AN ABSTRACT OF THE THESIS OF
Nancy Jade Lee for the degree of Honors Baccalaureate of Science in
Biochemistry & Biophysics presented on June 5, 2006. Title: Validation of Early
Predictors of Outcome in the Dallas Newborn Cohort
Abstract approved:
______________________________________________________
Kevin G. Ahern
Sickle cell disease (SCD) is a phenotypically variable disorder of hemoglobin that leads
to abnormally shaped and dysfunctional red blood cells. Several studies have attempted
to construct early predictive models for SCD, including Miller et al.’s (2000) model
which uses easily identifiable predictors in early life. The primary aim of this project is
to validate the model of Miller et al. in the Dallas Newborn Cohort, the world’s largest
newborn inception cohort of sickle cell disease. Specifically, we tested the predictive
utility of three clinical findings in the first years of life: painful swelling of the hands and
feet (dactylitis), severe anemia (Hgb <7 g/dL), and elevation of white blood cell count
(leukocytosis) for later complications, which includes death, stroke, painful episodes, and
acute chest syndrome. The predictive utility of the Miller model was found to be fairly
poor in the Dallas Newborn Cohort. None of the patients with an adverse outcome was
properly identified by the model. Thus, the Miller model is not practical to operate as a
guide to influence clinical decisions about early disease-modifying interventions for
young children with SCD.
Keywords: sickle cell disease
©Copyright by Nancy Jade Lee
June 5, 2006
All Rights Reserved
Validation of Early Predictors of
Outcome in the Dallas Newborn Cohort
by
Nancy Jade Lee
A PROJECT
Submitted to
Oregon State University
University Honors College
In partial fulfillment of
The requirements for the degree of
Honors Bachelor of Science in Biochemistry & Biophysics
(Honors Scholar)
Presented June 5, 2006
Commencement June 2006
Honors Baccalaureate of Science in Biochemistry & Biophysics project of Nancy
Jade Lee presented on June 5, 2006.
APPROVED:
Mentor, representing the Department of Biochemistry & Biophysics
Committee Member, representing Children’s Medical Center Dallas
Committee Member, representing the Department of Biochemistry & Biophysics
Dean, University Honors College
I understand that my project will become part of the permanent collection of
Oregon State University, University Honors College. My signature below
authorizes release of my project to any reader upon request.
Nancy Jade Lee, Author
ACKNOWLEDGMENT
I would like to express my appreciation and gratitude to Drs. Charles T. Quinn
and George Buchanan for providing me with an amazing opportunity to work
with children with sickle cell disease at the Center for Cancer and Blood
Disorders at Children’s Medical Center on the campus of University of Texas,
Southwestern Medical Center at Dallas, Texas. I would also like to acknowledge
Dr. Quinn’s support and guidance, which, without, I would not have been able to
write this manuscript. I appreciate the patience and help of each of my committee
members, and especially Dr. Kevin Ahern, my mentor, for pushing me to excel in
everything I do.
TABLE OF CONTENTS
_______________________________________________________Page
INTRODUCTION…………………………………………………..……….. 1
BACKGROUND…………………………………………………..………… 3
SYMPTOMS AND COMPLICATIONS….…………………….…………... 5
AVAILABLE THERAPIES…….……………………………….………….. 8
OBJECTIVE…………..…………………………………………………….. 10
MATERIALS AND METHODS……………………...…………………….. 13
DATA ANALYSIS……………….………………………………..………... 17
DISCUSSION AND CONCLUSION….…………………………..………... 20
BIBLIOGRAPHY…………………………………………...……………….. 21
LIST OF FIGURES
Figures
Page
Figure 1: Sickled erythrocytes……………………………….……..….2
Figure 2: Hemoglobin molecule with 2 α globins and two β globins….4
Figure 3: Ten Redefined by Hertz Nazaire…………………………..... 5
Figure 4: Estimated Probability of Severe Sickle Cell Disease.......…. 11
Figure 5: Receiver operating characteristic..………………………… 19
Tables
Page
Table 1: Characteristics of Subjects………………….………………. 17
Table 2: Early predictors……………………….…………………….. 17
Table 3: Adverse Events……………………………………………… 17
Table 4: Miller et al Model in the Dallas Newborn Cohort…………... 18