1. Emily S. Moses, M.D. September 13, 2017
Sickle Cell Disease
Emily S. Moses, M.D.
September 13, 2017

2. Sickle Cell Disease Facts
Affects ~100,000 Americans
1/365 African American births
1/16,300 Hispanic American births
1/13 African American babies has sickle cell trait

3. History 1870s: First described in African medical literature
“Ogbanjes” ("children who come and go")
1910: First case of sickle cell anemia described in a U.S. medical journal by Dr. James Herrick
The patient was Walter Clement Noel of Grenada who suffered from acute chest syndrome, a common complication of sickle cell disease
Dental College of Dental Surgery
Leg ulcers
ACS
Dr. Herrick & Dr. Irons; peculiar elongated and sickle-shaped red blood cells 1910; 2010 was 100 years of SCD
Died at 32yo; pneumonia; buried in a churchyard that overlooks the Carribean Sea
2ND case was described at UVA; Ellen Anthony (cook & house maid)

4. Herrick J. Archives of Internal Medicine, November 1910

5. History
In February of 1911, Benjamin E. Washburn, a 4th year medical school student at UVA, published the 2nd case report of sickle cell disease
The patient, Ellen Anthony, frequently received charity care from the UVA hospital from 1907 through 1918
Savitt T. “The Second Reported Case of Sickle Cell Anemia: Charlottesville, Virginia, 1911” Virginia Medical Quarterly, Spring 1997

6. Savitt T. “The Second Reported Case of Sickle Cell Anemia: Charlottesville, Virginia, 1911” Virginia Medical Quarterly, Spring 1997

7. History
1963
Sir John Dacie “Sickle Cell Anemia is essentially a disease of childhood.”
1973
Average life expectancy was 14.3 years
20% of patients died in the first 2 years of life
2000’s
Nearly all patients survive to adulthood

8. What is Sickle Cell Disease (SCD)?
Group of inherited disorders of red blood cells
Hemoglobin S forms due to a mutation of the Beta globin gene on chromosome 11
Defect occurs because of a single amino acid substitution
Glutamic Acid is replaced by Valine
Results in defective hemoglobin protein that causes the production of misshapen red blood cells
Sickle cells die early, causing shortage of red blood cells
Sickle cells get stuck in small blood vessels causing pain and other problems

9. Hemoglobin www.slideshare.net/NCSLS/hemoglobin-structure-67264726

10. Hemoglobin A
Hemoglobin S

11. Common Types of SCD Sickle Cell Anemia Hb SS
Hb S Beta thalassemia null
Hb SC
Hb S Beta thalassemia +

12. How is SCD inherited?
Autosomal Recessive

13. How is SCD diagnosed? Newborn screening FS – Hb SS or Hb S Beta null
FSA – Hb S Beta +
FSC – Hb SC
FAS – sickle cell trait

14. High Performance Liquid Chromatography (HPLC)
How is SCD diagnosed?
Isoelectric Focusing
High Performance Liquid Chromatography (HPLC)
erasmeinfo.ulb.ac.be/globule/English/sickle_diag.htm

15. How is SCD diagnosed? Hemoglobin electrophoresis

16. Acute Complications of Sickle Cell Disease
Vaso-occlusive Crisis
Fever
Acute chest syndrome
Stroke
Splenic sequestration
Priaprism
Aplastic anemia

17. Vaso-occlusive Crisis (VOC)
Occurs because of red blood cell sickling, small blood vessel occlusion and tissue ischemia/reperfusion
Most common cause of acute morbidity
Associated with severity of disease and early mortality among young adults
Most common triggers:
Cold temperature, cold water, dehydration, overexertion, and menses
Management:
NSAIDs, Opioids, Correct dehydration
In addition to these acute episodes of more severe pain, pain in patients with sickle cell is often chronic, underrecognized and underreported, and therefore undertreated

18. Fever
Patients with SCD are at increased risk of severe bacterial infection, because of impaired or absent spleen function
High risk of sepsis and meningitis from Streptococcus pneumoniae
Incidence of invasive pneumococcal infection is decreased due to use of prophylactic penicillin and pneumococcal vaccine, however fever is still considered an emergency

19. Acute chest syndrome
2nd most frequent reason for hospitalization in children and adults
Most common cause of death
Manifests as fever, signs and symptoms of respiratory distress, and an infiltrate on chest x-ray
Management: hospitalization,
antibiotics, possible blood
transfusion, do not fluid overload,
use incentive spirometry
reference.medscape.com/features/slideshow/sickle-cell#8

20. Stroke
To prevent stroke, in all children with HbSS or HbSBeta null, a transcranial doppler (TCD) is done yearly from 2 – 16 yrs of age
If at any time it is abnormal, the patient begins chronic transfusions or exchange transfusions to keep their Hb S < 30%
Without primary stroke prevention, 20-35% of children with HbSS have silent cerebral infarcts,
can cause cognitive decline
predisposes them to additional silent infarcts and overt strokes

21. Acute Anemia Splenic sequestration Aplastic crisis
Sudden enlargement of the spleen and reduction in hemoglobin concentration by at least 2 g/dL below the patient’s baseline value
Teach parents to palpate for the spleen
Aplastic crisis
Presents often with fever, lethargy, rapid heart rate, and occasionally heart failure
Hemoglobin is usually far below a patient’s baseline and the reticulocyte count (estimate of if the bone marrow is making red blood cells) is decreased or 0
Parvovirus B19

22. Priaprism Sustained, unwanted painful erection lasting 4 or more hours
Affects 35% of boys/men
Delayed diagnosis and therapy can result in impotence
Management: hydration and pain meds, may need surgical intervention

23. Chronic Complications of SCD
Avascular Necrosis
Chronic pain
Renal complications
Pulmonary Hypertension
Recurrent Priaprism

24. How far have we come? Newborn screening
Effective vaccination against pneumococcal disease
Hydroxyurea - only medication ever shown to decrease complications and increase life expectancy
Prophylactic penicillin
Bone marrow transplant

25. Where do we go from here?
People with SCD have less access to comprehensive care versus people with genetic disorders such as hemophilia and cystic fibrosis

26. Sickle Cell Trait and the Athlete
National Association of Athletic Trainers published a Consensus Statement in 2007
Since 2000, 9 athletes with sickle cell trait have died following collapse after exertional exercise
In over a decade, 136 sudden non-traumatic sports deaths in high school & college; 5% related to exertional sickling
Newborn Screen Results or Testing for all student athletes
SCDAA: “Nevertheless this approach carries great risk of stigmatization and discrimination against athletes with sickle cell trait. The NCAA mandate for sickle trait screening does not provide adequate assurance of the privacy of genetic information nor protection from the discriminatory use of such information.”

27. Don’t Forget: September is National Sickle Cell Awareness Month!