The role of heparin in sepsis: much more than just an anticoagulant

Abstract

Despite progress in antibiotic treatment, mechanical ventilation, fluid resuscitation and blood glucose maintenance, sepsis remains a cause of high mortality in the intensive care unit to date, there are no proven treatment strategies for the routine management of septic patients. The extensive interaction between inflammation and coagulation contributes to the basic pathophysiology of sepsis. Thus, the agents that attenuate the activation of both inflammation and coagulation may improve the outcome in sepsis. Apart from the well-known anticoagulant effects of heparin, it also possesses various immunomodulatory properties and protects glycocalyx from shedding. Hence, heparin seems to be such an agent. Immunothrombosis plays an important role in early host defence against bacterial dissemination, thus the proper timing for anticoagulant therapy should be determined. We review the available experimental and clinical data supporting the use of heparin in sepsis. At this time the use of heparin in the treatment of sepsis is conflicting. Future trials of heparin therapy for sepsis should concentrate on the very severely ill patients, in whom benefit is most likely to be demonstrated.

How I treat disseminated intravascular coagulation

“…61 However, a clinically relevant effect of heparin in patients with DIC has never been unequivocally demonstrated in controlled clinical trials, although indirect evidence is accumulating that heparin might be of benefit. 62,63 In addition, there are several studies showing that all critically ill patients need adequate prophylaxis for venous thromboembolism, usually with (low molecular weight) heparin. 64 Therapeutic doses of heparin are indicated in patients with clinically overt thromboembolism and may be considered in case of extensive thrombotic manifestations such as in purpura fulminans or acral ischemia.…”

COVID-19, Low-Molecular-Weight Heparin, and Hemodialysis

“…Antithrombin levels decrease in sepsis and, when low, may predict high mortality [13]. In addition, heparin is utilized in this context, also for its immunomodulatory and anti-inflammatory role [14].…”

The contact pathway and sepsis

“…These relationships can be collectively referred to as immunothrombosis and suggest a role for coagulation as a form of innate immune defense. Purported mechanisms of coagulation being protective against disseminated infection include trapping of pathogens and leukocytes within fibrin thrombi, as well as prevention of pathogens exiting the vascular space into the tissues . At its most extreme, progression of this immunothrombosis mechanism can lead to disseminated intravascular coagulation (DIC), characterized by systemic activation and consumption of coagulation factors, platelets, and fibrinogen, leading to both widespread thrombosis and bleeding, and contributing substantially to the morbidity of sepsis (Figure ).…”