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Background/objectives: A multicentre retrospective study was performed to assess the efficacy/safety of a French purified plasma-derived protein C (PC) concentrate in inherited PC deficiency., Materials and Methods: Nine patients were enrolled, five children aged < 5 weeks, among whom four with a severe deficiency were homozygous, and four patients < 37 years with PC levels ranging 14-25%, including one compound heterozygous., Results: Thirty replacement therapy courses were recorded with mean PC dosages ranging between 24-90 IU/kg/day for prophylactic courses and 51-209 IU/kg/day for treatment courses. Recoveries varied between 0.8 and 1.12% IU/kg in preventive situations and between 1.09 and 1.91% IU/kg for treatment courses; 23 treatment courses were performed in patients aged 1 day to 18 years, 19 out of 23 treatments resulted in complete recovery with no sequelae. Treatment efficacy was difficult to assess in four out of 23 cases because the thrombotic event was not confirmed in one case and due to late treatment initiation in the three other cases. Seven prophylactic treatments were used either in association of vitamin K antagonists or to prevent thrombotic events due to vitamin K antagonist introduction or withdrawal. The safety assessed during 914 infusions was excellent. No abnormal bleeding was reported, including with high doses, during surgery, with heparin therapy., Conclusions: Replacement therapy with this French PC concentrate is safe and effective in patients with inherited PC deficiency.

(1) Severe sepsis is fatal in 30-50% of cases, despite antibiotic therapy and intensive care. (2) The first specific treatment to be marketed in France was HA-IA monoclonal antibodies, in 1991. However, marketing approval was granted precipitously, on the basis of a single, controversial comparative trial, and the product was withdrawn after a second trial gave negative results. (3) Marketing authorization for drotrecogin alfa (recombinant activated protein C) was granted in 2002 for this indication. (4) The product was approved after a single comparative double-blind placebo-controlled trial in 1 690 patients. The protocol was modified during the trial, to exclude patients at high risk of death from causes unrelated to sepsis. The manufacturing process was also changed, making it difficult to interpret the results of this trial. (5) The trial found that drotrecogin alfa reduced mortality (by 6% in absolute values: 25% versus 31%), but also increased the risk of severe haemorrhage, the main adverse effect (3.5% versus 2%). (6) Retrospective subgroup analyses identified patients most likely to benefit from drotrecogin alfa, and also patients who would be needlessly exposed to an additional risk. (7) Drotrecogin alfa is a very expensive drug. (8) In practice, this clinical trial should be considered preliminary. Other, strictly designed and conducted trials are therefore required.