Acute Splenic Sequestration In a Newborn Cohort with Sickle Cell Anemia (SCA): Predictive Factors and Impact on Disease Severity

Abstract 263

Early occurrence of dactylitis, severe anemia and leukocytosis have been identified as risk factors for adverse outcome in children with SCA (Miller NEJM 2000), but the impact of acute splenic sequestrations (ASS) on disease severity has not yet been reported. The goal of this study was to define the predictive factors of ASS and to evaluate if this complication was a risk factor for disease severity. Methods. SS patients of the newborn cohort, seen at our SCA Center in Créteil before 3 months of age and older than 2 years at the last visit (n=197), were included in this study. Alpha and beta genotypes, and G6PD activity were determined. Blood parameters were recorded at steady state during the second year of life. ASS was defined as an Hb-decrease of ≥20% associated with a spleen-increase ≥2cm. Vaso-occlusive crises (VOC) requiring hospitalizations and acute chest syndromes (ACS) were recorded. The yearly rates of VOC and ACS were calculated for the entire follow-up and for the period before any intensification (transfusion program, hydroxyurea or SCT). Results. Median follow-up was 7.9 yr (range 2–24), providing 1820 patient-years. Alpha-Thal was present in 70/162 (43.2%); beta-haplotypes, available in 140 patients, were Car/Car in 62 (44.3%), Ben/Ben in 35 (25%), Sen/Sen in 7 (5%), and others in 34 (25.7%). G6PD deficiency was present in 24/171 (14%). At baseline, mean (SD) blood parameters were: Hb: 8g1/dL (1.2); Ht: 24.6% (3.9); MCV: 79.2 fL(8.3); HbF: 15.7% (8.2); LDH: 919 UI/L (369) and reticulocytes: 296 (114); WBC: 14.3 (5.2), neutrophils 5.8 (3.1) × 10⁹/L. Among the 197 SS-patients, 64 (32%) experienced their first ASS at the median age of 2.0 yr (range 0.1–12.9) and 36/64 recurred. ASS occurred before 1 yr of age in 10 (5%) and before 2 yr in 33/197 (17%). Splenectomy was performed in 24 of them at the median age of 5.1 yr (range 2.7–12.9). The KM-estimated cumulative risk of ASS occurrence at age 7 was 32% (95%CI: 25–39%). The Cox-regression analysis showed that gender, G6PD deficiency, beta haplotypes were not risk factors whereas alpha-Thal significantly increased the risk of ASS occurrence (HR: 1.9, 95% CI:1.1-3.3, p=0.021). Among blood parameters, multivariate Cox analysis retained low platelet (HR: 1.4 per 1×10⁷/L decrease; 95%CI:1.1-1.8, p=0.014) and high reticulocyte counts (HR=2.0 per 1×10⁷/L increase; 95%CI:1.6-2.6) as independent significant predictive factors for ASS. Comparison of patients with or without ASS history showed no significant difference in the rate of ACS but significantly higher rates of VOC during the entire follow-up (0.68±0.58 vs 0.47±0.55; p=0.014) and in the number of hospitalizations (1.64±0.83 vs 1.29±0.92; p=0.01) in patients with ASS history. Rates of VOC before intensification were 1.1±0.7 and even 2.2±2.0 in those having experienced ASS before age 1 vs 0.6±0.7 (p=0.001) in those with no ASS history. Conclusion. Results from this study in a newborn cohort show that ASS are more frequent in patients with alpha-Thal and are associated with a higher rate of VOC. Splenectomy is usually recommended in case or recurrent ASS; however, our previous results show that geno-identical SCT can cure 95%SCA children and partly restore splenic function. We suggest that this procedure be proposed to those with available donor before considering total splenectomy.