Mortality Due to Severe Malarial Anemia is Associated with Thrombocytopenia and Mitigated by Restoration of Platelet Counts Following Whole Blood Transfusion: A Retrospective Observational Study

Abstract

Background: Severe malaria due to Plasmodium falciparum is the leading parasitic cause of death in children worldwide, and severe malarial anemia (SMA) is the most common clinical presentation. The evidence in support of current transfusion guidelines for patients with SMA is limited. Methods: We conducted a retrospective cohort study of 911 hospitalized children with SMA in a holoendemic region of Zambia to examine the association of whole blood transfusion with in-hospital survival. Data were analyzed in adjusted logistic regression models using multiple imputation for missing data. Findings: The median age of patients was 24 months (interquartile range 16-30) and overall case fatality was 16%. Blood transfusion was associated with 35% reduced odds of death in children with SMA (odds ratio 0·65, 95% CI 0·52-0·81, p=0·002) corresponding to a number-needed-to-treat (NNT) of 14 patients. Children with SMA complicated by thrombocytopenia were more likely to benefit from transfusion than those without thrombocytopenia (NNT=5), and thrombocytopenia influenced the association between respiratory distress and death. Time-in-storage of whole blood was negatively associated with survival and with the post-transfusion rise in the platelet count but was not associated with the post-transfusion change in the hemoglobin concentration. Interpretation: Whole blood given to pediatric patients with SMA was associated with improved survival, mainly among those with thrombocytopenia who received fresh whole blood. The shelf life of whole blood may need to be reconsidered in this context. These findings point to a potential clinical role for platelet-directed transfusion strategies in the management of severe malaria, which can be further assessed in prospective studies, and underline the challenges of maintaining reliable blood donation networks in areas of high malaria transmission. Funding: National Institutes of Health, Johns Hopkins Malaria Research Institute, Bloomberg Philanthropies, Burroughs Wellcome Fund and the American Society of Tropical Medicine and Hygiene. Declaration of Interest: The authors declare no conflicts of interest. Ethical Approval: The study was approved in the United States by the Johns Hopkins Bloomberg School of Public Health Institutional Review Board, and by the Tropical Disease Research Centre Ethics Review Committee in Ndola, Zambia.