Abstract:
Background: Severe anemia (SA, hemoglobin <6 g/dl) is a leading cause of pediatric hospital admission in Africa,
with significant in-hospital mortality. The underlying etiology is often infectious, but specific pathogens are rarely
identified. Guidelines developed to encourage rational blood use recommend a standard volume of whole blood
(20 ml/kg) for transfusion, but this is commonly associated with a frequent need for repeat transfusion and poor
outcome. Evidence is lacking on what hemoglobin threshold criteria for intervention and volume are associated
with the optimal survival outcomes.
Methods: We evaluated the safety and efficacy of a higher volume of whole blood (30 ml/kg; Tx30: n = 78) against
the standard volume (20 ml/kg; Tx20: n = 82) in Ugandan children (median age 36 months (interquartile range
(IQR) 13 to 53)) for 24-hour anemia correction (hemoglobin >6 g/dl: primary outcome) and 28-day survival.
Results: Median admission hemoglobin was 4.2 g/dl (IQR 3.1 to 4.9). Initial volume received followed the
randomization strategy in 155 (97%) patients. By 24-hours, 70 (90%) children in the Tx30 arm had corrected SA
compared to 61 (74%) in the Tx20 arm; cause-specific hazard ratio = 1.54 (95% confidence interval 1.09 to 2.18, P = 0.01).
From admission to day 28 there was a greater hemoglobin increase from enrollment in Tx30 (global P <0.0001).
Serious adverse events included one non-fatal allergic reaction and one death in the Tx30 arm. There were six
deaths in the Tx20 arm (P = 0.12); three deaths were adjudicated as possibly related to transfusion, but none
secondary to volume overload.
Conclusion: A higher initial transfusion volume prescribed at hospital admission was safe and resulted in an
accelerated hematological recovery in Ugandan children with SA. Future testing in a large, pragmatic clinical
trial to establish the effect on short and longer-term survival is warranted.
