Yohan Kim

 First to described in 1904 by James B. Herrick. ◦ Found “elongated and sickle-shaped” red blood cells (RBCs) from a patient suffering from anemia  A multisystem disease, associated with episodes of acute illness and progressive organ damage  Most common in African heredity population ◦ Occurs in about 1 of every 500 births  Clinical management of sickle cell disease is still basic and no drugs have been developed that specifically target the pathophysiology of this disease  Affects about 70,000 people in the US

 2 Types of Hemoglobin HbF(More O2), HbA(Less O2) ◦ Newborn – 5:5~8:2, 6 months – 1:99  Sickled hemoglobin is caused by a mutation of the gene of HbA  In the amino acid sequence valine takes the place of glutamic acid at the sixth position.  HbA become C-shaped or sickled when the patient’s oxygen saturation is low.

 Reduced flexibility impairs blood flow through vessels  Repeated de-oxygenation can damage the cells enough to make sickling permanent  short-lived (10 to 20 days instead of the normal 120 days)

 No clear symptoms shown  Indications may be visible during growth  Newborns usually of normal length and weight at birth  Develop a gradually increasing deficit in height and weight as they age  After time of the normal adolescent growth spurt, they begin to catch up with their normal peers. ◦ (Girls 15 to 17, boys 18 to 19)  Delayed puberty also occurs.

 Treatment of sickle cell crisis is usually symptomatic  Referring the patient immediately

 Based on analysis of hemoglobin  Protein electrophoresis or chromatography  Hemoglobin mass spectrometry and DNA analysis increasingly used ◦ Enable high-throughput testing.

 HbSS - inherited two sickle cell genes (S); one from each parent. ◦ The most common type  HbSC - inherited a sickle cell gene (S) from one parent and a gene for abnormal hemoglobin (C) from the other ◦ 20% to 30% of cases, usually a milder form of sickle cell disease. ◦  HbS beta thalassemia - one sickle cell gene from one parent and one gene for beta thalassemia from the other parent.  Other: HbSD, HbSE, and HbSO -inherited one sickle cell gene and one gene for an abnormal type of hemoglobin  HbAS - sickle cell trait

 Not a disease, generally regarded as an asymptomatic condition.  When compared to controls, is no difference  Some physiological differences during exercise or at high altitudes  Following exercise -> increase in the number of sickled cells. ◦ exertional sickling  The presence of sickled cells after physical exertion is even greater at higher altitudes

 Explanations for sudden deaths due to sickle cell anemia are not entirely clear.  Data indicate an association between sickle cell trait and sudden death there is no direct evidence of causation.  Dehydration, hyperthermia and acidosis associated with extreme physical exertion suggested  Results include rhabdomyolysis (muscle break-down), acute renal failure and coronary vasoconstriction

 Hydroxyurea (medication) ◦ Oral efficacy and low toxic effects ◦ Increase hemoglobin concentrations ◦ Decreasing platelet and white cell counts ◦ Changing expression of adhesion molecules ◦ Nitric oxide generation

 Red blood cell transfusion ◦ Corrects anemia ◦ Decreases the percentage of sickled hemoglobin ◦ Suppresses sickle synthesis, ◦ Reduces polymerization. ◦ Necessary if the hemoglobin concentration is high, or if rapid decrease in sickled hemoglobin percentage needed

 Hematopoietic stem cell transplantation ◦ AKA bone marrow ◦ The only cure for sickle cell disease ◦ First bone marrow transplantation for sickle cell in 1983 on 8-year-old patient with leukemia and sickle cell disease  The bone marrow transplantation cured both diseases

 Hematopoietic stem cell transplantation ◦ Indications 1.Stroke or CNS event lasting longer than 24 hours 2.Abnormal brain MRI 3.Elevated transcranial Doppler 4.Acute chest syndrome with recurrent hospitalizations 5.Two or more vaso-occlusive crises requiring hospitalizations 6.RBC alloimmunization

 Splenectomy ◦ The spleen is the organ most often affected by sickle cell disease. ◦ To prevent complication ◦ Also reduces patients’ need for transfusion ◦ Decreases splenic complications ◦ Further eliminates pain

 Acute pain - most common cause of hospital admission  Infection - major cause of morbidity and mortality  Stroke  Acute chest syndrome - second most common cause of hospital admission  Pulmonary hypertension  Heart disease  Renal complications - almost inevitable, hemoglobin polymerize in the renal medulla, because of the low oxygen

 About 90% of patients survive to age 20  Close to 50% survive beyond the fifth decade.

 No methods to prevention sickle cell disease  Screening and diagnosing sickle cell in advance will help prevent complications in the future  Engaging and educating patients before complications begin are also good ways of preventing complications.

 A college football player with sickle cell trait (SCT) who collapsed minutes after running 16 successive sprints of 100 yards each at sea level.  The player, 19 year old, African American, was apparently healthy when running.  No exertional heat illness was present.  After collapsing, went into coma and developed fulminant rhabdomyolysis, profound lactic acidosis, acute myoglobinuric renal failure, refractory hyperkalemia, and disseminated intravascular coagulation.  Died about 15 hours after admission to hospital

 Cause of death was acute exertional rhabdomyolysis associated with SCT  appears that sickling can begin within 2-3 minutes of maximal exertion and can reach grave levels very soon  Being urged on by coaches can pose problem  Heat, dehydration, altitude, and asthma can increase the risk  Screening and simple precautions can prevent this unique syndrome and enable SCT athletes to thrive in their sports

 1. Redding-Lallinger R, Knoll C. Sickle cell disease--pathophysiology and treatment. Current Problems In Pediatric And Adolescent Health Care. 2006;36(10):346–376.  2. Parrish M R, Morrison J C. Sickle cell crisis and pregnancy. Seminars in Perinatology. 2013;37(4):274–279. doi: /j.semperi  3. Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010;376(9757):2018–2031. doi: /S (10)61029-X.  4. Sheth S, Licursi M, Bhatia M. Sickle cell disease: time for a closer look at treatment options? British Journal Of Haematology. 2013;162(4):455–464. doi: /bjh  5. Apanah S, Rizzolo D. Sickle cell disease: Taking a multidisciplinary approach. JAAPA: Journal of the American Academy of Physician Assistants (Lippincott Williams & Wilkins). 2013;26(8):28–33. doi: /01JAA d4.  6. Aloe A, Krishnamurti L, Kladny B. Testing of collegiate athletes for sickle cell trait: what we, as genetic counselors should know. Journal Of Genetic Counseling. 2011;20(4):337–340. doi: /s  7. Anzalone ML, Green VS, Buja M, Sanchez LA, Harrykissoon RI, Eichner ER. Sickle Cell Trait and Fatal Rhabdomyolysis in Football Training: A Case Study. Medicine & Science in Sports & Exercise. 2010;42(1):3–7.