Sickle cell anemia

Sickle cell anemia

1. Sickle Cell Anemia By: Nancy Saber Roba Shaat Mohamed Samir El- Asaly Under Supervision: Prof. Dr. Aziza Mahrous

2. Definition Genetics of SCD History Hemoglobin Genetics of SCD Inheritance of Sickle Cell Disease Mechanism Symptoms Complications Diagnosis Treatment

3. Sickle Cell Anemia I s an inherited form of anemia — a condition in which there aren't enough healthy red blood cells to carry adequate oxygen throughout your body . Normally, your red blood cells are flexible and round, moving easily through your blood vessels .

4. Sickle Cell Anemia In sickle cell anemia, the red blood cells become rigid and sticky and are shaped like sickles or crescent moons. These irregularly shaped cells can get stuck in small blood vessels , which can slow or block blood flow and oxygen to parts of the body .

5. Definition Sickle Cell disease : is a genetic disorder that affects erythrocytes (RBC) causing them to become sickle or crescent shaped. The effects of this condition due to an abnormality of the hemoglobin molecules found in erythrocytes.

6. History In 1904 , Walter Clement Noel traveled from Grenada to the United States to start studying at the Chicago College of Dental Surgery.   A few months later he was admitted to the Presbyterian Hospital in Chicago when he developed severe respiratory distress and a leg ulcer , both of which we now know are symptoms of sickle cell . Dr. Earnest E. Irons, the intern who was on duty that day, performed a routine blood test and a urine analysis for Noel and was the first to observed these “ pear shaped, elongated ” sickled blood cells.

7. Report of blood test on Walter Clement Noel dated 31 December 1904 .

8. It was not until 1910 that Dr James Herrick, the supervisor of Dr Irons, published his article describing these “peculiar elongated and sickle shaped red blood corpuscles in a case of severe anemia.”   This was the first documented and recorded case of Sickle cell in Western medicine.   Dr Noel returned to Grenada in 1907 and ran his dental practice in St. Georges, the capital city, until he died at the age of 32 from the acute chest syndrome .

9. 1917 – Genetic basis for SCD Dr. V. Emmel . The third cases of Sickle cell was described in 1915 by Cook and Meyer in a 21-year-old woman . Interestingly , blood samples from both the patient and her father, who displayed no symptoms , showed the sickling deformity of the red cells and three of her siblings had died from severe anemia . These observations made by Dr Emmel suggested a genetic basis for the disease but also led to a period of confusion with the genetics of the disease. 

10. 1922 – Dr V.R Mason names the disease Sickle Cell Anemia. Dr Mason, who observed the fourth reported case of Sickle cell, was also the first to call the disease “sickle cell anemia” and to notice the similarities between the cases.   He also noted that all of these patients were black , inadvertently giving rise to the popular misconception that sickle cell originated from people of African origin .

11. Hemoglobin The oxygen-carrying pigment and predominant protein in the red blood cells. Hemoglobin forms an unstable, reversible bond with oxygen . Oxyhemoglobin : Oxygenated ( bright red). Deoxyhemoglobin : Reduced ( purple-blue).

12. Hemoglobin Each hemoglobin molecule is made up of four heme groups surrounding a globin group. Heme contains iron and gives a red color to the molecule. Globin consists of two linked pairs of polypeptide chains.

13. Genetics of SCD The change in cell structure arises from a change in the structure of hemoglobin. A single cha nge in an amino acid causes hemoglobin to aggregate .

14. Hemoglobin A Hemoglobin S

15. Inheritance of Sickle Cell Disease If one parent has sickle cell trait ( HbAS ) and the other does not carry the sickle hemoglobin at all ( HbAA ) then none of the children will have sickle cell anemia. There is a one in two (50%) chance that any given child will get one copy of the HbAS gene and therefore have the sickle cell trait. It is equally likely that any given child will get two HbAA genes and be completely unaffected.

16. Inheritance of Sickle Cell Disease If both parents have sickle cell trait ( HbAS ) there is a one in four (25%) chance that any given child could be born with sickle cell anemia. There is also a one in four chance that any given child could be completely unaffected. There is a one in two (50%) chance that any given child will get the sickle cell trait.

17. Inheritance of Sickle Cell Disease If one parent has sickle cell trait ( HbAS ) and the other has sickle cell anemia ( HbSS ) there is a one in two (50%) chance that any given child will get sickle cell trait and a one in two (50%) chance that any given child will get sickle cell anemia. No children will be completely unaffected .

18. Inheritance of Sickle Cell Disease If one parent has sickle cell anemia ( HbSS ) and the other is completely unaffected ( HbAA ) then all the children will have sickle cell trait. None will have sickle cell anemia. The parent who has sickle cell anemia ( HbSS ) can only pass the sickle hemoglobin gene to each of their children .

19. Mechanism When sickle hemoglobin ( HbS ) gives up its oxygen to the tissues, HbS sticks together Forms long rods form inside RBC RBC become rigid, inflexible, and sickle-shaped Unable to squeeze through small blood vessels, instead blocks small blood vessels Less oxygen to tissues of body RBCs containing HbS have a shorter lifespan Normally 20 days Chronic state of anemia

20. Symptoms They vary from person to person and change over time, include: Anemia . Sickle cells break apart easily and die, leaving you without enough red blood cells. Red blood cells usually live for about 120 days before they need to be replaced. But sickle cells usually die in 10 to 20 days , leaving a shortage of red blood cells (anemia).

Without enough red blood cells, your body can't get the oxygen it needs to feel energized, causing fatigue .

21. Symptoms Episodes of pain . Periodic episodes of pain, called crises , are a major symptom of sickle cell anemia . Pain develops when sickle-shaped red blood cells block blood flow through tiny blood vessels to your chest, abdomen and joints. Pain can also occur in your bones . The pain varies in intensity and can last for a few hours to a few weeks. Some people have only a few pain episodes . Others have a dozen or more crises a year. If a crisis is severe enough, you might need to be hospitalized.
Some adolescents and adults with sickle cell anemia also have chronic pain, which can result from bone and joint damage, ulcers and other causes.

22. Symptoms Painful swelling of hands and feet. The swelling is caused by sickle-shaped red blood cells blocking blood flow to the hands and feet. Frequent infections. Sickle cells can damage an organ that fights infection (spleen), leaving you more vulnerable to infections. Doctors commonly give infants and children with sickle cell anemia vaccinations and antibiotics to prevent potentially life-threatening infections, such as pneumonia .

23. Symptoms Delayed growth . Red blood cells provide your body with the oxygen and nutrients you need for growth. A shortage of healthy red blood cells can slow growth in infants and children and delay puberty in teenagers. Vision problems . Tiny blood vessels that supply your eyes may become plugged with sickle cells. This can damage the retina — the portion of the eye that processes visual images, leading to vision problems .

24. Complications Sickle cell anemia can lead to a host of complications, including: Stroke. A stroke can occur if sickle cells block blood flow to an area of your brain . Signs of stroke include seizures, weakness or numbness of your arms and legs, sudden speech difficulties, and loss of consciousness. If your baby or child has any of these signs and symptoms, seek medical treatment immediately. A stroke can be fatal . Acute chest syndrome . This life-threatening complication causes chest pain, fever and difficulty breathing. Acute chest syndrome can be caused by a lung infection or by sickle cells blocking blood vessels in your lungs. It might require emergency medical treatment with antibiotics and other treatments. Pulmonary hypertension . People with sickle cell anemia can develop high blood pressure in their lungs (pulmonary hypertension). This complication usually affects adults rather than children. Shortness of breath and fatigue are common symptoms of this condition, which can be fatal .

25. Complications Organ damage . Sickle cells that block blood flow through blood vessels immediately deprive the affected organ of blood and oxygen. In sickle cell anemia, blood is also chronically low on oxygen. Chronic deprivation of oxygen-rich blood can damage nerves and organs in your body, including your kidneys, liver and spleen. Organ damage can be fatal . Blindness . Sickle cells can block tiny blood vessels that supply your eyes. Over time, this can damage the portion of the eye that processes visual images (retina) and lead to blindness. Leg ulcers . Sickle cell anemia can cause open sores, called ulcers, on your legs. Gallstones . The breakdown of red blood cells produces a substance called bilirubin . A high level of bilirubin in your body can lead to gallstones .

26. Diagnosis A blood test can check for hemoglobin S — the defective form of hemoglobin that underlies sickle cell anemia. In the United States, this blood test is part of routine newborn screening done at the hospital. But older children and adults can be tested, too. In adults , a blood sample is drawn from a vein in the arm . In young children and babies, the blood sample is usually collected from a finger or heel . If the screening test is negative , there is no sickle cell gene present . If the screening test is positive , further tests will be done to determine whether one or two sickle cell genes are present . Check for a low red blood cell count (anemia) will be done.

27. Genetic counseling Two tests can be used to help expectant parents find out if their child is affected. Amniocentesis , done usually at 14-16 weeks of pregnancy , tests a sample of the amniotic fluid in the womb for genetic defects (the fluid and the fetus have the same DNA). Under local anesthesia, a thin needle is inserted through the woman's abdomen and into the womb. About 20 milliliters of fluid (roughly 4 teaspoons) is withdrawn and sent to a lab for evaluation. Test results often take 1-2 weeks .

28. Genetic counseling Chorionic villus sampling , or CVS, involves the removal and testing of a very small sample of the placenta during early pregnancy . The sample, which contains the same DNA as the fetus, is removed by catheter or a fine needle inserted through the cervix or by a fine needle inserted through the abdomen. The tissue is tested for genetic changes identified in an affected family member. Results are usually available within 2 weeks .

29. Treatment Treatment is usually aimed at avoiding crises , relieving symptoms and preventing complications. Babies and children age 2 and younger with sickle cell anemia should make frequent visits to a doctor . Children older than 2 and adults with sickle cell anemia should see a doctor at least once a year , according to the Centers for Disease Control and Prevention. Treatments might include medications to reduce pain and prevent complications , and blood transfusions , as well as a bone marrow transplant .

30. Medications Antibiotics . Children with sickle cell anemia may begin taking the antibiotic penicillin when they're about 2 months old and continue taking it until they're at least 5 years old . Doing so helps prevent infections, such as pneumonia, which can be life-threatening to an infant or child with sickle cell anemia . As an adult , if you've had your spleen removed or had pneumonia , you might need to take penicillin throughout your life.

31. Medications Pain-relieving medications . To relieve pain during a sickle cell crisis. Hydroxyurea ( Droxia , Hydrea ) . When taken daily, hydroxyurea reduces the frequency of painful crises and might reduce the need for blood transfusions and hospitalizations. Hydroxyurea seems to work by stimulating production of fetal hemoglobin — a type of hemoglobin found in newborns that helps prevent the formation of sickle cells.
 Hydroxyurea increases the risk of infections, and there is some concern that long-term use of this drug might cause problems later in life for people who take it for many years. More studies are needed. 


32. Treatment Assessing stroke risk Using a special ultrasound machine ( transcranial ) , doctors can learn which children have a higher risk of stroke. This painless test, which uses sound waves to measure blood flow, can be used on children as young as 2 years. Regular blood transfusions can decrease stroke risk . Vaccinations to prevent infections Childhood vaccinations are important for preventing disease in all children. Vaccinations , such as the pneumococcal vaccine and the annual flu shot , are also important for adults with sickle cell anemia .

33. Treatment Blood transfusions In a red blood cell transfusion, red blood cells are removed from a supply of donated blood, then given intravenously to a person with sickle cell anemia. Blood transfusions increase the number of normal red blood cells in circulation, helping to relieve anemia. In children with sickle cell anemia at high risk of stroke, regular blood transfusions can decrease the risk. Transfusions can also be used to treat other complications of sickle cell anemia, or they can be given to prevent complications. Blood transfusions carry some risk, including infection and excess iron buildup in your body. Because excess iron can damage your heart, liver and other organs, people who undergo regular transfusions might need treatment to reduce iron levels .

34. Treatment Nitric oxide. People with sickle cell anemia have low levels of nitric oxide in their blood. Nitric oxide is a gas that helps keep blood vessels open and reduces the stickiness of red blood cells. Treatment with inhaled nitric oxide might prevent sickle cells from clumping together. Studies on nitric oxide have shown little benefit so far.

35. Bone Marrow Transplant Bone marrow transplant, also known as stem cell transplant, offers the only potential cure for sickle cell anemia. It's usually reserved for people younger than age 16 because the risks increase for people older than 16. Finding a donor is difficult, and the procedure has serious risks associated with it, including death . A bone marrow transplant involves replacing bone marrow affected by sickle cell anemia with healthy bone marrow from a donor. The procedure usually uses a matched donor, such as a sibling, who doesn't have sickle cell anemia. For many, donors aren't available. But stem cells from umbilical cord blood might be an option .

36. Bone Marrow Transplant Because of the risks associated with a bone marrow transplant, the procedure is recommended only for people, usually children, who have significant symptoms and problems from sickle cell anemia. If a donor is found, the person with sickle cell anemia receives radiation or chemotherapy to destroy or reduce his or her bone marrow stem cells. Healthy stem cells from the donor are injected intravenously into the bloodstream of the person with sickle cell anemia, where they migrate to the bone marrow and begin generating new blood cells. The procedure requires a lengthy hospital stay. After the transplant, you'll receive drugs to help prevent rejection of the donated stem cells. Even so, your body might reject the transplant, leading to life-threatening complications .

37. Experimental treatments Scientists are studying new treatments for sickle cell anemia, including: Gene therapy. Researchers are exploring whether inserting a normal gene into the bone marrow of people with sickle cell anemia will result in normal hemoglobin . Scientists are also exploring the possibility of turning off the defective gene while reactivating another gene responsible for the production of fetal hemoglobin — a type of hemoglobin found in newborns that prevents sickle cells from forming.
Potential treatments using gene therapy are a long way off, however.

38. Experimental treatments Although several of the initial hurdles to SCD gene therapy appear to have been overcome, it is prudent to recognize barriers that remain. Efficient transduction of HSCs with lentiviral vectors has become increasingly reliable, but the complicated components of many globin vectors present unique challenges for production of high-titer virus capable of robust transduction.

39. Experimental treatments Scaling up procedures to multiple patients is a nontrivial challenge. Safety and efficacy can only be established by careful clinical trials with extended patient follow-up. Gene engineering methods are rapidly evolving and should facilitate development of “second-generation” gene therapy approaches in the coming years. After many years of preclinical laboratory investigation, gene therapy options are now on the horizon for patients with SCD .