Sickle Cell Disease: Core Concepts for

the Emergency Physician and Nurse

Epidemiology, Genetics, Pathophysiology

Paula Tanabe, PhD, RN, FAEN, FAAN

Associate Professor
Duke University, Schools of Nursing and Medicine
 Objectives
• Identify the genotype associated with the most severe form of
sickle cell disease (SCD)
• Identify the median lifespan for individuals with SCD
 Pretest- Question 1
Which genotype is associated with the most severe
symptoms?
a. SS
b. SC
c. SB0
d. SB+
 Pretest- Question 2
What is the median lifespan for most individuals with SCD?
a. 20’s
b. 30’s
c. 40’s
d. 50’s
 Epidemiology of SCD
• SCD is a genetic disease affecting70,000 – 100,000
Americans, primarily of African descent 1
– 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
 SCD Common Genotypes

Genotype Approximate % of US Patients

• Sickle cell anemia (SS, most 65 %
severe form)
• Sickle/Hb C disease (SC, lesser
severity, but can still have pain 25 %
episodes, and life-threatening
complications)
• Sickle/Beta plus thalassemia 8%
(Sβ thalassemia, similar to SC)
+

• Sickle/Beta zero thalassemia

(Sβ° thalassemia, similar to SS) 2%
 Comparison of Life Expectancy
US Population vs. Sickle Cell Disease
 Changes in Life Expectancy
• National Center for Health Statistics 3
• 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 Sickle
• Biconcave disc-shaped • Sickle-shaped
• Deformable • Rigid
• Life span of 120 days • Life span of 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
• 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 &
the endothelial surface which
enhances the VOC process
• Results in tissue damage,
hypoxia, necrosis, & 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*
 Clinical Scenario

• Cut and paste this link into your browser to

view this short video
• https://www.youtube.com/watch?v=Uu5VTET
lbZM&feature=youtu.be
 Posttest- Question 1
Which genotype is associated with the most severe
symptoms?
a. SS
b. SC
c. SB0
d. SB+
 Posttest- Question 2
What is the median lifespan for most individuals with SCD?
a. 20’s
b. 30’s
c. 40’s
d. 50’s
 Posttest Answers & Rationale
• Question 1
– Answer : a) SS
– Rationale: 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.
• Question 2
– Answer: c) 40’s
– Rationale: The median lifespan continues to be 48 for females
and 42 for males.
 References
1. Hassell KL. Population estimates of sickle cell disease in the U.S. Am J Prev Med.
2010;38(4S):S512-S521.
2. Platt et al. Mortality in sickle cell disease, life expectancy and risk factors for early
death. NEJM 1994. 330: 1639-44.
3. 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
4. http://wonder.cdc.gov/controller/datarequest/D79