Sickle Cell Anemia

1. Sickle Cell Anemia By Sarah Ahmad

2. Definition Sickle cell anemia is: • a genetic and inherited disease • a chronic form of haemolytic anemia Sickle cell anemia gets its name from the shape of the blood cells (crescent, or sickle) that are characteristic of this disease.

3. Causes • Red blood cells get their colour from hemoglobin, which carries oxygen • A change in an amino acid in the hemoglobin molecule turns it to hemoglobin S (sickle hemoglobin)

4. Causes • Sickle hemoglobin cells are structurally fragile and die off quicker • the blood cell collapses from oxygen deprivation (since hemoglobin carries oxygen)

5. Sickle Cell Anemia • Individuals with sickle cell anemia have 2 sickle hemoglobin genes (homozygotes) • Sickle cell anemics produce more hemoglobin S than hemoglobin A

6. Sickle Cell Anemia Sickle cell anemia is more common in individuals from Africa, South or Central America, the Caribbean Islands, India, the Middle East, and Mediterranean countries such as: • Turkey • Greece • Italy

7. Sickle Cell Anemia - Stats • 70,000 – 100,000 individuals in the U.S have sickle cell anemia • Sickle cell anemia occurs in approximately 1 out of 500 African American births

8. Sickle Cell Trait • Individuals with sickle cell trait have only 1 hemoglobin S gene (heterozygotes) • Heterozygotes produce both hemoglobin S and A • Usually have few symptoms • May have medical problems

9. Sickle Cell Trait - Stats • 1 out of 12 African Americans have this condition • More than 2 million Americans have sickle cell trait

10. Sickle Cell Anemia Genetics

11. History Dr. Linus Pauling (1901 – 1994) identified the basis of sickle cell anemia, a flaw in the hemoglobin molecule that causes this condition.

12. History • This flaw altered the electric charge of the hemoglobin molecule, causing it to behave differently in an electrical field • This fact was used to detect the abnormal hemoglobin molecules

13. History • Sickle cell anemia was the first condition to be linked to the family of specific sections of DNA that contain the aberrant gene (in 1978)

14. History • Sickle hemoglobin gene originated thousands of years ago in Africa, the Mediterranean basin and the Middle East, where malaria was common • Individuals with sickle cell trait had a survival advantage

15. History Spread of this condition was caused by: • favoured individuals (who had sickle cell trait) passing their genes to their offspring (natural selection) • offspring with sickle cell trait migrating and spreading this condition over a long period of time

16. Malaria & Sickle Cell Trait Areas with malaria vs. areas with sickle cell trait in Africa.

17. Malaria & Sickle Cell Trait • Sickle cell trait is no longer a survival advantage (against malaria) because of medicine • Instead it is a problem, since 2 sickle hemoglobin genes mean sickle cell anemia and medical problems

18. Effects/Symptoms • Symptoms of sickle cell anemia are extremely variable • Some symptoms include: growth retardation, leg ulcers, fatigue, delay in secondary sexual development, ocular abnormalities, gallstones, jaundice, and stroke

19. Effects/Symptoms (video) • Main effect is the deprivation of oxygen, caused by the shape of the sickle cells which blogs blood vessels • Oxygen deprivation = more sickling = more oxygen deprivation

20. Effects/Symptoms • Vessel clogging and deprivation of oxygen = pain and can lead to organ damage • Sickling is most likely to happen after oxygen is released to the body, in small capillaries

21. Effects/Symptoms - Crises • Most common symptom is the incidence of crises, which are caused when there is little oxygen in the blood • Crises are painful recurrent attacks and may require hospitilization

22. Effects – Hand-foot Syndrome • Occurs when small blood vessels in the hands and feet are blocked by sickle cells • Most likely to occur in children under 4 years of age • Can cause pain, swelling, and fever

23. Effects – Splenic Crisis • Occurs when the spleen, an organ that filters blood and fights infections, traps too many red blood cells • Causes the spleen to enlarge and anemia • Blood transfusions might be needed

24. Effects – Infections • Children and adults with sickle cell anemia are more susceptible to infections and have trouble fighting them off because of the affected spleen

25. Effects – Acute Chest Syndrome • Acute chest syndrome is a fatal condition similar to pneumonia • Could be caused by sickle cells in the lungs or infections

26. Effects – Pulmonary Hypertension • Rise of the blood pressure in the lungs due to small vessels damaged by sickle cells

27. Effects – Growth Retardation • Children with sickle cell anemia grow slower and reach puberty later due to the shortage of red blood cells • Adults are usually smaller in size

28. Effects – Blindness • The retina can be damaged by sickle cells that affect small blood vessels • This can cause blindness (no oxygen to the eyes)

29. Effects – Gallstones • Gallstones are caused by too much bilirubin • Red blood cells release hemoglobin when they die • Body turns hemoglobin into bilirubin • Sickle cell anemiac’s red blood cell’s life span is short = more bilirubin = more gallstones

30. Effects – Organ Failure • Multiple organ failure (2/3 major organs fail) can be caused by sickle cell anemia • Occurs when there is a severe crisis • This is rare but possible

31. Effects – Shortened Lifespan • Sickle cell anemia shortens lifespan • Women with sickle cell anemia live longer than men with sickle cell anemia

32. Diagnosis • Sickle cell anemia is diagnosed by hemoglobin electrophoresis • A second test is used to confirm a diagnosis • Sickle hemoglobin can be detected in early pregnancy by amniocentesis

33. Treatment Treatment methods aim to: • Releive pain • Prevent/heal infections • Manage complications

34. Treatment – Bone Marrow Transplants • Potential cure, but difficult to find donors • Work’s by replacing diseased bone marrow with normal bone marrow • Bone marrow is responsible for creating stem cells -> blood cells • In this way sickle cell anemics can produce normal hemoglobin A

35. Treatment – Bone Marrow Transplants • 80-85% of sickle cell anemics that get bone marrow transplants remain disease free • But only 7% of sickle cell anemics qualify • About 10% of individuals that get bone marrow transplants die because of the treatment

36. Treatment – Bone Marrow Transplants Complications include: • Bleeding • Pneumonia • Severe infection • GVHD (Graft Vs. Host Disease)

37. Treatment – Blood Transfusions • Blood transfusions are given to stop stroke and worsening anemia • There are 2 kinds of blood transfusions: episodic and chronic

38. Treatment – Blood Transfusions Episodic transfusions are used for: • Sudden events and before major surgeries Chronic transfusions are used for: • Heart and chronic kidney failure • Stroke prevention and severe anemia

39. Treatment – Blood Transfusions Risks of chronic transfusions: • Iron overload • Alloimmunization • Exposure to bloodborne pathogens But, the risks of stroke are higher.

40. Drug Treatments Drug treatments include: • Antibiotics for infections • Pain medications to control pain • Hydroxyurea to help reduce acute chest syndrome episodes

41. Drug Treatments - Hydroxyurea • Hydroxyurea stimulates production of HbF (fetal hemoglobin) • HbF blocks the sickling of red blood cells • Currently the only drug to reduce pain crises and episodes of acute chest syndrome

42. Drug Treatments - Hydroxyurea • Hydroxyurea does not work on everyone • Has side effects including: nausea, drowsiness, hair loss, and inflammation of the mouth

43. Treatments • Treatments for sickle cell anemia have improved over the years • In 1973 the life span of sickle cell anemics was 14 • Lifespan is currently 50+

44. Future Outlook/Research • Gene therapy could be a cure for sickle cell anemia, since there is a defective gene that is supposed to “turn on” adult hemoglobin A before birth (hemoglobin A is found in large quantities after birth) • There are 2 different directions to the research of gene therapy for sickle cell anemia

45. Future Outlook/Research • One direction is to correct the defective gene and replace it • Another direction is to “turn off” the defective gene and “turn on” a HbF gene

46. Future Outlook/Research • Medications that can stimulate HbF production are also being researched • So are medications that can prevent the dehydration of the red blood cells (dehydration leads to sickling)

47. References What is Sickle Cell Anemia? (2011, February 1). In National Heart Lung and Blood Institute. Retrieved November 8, 2011, from http://www.nhlbi.nih.gov/health/health-topics/topics/sca/ What is Sickle Cell Anemia? (1996, November). In The Foundation for Better Health Care. Retrieved November 9, 2011, from http://fbhc.org/patients/modules/sicklecell.cfm

48. References Sickle Cell Disease (2009). In University of Maryland Medical Center. Retrieved November 10, 2011, from http://www.umm.edu/patiented/articles/how_serious_sickle-cell_disease_000058_5.htm Wynbrandt, J., & Ludman, M. D. (1999). The Encyclopedia of Genetic Disorders and Birth Defects (2nd ed., pp. 290-291). N.p.: Facts on File, Inc

49. References (2005). Encyclopedia of Family Health (3rd ed., Vol. 14, pp. 1954-1955). Pictures: (n.d.). Retrieved December 2, 2011, from http://www.highlighthealth.com/wp-content/uploads/2011/11/normal-hemoglobin-vs-sickle-cell.jpg (n.d.). Retrieved December 2, 2011, from http://www.healthy-associates.com/images/sickle-cell-global-picture.jpg

50. References Pictures: (n.d.). Retrieved December 2, 2011, from http://upload.wikimedia.org/wikipedia/commons/1/10/Malaria_versus_sickle-cell_trait_distributions.png (n.d.). Retrieved December 2, 2011, from http://ph-central.com/wp-content/uploads/2011/03/Pulmonary_Hypertension.jpg