title: Longitudinal Analysis of Patient Specific Predictors for Mortality in Sickle Cell Disease.
abstract: BACKGROUND
  White Blood Cell (WBC) count, %HbF, and serum creatinine (Cr), have been identified as markers for increased mortality in sickle cell anemia (SCA) but no studies have examined the significance of longitudinal rate of change in these or other biomarkers for SCA individuals.
  
  
  METHODS
  Clinical, demographic and laboratory data from SCA patients seen in 2002 by our hospital system were obtained. Those who were still followed in 2012 (survival cohort) were compared to those who had died in the interim (mortality cohort). Patients lost to follow-up were excluded. Age adjusted multivariable Cox proportional hazards models were constructed to assess hazard ratios of mortality risk associated with the direction and degree of change for each variable.
  
  
  RESULTS
  359 SCA patients were identified. Baseline higher levels of WBC, serum creatinine and hospital admissions were associated with increased mortality, as were alkaline phosphatase and aspartate aminotransaminase levels. Lower baseline levels of %HbF were also associated with increased mortality. When longitudinal rates of change for individuals were assessed, increases in Hb or WBC over patient baseline values were associated with greater mortality risk (HR 1.54, p = 0.02 and HR 1.16, p = 0.01 with negative predictive values of 87.8 and 94.4 respectively), while increasing ED use was associated with decreased mortality (HR 0.84, p = 0.01). We did not detect any increased mortality risk for longitudinal changes in annual clinic visits or admissions, creatinine or %HbF.
  
  
  CONCLUSIONS
  Although initial steady state observations can help predict survival in SCA, the longitudinal course of a patient may give additional prognostic information.
authors.affiliation: Department of Medical Oncology and Hematology, Yale New Haven Medical Center, New Haven, CT, 06510, United States of America.
authors.forename: Susanna A
authors.initials: SA
authors.lastname: Curtis
authors.affiliation: Division of Hematology, Department of Medicine and Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, 10467, United States of America.
authors.forename: Neeraja
authors.initials: N
authors.lastname: Danda
authors.affiliation: Division of Hematology, Department of Medicine and Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, 10467, United States of America.
authors.forename: Zipora
authors.initials: Z
authors.lastname: Etzion
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, 10467, United States of America.
authors.forename: Hillel W
authors.initials: HW
authors.lastname: Cohen
authors.affiliation: Division of Hematology, Department of Medicine and Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, 10467, United States of America.
authors.forename: Henny H
authors.initials: HH
authors.lastname: Billett
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000378:metabolism / Q000401:mortality*; D015415:Biomarkers / Q000097:blood*; D002648:Child; D003404:Creatinine / Q000097:blood*; D005260:Female; D005319:Fetal Hemoglobin / Q000378:metabolism*; D006801:Humans; D007958:Leukocyte Count; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005319:Fetal Hemoglobin; D003404:Creatinine