Secretory Phospholipase A₂ in Patients With Sickle Cell Disease Hospitalized for Vaso-Occlusive Pain Episodes

Secretory phospholipase A₂ (sPLA₂) is an inflammatory mediator linked to acute chest syndrome (ACS) in sickle cell disease (SCD), a serious complication that can develop during an acute vaso-occlusive pain episode (VOE). Plasma sPLA₂ levels have been proposed as a potential biomarker for predicting ACS onset.

To assess serial plasma sPLA₂ levels in 105 pediatric patients hospitalized for SCD-VOE and determine the effects of arginine therapy compared to placebo.

This is a pharmacokinetics/pharmacodynamics and randomized controlled trial of intravenous arginine therapy. Statistical methods included t-tests, chi-square, and correlation analyses.

Mean age was 12.7 ± 3.7 years, 48% were male, 67% had Hb-SS, and 70% were prescribed hydroxyurea. Using a previously established SCD-specific cutoff of 48 ng/mL, presenting sPLA₂ levels were elevated in 33% of patients (mean sPLA₂ level 85.7 ± 32.9 ng/mL). SPLA₂ elevation in the emergency department was more common in patients with ACS compared to those without ACS (64% vs. 30%; p = 0.02; negative predictive value of 94%). Peak sPLA₂ levels were significantly higher in febrile (n = 34) versus afebrile patients (n = 71;101.0 ± 45.3 vs. 48.7 ± 35.4 ng/mL; p < 0.0001). Among subjects with elevated baseline sPLA₂, arginine therapy resulted in a significant reduction in sPLA₂ levels by discharge compared to placebo (-27.8 ± 38.1 ng/mL; p = 0.002; n = 23 vs. -15.0 ± 41.2 ng/mL; p = 0.23; n = 12).

SPLA₂ is an underutilized biomarker of ACS given accumulating evidence of its role. In particular, low levels may identify patients at low risk for ACS. Arginine therapy may modulate inflammation in patients with SCD during VOE and/or ACS.

ClinicalTrials.gov identifiers: NCT02447874; NCT02536170.