The relation of C-reactive protein to vasoocclusive crisis in children with sickle cell disease

Abstract

In view of evidence linking sickle cell anemia (SCA) with chronic inflammation, and given the role of high sensitivity C-reactive protein (hs-CRP) as inflammatory mediator, we hypothesized that SCA vasoocclusive crisis (VOC) is associated with heightened hs-CRP levels. Study subjects comprised 104 SCA patients who experienced VOC event during the study period (VOC group), and 40 SCA patients who did not develop VOC for at least 9 months prior to blood collection (Steady-state group). hs-CRP determination was done by latex-enhanced nephelometry. Higher hs-CRP levels were seen in VOC [median(range) = 31.3(1.14–363.0)] than steady-state [median(range) = 5(0.16–185.0)] groups (P < 0.001), with enrichment in high hs-CRP percentiles in VOC cases, which translated into step-wise increased VOC risk. Receiver-operating characteristic (ROC) analysis was employed in assessing the usefulness of hs-CRP as predictor of the frequency and severity of VOC. Spearman's correlation coefficient between hs-CRP and VOC was 0.65 (P < 0.001) among unselected patients (0.71 in males and 0.59 in females). hs-CRP area under ROC curves was 0.90 (95% CI = 0.85–0.94) among unselected patients, 0.94 (95% CI = 0.89–0.98) for males, and 0.85 (95% CI = 0.77–0.93) for females. Logistic regression analysis confirmed the positive association of increased hs-CRP levels with VOC, which correlated positively with VOC frequency (P < 0.001), type (P < 0.001), pain (P < 0.001), and need for hospitalization (P = 0.024). These data support strong association of increased hs-CRP levels with VOC, which impacts VOC-related parameters, and support a role for hs-CRP in VOC follow-up.