SICKLE CELL DISEASE PED-MD4-1.udom-chas pptx

Give more information on sickle cell disease best for medical students and other health professionals

1. Presenters: Delel Peter, Colmann Priscus, Majaliwa Juma. Facilitator: Doctor Hafsa 15/02/2025 1 SICKLE CELL DISEASE

2. Presentation Outline Introduction Etiology/Genetics Epidemiology Clinical features Complications Diagnosis Management 15/02/2025 2

3. Normal Hemoglobin Structure Hemoglobin A is a tetramer composed of 4 subunits: 2 α and 2 β Each subunit has a ring (porphyrin ring) which holds an iron molecule. This is the binding site of oxygen 15/02/2025 3

4. Hemoglobin variant Hemoglobin variants are mutant forms of hemoglobin in a population (usually of humans), caused by variations in genetics. Some hemoglobin variants such as sickle-cell anemia causes diseases, hence they are hemoglobinopathies. Other variants cause no detectable disease, thus considered non-pathological variants. 15/02/2025 4

5. Hemoglobin Abnormalities There are 3 main categories of inherited Hemoglobin abnormalities: Structural or qualitative: The amino acid sequence is altered because of incorrect DNA code (Hemoglobinopathy). Quantitative: Production of one or more globin chains is reduced or absent (Thalassemia). Hereditary persistence of Fetal Hemoglobin (HPFH): Complete or partial failure of γ globin to switch to β globin. 15/02/2025 5

6. Hemoglobinopathy? Hemoglobinopathy is a genetic defect that results in abnormal structure of one of the globin chains of the hemoglobin molecule. Causes the depletion in the synthesis of sufficient normal hemoglobins 15/02/2025 6

7. Pathological variants Hemoglobin H ( β4) - A variant form of hemoglobin, formed by a tetramer of β chains, which may be present in variants of α thalassemia. Hemoglobin Barts ( γ4) - A variant form of hemoglobin, formed by a tetramer of γ chains, which may be present in variants of α thalassemia. 15/02/2025 7

8. Pathological variants Hemoglobin S ( α2β S2) - A variant form of hemoglobin found in people with sickle cell disease. There is a variation in the β- chain gene, causing a change in the properties of hemoglobin, which results in sickling of red blood cells. Hemoglobin C ( α2β C2) - Another variant due to a variation in the β- chain gene. This variant causes a mild chronic hemolytic anemia. 15/02/2025 8

9. Pathological variants Hemoglobin E ( α2β E2) - Another variant due to a variation in the β- chain gene. This variant causes a mild chronic hemolytic anemia. Hemoglobin AS - A heterozygous form causing Sickle cell trait with one adult gene and one sickle cell disease gene Hemoglobin SC disease - A compound heterozygous form with one sickle gene and another encoding Hemoglobin C. 15/02/2025 9

10. What is Sickle Cell Disease? A serious condition in which red blood cells can become sickle-shaped Normal red blood cells are smooth and round. They move easily through blood vessels to carry oxygen to all parts of the body. Sickle-shaped cells don’t move easily through blood. They’re stiff and sticky and tend to form clumps and get stuck in blood vessels. The clumps of sickle cell block blood flow in the blood vessels that lead to the limbs and organs. Blocked blood vessel can cause pain, serious infection, and organ damage. 15/02/2025 10

11. Cont… Sickle cell disease denotes all genotypes that contain AT LEAST 1 sickle gene Included in this HB SS HB S-beta-0-thal HB SC HB/hereditary persistence of fetal HB HB SE HB SS=sickle cell anemia Most common and severe Causes wide range of clinical problems 15/02/2025 11

12. Sickle Cell Disease vs. Sickle Cell Trait People who have sickle cell disease are born with it; means inherited, lifelong condition. They inherit two copies of sickle cell gene, one from each parent. Sickle cell trait is different from sickle cell disease. People with sickle cell trait don’t have the condition, but they have one of the genes that cause the condition. People with sickle cell disease and sickle cell trait can pass the gene on when they have children. 15/02/2025 12

13. Etiology/Genetics Autosomal Recessive Disease Valine substituted for Glutamic Acid in the polypeptide chain of the beta globin gene at position 6 of chromosome eleven Stacking of deoxygenated sickle hemoglobin molecules into monofilaments Monofilaments aggregate into elongated crystals ultimately forming the sickle cell Inflammation also plays large role; Inflammatory factors activated by vascular endothelium 15/02/2025 13

14. Normal and Sickled Red Blood Cells in Blood Vessels Figure A: shows normal red blood cells flowing freely in a blood vessel. The inset image shows a cross-section of a normal red blood cell with normal hemoglobin. Figure B: shows abnormal, sickled red blood cells clumping and blocking the blood flow in a blood vessel. The inset image shows a cross-section of a sickled red blood cell with abnormal strands of hemoglobin. 15/02/2025 14

15. Inheritance of Sickle Cell Disease If one parent has sickle cell anaemia (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 disease(HbSS) can only pass the sickle hemoglobin gene to each of their children. 15/02/2025 15

16. Incidence Carrier state: 8% in black Americans more in Africa (30 to 50%) Homozygous state (sickle cell anemia) occurs in 1 in 500 African-Americans Incidence is much higher in Africa 15/02/2025 16

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19. Signs and Symptoms Individual signs and symptoms varies. Some have mild symptoms, others have very severe symptoms and may be hospitalized for treatment. Present at birth, many infants doesn’t show signs until after 4 months of age. Anemia: Fatigue (tiredness), pale skin and nail beds, jaundice, and shortness of breath. Pain (Sickle Cell Crisis): Sudden episode of pain throughout the body. Common sites: bones, lungs, abdomen, and joints. Lack of blood flow can cause pain and organ damage. 15/02/2025 19

20. Complication of Sickle Cell Disease Hand-Food Syndrome Splenic Crisis Infections Acute Chest Syndrome Delayed growth and puberty in children Stroke Eye problems Priapism Gallstone Ulcers on the legs Pulmonary Arterial Hypertension Multiple Organ Failure 15/02/2025 20

21. Cont… Hand-Foot Syndrome Pain may be felt in many bones of the hands and feet. Swelling usually occurs on the back of the hands and feet and moves into the fingers and toes. This may be the first sign of sickle cell anemia in infants. Splenic (Sequestration) Crisis Sometimes , the spleen traps many cells that should be in the bloodstream and it grows large. This causes anemia. If the spleen becomes too clogged with sickle cells, it can’t work normally. It begins to shrink and stop working. 15/02/2025 21

22. Cont… Infections Infants and young children with a damaged spleen are more likely to get infections that can kill them within hours or days. Pneumonia is the most common cause of death in young children who have sickle cell anemia. Meningitis , influenza, and hepatitis are other infections that are common in people with sickle cell anemia. Acute Chest Syndrome It's similar to pneumonia and is caused by an infection or by sickle cells trapped in the lungs. People with this condition usually have chest pain, fever, and an abnormal chest x ray. Over time, lung damage may lead to pulmonary arterial hypertension . 15/02/2025 22

23. Cont… Stroke Sickle-shaped red blood cells may stick to the walls of the tiny blood vessels in the brain. This can cause a stroke. This type of stroke occurs mainly in children. The stroke can cause learning disabilities or more severe problems. Eye Problems The retina, a thin layer of tissue at the back of the eye, takes the images you see and sends them to your brain. When the retina doesn’t get enough blood, it can weaken. A weak retina can cause serious problems, including blindness. Priapism Males with sickle cell anemia may have painful and unwanted erections called priapism. This happens because the sickle cells stop blood flow out of an erect penis. Over time, priapism can damage the penis and lead to impotence. Considered prolonged if lasting >3 hours. 15/02/2025 23

24. Avascular Necrosis of Hip Vascular occlusion of blood flow to bone leads to bone infarction and collapse High baseline hemoglobin increased risk 30% have hip pathology by 30 years Must think about this in the patient presenting with hip pain (not a straight forward vaso-occlusive crisis) Needs to be evaluated for Orthopedic Surgeon 15/02/2025 24

25. Cont… Gallstones When red blood cells die, they release their hemoglobin, which the body breaks down into a compound called bilirubin. When there is too much bilirubin in the body, stones can form in the gallbladder. The pain may happen after eating fatty meals. People with gallstones may present with Charcot’s triad. 15/02/2025 25

26. Cont… Delayed Growth and Puberty in Children Children with sickle cell anemia often grow more slowly and reach puberty later than other children. A shortage of red blood cells (anemia) causes the slow growth rate. Adults with sickle cell anemia often are slender or small in size. Multiple Organ Failure Multiple organ failure is rare, but serious. It happens when a person has a sickle cell crisis that causes two out of three major organs (lungs, liver, or kidney) to fail. Symptoms linked to this complication are a fever and changes in mental status such as sudden tiredness and loss of interest in your surroundings. 15/02/2025 26

27. Who to Evaluate for Sickle Cell Disease?? Any child admitted to the hospital with anemia of unknown etiology that does not seem to be Iron deficiency, particularly if associated with jaundice or splenomegaly A child with bony pain and anemia A child with a history of blood transfusions SCREENING TEST Solubility test (Sickledex) Sickling test 15/02/2025 27

28. DIAGNOSTIC INVESTIGATIONS Hemoglobin Electrophoresis : The gold standard for diagnosing SCD and differentiating between the various hemoglobin variants (HbSS, HbSC, HbSβ-thal ). It separates hemoglobin types based on their movement in an electric field. Sensitivity approaches 100 %. High-Performance Liquid Chromatography (HPLC ). 15/02/2025 28

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30. SUPPORTIVE INVESTIGATIONS Peripheral Blood Smear: Reveals sickle-shaped RBCs, target cells, and Howell-Jolly bodies (indicative of splenic dysfunction ). Red cell morphologies:HbS : Sickle cells,HbC : Target cells, crystals after splenectomy,Thalassemias : Microcystosis, target cells, basophilic stippling Complete Blood Count (CBC): Demonstrates normocytic, normochromic anemia with reticulocytosis (increased immature RBCs) and often leukocytosis . 15/02/2025 30

31. PART I: EMERGENCY MANAGEMENT PAIN RELIEF Give initial dose within 10 MINUTES of arrival at hospital Give Paracetamol 15mg/kg PO +/- either Ibuprofen 10mg/kg PO or Diclofenac 1mg/kg PO 8 hourly Give morphine 0.1mg/kg IV 6 hourly(not more than 15mg per day) Fluid Bolus (HYDRATION) Within 10 MINUTES of arrival at hospital; Initiate fluid bolus to hydrate the patient ) should be 20mls/kg and may be repeated up-to three times . Blood Transfusion within 30-60 minutes: Transfuse 10-15 mls/kg of blood (PRBCs) or 20mls/kg of whole blood within 30-60 minutes on arrival. 15/02/2025 31

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33. PART II: MANAGING ACUTE COMPLICATIONS OF SCD 15/02/2025 33

34. 2 . Febrile illness Patients with SCD are at risk of overwhelming septicemia with encapsulated organisms, due to loss of normal splenic function. Indications for inpatient care. Temperature >40 degrees Celsius, or temperature 38 - 40 degrees Celsius with any one of the following: Tachycardic, tachypneic, poorly perfused, drowsy or hypotensive. Severe painful crisis Acute changes in spleen size reported by parent Infiltrates on chest X-ray Hb 2g/dl from steady state hemoglobin value. Symptoms indicative of stroke or neurological deficit. 15/02/2025 34

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36. 3 . Acute chest syndrome P ain relief. Place an intravenous cannula and collect blood for investigations. Oxygen - Give supplemental oxygen to maintain oxygen saturation of greater than 95 percent Fluids (60%) Give broad spectrum antibiotics such as IV ceftriaxone 70-100mg/ kg once daily or amoxicillin clavulinic acid 30mg/kg/dose 8hourly for10 days. Give Macrolides such as Azithrmycin or Clarithromycin to cover for atypical microorganisms. Exchange blood transfusion. 15/02/2025 36

37. 4 . Acute severe anaemia Defined as hemoglobin <5g/dl or recent acute drop in Hb ≥2g/dl below steady state or acutely symptomatic anemia (tachycardia, tachypnea, tender hepatomegaly) 15/02/2025 37

38. 5. Acute splenic sequestration 15/02/2025 38

39. 6 . Cholelithiasis (Gallstones) and acute cholecystitis 15/02/2025 39

40. 7. Stroke 15/02/2025 40

41. 8. Convulsions/Seizure 15/02/2025 41

42. 9. Priapism Management If episodes less than 2 hours from onset: Give analgesia as per pain guideline Document the time of onset and precipitating factors e.g. trauma, infection, use of drugs (e.g. alcohol, psychotropic agents, Sildenafil, Testosterone, Cocaine) Give anxiolytic agents for anxiety if indicated (e.g. lorazepam 0.05mg/kg/dose given 2-3 times per day, do not exceed 2mg/ dose). Increase fluid intake orally or IV if indicated as per rehydration guideline Encourage patients to micturate, walk or have a warm bath. For episodes lasting more than 2 hours: Keep the patient nil per oral in case of surgical intervention Continue IV hydration, analgesics and anxiolytics Catheterize if unable to micturate Grouping and cross match for possible exchange transfusion consult urologist/surgeon (for possible penile aspiration, intracorporeal injection of Phenylephrine Or wash out) OR refer to the next level facility with adequate expertise and facilities. 15/02/2025 42

43. PART III. Long-term / Chronic Complications of SCD 1. Chronic pain This is pain lasting for 3 or more months. Chronic pain may occur with or without objective signs of avascular necrosis, arthropathy, arthritis, leg ulcers or vertebral body collapse. Use long (e.g. Morphine extended release capsules, tramadol) and short acting opioid to manage chronic pain that is not relieved by non-opioids. 15/02/2025 43

44. 2. Hypersplenism Hypersplenism is characterized by splenomegaly and cytopenia of at least two cell lines. 15/02/2025 44

45. 3 . ORTHOPAEDIC COMPLICATIONS Avascular Necrosis (AVN) 15/02/2025 45

46. Cont … Osteomyelitis and Septic Arthritis 15/02/2025 46

47. 4. Renal complications Renal involvement is common; up to 20% of patients with SCD develop renal insufficiency. 15/02/2025 47

48. 5. Ophthalmologic complications 15/02/2025 48

49. PART IV.PREVENTIVE STRATEGIES AND HEALTH MAINTENANCE IN PATIENTS WITH SCD 15/02/2025 49

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53. Cont… Dosage Initiation: For adults: Start with 15 mg/kg/day (round up to the nearest 500 mg); 5–10 mg/kg/day if patient has chronic kidney disease For infants and children below 15 years of age: Start with 20 mg/kg/day (in cases where only 500 capsules are available; calculate weekly dose in terms of number of capsules per week and distribute the required capsules throughout the week) 15/02/2025 53

54. Cont… Dose adjustment for toxicity: If one or more blood count parameters fall into toxic range (ANC <1 x 10^/L/ µL or Platelets <50 x 10^/L), stop hydroxyurea and do FBP every 2 weeks. Restart hydroxyurea at the same dose if affected blood count recovers in 2 weeks. Reduce hydroxyurea dose by 2.5 mg/kg if toxicity persists for more than 2 weeks or if there is a previous history of toxicity at the current dose. Do FBP according to the initiation schedule. 15/02/2025 54

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56. 15/02/2025 56 4. NUTRITION Encourage exclusive breast feeding for the first 6 months of life. Complementary feeding should be introduced from 6 months with proteins, fruits, starches, and green leafy vegetables. During illness episodes, the appetite will be poor. If this occurs encourage frequent small feeds of a well-balanced diet. 5. GROWTH AND DEVELOPMENT MONITORING IN CHILDREN Serial growth measurements should be performed to capture both acute changes and long-term growth velocity 6. TRANSITION OF ADOLESCENTS TO ADULT CARE Start preparation and plan the transfer at an early age (between 14 years and 15 years) in a developmentally appropriate manner. There should be a collaboration between pediatric and adult SCD health care providers to facilitate an effective transition

57. PART V: BLOOD TRANSFUSION IN THE MANAGEMENT OF SICKLE CELL DISEASE There are three main types of transfusion and rationales of transfusing sickle cell patients Acute simple transfusion. Exchange transfusion, Manual/Automated erythrocytapheresis Chronic top up transfusion 15/02/2025 57

58. PART VI: Follow-up plan RFT, electrolytes, , LFTs when necessary to check for signs of haemolysis Check Vaccinations if not up-to-date Arrange for Annual TCD from age 2 -16 years Document COMPLETE BLOOD COUNT/ Hemoglobin level results in SCD health passport. 15/02/2025 58

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