Immediate Transfusion in African Children with Uncomplicated Severe Anemia

Abstract

BACKGROUNDThe World Health Organization recommends not performing transfusions in African children hospitalized for uncomplicated severe anemia (hemoglobin level of 4 to 6 g per deciliter and no signs of clinical severity). However, high mortality and readmission rates suggest that less restrictive transfusion strategies might improve outcomes. METHODSIn this factorial, open-label, randomized, controlled trial, we assigned Ugandan and Malawian children 2 months to 12 years of age with uncomplicated severe anemia to immediate transfusion with 20 ml or 30 ml of whole-blood equivalent per kilogram of body weight, as determined in a second simultaneous randomization, or no immediate transfusion (control group), in which transfusion with 20 ml of whole-blood equivalent per kilogram was triggered by new signs of clinical severity or a drop in hemoglobin to below 4 g per deciliter. The primary outcome was 28-day mortality. Three other randomizations investigated transfusion volume, postdischarge supplementation with micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole. RESULTSA total of 1565 children (median age, 26 months) underwent randomization, with 778 assigned to the immediate-transfusion group and 787 to the control group; 984 children (62.9%) had malaria. The children were followed for 180 days, and 71 (4.5%) were lost to follow-up. During the primary hospitalization, transfusion was performed in all the children in the immediate-transfusion group and in 386 (49.0%) in the control group (median time to transfusion, 1.3 hours vs. 24.9 hours after randomization). The mean (±SD) total blood volume transfused per child was 314±228 ml in the immediatetransfusion group and 142±224 ml in the control group. Death had occurred by 28 days in 7 children (0.9%) in the immediate-transfusion group and in 13 (1.7%) in the control group (hazard ratio, 0.54; 95% confidence interval [CI], 0.22 to 1.36; P = 0.19) and by 180 days in 35 (4.5%) and 47 (6.0%), respectively (hazard ratio, 0.75; 95% CI, 0.48 to 1.15), without evidence of interaction with other randomizations (P>0.20) or evidence of between-group differences in readmissions, serious adverse events, or hemoglobin recovery at 180 days. The mean length of hospital stay was 0.9 days longer in the control group. CONCLUSIONSThere was no evidence of differences in clinical outcomes over 6 months between the children who received immediate transfusion and those who did not. The triggeredtransfusion strategy in the control group resulted in lower blood use; however, the length of hospital stay was longer, and this strategy required clinical and hemoglobin monitoring. (Funded by the Medical Research Council and Department for International Development; TRACT Current Controlled Trials number, ISRCTN84086586.

The clinical spectrum of severe childhood malaria in Eastern Uganda

“…In contrast to the recent mortality rates reported from the TRACT trial [31,32], which examined blood transfusion strategies in multiple settings (including two centres from Eastern Uganda), inpatient mortality among children presenting with severe malarial anaemia in the current observational study was high (19.5%). The lower mortality seen in TRACT might have reflected the fact that recruitment to the trial was halted when blood for transfusion was not available or because of improvements in blood transfusion services in Uganda during the intercurrent period.…”

“…In the current study, the receipt of blood transfusions was not recorded; however, a high rate of early mortality among critically sick children with severe anaemia while awaiting a blood transfusion has been previously described [33]. The importance of adhering to the restrictive blood transfusion policy from the WHO was underpinned by evidence from children with severe and uncomplicated anaemia within TRACT [31], who did not require immediate transfusion, allowing donor blood to be targeted to those with severe and complicated anaemia in situations where supplies are limited.…”

The age-specific incidence of hospitalized paediatric malaria in Uganda

“…Those with SMA, while younger than patients presenting with cerebral malaria, include older children and this severe disease phenotype is not restricted to very young children, with 37.5% of those defined as SMA being 5–14 years of age. The observation of higher rates of SMA among older children requires further investigation and how to improve case-management in all pediatric age groups [ 51 , 52 ]. Haemoglobinuria was reported as the presence of “tea colored urine” by caretakers among 4.8% of all malaria admissions (Table 3 ).…”

Characterising demographics, knowledge, practices and clinical care among patients attending sickle cell disease clinics in Eastern Uganda

“…This reinforces the message from a number of recent studies that have reported the heavy demand that patients with SCD place on blood transfusion services in a number of African settings 19 , 22 – 24 . For example, in the recently reported multi-centre Transfusion and Treatment of Severe Anaemia in African Children Trial (TRACT), 33% of those recruited with severe and complicated anaemia had SCD, of whom almost half had not been previously diagnosed 23 , 24 .…”