Dr. Nwaneri has raised important questions and simultaneously made useful comments on our paper recently published in the Journal.1
He expresses a major concern regarding the high risk of mortality in our study population of severely anemic children despite receiving a blood transfusion. Our paper reported that, among severely anemic children, transfusion was associated with an increased risk of mortality (relative risk = 2.08; 95% confidence interval: 0.88–4.91). This means that, in our study, administration of blood transfusion to severely anemic children was associated with beneficial and harmful effects on mortality; that is, some children experienced a reduced risk of death, whereas in others, this risk was increased. This finding is consistent with results of previous studies in which transfusion was found to reduce mortality risk in only a subgroup of severely anemic children (e.g., those with very low hemoglobin and respiratory distress) and only when given early during admission.2–4 In a more recent report from Uganda, a higher risk of mortality and higher re-admission rates were found among HIV-positive compared with HIV-negative children during a 6-month follow-up after receiving transfusion therapy for severe anemia.5 We did not test for HIV in our study population, but HIV was strongly associated with severe anemia in children hospitalized with severe malaria at our study site.6 A review of published studies investigating whether high transfusion rates were associated with a lower risk of in-hospital mortality among African children with severe anemia failed to find a consistent association.7 In the absence of randomized trials evaluating the efficacy and safety of blood transfusion, treatment guidelines have been based on weak evidence. Consequently, authors of a recent Cochrane systematic review concluded that there is insufficient evidence to be sure that routine blood transfusion of clinically stable children with severe anemia in malaria-endemic regions reduces the risk of death.8 We speculate that this high mortality could arise for several reasons including late presentation of the children to hospital, underlying conditions (e.g., bacteremia, fluid overload, lactic acidosis), or delayed transfusion procedures.9
We agree with the recommendation of Nwaneri that transfusion of packed red cells to severely anemic children may be an effective means of reducing the net volume of transfused blood while enhancing tissue oxygenation. In our study, severely anemic children received 20 mg/kg body weight of HIV-negative whole blood. With the chronic shortages of blood and staff in the blood banks, routine preparation of packed cells may not be financially and practically feasible in settings where severe malarial anemia is treated.10 Traditionally, clinicians have attempted to solve this problem by reducing the effective fluid volume transfused by simultaneously administering an injection of a diuretic (e.g., frusemide) midway between the initiation and end of a transfusion.11 Nurses often try to allow the packed cells to settle at the bottom of the pack by administering the transfusion slowly.
We agree that timing is essential for improving the effectiveness of transfusion therapy. Commonly, 50% of children with severe anemia die during the first 12 hours of admission. Studies in western Kenya and in West Africa have shown that the risk of mortality among severely anemic children is inversely proportional to time since admission spent waiting for a transfusion,2,12 consistent with the results of a transfusion decision-analysis model.13 To reduce this high risk of mortality shortly after admission requires timely recognition of the condition and ready availability of screened blood.
We differ with the statement regarding heart failure in severely anemic children. Previously, the following clinical features, which make up the typical textbook description of a child with severe anemia, were presumed to indicate impending congestive heart failure: dyspnea, lethargy, tachypnea, tachycardia, grunting, gallop rhythm, and hepatomegaly. From a better understanding of the pathophysiology of severe malarial anemia, these features are now understood to arise from lactic acidosis.14,15
Finally, Nwaneri asked what targets should be set to improve transfusion services in Africa. We suggest the following, which may not apply in all malaria-endemic regions because of differences in the organization of transfusion services. At a minimum, every district hospital should have blood collection and transfusion services. Blood should be available to a severely anemic child within 2 hours of admission. Efficacy of a transfusion should be established by doing pre- and post-transfusion hemoglobin. Every hospital offering transfusion services should have a transfusion committee. Finally, a regular transfusion audit and educational program for prescribers of blood is necessary.
Obonyo CO, Vulule J, Akhwale WS, Grobbee DE, 2007. Inhospital morbidity and mortality due to severe malarial anemia in western Kenya. Am J Trop Med Hyg 77 (6 Suppl):23–28.
Lackritz EM, Campbell CC, Ruebush TK II, Hightower AW, Wakube W, Steketee RW, Were JB, 1992. Effect of blood transfusion on survival among children in a Kenyan hospital. Lancet 340 :524–528.
Bojang KA, van Hensbroek MB, Palmer A, Banya WA, Jaffer S, Greenwood BM, 1997. Predictors of mortality in Gambian children with severe malarial anemia. Ann Trop Paediatr 17 :355–359.
English M, Ahmed M, Ngando C, Berkley J, Ross A, 2002. Blood transfusion for severe anemia in children in a Kenyan hospital. Lancet 359 :494–495.
Malamba S, Hladik W, Reingold A, Banage F, McFarland W, Rutherford G, Mimbe D, Nzaro E, Downing R, Mermin J, 2007. The effect of HIV on morbidity and mortality in children with severe malarial anemia. Malar J 6 :143.
Otieno RO, Ouma C, Ong’echa JM, Keller CC, Were T, Waindi EN, Michaels MG, Day RD, Vulule JM, Perkins DJ, 2006. Increased severe anemia in HIV-1-exposed and HIV-1-positive infants and children during acute malaria. AIDS 20 :275–280.
Lackritz EM, Ruebush TK 2nd, Zucker JR, Adungosi JE, Were JB, Campbell CC, 1993. Blood transfusion practices and blood-banking services in a Kenyan hospital. AIDS 7 :995–999.
Ernest SK, Anunobi NE, Adeniyi A, 2002. Correlates of emergency response interval and mortality from severe anemia in childhood. West Afr J Med 21 :177–179.
Obonyo CO, Steyerberg EW, Oloo AJ, Habbema JD, 1998. Blood transfusions for severe malaria-related anemia in Africa: a decision analysis. Am J Trop Med Hyg 59 :808–812.
English M, Muambi B, Mithwani S, Marsh K, 1997. Lactic acidosis and oxygen debt in African children with severe anemia. QJM 90 :563–569.
English M, Waruiru C, Marsh K, 1996. Transfusion for life threatening respiratory distress in severe childhood malaria. Am J Trop Med Hyg 55 :525–530.