Sickle Cell Disease
Core Concepts for the Emergency
Physician and Nurse
Epidemiology, Genetics, Pathophysiology
Spring 2013
Paula Tanabe, PhD, RN, FAEN, FAAN
Associate Professor
Duke University, Schools of Nursing and Medicine
Epidemiology of SCD
• SCD is a genetic disease affecting 70,000 – 100,000 Americans,
primarily of African descent (Hassell, 2010)
• Most common genetic disease among blacks
• SCD occurs in 1 of every 500 black births
• 1:1,100 Hispanics (eastern states)
• 1:32,000 Hispanics (western states)
• SCD occurs in many other ethnic groups, including Northern
Europeans and those that live in the Middle Eastern Countries
• 1:12 African-Americans are carriers (trait) for the disorder
Comparison of Life Expectancy
US Population vs. Sickle Cell Disease
Changes in Life Expectancy
• National Center for Health Statistics (CDC)
• Compared 1999-2007 with 1979-1998
• Largest declines in ages 0-4
• Smaller but significant declines up to age 19
– Due to prophylactic treatment with penicillin and vaccinations
– Transcranial doppler screening identifies children at risk of stroke;
placed on chronic transfusion therapy to prevent stroke
• No differences in the 20-24 age group
• Increase in death rate ages: 45-54, 55-65, and 65-75
What is the pathophysiology?
Normal Vs. Sickle Red Cells
Normal
• Biconcave disc-shaped
• Deformable
• Life span of 120 days
•
•
•
•
Sickle
Sickle-shaped
Rigid
Live for 20 days or less
Sticky surface, abnormal
properties
Prolonged Sickling of RBC’s
• After recurrent episodes of
sickling
– membrane damage occurs
– cells not capable of
resuming biconcave shape
upon re-oxygenation
• Deformed sickle cells adhere
to endothelium &
macrophages
– induces hemolytic process
Hemolysis and Vaso-occlusion
Hemolysis:
▪ Anemia in SCD is caused
by red cell destruction, or
hemolysis
▪ The degree of anemia
varies widely between
patients
▪ Red cell production by the
bone marrow increases
dramatically, but is unable
to keep pace with the
destruction
Vaso-occlusion:
• Complex process initiated
by rigid and abnormally
shaped sickled RBC’s
• Abnormal adhesion occurs to
the endothelium
• Activation of WBC’s, RBC’s
and the endothelial surface
which enhances the VOC
process
• Results in tissue damage,
hypoxia, necrosis and organ
dysfunction
Acute and Chronic Manifestations
Acute Manifestations:
• Bacterial sepsis or
meningitis*
• Recurrent vaso-occlusive pain
(dactylitis, musculo-skeletal
or abdominal pain)
• Splenic sequestration*
• Aplastic crisis*
• Acute chest syndrome*
• Stroke*
• Priapism
• Hematuria, including
papillary necrosis
*Potential cause of mortality
Chronic Manifestations:
• Anemia
• Jaundice
• Splenomegaly
• Functional asplenia
• Cardiomegaly and functional
murmurs
• Hyposthenuria and enuresis
• Proteinemia
• Cholelithiasis
• Delayed growth and sexual
maturation
• Restrictive lung disease*
• Pulmonary hypertension*
• Avascular necrosis
• Proliferative retinopathy
• Leg ulcers
• Transfusional hemosiderosis*
Sickle Cell Disease (SCD)
Common Genotypes
Genotype
Sickle cell anemia (SS, most severe
form)
Sickle/Hb C disease (SC, lesser
severity, but can still have pain
episodes, and life-threatening
complications)
Sickle/Beta plus thalassemia (Sβ+
thalassemia, similar to SC)
Sickle/Beta zero thalassemia
(Sβ° thalassemia, similar to SS)
Approximate % of US
Patients
65 %
25 %
8%
2%
References
• Hassell KL. Population estimates of sickle cell disease in the U.S. Am J
Prev Med. 2010;38(4S):S512-S521.
• Platt et al. Mortality in sickle cell disease, life expectancy and risk
factors for early death. NEJM 1994. 330: 1639-44.
• Hamideh, D. Trends in Mortality Among Patients with SCD in the
United States. Is there any change in the past 10 years? 2012. 6th
Annual Sickle Cell Disease Research and Educational Symposium &
Annual National SCD Scientific Meeting
• http://wonder.cdc.gov/controller/datarequest/D79
Post-Test
1.
Which genotype is associated with the most severe
symptoms?
a) SS
b) SC
c) SB0
d) SB+
Post-Test
2. What is the median lifespan for most individuals with
SCD?
a)
20’s
b)
30’s
c)
40’s
d)
50’s
Post Test Answers
1.
A – Patients with SS have the most severe form of the
disease which is associated with more complications.
However, all patients can experience pain and multiple
other complications.
2. C – The median lifespan continues to be 48 for females
and 42 for males.