The Role of Microvascular Thrombosis in Sepsis

The acute inflammatory response to sepsis gives rise to significant morbidity and mortality. The mechanisms underlying this form of tissue injury are poorly understood. This review examines the evidence that tissue ischaemia due, to generalized microvascular thrombosis may play an important role. Microvascular thrombosis is probably an adaptive response that prevents bacteria in the tissues reaching the systemic circulation via the capillaries. In time, a definitive response by leucocytes removes the bacteria and repairs the damaged tissues. There is however evidence that if microvascular thrombosis becomes generalized, then extensive tissue ischaemia may precipitate organ failure and death. Post-mortem studies of patients with sepsis demonstrate microvascular thrombi in many organs including the kidney, liver, lung, gut, adrenals and brain, and the degree of organ injury is related to the quantity of thrombi. Furthermore studies in human and animal models of sepsis demonstrate therapies that inhibit coagulation or promote fibrinolysis reduce organ failure and mortality. In view of the personal and economic burdens that tissue injury associated with the acute inflammatory response places on the community, further studies to establish the role of microvascular thrombosis are clearly required. Such studies may lead to new therapies to limit or prevent this form of injury.