Semin Thromb Hemost 2010; 36(4): 367-377
DOI: 10.1055/s-0030-1254046
© Thieme Medical Publishers

Disseminated Intravascular Coagulation in Infectious Disease

Marcel Levi1 , Marcus Schultz2 , Tom van der Poll1 , 3 , 4
  • 1Department of Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  • 2Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  • 3Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  • 4Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Further Information

Publication History

Publication Date:
07 July 2010 (online)

ABSTRACT

Severe infection and inflammation almost invariably lead to hemostatic abnormalities, ranging from insignificant laboratory changes to severe disseminated intravascular coagulation. Systemic inflammation as a result of severe infection leads to activation of coagulation, due to tissue factor–mediated thrombin generation, downregulation of physiological anticoagulant mechanisms, and inhibition of fibrinolysis. Proinflammatory cytokines play a central role in the differential effects on the coagulation and fibrinolysis pathways. Vice versa, activation of the coagulation system may importantly affect inflammatory responses by direct and indirect mechanisms. Apart from the general coagulation response to inflammation associated with severe infection, specific infections may cause distinct features, such as hemorrhagic fever or thrombotic microangiopathy. The relevance of the cross-talk between inflammation and coagulation is underlined by the results of the treatment of severe systemic infection with modulators of coagulation and inflammation.

REFERENCES

  • 1 Levi M. Disseminated intravascular coagulation.  Crit Care Med. 2007;  35(9) 2191-2195
  • 2 Levi M, Ten Cate H. Disseminated intravascular coagulation.  N Engl J Med. 1999;  341(8) 586-592
  • 3 Levi M, van der Poll T. Inflammation and coagulation.  Crit Care Med. 2010;  38(2, suppl) S26-S34
  • 4 Aird W C. Vascular bed-specific hemostasis: role of endothelium in sepsis pathogenesis.  Crit Care Med. 2001;  29(7, suppl) S28-S34, discussion S34–S35
  • 5 Wheeler A P, Bernard G R. Treating patients with severe sepsis.  N Engl J Med. 1999;  340(3) 207-214
  • 6 Levi M, de Jonge E, van der Poll T, ten Cate H. Disseminated intravascular coagulation.  Thromb Haemost. 1999;  82(2) 695-705
  • 7 Anas A, Wiersinga W J, de Vos A F, van der Poll T. Recent insights into the pathogenesis of bacterial sepsis.  Neth J Med. 2010;  68 147-152
  • 8 ten Cate J W, van der Poll T, Levi M, ten Cate H, van Deventer S J. Cytokines: triggers of clinical thrombotic disease.  Thromb Haemost. 1997;  78(1) 415-419
  • 9 Levi M, ten Cate H, van der Poll T. Endothelium: interface between coagulation and inflammation.  Crit Care Med. 2002;  30(5, suppl) S220-S224
  • 10 Vallet B. Microthrombosis in sepsis.  Minerva Anesthesiol. 2001;  67(4) 298-301
  • 11 Levi M, van der Poll T, ten Cate H, van Deventer S J. The cytokine-mediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxaemia.  Eur J Clin Invest. 1997;  27(1) 3-9
  • 12 Ruf W, Edgington T S. Structural biology of tissue factor, the initiator of thrombogenesis in vivo.  FASEB J. 1994;  8(6) 385-390
  • 13 Camerer E, Kolstø A B, Prydz H. Cell biology of tissue factor, the principal initiator of blood coagulation.  Thromb Res. 1996;  81(1) 1-41
  • 14 Banner D W, D'Arcy A, Chène C et al.. The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor.  , [see comments] Nature. 1996;  380(6569) 41-46
  • 15 ten Cate H, Bauer K A, Levi M et al.. The activation of factor X and prothrombin by recombinant factor VIIa in vivo is mediated by tissue factor.  J Clin Invest. 1993;  92(3) 1207-1212
  • 16 Osterud B. Tissue factor expression by monocytes: regulation and pathophysiological roles.  Blood Coagul Fibrinolysis. 1998;  9(suppl 1) S9-S14
  • 17 Giesen P L, Rauch U, Bohrmann B et al.. Blood-borne tissue factor: another view of thrombosis.  Proc Natl Acad Sci U S A. 1999;  96(5) 2311-2315
  • 18 Nieuwland R, Berckmans R J, McGregor S et al.. Cellular origin and procoagulant properties of microparticles in meningococcal sepsis.  Blood. 2000;  95(3) 930-935
  • 19 Koyama T, Nishida K, Ohdama S et al.. Determination of plasma tissue factor antigen and its clinical significance.  Br J Haematol. 1994;  87(2) 343-347
  • 20 Levi M, Schouten M, van der Poll T. Sepsis, coagulation, and antithrombin: old lessons and new insights.  Semin Thromb Hemost. 2008;  34(8) 742-746
  • 21 Mann K G. Biochemistry and physiology of blood coagulation.  Thromb Haemost. 1999;  82(2) 165-174
  • 22 Mesters R M, Mannucci P M, Coppola R, Keller T, Ostermann H, Kienast J. Factor VIIa and antithrombin III activity during severe sepsis and septic shock in neutropenic patients.  , [see comments] Blood. 1996;  88(3) 881-886
  • 23 Jochum M, Lander S, Heimburger N, Fritz H. Effect of human granulocytic elastase on isolated human antithrombin III.  Hoppe Seylers Z Physiol Chem. 1981;  362(2) 103-112
  • 24 Bourin M C, Lindahl U. Glycosaminoglycans and the regulation of blood coagulation.  Biochem J. 1993;  289(Pt 2) 313-330
  • 25 Kobayashi M, Shimada K, Ozawa T. Human recombinant interleukin-1 beta- and tumor necrosis factor alpha-mediated suppression of heparin-like compounds on cultured porcine aortic endothelial cells.  J Cell Physiol. 1990;  144(3) 383-390
  • 26 Kessler C M, Tang Z, Jacobs H M, Szymanski L M. The suprapharmacologic dosing of antithrombin concentrate for Staphylococcus aureus-induced disseminated intravascular coagulation in guinea pigs: substantial reduction in mortality and morbidity.  Blood. 1997;  89(12) 4393-4401
  • 27 Taylor Jr F BJ, Chang A C, Peer G T et al.. DEGR-factor Xa blocks disseminated intravascular coagulation initiated by Escherichia coli without preventing shock or organ damage.  Blood. 1991;  78(2) 364-368
  • 28 Minnema M C, Chang A C, Jansen P M et al.. Recombinant human antithrombin III improves survival and attenuates inflammatory responses in baboons lethally challenged with Escherichia coli .  Blood. 2000;  95(4) 1117-1123
  • 29 Levi M. Activated protein C in sepsis: a critical review.  Curr Opin Hematol. 2008;  15(5) 481-486
  • 30 Esmon C T. The roles of protein C and thrombomodulin in the regulation of blood coagulation.  J Biol Chem. 1989;  264(9) 4743-4746
  • 31 Bouma B N, Meijers J C. Fibrinolysis and the contact system: a role for factor XI in the down-regulation of fibrinolysis.  Thromb Haemost. 1999;  82(2) 243-250
  • 32 Esmon C T, Xu J, Gu J M et al.. Endothelial protein C receptor.  Thromb Haemost. 1999;  82(2) 251-258
  • 33 Hancock W W, Tsuchida A, Hau H, Thomson N M, Salem H H. The anticoagulants protein C and protein S display potent antiinflammatory and immunosuppressive effects relevant to transplant biology and therapy.  Transplant Proc. 1992;  24(5) 2302-2303
  • 34 Taylor Jr F BJ, Dahlback B, Chang A C et al.. Role of free protein S and C4b binding protein in regulating the coagulant response to Escherichia coli .  Blood. 1995;  86(7) 2642-2652
  • 35 Taylor Jr F BJ, Stearns-Kurosawa D J, Kurosawa S et al.. The endothelial cell protein C receptor aids in host defense against Escherichia coli sepsis.  Blood. 2000;  95(5) 1680-1686
  • 36 Taylor Jr F BJ, Chang A, Esmon C T, D'Angelo A, Vigano-D'Angelo S, Blick K E. Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon.  J Clin Invest. 1987;  79(3) 918-925
  • 37 Furlan M, Robles R, Galbusera M et al.. Von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome.  , [see comments] N Engl J Med. 1998;  339(22) 1578-1584
  • 38 Randolph M M, White G L, Kosanke S D et al.. Attenuation of tissue thrombosis and hemorrhage by ala-TFPI does not account for its protection against E. coli—a comparative study of treated and untreated non-surviving baboons challenged with LD100 E. coli. .  Thromb Haemost. 1998;  79(5) 1048-1053
  • 39 de Jonge E, Dekkers P E, Creasey A A et al.. Tissue factor pathway inhibitor dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia.  Blood. 2000;  95(4) 1124-1129
  • 40 Biemond B J, Friederich P W, Koschinsky M L et al.. Apolipoprotein(a) attenuates endogenous fibrinolysis in the rabbit jugular vein thrombosis model in vivo.  Circulation. 1997;  96(5) 1612-1615
  • 41 Schleef R R, Bevilacqua M P, Sawdey M, Gimbrone Jr M AJ, Loskutoff D J. Cytokine activation of vascular endothelium. Effects on tissue-type plasminogen activator and type 1 plasminogen activator inhibitor.  J Biol Chem. 1988;  263(12) 5797-5803
  • 42 Yamamoto K, Loskutoff D J. Fibrin deposition in tissues from endotoxin-treated mice correlates with decreases in the expression of urokinase-type but not tissue-type plasminogen activator.  J Clin Invest. 1996;  97(11) 2440-2451
  • 43 Sawdey M S, Loskutoff D J. Regulation of murine type 1 plasminogen activator inhibitor gene expression in vivo. Tissue specificity and induction by lipopolysaccharide, tumor necrosis factor-alpha, and transforming growth factor-beta.  J Clin Invest. 1991;  88(4) 1346-1353
  • 44 ten Cate H. Pathophysiology of disseminated intravascular coagulation in sepsis.  Crit Care Med. 2000;  28(9, suppl) S9-S11
  • 45 Hermans P W, Hibberd M L, Booy R et al.. 4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease. Meningococcal Research Group.  Lancet. 1999;  354(9178) 556-560
  • 46 Westendorp R G, Hottenga J J, Slagboom P E. Variation in plasminogen-activator-inhibitor-1 gene and risk of meningococcal septic shock.  Lancet. 1999;  354(9178) 561-563
  • 47 Mesters R M, Flörke N, Ostermann H, Kienast J. Increase of plasminogen activator inhibitor levels predicts outcome of leukocytopenic patients with sepsis.  Thromb Haemost. 1996;  75(6) 902-907
  • 48 Altieri D C. Molecular cloning of effector cell protease receptor-1, a novel cell surface receptor for the protease factor Xa.  J Biol Chem. 1994;  269(5) 3139-3142
  • 49 Degen J L. Hemostatic factors and inflammatory disease.  Thromb Haemost. 1999;  82(2) 858-864
  • 50 Johnson K, Choi Y, DeGroot E, Samuels I, Creasey A, Aarden L. Potential mechanisms for a proinflammatory vascular cytokine response to coagulation activation.  J Immunol. 1998;  160(10) 5130-5135
  • 51 Kahn M L, Nakanishi-Matsui M, Shapiro M J, Ishihara H, Coughlin S R. Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin.  J Clin Invest. 1999;  103(6) 879-887
  • 52 Cunningham M A, Romas P, Hutchinson P, Holdsworth S R, Tipping P G. Tissue factor and factor VIIa receptor/ligand interactions induce proinflammatory effects in macrophages.  Blood. 1999;  94(10) 3413-3420
  • 53 de Jonge E, Friederich P W, Vlasuk G P et al.. Activation of coagulation by administration of recombinant factor VIIa elicits interleukin 6 (IL-6) and IL-8 release in healthy human subjects.  Clin Diagn Lab Immunol. 2003;  10(3) 495-497
  • 54 Esmon C T. Does inflammation contribute to thrombotic events?.  Haemostasis. 2000;  30(suppl 2) 34-40
  • 55 Levi M, de Jonge E, van der Poll T. Rationale for restoration of physiological anticoagulant pathways in patients with sepsis and disseminated intravascular coagulation.  Crit Care Med. 2001;  29(7 suppl) S90-S94
  • 56 Bernard G R, Vincent J L, Laterre P F Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group et al. Efficacy and safety of recombinant human activated protein C for severe sepsis.  N Engl J Med. 2001;  344(10) 699-709
  • 57 Levi M, Keller T T, van Gorp E, ten Cate H. Infection and inflammation and the coagulation system.  Cardiovasc Res. 2003;  60(1) 26-39
  • 58 Baglin T. Disseminated intravascular coagulation: diagnosis and treatment.  BMJ. 1996;  312(7032) 683-687
  • 59 Bhamarapravati N. Hemostatic defects in dengue hemorrhagic fever.  Rev Infect Dis. 1989;  11(suppl 4) S826-S829
  • 60 Mohanty D, Ghosh K, Nandwani S K et al.. Fibrinolysis, inhibitors of blood coagulation, and monocyte derived coagulant activity in acute malaria.  Am J Hematol. 1997;  54(1) 23-29
  • 61 Chuttani K, Tischler M D, Pandian N G, Lee R T, Mohanty P K. Diagnosis of cardiac tamponade after cardiac surgery: relative value of clinical, echocardiographic, and hemodynamic signs.  Am Heart J. 1994;  127(4 Pt 1) 913-918
  • 62 Fera G, Semeraro N, De Mitrio V, Schiraldi O. Disseminated intravascular coagulation associated with disseminated cryptococcosis in a patient with acquired immunodeficiency syndrome.  Infection. 1993;  21(3) 171-173
  • 63 Schröder S, Spyridopoulos I, König J, Jaschonek K G, Luft D, Seif F J. Thrombotic thrombocytopenic purpura (TTP) associated with a Borrelia burgdorferi infection.  Am J Hematol. 1995;  50(1) 72-73
  • 64 Gärdlund B. The Heparin Prophylaxis Study Group . Randomised, controlled trial of low-dose heparin for prevention of fatal pulmonary embolism in patients with infectious diseases.  Lancet. 1996;  347(9012) 1357-1361
  • 65 Laing R B, Brettle R P, Leen C L. Venous thrombosis in HIV infection.  , [editorial] Int J STD AIDS. 1996;  7(2) 82-85
  • 66 Hayes E B, Gubler D J. Dengue and dengue hemorrhagic fever.  Pediatr Infect Dis J. 1992;  11(4) 311-317
  • 67 Gear J S, Cassel G A, Gear A J et al.. Outbreak of Marburg virus disease in Johannesburg.  Br Med J. 1975;  4 489-493
  • 68 Limbos M A, Lieberman J M. Disseminated intravascular coagulation associated with rotavirus gastroenteritis: report of two cases.  , [see comments] Clin Infect Dis. 1996;  22(5) 834-836
  • 69 McKay D G, Margaretten W. Disseminated intravascular coagulation in virus diseases.  Arch Intern Med. 1967;  120(2) 129-152
  • 70 Linder M, Müller-Berghaus G, Lasch H G, Gagel C. Virus infection and blood coagulation.  Thromb Diath Haemorrh. 1970;  23(1) 1-11
  • 71 Clemens R, Pramoolsinsap C, Lorenz R, Pukrittayakamee S, Bock H L, White N J. Activation of the coagulation cascade in severe falciparum malaria through the intrinsic pathway.  Br J Haematol. 1994;  87(1) 100-105
  • 72 Badesha P S, Saklayen M G. Hemolytic uremic syndrome as a presenting form of HIV infection.  Nephron. 1996;  72(3) 472-475
  • 73 Laing R W, Teh C, Toh C H. Thrombotic thrombocytopenic purpura (TTP) complicating leptospirosis: a previously undescribed association.  , [letter]. J Clin Pathol. 1990;  43(11) 961-962
  • 74 Ackerman A B, Chongchitnant N, Sanchez J, Guo Y. Inflammatory Diseases. Histologic Diagnosis of Inflammatory Skin Diseases. Baltimore, MD; Williams and Wilkins 1997: 170-186
  • 75 Golden M P, Hammer S M, Wanke C A, Albrecht M A. Cytomegalovirus vasculitis. Case reports and review of the literature.  Medicine (Baltimore). 1994;  73(5) 246-255
  • 76 Booss J, Dann P R, Winkler S R, Griffith B P, Kim J H. Mechanisms of injury to the central nervous system following experimental cytomegalovirus infection.  Am J Otolaryngol. 1990;  11(5) 313-317
  • 77 Libman B S, Quismorio Jr F PJ, Stimmler M M. Polyarteritis nodosa-like vasculitis in human immunodeficiency virus infection.  J Rheumatol. 1995;  22(2) 351-355
  • 78 Calabrese L H. Vasculitis and infection with the human immunodeficiency virus.  , [review]. [53 refs] Rheum Dis Clin North Am. 1991;  17(1) 131-147
  • 79 Carson C W, Conn D L, Czaja A J, Wright T L, Brecher M E. Frequency and significance of antibodies to hepatitis C virus in polyarteritis nodosa.  J Rheumatol. 1993;  20(2) 304-309
  • 80 Leruez-Ville M, Laugé A, Morinet F, Guillevin L, Dény P. Polyarteritis nodosa and parvovirus B19.  Lancet. 1994;  344(8917) 263-264
  • 81 Nikkari S, Mertsola J, Korvenranta H, Vainionpää R, Toivanen P. Wegener's granulomatosis and parvovirus B19 infection.  , [see comments] Arthritis Rheum. 1994;  37(11) 1707-1708
  • 82 Stemerman M B, Colton C, Morell E. Perturbations of the endothelium.  Prog Hemost Thromb. 1984;  7 289-324
  • 83 Kaiser L, Sparks Jr H V. Endothelial cells. Not just a cellophane wrapper.  Arch Intern Med. 1987;  147(3) 569-573
  • 84 Friedman H M. Infection of endothelial cells by common human viruses.  , [see comments] Rev Infect Dis. 1989;  11(suppl 4) S700-S704
  • 85 Wiley C A, Schrier R D, Nelson J A, Lampert P W, Oldstone M B. Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients.  Proc Natl Acad Sci U S A. 1986;  83(18) 7089-7093
  • 86 Butthep P, Bunyaratvej A, Bhamarapravati N. Dengue virus and endothelial cell: a related phenomenon to thrombocytopenia and granulocytopenia in dengue hemorrhagic fever.  Southeast Asian J Trop Med Public Health. 1993;  24(suppl 1) 246-249
  • 87 van Dam-Mieras M C, Muller A D, van Hinsbergh V W, Mullers W J, Bomans P H, Bruggeman C A. The procoagulant response of cytomegalovirus infected endothelial cells.  Thromb Haemost. 1992;  68(3) 364-370
  • 88 McEver R P. GMP-140: a receptor for neutrophils and monocytes on activated platelets and endothelium.  J Cell Biochem. 1991;  45(2) 156-161
  • 89 Anderson R, Wang S, Osiowy C, Issekutz A C. Activation of endothelial cells via antibody-enhanced dengue virus infection of peripheral blood monocytes.  J Virol. 1997;  71(6) 4226-4232
  • 90 Sugerman R W, Church J A, Goldsmith J C, Ens G E. Acquired protein S deficiency in children infected with human immunodeficiency virus.  Pediatr Infect Dis J. 1996;  15(2) 106-111
  • 91 Stahl C P, Wideman C S, Spira T J, Haff E C, Hixon G J, Evatt B L. Protein S deficiency in men with long-term human immunodeficiency virus infection.  Blood. 1993;  81(7) 1801-1807
  • 92 Hassell K L, Kressin D C, Neumann A, Ellison R, Marlar R A. Correlation of antiphospholipid antibodies and protein S deficiency with thrombosis in HIV-infected men.  Blood Coagul Fibrinolysis. 1994;  5(4) 455-462
  • 93 van Gorp E C, Minnema M C, Suharti C et al.. Activation of coagulation factor XI, without detectable contact activation in dengue haemorrhagic fever.  Br J Haematol. 2001;  113(1) 94-99
  • 94 Levin J. Bleeding with infectious disease. In: Ratnoff OD, Forbes CD Disorders of Hemostasis. Orlando, FL; Grune and Stratton 1984: 367-378
  • 95 Nakao S, Lai C J, Young N S. Dengue virus, a flavivirus, propagates in human bone marrow progenitors and hematopoietic cell lines.  , [see comments] Blood. 1989;  74(4) 1235-1240
  • 96 Halstead S B. Antibody, macrophages, dengue virus infection, shock, and hemorrhage: a pathogenetic cascade.  Rev Infect Dis. 1989;  11(suppl 4) S830-839
  • 97 Myllylä G, Vaheri A, Vesikari T, Penttinen K. Interaction between human blood platelets, viruses and antibodies. IV. Post-rubella thrombocytopenic purpura and platelet aggregation by rubella antigen-antibody interaction.  Clin Exp Immunol. 1969;  4(3) 323-332
  • 98 Charkes N D. Purpuric chickenpox: report of a case, review of the literature, and classification by clinical features.  Ann Intern Med. 1961;  54 745-759
  • 99 Chanarin I, Walford D M. Thrombocytopenic purpura in cytomegalovirus mononucleosis.  Lancet. 1973;  2(7823) 238-239
  • 100 Levi M, Toh C H, Thachil J, Watson H G. British Committee for Standards in Haematology . Guidelines for the diagnosis and management of disseminated intravascular coagulation.  Br J Haematol. 2009;  145(1) 24-33
  • 101 Schultz M J. Early recognition of critically ill patients.  Neth J Med. 2009;  67(9) 266-267
  • 102 Tromp M, Bleeker-Rovers C P, van Achterberg T et al.. Internal medicine residents' knowledge about sepsis: effects of a teaching intervention.  Neth J Med. 2009;  67(9) 312-315
  • 103 Warren B L, Eid A, Singer P KyberSept Trial Study Group et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial.  JAMA. 2001;  286(15) 1869-1878
  • 104 Kienast J, Juers M, Wiedermann C J KyberSept investigators et al. Treatment effects of high-dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation.  J Thromb Haemost. 2006;  4(1) 90-97
  • 105 Vincent J L, Angus D C, Artigas A Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Study Group et al. Effects of drotrecogin alfa (activated) on organ dysfunction in the PROWESS trial.  Crit Care Med. 2003;  31(3) 834-840
  • 106 Dhainaut J F, Yan S B, Joyce D E et al.. Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation.  J Thromb Haemost. 2004;  2(11) 1924-1933
  • 107 Abraham E, Laterre P F, Garg R Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) Study Group et al. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death.  N Engl J Med. 2005;  353(13) 1332-1341
  • 108 Dellinger R P, Levy M M, Carlet J M International Surviving Sepsis Campaign Guidelines Committee et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.  Crit Care Med. 2008;  36(1) 296-327
  • 109 Wiedermann C J, Kaneider N C. A meta-analysis of controlled trials of recombinant human activated protein C therapy in patients with sepsis.  BMC Emerg Med. 2005;  5 7
  • 110 Martí-Carvajal A, Salanti G, Cardona A F. Human recombinant activated protein C for severe sepsis.  Cochrane Database Syst Rev. 2007;  (3) CD004388
  • 111 Barie P S. “All in” for a huge pot: the PROWESS-SHOCK trial for refractory septic shock.  Surg Infect (Larchmt). 2007;  8(5) 491-494

Marcel LeviM.D. 

Department Internal Medicine (F-4), Academic Medical Center, University of Amsterdam

Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

Email: m.m.levi@amc.uva.nl

    >