USE OF PROTEIN-C CONCENTRATE, HEPARIN, AND HEMODIAFILTRATION IN MENINGOCOCCUS-INDUCED PURPURA FULMINANS

Background Inflammatory and coagulation processes are both affected in meningococcaemia. Severe acquired protein-C deficiency in meningococc aemia is usually associated with substantial mortality; in survivors, skin grafts, amputation, and end-organ failure are not uncommon. Prote in C is a natural anticoagulant and also has important anti-inflammato ry activity. We assessed the effects of early replacement therapy with protein-C, concentrate together with continuous veno-venous haemodiaf iltration and conventional treatment in meningococcaemia. Methods 12 p atients aged between 3 months and 27 years with meningococcaemia and s evere acquired protein-C deficiency (mean 0.20 IU/mL) were studied. Ai l patients had septic shock, widespread purpura, skin necrosis, and di sseminated intravascular coagulopathy, After a test dose of protein-C concentrate, patients received a continuous infusion with the dose adj usted daily to keep the plasma concentration between 0.8 and 12 IU/mL, 11 patients were given unfractionated intravenous heparin (10-15 IU k g(-1) h(-1)). Nine patients had haemodiafiltration and one had periton eal dialysis. The Glasgow meningococcal septicaemia prognostic score a nd the paediatric risk of mortality score predicted a minimum mortalit y of 80% and 57%, respectively. Findings No patient died, No adverse r eactions to the treatment were seen. Two patients had lower-limb amput ations, one of whom had a thrombotic cerebrovascular accident; both pa tients had received the protein-C concentrate and heparin later than t he rest of the group (60 h [16.97] vs 12 h [3.13].). One patient devel oped chronic renal failure despite receiving protein-e infusion 15 h a fter admission. Interpretation The acquired severe deficiency of prote in C in meningococcaemia contributes to the pathogenesis of the thromb otic necrotic lesions in the shin and other organs and probably has an important role in the inflammatory response, Protein-C therapy is mer ely one approach to improve the host response in this syndrome, We sug gest that-a double-blind, randomised, controlled multicentre trial is needed to confirm our results.