Human protein C concentrate in the treatment of hemolytic uremic syndrome

Introduction

Human protein C (PC) concentrate may anticipate thrombotic microangiopathy and facilitate fibrinolysis in the severe hemolytic uremic syndrome (HUS). 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. Postdiarrheal HUS is often based on an infection with EHEC 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.

Methods

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 them received 100–200 U/day PC.

Results

All of the patients showed signs of disseminated intravascular coagulation. We found typical hypodense lesions in basal ganglia and edema of the brain in CT. During the therapy with PC, MODS was remarkable improved and abnormal D-dimer and PAI-1 levels could be normalised. 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.

Conclusion

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.