Tricuspid Regurgitation Velocity and Other Biomarkers of Mortality in Children, Adolescents and Young Adults with Sickle Cell Disease in the United States: the PUSH Study.

In the US, mortality in sickle cell disease (SCD) increases after age 18-20 years. Biomarkers of mortality risk can identify patients who need intensive follow-up and early or novel interventions. We prospectively enrolled 510 SCD patients aged 3-20 years into an observational study in 2006-2010 and followed 497 patients for a median of 88 months (range 1-105). We hypothesized that elevated pulmonary artery systolic pressure as reflected in tricuspid regurgitation velocity (TRV) would be associated with mortality. Estimated survival to 18 years was 99% and to 25 years, 94%. Causes of death were known in 7 of 10 patients: stroke in 4 (hemorrhagic 2, infarctive 1, unspecified 1), multiorgan failure 1, parvovirus B19 infection 1, sudden death 1. Baseline TRV ≥2.7 m/sec (>2 SD above the mean in age- and gender-matched non-SCD controls) was observed in 20.0% of patients who died versus 4.6% of those who survived (p=0.012 by the log rank test for equality of survival). Additional biomarkers associated with mortality were ferritin ≥2000 μg/L (observed in 60% of patients who died versus 7.8% of survivors, p<0.001), forced expiratory volume in one minute to forced vital capacity ratio (FEV1/FVC) <0.80 (71.4% of patients who died versus 18.8% of survivors, p<0.001) and neutrophil count ≥10x109 /L (30.0% of patients who died versus 7.9% of survivors, p=0.018). In children, adolescents and young adults, steady-state elevations of TRV, ferritin and neutrophils and a low FEV1/FVC ratio may be biomarkers associated with increased risk of death in SCD patients who transition to adulthood. This article is protected by copyright. All rights reserved.