Thromboinflammation in acute injury: infections, heatstroke, and trauma

Abstract

Tissue microcirculation is essential for the maintenance of organ homeostasis. Following acute infections, activation of coagulation and inflammation, which are critical interconnected responses, lead to thromboinflammation and microthrombosis, thereby contributing to multiorgan dysfunction. Sepsis is the most common underlying disease and has been extensively studied. However, the COVID-19 pandemic further illustrated the pathomechanisms of diseases in which thromboinflammation plays a critical role. During thromboinflammation, injury to monocytes, neutrophils, platelets, and endothelial cells, along with coagulation and complement activation, was further characterized. Thrombin is pivotal in orchestrating thrombosis and inflammation and has long been considered a potential therapeutic target in sepsis. Although thromboprophylaxis for venous thromboembolism with heparins is part of standard management for COVID-19, it also potentially attenuates organ dysfunction due to thrombotic sequela. In contrast, the effectiveness of anticoagulation with heparin, antithrombin, or thrombomodulin to reduce mortality has not conclusively been proven in sepsis. Nonetheless, thromboinflammation has also been reported as an important pathophysiologic mechanism in other critical illnesses, including heatstroke, trauma, and ischemia/reperfusion injury, and may provide a potential therapeutic target for future clinical studies.