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

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 www.cdc.gov

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 Student @Chicago 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)

Herrick J. Archives of Internal Medicine, November 1910

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

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

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

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

Hemoglobin www.slideshare.net/NCSLS/hemoglobin-structure-67264726 http://www.studydroid.com/printerFriendlyViewPack.php?packId=580177

Hemoglobin A Hemoglobin S

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

How is SCD inherited? Autosomal Recessive www.cdc.gov

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

High Performance Liquid Chromatography (HPLC) How is SCD diagnosed? Isoelectric Focusing High Performance Liquid Chromatography (HPLC) www.researchgate.net/figure/51804206_fig1_Isoelectric-focusing-analysis-of-red-blood-cells-lysates-containing-different-Hb erasmeinfo.ulb.ac.be/globule/English/sickle_diag.htm

How is SCD diagnosed? Hemoglobin electrophoresis http://slideplayer.com/slide/4463236/

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

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

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

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 http://www.nrsg101.com/incentive-spirometry.html reference.medscape.com/features/slideshow/sickle-cell#8

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

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

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

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

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

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

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.”

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