Delayed haemolysis after parenteral artesunate therapy eP582 for severe malaria in a returning Canadian traveler Marthe Charles, Jeffrey Patterson, Leyla Asadi, Stan Houston* University of Alberta, Edmonton, Alberta, Canada. Correspondin Author: [email protected]

Background Laboratory results Discussion/Conclusion

Severe malaria is uncommon in Canada, with an average of 14 Since 2010, the World Health Organization (WHO) has cases per year, all imported. Multiple mechanisms contribute to malarial anemia aside from the direct effect on parasitized red cells, recommended the use of artemesinin derivatives as the including shortened lifespan in the non-infected red cells due to first-line treatment for severe malaria. Despite the low immune and other mechanisms, enhanced splenic activity and bone prevalence of severe malaria in Canada, parenteral marrow suppression. It seems likely that previous cases of artesunate is available across the country through the artesunate’-related hemolysis may have not have been recognized Canadian Malaria Network (CMN) in collaboration with because they were attributed to these established mechanisms of Health Canada's Special Access Program. Recently, reports Figure 1: Evolution of hemoglobin and timing of blood Figure 2: Evolution of hematocrit post days of anemia, one or more of which may be present in most cases of transfusion and unit of blood received. admission. have been published from Europe and Asia of delayed malaria. In our patient, hemoglobin recovery was presumably delayed by haemolytic anaemia attributed to artesunate. No such marrow suppression, attributable to malaria itself and possibly experience has previously been reported from North multifactorial in this acutely ill patient. The relatively rapid recovery America where the same product is used in both the US of renal function suggests this played little if any role in his anemia. and Canada. The clearly documented hemolysis up until six weeks after admission was the major contributor to his prolonged anemia. Based on thorough investigation and review by a transfusion Case Presentation specialist, the observed degree of hemolysis is not readily explained Figure 3: Evolution of LDH post days of admission. Figure 4: Evolution of Reticulocyte Production by delayed transfusion reaction. Index (RPI) or corrected reticulocyte count post Previously, it was suggested that the cases reported only from days of admission. Europe and Asia might be explained by possible differences between the product used in those patients and that used in Canada A 44 year old male presented to the Emergency department and the US. Our patient’s experience, calls this hypothesis into with fever and confusion four days after his return from a question. month working in Cameroon. He had not taken any malaria In the previously reported cases of hemolytic anemia, most patients chemoprophylaxis or treatment and specifically, had not Clinical Evolution described had higher peak parasitemias and were treated with received any artemesinin derivative. His past medical higher doses of intravenous artesunate (8-20 mg/kg). One in vitro history consisted of treated hypertension; chronic hepatitis study showed hemolysis with exposure of red blood cells to high doses of several artemesinin derivatives. C infection was diagnosed during this hospitalization. On day 2, the haptoglobin was undetectable. The haptoglobin became detectable on day 8 of admission but again dropped below All patients receiving intravenous artesunate should have On examination the patient was hypotensive, with a the level of detection (<0.10 g/L, normal 0.30-2.00 g/L) and systematic follow up of hemoglobin levels up to 4 weeks post temperature of 40°C, marked jaundice, Kussmaul remained undetectable even at 32 days post admission. It had treatment. This will enable recognition of potentially serious degrees breathing and disorientation (Glasgow Coma Scale 14/15). finally normalized by six weeks after diagnosis. The reticulocyte of anemia and may better characterize the frequency of this At presentation, his hemoglobin was 164 g/L, white blood response remained suppressed 23 days after treatment initiation at phenomenon and contribute to our understanding of the 9 cell count 17.3x109/L and platelets were profoundly 0.7% (15.7 x 10 /L). Between days 15 and 28, the patient received a mechanism(s) involved. depressed at 4x109/L. He had acute kidney injury total of 11 units of packed red blood cells before hematological 2 recovery; by day 47 his hemoglobin was up to 98 g/L, and had (calculated GFR 38 mL/min/1.73m ) with hemoglobinuria. finally normalized, (Hb 141 g/L) by 3.5 months post presentation. Plasmodium falciparum trophozoites with schizonts were References observed in the peripheral blood smear at 2.7% At no time were the blood film findings consistent with a

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