Human protein C concentrate in the treatment of hemolytic uremic syndrome
© BioMed Central Ltd 2007
Published: 26 September 2007
Human protein C (PC) concentrate may anticipate thrombotic microangiopathy and facilitate fibrinolysis in the severe hemolytic uremic syndrome (HUS).
Materials and methods
We report the effects of PC in six HUS patients. HUS is characterized by a simultaneous occurrence of hemolytic anemia, thrombocytopenia and acute renal failure. Post-diarrheal HUS is often based on an infection with enterohemorrhagic Escherichia coli producing Shiga toxins. Our current pathogenetic understanding is that Shiga toxins cause endothelial injury, leading to thrombotic microangiopathy. There is still a 5% rate of mortality particularly caused by cerebral involvement. We treated six children with a severe cerebral manifestation, five of them suffered from a multiple organ dysfunction syndrome (MODS), of HUS with PC over 7–10 days. All patients suffered peritoneal dialysis, one patient a plasmapheresis. In addition to the treatment of the MODS, all of the patients received 100–200 U/day PC.
All of the patients showed signs of disseminated intravascular coagulation. We found typical hypodense lesions in basal ganglia and edema of the brain in computed tomography. During the therapy with PC, MODS was remarkably improved and abnormal D-dimer and plasminogen activator inhibitor 1 levels could be normalized. All of the patients recovered a nearly normal kidney function. Two patients persisted in a severe reduced neurological status. The others showed only slight or no neurological disabilities on discharge. No adverse effects were observed with the PC concentrate administration.
There is no generally accepted therapy regimen to treat HUS in case of neurological involvement. Mortality in HUS accompanied with cerebral microangiopathy is high and difficult to alter. This is the first trial of human PC concentrate administration to anticipate thrombotic microangiopathy in HUS. All of our patients showed rapid clinical improvement under PC administration. Four of six patients were discharged in a healthy condition despite their severe disease. The containment of the severe neurological involvement and the lack of side effects in the treatment with human PC concentrate administration in our patients yield hope that PC treatment may be an effective therapy regimen in the treatment of severe HUS.