Factor XIII and Fibrin Clot Properties in Acute Venous Thromboembolism

Abstract

Coagulation factor XIII (FXIII) is converted by thrombin into its active form, FXIIIa, which crosslinks fibrin fibers, rendering clots more stable and resistant to degradation. FXIII affects fibrin clot structure and function leading to a more prothrombotic phenotype with denser networks, characterizing patients at risk of venous thromboembolism (VTE). Mechanisms regulating FXIII activation and its impact on fibrin structure in patients with acute VTE encompassing pulmonary embolism (PE) or deep vein thrombosis (DVT) are poorly elucidated. Reduced circulating FXIII levels in acute PE were reported over 20 years ago. Similar observations indicating decreased FXIII plasma activity and antigen levels have been made in acute PE and DVT with their subsequent increase after several weeks since the index event. Plasma fibrin clot proteome analysis confirms that clot-bound FXIII amounts associated with plasma FXIII activity are decreased in acute VTE. Reduced FXIII activity has been associated with impaired clot permeability and hypofibrinolysis in acute PE. The current review presents available studies on the role of FXIII in the modulation of fibrin clot properties during acute PE or DVT and following these events. Better understanding of FXIII’s involvement in the pathophysiology of acute VTE might help to improve current therapeutic strategies in patients with acute VTE.

Malignant cerebral infarction after ChAdOx1 nCov-19 vaccination: a catastrophic variant of vaccine-induced immune thrombotic thrombocytopenia

“…A hypercoagulable state was observed in both the patients with a high level of VWF and VWF:RCo, D-dimer, and coagulation Factor VIII. Factor XIII was markedly decreased in patient 1, probably due to excessive consumption within thrombi 19 .…”

Malignant cerebral infarction, systemic venous thrombosis and thrombocytopenia after ChAdOx1 nCov vaccination: a possible catastrophic variant of vaccine induced thrombotic thrombocytopenia

“…Factor XIII was markedly decreased in patient 1, probably due to excessive consumption within thrombi. 10 Treatment of this new syndrome is challenging. Administration of high-dose IVIg has been suggested in attempt to inhibit Fcγ receptor-mediated platelet activation, since in the treatment of severe autoimmune HIT this treatment resulted in rapid increase in platelet count.…”

Fibrinogen β chain and FXIII polymorphisms affect fibrin clot properties in acute pulmonary embolism

“…The FGB rs1800790 polymorphism was also found to prolong CLT and promote thinner fibrin fibres formation in patients with type 2 diabetes mellitus 16 . In several studies, F13 rs5985 T allele has been shown as a ‘protective’ genetic factor associated with a lower risk of VTE 10,17–19 . The protection has been suggested to be linked to high fibrinogen levels, 19 which in association with F13 rs5985 T allele predisposed to the formation of thicker fibrin fibres, increased K s and susceptibility to lysis.…”

“…16 In several studies, F13 rs5985 T allele has been shown as a 'protective' genetic factor associated with a lower risk of VTE. 10,[17][18][19] The protection has been suggested to be linked to high fibrinogen levels, 19 which in association with F13 rs5985 T allele predisposed to the formation of thicker fibrin fibres, increased K s and susceptibility to lysis. On the contrary, individuals with normal fibrinogen levels, F13 rs5985 T allele carriers, are characterized by thinner fibrin fibres and reduced K s , which may be due to faster FXIII activation and faster fibrin cross-linking.…”