A predictive algorithm for identifying children with sickle cell anemia among children admitted to hospital with severe anemia in Africa

Abstract

Sickle cell anemia (SCA) is common in sub-Saharan Africa where approximately 1% of births are affected. Severe anemia is a common cause for hospital admission within the region yet few studies have investigated the contribution made by SCA. The Transfusion and Treatment of severe anemia in African Children Trial (ISRCTN84086586) investigated various treatment strategies in 3983 children admitted with severe anemia (hemoglobin < 6.0 g/dl) based on two severity strata to four hospitals in Africa (three Uganda and one Malawi). Children with known-SCA were excluded from the uncomplicated stratum and capped at 25% in the complicated stratum. All participants were genotyped for SCA at trial completion. SCA was rare in Malawi (six patients overall), so here we focus on the participants recruited in Uganda. We present baseline characteristics by SCA status and propose an algorithm for identifying children with unknown-SCA. Overall, 430 (12%) and 608 (17%) of the 3483 Ugandan participants had known- or unknown-SCA, respectively. Children with SCA were less likely to be malaria-positive and more likely to have an affected sibling, have gross splenomegaly, or to have received a previous blood transfusion. Most outcomes, including mortality and readmission, were better in children with either known or unknown-SCA than non-SCA children. A simple algorithm based on seven admission criteria detected 73% of all children with unknown-SCA with a number needed to test to identify one new SCA case of only two. Our proposed algorithm offers an efficient and cost-effective approach to identifying children with unknown-SCA among all children admitted with severe anemia to African hospitals where screening is not widely available.

FIGURE 1

Hemoglobin recovery by trial arm and SCA status. (A and B) Mean hemoglobin (g/L) over time in by SCA group and transfusion randomization. Data for the control arm is shown separately for children who went on to have a triggered transfusion (C and D). Total N = 1380 in 30 ml/kg, N = 1393 in 20 ml/kg, N = 347 in control, not transfused, N = 363 in control, transfused. Children with known SCA at enrolment were not eligible for the control arm. (D) Results separately according to the time from randomization until children were transfused. The AS and AA groups were combined due to small numbers of AS patients. (E) Receiver operating characteristic (ROC) curve for model to predict unknown‐SCA. ROC curve and summary statistics were considered positive for SCA if scored above the “Cut point”, with the true status defined according to genotype results (SS = positive, AA/AS = negative). A score of 5 was selected as the optimal cut point based on sensitivity and PPV. The number needed to test was calculated as 1/PPV. PPV, positive predictive value; SCA, sickle cell anemia