Markers of severe vaso-occlusive painful episode frequency in children and adolescents with sickle cell anemia

Abstract

Objective: To identify factors associated with frequent severe vaso-occlusive pain crises in a contemporary pediatric cohort of patients with sickle cell anemia (SCA) enrolled in a prospective study of pulmonary hypertension and the hypoxic response in sickle cell disease.

Study design: Clinical and laboratory characteristics of children with SCA who had ≥3 severe pain crises requiring health care in the preceding year were compared with those of subjects with <3 such episodes.

Results: Seventy-five children (20%) reported ≥3 severe pain episodes in the preceding year, and 232 (61%) had none. Frequent pain episodes were associated with older age (OR, 1.2; 95% CI, 1.1-1.3; P < .0001), α-thalassemia trait (OR 3.5; 1.6-6.7; P = .002), higher median hemoglobin (OR 1.7; 95% CI: 1.2-2.4; P < .003), and lower lactate dehydrogenase concentration (OR 1.82; 95% CI: 1.07-3.11; P = .027). Children with high pain frequency also had an increased iron burden (serum ferritin, 480 vs 198 μg/L; P = .006) and higher median tricuspid regurgitation jet velocity (2.41 vs 2.31 m/s; P = .001). Neither hydroxyurea use nor fetal hemoglobin levels were significantly different according to severe pain history.

Conclusions: In our cohort of children with SCA, increasing age was associated with higher frequency of severe pain episodes as were α-thalassemia, iron overload, higher hemoglobin and lower lactate dehydrogenase concentration, and higher tricuspid regurgitation velocity.

Trial registration: ClinicalTrials.gov NCT00495638.

Figure 1

Pathway analysis of pain episode frequency in children with sickle cell anemia. Model was adequately fitted to data with root mean square error approximation (RMSEA) =0.01 (90% CI=0.0–0.08). Model chi-square is 4.2 (P=0.4, Degree of freedom = 4). Standardized beta are shown in the figure. All p values are < 0.04. A similar pathway in which severe pain was a predictor of higher tricuspid regurgitation velocity was not significantly different from this pathway as a result the direction of causation between pain and TRV could not be differentiated by this analysis.