Sickle Cell DiseaseCore Concepts for the

Emergency Physician and Nurse

Epidemiology, Genetics, PathophysiologySpring 2013

Paula Tanabe, PhD, RN, FAEN, FAANAssociate 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 ExpectancyUS 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

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

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

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*

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

Acute and Chronic Manifestations

*Potential cause of mortality

Sickle Cell Disease (SCD) Common Genotypes

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)

65 %

25 %

8 %

2 %

Genotype Approximate % of US Patients

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) SSb) SCc) SB0

d) SB+

Post-Test

2. What is the median lifespan for most individuals with SCD?a) 20’sb) 30’sc) 40’sd) 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.