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

Mehdi Nouraie, Deepika S. Darbari, Sohail Rana, Caterina P. Minniti, Oswaldo L. Castro, Lori Luchtman-Jones, Craig Sable, Niti Dham, Gregory J. Kato, Mark T. Gladwin, Gregory Ensing, Manuel Arteta, Andrew Campbell, James G. Taylor, Sergei Nekhai, Victor R. Gordeuk

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Abstract

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 seven of 10 patients: stroke in four (hemorrhagic two, infarctive one, unspecified one), multiorgan failure one, parvovirus B19 infection one, sudden death one. Baseline TRV ≥2.7 m/second (>2 SD above the mean in age-matched and gender-matched non-SCD controls) was observed in 20.0% of patients who died vs 4.6% of those who survived (P =.012 by the log rank test for equality of survival). The baseline variable most strongly associated with an elevated TRV was a high hemolytic rate. Additional biomarkers associated with mortality were ferritin ≥2000 μg/L (observed in 60% of patients who died vs 7.8% of survivors, P <.001), forced expiratory volume in 1 minute to forced vital capacity ratio (FEV1/FVC) <0.80 (71.4% of patients who died vs 18.8% of survivors, P <.001), and neutrophil count ≥10x109/L (30.0% of patients who died vs 7.9% of survivors, P =.018). In SCD 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.

Original languageEnglish (US)
Pages (from-to)766-774
Number of pages9
JournalAmerican Journal of Hematology
Volume95
Issue number7
DOIs
StatePublished - Jul 1 2020

ASJC Scopus subject areas

  • Hematology

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    Nouraie, M., Darbari, D. S., Rana, S., Minniti, C. P., Castro, O. L., Luchtman-Jones, L., Sable, C., Dham, N., Kato, G. J., Gladwin, M. T., Ensing, G., Arteta, M., Campbell, A., Taylor, J. G., Nekhai, S., & Gordeuk, V. R. (2020). 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. American Journal of Hematology, 95(7), 766-774. https://doi.org/10.1002/ajh.25799