Sickle Cell Anemia PDF

Sickle Cell Disease Siti Balkis Budin Sickle Cell Disease: Pharmacologic Treatment Sickle cells - first observation Walter Noel’s blood smear - Dec 31, 1904 Sickle Cell Disease: Pharmacologic Treatment Pathophysiology of SCD 1. Molecular pathology 2....

Sickle Cell Disease Siti Balkis Budin Sickle Cell Disease: Pharmacologic Treatment Sickle cells - first observation Walter Noel’s blood smear - Dec 31, 1904 Sickle Cell Disease: Pharmacologic Treatment Pathophysiology of SCD 1. Molecular pathology 2. Biochemical pathology 3. Cellular pathology 4. Vascular pathology 5. Clinical pathology Sickle Cell Disease: Pharmacologic Treatment Molecular pathology of SCD Regular Hemoglobin Genes and Products Gower 1: 2 2 Gower 2: 2 2 Portland: 2 2 ------------------ F: < 2% 2 2 < 3% A 2: 2 2 96% A: Hemoglobins 2 2 by age > 1 yr Sickle Cell Disease: Pharmacologic Treatment Molecular pathology of SCD The sickle mutation The s Mutation 6th Codon of -Globin Gene GAG GTG Glutamic Valine acid The same mutation found in all s genes around the world Sickle Cell Disease: Pharmacologic Treatment Molecular pathology of SCD Normal versus sickle beta globin Norma l1 2 3 4 5 6 7 8 9 1 14 0 ------- 6 A - glu Sickl va e l ------- S 1 - 14 1 2 3 4 5 6 7 8 9 0 6 Sickle Cell Disease: Pharmacologic Treatment Molecular pathology of SCD Hemoglobin Genes and Products in SCD Gower 1: 2 2 Gower 2: 2 2 Portland: 2 2 ------------------ F: 2 2 2-20% A 2: 2 2 3% s S: 2 2 80-95% Hemoglobins in SCD by age > 1 yr  RBC containing mostly normal Hb - O2 + O2 oxygenate deoxygenate d d RBC containing mostly Hb S - O2 + O2 + O2 oxygenate deoxygenate Sickle Cell Disease: Pharmacologic Treatment Pathophysiology of SCD Red blood cell containing mostly Hb S… When oxygenated… When deoxygenated - - O2 + O 2 O2 + O2 …single Hb S …Hb S molecules molecules is free, polymerize into soft, round, and long fibers; deformable mishapen, characteristic dehydrated and adherent sickle cells. Sickle Cell Disease: Pharmacologic Treatment Pathophysiology of SCD Consequences of Hb S polymerization and RBC sickling Red cell injury Hemolysis RBC dehydration and dense cell formation Adhesion of RBC to venule endothelium Formation of heterocellular aggregates (WBC, SC) Vasooclusion Local hypoxia, increased Hb S polymer formation Propagation of vasooclusion in adjacent vasculature  Normal vs. Sickle Normal vs. Hemoglobin Sickle Hemoglobin Normal Sickle disc-Shaped sickle-Shaped soft(like a bag of jelly) hard (like a piece of easily flow through wood) small blood vessels often get stuck in small lives for 120 days blood vessels Block small blood vessels lives for 20 days or less Sickle Cell Disease: Pharmacologic Treatment Clinical Pathology of SCD 1. Anemia 2. Vasoocclusion 3. Chronic organ damage Sickle Cell Disease: Pharmacologic Treatment Clinical Pathology of SCD 1. Anemia Chronic intravascular hemolytic anemia Acute episodes of severe anemia ▪ Acute splenic sequestration ▪ Acute hemolysis (“hyperhemolysis”) Sickle Cell Disease: Pharmacologic Treatment Clinical Pathology of SCD 2. Vasoocclusive complications Microvascular occlusion ▪ clinically silent Macrovascular occlusion ▪ acute occlusion cause ischemic/infarctive damage pain episodes stroke acute chest syndrome renal papillary necrosis splenic infarction Sickle Cell Disease: Pharmacologic Treatment Clinical Pathology of SCD 3. Chronic organ damage Splenic dysfunction ▪ high risk of bacterial infection Chronic vascular occlusion cause progressive dysfunction of: ▪ lungs - oxyhemoglobin desaturation, pulmonary hypertension ▪ kidneys - proteinuria, renal failure ▪ gallbladder - gallstones ▪ eyes - proliferative retinopathy ▪ joints - osteonecrosis, arthritis ▪ heart - CHF Laboratory finding □ Hb 6-9g/dl □ Sickle cell and target cell □ Splenic atrophy □ Screening test for sickling positive Blood is deoxygenated with Na2 HPO4 Hb electrophoresis □ Hb SS □ No Hb A detected Managing Sickle Cell □ Fluids □ Antibiotics □ Rest □ Pain Medication □ Prevention of infections □ Healthy lifestyle THANK YOU