Effects of Post-Translational Modifications of Fibrinogen on Clot Formation, Clot Structure, and Fibrinolysis

Abstract

Objective: Post-translational modifications of fibrinogen influence the occurrence and progression of thrombotic diseases. In this systematic review, we assessed the current literature on post-translational modifications of fibrinogen and their effects on fibrin formation and clot characteristics. Approach and Results: A systematic search of Medline, Embase, Cochrane Library, and Web of Science was performed to find studies reporting post-translational modifications of fibrinogen and the effects on clot formation and structure. Both in vitro studies and ex vivo studies using patient material were included. One hundred five articles were included, describing 11 different modifications of fibrinogen. For the best known and studied modifications, conclusions could be drawn about their effect on clot formation and structure. Oxidation, high levels of nitration, and glycosylation inhibit the rate of polymerization, resulting in dense clots with thinner fibers, while low levels of nitration increase the rate of polymerization. Glycation showed different results for polymerization, but fibrinolysis was found to be decreased, as a consequence of increased density and decreased permeability of clots. Acetylation also decreases the rate of polymerization but results in increased fiber diameters and susceptibility to fibrinolysis. Other modifications were studied less or contrasting results were found. Therefore, substantial gaps in the knowledge about the effect of post-translational modifications remain. Conclusions: Overall, post-translational modifications do affect clot formation and characteristics. More studies need to be performed to reveal the effects of all post-translational modifications and the effects on thrombotic diseases. Expanding the knowledge about modifications of fibrinogen can ultimately contribute to optimizing treatments for thrombotic diseases.

Fibrinolysis in Acute and Chronic Cardiovascular Disease

“…These can affect fibrinolysis indirectly by altering structure of the clot, secondary to raised fibrinogen levels or the presence of posttranslational modification of the protein. 20,21 Fibrinolysis can also be directly affected due to raised levels of antifibrinolytic proteins such as PAI-1, 42,43 increased incorporation of A2AP into the clot, 29 or increased glycation of plasminogen. 110 Importantly, recent evidence indicates that impaired fibrinolysis is a key factor responsible for atherothrombotic events in high-risk patients, even when adequately covered with modern antiplatelet therapies.…”

Effects of rotor angle and time after centrifugation on the biological in vitro properties of platelet rich fibrin membranes

“…Previous reports indicate the presence of in vitro fibrinolysis on blood clots provided by limited activation of plasma proteins with time (Elnager et al, 2014), which may cause a reduction in mean fiber diameter (Hudson, 2017). Furthermore, there is evidence on the literature that posttranslational changes on fibrinogen (de Vries, Snoek, Rijken, & de Maat, 2020) caused by low levels of oxidation and photooxidation results in more dense fibrin clots with thinner fibers. Therefore, this is an intriguing finding which remains to be confirmed with other quantitative approaches in order to understand better the effects of storage of PRF membranes after centrifugation and its possible clinical implications.…”

Mechanical and Physical Behavior of Fibrin Clot Formation and Lysis in Combined Oral Contraceptive Users

“…Oxidation, most frequently studied, is not the only post-translational modification of fibrinogen. Nitration and glycation, amongst others, can influence the fibrin polymerization (including initiation and maximum turbidity), clot characteristic (such as fibrin diameter, clot stiffness, and cross-linking), and the fibrinolysis rate of the fibrin clot (De Vries et al, 2020). Further investigations into these modifications, therefore, need to be done to ascertain the full effect of these COCs on clot formation, lysis, and its biophysical properties.…”