Download PDF
CC BY 4.0 · Semin Thromb Hemost 2018; 44(03): 224-238
DOI: 10.1055/s-0037-1604108
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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
1   School of Chemistry, The University of Manchester, Manchester, United Kingdom
2   Manchester Institute of Biotechnology, The University of Manchester, Manchester, United Kingdom
3   Centre for Synthetic Biology of Fine and Speciality Chemicals, The University of Manchester, Manchester, United Kingdom
,
Etheresia Pretorius
4   Department of Physiological Sciences, Stellenbosch University, Matieland, South Africa
› Author Affiliations 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.
Further Information

Publication History

Publication Date:
04 August 2017 (online)

   Permissions and Reprints

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.

Keywords

sepsis - SIRS - dormant bacteria - septic shock - MODS

Ethical Approval Disclosure

Ethical approval was granted by the University of Pretoria for all human studies (Human Ethics Committee: Faculty of Health Sciences) to Etheresia Pretorius.


 

  • References

  • 1 Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003; 348 (16) 1546-1554
    CrossrefPubMedGoogle Scholar
  • 2 Ranieri VM, Thompson BT, Barie PS. , et al; PROWESS-SHOCK Study Group. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 2012; 366 (22) 2055-2064
    CrossrefPubMedGoogle Scholar
  • 3 Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med 2013; 369 (09) 840-851
    CrossrefPubMedGoogle Scholar
  • 4 Dellinger RP, Levy MM, Rhodes A. , et al; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013; 41 (02) 580-637
    CrossrefPubMedGoogle Scholar
  • 5 Stevenson EK, Rubenstein AR, Radin GT, Wiener RS, Walkey AJ. Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis. Crit Care Med 2014; 42 (03) 625-631
    CrossrefPubMedGoogle Scholar
  • 6 Fleischmann C, Scherag A, Adhikari NK. , et al; International Forum of Acute Care Trialists. Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am J Respir Crit Care Med 2016; 193 (03) 259-272
    CrossrefPubMedGoogle Scholar
  • 7 Beck MK, Jensen AB, Nielsen AB, Perner A, Moseley PL, Brunak S. Diagnosis trajectories of prior multi-morbidity predict sepsis mortality. Sci Rep 2016; 6: 36624
    CrossrefPubMedGoogle Scholar
  • 8 Cohen J. The immunopathogenesis of sepsis. Nature 2002; 420 (6917): 885-891
    CrossrefPubMedGoogle Scholar
  • 9 Bhatia M, Moochhala S. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J Pathol 2004; 202 (02) 145-156
    CrossrefPubMedGoogle Scholar
  • 10 Russell JA. Management of sepsis. N Engl J Med 2006; 355 (16) 1699-1713
    CrossrefPubMedGoogle Scholar
  • 11 Wiersinga WJ, Leopold SJ, Cranendonk DR, van der Poll T. Host innate immune responses to sepsis. Virulence 2014; 5 (01) 36-44
    CrossrefPubMedGoogle Scholar
  • 12 Kaprelyants AS, Gottschal JC, Kell DB. Dormancy in non-sporulating bacteria. FEMS Microbiol Rev 1993; 10 (3-4): 271-285
    PubMedGoogle Scholar
  • 13 Kell DB, Kaprelyants AS, Weichart DH, Harwood CR, Barer MR. Viability and activity in readily culturable bacteria: a review and discussion of the practical issues. Antonie van Leeuwenhoek 1998; 73 (02) 169-187
    CrossrefPubMedGoogle Scholar
  • 14 Lewis K. Persister cells, dormancy and infectious disease. Nat Rev Microbiol 2007; 5 (01) 48-56
    CrossrefPubMedGoogle Scholar
  • 15 Buerger S, Spoering A, Gavrish E, Leslin C, Ling L, Epstein SS. Microbial scout hypothesis, stochastic exit from dormancy, and the nature of slow growers. Appl Environ Microbiol 2012; 78 (09) 3221-3228
    CrossrefPubMedGoogle Scholar
  • 16 Kell D, Potgieter M, Pretorius E. Individuality, phenotypic differentiation, dormancy and ‘persistence’ in culturable bacterial systems: commonalities shared by environmental, laboratory, and clinical microbiology. F1000 Res 2015; 4: 179
    CrossrefPubMedGoogle Scholar
  • 17 Lew WY, Bayna E, Molle ED. , et al. Recurrent exposure to subclinical lipopolysaccharide increases mortality and induces cardiac fibrosis in mice. PLoS One 2013; 8 (04) e61057
    CrossrefPubMedGoogle Scholar
  • 18 Kell DB, Pretorius E. On the translocation of bacteria and their lipopolysaccharides between blood and peripheral locations in chronic, inflammatory diseases: the central roles of LPS and LPS-induced cell death. Integr Biol 2015; 7 (11) 1339-1377
    CrossrefPubMedGoogle Scholar
  • 19 Morath S, Geyer A, Hartung T. Structure-function relationship of cytokine induction by lipoteichoic acid from Staphylococcus aureus . J Exp Med 2001; 193 (03) 393-397
    CrossrefPubMedGoogle Scholar
  • 20 Schröder NW, Morath S, Alexander C. , et al. Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved. J Biol Chem 2003; 278 (18) 15587-15594
    CrossrefPubMedGoogle Scholar
  • 21 Baik JE, Ryu YH, Han JY. , et al. Lipoteichoic acid partially contributes to the inflammatory responses to Enterococcus faecalis. J Endod 2008; 34 (08) 975-982
    CrossrefPubMedGoogle Scholar
  • 22 Jeon JH, Kim SK, Baik JE. , et al. Lipoteichoic acid of Staphylococcus aureus enhances IL-6 expression in activated human basophils. Comp Immunol Microbiol Infect Dis 2012; 35 (04) 363-374
    CrossrefPubMedGoogle Scholar
  • 23 Belum GR, Belum VR, Chaitanya Arudra SK, Reddy BS. The Jarisch-Herxheimer reaction: revisited. Travel Med Infect Dis 2013; 11 (04) 231-237
    CrossrefPubMedGoogle Scholar
  • 24 Cheung CM, Chee SP. Jarisch-Herxheimer reaction: paradoxical worsening of tuberculosis chorioretinitis following initiation of antituberculous therapy. Eye (Lond) 2009; 23 (06) 1472-1473
    PubMedGoogle Scholar
  • 25 Fekade D, Knox K, Hussein K. , et al. Prevention of Jarisch-Herxheimer reactions by treatment with antibodies against tumor necrosis factor alpha. N Engl J Med 1996; 335 (05) 311-315
    CrossrefPubMedGoogle Scholar
  • 26 Guerrier G, D'Ortenzio E. The Jarisch-Herxheimer reaction in leptospirosis: a systematic review. PLoS One 2013; 8 (03) e59266
    CrossrefPubMedGoogle Scholar
  • 27 Prins JM, van Deventer SJ, Kuijper EJ, Speelman P. Clinical relevance of antibiotic-induced endotoxin release. Antimicrob Agents Chemother 1994; 38 (06) 1211-1218
    CrossrefPubMedGoogle Scholar
  • 28 Kirikae T, Nakano M, Morrison DC. Antibiotic-induced endotoxin release from bacteria and its clinical significance. Microbiol Immunol 1997; 41 (04) 285-294
    CrossrefPubMedGoogle Scholar
  • 29 Holzheimer RG. Antibiotic induced endotoxin release and clinical sepsis: a review. J Chemother 2001; 13 (Spec No 1): 159-172
    CrossrefPubMedGoogle Scholar
  • 30 Lepper PM, Held TK, Schneider EM, Bölke E, Gerlach H, Trautmann M. Clinical implications of antibiotic-induced endotoxin release in septic shock. Intensive Care Med 2002; 28 (07) 824-833
    CrossrefPubMedGoogle Scholar
  • 31 Levy MM, Fink MP, Marshall JC. , et al; SCCM/ESICM/ACCP/ATS/SIS. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003; 31 (04) 1250-1256
    CrossrefPubMedGoogle Scholar
  • 32 Bozza FA, Salluh JI, Japiassu AM. , et al. Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. Crit Care 2007; 11 (02) R49
    CrossrefPubMedGoogle Scholar
  • 33 D'Elia RV, Harrison K, Oyston PC, Lukaszewski RA, Clark GC. Targeting the “cytokine storm” for therapeutic benefit. Clin Vaccine Immunol 2013; 20 (03) 319-327
    CrossrefPubMedGoogle Scholar
  • 34 Harrison C. Sepsis: calming the cytokine storm. Nat Rev Drug Discov 2010; 9 (05) 360-361
    CrossrefPubMedGoogle Scholar
  • 35 Oldstone MB, Rosen H. Cytokine storm plays a direct role in the morbidity and mortality from influenza virus infection and is chemically treatable with a single sphingosine-1-phosphate agonist molecule. Curr Top Microbiol Immunol 2014; 378: 129-147
    PubMedGoogle Scholar
  • 36 Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the eye of the cytokine storm. Microbiol Mol Biol Rev 2012; 76 (01) 16-32
    CrossrefPubMedGoogle Scholar
  • 37 Wang H, Ma S. The cytokine storm and factors determining the sequence and severity of organ dysfunction in multiple organ dysfunction syndrome. Am J Emerg Med 2008; 26 (06) 711-715
    CrossrefPubMedGoogle Scholar
  • 38 Weigand MA, Hörner C, Bardenheuer HJ, Bouchon A. The systemic inflammatory response syndrome. Best Pract Res Clin Anaesthesiol 2004; 18 (03) 455-475
    CrossrefPubMedGoogle Scholar
  • 39 Matsuda N, Hattori Y. Systemic inflammatory response syndrome (SIRS): molecular pathophysiology and gene therapy. J Pharmacol Sci 2006; 101 (03) 189-198
    CrossrefPubMedGoogle Scholar
  • 40 Ratzinger F, Schuardt M, Eichbichler K. , et al. Utility of sepsis biomarkers and the infection probability score to discriminate sepsis and systemic inflammatory response syndrome in standard care patients. PLoS One 2013; 8 (12) e82946
    CrossrefPubMedGoogle Scholar
  • 41 Reichsoellner M, Raggam RB, Wagner J, Krause R, Hoenigl M. Clinical evaluation of multiple inflammation biomarkers for diagnosis and prognosis for patients with systemic inflammatory response syndrome. J Clin Microbiol 2014; 52 (11) 4063-4066
    CrossrefPubMedGoogle Scholar
  • 42 Dunne Jr WM. Laboratory diagnosis of sepsis? No SIRS, not just yet. J Clin Microbiol 2015; 53 (08) 2404-2409
    CrossrefPubMedGoogle Scholar
  • 43 Stubljar D, Skvarc M. Effective strategies for diagnosis of systemic inflammatory response syndrome (SIRS) due to bacterial infection in surgical patients. Infect Disord Drug Targets 2015; 15 (01) 53-56
    CrossrefPubMedGoogle Scholar
  • 44 Brown KA, Brain SD, Pearson JD, Edgeworth JD, Lewis SM, Treacher DF. Neutrophils in development of multiple organ failure in sepsis. Lancet 2006; 368 (9530): 157-169
    CrossrefPubMedGoogle Scholar
  • 45 Johnson D, Mayers I. Multiple organ dysfunction syndrome: a narrative review. Can J Anaesth 2001; 48 (05) 502-509
    CrossrefPubMedGoogle Scholar
  • 46 Gando S. Microvascular thrombosis and multiple organ dysfunction syndrome. Crit Care Med 2010; 38 (02) S35-S42
    CrossrefPubMedGoogle Scholar
  • 47 Laster SM, Wood JG, Gooding LR. Tumor necrosis factor can induce both apoptic and necrotic forms of cell lysis. J Immunol 1988; 141 (08) 2629-2634
    PubMedGoogle Scholar
  • 48 Sridharan H, Upton JW. Programmed necrosis in microbial pathogenesis. Trends Microbiol 2014; 22 (04) 199-207
    CrossrefPubMedGoogle Scholar
  • 49 Singer M. The role of mitochondrial dysfunction in sepsis-induced multi-organ failure. Virulence 2014; 5 (01) 66-72
    CrossrefPubMedGoogle Scholar
  • 50 Singer M. Biomarkers in sepsis. Curr Opin Pulm Med 2013; 19 (03) 305-309
    CrossrefPubMedGoogle Scholar
  • 51 Singer M, Deutschman CS, Seymour CW. , et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315 (08) 801-810
    CrossrefPubMedGoogle Scholar
  • 52 Churpek MM, Snyder A, Han X. , et al. qSOFA, SIRS, and early warning scores for detecting clinical deterioration in infected patients outside the ICU. Am J Respir Crit Care Med 2017; 195 (07) 906-911
    CrossrefPubMedGoogle Scholar
  • 53 Vincent JL, Moreno R, Takala J. , et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996; 22 (07) 707-710
    CrossrefPubMedGoogle Scholar
  • 54 Eisele B, Lamy M. Clinical experience with antithrombin III concentrates in critically ill patients with sepsis and multiple organ failure. Semin Thromb Hemost 1998; 24 (01) 71-80
    Article in Thieme ConnectPubMedGoogle Scholar
  • 55 Satran R, Almog Y. The coagulopathy of sepsis: pathophysiology and management. Isr Med Assoc J 2003; 5 (07) 516-520
    PubMedGoogle Scholar
  • 56 Dempfle CE. Coagulopathy of sepsis. Thromb Haemost 2004; 91 (02) 213-224
    Article in Thieme ConnectPubMedGoogle Scholar
  • 57 Kinasewitz GT, Yan SB, Basson B. , et al; PROWESS Sepsis Study Group Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism [ISRCTN74215569]. Crit Care 2004; 8 (02) R82-R90
    CrossrefPubMedGoogle Scholar
  • 58 Iba T, Gando S, Murata A. , et al; Japanese Association for Acute Medicine Disseminated Intravascular Coagulation Study Group. Predicting the severity of systemic inflammatory response syndrome (SIRS)-associated coagulopathy with hemostatic molecular markers and vascular endothelial injury markers. J Trauma 2007; 63 (05) 1093-1098
    CrossrefPubMedGoogle Scholar
  • 59 Ogura H, Gando S, Iba T. , et al; Japanese Association for Acute Medicine Disseminated Intravascular Coagulation Study Group. SIRS-associated coagulopathy and organ dysfunction in critically ill patients with thrombocytopenia. Shock 2007; 28 (04) 411-417
    CrossrefPubMedGoogle Scholar
  • 60 Gando S. Role of fibrinolysis in sepsis. Semin Thromb Hemost 2013; 39 (04) 392-399
    Article in Thieme ConnectPubMedGoogle Scholar
  • 61 Hoppensteadt D, Tsuruta K, Cunanan J. , et al. Thrombin generation mediators and markers in sepsis-associated coagulopathy and their modulation by recombinant thrombomodulin. Clin Appl Thromb Hemost 2014; 20 (02) 129-135
    CrossrefPubMedGoogle Scholar
  • 62 Levi M, Schultz M, van der Poll T. Sepsis and thrombosis. Semin Thromb Hemost 2013; 39 (05) 559-566
    Article in Thieme ConnectPubMedGoogle Scholar
  • 63 Ostrowski SR, Berg RM, Windeløv NA. , et al. Coagulopathy, catecholamines, and biomarkers of endothelial damage in experimental human endotoxemia and in patients with severe sepsis: a prospective study. J Crit Care 2013; 28 (05) 586-596
    CrossrefPubMedGoogle Scholar
  • 64 Saracco P, Vitale P, Scolfaro C, Pollio B, Pagliarino M, Timeus F. The coagulopathy in sepsis: significance and implications for treatment. Pediatr Rep 2011; 3 (04) e30
    CrossrefPubMedGoogle Scholar
  • 65 Semeraro N, Ammollo CT, Semeraro F, Colucci M. Coagulopathy of acute sepsis. Semin Thromb Hemost 2015; 41 (06) 650-658
    Article in Thieme ConnectPubMedGoogle Scholar
  • 66 Simmons J, Pittet JF. The coagulopathy of acute sepsis. Curr Opin Anaesthesiol 2015; 28 (02) 227-236
    CrossrefPubMedGoogle Scholar
  • 67 Muronoi T, Koyama K, Nunomiya S. , et al. Immature platelet fraction predicts coagulopathy-related platelet consumption and mortality in patients with sepsis. Thromb Res 2016; 144: 169-175
    CrossrefPubMedGoogle Scholar
  • 68 Tan L, Huang Y, Pan X. , et al. Administration of bone marrow stromal cells in sepsis attenuates sepsis-related coagulopathy. Ann Med 2016; 48 (04) 235-245
    CrossrefPubMedGoogle Scholar
  • 69 Levi M, van der Poll T. Coagulation and sepsis. Thromb Res 2017; 149: 38-44
    CrossrefPubMedGoogle Scholar
  • 70 Kell DB. Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med Genomics 2009; 2: 2
    CrossrefPubMedGoogle Scholar
  • 71 Kell DB. Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson's, Huntington's, Alzheimer's, prions, bactericides, chemical toxicology and others as examples. Arch Toxicol 2010; 84 (11) 825-889
    CrossrefPubMedGoogle Scholar
  • 72 Kell DB, Pretorius E. Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics 2014; 6 (04) 748-773
    CrossrefPubMedGoogle Scholar
  • 73 Pretorius E, Kell DB. Diagnostic morphology: biophysical indicators for iron-driven inflammatory diseases. Integr Biol 2014; 6 (05) 486-510
    CrossrefPubMedGoogle Scholar
  • 74 Kell DB, Pretorius E. The simultaneous occurrence of both hypercoagulability and hypofibrinolysis in blood and serum during systemic inflammation, and the roles of iron and fibrin(ogen). Integr Biol 2015; 7 (01) 24-52
    CrossrefPubMedGoogle Scholar
  • 75 Potgieter M, Bester J, Kell DB, Pretorius E. The dormant blood microbiome in chronic, inflammatory diseases. FEMS Microbiol Rev 2015; 39 (04) 567-591
    CrossrefPubMedGoogle Scholar
  • 76 Kell DB, Kenny LC. A dormant microbial component in the development of pre-eclampsia. Front Med Obs Gynecol 2016; 3: 60
    PubMedGoogle Scholar
  • 77 Kell DB, Pretorius E. Proteins behaving badly. Substoichiometric molecular control and amplification of the initiation and nature of amyloid fibril formation: lessons from and for blood clotting. Prog Biophys Mol Biol 2017; 123: 16-41
    CrossrefPubMedGoogle Scholar
  • 78 Pretorius E, Akeredolu OO, Soma P, Kell DB. Major involvement of bacterial components in rheumatoid arthritis and its accompanying oxidative stress, systemic inflammation and hypercoagulability. Exp Biol Med (Maywood) 2017; 242 (04) 355-373
    CrossrefPubMedGoogle Scholar
  • 79 Pretorius E, Bester J, Kell DB. A bacterial component to Alzheimer-type dementia seen via a systems biology approach that links iron dysregulation and inflammagen shedding to disease. J Alzheimers Dis 2016; 53 (04) 1237-1256
    CrossrefPubMedGoogle Scholar
  • 80 Pretorius E, Mbotwe S, Bester J, Robinson CJ, Kell DB. Acute induction of anomalous and amyloidogenic blood clotting by molecular amplification of highly substoichiometric levels of bacterial lipopolysaccharide. J R Soc Interface 2016; 13 (122) 20160539
    CrossrefPubMedGoogle Scholar
  • 81 Ebringer A, Rashid T, Wilson C. Rheumatoid arthritis, Proteus, anti-CCP antibodies and Karl Popper. Autoimmun Rev 2010; 9 (04) 216-223
    CrossrefPubMedGoogle Scholar
  • 82 Ebringer A. Rheumatoid Arthritis and Proteus. London: Springer; 2012
    Google Scholar
  • 83 Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984; 1 (8390): 1311-1315
    PubMedGoogle Scholar
  • 84 Itzhaki RF, Lathe R, Balin BJ. , et al. Microbes and Alzheimer's disease. J Alzheimers Dis 2016; 51 (04) 979-984
    CrossrefPubMedGoogle Scholar
  • 85 Weisel JW. Fibrinogen and fibrin. Adv Protein Chem 2005; 70: 247-299
    PubMedGoogle Scholar
  • 86 Cilia La Corte AL, Philippou H, Ariëns RA. Role of fibrin structure in thrombosis and vascular disease. Adv Protein Chem Struct Biol 2011; 83: 75-127
    PubMedGoogle Scholar
  • 87 Undas A, Ariëns RA. Fibrin clot structure and function: a role in the pathophysiology of arterial and venous thromboembolic diseases. Arterioscler Thromb Vasc Biol 2011; 31 (12) e88-e99
    CrossrefPubMedGoogle Scholar
  • 88 Undas A, Nowakowski T, Cieśla-Dul M, Sadowski J. Abnormal plasma fibrin clot characteristics are associated with worse clinical outcome in patients with peripheral arterial disease and thromboangiitis obliterans. Atherosclerosis 2011; 215 (02) 481-486
    CrossrefPubMedGoogle Scholar
  • 89 Wolberg AS. Determinants of fibrin formation, structure, and function. Curr Opin Hematol 2012; 19 (05) 349-356
    CrossrefPubMedGoogle Scholar
  • 90 Undas A. Fibrin clot properties and their modulation in thrombotic disorders. Thromb Haemost 2014; 112 (01) 32-42
    Article in Thieme ConnectPubMedGoogle Scholar
  • 91 Pretorius E, Vermeulen N, Bester J, Lipinski B, Kell DB. A novel method for assessing the role of iron and its functional chelation in fibrin fibril formation: the use of scanning electron microscopy. Toxicol Mech Methods 2013; 23 (05) 352-359
    CrossrefPubMedGoogle Scholar
  • 92 Pretorius E, Bester J, Vermeulen N, Lipinski B, Gericke GS, Kell DB. Profound morphological changes in the erythrocytes and fibrin networks of patients with hemochromatosis or with hyperferritinemia, and their normalization by iron chelators and other agents. PLoS One 2014; 9 (01) e85271
    CrossrefPubMedGoogle Scholar
  • 93 Pretorius E, Bester J, Vermeulen N. , et al. Poorly controlled type 2 diabetes is accompanied by significant morphological and ultrastructural changes in both erythrocytes and in thrombin-generated fibrin: implications for diagnostics. Cardiovasc Diabetol 2015; 14: 30
    CrossrefPubMedGoogle Scholar
  • 94 Pretorius E, Windberger UB, Oberholzer HM, Auer RE. Comparative ultrastructure of fibrin networks of a dog after thrombotic ischaemic stroke. Onderstepoort J Vet Res 2010; 77 (01) E1-E4
    PubMedGoogle Scholar
  • 95 Pretorius E, Swanepoel AC, Oberholzer HM, van der Spuy WJ, Duim W, Wessels PF. A descriptive investigation of the ultrastructure of fibrin networks in thrombo-embolic ischemic stroke. J Thromb Thrombolysis 2011; 31 (04) 507-513
    CrossrefPubMedGoogle Scholar
  • 96 Pretorius E, Steyn H, Engelbrecht M, Swanepoel AC, Oberholzer HM. Differences in fibrin fiber diameters in healthy individuals and thromboembolic ischemic stroke patients. Blood Coagul Fibrinolysis 2011; 22 (08) 696-700
    CrossrefPubMedGoogle Scholar
  • 97 Pretorius E, Oberholzer HM, van der Spuy WJ, Swanepoel AC, Soma P. Qualitative scanning electron microscopy analysis of fibrin networks and platelet abnormalities in diabetes. Blood Coagul Fibrinolysis 2011; 22 (06) 463-467
    CrossrefPubMedGoogle Scholar
  • 98 Bester J, Soma P, Kell DB, Pretorius E. Viscoelastic and ultrastructural characteristics of whole blood and plasma in Alzheimer-type dementia, and the possible role of bacterial lipopolysaccharides (LPS). Oncotarget 2015; 6 (34) 35284-35303
    CrossrefPubMedGoogle Scholar
  • 99 Lipinski B, Pretorius E. Iron-induced fibrin formation may explain vascular pathology in Alzheimer's disease. Folia Neuropathol 2014; 52 (02) 205
    PubMedGoogle Scholar
  • 100 Lipinski B, Pretorius E. Novel pathway of iron‑induced blood coagulation: implications for diabetes mellitus and its complications. Pol Arch Med Wewn 2012; 122 (03) 115-122
    CrossrefPubMedGoogle Scholar
  • 101 Lipinski B, Pretorius E. Iron-induced fibrin in cardiovascular disease. Curr Neurovasc Res 2013; 10 (03) 269-274
    CrossrefPubMedGoogle Scholar
  • 102 Pretorius E, Vermeulen N, Bester J, Lipinski B. Novel use of scanning electron microscopy for detection of iron-induced morphological changes in human blood. Microsc Res Tech 2013; 76 (03) 268-271
    CrossrefPubMedGoogle Scholar
  • 103 Asakura H. Classifying types of disseminated intravascular coagulation: clinical and animal models. J Intensive Care 2014; 2 (01) 20
    CrossrefPubMedGoogle Scholar
  • 104 Duburcq T, Tournoys A, Gnemmi V. , et al. Impact of obesity on endotoxin-induced disseminated intravascular coagulation. Shock 2015; 44 (04) 341-347
    CrossrefPubMedGoogle Scholar
  • 105 Bick RL. Disseminated intravascular coagulation: a review of etiology, pathophysiology, diagnosis, and management: guidelines for care. Clin Appl Thromb Hemost 2002; 8 (01) 1-31
    CrossrefPubMedGoogle Scholar
  • 106 Kaneko T, Wada H. Diagnostic criteria and laboratory tests for disseminated intravascular coagulation. J Clin Exp Hematop 2011; 51 (02) 67-76
    CrossrefPubMedGoogle Scholar
  • 107 Levi M. The coagulant response in sepsis and inflammation. Hamostaseologie 2010; 30 (01) 10-12 , 14–16
    Article in Thieme ConnectPubMedGoogle Scholar
  • 108 Paulus P, Jennewein C, Zacharowski K. Biomarkers of endothelial dysfunction: can they help us deciphering systemic inflammation and sepsis?. Biomarkers 2011; 16 (Suppl. 01) S11-S21
    CrossrefPubMedGoogle Scholar
  • 109 Khemani RG, Bart RD, Alonzo TA, Hatzakis G, Hallam D, Newth CJ. Disseminated intravascular coagulation score is associated with mortality for children with shock. Intensive Care Med 2009; 35 (02) 327-333
    CrossrefPubMedGoogle Scholar
  • 110 Levi M, van der Poll T. Disseminated intravascular coagulation: a review for the internist. Intern Emerg Med 2013; 8 (01) 23-32
    PubMedGoogle Scholar
  • 111 Thachil J, Toh CH. Current concepts in the management of disseminated intravascular coagulation. Thromb Res 2012; 129 (Suppl. 01) S54-S59
    PubMedGoogle Scholar
  • 112 Wada H, Matsumoto T, Yamashita Y, Hatada T. Disseminated intravascular coagulation: testing and diagnosis. Clin Chim Acta 2014; 436: 130-134
    CrossrefPubMedGoogle Scholar
  • 113 Wu LC, Lin X, Sun H. Tanshinone IIA protects rabbits against LPS-induced disseminated intravascular coagulation (DIC). Acta Pharmacol Sin 2012; 33 (10) 1254-1259
    CrossrefPubMedGoogle Scholar
  • 114 Wu Z, Li JN, Bai ZQ, Lin X. Antagonism by salvianolic acid B of lipopolysaccharide-induced disseminated intravascular coagulation in rabbits. Clin Exp Pharmacol Physiol 2014; 41 (07) 502-508
    CrossrefPubMedGoogle Scholar
  • 115 Yu PX, Zhou QJ, Zhu WW. , et al. Effects of quercetin on LPS-induced disseminated intravascular coagulation (DIC) in rabbits. Thromb Res 2013; 131 (06) e270-e273
    CrossrefPubMedGoogle Scholar
  • 116 Nguyen TC, Gushiken F, Correa JI. , et al. A recombinant fragment of von Willebrand factor reduces fibrin-rich microthrombi formation in mice with endotoxemia. Thromb Res 2015; 135 (05) 1025-1030
    CrossrefPubMedGoogle Scholar
  • 117 Zeerleder S, Hack CE, Wuillemin WA. Disseminated intravascular coagulation in sepsis. Chest 2005; 128 (04) 2864-2875
    CrossrefPubMedGoogle Scholar
  • 118 Gando S, Saitoh D, Ogura H. , et al; Japanese Association for Acute Medicine Disseminated Intravascular Coagulation (JAAM DIC) Study Group. Natural history of disseminated intravascular coagulation diagnosed based on the newly established diagnostic criteria for critically ill patients: results of a multicenter, prospective survey. Crit Care Med 2008; 36 (01) 145-150
    CrossrefPubMedGoogle Scholar
  • 119 Semeraro N, Ammollo CT, Semeraro F, Colucci M. Sepsis-associated disseminated intravascular coagulation and thromboembolic disease. Mediterr J Hematol Infect Dis 2010; 2 (03) e2010024
    CrossrefPubMedGoogle Scholar
  • 120 Gando S, Meziani F, Levi M. What's new in the diagnostic criteria of disseminated intravascular coagulation?. Intensive Care Med 2016; 42 (06) 1062-1064
    CrossrefPubMedGoogle Scholar
  • 121 Cunningham FG, Nelson DB. Disseminated intravascular coagulation syndromes in obstetrics. Obstet Gynecol 2015; 126 (05) 999-1011
    CrossrefPubMedGoogle Scholar
  • 122 Anfinsen CB, Haber E, Sela M, White Jr FH. The kinetics of formation of native ribonuclease during oxidation of the reduced polypeptide chain. Proc Natl Acad Sci U S A 1961; 47: 1309-1314
    CrossrefPubMedGoogle Scholar
  • 123 Anfinsen CB. Principles that govern the folding of protein chains. Science 1973; 181 (4096): 223-230
    CrossrefPubMedGoogle Scholar
  • 124 Cohen FE, Prusiner SB. Pathologic conformations of prion proteins. Annu Rev Biochem 1998; 67: 793-819
    CrossrefPubMedGoogle Scholar
  • 125 Harrison PM, Chan HS, Prusiner SB, Cohen FE. Thermodynamics of model prions and its implications for the problem of prion protein folding. J Mol Biol 1999; 286 (02) 593-606
    CrossrefPubMedGoogle Scholar
  • 126 Prusiner SB. Prions. Proc Natl Acad Sci U S A 1998; 95 (23) 13363-13383
    CrossrefPubMedGoogle Scholar
  • 127 Aguzzi A. Prion diseases of humans and farm animals: epidemiology, genetics, and pathogenesis. J Neurochem 2006; 97 (06) 1726-1739
    CrossrefPubMedGoogle Scholar
  • 128 Aguzzi A, Sigurdson C, Heikenwaelder M. Molecular mechanisms of prion pathogenesis. Annu Rev Pathol 2008; 3: 11-40
    CrossrefPubMedGoogle Scholar
  • 129 Aguzzi A, Lakkaraju AK. Cell biology of prions and prionoids: a status report. Trends Cell Biol 2016; 26 (01) 40-51
    CrossrefPubMedGoogle Scholar
  • 130 Colby DW, Prusiner SB. Prions. Cold Spring Harb Perspect Biol 2011; 3 (01) a006833
    PubMedGoogle Scholar
  • 131 Prusiner SB. Biology and genetics of prions causing neurodegeneration. Annu Rev Genet 2013; 47: 601-623
    CrossrefPubMedGoogle Scholar
  • 132 Collinge J, Clarke AR. A general model of prion strains and their pathogenicity. Science 2007; 318 (5852): 930-936
    CrossrefPubMedGoogle Scholar
  • 133 Aguzzi A, Calella AM. Prions: protein aggregation and infectious diseases. Physiol Rev 2009; 89 (04) 1105-1152
    CrossrefPubMedGoogle Scholar
  • 134 Ashe KH, Aguzzi A. Prions, prionoids and pathogenic proteins in Alzheimer disease. Prion 2013; 7 (01) 55-59
    CrossrefPubMedGoogle Scholar
  • 135 Watts JC, Condello C, Stöhr J. , et al. Serial propagation of distinct strains of Aβ prions from Alzheimer's disease patients. Proc Natl Acad Sci U S A 2014; 111 (28) 10323-10328
    CrossrefPubMedGoogle Scholar
  • 136 Woerman AL, Stöhr J, Aoyagi A. , et al. Propagation of prions causing synucleinopathies in cultured cells. Proc Natl Acad Sci U S A 2015; 112 (35) E4949-E4958
    CrossrefPubMedGoogle Scholar
  • 137 Benson MD, Liepnieks J, Uemichi T, Wheeler G, Correa R. Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-chain. Nat Genet 1993; 3 (03) 252-255
    CrossrefPubMedGoogle Scholar
  • 138 Hamidi Asl L, Liepnieks JJ, Uemichi T. , et al. Renal amyloidosis with a frame shift mutation in fibrinogen aalpha-chain gene producing a novel amyloid protein. Blood 1997; 90 (12) 4799-4805
    PubMedGoogle Scholar
  • 139 Serpell LC, Benson M, Liepnieks JJ, Fraser PE. Structural analyses of fibrinogen amyloid fibrils. Amyloid 2007; 14 (03) 199-203
    CrossrefPubMedGoogle Scholar
  • 140 Gillmore JD, Lachmann HJ, Rowczenio D. , et al. Diagnosis, pathogenesis, treatment, and prognosis of hereditary fibrinogen A alpha-chain amyloidosis. J Am Soc Nephrol 2009; 20 (02) 444-451
    CrossrefPubMedGoogle Scholar
  • 141 Picken MM. Fibrinogen amyloidosis: the clot thickens!. Blood 2010; 115 (15) 2985-2986
    CrossrefPubMedGoogle Scholar
  • 142 Stangou AJ, Banner NR, Hendry BM. , et al. Hereditary fibrinogen A alpha-chain amyloidosis: phenotypic characterization of a systemic disease and the role of liver transplantation. Blood 2010; 115 (15) 2998-3007
    CrossrefPubMedGoogle Scholar
  • 143 Haidinger M, Werzowa J, Kain R. , et al. Hereditary amyloidosis caused by R554L fibrinogen Aα-chain mutation in a Spanish family and review of the literature. Amyloid 2013; 20 (02) 72-79
    CrossrefPubMedGoogle Scholar
  • 144 Zhmurov A, Brown AE, Litvinov RI, Dima RI, Weisel JW, Barsegov V. Mechanism of fibrin(ogen) forced unfolding. Structure 2011; 19 (11) 1615-1624
    CrossrefPubMedGoogle Scholar
  • 145 Litvinov RI, Faizullin DA, Zuev YF, Weisel JW. The α-helix to β-sheet transition in stretched and compressed hydrated fibrin clots. Biophys J 2012; 103 (05) 1020-1027
    CrossrefPubMedGoogle Scholar
  • 146 Zhmurov A, Kononova O, Litvinov RI, Dima RI, Barsegov V, Weisel JW. Mechanical transition from α-helical coiled coils to β-sheets in fibrin(ogen). J Am Chem Soc 2012; 134 (50) 20396-20402
    CrossrefPubMedGoogle Scholar
  • 147 Kreplak L, Doucet J, Dumas P, Briki F. New aspects of the alpha-helix to beta-sheet transition in stretched hard alpha-keratin fibers. Biophys J 2004; 87 (01) 640-647
    CrossrefPubMedGoogle Scholar
  • 148 Guthold M, Liu W, Sparks EA. , et al. A comparison of the mechanical and structural properties of fibrin fibers with other protein fibers. Cell Biochem Biophys 2007; 49 (03) 165-181
    CrossrefPubMedGoogle Scholar
  • 149 Liu W, Carlisle CR, Sparks EA, Guthold M. The mechanical properties of single fibrin fibers. J Thromb Haemost 2010; 8 (05) 1030-1036
    PubMedGoogle Scholar
  • 150 Miserez A, Guerette PA. Phase transition-induced elasticity of α-helical bioelastomeric fibres and networks. Chem Soc Rev 2013; 42 (05) 1973-1995
    CrossrefPubMedGoogle Scholar
  • 151 Kell DB, Pretorius E. Substoichiometric molecular control and amplification of the initiation and nature of amyloid fibril formation: lessons from and for blood clotting. bioRxiv preprint. bioRxiv 2016; 054734
    PubMedGoogle Scholar
  • 152 Weisel JW. Structure of fibrin: impact on clot stability. J Thromb Haemost 2007; 5 (Suppl. 01) 116-124
    CrossrefPubMedGoogle Scholar
  • 153 Wolberg AS. Thrombin generation and fibrin clot structure. Blood Rev 2007; 21 (03) 131-142
    CrossrefPubMedGoogle Scholar
  • 154 Biancalana M, Makabe K, Koide A, Koide S. Molecular mechanism of thioflavin-T binding to the surface of beta-rich peptide self-assemblies. J Mol Biol 2009; 385 (04) 1052-1063
    CrossrefPubMedGoogle Scholar
  • 155 Biancalana M, Koide S. Molecular mechanism of Thioflavin-T binding to amyloid fibrils. Biochim Biophys Acta 2010; 1804 (07) 1405-1412
    CrossrefPubMedGoogle Scholar
  • 156 Groenning M. Binding mode of Thioflavin T and other molecular probes in the context of amyloid fibrils-current status. J Chem Biol 2010; 3 (01) 1-18
    CrossrefPubMedGoogle Scholar
  • 157 Kuznetsova IM, Sulatskaya AI, Uversky VN, Turoverov KK. Analyzing thioflavin T binding to amyloid fibrils by an equilibrium microdialysis-based technique. PLoS One 2012; 7 (02) e30724
    CrossrefPubMedGoogle Scholar
  • 158 Kuznetsova IM, Sulatskaya AI, Uversky VN, Turoverov KK. A new trend in the experimental methodology for the analysis of the thioflavin T binding to amyloid fibrils. Mol Neurobiol 2012; 45 (03) 488-498
    CrossrefPubMedGoogle Scholar
  • 159 Kuznetsova IM, Sulatskaya AI, Maskevich AA, Uversky VN, Turoverov KK. High fluorescence anisotropy of thioflavin T in aqueous solution resulting from its molecular rotor nature. Anal Chem 2016; 88 (01) 718-724
    CrossrefPubMedGoogle Scholar
  • 160 Lindberg DJ, Wranne MS, Gilbert Gatty M, Westerlund F, Esbjörner EK. Steady-state and time-resolved Thioflavin-T fluorescence can report on morphological differences in amyloid fibrils formed by Aβ(1-40) and Aβ(1-42). Biochem Biophys Res Commun 2015; 458 (02) 418-423
    CrossrefPubMedGoogle Scholar
  • 161 Sulatskaya AI, Kuznetsova IM, Turoverov KK. Interaction of thioflavin T with amyloid fibrils: fluorescence quantum yield of bound dye. J Phys Chem B 2012; 116 (08) 2538-2544
    CrossrefPubMedGoogle Scholar
  • 162 Younan ND, Viles JH. A comparison of three fluorophores for the detection of amyloid fibers and prefibrillar oligomeric assemblies. ThT (thioflavin T); ANS (1-anilinonaphthalene-8-sulfonic acid); and bisANS (4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonic acid). Biochemistry 2015; 54 (28) 4297-4306
    CrossrefPubMedGoogle Scholar
  • 163 Zhang X, Ran C. Dual functional small molecule probes as fluorophore and ligand for misfolding proteins. Curr Org Chem 2013; 17 (06) 6
    PubMedGoogle Scholar
  • 164 Ahn HJ, Zamolodchikov D, Cortes-Canteli M, Norris EH, Glickman JF, Strickland S. Alzheimer's disease peptide beta-amyloid interacts with fibrinogen and induces its oligomerization. Proc Natl Acad Sci U S A 2010; 107 (50) 21812-21817
    CrossrefPubMedGoogle Scholar
  • 165 Ahn HJ, Glickman JF, Poon KL. , et al. A novel Aβ-fibrinogen interaction inhibitor rescues altered thrombosis and cognitive decline in Alzheimer's disease mice. J Exp Med 2014; 211 (06) 1049-1062
    CrossrefPubMedGoogle Scholar
  • 166 Cortes-Canteli M, Strickland S. Fibrinogen, a possible key player in Alzheimer's disease. J Thromb Haemost 2009; 7 (Suppl. 01) 146-150
    CrossrefPubMedGoogle Scholar
  • 167 Cortes-Canteli M, Zamolodchikov D, Ahn HJ, Strickland S, Norris EH. Fibrinogen and altered hemostasis in Alzheimer's disease. J Alzheimers Dis 2012; 32 (03) 599-608
    CrossrefPubMedGoogle Scholar
  • 168 Cortes-Canteli M, Mattei L, Richards AT, Norris EH, Strickland S. Fibrin deposited in the Alzheimer's disease brain promotes neuronal degeneration. Neurobiol Aging 2015; 36 (02) 608-617
    CrossrefPubMedGoogle Scholar
  • 169 Paul J, Strickland S, Melchor JP. Fibrin deposition accelerates neurovascular damage and neuroinflammation in mouse models of Alzheimer's disease. J Exp Med 2007; 204 (08) 1999-2008
    CrossrefPubMedGoogle Scholar
  • 170 Zamolodchikov D, Strickland S. A possible new role for Aβ in vascular and inflammatory dysfunction in Alzheimer's disease. Thromb Res 2016; 141 (Suppl. 02) S59-S61
    CrossrefPubMedGoogle Scholar
  • 171 Cortes-Canteli M, Paul J, Norris EH. , et al. Fibrinogen and beta-amyloid association alters thrombosis and fibrinolysis: a possible contributing factor to Alzheimer's disease. Neuron 2010; 66 (05) 695-709
    CrossrefPubMedGoogle Scholar
  • 172 Zamolodchikov D, Strickland S. Aβ delays fibrin clot lysis by altering fibrin structure and attenuating plasminogen binding to fibrin. Blood 2012; 119 (14) 3342-3351
    CrossrefPubMedGoogle Scholar
  • 173 Zamolodchikov D, Berk-Rauch HE, Oren DA. , et al. Biochemical and structural analysis of the interaction between β-amyloid and fibrinogen. Blood 2016; 128 (08) 1144-1151
    CrossrefPubMedGoogle Scholar
  • 174 Akassoglou K, Adams RA, Bauer J. , et al. Fibrin depletion decreases inflammation and delays the onset of demyelination in a tumor necrosis factor transgenic mouse model for multiple sclerosis. Proc Natl Acad Sci U S A 2004; 101 (17) 6698-6703
    CrossrefPubMedGoogle Scholar
  • 175 Levi M, van der Poll T, Büller HR. Bidirectional relation between inflammation and coagulation. Circulation 2004; 109 (22) 2698-2704
    CrossrefPubMedGoogle Scholar
  • 176 Flick MJ, LaJeunesse CM, Talmage KE. , et al. Fibrin(ogen) exacerbates inflammatory joint disease through a mechanism linked to the integrin alphaMbeta2 binding motif. J Clin Invest 2007; 117 (11) 3224-3235
    CrossrefPubMedGoogle Scholar
  • 177 Jennewein C, Tran N, Paulus P, Ellinghaus P, Eble JA, Zacharowski K. Novel aspects of fibrin(ogen) fragments during inflammation. Mol Med 2011; 17 (5-6): 568-573
    CrossrefPubMedGoogle Scholar
  • 178 Jennewein C, Paulus P, Zacharowski K. Linking inflammation and coagulation: novel drug targets to treat organ ischemia. Curr Opin Anaesthesiol 2011; 24 (04) 375-380
    CrossrefPubMedGoogle Scholar
  • 179 Schuliga M. The inflammatory actions of coagulant and fibrinolytic proteases in disease. Mediators Inflamm 2015; 2015: 437695
    PubMedGoogle Scholar
  • 180 Cahill CM, Lahiri DK, Huang X, Rogers JT. Amyloid precursor protein and alpha synuclein translation, implications for iron and inflammation in neurodegenerative diseases. Biochim Biophys Acta 2009; 1790 (07) 615-628
    CrossrefPubMedGoogle Scholar
  • 181 Hirohata M, Ono K, Yamada M. Non-steroidal anti-inflammatory drugs as anti-amyloidogenic compounds. Curr Pharm Des 2008; 14 (30) 3280-3294
    CrossrefPubMedGoogle Scholar
  • 182 Minter MR, Taylor JM, Crack PJ. The contribution of neuroinflammation to amyloid toxicity in Alzheimer's disease. J Neurochem 2016; 136 (03) 457-474
    CrossrefPubMedGoogle Scholar
  • 183 Spaulding CN, Dodson KW, Chapman MR, Hultgren SJ. Fueling the fire with fibers: bacterial amyloids promote inflammatory disorders. Cell Host Microbe 2015; 18 (01) 1-2
    CrossrefPubMedGoogle Scholar
  • 184 Lin IH, Miller DS, Bertics PJ, Murphy CJ, de Pablo JJ, Abbott NL. Endotoxin-induced structural transformations in liquid crystalline droplets. Science 2011; 332 (6035): 1297-1300
    CrossrefPubMedGoogle Scholar
  • 185 Miller DS, Abbott NL. Influence of droplet size, pH and ionic strength on endotoxin-triggered ordering transitions in liquid crystalline droplets. Soft Matter 2013; 9 (02) 374-382
    CrossrefPubMedGoogle Scholar
  • 186 Carter MC, Miller DS, Jennings J. , et al. Synthetic mimics of bacterial lipid A trigger optical transitions in liquid crystal microdroplets at ultralow picogram-per-milliliter concentrations. Langmuir 2015; 31 (47) 12850-12855
    CrossrefPubMedGoogle Scholar
  • 187 Singh N, Haldar S, Tripathi AK, McElwee MK, Horback K, Beserra A. Iron in neurodegenerative disorders of protein misfolding: a case of prion disorders and Parkinson's disease. Antioxid Redox Signal 2014; 21 (03) 471-484
    CrossrefPubMedGoogle Scholar
  • 188 Singh N. The role of iron in prion disease and other neurodegenerative diseases. PLoS Pathog 2014; 10 (09) e1004335
    CrossrefPubMedGoogle Scholar
  • 189 Singh N, Asthana A, Baksi S. , et al. The prion-ZIP connection: from cousins to partners in iron uptake. Prion 2015; 9 (06) 420-428
    CrossrefPubMedGoogle Scholar
  • 190 Ahmed M, Davis J, Aucoin D. , et al. Structural conversion of neurotoxic amyloid-beta(1-42) oligomers to fibrils. Nat Struct Mol Biol 2010; 17 (05) 561-567
    CrossrefPubMedGoogle Scholar
  • 191 Hefti F, Goure WF, Jerecic J, Iverson KS, Walicke PA, Krafft GA. The case for soluble Aβ oligomers as a drug target in Alzheimer's disease. Trends Pharmacol Sci 2013; 34 (05) 261-266
    CrossrefPubMedGoogle Scholar
  • 192 Kayed R, Lasagna-Reeves CA. Molecular mechanisms of amyloid oligomers toxicity. J Alzheimers Dis 2013; 33 (Suppl. 01) S67-S78
    PubMedGoogle Scholar
  • 193 Liu B, Moloney A, Meehan S. , et al. Iron promotes the toxicity of amyloid beta peptide by impeding its ordered aggregation. J Biol Chem 2011; 286 (06) 4248-4256
    CrossrefPubMedGoogle Scholar
  • 194 Meyer-Luehmann M, Spires-Jones TL, Prada C. , et al. Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease. Nature 2008; 451 (7179): 720-724
    CrossrefPubMedGoogle Scholar
  • 195 Miranda S, Opazo C, Larrondo LF. , et al. The role of oxidative stress in the toxicity induced by amyloid beta-peptide in Alzheimer's disease. Prog Neurobiol 2000; 62 (06) 633-648
    CrossrefPubMedGoogle Scholar
  • 196 Rival T, Page RM, Chandraratna DS. , et al. Fenton chemistry and oxidative stress mediate the toxicity of the beta-amyloid peptide in a Drosophila model of Alzheimer's disease. Eur J Neurosci 2009; 29 (07) 1335-1347
    CrossrefPubMedGoogle Scholar
  • 197 Sengupta U, Nilson AN, Kayed R. The role of amyloid-β oligomers in toxicity, propagation, and immunotherapy. EBioMedicine 2016; 6: 42-49
    CrossrefPubMedGoogle Scholar
  • 198 Uversky VN. Mysterious oligomerization of the amyloidogenic proteins. FEBS J 2010; 277 (14) 2940-2953
    CrossrefPubMedGoogle Scholar
  • 199 Janson J, Ashley RH, Harrison D, McIntyre S, Butler PC. The mechanism of islet amyloid polypeptide toxicity is membrane disruption by intermediate-sized toxic amyloid particles. Diabetes 1999; 48 (03) 491-498
    CrossrefPubMedGoogle Scholar
  • 200 Bucciantini M, Giannoni E, Chiti F. , et al. Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 2002; 416 (6880): 507-511
    CrossrefPubMedGoogle Scholar
  • 201 Kayed R, Head E, Thompson JL. , et al. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 2003; 300 (5618): 486-489
    CrossrefPubMedGoogle Scholar
  • 202 Baglioni S, Casamenti F, Bucciantini M. , et al. Prefibrillar amyloid aggregates could be generic toxins in higher organisms. J Neurosci 2006; 26 (31) 8160-8167
    CrossrefPubMedGoogle Scholar
  • 203 Glabe CG. Common mechanisms of amyloid oligomer pathogenesis in degenerative disease. Neurobiol Aging 2006; 27 (04) 570-575
    CrossrefPubMedGoogle Scholar
  • 204 Konarkowska B, Aitken JF, Kistler J, Zhang S, Cooper GJ. The aggregation potential of human amylin determines its cytotoxicity towards islet beta-cells. FEBS J 2006; 273 (15) 3614-3624
    CrossrefPubMedGoogle Scholar
  • 205 Meier JJ, Kayed R, Lin CY. , et al. Inhibition of human IAPP fibril formation does not prevent beta-cell death: evidence for distinct actions of oligomers and fibrils of human IAPP. Am J Physiol Endocrinol Metab 2006; 291 (06) E1317-E1324
    CrossrefPubMedGoogle Scholar
  • 206 Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol 2007; 8 (02) 101-112
    CrossrefPubMedGoogle Scholar
  • 207 Xue WF, Hellewell AL, Gosal WS, Homans SW, Hewitt EW, Radford SE. Fibril fragmentation enhances amyloid cytotoxicity. J Biol Chem 2009; 284 (49) 34272-34282
    CrossrefPubMedGoogle Scholar
  • 208 Aitken JF, Loomes KM, Scott DW. , et al. Tetracycline treatment retards the onset and slows the progression of diabetes in human amylin/islet amyloid polypeptide transgenic mice. Diabetes 2010; 59 (01) 161-171
    CrossrefPubMedGoogle Scholar
  • 209 Xue WF, Hellewell AL, Hewitt EW, Radford SE. Fibril fragmentation in amyloid assembly and cytotoxicity: when size matters. Prion 2010; 4 (01) 20-25
    CrossrefPubMedGoogle Scholar
  • 210 Fändrich M. Oligomeric intermediates in amyloid formation: structure determination and mechanisms of toxicity. J Mol Biol 2012; 421 (4-5): 427-440
    CrossrefPubMedGoogle Scholar
  • 211 Göransson AL, Nilsson KPR, Kågedal K, Brorsson AC. Identification of distinct physiochemical properties of toxic prefibrillar species formed by Aβ peptide variants. Biochem Biophys Res Commun 2012; 420 (04) 895-900
    CrossrefPubMedGoogle Scholar
  • 212 Stefani M. Structural features and cytotoxicity of amyloid oligomers: implications in Alzheimer's disease and other diseases with amyloid deposits. Prog Neurobiol 2012; 99 (03) 226-245
    CrossrefPubMedGoogle Scholar
  • 213 Dobson CM. The amyloid phenomenon and its significance. . In: Otzen DE. , ed. Amyloid Fibrils and Prefibrillar Aggregates: Molecular and Biological Properties. Weinheim, Germany: Wiley-VCH; 2013: 1-19
    CrossrefGoogle Scholar
  • 214 Pillay K, Govender P. Amylin uncovered: a review on the polypeptide responsible for type II diabetes. BioMed Res Int 2013; 2013: 826706
    PubMedGoogle Scholar
  • 215 Trikha S, Jeremic AM. Distinct internalization pathways of human amylin monomers and its cytotoxic oligomers in pancreatic cells. PLoS One 2013; 8 (09) e73080
    CrossrefPubMedGoogle Scholar
  • 216 Zhang S, Liu H, Chuang CL. , et al. The pathogenic mechanism of diabetes varies with the degree of overexpression and oligomerization of human amylin in the pancreatic islet β cells. FASEB J 2014; 28 (12) 5083-5096
    CrossrefPubMedGoogle Scholar
  • 217 Holm NK, Jespersen SK, Thomassen LV. , et al. Aggregation and fibrillation of bovine serum albumin. Biochim Biophys Acta 2007; 1774 (09) 1128-1138
    CrossrefPubMedGoogle Scholar
  • 218 Barton CH, Vaziri ND, Gordon S, Tilles S. Renal pathology in end-stage renal disease associated with paraplegia. Paraplegia 1984; 22 (01) 31-41
    CrossrefPubMedGoogle Scholar
  • 219 Jadoul M, Garbar C, Noël H. , et al. Histological prevalence of beta 2-microglobulin amyloidosis in hemodialysis: a prospective post-mortem study. Kidney Int 1997; 51 (06) 1928-1932
    CrossrefPubMedGoogle Scholar
  • 220 Ben-Dov IZ, Pizov G, Ben-Chetrit E, Rubinger D, Or R. Fatal nephrotic syndrome complicating allogeneic stem cell transplantation: a case report. Nephrol Dial Transplant 2009; 24 (09) 2946-2949
    CrossrefPubMedGoogle Scholar
  • 221 Lachmann HJ. Secondary AA amyloidosis. Contemp Hematol 2010; 179-189
    PubMedGoogle Scholar
  • 222 Lucas S. The Autopsy Pathology of Sepsis-Related Death, Severe Sepsis and Septic Shock - Understanding a Serious Killer. In: Fernandez R. , ed. Rijeka: InTech Open; 2012. . Available at: http://www.intechopen.com/books/severe-sepsis-and-septic-shock-understanding-a-serious-killer/theautopsy-pathology-of-sepsis-and-septic-shock. Accessed July 27, 2017
    Google Scholar
  • 223 Díez R, Madero M, Gamba G, Soriano J, Soto V. Renal AA amyloidosis in patients with type 2 diabetes mellitus. Nephron Extra 2014; 4 (02) 119-126
    CrossrefPubMedGoogle Scholar
  • 224 Gross PA. Hypotension and mortality in septic shock: the “golden hour”. Crit Care Med 2006; 34 (06) 1819-1820
    CrossrefPubMedGoogle Scholar
  • 225 Kumar A, Roberts D, Wood KE. , et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34 (06) 1589-1596
    CrossrefPubMedGoogle Scholar
  • 226 Bagshaw SM, Lapinsky S, Dial S. , et al; Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group. Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy. Intensive Care Med 2009; 35 (05) 871-881
    CrossrefPubMedGoogle Scholar
  • 227 Holler JG, Bech CN, Henriksen DP, Mikkelsen S, Pedersen C, Lassen AT. Nontraumatic hypotension and shock in the emergency department and the prehospital setting, prevalence, etiology, and mortality: a systematic review. PLoS One 2015; 10 (03) e0119331
    CrossrefPubMedGoogle Scholar
  • 228 Gamper G, Havel C, Arrich J. , et al. Vasopressors for hypotensive shock. Cochrane Database Syst Rev 2016; 2: CD003709
    PubMedGoogle Scholar
  • 229 Calabrese EJ. Hormesis and medicine. Br J Clin Pharmacol 2008; 66 (05) 594-617
    PubMedGoogle Scholar
  • 230 Cox Jr LA. Hormesis without cell killing. Risk Anal 2009; 29 (03) 393-400
    CrossrefPubMedGoogle Scholar
  • 231 Mattson MP. Hormesis and disease resistance: activation of cellular stress response pathways. Hum Exp Toxicol 2008; 27 (02) 155-162
    CrossrefPubMedGoogle Scholar
  • 232 Wang D, Wei J, Hsu K. , et al. Effects of nitric oxide synthase inhibitors on systemic hypotension, cytokines and inducible nitric oxide synthase expression and lung injury following endotoxin administration in rats. J Biomed Sci 1999; 6 (01) 28-35
    CrossrefPubMedGoogle Scholar
  • 233 Harada N, Okajima K, Isobe H, Uchiba M. Antithrombin reduces endotoxin-induced hypotension by enhancing pulmonary sensory neuron activation in rats. Thromb Haemost 2006; 95 (06) 1011-1018
    Article in Thieme ConnectPubMedGoogle Scholar
  • 234 Cayla C, Todiras M, Iliescu R. , et al. Mice deficient for both kinin receptors are normotensive and protected from endotoxin-induced hypotension. FASEB J 2007; 21 (08) 1689-1698
    CrossrefPubMedGoogle Scholar
  • 235 Uchiba M, Okajima K, Murakami K, Okabe H, Takatsuki K. Attenuation of endotoxin-induced pulmonary vascular injury by antithrombin III. Am J Physiol 1996; 270 (6 Pt 1): L921-L930
    PubMedGoogle Scholar
  • 236 Fourrier F, Jourdain M, Tournoys A. Clinical trial results with antithrombin III in sepsis. Crit Care Med 2000; 28 (09) S38-S43
    CrossrefPubMedGoogle Scholar
  • 237 Hoffmann JN, Vollmar B, Römisch J, Inthorn D, Schildberg FW, Menger MD. Antithrombin effects on endotoxin-induced microcirculatory disorders are mediated mainly by its interaction with microvascular endothelium. Crit Care Med 2002; 30 (01) 218-225
    CrossrefPubMedGoogle Scholar
  • 238 Isobe H, Okajima K, Uchiba M, Harada N, Okabe H. Antithrombin prevents endotoxin-induced hypotension by inhibiting the induction of nitric oxide synthase in rats. Blood 2002; 99 (05) 1638-1645
    CrossrefPubMedGoogle Scholar
  • 239 Iba T, Kidokoro A. High-dose antithrombin therapy for sepsis: mechanisms of action. Shock 2002; 18 (05) 389-394
    CrossrefPubMedGoogle Scholar
  • 240 Ostermann H. Antithrombin III in Sepsis. New evidences and open questions. Minerva Anestesiol 2002; 68 (05) 445-448
    PubMedGoogle Scholar
  • 241 Iba T, Kidokoro A, Fukunaga M. , et al. Antithrombin ameliorates endotoxin-induced organ dysfunction more efficiently when combined with danaparoid sodium than with unfractionated heparin. Intensive Care Med 2005; 31 (08) 1101-1108
    CrossrefPubMedGoogle Scholar
  • 242 Wiedermann CJ. Clinical review: molecular mechanisms underlying the role of antithrombin in sepsis. Crit Care 2006; 10 (01) 209
    CrossrefPubMedGoogle Scholar
  • 243 Komura H, Uchiba M, Mizuochi Y. , et al. Antithrombin inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production by monocytes in vitro through inhibition of Egr-1 expression. J Thromb Haemost 2008; 6 (03) 499-507
    CrossrefPubMedGoogle Scholar
  • 244 Levi M, Schouten M, van der Poll T. Sepsis, coagulation, and antithrombin: old lessons and new insights. Semin Thromb Hemost 2008; 34 (08) 742-746
    Article in Thieme ConnectPubMedGoogle Scholar
  • 245 Iba T, Saitoh D. Efficacy of antithrombin in preclinical and clinical applications for sepsis-associated disseminated intravascular coagulation. J Intensive Care 2014; 2 (01) 66
    CrossrefPubMedGoogle Scholar
  • 246 Tagami T, Matsui H, Horiguchi H, Fushimi K, Yasunaga H. Antithrombin and mortality in severe pneumonia patients with sepsis-associated disseminated intravascular coagulation: an observational nationwide study. J Thromb Haemost 2014; 12 (09) 1470-1479
    CrossrefPubMedGoogle Scholar
  • 247 Iba T, Thachil J. Present and future of anticoagulant therapy using antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation: a perspective from Japan. Int J Hematol 2016; 103 (03) 253-261
    CrossrefPubMedGoogle Scholar
  • 248 Helmerhorst EJ, Maaskant JJ, Appelmelk BJ. Anti-lipid A monoclonal antibody centoxin (HA-1A) binds to a wide variety of hydrophobic ligands. Infect Immun 1998; 66 (02) 870-873
    CrossrefPubMedGoogle Scholar
  • 249 Marks L. The birth pangs of monoclonal antibody therapeutics: the failure and legacy of Centoxin. MAbs 2012; 4 (03) 403-412
    CrossrefPubMedGoogle Scholar
  • 250 Murphy ST, Bellamy MC. The quest for the magic bullet: Centoxin, Drotrecogin Alfa and lessons not learned. Trends Anaesth Crit Care 2013; 3: 316-319
    PubMedGoogle Scholar
  • 251 Martí-Carvajal AJ, Solà I, Gluud C, Lathyris D, Cardona AF. Human recombinant protein C for severe sepsis and septic shock in adult and paediatric patients. Cochrane Database Syst Rev 2012; 12: CD004388
    PubMedGoogle Scholar
  • 252 Lai PS, Matteau A, Iddriss A, Hawes JC, Ranieri V, Thompson BT. An updated meta-analysis to understand the variable efficacy of drotrecogin alfa (activated) in severe sepsis and septic shock. Minerva Anestesiol 2013; 79 (01) 33-43
    PubMedGoogle Scholar
  • 253 Nadel S, Goldstein B, Williams MD. , et al; REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspective (RESOLVE) study group. Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial. Lancet 2007; 369 (9564): 836-843
    CrossrefPubMedGoogle Scholar
  • 254 Minnich DJ, Moldawer LL. Anti-cytokine and anti-inflammatory therapies for the treatment of severe sepsis: progress and pitfalls. Proc Nutr Soc 2004; 63 (03) 437-441
    CrossrefPubMedGoogle Scholar
  • 255 Aziz M, Jacob A, Yang WL, Matsuda A, Wang P. Current trends in inflammatory and immunomodulatory mediators in sepsis. J Leukoc Biol 2013; 93 (03) 329-342
    CrossrefPubMedGoogle Scholar
  • 256 Kell DB. Finding novel pharmaceuticals in the systems biology era using multiple effective drug targets, phenotypic screening and knowledge of transporters: where drug discovery went wrong and how to fix it. FEBS J 2013; 280 (23) 5957-5980
    CrossrefPubMedGoogle Scholar
  • 257 Weinberg ED. Iron withholding: a defense against infection and neoplasia. Physiol Rev 1984; 64 (01) 65-102
    CrossrefPubMedGoogle Scholar
  • 258 Xia Y, Farah N, Maxan A, Zhou J, Lehmann C. Therapeutic iron restriction in sepsis. Med Hypotheses 2016; 89: 37-39
    CrossrefPubMedGoogle Scholar
  • 259 Chapin JC, Hajjar KA. Fibrinolysis and the control of blood coagulation. Blood Rev 2015; 29 (01) 17-24
    CrossrefPubMedGoogle Scholar
  • 260 Cornet AD, Smit EG, Beishuizen A, Groeneveld AB. The role of heparin and allied compounds in the treatment of sepsis. Thromb Haemost 2007; 98 (03) 579-586
    Article in Thieme ConnectPubMedGoogle Scholar
  • 261 Wang C, Chi C, Guo L. , et al. Heparin therapy reduces 28-day mortality in adult severe sepsis patients: a systematic review and meta-analysis. Crit Care 2014; 18 (05) 563
    CrossrefPubMedGoogle Scholar
  • 262 Zarychanski R, Abou-Setta AM, Kanji S. , et al; Canadian Critical Care Trials Group. The efficacy and safety of heparin in patients with sepsis: a systematic review and metaanalysis. Crit Care Med 2015; 43 (03) 511-518
    CrossrefPubMedGoogle Scholar
  • 263 van Roessel S, van der Laan AM, de Pont A-CJM. What is the best heparin to treat sepsis with?. Crit Care Med 2015; 43 (06) e212-e213
    CrossrefPubMedGoogle Scholar
  • 264 Okamoto K, Tamura T, Sawatsubashi Y. Sepsis and disseminated intravascular coagulation. J Intensive Care 2016; 4: 23
    CrossrefPubMedGoogle Scholar
  • 265 Rosenberg VA, Buhimschi IA, Lockwood CJ. , et al. Heparin elevates circulating soluble fms-like tyrosine kinase-1 immunoreactivity in pregnant women receiving anticoagulation therapy. Circulation 2011; 124 (23) 2543-2553
    CrossrefPubMedGoogle Scholar
  • 266 Iba T, Hashiguchi N, Nagaoka I, Tabe Y, Kadota K, Sato K. Heparins attenuated histone-mediated cytotoxicity in vitro and improved the survival in a rat model of histone-induced organ dysfunction. Intensive Care Med Exp 2015; 3 (01) 36
    CrossrefPubMedGoogle Scholar
  • 267 Wiedermann CJ, Kaneider NC. A systematic review of antithrombin concentrate use in patients with disseminated intravascular coagulation of severe sepsis. Blood Coagul Fibrinolysis 2006; 17 (07) 521-526
    CrossrefPubMedGoogle Scholar
  • 268 Iba T, Saitoh D, Gando S, Thachil J. The usefulness of antithrombin activity monitoring during antithrombin supplementation in patients with sepsis-associated disseminated intravascular coagulation. Thromb Res 2015; 135 (05) 897-901
    CrossrefPubMedGoogle Scholar
  • 269 Warren BL, Eid A, Singer P. , et al; KyberSept Trial Study Group. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 2001; 286 (15) 1869-1878
    CrossrefPubMedGoogle Scholar
  • 270 Iba T, Yamada A, Hashiguchi N, Nagaoka I. New therapeutic options for patients with sepsis and disseminated intravascular coagulation. Pol Arch Med Wewn 2014; 124 (06) 321-328
    PubMedGoogle Scholar
  • 271 Yamakawa K, Umemura Y, Hayakawa M. , et al; Japan Septic Disseminated Intravascular Coagulation (J-Septic DIC) study group. Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan. Crit Care 2016; 20 (01) 229
    CrossrefPubMedGoogle Scholar
  • 272 Chien JY, Jerng JS, Yu CJ, Yang PC. Low serum level of high-density lipoprotein cholesterol is a poor prognostic factor for severe sepsis. Crit Care Med 2005; 33 (08) 1688-1693
    CrossrefPubMedGoogle Scholar
  • 273 Levels JHM, Geurts P, Karlsson H. , et al. High-density lipoprotein proteome dynamics in human endotoxemia. Proteome Sci 2011; 9 (01) 34
    CrossrefPubMedGoogle Scholar
  • 274 Catapano AL, Pirillo A, Bonacina F, Norata GD. HDL in innate and adaptive immunity. Cardiovasc Res 2014; 103 (03) 372-383
    CrossrefPubMedGoogle Scholar
  • 275 Bandeali S, Farmer J. High-density lipoprotein and atherosclerosis: the role of antioxidant activity. Curr Atheroscler Rep 2012; 14 (02) 101-107
    CrossrefPubMedGoogle Scholar
  • 276 Tabet F, Rye KA. High-density lipoproteins, inflammation and oxidative stress. Clin Sci (Lond) 2009; 116 (02) 87-98
    CrossrefPubMedGoogle Scholar
  • 277 Guo L, Ai J, Zheng Z. , et al. High density lipoprotein protects against polymicrobe-induced sepsis in mice. J Biol Chem 2013; 288 (25) 17947-17953
    CrossrefPubMedGoogle Scholar
  • 278 Contreras-Duarte S, Varas P, Awad F, Busso D, Rigotti A. Protective role of high density lipoproteins in sepsis: basic issues and clinical implications . [in Spanish]. Rev Chilena Infectol 2014; 31 (01) 34-43
    CrossrefPubMedGoogle Scholar
  • 279 Pirillo A, Catapano AL, Norata GD. HDL in infectious diseases and sepsis. Handb Exp Pharmacol 2015; 224: 483-508
    PubMedGoogle Scholar
  • 280 Almog Y, Shefer A, Novack V. , et al. Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation 2004; 110 (07) 880-885
    CrossrefPubMedGoogle Scholar
  • 281 Dobesh PP, Olsen KM. Statins role in the prevention and treatment of sepsis. Pharmacol Res 2014; 88: 31-40
    CrossrefPubMedGoogle Scholar
  • 282 Harvey M, Cave G. Co-administration of phospholipid emulsion with first dose bacteriocidal antibiotic may retard progression of the sepsis response in gram negative septicaemia. Med Hypotheses 2014; 83 (05) 563-565
    CrossrefPubMedGoogle Scholar
  • 283 Saito H, Maruyama I, Shimazaki S. , et al. Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial. J Thromb Haemost 2007; 5 (01) 31-41
    CrossrefPubMedGoogle Scholar
  • 284 Levi M, Van Der Poll T. Thrombomodulin in sepsis. Minerva Anestesiol 2013; 79 (03) 294-298
    PubMedGoogle Scholar
  • 285 Mimuro J, Takahashi H, Kitajima I. , et al. Impact of recombinant soluble thrombomodulin (thrombomodulin alfa) on disseminated intravascular coagulation. Thromb Res 2013; 131 (05) 436-443
    CrossrefPubMedGoogle Scholar
  • 286 Vincent JL, Ramesh MK, Ernest D. , et al. A randomized, double-blind, placebo-controlled, Phase 2b study to evaluate the safety and efficacy of recombinant human soluble thrombomodulin, ART-123, in patients with sepsis and suspected disseminated intravascular coagulation. Crit Care Med 2013; 41 (09) 2069-2079
    CrossrefPubMedGoogle Scholar
  • 287 Eguchi Y, Gando S, Ishikura H. , et al. Post-marketing surveillance data of thrombomodulin alfa: sub-analysis in patients with sepsis-induced disseminated intravascular coagulation. J Intensive Care 2014; 2 (01) 30
    CrossrefPubMedGoogle Scholar
  • 288 Shirahata A, Mimuro J, Takahashi H. , et al. Recombinant soluble human thrombomodulin (thrombomodulin alfa) in the treatment of neonatal disseminated intravascular coagulation. Eur J Pediatr 2014; 173 (03) 303-311
    CrossrefPubMedGoogle Scholar
  • 289 Yamakawa K, Aihara M, Ogura H, Yuhara H, Hamasaki T, Shimazu T. Recombinant human soluble thrombomodulin in severe sepsis: a systematic review and meta-analysis. J Thromb Haemost 2015; 13 (04) 508-519
    CrossrefPubMedGoogle Scholar
  • 290 Yoshimura J, Yamakawa K, Ogura H. , et al. Benefit profile of recombinant human soluble thrombomodulin in sepsis-induced disseminated intravascular coagulation: a multicenter propensity score analysis. Crit Care 2015; 19: 78
    CrossrefPubMedGoogle Scholar
  • 291 Levi M. Recombinant soluble thrombomodulin: coagulation takes another chance to reduce sepsis mortality. J Thromb Haemost 2015; 13 (04) 505-507
    CrossrefPubMedGoogle Scholar
  • 292 Hayakawa M, Yamakawa K, Saito S. , et al; Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study group. Recombinant human soluble thrombomodulin and mortality in sepsis-induced disseminated intravascular coagulation. A multicentre retrospective study. Thromb Haemost 2016; 115 (06) 1157-1166
    Article in Thieme ConnectPubMedGoogle Scholar
  • 293 Iba T, Gando S, Saitoh D, Wada H, Di Nisio M, Thachil J. Antithrombin supplementation and risk of bleeding in patients with sepsis-associated disseminated intravascular coagulation. Thromb Res 2016; 145: 46-50
    CrossrefPubMedGoogle Scholar
  • 294 Wada H, Thachil J, Di Nisio M, Kurosawa S, Gando S, Toh CH. ; Scientific and Standardization Committee on DIC of the International Society on Thrombosis and Haemostasis. Harmonized guidance for disseminated intravascular coagulation from the International Society on Thrombosis and Haemostasis and the current status of anticoagulant therapy in Japan: a rebuttal. J Thromb Haemost 2013; 11 (11) 2078-2079
    CrossrefPubMedGoogle Scholar
  • 295 Iba T, Thachil J. Is antithrombin III for sepsis-associated disseminated intravascular coagulation really ineffective?. Intensive Care Med 2016; 42 (07) 1193-1194
    CrossrefPubMedGoogle Scholar
  • 296 Dellinger RP, Levy MM, Rhodes A. , et al; Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013; 39 (02) 165-228
    CrossrefPubMedGoogle Scholar
  • 297 Iba T, Gando S, Thachil J. Anticoagulant therapy for sepsis-associated disseminated intravascular coagulation: the view from Japan. J Thromb Haemost 2014; 12 (07) 1010-1019
    CrossrefPubMedGoogle Scholar
  • 298 Oda S, Aibiki M, Ikeda T. , et al; Sepsis Registry Committee of The Japanese Society of Intensive Care Medicine. The Japanese guidelines for the management of sepsis. J Intensive Care 2014; 2 (01) 55
    CrossrefPubMedGoogle Scholar
  • 299 Wada H, Asakura H, Okamoto K. , et al; Japanese Society of Thrombosis Hemostasis/DIC subcommittee. Expert consensus for the treatment of disseminated intravascular coagulation in Japan. Thromb Res 2010; 125 (01) 6-11
    CrossrefPubMedGoogle Scholar
  • 300 Wada H, Okamoto K, Iba T. , et al; Japanese Society of Thrombosis Hemostasis/DIC subcommittee. Addition of recommendations for the use of recombinant human thrombomodulin to the “Expert consensus for the treatment of disseminated intravascular coagulation in Japan”. Thromb Res 2014; 134 (04) 924-925
    CrossrefPubMedGoogle Scholar
  • 301 Krishnan R, Tsubery H, Proschitsky MY. , et al. A bacteriophage capsid protein provides a general amyloid interaction motif (GAIM) that binds and remodels misfolded protein assemblies. J Mol Biol 2014; 426 (13) 2500-2519
    CrossrefPubMedGoogle Scholar
  • 302 Barber M, Tait RC, Scott J, Rumley A, Lowe GD, Stott DJ. Dementia in subjects with atrial fibrillation: hemostatic function and the role of anticoagulation. J Thromb Haemost 2004; 2 (11) 1873-1878
    CrossrefPubMedGoogle Scholar
  • 303 Murthy SB, Jawaid A, Qureshi SU, Schulz PE, Schulz PE. The apolipoprotein 2 allele in Alzheimer's disease: suggestions for a judicious use of antiplatelet and anticoagulant medications. J Am Geriatr Soc 2009; 57 (06) 1124-1125
    CrossrefPubMedGoogle Scholar
  • 304 Nilsson KP, Lindgren M, Hammarström P. A pentameric luminescent-conjugated oligothiophene for optical imaging of in vitro-formed amyloid fibrils and protein aggregates in tissue sections. Methods Mol Biol 2012; 849: 425-434
    PubMedGoogle Scholar
  • 305 Eisenberg D, Jucker M. The amyloid state of proteins in human diseases. Cell 2012; 148 (06) 1188-1203
    CrossrefPubMedGoogle Scholar
  • 306 Tycko R, Wickner RB. Molecular structures of amyloid and prion fibrils: consensus versus controversy. Acc Chem Res 2013; 46 (07) 1487-1496
    CrossrefPubMedGoogle Scholar
  • 307 Langkilde AE, Morris KL, Serpell LC, Svergun DI, Vestergaard B. The architecture of amyloid-like peptide fibrils revealed by X-ray scattering, diffraction and electron microscopy. Acta Crystallogr D Biol Crystallogr 2015; 71 (Pt 4): 882-895
    CrossrefPubMedGoogle Scholar
  • 308 Bembde AS. A study of plasma fibrinogen level in type-2 diabetes mellitus and its relation to glycemic control. Indian J Hematol Blood Transfus 2012; 28 (02) 105-108
    CrossrefPubMedGoogle Scholar