Heparin: the cheap alternative for immunomodulation in sepsis?

Severe sepsis, involving a systemic inflammatory response caused by infection and acute organ dysfunction, is one of the most common non-cardiac causes of death in intensive care unit patients worldwide. The mainstay of treatment for severe sepsis is aggressive antibiotic therapy combined with supportive care for associated organ dysfunction. In 2001, recombinant human activated protein C was shown to improve survival in patients with severe sepsis, but two further studies of the immunomodulatory effects of endogenous anticoagulant agents did not show any survival benefit. Importantly, all three studies showed potential confounding by patients receiving low-dose heparin during the study period, raising the possibility that heparin may also have important immunomodulatory actions. This has increased the focus on the non-anticoagulatory actions of heparin, and its potential therapeutic immunodulatory effects during severe sepsis. This review summarises the known clinical effects of heparin and explores the significant implications of its widespread therapeutic use.