Dysfibrinogenemia and Thrombosis

Abstract

Congenital abnormal fibrinogen molecules (dysfibrinogenemias) are due to structural defects in the molecule. The molecular structure of the fibrinogen molecule is to a great extent known and this has allowed identification of the abnormalities at a molecular level. While most patients with dysfibrinogenemia are clinically asymptomatic, some present with a bleeding diathesis, others with thrombophilia, and occasionally with both, bleeding and thromboembolism. In principle, the dysfibrinogenemias are due to either impaired release of the fibrinopeptides, defective fibrin polymerization, or abnormal cross-linking by factor XIIIa. Dysfibrinogenemias associated with thrombophilia have been reported in those related to abnormal fibrinopeptide release or defective polymerization. In addition, abnormal interactions with platelets, defective fibrinolysis, defective assembly of the fibrinolytic system, and abnormal calcium binding have been described. The presently identified dysfibrinogenemias associated with thrombosis and their molecular defects are described in this review. It must also be recognized that some patients with abnormal fibrinogen molecules have additional hemostasis defects, such as abnormalities of antithrombin, protein C, protein S, factor V Leiden, and others. On rare occasions, dysfibrinogenemias can be associated with hypofibrinogenemia.

Laboratory testing for fibrinogen abnormalities

“…Some patients with dysfibrinogenemia suffer from thrombosis, with or without bleeding [23]. Thrombotic complications have been reported in individuals with dysfibrinogenemias associated with impaired release of FPA and/or FPB, or defects in fibrin polymerization, although the relationship between these abnormalities and thrombophilia is unclear [25]. The thrombotic tendency in fibrinogen Caracas V is attributed to an abnormally tight fibrin network that impedes fibrinolysis [26].…”

Genetic variation in the fibrinogen gamma gene increases the risk for deep venous thrombosis by reducing plasma fibrinogen γ′ levels

“…12,13 In addition, genetic variants of fibrinogen (dysfibrinogenemias) have been found in patients with thrombosis and prolonged thrombin time. 14,15 Most of these patients have a mutation in the FGA or the FGG gene, though the precise relation between carriership of these mutations and venous thrombosis is poorly documented. 16 We hypothesized that relatively common variations among the fibrinogen genes might exist and might influence the risk for deep venous thrombosis.…”

Endothelial Cell VE-cadherin Functions as a Receptor for the β15–42 Sequence of Fibrin

“…In the final steps of blood coagulation, the soluble plasma protein fibrinogen is enzymatically converted by the action of thrombin into insoluble fibrin monomers, which spontaneously polymerize to yield a fibrin mesh containing entrapped platelets and red blood cells (1). The fibrin blood clot plays a vital role in many physiologic and pathophysiologic processes including hemostasis and thrombosis (1), and in angiogenic processes such as wound healing and tumor growth (2,3).…”

“…The fibrin blood clot plays a vital role in many physiologic and pathophysiologic processes including hemostasis and thrombosis (1), and in angiogenic processes such as wound healing and tumor growth (2,3). In these processes fibrin interacts with a variety of plasma proteins, cells, and tissue matrix components.…”