Phase II trial of standard versus increased transfusion volume in Ugandan children with acute severe anemia.
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.


CONCLUSIONS
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.


BACKGROUND
ClinicalTrials.Gov identifier: NCT01461590 registered 26 October 2011.
Peter
P
Olupot-Olupot
Charles
C
Engoru
Jennifer
J
Thompson
Julius
J
Nteziyaremye
Martin
M
Chebet
Tonny
T
Ssenyondo
Cornelius M
CM
Dambisya
Vicent
V
Okuuny
Ronald
R
Wokulira
Denis
D
Amorut
Paul
P
Ongodia
Ayub
A
Mpoya
Thomas N
TN
Williams
Sophie
S
Uyoga
Alex
A
Macharia
Diana M
DM
Gibb
A Sarah
AS
Walker
Kilifi Clinical Trials Facility, KEMRI-Wellcome Trust Research Programme, PO Box 230, Kilifi, Kenya. k.maitland@imperial.ac.uk.
Kathryn
K
Maitland
D000208:Acute Disease; D000349:Africa; D000740:Anemia / Q000097:blood / Q000628:therapy*; D001803:Blood Transfusion / Q000706:statistics & numerical data; D002675:Child, Preschool; D005260:Female; D006441:Hemoglobin A; D006760:Hospitalization; D006801:Humans; D007223:Infant; D008297:Male; D065227:Transfusion Reaction
D006441:Hemoglobin A