The interaction between the complement system and hemostatic factors

Abstract

Purpose of review To discuss the crosstalk between the complement system and hemostatic factors (coagulation cascade, platelet, endothelium, and Von Willebrand Factor), and the consequences of this interaction under physiologic and pathologic conditions. Recent findings The complement and coagulation systems are comprised of serine proteases and are genetically related. In addition to the common ancestral genes, the complement system and hemostasis interact directly, through protein–protein interactions, and indirectly, on the surface of platelets and endothelial cells. The close interaction between the complement system and hemostatic factors is manifested both in physiologic and pathologic conditions, such as in the inflammatory response to thrombosis, thrombosis at the inflamed area, and thrombotic complications of complement disorders. Summary The interaction between the complement system and hemostasis is vital for homeostasis and the protective response of the host to tissue injury, but also results in the pathogenesis of several thrombotic and inflammatory disorders.

Novel Inhibitors and Activity-Based Probes Targeting Trypsin-Like Serine Proteases

“…The most comprehensively studied groups of TLPs are those involved in the coagulation cascade (thrombin, protein C, factors VIIa, IXa, Xa and XIIa) and complement system (C1r, C1s, C3 convertase, C5 convertase and factor D) ( Forneris et al, 2012 ; Oncul and Afshar-Kharghan, 2020 ; Winter et al, 2020 ). Classical biochemical studies carried out on the clotting factor proteases (such as those alluded to above) have been foundational to the development of a number of novel orally active anticoagulants that function as direct inhibitors of thrombin and factor Xa ( Liang and Bowen, 2016 ).…”

Potential Candidates for Biomarkers in Bipolar Disorder: A Proteomic Approach through Systems Biology

“…Although the precise mechanisms underlying the interaction between the complement system (CS) and the CC are still not fully elucidated, current research has indicated a bidirectional modulation between these sys-tems. The CS seems to be derived from the serine protease reaction cascade, which is encoded by the same ancestor genes as the coagulation factors [ 92 , 93 ]. Besides a common origin, these systems also share similar roles, including promoting the first defense line against infections and tissue repairing, while potentially contributing to either homeostasis or the development of pathological conditions [ 94 ].…”

“…Throughout the CC, there are several steps involving the activation of the CS components. For instance, activated platelets present surface molecules, such as P-selectin and C1q receptor, that activate the alternative and classical pathways of the CS, respectively [ 93 , 94 ]. Fibrinogen is a potent acute phase reactant and inflamma-tory mediator [ 101 ].…”

Immune Modulation in Critically Ill Septic Patients

“…However, no definitive clinical data support the use of this therapy in daily clinical life. On top of that, an increasing amount of evidence has shown the interaction between complement and coagulative systems [27]. The latter is frequently altered in patients with sepsis and many drugs have been tested with the aim to improve coagulative dysfunction.…”