrinogen. Afibrinogenemia is often diagnosed at birth following prolonged umbilical cord bleeding and is characterized by spontaneous bleeding in all tissues, while hypofibrinogenemic patients are more often asymptomatic. Spontaneous spleen ruptures, painful bone cysts, cardiovascular events, and intrahepatic inclusions can complicate the clinical course of patients with quantitative fibrinogen disorders. Clinical manifestations of dysfibrinogenemia are very heterogeneous, from absence of symptoms to major bleeding or thrombosis, chronic thromboembolic pulmonary hypertension, and renal amyloidosis. Hypodysfibrinogenemic patients can suffer from both major bleeding and recurrent thrombosis. Pregnancy of women with congenital fibrinogen disorders is a high-risk situation. Owing to the absence of controlled randomized studies, clinical management is mainly based on expert consensus. For the treatment and/or the prevention of bleeding, plasma-derived fibrinogen concentrates are the optimal choice. Treatment of thrombosis may be challenging. More specifically, management strategies should be tailored to each patient, taking the personal and familial history of bleeding and thrombosis, the genotype, and the specific clinical situation into account.

Quality Assessment of Established and Emerging Blood Components for Transfusion

“…Immunoglobulin therapy clearly benefits some patients, such as those with primary or secondary immune deficiency, immune thrombocytopenia, and chronic inflammatory demyelinating polyradiculoneuropathy [94]. vWF [95] or fibrinogen concentrates benefit patients with deficiencies of these factors [96], and prothrombin complex concentrates reverse warfarin therapy more rapidly than plasma transfusion with respect to laboratory values and more effectively with respect to restoration of hemostasis [97]. Fibrinogen concentrates and PCCs may provide superior therapy compared to plasma in bleeding patients without genetic deficits due to the possibility of rapid restoration of hemostasis and are under active investigation.…”

Fibrinogen as a Pleiotropic Protein Causing Human Diseases: The Mutational Burden of Aα, Bβ, and γ Chains

“…Monoallelic and biallelic mutations in FGA , FGB , and FGG genes are associated with different inherited conditions, reflecting the pleiotropic function of the fibrinogen protein [ 13 ]. Congenital fibrinogen defects are conventionally classified on the basis of plasma concentration as quantitative (type I) and qualitative (type II) deficiencies [ 14 , 15 , 16 ]. Quantitative deficiencies include afibrinogenemia/severe hypofibrinogenemia (Online Mendelian Inheritance in Man (OMIM) #202400; [ 17 ]) and hypofibrinogenemia (OMIM +134820, *134830, *134850), which are characterized by the lack/extremely low or by reduced amounts of immunoreactive fibrinogen (<150–160 mg/dL), leading to hemorrhagic manifestations, which can vary from very mild to life threatening.…”

“…Qualitative deficiencies comprise dysfibrinogenemia (OMIM +134820, *134830, *134850) and hypo-dysfibrinogenemia, and are characterized by a discrepancy between antigen levels and functional (abnormally low) activity. Patients that are diagnosed with these conditions are either asymptomatic, or can suffer from bleeding symptoms, thrombophilia, or even both [ 15 ].…”

Raw Cucumber (Cucumis sativus) Fruit Juice as Possible First-Aid Antidote in Drug-Induced Toxicity

“…Fibrinogen is synthesized in the liver. Decrease in fibrinogen level in this study after amoxicillin overdose could be associated with the hepatotoxic effect of amoxicillin that can cause a decrease in the physiological function of the liver, which includes the production of fibrinogen [20][21][22][23][24][25][26][27].…”

“…Fibrinogen is a plasma glycoprotein and an acute phase protein produced by liver cells and the most abundant clotting factor. Plasma fibrinogen is used to determine inherited deficiency, unexplained or prolonged bleeding, and risk of cardiovascular and heart disease [20][21][22][23][24][25][26][27]. Increased fibrinogen concentration can be due to chronic inflammation [20][21][22][23][24][25][26][27].…”