Sickle cell Disorders1 Sickle Cell Anemia

Sickle cell Disorders2 Sickle Cell Anemia HbS: a 2 ß 2 6Glu Val Sickle cell disorders: sickling with o 2 Sickle cell diseases: SS (the most severe), SD (the mildest), S-thal & SC (somewhat milder)

Sickle cell Disorders3 Sickle Cell Anemia HbS undergoes sickling with o strands of the fibers pairs a fiber with 21 nm diameter firm gel sickled red cells

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Sickle cell Disorders5 Inheritance Homozygous state Homozygous state Heterozygous state Heterozygous state

Sickle cell Disorders6 Clinical Features Manifestation by weeks of age (decrease in HbF). Manifestation by weeks of age (decrease in HbF). Crises: vaso-occlusive, aplastic (folate, parvovirus B 19 and marrow necrosis), sequestration (drop of Hb to <6 or 3gr fall), hemolytic. Crises: vaso-occlusive, aplastic (folate, parvovirus B 19 and marrow necrosis), sequestration (drop of Hb to <6 or 3gr fall), hemolytic. Growth Growth

Sickle cell Disorders7 Clinical Features Bony abnormalities: thalassemic feature, codfish spine and steplike depressions, dactylitis, avascular necrosis (femur and humerus head). Bony abnormalities: thalassemic feature, codfish spine and steplike depressions, dactylitis, avascular necrosis (femur and humerus head). BM necrosis (Staf. & Salm.infection BM necrosis (Staf. & Salm.infection or embolization to lung and chest syndrome) or embolization to lung and chest syndrome)

Sickle cell Disorders8 Sickle Cell Anemia Sickle cell dactylitis Sickle cell dactylitis (hand-foot syndrome) (hand-foot syndrome)

Sickle cell Disorders9 Sickle Cell Anemia Vascular occlusion : sickle cell dactylitis (soft tissue swelling, osteolytic lesions, osteosclerosis and periostitis). Vascular occlusion : sickle cell dactylitis (soft tissue swelling, osteolytic lesions, osteosclerosis and periostitis).

Sickle cell Disorders10 Sickle Cell Anemia Vascular occlusion: Vascular occlusion: epiphyseal infarction A&B Progressive changes of osteonecrosis: initial focal areas of sclerosis and subsequent collapse with irregularity of the articular surface(arrowhead: lateral femoral osteophytes) C The snow-capped appearance of the humeral head: patchy sclerosis (arrow) and collapse of the articular surface (arrowhead)

Sickle cell Disorders11 Sickle Cell Anemia Growth disturbance : H vertebrae Growth disturbance : H vertebrae A&B Central indentation of the vertebral bodies, initially may simulate fish vertebrae. C-1 Normal discovertebral junction C-2 Sickle cell anemia (ischemia of the central portions of the cartilaginous end plates).

Sickle cell Disorders12 Sickle Cell Anemia Osteomyelitis and septic arthritis Osteomyelitis and septic arthritis A Salmonella infection: lytic lesion and periostitis B Staphylococcal septic arthritis: lytic lesions and joint space narrowing

Sickle cell Disorders13 Sickle Cell Anemia Radionuclide abnormalities: Radionuclide abnormalities: technetium-labeled polyphosphate bone scanning A&B Infarctions C Old infarctions and calcifications D New focal area of augmented activity

Sickle cell Disorders14 Clinical Features G.U system: renal medulla damage, papillary necrosis, renal failure, priapism G.U system: renal medulla damage, papillary necrosis, renal failure, priapism

Sickle cell Disorders15 Clinical Features Spleen: enlargement & infarction, autosplenectomy(role of Plasmodium in Africa) Spleen: enlargement & infarction, autosplenectomy(role of Plasmodium in Africa) Liver: jaundice, enlargement, gallstone Liver: jaundice, enlargement, gallstone Cardiopulmonary: tachycardia, murmur, cardiomegaly, hypotension, pulmonary infarction, acute chest syndrome Cardiopulmonary: tachycardia, murmur, cardiomegaly, hypotension, pulmonary infarction, acute chest syndrome

Sickle cell Disorders16 Clinical Features Eye: retinopathy Eye: retinopathy (resembling sea - fans), lower bulbar conjunctival segmentation of vessels (comma - shaped), the orbital compression synd. (orbital marrow infarction) (resembling sea - fans), lower bulbar conjunctival segmentation of vessels (comma - shaped), the orbital compression synd. (orbital marrow infarction)

Sickle cell Disorders17 Clinical Features CNS: CVA( obstruction of major vessels, in children and older patients) CNS: CVA( obstruction of major vessels, in children and older patients) Infections: asplenia, impaired phagocytosis, defective complement pathway(pneumonia most common) Infections: asplenia, impaired phagocytosis, defective complement pathway(pneumonia most common)

Sickle cell Disorders18 Clinical Features Pregnancy: pyelonephritis, pulm. Infarction, chest synd., antepartum hemorrhage, prematurity, fetal death, folate def., maternal mortality~1.5% (in some parts >10%) Pregnancy: pyelonephritis, pulm. Infarction, chest synd., antepartum hemorrhage, prematurity, fetal death, folate def., maternal mortality~1.5% (in some parts >10%) Leg ulcers Leg ulcers

Sickle cell Disorders19 Laboratory Features Hb 5-11 gr/dL Hb 5-11 gr/dL Normocytic normochromic anemia Normocytic normochromic anemia Lab. signs of hemolysis Lab. signs of hemolysis Plasma Tocopherol and Zinc often low(Zincuria) Plasma Tocopherol and Zinc often low(Zincuria)

Sickle cell Disorders20 Diagnosis Hb electrophoresis No normal HbA in SS, SC & heterozygotes for sickle cell and ß 0 -thalassemia No normal HbA in SS, SC & heterozygotes for sickle cell and ß 0 -thalassemia Increased HbA 2 in heterozygotes for sickle cell and ß 0 -thalassemia but not in SS disease Increased HbA 2 in heterozygotes for sickle cell and ß 0 -thalassemia but not in SS disease Sickling test and solubility test less reliable Sickling test and solubility test less reliable PCR for prenatal diagnosis PCR for prenatal diagnosis

Sickle Thalassemia Splenomegaly Splenomegaly S/Beta + thalassemia Rare crises and aseptic necrosis, Hb:10– 14, MCV: 70–80, Hb S/A:60/40 S/Beta + thalassemia Rare crises and aseptic necrosis, Hb:10– 14, MCV: 70–80, Hb S/A:60/40 S/Beta° thalassemia S/Beta° thalassemia Vaso-occlusive crises, aseptic necrosis of bone, Hb: 7–10, MCV: 60–80, Hb S/A:100/0, Hb F:1–10% Vaso-occlusive crises, aseptic necrosis of bone, Hb: 7–10, MCV: 60–80, Hb S/A:100/0, Hb F:1–10% Sickle cell Disorders21

Sickle cell Disorders22 Sickle Cell Anemia

Sickle cell Disorders23 Sickle Cell Anemia

Sickle cell Disorders24 Sickle Cell Anemia

Sickle cell Disorders25 Sickle Cell Anemia

Sickle cell Disorders26 Hemoglobin SC disease

Sickle cell Disorders27 Therapy Folic acid Folic acid Blood transfusion Blood transfusion Cold & high altitude avoidance Cold & high altitude avoidance Antibiotics Antibiotics Hydration Hydration Keeping warm Keeping warm

Sickle cell Disorders28 Therapy Splenectomy & exchange transfusion in sequestration crisis Splenectomy & exchange transfusion in sequestration crisis Regular transfusion to maintain HbS ~ 30% in stroke Regular transfusion to maintain HbS ~ 30% in stroke Cholecystectomy for symptomatic gall - stone Cholecystectomy for symptomatic gall - stone Joint replacement Joint replacement BMT BMT Hydroxyurea Hydroxyurea

Sickle cell Disorders29 Sickle Cell Trait Heterozygous state Heterozygous state HbS<50% in RBCs HbS<50% in RBCs HbS HbA ) HbS HbA ) Lab. findings Lab. findings Clinical features Clinical features

Other Hemoglobinopathies Hb C disease Hb C disease Hb D disease Hb D disease Methemoglobine Methemoglobine Sickle cell Disorders30