Severe Painful Vaso-Occlusive Crises and Mortality in a Contemporary Adult Sickle Cell Anemia Cohort Study

Deepika S Darbari,Catherine Seamon,James Nichols,Minjung Kwak,Gregory J Kato,Marlene Peters-Lawrence,Darlene Allen,James G Taylor Vi,Mary K Hall,Mariana Hildesheim,Zhengyuan Wang,Anna Conrey,T Mark Doherty

doi:10.1371/journal.pone.0079923

Abstract

BackgroundFrequent painful vaso-occlusive crises (VOCs) were associated with mortality in the Cooperative Study of Sickle Cell Disease (CSSCD) over twenty years ago. Modern therapies for sickle cell anemia (SCA) like hydroxyurea are believed to have improved overall patient survival. The current study sought to determine the relevance of the association between more frequent VOCs and death and its relative impact upon overall mortality compared to other known risk factors in a contemporary adult SCA cohort.MethodsTwo hundred sixty four SCA adults were assigned into two groups based on patient reported outcomes for emergency department (ED) visits or hospitalizations for painful VOC treatment during the 12 months prior to evaluation.ResultsHigher baseline hematocrit (p = 0.0008), ferritin (p = 0.005), and HDL cholesterol (p = 0.01) were independently associated with 1 or more painful VOCs requiring an ED visit or hospitalization for acute pain. During a median follow-up of 5 years, mortality was higher in the ED visit/hospitalization group (relative risk [RR] 2.68, 95% CI 1.1-6.5, p = 0.03). Higher tricuspid regurgitatant jet velocity (TRV) (RR 2.41, 95% CI 1.5-3.9, p < 0.0001), elevated ferritin (RR 4.00, 95% CI 1.8-9.0, p = 0.001) and lower glomerular filtration rate (RR=2.73, 95% CI 1.6-4.6, p < 0.0001) were also independent risk factors for mortality. ConclusionsSevere painful VOCs remain a marker for SCA disease severity and premature mortality in a modern cohort along with other known risk factors for death including high TRV, high ferritin and lower renal function. The number of patient reported pain crises requiring healthcare utilization is an easily obtained outcome that could help to identify high risk patients for disease modifying therapies.Trial RegistrationClinicalTrials.gov NCT00011648 http://clinicaltrials.gov/

Highlights

Sickle cell disease (SCD) is the most common monogenic disease in the United States, resulting from mutations in the beta-subunit of the hemoglobin molecule
Frequent vaso-occlusive crisis (VOC) defined by physician treatment and a duration of more than 2 hours were associated with higher mortality in the Cooperative Study of Sickle Cell Disease (CSSCD) this association has not been evaluated in contemporary populations where health care utilization for acute painful episodes remains common despite the availability of sickle cell anemia (SCA) specific treatments[3,4,7]
We examined VOCs with healthcare utilization and their association with mortality in a contemporary SCA cohort with a high prevalence of HU treatment, a therapy that was not available to subjects included in the first report of this association[4]

Summary

Introduction

Sickle cell disease (SCD) is the most common monogenic disease in the United States, resulting from mutations in the beta-subunit of the hemoglobin molecule. Frequent VOCs defined by physician treatment and a duration of more than 2 hours were associated with higher mortality in the Cooperative Study of Sickle Cell Disease (CSSCD) this association has not been evaluated in contemporary populations where health care utilization for acute painful episodes remains common despite the availability of SCA specific treatments[3,4,7]. Frequent painful vaso-occlusive crises (VOCs) were associated with mortality in the Cooperative Study of Sickle Cell Disease (CSSCD) over twenty years ago. The current study sought to determine the relevance of the association between more frequent VOCs and death and its relative impact upon overall mortality compared to other known risk factors in a contemporary adult SCA cohort.

Methods

Results

Conclusion