SICKLE CELLLLLLLLLLLLLLLLLLLLLLLLLL.pptx

SICKLECELL

1. SICKLE CELL DISEASE IN CHILDREN PRESENTED BY seremba elvis

2. backround Sickle cell disease is a group of genetic disorders of hemoglobin which results into abnormal sickle hemoglobin It is a result of substitution of valine for glutamate at position 7(formerly 6) on the beta chain of hemoglobin on xme 11 Sickle cell trait is a heterozygous genotype Sickle cell anemia is the most common and sever form of SCD

3. epidemiology Globally 400,000 neonates are born with SCD each year and 7.74 million people have SCD (Health data.org) 300,000 neonates are in sub-Saharan Africa ( multeser 2021) In Uganda 20,000 children are born with SCD ( Ndezi et al 2016) Most of these, if no intervention is done die before age 5.

4. pathophysiology Hb polymerization Hemolysis Vascular obstruction Deoxygenation and sickling cycle

5. Hb polymerization HBS polymerizes and so changes from solution to gel form Polymerization damages cell membrane of the sickled cells hence irreversible damage Factors promoting polymerization Deoxygenation/hypoxia Dehydration Acidosis coldness

6. hemolysis Occurs both intravascular and extravascular leading to anemia It’s a continuous process Intravascular hemolysis leads to decrease in nitric oxide synthesis hence, generation of ROS, endothelial damage, activation of neutrophils and scavenging of NO. The result is: leg ulcers, nephropathy, priapism, stoke Extravascular hemolysis occurs in the liver, bone marrow and spleen if intact

7. Vascular obstruction Microvascular obstruction by sickled cells Adherence of sickled cells to vascular endothelium This leads to damage of endothelium, inflammation, vasoconstriction and ischemic reperfusion injury

8. Deoxygenation and sickling cycle Modulated by 2,3 bisphosphoglycerate in RBC Lowers oxygen affinity Reduces intracellular Ph Alters conformation of deoxy HBS

9. Crises in SCD Aplastic crisis Usually follows infection with parvovirus that destroys RBC precursor cells leading to cessation of RBC production. HEMOLYTIC CRISIS Due to RBC breakdown both intravascular and extravascular VASOOCCLUSSIVE CRISIS Sickling in microvasculature leading to regional hypoxemia, ischemia with or without tissue infarction Clinically presents as;

10. Clinical presentation of vasoocclusive crisis Acute chest syndrome Leg ulcers Priapism Mesenteric crisis; abdominal pain Renal infarction; hematuria Hand and foot syndrome Pulmonary emboli of necrotic bone marrow

11. Crises cont ….. Sequestration crisis Sudden pooling of blood in the spleen and liver Manifests as, acute pallor, hypovolemic shock, acute abdominal Pain, hepato-splenomegaly INFECTIOUS CRISIS Mainly due to hyposplenism,reduced abs, opsoninsand reduced phagocytosis Common pathogens are encapsulated bacteria Pneumococci, H.influenza , salmonella, staphylococcus aureus

12. Complications of SCD ACUTE Pain crises Severe acute anemia Acute stroke Splenic sequestration Priapism Pulmonary emboli AKI

13. COMPLICATIONS CONT… CHRONIC Leg ulcers Stroke Recurrent priapism Osteomyelites CKD Avascular necrosis

14. Clinical picture Crisis Features of anemia Features of hemolysis May present with complications Prominent maxillo-facial bones Big incisors Frontal bossing Swelling of joints and pain

15. INVESTIGATIONS Rapid sickle cell tests for screening Hb electrophoresis High performance liquid chromatography CBC Thin film RFTs LFTs Blood smear

16. MANAGEMENT Comprehensive approach, multi displinary team Involves prevention, screening for and treating of SCD associated complications Educate and counsel patients and care givers Prophylaxis against infections Penicillin V twice daily till 5 years. Don’t discontinue if child had splenectomy Malaria chemoprophylaxis Immunization ;all vaccines according to schedule. Additional PCV 2,3 at ages 2 and 5

17. MANAGEMENT CONT … Micronutrient deficiencies are common with SCD. Role of micronutrient supplementation is not well studied Routine folic acid 5mg daily given as local standard of care Screen for complications, stroke, renal disease, pulmonary disease Reproductive counselling for patients with SCD Treatment of acute and chronic complications offer hydroxyurea to all children older than 9months Blood transfusion

18. Dosing and monitoring hydroxyurea Baseline investigations, cbc , quantitative HB electrophoresis, creatinine and urea,LFTS , ALT Discuss rationale and potential adverse effects of hydroxyurea Document that family agrees to have regular clinic monitoring Start 20mg/kg/day for children,15mg/kg/day for adults Monitor cbc every month for 3 months, then every 3 months Escalate when indicated eg abn TCD,stroke , no clinical response Monitor liver and renal function annually

19. Challenges of hydroxyurea Formulations of 250mg and 500mg capsule Capsule formulations and no syrups Erratic availability of drugs When to stop hydoxyurea Absolute neutrophil count less than 100 Platelets less than 8000 Hb less than 6g/dl

20. transfusion When to transfuse ACS Stroke Aplastic crisis Severe anemia below 5g/dl

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