Coagulation and complement: Key innate defense participants in a seamless web

Abstract

In 1969, Dr. Oscar Ratnoff, a pioneer in delineating the mechanisms by which coagulation is activated and complement is regulated, wrote, “In the study of biological processes, the accumulation of information is often accelerated by a narrow point of view. The fastest way to investigate the body’s defenses against injury is to look individually at such isolated questions as how the blood clots or how complement works. We must constantly remind ourselves that such distinctions are man-made. In life, as in the legal cliché, the devices through which the body protects itself form a seamless web, unwrinkled by our artificialities.” Our aim in this review, is to highlight the critical molecular and cellular interactions between coagulation and complement, and how these two major component proteolytic pathways contribute to the seamless web of innate mechanisms that the body uses to protect itself from injury, invading pathogens and foreign surfaces.

Physiology and pathology of the C3 amplification cycle: A retrospective

“…His plasma and serum complement profile closely resembled that of the FI deficiency of TJ, and subsequently it has been established that FH and related deficiencies of the amplification loop, including FI and MCP, and gain of function mutations in C3 and FB, provide the genetic basis of this disease 14,15 . In aHUS the occlusion of glomerular capillaries by platelets and fibrin leads to fragmentation of erythrocytes and severe impairment of glomerular filtration, and provides clear evidence of the links between the coagulation and complement systems 16 . The recognition of the causal role complement deficiency and pathological complement activation plays in aHUS led to a major therapeutic advances in this field, initially through plasma exchange to provide deficient factors, then by the anti‐C5 monoclonal antibody eculizumab 17 …”

Leukocyte metabolism in obese type 2 diabetic individuals associated with COVID-19 severity

“…If this immune response is ineffective, considerable damage might emerge in capillaries (or other small vessels nearby the alveolar spaces), an event that can activate a pro-coagulant condition. With further virus persistence, complement-initiated damage to vessels increases, and inflammatory cells promote a stronger and wider burst of cytokines, which sustains bidirectional progress of the immune–coagulation axis ( Pryzdial et al, 2022 ).…”

“…Complex type serine proteases are extended by independent additional areas primarily at the N-terminus and interact with many other proteins in complex patterns. In this sense, typical representatives are clotting components and elements of the complement cascade ( Pryzdial et al, 2022 ). Interestingly, the acceleration of the clotting process and clot formation in whole blood and platelet-poor plasma are physiological events that can be noted in the pathophysiology of COVID-19 ( Parato et al, 2021 ).…”

Unveiling the Great Therapeutic Potential of MASPs as Hemostatic Agents

“…In addition, they can also be contemplated for the management of bleeding in patients with hemophilia A and B where the basic biochemical abnormality is the inability to activate FX that generate thrombin and fibrin in order to stabilize the platelet clot [ 69 ]. In summary, the complement and coagulation systems must be viewed as inextricably intertwined [ 70 ]. MASP-1 and MASP-2 link innate immunity to secondary hemostasis, and by virtue of their hemostatic potential, are promising novel agents for the treatment and/or prevention of acute bleeding.…”