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?

Douglas B. Kell, Etheresia Pretorius

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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.

    Original languageEnglish
    JournalSeminars in Thrombosis and Hemostasis
    Early online date4 Aug 2017
    DOIs
    Publication statusPublished - 2017

    Keywords

    • dormant bacteria
    • MODS
    • sepsis
    • septic shock
    • SIRS

    Research Beacons, Institutes and Platforms

    • Manchester Institute of Biotechnology

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