Postartesunate delayed hemolysis is a predictable event related to the lifesaving effect of artemisinins

Abstract

Key Points After being killed by artesunate, malaria parasites are expelled from red cells and then these pitted red cells reenter the circulation. When many pitted red cells are produced during therapy, their delayed clearance a few weeks later triggers hemolytic episodes.

Artemisinin-induced delayed hemolysis after administration of artesunate and artesunate-amodiaquine in malaria-free Wistar rats

“…In the absence of malaria parasites, free iron bioactivation of the endoperoxide bridge of artemisinin drugs can be used to modulate its effects (Conran, 2014;Krishna et al, 2004;Meshnick et al, 1989;Meshnick et al, 1993;Muhia et al, 1994;Tangnitipong et al, 2012). Delayed hemolysis in AS group follows a pattern similar to that reported in malaria infected persons (Arguin, 2014;Boillat et al, 2015;Chavada et al, 2015;Conran, 2014;Jauréguiberry et al, 2014;Kurth et al, 2016;Lee et al, 2015;Rehman et al, 2014;Rolling et al, 2015;WHO, 2013), although no anemia was recorded throughout this study.…”

“…Different hypothesis have been proposed to explain the underlying cause of hemolysis after artemisinin treatment, however the hypothesis that pitted erythrocytes are destroyed during recovery best explains post-artesunate delayed hemolysis after treatment of malaria infection (Jauréguiberry et al, 2014). Hemolysis may occur after treatment with different classes of antimalarials ISSN: 2198-4093 www.bmrat.org (Ngole et al, 2010;Price et al, 2001;Sowunmi et al, 2009), however studies have not reported delayed post-treatment hemolysis occurring with antimalarials other than artemisinin derivatives.…”

“…Delayed hemolysis was first recognized after parenteral artesunate in naïve patients, studies have also reported delayed hemolytic anemia after administration of oral artemisinin derivatives in immune and non-immune subjects with severe malaria or hyperparasitemia (Control and Prevention, 2013;Jauréguiberry et al, 2014;Molta et al, 2003;Rehman et al, 2014;WHO, 2013). Different hypothesis have been proposed to explain the underlying cause of hemolysis after artemisinin treatment, however the hypothesis that pitted erythrocytes are destroyed during recovery best explains post-artesunate delayed hemolysis after treatment of malaria infection (Jauréguiberry et al, 2014).…”

Case definition: postartemisinin delayed hemolysis

“…1 Early destruction of pitted erythrocytes has been the leading hypothesis for postartesunate delayed hemolysis since it was first recognized a few years ago.…”

Delayed Hemolysis After Parenteral Artesunate Therapy for Severe Malaria in Two Returning Canadian Travelers

“…The delayed, synchronous destruction of this population of pitted erythrocytes accounts for the delayed hemolysis. 20 Hemolysis with exposure of RBCs to high doses of several artemisinin derivatives has also been described in vitro. 21 …”