Congenital structural and functional fibrinogen disorders: a primer for internists

Abstract

Congenital qualitative and quantitative fibrinogen disorders represent heterogeneous rare abnormalities caused by mutations in one of the 3 genes encoding individual fibrinogen polypeptide chains, located on chromosome 4q28. It is estimated that congenital fibrinogen disorder accounts for 8% of rare coagulation factor deficiencies. Most of congenital fibrinogen disorders are suspected in individuals with bleeding tendency or coincidentally discovered, for instance prior to surgery. Fibrinogen disorders could be also found in patients with thrombotic events, impaired wound healing, and recurrent spontaneous abortions. Afibrinogenemia manifests as mild to severe bleeding, while hypofibrinogenemia is often asymptomatic. Dysfibrinogenemia, a qualitative fibrinogen disorder, is associated with bleeding, thrombosis, or with no symptoms. Recent recommendations issued by the International Society on Thrombosis and Haemostasis in 2018 do not encourage routine evaluation of thrombin time or other coagulation tests in patients with suspected congenital fibrinogen disorders, highlighting the value of fibrinogen antigen measurement and genetic analysis, added to the key finding, that is, reduced fibrinogen concentration determined with a coagulometric assay. The current review summarizes practical issues in diagnostic work up and clinical management of patients with afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia from a perspective of internists who may encounter patients with reduced fibrinogen concentration in everyday practice. Despite the fact that hematologists are in front line for the management of patients with bleeding tendency, internists should be aware of the clinical and laboratory findings in patients with inherited fibrinogen disorders including the risk of thromboembolism and management prior to invasive procedures.

Patients scheduled for TAVI tend to form abnormal fibrin clots more resistant to lysis: the impact of age

“…Second, several fibrinolysis and coagulation proteins which are involved in thrombin generation, fibrin formation, and fibrinolysis, including prothrombin, antiplasmin, plasminogen, and platelet-derived proteins, have not been evaluated [22,29,32]. Genetic modifiers of fibrin clot properties have not been assessed by us [33]. However, the mechanisms underlying the observed differences between two groups of patients were beyond the scope of the current research.…”

Inherited Thrombophilias in Thrombosis Advancement in Microvascular Flap Surgery

“…The latter genotype was found in 5 of 12 patients with free flap thrombosis, as shown in Table 4. Undas and Casini (2019) previously reported that patients with hereditary dysfibrinogenemia are highly heterogeneous in clinical manifestation.…”

Fibrin Clot Properties in Atherosclerotic Vascular Disease: From Pathophysiology to Clinical Outcomes

“…Moreover, high levels of plasminogen activator inhibitor type 1 (PAI-1) have been identified both in the blood of coronary artery disease (CAD) patients and within unstable plaques [28]. Some genetically determined fibrinogen disorders, dysfibrinogenemias, have also been linked to atherosclerotic vascular disease and its thromboembolic manifestations, supporting the view that alterations to fibrin structure and function might be of greater importance than the fibrinogen concentration itself [29][30][31].…”