Case Presentation: Case Presentation: This is a 3 year old male who recently returned from two months traveling in Liberia. In Liberia, he contracted malaria and was treated with two days of IV antimalarial treatment (thought to be artesunate) followed by three days of oral artemether-lumefantrine with improvement in symptoms. Ten days after completing treatment, he presented to our institution with pallor, abdominal distension, and edema. He was found to have macrocytic anemia with Hgb of 4.0 g/dL and MCV of 111 fL, with an appropriate reticulocyte index of 5.18. His CBC was otherwise normal. Other notable labs included elevated CRP to 4.81 mg/dL, elevated LDH to 1399 U/L, and decreased albumin to 2.8 g/dL. A rapid malaria screen was positive for Plasmodium falciparum. His thick and thin smears did not show any P. falciparum. Physical exam was notable for mildly tender abdominal distension and mucosal pallor with normal vitals. He received two RBC transfusions, with recovery of Hgb to 6.8 g/dL. He required a third transfusion, with Hgb recovery to 8.1g/dL. He was discharged home with close hematology follow up and iron supplementation.
Discussion: Discussion: Post-artemisinin delayed hemolysis (PADH) is an uncommon complication of artesunate treatment for severe malaria in both adults and children. PADH more often occurs in endemic areas or in non-immune travelers with severe P. falciparum infection. The exact mechanism of PADH is unclear. One theory is that after artesunate-derivatives induce the destruction of Plasmodium species in erythrocytes through the production of reactive oxygen species, the parasite debris is engulfed by splenic macrophages, allowing recirculation of the previously infected RBCs. These RBCs are small and have impaired structural integrity, leading to their destruction. This helps explain why patients with high parasitemia seem to experience more severe PADH, as more RBCs are impacted. Other possible pathways include drug-induced suppression of erythropoiesis and drug-induced immune hemolytic anemia, suggested by the high prevalence of positive DAT in patients with PADH. A mechanism for quantification of once-infected erythrocytes (after artemisinin treatment) using flow cytometry has been used retrospectively to stratify patients based on risk of PADH. Currently, however, there is not a reliable method of calculating risk of PADH based on parasite density on thick and thin smears collected prior to treatment. This would be more accessible to centers without easy access to flow cytometry and to patients who are traveling after treatment.
Conclusions: Conclusions: Patients should be monitored for post-artemisinin delayed hemolysis, particularly if they had severe infection or high parasite load. Further research needs to be done to effectively predict risk of PADH. In our state, 100% of malaria cases in recent years have been in returning travelers who acquired malaria while visiting family and friends or before immigrating, highlighting the relevance of PADH monitoring in communities with residents who are from or travel to malaria-endemic areas. Effective screening and monitoring could avoid the need for blood transfusions or dangerously low hemoglobin.