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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?
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 accompan...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Thieme Medical Publishers
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193370/ https://www.ncbi.nlm.nih.gov/pubmed/28778104 http://dx.doi.org/10.1055/s-0037-1604108 |
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author | Kell, Douglas B. Pretorius, Etheresia |
author_facet | Kell, Douglas B. Pretorius, Etheresia |
author_sort | Kell, Douglas B. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6193370 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Thieme Medical Publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-61933702018-10-30 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? Kell, Douglas B. Pretorius, Etheresia Semin Thromb Hemost 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. Thieme Medical Publishers 2018-04 2017-08-04 /pmc/articles/PMC6193370/ /pubmed/28778104 http://dx.doi.org/10.1055/s-0037-1604108 Text en https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Kell, Douglas B. Pretorius, Etheresia 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? |
title | 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? |
title_full | 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? |
title_fullStr | 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? |
title_full_unstemmed | 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? |
title_short | 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? |
title_sort | 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? |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193370/ https://www.ncbi.nlm.nih.gov/pubmed/28778104 http://dx.doi.org/10.1055/s-0037-1604108 |
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