Teaching Topic 

Immediate Transfusion in African Children with Severe Anemia 

ORIGINAL ARTICLE 

Immediate Transfusion in African Children with Uncomplicated Severe Anemia 

K. Maitland and Others

         

Severe anemia (hemoglobin level <6 g per deciliter) is a leading cause of hospital admission among children in sub-Saharan Africa. Maitland et al. conducted a factorial, open-label, randomized, controlled trial, which compared immediate transfusion with no immediate transfusion (with transfusion triggered by the development of new signs of clinical severity or a drop in the hemoglobin level to below 4 g per deciliter) in African children with uncomplicated severe anemia.

Clinical Pearls

  What is the toll of severe anemia among children in sub-Saharan Africa?

Outcomes remain unsatisfactory, with high reported in-hospital mortality (9 to 10%) and 6-month mortality (12%) and high rates of readmission.

  Who was eligible for the trial by Maitland et al.?

The trial was performed at three hospitals in Uganda and one hospital in Malawi. In the part of the factorial trial reported here, children 2 months to 12 years of age were eligible if they were hospitalized for uncomplicated severe anemia (defined as a hemoglobin level of 4 to 6 g per deciliter and no signs of clinical severity [i.e., no evidence of reduced level of consciousness, respiratory distress, acute hemoglobinuria, or reported sickle cell disease]).

Morning Report Questions

Q. Did the trial by Maitland et al. report reduced mortality with a strategy of immediate transfusion as compared to triggered transfusion?

A. Vital status was known for 1556 children (99.4%) at day 28 (primary outcome) and for 1494 children (95.5%) at day 180 (end of follow-up). By day 28, death had occurred in 7 children (0.9%) in the immediate-transfusion group (6 [0.8%] who received 20 ml and 1 [0.1%] who received 30 ml of whole-blood equivalent per kilogram) and in 13 children (1.7%) in the control group (hazard ratio, 0.54; 95% confidence interval [CI], 0.22 to 1.36; P=0.19). By day 180, death had occurred in 35 children (4.5%) in the immediate-transfusion group and 47 (6.0%) in the control group (hazard ratio, 0.75; 95% CI, 0.48 to 1.15).

Q. What were some limitations in the trial by Maitland et al.?

A. A key limitation of this trial was the lower overall mortality (2%) than the 9% predicted according to other studies of uncomplicated severe anemia in African children, which showed consistently higher mortality. Although mortality was too low to either show or refute any benefits from immediate transfusion, the trial showed that among children with uncomplicated severe anemia, the immediate-transfusion strategy resulted in fewer children who had development of profound anemia (hemoglobin level <4 g per deciliter), which is an absolute indication for transfusion, and more children who had early hemoglobin recovery (to a level >9 g per deciliter) than the triggered-transfusion strategy. However, these findings in the immediate-transfusion group did not translate into fewer readmissions (15.1% of the children) or fewer serious adverse events related to anemia (10.3% of the children).