Download PDF
Thromb Haemost 1996; 76(06): 0932-0938
DOI: 10.1055/s-0038-1650688
Original Article
Schattauer GmbH Stuttgart

Age-related Differences in Outcome and Severity of DIC in Children with Septic Shock and Purpura

Jan A Hazelzet
1   The Department of Pediatrics, Division of Pediatric Intensive Care, The Netherland
,
Inge M Risseeuw-Appe
2   Division of Pediatric Hematology and Oncology, The Netherland
,
René F Kornelisse
3   Division of Pediatric Infectious Diseases and Immunology, Sophia Children’s Hospital/University Hospital Rotterdam, The Netherland
,
Wim C J Hop
4   Department of Biostatistics and Epidemiology, Erasmus University, Rotterdam, The Netherland
,
Ina Dekker
2   Division of Pediatric Hematology and Oncology, The Netherland
,
Koen F M Joosten
1   The Department of Pediatrics, Division of Pediatric Intensive Care, The Netherland
,
Ronald de Groot
3   Division of Pediatric Infectious Diseases and Immunology, Sophia Children’s Hospital/University Hospital Rotterdam, The Netherland
,
C Erik Hack
5   Central Laboratory of the Netherlands Red Cross Blood Transfusion Services and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Amsterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 26 April 1996

Accepted after resubmission 05 September 1996

Publication Date:
11 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

We studied the influence of age on mortality and severity of clotting abnormalities in 79 children (median age: 3.1 years) with meningococcal sepsis. Parameters of coagulation and fibrinolysis and plasma levels of cytokines were prospectively measured on admission. The mortality rate was 27%. The age of survivors was significantly different from that of non-survivors (p = 0.013). With the exception of FVII, vWF and t-PA, parameters of coagulation and fibrinolysis, as well as plasma cytokine levels were related to outcome. Patients were divided in two groups: younger and older than median age. The mortality in children ≤3.1 years was 40% versus 13% in children >3.1 years (p = 0.006). In contrast to cytokine levels, which were not different between the two age groups, fibrinogen, prothrombin, factors V, VII, VIII, vWF, protein C, antithrombin, FDP, and the ratio PAI-l/t-PA were related to age, indicating a more severe coagulopathy in children ≤ 3.1 years despite a similar degree of inflammatory response. A relative deficiency of coagulation factors due to an immature state of the clotting system, as well as an inadequate fibrinolytic response, both related to age may have caused this more severe coagulative response in younger children, and may have contributed to the higher mortality rate.

 

  • References

  • 1 Blick RL. Disseminated intravascular coagulation. Hematology/Oncology Clinics of North America 1992; 6: 1259-1285
    CrossrefPubMedSearch in Google Scholar
  • 2 Hesselvik JF, Blombäck M, Brodin B, Mailer R. Coagulation, fibrinolysis, and kallikrein systems in sepsis: relation to outcome. Crit Care Med 1989; 17: 724-733
    CrossrefPubMedSearch in Google Scholar
  • 3 Levi M, Cate Hten, Poll TVan der, Deventer SJHvan. Pathogenesis of disseminated intravascular coagulation in sepsis. JAMA 1993; 270: 975-979
    CrossrefPubMedSearch in Google Scholar
  • 4 Suffredini AF, Harpel PC, Parrillo JE. Promotion and subsequent inhibition of plasminogen activation after administration of intravenous endotoxin to normal subjects. N Engl J Med 1989; 320: 1165-1172
    CrossrefPubMedSearch in Google Scholar
  • 5 Thijs LG, Boer JP de, Groot MCMde, Hack CE. Coagulation disorders in septic shock. Intens Care Med 1993; 19: S8-S15
    CrossrefPubMedSearch in Google Scholar
  • 6 Esmon NL, D’Angelo A, Vigano-D’Angelo S, Esmon CT, Comp PC. Analysis of protein C and protein S in disease states. Dev Biol Stand 1987; 67: 75-82
    PubMedSearch in Google Scholar
  • 7 Esmon CT. The roles of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem 1989; 264: 4743-4746
    PubMedSearch in Google Scholar
  • 8 Fourrier F, Lestavel P, Chopin C, Marey A, Goudemand J, Rime A, Mangalaboyi J. Meningococcemia and purpura fulminans in adults: acute deficiencies of proteins C and S and early treatment with antithrombin III concentrates. Intens Care Med 1990; 16: 121-124
    CrossrefPubMedSearch in Google Scholar
  • 9 Fourrier F, Chopin C, Goudemand J, Hendrycx S, Caron C, Rime A, Marey A, Lestavel P. Septic shock, multiple organ failure, and disseminated intravascular coagulation. Compared patterns of antithrombin III, protein C, and protein S deficiencies. Chest 1992; 101: 816-823
    CrossrefPubMedSearch in Google Scholar
  • 10 Powars DR, Rogers ZR, Patch MJ, McGehee WG, Francis RB. Purpura fulminans in meningococcemia: association with acquired deficiencies of protein C and S. N Engl J Med 1987; 317: 571-572
    CrossrefPubMedSearch in Google Scholar
  • 11 Brandtzaeg P, Sandset PM, Joo GB, Ovstebo R, Abildgaard U, Kierulf P. The quantitative association of plasma endotoxin, antithrombin, protein C, extrinsic pathway inhibitor and fibrinopeptide A in systemic meningococcal disease. Thromb Res 1989; 55: 459-470
    CrossrefPubMedSearch in Google Scholar
  • 12 Sheth SB, Carvalho AC. Protein S and C alterations in acutely ill patients. Am J Hematol 1991; 36: 14-19
    CrossrefPubMedSearch in Google Scholar
  • 13 Hesselvik JF, Malm J, Dahlbäck B, Blombäck M. Protein C, protein S and C4b-binding protein in severe infection and septic shock. Thromb Haemost 1991; 65: 126-129
    Thieme ConnectPubMedSearch in Google Scholar
  • 14 Leclerc F, Hazelzet JA, Jude B, Hofhuis W, Hue V, Martinot A, Voort Evan der. Protein C and S deficiency in severe infectious purpura of children: a collaborative study of 40 cases. Intens Care Med 1992; 18: 202-205
    CrossrefPubMedSearch in Google Scholar
  • 15 Gerson WT, Dickerman JD, Bovill EG, Golden E. Severe acquired protein C deficiency in purpura fulminans associated with disseminated intravascular coagulation: treatment with protein C concentrate. Pediatrics 1993; 91: 418-422
    PubMedSearch in Google Scholar
  • 16 Powars D, Larsen R, Johnson J, Hulbert T, Sun T, Patch MJ, Francis R, Chan L. Epidemic meningococcemia and purpura fulminans with induced protein C deficiency. Clin Infect Dis 1993; 17: 254-261
    CrossrefPubMedSearch in Google Scholar
  • 17 Fijnvandraat K, Derkx B, Peters M, Bijlmer R, Sturk A, Prins MH, Deventer SJH van, Cate JWten. Coagulation activation and tissue necrosis in meningococcal septic shock: severely reduced protein C levels predict a high mortality. Thromb Haemost 1995; 73: 15-20
    Thieme ConnectPubMedSearch in Google Scholar
  • 18 Pollack MM, Ruttimann UE, Getson PR. Pediatric risk of mortality (PRISM) score. Crit Care Med 1988; 16: 1110-1116
    CrossrefPubMedSearch in Google Scholar
  • 19 Sternberg JC. A rate nephelometer for measuring specific proteins by immunoprecipitation reaction. Clin Chem 1977; 23: 1456-1464
    PubMedSearch in Google Scholar
  • 20 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 17: 237-246
    CrossrefPubMedSearch in Google Scholar
  • 21 Boer JPde, Abbink J, Brouwer M, Meijer C, Roem D, Voom G, Lambers J, Mourik Jvan, Hack CE. PAI-1 synthesis in the human hepatoma cell line Hep G2 is increased by cytokines. Evidence that the liver contributes to acute phase behaviour of PAI-1. Thromb Haemost 1991; 65: 181-185
    Thieme ConnectPubMedSearch in Google Scholar
  • 22 Boermeester MA, Leeuwen PAM, Coyle SM, Wolbink GJ, Hack CE, Lowry SF. IL-1 blockade attenuates mediator release and dysregulation of the hemostatic mechanism during human sepsis. Arch Surg 1995; 130: 739-748
    CrossrefPubMedSearch in Google Scholar
  • 23 Marlar RA, Endres-Brooks J, Miller C. Serial studies of protein C and its plasma inhibitor in patients with disseminated intravascular coagulation. Blood 1985; 66: 59-63
    PubMedSearch in Google Scholar
  • 24 Taylor FB, Chang A, Esmon CT, D’Angelo A, Vigano-D’Angelo S, Blick KE. Protein C prevens the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. J Clin Invest 1987; 79: 918-925
    CrossrefPubMedSearch in Google Scholar
  • 25 Clouse LH, Comp PC. The regulation of hemostasis: the protein C system. N Engl J Med 1986; 314: 1298-1304
    CrossrefPubMedSearch in Google Scholar
  • 26 Boer JPde, Creasy AA, Chang AK, Roem D, Brouwer MC, Eerenberg AJM, Hack CE, Taylor FB. Activation patterns of coagulation and fibrinolysis in baboons following infusion with lethal or sublethal dose of Escherichia coli. Circ Shock 1993; 39: 59-67
    PubMedSearch in Google Scholar
  • 27 Philippe J, Offner F, Declerck PJ, Leroux-Roels G, Vogelaers D, Baele G, Collen D. Fibrinolysis and coagulation in patients with infectious disease and sepsis. Thromb Haemost 1991; 65: 291-295
    Thieme ConnectPubMedSearch in Google Scholar
  • 28 Voss R, Matthias FR, Borkowski G, Reitz D. Activation and inhibition of fibrinolysis in septic patients in an internal intensive care unit. Br J Haematol 1990; 75: 99-105
    CrossrefPubMedSearch in Google Scholar
  • 29 Brandtzaeg P, Joo GB, Brusletto B, Kierulf P. Plasminogen activator inhibitor 1 and 2, alpha-2-antiplasmin, plasminogen, and endotoxin levels in systemic meningococcal disease. Thromb Res 1990; 57: 271-278
    CrossrefPubMedSearch in Google Scholar
  • 30 Engebretsen LF, Kierulf P, Brandtzaeg P. Extreme plasminogen activator inhibitor and endotoxin values in patients with meningococcal disease. Thromb Res 1986; 42: 713-716
    CrossrefPubMedSearch in Google Scholar
  • 31 Pralong G, Calandra T, Glauser MP, Schellekens J, Verhoef J, Bachmann F, Kruithof EK. Plasminogen activator inhibitor 1: a new prognostic marker in septic shock. Thromb Haemost 1989; 61: 459-462
    Thieme ConnectPubMedSearch in Google Scholar
  • 32 Poll Tvan der, Levi M, Büller HR, Deventer SJHvan, Boer JPde, Hack CE, Cate JWten. Fibrinolytic response to tumor necrosis factor in healthy subjects. J Exp Med 1991; 174: 729-732
    CrossrefPubMedSearch in Google Scholar
  • 33 Komelisse RF, Hazelzet JA, Savelkoul HFJ, Hop WCJ, Suur MH, Borsboom ANJ, Risseeuw-Appel IM, Voort Evan der, Groot Rde. The relationship between plasminogen activator inhibitor-1 and proinflamma-tory and counterinflammatory mediators in children with meningococcal septic shock. J Infect Dis 1996; 173: 1148-1156
    CrossrefPubMedSearch in Google Scholar
  • 34 Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, Powers P. Development of the human coagulation system in the full-term infant. Blood 1987; 70: 165-172
    CrossrefPubMedSearch in Google Scholar
  • 35 Nardi M, Karpatkin M. Prothrombin and protein C in early childhood: normal adult levels are not achieved until the fourth year of life. J Pediatr 1986; 109: 843-845
    CrossrefPubMedSearch in Google Scholar
  • 36 Pixley R, Cadena RDL, Page J, Kaufman N, Wyshock E, Chang A, Taylor F, Colman R. The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. J Clin Invest 1993; 91: 61-68
    CrossrefPubMedSearch in Google Scholar
  • 37 Carr C, Bild GS, Chang ACK, Peer GT, Palmier MO, Frazier RB, Gustafson ME, Wun T-C, Creasy AA, Hinshaw LB, Taylor FB, Galluppi GR. Recombinant E. coli-derived tissue factor pathway inhibitor reduces coagulopathic and lethal effects in the baboon gram negative model of septic shock. Circ Shock 1995; 44: 126-137
    PubMedSearch in Google Scholar