Decreased lactic acidosis and anemia after transfusion of O-raffinose cross-linked and polymerized hemoglobin in severe murine malaria

Severe anemia is a major cause of death in falciparum malaria. Blood transfusion increases survival in humans and in animal models of this disease. Because of logistic constraints and viral contamination of the blood supply, transfusions are frequently not practical in endemic regions. Modified hemoglobin is an effective O2 carrier in hemorrhagic shock. It is free of infectious contamination, may not require refrigeration, and because of its nitric oxide scavenging and small size, may have pharmacologic benefits in malaria. The effects of transfusions of modified hemoglobin in rats with high-grade parasitemia were evaluated. Modified hemoglobin decreased lactic acidosis and corrected anemia as well as transfusions with red blood cells; these findings may correlate with improved survival and suggest a possible proerythropoietic effect. Further study of this novel therapy is warranted. Plasmodium species cause more than two million deaths per year worldwide; at least 30-40% of P. falciparum-re- lated deaths are secondary to severe anemia. 1,2 Anemia is caused by hemolysis, erythrophagocytosis, dyserythropoies- is, and sequestration of infected red blood cells (RBCs) in peripheral vessels. 3-5 Blood transfusion for the treatment of severe malaria anemia decreases mortality in some patients and in murine models. 6-9 However, blood transfusions in un- derdeveloped countries where malaria is endemic are fre- quently impractical. Modified hemoglobin solutions have been developed as alternative transfusion agents. Modifications have included o-raffinose cross-linking and polymerization, recombinant molecular manipulation, pyridoxylation, polyoxyethylene conjugation, and intramolecular cross-linking. In hemorrhag- ic shock, modified hemoglobin is an effective O 2 carrier. 10