Life Expectancy and Risk Factors for

Early Death In Sickle Cell Disease

Preparedby :Saksham Pokharel

Ruchi Sharma
Samjana Chaudhary
Satya Saroj Sahani
Sashi Fauder
Crimson College of Technology
Department of Laboratory Technology
Butwal-11, Devinagar, Rupandehi, Nepal 1
 Contents
• Introduction
• Materials and methods
• Result
• Conclusion

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 Introduction

 Sickle cell disease is the most common

hematologic hereditary disorder in humans.
SCD is characterized by vaso-occlusive
episodes due to erythrocyte sickling ,
hemolytic anemia and increased susceptibility
to infections.
 Chronic organ damage can be observed with
high mortality, depending on the involved
organ.

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 The life expectancy of patients with sickle celll
disease has improved considerably since 1960,
when Sir John Dacie described sickle cell
disease as essentially a disease of childhood.
 He wrote the mortality rate is high and
relatively only few patients reach adult life,
even when the standard of medical care is high.
 A low level of fetal hemoglobin, a low level of
total hemoglobin and an elevated base-line
white cell count were associated with an
increased risk of death.
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 Materials and methods
 The co-operative study of sickle cell disease
(CSSCD) is a prospective study of clinical
course of sickle cell disease in which more than
3764 patients were enrolled from birth to 66
years of age at 23 clinical centers throughout
the continental United States.
 Patients were enrolled at these centers between
1978 and 1988 and were seen at regular
intervals for laboratory evaluation and physical
examination.
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 At enrollment, genotype was determined by
review of hematologic data and by qualitative
hemoglobin electrophoresis.
 The laboratory results analyzed in this report
were obtained at routine visits, not during acute
illness.
 All the acute and chronic illness were
documented at these centers.
 For all patients with sickle cell anemia or sickle
cell-hemoglobin C disease , proportional-
shazarads regression and 2L program of BMDP
to model age at death.
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 The Cnaan and Ryan approach is appropriate
for analysis of data in this study.
 The probability of survival 10 years after
enrollment was estimated as:
P2/ P1
where P1= proportion of the study population
alive at the beginning of decade
P2= proportion alive at end.
 The proportion were estimated from Kaplan-
Meier plots.

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 Therefore this study concentrated on risk
factors for early death among the patients over
20 years of age.
 This study investigated about the circumstances
of death in 209 patients with sickle cell disease
who were 20 years of age or older when they
died.
 For each patients, review of the complete roster
forms of recording chronic and acute
complications and schedule visits to medical
center, the death form , final hospital discharge
summary and autopsy report was done.
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 Results

Genotype and No:of patients Age at Entry Average follo- No: of death
sex up

SCA, no
thalassemia
Male 602 12.6±10.08 7.84 35
Female 684 14.7±12.2 7.89 22
SCA with
thalassemia
Male 283 13.5 ±12.5 7.59 16
Female 285 15.7 ±13.2 7.98 13
SCA Unmapped
Male 344 12.6 ±12.6 3.72 58
Female 344 14.0±12.6 4.04 66
SCA Hb-C
disease
Male 417 11.5 ± 12.0 6.10 15
Female 427 15.5 ±15.4 6.44 12

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Sickle cell-β+
thalassemia
Male 91 13.7 ±12.0 5.97 3
Female 100 17.7 ±13.8 6.42 2

Sickle cell-β0
Thalassemia
Male 107 15.6 ±11.9 7.07 5
Female 80 15.2±10.9 7.37 2

Table 1: Characteristics of Patients in the Cooperative Study of Sickle

Cell Disease

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Table 2: Cricumstances of death in 209 patients with sickle cell
diease who were 20 years of Age or older at the time of death

Patients without evidence of chronic Number

renal failure, heart faiure or chronic
debiliating stroke
Pain episode 45
Chest syndrome 9
Stroke 15
Infection 13
Perioperative death 14
Cancer 4
GI bleeding 3
Suddenly at home 10
Trauma 14
Miscellaneous 7
Circumstances not known 37
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Patients with clinically diagnosed chronic
organ failure

Chronic renal failure 22

Chronic congestive heart failure 11

Chronic debiliating stroke 5

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Table 3: Acute and chronic conditions as risk factors for early death in patients with sickle cell
anemia who were 20 years of age or older

Variable Definition Variable estimate P value

Sepsis +ve blood culture 0.70± 0.36 0.07
Seizures Major and minor 1.32 ± 0.36 0.002
seizures, not stroke
or meningitis
Right upper Clinic visit with any 0.40± 0.28 0.17
quadrant syndrome 2 : right upper
quadrant pain,
twofold elevation in
base-line bilirubin
or alanine
aminotransferase
level, 2 cm increase
in base-line liver
span
Acute Stroke Acute neurologic 0.48± 0.59 0.45
syndrome from
hemorrage or
occlusion

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Acute anemic 30% decrease in 0.48 0.59 0.45
episode base-line
hemoglobin level,
no bleeding
Febrile episode Clinic visit with 0.66± 0.27 0.02
documented
temperature
>38.3C(oral) or >
38.9C(rectal)
Leg Ulcer Skin ulcer on lower 0.38± 0.29 0.21
legs, unhealed in 14
days
Avascular necrosis Early radiographic -0.18± 0.29 0.53
changes
UTI infection Dysuria and >20 0.09± 0.24 0.72
white cells per high
power field or >
10^5 colonies per
ml

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Renal failure 20% increase in 1.60 ± 0.40 0.001
base line creatinine
level and
creatinine
clearance <
100ml/min
Pain episode Clinic visit for pain 0.59 ± 0.22 0.01
lasting more than 2
hr
Acute chest Clinic visit with new 0.97± 0.26 <0.001
syndrome pulmonary infiltrate
or abnormal lung
scan
Surgery Surgical procedure 0.05± 0.23 0.82

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Table 4: Laboratory Values as risk factors for early death in
patients with sickle cell anemia who were 20 years of age or older

Variable Variable estimate P value

Hemoglobin -0.26± 0.089 0.003
Fetal hemoglobin -0.11± 0.04 0.001
White-cell count 0.13± 0.04 <0.001
Mean corpuscular volume -0.003± 0.01 0.81
Platelet count 0.001± 0.001 0.43
Blood urea nitrogen 0.02± 0.01 0.09
Bilirubin 0.01± 0.06 0.88
Creatinine 0.12± 0.20 0.57
Alanine amino transferase 0.004± 0.004 0.40
Alpha-thalassemia 0.002± 0.23 0.99

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Table 5: Risk factors for early death in patients with sickle
cell anemia who were 20 years of age or older

Variable Variable estimate P value

Fetal hemoglobin(%) -0.09± 0.04 <0.001

Acute chest syndrome 0.80± 0.27 0.005

Renal failure 1.10± 0.47 0.03

Seizures 0.91± 0.42 0.04

White-cell count 0.10± 0.04 0.01

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 Conclusion
 This study concluded that the most important
risk factor were high white cell count and low
fetal hemoglobin level. Also the patients with
white-cell count over 15000 per cubic
milimeter were at increased risk.
 Patients with high level of fetal Hb had an
improved life expectancy
 This study resulted that risk factor for SCD is
independent of smoking which is known to
raise the base-line white cell count.
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 This study revealed that ,the children will die
earlier of adults who had low level of fetal
hemoglobin than those who had high levels.
 The fetal hemoglobin level should be
considered as an important factor in selecting
children for high-risk interventions such as
bone-marrow transplantation and long term
treatment with agents that stimulate the
production of fetal hemoglobin.

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 References
Platt S O, Brambilla J D, Rosse F W, Castro O,
Steinberg H M, Klug P P et al (2022), Life
expectancy and risk factors for Early Death In
Sickle Cell Disease, The New England Journal
of Medicine, 330 (23).

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