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Septic shock and multiple organ failure after hematopoietic stem cell transplantation: treatment with recombinant human activated protein C

Abstract

Severe sepsis with multiple organ failure after hematopoietic stem cell transplantation (HSCT) results in extremely high morbidity and mortality. Recent studies have highlighted the importance of sepsis-induced activation of the coagulation system in the pathophysiology of severe sepsis. Activated protein C is an important modulator of coagulation and inflammatory derangements during severe sepsis. Low levels of protein C occur in severe sepsis and are predictive of poor outcome. Recombinant human activated protein C (drotrecogin alfa (activated)) was recently approved by the Food and Drug Administration (FDA) for severe sepsis. The phase III trial that resulted in the approval of this agent, however, enrolled a general sepsis population and excluded patients undergoing HSCT. We report a case of fulminant septic shock and multiple organ failure after HSCT that was treated with drotrecogin alfa (activated) in addition to standard therapy, and recovered. The high mortality rates of patients who develop severe sepsis after HSCT demand that new avenues of treatment be considered for this very high-risk patient population. This case illustrates the potential application of a novel therapeutic approach. Clinical trials are warranted to further investigate the safety and efficacy of drotrecogin alfa (activated) in patients with severe sepsis after HSCT.

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References

  1. Armitage JO . Bone marrow transplantation New Engl J Med 1994 330: 827 838

    Article  CAS  Google Scholar 

  2. Horak DA, Forman SJ . Critical care of the hematopoietic stem cell patient Crit Care Clin 2001 17: 671 696

    Article  CAS  Google Scholar 

  3. Bach PB, Schrag D, Nierman DM et al. Identification of poor prognostic features among patients requiring mechanical ventilation after hematopoietic stem cell transplantation Blood 2001 98: 3234 3240

    Article  CAS  Google Scholar 

  4. Huaringa AJ, Leyva FJ, Girald SA et al. Outcome of bone marrow transplantation patients requiring mechanical ventilation Crit Care Med 2000 28: 1014 1017

    Article  CAS  Google Scholar 

  5. Jackson SR, Tweeddale MG, Barnett MJ et al. Admission of bone marrow transplant recipients to the intensive care unit: outcome, survival and prognostic factors Bone Marrow Transplant 1998 21: 697 704

    Article  CAS  Google Scholar 

  6. Bone RC, Grodzin CJ, Balk RA . Sepsis: a new hypothesis for pathogenesis of the disease process Chest 1997 112: 235 243

    Article  CAS  Google Scholar 

  7. Esmon CT . Regulation of blood coagulation Biochim Biophys Acta 2000 1477: 349 360

    Article  CAS  Google Scholar 

  8. Grinell BW, Joyce D . Recombinant human activated protein C: a system modulator of vascular function for treatment of severe sepsis Crit Care Med 2001 29: (Suppl.) S53 S61

    Article  Google Scholar 

  9. Mesters RM, Helterbrand J, Utterback BG et al. Prognostic value of protein C concentrations in neutropenic patients at high risk of severe septic complications Crit Care Med 2000 28: 2209 2216

    Article  CAS  Google Scholar 

  10. Yan SB, Helterbrand J, Hartman DL et al. Low levels of protein C are associated with poor outcome in severe sepsis Chest 2001 120: 915 922

    Article  CAS  Google Scholar 

  11. www.fda.gov

  12. Knaus WA, Draper EA, Wagner DP et al. APACHE II: a severity of disease classification system Crit Care Med 1985 13: 818 829

    Article  CAS  Google Scholar 

  13. Groeger JS, Lemeshow S, Price K et al. Multicenter outcome study of cancer patients admitted to the intensive care unit: a probability of mortality model J Clin Oncol 1998 16: 761 770

    Article  CAS  Google Scholar 

  14. Bernard GR, Ely EW, Wright TJ et al. Safety and dose relationship of recombinant human activated protein C for coagulopathy in severe sepsis Crit Care Med 2001 29: 2051 2059

    Article  CAS  Google Scholar 

  15. Bernard GR, Vincent JL, Laterre PF et al. Efficacy and safety of recombinant human activated protein C for severe sepsis New Engl J Med 2001 344: 699 709

    Article  CAS  Google Scholar 

  16. Haire WD, Ruby EI, Gordon BG et al. Multiple organ dysfunction syndrome in bone marrow transplantation JAMA 1995 274: 1289 1295

    Article  CAS  Google Scholar 

  17. Faioni EM, Krachmalnicoff A, Bearman SI et al. Naturally occurring anticoagulants and bone marrow transplantation: plasma protein C predicts the development of veno-occlusive disease of the liver Blood 1993 81: 3458 3462

    CAS  Google Scholar 

  18. McGuire TR, Bociek GR, Pavletic SZ et al. Organ dysfunction following stem cell transplantation: relationship to plasma cytokine concentrations Bone Marrow Transplant 2001 28: 889 893

    Article  CAS  Google Scholar 

  19. Wheeler AP, Bernard GR . Treating patients with severe sepsis New Engl J Med 1999 340: 207 214

    Article  CAS  Google Scholar 

  20. Kieft H, Hoepelman AIM, Zhou W et al. The sepsis syndrome in a Dutch university hospital: clinical observations Arch Intern Med 1993 153: 2241 2247

    Article  CAS  Google Scholar 

  21. Bernard GR, Wheeler AP, Russell JA et al. Effects of ibuprofen on the physiology and survival of patients with sepsis New Engl J Med 1997 336: 912 918

    Article  CAS  Google Scholar 

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Pastores, S., Papadopoulos, E., van den Brink, M. et al. Septic shock and multiple organ failure after hematopoietic stem cell transplantation: treatment with recombinant human activated protein C. Bone Marrow Transplant 30, 131–134 (2002). https://doi.org/10.1038/sj.bmt.1703618

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