Use of protein-C concentrate, heparin, and haemodiafiltration in meningococcus-induced purpura fulminans

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Abstract

Background. Inflammatory and coagulation processes are both affected in meningococcaemia. Severe acquired protein-C deficiency in meningococcaemia is usually associated with substantial mortality; in survivors, skin grafts, amputation, and end-organ failure are not uncommon. Protein C is a natural anticoagulant and also has important anti-inflammatory activity. We assessed the effects of early replacement therapy with protein-C concentrate together with continuous veno-venous haemodiafiltration and conventional treatment in meningococcaemia. Methods. 12 patients aged between 3 months and 27 years with meningococcaemia and severe acquired protein-C deficiency (mean 0.20 IU/mL) were studied. All patients had septic shock, widespread purpura, skin necrosis, and disseminated intravascular coagulopathy. After a test dose of protein-C concentrate, patients received a continuous infusion with the dose adjusted daily to keep the plasma concentration between 0.8 and 1.2 IU/mL. 11 patients were given unfractionated intravenous heparin (10-15 IU kg-1 h-1). Nine patients had haemodiafiltration and one had peritoneal dialysis. The Glasgow meningococcal septicaemia prognostic score and the paediatric risk of mortality score predicted a minimum mortality of 80% and 57%, respectively. Findings. No patient died. No adverse reactions to the treatment were seen, Two patients had lower-limb amputations, one of whom had a thrombotic cerebrovascular accident; both patients had received the protein-C concentrate and heparin later than the rest of the group (60 h [16.97] vs 12 h [3.13]). One patient developed chronic renal failure despite receiving protein-C infusion 15 h after admission. Interpretation. The acquired severe deficiency of protein C in meningococcaemia contributes to the pathogenesis of the thrombotic necrotic lesions in the shin and other organs and probably has an important role in the inflammatory response. Protein-C therapy is merely one approach to improve the host response in this syndrome. We suggest that a double-blind, randomised, controlled multicentre trial is needed to confirm our results.

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Smith, O. P., White, B., Vaughan, D., Rafferty, M., Claffey, L., Lyons, B., & Casey, W. (1997). Use of protein-C concentrate, heparin, and haemodiafiltration in meningococcus-induced purpura fulminans. Lancet, 350(9091), 1590–1593. https://doi.org/10.1016/S0140-6736(97)06356-3

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