Pathophysiological dynamics in the contact, coagulation, and complement systems during sepsis: Potential targets for nafamostat mesilate

Abstract

Sepsis is a life-threatening syndrome resulting from a dysregulated host response to infection. It is the primary cause of death in the intensive care unit, posing a substantial challenge to human health and medical resource allocation. The pathogenesis and pathophysiology of sepsis are complex. During its onset, pro-inflammatory and anti-inflammatory mechanisms engage in intricate interactions, possibly leading to hyperinflammation, immunosuppression, and long-term immune disease. Of all critical outcomes, hyperinflammation is the main cause of early death among patients with sepsis. Therefore, early suppression of hyperinflammation may improve the prognosis of these patients. Nafamostat mesilate is a serine protease inhibitor, which can inhibit the activation of the complement system, coagulation system, and contact system. In this review, we discuss the pathophysiological changes occurring in these systems during sepsis, and describe the possible targets of the serine protease inhibitor nafamostat mesilate in the treatment of this condition.

Keywords: Coagulation system; Complement system; Contact system; Nafamostat; Sepsis.

Figure 1

Potential effects of NM on the contact and intrinsic coagulation systems. Dark/light yellow indicates the intrinsic/extrinsic pathway of the coagulation system. Green indicates the contact system. Orange indicates the common pathway of coagulation.

Figure 2

Potential effects of NM on the complement system. Yellow indicates the classical pathway of the complement system. Green indicates the alternative pathway of the complement system. Yellow-green represents the common path of both pathways.

Figure 3

Potential therapeutic effect of NM on the pathophysiological changes in sepsis.