Drotrecogin alfa (activated) for the treatment of meningococcal purpura fulminans

Abstract

interleukin-6) showed a rapid tendency towards normalization. Similarly, the extent of skin necrosis declined markedly, and in three patients full recovery was achieved. One patient lost three toes on both feet, but all other digits recovered fully. No complications that could be attributed to an adverse effect of drotrecogin alfa (activated) were noted. No bleeding events were observed under strict control of the platelet count and a limited dose of heparin. Patients 3 and 4 received 6 platelet concentrates to maintain platelet count above 30×10 3 /µl. There was no need for freshfrozen plasma or red blood cell transfusions. The median ICU stay was 6 days (range 2-9 days) and hospital stay was 18 days (range 14-28 days).The excellent outcome in all cases despite septic shock with purpura fulminans and in two patients platelets counts below 30×10 3 /µl on ICU admission underlines the potential advantage of drotrecogin alfa (activated) for the treatment of severe meningococcal infection. We suggest that a platelet count below 30×10 3 /µl should not be an absolute exclusion criteria for treatment with drotrecogin alfa, provided that they can be kept above this limit during drotrecogin alfa (activated) substitution. References 1. Faust SN, Levin M, Harrison OB, et al (2001) Dysfunction of endothelial protein C activation in severe meningococcal sepsis. N Engl J Med 345:408-416 2. Bernard GR, Vincent JL, Laterre PF, et al (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699-709 3. Wcisel G, Joyce D, Gudmundsdottir A, Shasby DM (2002) Human recombinant activated protein C in meningococcal sepsis. Chest 121:292-295

Activated Protein C for the Treatment of Fulminant Meningococcal Septicaemia

“…This patient required IPPV, CVVH and a total of 23 days in the Intensive Care Unit. Bachli et al 15 report survival in four patients with meningococcal septicaemia treated with activated protein C, with a corresponding improvement in coagulation, inflammatory markers and protein C levels. Two patients required platelet transfusions to maintain a platelet count >30 x 10 9 /l.…”

“…Although the methodology of the PROWESS study has been questioned 13 , activated protein C should be considered early (within 4-12 hours) in certain clinical scenarios-purpura fulminans, toxic shock syndrome, severe community acquired pneumonia, and meningitis with multiple organ dysfunction (P-F Laterre, personal communication). There is increasing evidence to support the use of activated protein C in meningococcal septicaemia 14,15 . Wcisel 14 et al report survival in a 19-year- old female treated with activated protein C, despite a poor prognosis as predicted by protein C level and APACHE II score.…”

Activated Protein C for the Treatment of Fulminant Meningococcal Septicaemia

“…This patient required IPPV, CVVH and a total of 23 days in the Intensive Care Unit. Bachli et al 15 report survival in four patients with meningococcal septicaemia treated with activated protein C, with a corresponding improvement in coagulation, inflammatory markers and protein C levels. Two patients required platelet transfusions to maintain a platelet count >30 x 10 9 /l.…”

“…Although the methodology of the PROWESS study has been questioned 13 , activated protein C should be considered early (within 4-12 hours) in certain clinical scenarios-purpura fulminans, toxic shock syndrome, severe community acquired pneumonia, and meningitis with multiple organ dysfunction (P-F Laterre, personal communication). There is increasing evidence to support the use of activated protein C in meningococcal septicaemia 14,15 . Wcisel 14 et al report survival in a 19-year- old female treated with activated protein C, despite a poor prognosis as predicted by protein C level and APACHE II score.…”

Gonococcal septic shock, acute respiratory distress syndrome, and multisystem organ failure: a case report

“…Although somewhat controversial, 12 its use has been shown to decrease morbidity and mortality in patients with septic shock, including those with meningococcemia and particularly those with purpura fulminans. [13][14][15][16] Neisseria meningitidis and N. gonorrhoeae share multiple virulence factors and presumably common pathophysiology in human infection. Lipooligosaccharide endotoxemia causes the release of inflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor (TNF), and interferon (IFN)-g. [17][18][19] Given this common pathophysiology, APC may also be beneficial in the treatment of gonococcal sepsis, and might have contributed to our patient's favorable outcome.…”

Drotrecogin alfa (activated) in patients with severe sepsis presenting with purpura fulminans, meningitis, or meningococcal disease: a retrospective analysis of patients enrolled in recent clinical studies

“…So far, data on DrotAA use in the management of PF, MEN, or MD have been limited to case reports [22-28]. Four reports noted a positive outcome in 9 of 10 patients and no serious bleeding complications with meningococcal PF [22,24,27,28]. One report documented a subarachnoid hemorrhage and a fatal outcome for a 67-year-old patient with pneumococcal MEN and septicemia [23].…”

Activated Protein C for the Treatment of Fulminant Meningococcal Septicaemia

“…This patient required IPPV, CVVH and a total of 23 days in the Intensive Care Unit. Bachli et al 15 report survival in four patients with meningococcal septicaemia treated with activated protein C, with a corresponding improvement in coagulation, inflammatory markers and protein C levels. Two patients required platelet transfusions to maintain a platelet count >30 x 10 9 /l.…”

“…Although the methodology of the PROWESS study has been questioned 13 , activated protein C should be considered early (within 4-12 hours) in certain clinical scenarios-purpura fulminans, toxic shock syndrome, severe community acquired pneumonia, and meningitis with multiple organ dysfunction (P-F Laterre, personal communication). There is increasing evidence to support the use of activated protein C in meningococcal septicaemia 14,15 . Wcisel 14 et al report survival in a 19-year- old female treated with activated protein C, despite a poor prognosis as predicted by protein C level and APACHE II score.…”

Gonococcal septic shock, acute respiratory distress syndrome, and multisystem organ failure: a case report

“…Although somewhat controversial, 12 its use has been shown to decrease morbidity and mortality in patients with septic shock, including those with meningococcemia and particularly those with purpura fulminans. [13][14][15][16] Neisseria meningitidis and N. gonorrhoeae share multiple virulence factors and presumably common pathophysiology in human infection. Lipooligosaccharide endotoxemia causes the release of inflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor (TNF), and interferon (IFN)-g. [17][18][19] Given this common pathophysiology, APC may also be beneficial in the treatment of gonococcal sepsis, and might have contributed to our patient's favorable outcome.…”

Drotrecogin alfa (activated) in patients with severe sepsis presenting with purpura fulminans, meningitis, or meningococcal disease: a retrospective analysis of patients enrolled in recent clinical studies

“…So far, data on DrotAA use in the management of PF, MEN, or MD have been limited to case reports [22-28]. Four reports noted a positive outcome in 9 of 10 patients and no serious bleeding complications with meningococcal PF [22,24,27,28]. One report documented a subarachnoid hemorrhage and a fatal outcome for a 67-year-old patient with pneumococcal MEN and septicemia [23].…”

Activated Protein C for the Treatment of Fulminant Meningococcal Septicaemia

“…This patient required IPPV, CVVH and a total of 23 days in the Intensive Care Unit. Bachli et al 15 report survival in four patients with meningococcal septicaemia treated with activated protein C, with a corresponding improvement in coagulation, inflammatory markers and protein C levels. Two patients required platelet transfusions to maintain a platelet count >30 x 10 9 /l.…”

“…Although the methodology of the PROWESS study has been questioned 13 , activated protein C should be considered early (within 4-12 hours) in certain clinical scenarios-purpura fulminans, toxic shock syndrome, severe community acquired pneumonia, and meningitis with multiple organ dysfunction (P-F Laterre, personal communication). There is increasing evidence to support the use of activated protein C in meningococcal septicaemia 14,15 . Wcisel 14 et al report survival in a 19-year- old female treated with activated protein C, despite a poor prognosis as predicted by protein C level and APACHE II score.…”

Gonococcal septic shock, acute respiratory distress syndrome, and multisystem organ failure: a case report

“…Although somewhat controversial, 12 its use has been shown to decrease morbidity and mortality in patients with septic shock, including those with meningococcemia and particularly those with purpura fulminans. [13][14][15][16] Neisseria meningitidis and N. gonorrhoeae share multiple virulence factors and presumably common pathophysiology in human infection. Lipooligosaccharide endotoxemia causes the release of inflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor (TNF), and interferon (IFN)-g. [17][18][19] Given this common pathophysiology, APC may also be beneficial in the treatment of gonococcal sepsis, and might have contributed to our patient's favorable outcome.…”

Drotrecogin alfa (activated) in patients with severe sepsis presenting with purpura fulminans, meningitis, or meningococcal disease: a retrospective analysis of patients enrolled in recent clinical studies

“…So far, data on DrotAA use in the management of PF, MEN, or MD have been limited to case reports [22-28]. Four reports noted a positive outcome in 9 of 10 patients and no serious bleeding complications with meningococcal PF [22,24,27,28]. One report documented a subarachnoid hemorrhage and a fatal outcome for a 67-year-old patient with pneumococcal MEN and septicemia [23].…”