Immunohaemostasis: a new view on haemostasis during sepsis

Immunohaemostasis: a new view on haemostasis during sepsis Host infection by a micro-organism triggers systemic inflammation, innate immunity and complement pathways, but also haemostasis activation. The role of thrombin and fibrin generation in host defence is now recognised, and thrombin has become a partner for survival, while it was seen only as one of the “principal suspects” of multiple organ failure and death during septic shock. This review is first focused on pathophysiology. The role of contact activation system, polyphosphates and neutrophil extracellular traps has emerged, offering new potential therapeutic targets. Interestingly, newly recognised host defence peptides (HDPs), derived from thrombin and other “coagulation” factors, are potent inhibitors of bacterial growth. Inhibition of thrombin generation could promote bacterial growth, while HDPs could become novel therapeutic agents against pathogens when resistance to conventional therapies grows. In a second part, we focused on sepsis-induced coagulopathy diagnostic challenge and stratification from “adaptive” haemostasis to “noxious” disseminated intravascular coagulation (DIC) either thrombotic or haemorrhagic. Besides usual coagulation tests, we discussed cellular haemostasis assessment including neutrophil, platelet and endothelial cell activation. Then, we examined therapeutic opportunities to prevent or to reduce “excess” thrombin generation, while preserving “adaptive” haemostasis. The fail of international randomised trials involving anticoagulants during septic shock may modify the hypothesis considering the end of haemostasis as a target to improve survival. On the one hand, patients at low risk of mortality may not be treated to preserve “immunothrombosis” as a defence when, on the other hand, patients at high risk with patent excess thrombin and fibrin generation could benefit from available (antithrombin, soluble thrombomodulin) or ongoing (FXI and FXII inhibitors) therapies. We propose to better assess coagulation response during infection by an improved knowledge of pathophysiology and systematic testing including determination of DIC scores. This is one of the clues to allocate the right treatment for the right patient at the right moment. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Intensive Care Springer Journals

Immunohaemostasis: a new view on haemostasis during sepsis

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Abstract

Host infection by a micro-organism triggers systemic inflammation, innate immunity and complement pathways, but also haemostasis activation. The role of thrombin and fibrin generation in host defence is now recognised, and thrombin has become a partner for survival, while it was seen only as one of the “principal suspects” of multiple organ failure and death during septic shock. This review is first focused on pathophysiology. The role of contact activation system, polyphosphates and neutrophil extracellular traps has emerged, offering new potential therapeutic targets. Interestingly, newly recognised host defence peptides (HDPs), derived from thrombin and other “coagulation” factors, are potent inhibitors of bacterial growth. Inhibition of thrombin generation could promote bacterial growth, while HDPs could become novel therapeutic agents against pathogens when resistance to conventional therapies grows. In a second part, we focused on sepsis-induced coagulopathy diagnostic challenge and stratification from “adaptive” haemostasis to “noxious” disseminated intravascular coagulation (DIC) either thrombotic or haemorrhagic. Besides usual coagulation tests, we discussed cellular haemostasis assessment including neutrophil, platelet and endothelial cell activation. Then, we examined therapeutic opportunities to prevent or to reduce “excess” thrombin generation, while preserving “adaptive” haemostasis. The fail of international randomised trials involving anticoagulants during septic shock may modify the hypothesis considering the end of haemostasis as a target to improve survival. On the one hand, patients at low risk of mortality may not be treated to preserve “immunothrombosis” as a defence when, on the other hand, patients at high risk with patent excess thrombin and fibrin generation could benefit from available (antithrombin, soluble thrombomodulin) or ongoing (FXI and FXII inhibitors) therapies. We propose to better assess coagulation response during infection by an improved knowledge of pathophysiology and systematic testing including determination of DIC scores. This is one of the clues to allocate the right treatment for the right patient at the right moment.

Journal

Annals of Intensive Care – Springer Journals

Published: Dec 2, 2017

References

  • Directing thrombin
    Lane, DA; Philippou, H; Huntington, JA
  • The contact activation and kallikrein/kinin systems: pathophysiologic and physiologic activities
    Schmaier, AH
  • Contact system revisited: an interface between inflammation, coagulation, and innate immunity
    Long, AT; Kenne, E; Jung, R; Fuchs, TA; Renne, T
  • Assessment of the interplay between blood and skin vascular abnormalities in adult purpura fulminans
    Lerolle, N; Carlotti, A; Melican, K
  • Amplification of bacteria-induced platelet activation is triggered by FcγRIIA, integrin αIIbβ3, and platelet factor 4
    Arman, M; Krauel, K; Tilley, DO
  • Polyphosphate: a link between platelets, coagulation and inflammation
    Morrissey, JH
  • Cellular origin and procoagulant properties of microparticles in meningococcal sepsis
    Nieuwland, R; Berckmans, RJ; McGregor, S
  • Microparticles are new biomarkers of septic shock-induced disseminated intravascular coagulopathy
    Delabranche, X; Boisrame-Helms, J; Asfar, P
  • Extracellular histones are major mediators of death in sepsis
    Xu, J; Zhang, X; Pelayo, R
  • The emerging role of neutrophils in thrombosis-the journey of TF through NETs
    Kambas, K; Mitroulis, I; Ritis, K
  • Why have clinical trials in sepsis failed?
    Marshall, JC
  • Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012
    Dellinger, RP; Levy, MM; Rhodes, A
  • Anticoagulant therapy for sepsis-associated disseminated intravascular coagulation: the view from Japan
    Iba, T; Gando, S; Thachil, J
  • Thrombosis as an intravascular effector of innate immunity
    Engelmann, B; Massberg, S
  • Thrombin contributes to protective immunity in pneumonia-derived sepsis via fibrin polymerization and platelet-neutrophil interactions
    Claushuis, TA; Stoppelaar, SF; Stroo, I
  • Severe sepsis and septic shock
    Angus, DC; Poll, T
  • The coagulation system and its function in early immune defense
    Poll, T; Herwald, H
  • Diagnosis and treatment of disseminated intravascular coagulation (DIC) according to four DIC guidelines
    Wada, H; Matsumoto, T; Yamashita, Y
  • Scientific and Standardization Committee on DIC of the International Society on Thrombosis and Haemostasis (ISTH). Differentiating disseminated intravascular coagulation (DIC) with the fibrinolytic phenotype from coagulopathy of trauma and acute coagulopathy of trauma-shock (COT/ACOTS)
    Gando, S; Wada, H; Thachil, J
  • Local hemostasis, immunothrombosis, and systemic disseminated intravascular coagulation in trauma and traumatic shock
    Gando, S; Otomo, Y
  • Severe sepsis, coagulation, and fibrinolysis: dead end or one way?
    Fourrier, F
  • Endothelial injury in sepsis
    Levi, M; Poll, T
  • New fundamentals in hemostasis
    Versteeg, HH; Heemskerk, JW; Levi, M; Reitsma, PH
  • Sequence determinants of function and evolution in serine proteases
    Krem, MM; Rose, T; Cera, E
  • 450 million years of hemostasis
    Davidson, CJ; Tuddenham, EG; McVey, JH
  • Interactions between coagulation and complement–their role in inflammation
    Oikonomopoulou, K; Ricklin, D; Ward, PA; Lambris, JD
  • Bacteria under stress by complement and coagulation
    Berends, ET; Kuipers, A; Ravesloot, MM; Urbanus, RT; Rooijakkers, SH
  • The partial thromboplastin time: defining an era in coagulation
    White, GC
  • Impact of thrombosis on pulmonary endothelial injury and repair following sepsis
    Evans, CE; Zhao, YY
  • The dual role of the contact system in bacterial infectious disease
    Frick, IM; Bjorck, L; Herwald, H
  • Inorganic polyphosphate in the origin and survival of species
    Brown, MR; Kornberg, A
  • Inorganic polyphosphate: a molecule of many functions
    Kornberg, A; Rao, NN; Ault-Riche, D
  • Polyphosphate exerts differential effects on blood clotting, depending on polymer size
    Smith, SA; Choi, SH; Davis-Harrison, R
  • Sepsis, thrombosis and organ dysfunction
    Semeraro, N; Ammollo, CT; Semeraro, F; Colucci, M
  • Polyphosphate colocalizes with factor XII on platelet-bound fibrin and augments its plasminogen activator activity
    Mitchell, JL; Lionikiene, AS; Georgiev, G
  • Polyphosphate strikes back
    Maas, C
  • Polyphosphate nanoparticles on the platelet surface trigger contact system activation
    Verhoef, JJ; Barendrecht, AD; Nickel, KF
  • Platelet polyphosphate: the long and the short of it
    Weitz, JI; Fredenburgh, JC
  • Polyphosphate delays fibrin polymerisation and alters the mechanical properties of the fibrin network
    Whyte, CS; Chernysh, IN; Domingues, MM
  • Diverse novel functions of neutrophils in immunity, inflammation, and beyond
    Mocsai, A
  • Neutrophil function: from mechanisms to disease
    Amulic, B; Cazalet, C; Hayes, GL; Metzler, KD; Zychlinsky, A
  • Neutrophil activation during septic shock
    Stiel, L; Meziani, F; Helms, J
  • Neutrophil extracellular traps kill bacteria
    Brinkmann, V; Reichard, U; Goosmann, C
  • Novel cell death program leads to neutrophil extracellular traps
    Fuchs, TA; Abed, U; Goosmann, C
  • Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps
    Papayannopoulos, V; Metzler, KD; Hakkim, A; Zychlinsky, A
  • A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus
    Pilsczek, FH; Salina, D; Poon, KK
  • The neutrophil in vascular inflammation
    Phillipson, M; Kubes, P
  • In vitro activation of coagulation by human neutrophil DNA and histone proteins but not neutrophil extracellular traps
    Noubouossie, DF; Whelihan, MF; Yu, YB
  • Human CRP defends against the toxicity of circulating histones
    Abrams, ST; Zhang, N; Dart, C
  • The streptococcal M protein: a highly versatile molecule
    Smeesters, PR; McMillan, DJ; Sriprakash, KS
  • Staphylococcus aureus secretes coagulase and von Willebrand factor binding protein to modify the coagulation cascade and establish host infections
    McAdow, M; Missiakas, DM; Schneewind, O
  • Multiple ligands of von Willebrand factor-binding protein (vWbp) promote Staphylococcus aureus clot formation in human plasma
    Thomer, L; Schneewind, O; Missiakas, D
  • Fibronectin-binding proteins of Staphylococcus aureus mediate activation of human platelets via fibrinogen and fibronectin bridges to integrin GPIIb/IIIa and IgG binding to the FcγRIIa receptor
    Fitzgerald, JR; Loughman, A; Keane, F
  • Induction of vascular leakage through release of bradykinin and a novel kinin by cysteine proteinases from Staphylococcus aureus
    Imamura, T; Tanase, S; Szmyd, G; Kozik, A; Travis, J; Potempa, J
  • Streptococcal surface proteins activate the contact system and control its antibacterial activity
    Wollein Waldetoft, K; Svensson, L; Morgelin, M
  • Degradation of circulating von Willebrand factor and its regulator ADAMTS13 implicates secreted Bacillus anthracis metalloproteases in anthrax consumptive coagulopathy
    Chung, MC; Popova, TG; Jorgensen, SC
  • Spatial localization of bacteria controls coagulation of human blood by ‘quorum acting’
    Kastrup, CJ; Boedicker, JQ; Pomerantsev, AP
  • Reduced thrombin generation increases host susceptibility to group A streptococcal infection
    Sun, H; Wang, X; Degen, JL; Ginsburg, D
  • Fibrinogen-binding proteins of Gram-positive bacteria
    Rivera, J; Vannakambadi, G; Hook, M; Speziale, P
  • Fibrin and fibrinolysis in infection and host defense
    Degen, JL; Bugge, TH; Goguen, JD
  • Borrelia burgdorferi infection-associated surface proteins ErpP, ErpA, and ErpC bind human plasminogen
    Brissette, CA; Haupt, K; Barthel, D
  • Haemophilus influenzae uses the surface protein E to acquire human plasminogen and to evade innate immunity
    Barthel, D; Singh, B; Riesbeck, K; Zipfel, PF
  • alpha-enolase, a novel strong plasmin(ogen) binding protein on the surface of pathogenic streptococci
    Pancholi, V; Fischetti, VA
  • Alpha-enolase of Streptococcus pneumoniae is a plasmin(ogen)-binding protein displayed on the bacterial cell surface
    Bergmann, S; Rohde, M; Chhatwal, GS; Hammerschmidt, S
  • Bacillus anthracis interacts with plasmin(ogen) to evade C3b-dependent innate immunity
    Chung, MC; Tonry, JH; Narayanan, A
  • Borrelia burgdorferi enolase is a surface-exposed plasminogen binding protein
    Floden, AM; Watt, JA; Brissette, CA
  • Molecular basis of group A streptococcal virulence
    Bisno, AL; Brito, MO; Collins, CM
  • Pathogen activators of plasminogen
    Verhamme, IM; Panizzi, PR; Bock, PE
  • Skizzle is a novel plasminogen- and plasmin-binding protein from Streptococcus agalactiae that targets proteins of human fibrinolysis to promote plasmin generation
    Wiles, KG; Panizzi, P; Kroh, HK; Bock, PE
  • Structural features, physiological roles, and biotechnological applications of the membrane proteases of the OmpT bacterial endopeptidase family: a micro-review
    Stathopoulos, C
  • Invited review: breaking barriers—attack on innate immune defences by omptin surface proteases of enterobacterial pathogens
    Haiko, J; Suomalainen, M; Ojala, T; Lahteenmaki, K; Korhonen, TK
  • Fibrinolytic and coagulative activities of Yersinia pestis
    Korhonen, TK; Haiko, J; Laakkonen, L; Jarvinen, HM; Westerlund-Wikstrom, B
  • Fibrinolytic and procoagulant activities of Yersinia pestis and Salmonella enterica
    Korhonen, TK
  • Common mutation of plasminogen detected in three Asian populations by an amplification refractory mutation system and rapid automated capillary electrophoresis
    Ooe, A; Kida, M; Yamazaki, T
  • OmpT outer membrane proteases of enterohemorrhagic and enteropathogenic Escherichia coli contribute differently to the degradation of human LL-37
    Thomassin, JL; Brannon, JR; Gibbs, BF; Gruenheid, S; Moual, H
  • Activation of TAFI on the surface of Streptococcus pyogenes evokes inflammatory reactions by modulating the kallikrein/kinin system
    Bengtson, SH; Sanden, C; Morgelin, M
  • Thrombin-activatable fibrinolysis inhibitor influences disease severity in humans and mice with pneumococcal meningitis
    Mook-Kanamori, BB; Valls Seron, M; Geldhoff, M
  • Streptococcal inhibitor of complement-mediated lysis (SIC): an anti-inflammatory virulence determinant
    Akesson, P; Herwald, H; Rasmussen, M
  • Antibacterial activity of the contact and complement systems is blocked by SIC, a protein secreted by Streptococcus pyogenes
    Frick, IM; Shannon, O; Akesson, P
  • Staphylococcal superantigen-like protein 10 (SSL10) inhibits blood coagulation by binding to prothrombin and factor Xa via their gamma-carboxyglutamic acid (Gla) domain
    Itoh, S; Yokoyama, R; Kamoshida, G
  • Peptide antimicrobials: cell wall as a bacterial target
    Yount, NY; Yeaman, MR
  • Emerging themes and therapeutic prospects for anti-infective peptides
    Yount, NY; Yeaman, MR
  • The C-terminal sequence of several human serine proteases encodes host defense functions
    Kasetty, G; Papareddy, P; Kalle, M
  • Proteolysis of human thrombin generates novel host defense peptides
    Papareddy, P; Rydengard, V; Pasupuleti, M
  • Host defense peptides of thrombin modulate inflammation and coagulation in endotoxin-mediated shock and Pseudomonas aeruginosa sepsis
    Kalle, M; Papareddy, P; Kasetty, G
  • Proteolytic activation transforms heparin cofactor II into a host defense molecule
    Kalle, M; Papareddy, P; Kasetty, G
  • A peptide of heparin cofactor II inhibits endotoxin-mediated shock and invasive Pseudomonas aeruginosa infection
    Kalle, M; Papareddy, P; Kasetty, G
  • Antimicrobial effects of helix D-derived peptides of human antithrombin III
    Papareddy, P; Kalle, M; Bhongir, RK; Morgelin, M; Malmsten, M; Schmidtchen, A
  • Protein C inhibitor–a novel antimicrobial agent
    Malmstrom, E; Morgelin, M; Malmsten, M
  • Protein C inhibitor (PCI) binds to phosphatidylserine exposing cells with implications in the phagocytosis of apoptotic cells and activated platelets
    Rieger, D; Assinger, A; Einfinger, K; Sokolikova, B; Geiger, M
  • Disseminated intravascular coagulation. Findings in 346 patients
    Spero, JA; Lewis, JH; Hasiba, U
  • The Yin-Yang of thrombin and activated protein C
    Dutt, T; Toh, CH
  • Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines
    Wada, H; Thachil, J; Nisio, M
  • Ischemic Limb Gangrene with Pulses
    Warkentin, TE
  • Ischemic limb gangrene with pulses [Correspondance]
    Lipsker, D
  • The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis
    Shapiro, NI; Schuetz, P; Yano, K
  • Severe secondary deficiency of von Willebrand factor-cleaving protease (ADAMTS13) in patients with sepsis-induced disseminated intravascular coagulation: its correlation with development of renal failure
    Ono, T; Mimuro, J; Madoiwa, S
  • Syndromes of thrombotic microangiopathy
    George, JN; Nester, CM
  • Bleeding and coagulopathies in critical care
    Hunt, BJ
  • Shock, acute disseminated intravascular coagulation, and microvascular thrombosis: is ‘shock liver’ the unrecognized provocateur of ischemic limb necrosis?
    Warkentin, TE; Pai, M
  • Microparticles and infectious diseases
    Delabranche, X; Berger, A; Boisrame-Helms, J; Meziani, F
  • Bench-to-bedside review: circulating microparticles—a new player in sepsis?
    Meziani, F; Delabranche, X; Asfar, P; Toti, F
  • Role of microparticles in sepsis
    Reid, VL; Webster, NR
  • Plasma levels of soluble E-selectin in patients with disseminated intravascular coagulation
    Okajima, K; Uchiba, M; Murakami, K; Okabe, H; Takatsuki, K
  • Combination of thrombin-antithrombin complex, plasminogen activator inhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study
    Koyama, K; Madoiwa, S; Nunomiya, S
  • Endothelial endoglin is involved in inflammation: role in leukocyte adhesion and transmigration
    Rossi, E; Sanz-Rodriguez, F; Eleno, N
  • Endoglin regulates mural cell adhesion in the circulatory system
    Rossi, E; Smadja, DM; Boscolo, E
  • Is inflammation the cause of pre-eclampsia?
    Ramma, W; Ahmed, A
  • Early detection of disseminated intravascular coagulation during septic shock: a multicentre prospective study
    Delabranche, X; Quenot, JP; Lavigne, T
  • Early rise in circulating endothelial protein C receptor correlates with poor outcome in severe sepsis
    Guitton, C; Gerard, N; Sebille, V
  • Activated protein C induces the release of microparticle-associated endothelial protein C receptor
    Perez-Casal, M; Downey, C; Fukudome, K; Marx, G; Toh, CH
  • The clinical and functional relevance of microparticles induced by activated protein C treatment in sepsis
    Perez-Casal, M; Thompson, V; Downey, C
  • Tissue factor expression in blood cells
    Osterud, B
  • Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction
    Stakos, DA; Kambas, K; Konstantinidis, T
  • Extracellular DNA and histones: double-edged swords in immunothrombosis
    Gould, TJ; Lysov, Z; Liaw, PC
  • Evidence of netosis in septic shock-induced disseminated intravascular coagulation
    Delabranche, X; Stiel, L; Severac, F
  • Neutrophil fluorescence: a new indicator of cell activation during septic shock-induced disseminated intravascular coagulation
    Stiel, L; Delabranche, X; Galoisy, AC
  • Schistocytes in disseminated intravascular coagulation
    Lesesve, JF; Martin, M; Banasiak, C
  • Fibrin detected in plasma of patients with disseminated intravascular coagulation by fibrin-specific antibodies consists primarily of high molecular weight factor XIIIa-crosslinked and plasmin-modified complexes partially containing fibrinopeptide A
    Pfitzner, SA; Dempfle, CE; Matsuda, M; Heene, DL
  • Diagnosis and prognosis of overt disseminated intravascular coagulation in a general hospital—meaning of the ISTH score system, fibrin monomers, and lipoprotein-C-reactive protein complex formation
    Cauchie, P; Cauchie, C; Boudjeltia, KZ
  • Formation of fibrin monomers in experimental disseminated intravascular coagulation and its inhibition by recombinant hirudin
    Dickneite, G; Czech, J; Keuper, H
  • ISTH overt disseminated intravascular coagulation score in patients with septic shock: automated immunoturbidimetric soluble fibrin assay vs. D-dimer assay
    Gris, JC; Faillie, JL; Cochery-Nouvellon, E; Lissalde-Lavigne, G; Lefrant, JY
  • Fibrin-related markers in patients with septic shock: individual comparison of D-dimers and fibrin monomers impacts on prognosis
    Gris, JC; Bouvier, S; Cochery-Nouvellon, E; Faillie, JL; Lissalde-Lavigne, G; Lefrant, JY
  • Measurement of plasma fibrin D-dimer levels with the use of a monoclonal antibody coupled to latex beads
    Greenberg, CS; Devine, DV; McCrae, KM
  • Plasma D-dimer levels and their relationship to serum fibrinogen/fibrin degradation products in hypercoagulable states
    Wilde, JT; Kitchen, S; Kinsey, S; Greaves, M; Preston, FE
  • Diagnosis of disseminated intravascular coagulation. Role of D-dimer
    Carr, JM; McKinney, M; McDonagh, J
  • Assessment of hypercoagulable states by measurement of activation fragments and peptides
    Boisclair, MD; Ireland, H; Lane, DA
  • A comparative evaluation of assays for markers of activated coagulation and/or fibrinolysis: thrombin-antithrombin complex, D-dimer and fibrinogen/fibrin fragment E antigen
    Boisclair, MD; Lane, DA; Wilde, JT; Ireland, H; Preston, FE; Ofosu, FA
  • Coagulation inhibitor substitution during sepsis
    Fourrier, F; Jourdain, M; Tournois, A; Caron, C; Goudemand, J; Chopin, C
  • Septic shock, multiple organ failure, and disseminated intravascular coagulation. Compared patterns of antithrombin III, protein C, and protein S deficiencies
    Fourrier, F; Chopin, C; Goudemand, J
  • Serial changes in neutrophil-endothelial activation markers during the course of sepsis associated with disseminated intravascular coagulation
    Gando, S; Kameue, T; Matsuda, N; Hayakawa, M; Hoshino, H; Kato, H
  • The place of viscoelastic testing in clinical practice
    Hans, GA; Besser, MW
  • Viscoelastic and aggregometric point-of-care testing in patients with septic shock—cross-links between inflammation and haemostasis
    Brenner, T; Schmidt, K; Delang, M
  • Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial
    Abraham, E; Reinhart, K; Opal, S
  • Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial
    Warren, BL; Eid, A; Singer, P
  • Drotrecogin alfa (activated) in adults with septic shock
    Ranieri, VM; Thompson, BT; Barie, PS
  • Should all patients with sepsis receive anticoagulation? Yes
    Meziani, F; Vincent, JL; Gando, S
  • Should all septic patients be given systemic anticoagulation? No
    Poll, T; Opal, SM
  • Factor XII: a drug target for safe interference with thrombosis and inflammation
    Kenne, E; Renne, T
  • Inhibition of Factor XI activity as a promising antithrombotic strategy
    Chen, Z; Seiffert, D; Hawes, B
  • New agents for thromboprotection. A role for factor XII and XIIa inhibition
    Labberton, L; Kenne, E; Renne, T
  • C1-inhibitor in patients with severe sepsis and septic shock: beneficial effect on renal dysfunction
    Caliezi, C; Zeerleder, S; Redondo, M
  • Administration of C1 inhibitor reduces neutrophil activation in patients with sepsis
    Zeerleder, S; Caliezi, C; Mierlo, G
  • C1-esterase inhibitor infusion increases survival rates for patients with sepsis
    Igonin, AA; Protsenko, DN; Galstyan, GM
  • The role of bradykinin and the effect of the bradykinin receptor antagonist icatibant in porcine sepsis
    Barratt-Due, A; Johansen, HT; Sokolov, A
  • The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. In vivo use of a monoclonal anti-factor XII antibody to block contact activation in baboons
    Pixley, RA; Cadena, R; Page, JD
  • The factor XIIa blocking antibody 3F7: a safe anticoagulant with anti-inflammatory activities
    Worm, M; Kohler, EC; Panda, R
  • Inhibition of factor XI activation attenuates inflammation and coagulopathy while improving the survival of mouse polymicrobial sepsis
    Tucker, EI; Verbout, NG; Leung, PY
  • Coagulation factor XI improves host defence during murine pneumonia-derived sepsis independent of factor XII activation
    Stroo, I; Zeerleder, S; Ding, C
  • Simultaneous targeting of CD14 and factor XIa by a fusion protein consisting of an anti-CD14 antibody and the modified second domain of bikunin improves survival in rabbit sepsis models
    Nakamura, M; Takeuchi, T; Kawahara, T
  • Is thrombocytopenia an early prognostic marker in septic shock?
    Thiery-Antier, N; Binquet, C; Vinault, S
  • Thrombocytopenia in critically ill patients with severe sepsis/septic shock: prognostic value and association with a distinct serum cytokine profile
    Tsirigotis, P; Chondropoulos, S; Frantzeskaki, F
  • Septic shock from community-onset pneumonia: is there a role for aspirin plus macrolides combination?
    Falcone, M; Russo, A; Farcomeni, A
  • Lower mortality rate in elderly patients with community-onset pneumonia on treatment with aspirin
    Falcone, M; Russo, A; Cangemi, R
  • Outcomes of severe sepsis and septic shock patients on chronic antiplatelet treatment: a historical cohort study
    Valerio-Rojas, JC; Jaffer, IJ; Kor, DJ; Gajic, O; Cartin-Ceba, R
  • Inhibition of polyphosphate as a novel strategy for preventing thrombosis and inflammation
    Smith, SA; Choi, SH; Collins, JN; Travers, RJ; Cooley, BC; Morrissey, JH
  • Nontoxic polyphosphate inhibitors reduce thrombosis while sparing hemostasis
    Travers, RJ; Shenoi, RA; Kalathottukaren, MT; Kizhakkedathu, JN; Morrissey, JH
  • Alkaline phosphatase treatment improves renal function in severe sepsis or septic shock patients
    Heemskerk, S; Masereeuw, R; Moesker, O
  • Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial
    Pickkers, P; Heemskerk, S; Schouten, J
  • Beneficial effects of alkaline phosphatase in septic shock
    Su, F; Brands, R; Wang, Z
  • Human recombinant alkaline phosphatase inhibits ex vivo platelet activation in humans
    Tunjungputri, RN; Peters, E; Ven, A; Groot, PG; Mast, Q; Pickkers, P
  • Anti-inflammatory effects of dabrafenib on polyphosphate-mediated vascular disruption
    Lee, S; Ku, SK; Bae, JS
  • Neutrophil extracellular traps promote deep vein thrombosis in mice
    Brill, A; Fuchs, TA; Savchenko, AS
  • Delayed but not early treatment with DNase reduces organ damage and improves outcome in a murine model of sepsis
    Mai, SH; Khan, M; Dwivedi, DJ
  • Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice
    McDonald, B; Davis, RP; Kim, SJ
  • Exogenous deoxyribonuclease has a protective effect in a mouse model of sepsis
    Laukova, L; Konecna, B; Babickova, J
  • Interferon lambda1/IL-29 and inorganic polyphosphate are novel regulators of neutrophil-driven thromboinflammation
    Chrysanthopoulou, A; Kambas, K; Stakos, D

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