SummaryFactor VIII or factor IX replacement is frequently impossible in inhibitor-developing hemophiliacs, because of the level of the inhibitor titer. Activated prothrombin complex concentrates are one of the available options to treat the bleeding episodes in such patients. However, the efficacy of these products and the associated thrombogenic risk, particularly in prolonged administration such as employed during surgeries, are important concerns for hemophilia care providers. We performed a multicenter retrospective study to evaluate the use of FEIBA (Factor Eight Bypassing Activity) in France, and data is presented on 433 bleeding episodes, including surgical procedures, concerning 60 patients from 15 hemophilia centers.The efficacy was judged as good or excellent in 352 episodes (81.3%), poor in 73 episodes (16.9%) and non-existent in 8 episodes (1.8%). Minor and major surgical procedures were successfully performed using FEIBA as a second-line therapy after human or porcine factor VIII, and in some occasions FEIBA was utilized as the only substitution product. The tolerance was assessed as good in 428 episodes (98.8%), but in 5 cases adverse effects were reported. Only 3 patients out of 52 regularly evaluated (5.8%) were HIV-seropositive, and for two of them the seroconversion occurred prior to the first use of FEIBA. In contrast, 80.4% of the patients were HCV-seropositive. An anamnestic response after the administration of FEIBA was noted in 31.5% of cases. This study points out the main features of the use of FEIBA in France, and particularly the low HIV seroprevalence in the patients treated. The good efficacy and the excellent tolerance still confer to this product a place to consider in the therapeutic options for the treatment of inhibitor-developing hemophiliacs or in acquired hemophilia.

Although the frequency of the new RHD alleles presented herein is low, their phenotypic and genotypic description adds to the repertoire of reported RHD alleles. These data can be useful for optimization of molecular screening tools.

BackgroundParenteral artesunate is recommended as first-line therapy for severe and complicated malaria. Although its efficacy has been proven, long-term safety profile is still under evaluation. Several cases of delayed haemolytic anaemia occurred after initial clinical improvement and resolution of parasitaemia in non-immune travellers and children living in endemic areas. Reports have generated concern that this phenomenon might be related to the treatment itself, either by direct toxicity or immune-related mechanism. This is a report of the first case of autoimmune haemolytic anaemia following treatment of severe malaria initially managed with parenteral artesunate with strong indication for drug-immune related mechanism.CaseA 17-year old Ivoirian female travelling in France presented with fever, headache and abdominal pain seven days after her arrival. Physical examination was indicative of septic shock while blood analysis showed normal haemoglobin level, but profound thrombocytopaenia and hyperlactataemia. Blood smear analysis showed Plasmodium falciparum infection with a parasitaemia of 0.8%. Severe malaria was diagnosed according to the WHO criteria. The patient was initially managed with artemether/lumefantrine combination and then parenteral artesunate for 48 hours. Empiric antibiotic course was also initiated with ceftriaxone, metronidazole, gentamycin, and then piperacillin and ciprofloxacin. At day 14, haemoglobin dropped to 4.6 g/dL with biologic features indicative of haemolysis (LDH 658 U/L, haptoglobin <0.15 g/L). At that time, parasitaemia was negative and other infections or hereditary disorders were excluded, while Coombs’ direct antiglobulin test was positive for IgG and C3d. Antinuclear antibodies were absent. Further investigations evidenced drug-induced antibodies related to artesunate. It was concluded a drug-mediated autoimmune haemolytic anaemia. A corticosteroids regimen was initiated at 1 mg/kg/day. Outcome was favourable and corticosteroids were progressively tapered during two months. At present the patient’s condition remains stable without recurrence of haemolytic anaemia.ConclusionThis is the first case of delayed haemolytic anaemia related to artesunate with a strong indication for drug-immune related mechanism. Further research is warranted to better characterize this plausible cause of post-treatment haemolysis following parenteral artesunate administration in severe malaria patients.Electronic supplementary materialThe online version of this article (doi:10.1186/1475-2875-13-398) contains supplementary material, which is available to authorized users.