Hemoglobin Disorders Sickle cell anemia and Thalassemias Prepared by : Ahmed Ayasa Supervised by :Dr. Abdullateef Al Khateeb 1

SICKLE CELL ANEMIA 2

Sickle cell Anemia Single base-pair change (thymine for adenine) at 6 th codon of beta gene (valine instead of glutamine) – Polymerization of Hb under hypoxic conditions 3

Sickle cell Sickle cell disease compound heterozygotes where one β- globin gene mutation includes the sickle cell mutation Sickle cell anemia homozygous Hb S, occurs when both β-globin genes have the sickle cell mutation. 4

Sickle Cell Anemia Presentation Anemia Cerebrovascular accidents Acute chest syndrome Infection Skeletal Painful crisis Hemolytic crisis Sequestration crisis Aplastic crisis 5

Sickle Cell-Laboratory Findings Increased reticulocytes Mild-to-moderate anemia Normal MCV, nucleated RBCs If severe: 1.Target cells, poikilocytes, hypochromasia 2.Sickle RBCs, nRBCs, Howell-Jolly bodies 6

Peripheral blood smear with sickled cells Peripheral blood smear with sickled cells at 1000X magnification. Image courtesy of Ulrich Woermann, MD. 7

Howell-Jolly body Peripheral blood smear with Howell-Jolly body, indicating functional asplenism. Image courtesy of Ulrich Woermann, MD. 8

Sickle Cell-Diagnosis and Management Diagnosis: – Confirm with Hb electrophoresis – Most states with newborn screen-then confirm Treatment: – Prevent complications Immunizations + 23 valent PPV Penicillin prophylaxis at 2 months Education Folate supplementation 9

Sickle Cell Treatment (cont’d.) 1.Aggressive antibiotic treatment of infection 2.Pain control 3.Transfusion as needed 4.Monitor for risk of stroke with transcranial Doppler 5.Hydroxyurea 6.Bone marrow transplant 10

THALASSEMIAS 11

Beta Thalassemia if one is deficient  beta thalssemia minor (triat)  no significant hemolysis Both genes  beta thalssemia major  significant hemolysis. Thalassemia intermedia  both genes are absents but there is milder degree of hemolysis  Hb 8-7 mg/dl but minimal or no transfusion with normal growth. 12

Beta-Thalassemia Major-Cooley’s Anemia Excess alpha globin chains→ alpha tetramers Increase in HbF (no problems with gamma chain production) Second month of life with progressive anemia, hypersplenism, and cardiac decompensation(Hb <4 mg/dL) Expanded medullary space-face and skull, liver and spleen 13

Beta-Thalassemia Major-Cooley’s Anemia

Mongoloid facies Thalassemia 15

Hair brush appearance The classic "hair on end" appearance on plain skull radiographs of a patient with Cooley anemia. 16

Laboratory Findings Basophilic stippling can be present due to a chains presipitation Hypochronic microcytic anemia Hb g / L Diagnosis baced on ↑ HbF & HbA2 17

Peripheral blood film in Cooley anemia. 18

Peripheral smear in beta-zero thalassemia minor showing microcytes (M), target cells (T), and poikilocytes. 19

Treatment of Beta thalassemia Major ( COOLEY ANEMIA) : should be started since age 6m-1yr to keep Hb > 10 for normal growth and development, after epiphesial closure 7-8 mg/dl is accepted 1- TRANSFUSION given with transfusion, deferoximine ( start at 3-4 yr old) – complications: deafness, color & night blindness, yersinia and mucomycosisi infections. 2-celation reduce iron toxicity indicated if : spleen very enlarged, hypersplenism, RBC requirement >200ml/kg/yr 3- splenectomy 4- BM TRANSPLANTATION ::  definitive cure is bone marrow transplantation  success rate is 75-80%. 20

Alpha thalassemia: There are four genes : one gene  silent carrier tow genes  alpha thalseemia triat  no symptoms three genes  HBH(4 beta)  anemia, HSM and jaundice, Heinz bodies. 4 genes  HB bart (4 gamma)  hydrops fitalies  incompatabile with life ( the most severe one) 21

Diagnosis by electrophoresis  Hb bart or H. Hemolysisi may presipetated by infection, oxidants eg. Iron, sulfonamides Alpha thalassemia 22

Peripheral smear from patient with hemoglobin H disease showing target cells, microcytosis, hypochromia, and anisopoikilocytosis. Morphologic abnormalities are similar to those observed in beta thalassemia. In silent carriers, only mild microcytosis is observed. 23

Treatment of alpha Thalassemia Individuals with mild forms of alpha thalassemia may not require specific treatment except as needed for management of low hemoglobin levels. In some patients, supplementation of iron or folic acid may be useful. Patients with more severe anemia may require lifelong transfusion therapy. Surgical therapy is considered only in selected cases. 24

Thank You 25