To What Extent Are the Terminal Stages of Sepsis, Septic Shock, Systemic Inflammatory Response Syndrome, and Multiple Organ Dysfunction Syndrome Actually Driven by a Prion/Amyloid Form of Fibrin?

Semin Thromb Hemost. 2018 Apr;44(3):224-238. doi: 10.1055/s-0037-1604108. Epub 2017 Aug 4.


A well-established development of increasing disease severity leads from sepsis through systemic inflammatory response syndrome, septic shock, multiple organ dysfunction syndrome, and cellular and organismal death. Less commonly discussed are the equally well-established coagulopathies that accompany this. We argue that a lipopolysaccharide-initiated (often disseminated intravascular) coagulation is accompanied by a proteolysis of fibrinogen such that formed fibrin is both inflammatory and resistant to fibrinolysis. In particular, we argue that the form of fibrin generated is amyloid in nature because much of its normal α-helical content is transformed to β-sheets, as occurs with other proteins in established amyloidogenic and prion diseases. We hypothesize that these processes of amyloidogenic clotting and the attendant coagulopathies play a role in the passage along the aforementioned pathways to organismal death, and that their inhibition would be of significant therapeutic value, a claim for which there is considerable emerging evidence.

Publication types

  • Review

MeSH terms

  • Fibrin / metabolism*
  • Humans
  • Multiple Organ Failure / genetics*
  • Multiple Organ Failure / pathology
  • Prions / adverse effects*
  • Shock, Septic / genetics*


  • Prions
  • Fibrin

Grant support

Funding We thank the Biotechnology and Biological Sciences Research Council (grant BB/L025752/1) as well as the National Research Foundation (NRF) and Medical Research Council (MRC) of South Africa for supporting this collaboration.