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Sickle cell Disorders Sickle cell Disorders 1 1 Sickle Cell Sickle Cell Anemia Anemia
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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.

Dec 16, 2015

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Page 1: 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.

Sickle cell DisordersSickle cell Disorders 11

Sickle Cell AnemiaSickle Cell Anemia

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Sickle cell DisordersSickle cell Disorders 22

Sickle Cell AnemiaSickle Cell Anemia

HbS: a2 ß2 6Glu Val

Sickle cell disorders: sickling with o2

Sickle cell diseases: SS (the most severe), SD (the mildest), S-thal & SC (somewhat milder)

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Sickle Cell AnemiaSickle Cell Anemia

HbS undergoes sickling with o2 - 14 strands of the fibers pairs a fiber with 21 nm diameter firm gel sickled red cells

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Sickle cell DisordersSickle cell Disorders 55

InheritanceInheritanceHomozygous stateHomozygous stateHeterozygous stateHeterozygous state

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Sickle cell DisordersSickle cell Disorders 66

Clinical FeaturesClinical Features Manifestation by 10-12 weeks of age Manifestation by 10-12 weeks of age

(decrease in HbF).(decrease in HbF). Crises: vaso-occlusive, aplastic Crises: vaso-occlusive, aplastic

(folate, parvovirus B(folate, parvovirus B1919 and marrow and marrow necrosis), sequestration (drop of Hb necrosis), sequestration (drop of Hb to <6 or 3gr fall), hemolytic.to <6 or 3gr fall), hemolytic.

GrowthGrowth

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Sickle cell DisordersSickle cell Disorders 77

Clinical FeaturesClinical Features Bony abnormalities: thalassemic Bony abnormalities: thalassemic

feature, codfish spine and steplike feature, codfish spine and steplike depressions, dactylitis, avascular depressions, dactylitis, avascular necrosis (femur and humerus head). necrosis (femur and humerus head).

BM necrosis (Staf. & Salm.infection BM necrosis (Staf. & Salm.infection

or embolization to lung and chest or embolization to lung and chest syndrome)syndrome)

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Sickle cell DisordersSickle cell Disorders 88

Sickle Cell AnemiaSickle Cell Anemia

Sickle cell dactylitisSickle cell dactylitis (hand-foot syndrome)(hand-foot syndrome)

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Sickle cell DisordersSickle cell Disorders 99

Sickle Cell AnemiaSickle Cell Anemia

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

Page 10: 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.

Sickle cell DisordersSickle cell Disorders 1010

Sickle Cell AnemiaSickle Cell Anemia Vascular occlusion:Vascular occlusion:epiphyseal infarctionepiphyseal infarction

A&BA&B Progressive changes of Progressive changes of osteonecrosis: initial focal osteonecrosis: initial focal areas of sclerosis and areas of sclerosis and subsequent collapse with subsequent collapse with irregularity of the articular irregularity of the articular surface(arrowhead: lateral surface(arrowhead: lateral femoral osteophytes)femoral osteophytes)

CC The The snow-capped snow-capped appearance of the humeral appearance of the humeral head: patchy sclerosishead: patchy sclerosis(arrow)(arrow) and collapse of the and collapse of the articular surface articular surface (arrowhead)(arrowhead)

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Sickle Cell AnemiaSickle Cell Anemia

Growth disturbance Growth disturbance : H vertebrae: H vertebrae

A&B A&B Central indentation of Central indentation of the vertebral bodies, the vertebral bodies, initially may simulate fish initially may simulate fish vertebrae.vertebrae.

C-1C-1 Normal discovertebral Normal discovertebral junctionjunction

C-2C-2 Sickle cell anemia Sickle cell anemia (ischemia of the central (ischemia of the central portions of the cartilaginous portions of the cartilaginous end plates).end plates).

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Sickle Cell AnemiaSickle Cell Anemia

Osteomyelitis and Osteomyelitis and septic arthritisseptic arthritis

A A Salmonella infection: lytic Salmonella infection: lytic lesion and periostitislesion and periostitis

B B Staphylococcal septic Staphylococcal septic arthritis: lytic lesions and arthritis: lytic lesions and joint space narrowingjoint space narrowing

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Sickle cell DisordersSickle cell Disorders 1313

Sickle Cell AnemiaSickle Cell Anemia

Radionuclide Radionuclide abnormalities:abnormalities:

technetium-labeled technetium-labeled polyphosphate bone scanningpolyphosphate bone scanning

A&B A&B InfarctionsInfarctions

C C Old infarctions and Old infarctions and calcificationscalcifications

D D New focal area of augmented New focal area of augmented activity activity

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Sickle cell DisordersSickle cell Disorders 1414

Clinical FeaturesClinical Features

G.U system: renal G.U system: renal medulla damage, medulla damage, papillary necrosis, papillary necrosis, renal failure, renal failure, priapismpriapism

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Sickle cell DisordersSickle cell Disorders 1515

Clinical FeaturesClinical Features

Spleen: enlargement & infarction, Spleen: enlargement & infarction, autosplenectomy(role of Plasmodium in autosplenectomy(role of Plasmodium in Africa)Africa)

Liver: jaundice, enlargement, gallstoneLiver: jaundice, enlargement, gallstone

Cardiopulmonary: tachycardia, murmur, Cardiopulmonary: tachycardia, murmur, cardiomegaly, hypotension, pulmonary cardiomegaly, hypotension, pulmonary infarction, acute chest syndromeinfarction, acute chest syndrome

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Sickle cell DisordersSickle cell Disorders 1616

Clinical FeaturesClinical Features

Eye: retinopathyEye: retinopathy

(resembling sea - (resembling sea - fans), lower bulbar fans), lower bulbar

conjunctival conjunctival segmentation of segmentation of vessels (comma - vessels (comma -

shaped), the orbital shaped), the orbital compression synd. compression synd. (orbital marrow infarction)(orbital marrow infarction)

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Sickle cell DisordersSickle cell Disorders 1717

Clinical FeaturesClinical Features

CNS: CVA( obstruction of major CNS: CVA( obstruction of major vessels, in children and older vessels, in children and older patients)patients)

Infections: asplenia, impaired Infections: asplenia, impaired phagocytosis, defective phagocytosis, defective complement pathway(pneumonia complement pathway(pneumonia most common)most common)

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Sickle cell DisordersSickle cell Disorders 1818

Clinical FeaturesClinical Features Pregnancy: pyelonephritis, pulm. Pregnancy: pyelonephritis, pulm.

Infarction, chest synd., Infarction, chest synd., antepartum hemorrhage, antepartum hemorrhage, prematurity, fetal death, folate prematurity, fetal death, folate def., maternal mortality~1.5% def., maternal mortality~1.5% (in some parts >10%)(in some parts >10%)

Leg ulcersLeg ulcers

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Sickle cell DisordersSickle cell Disorders 1919

Laboratory FeaturesLaboratory Features

Hb 5-11 gr/dL Hb 5-11 gr/dL Normocytic normochromic Normocytic normochromic

anemiaanemiaLab. signs of hemolysisLab. signs of hemolysisPlasma Tocopherol and Zinc Plasma Tocopherol and Zinc

often low(Zincuria)often low(Zincuria)

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Sickle cell DisordersSickle cell Disorders 2020

DiagnosisDiagnosisHb electrophoresisHb electrophoresis

No normal HbA in SS, SC & No normal HbA in SS, SC & heterozygotes for sickle cell and heterozygotes for sickle cell and ßß0 0 --thalassemia thalassemia

Increased HbAIncreased HbA22 in heterozygotes for in heterozygotes for sickle cell and sickle cell and ßß0 0 -thalassemia but not -thalassemia but not in SS disease in SS disease

Sickling test and solubility test less Sickling test and solubility test less reliablereliable

PCR for prenatal diagnosisPCR for prenatal diagnosis

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Sickle ThalassemiaSickle Thalassemia

SplenomegalySplenomegaly S/BetaS/Beta++ thalassemia thalassemia

Rare crises and aseptic necrosis, Rare crises and aseptic necrosis, Hb:10– 14, MCV: 70–80, Hb S/A:60/40Hb:10– 14, MCV: 70–80, Hb S/A:60/40

S/Beta° thalassemia S/Beta° thalassemia

Vaso-occlusive crises, aseptic necrosis Vaso-occlusive crises, aseptic necrosis of bone, Hb: 7–10, MCV: 60–80, Hb of bone, Hb: 7–10, MCV: 60–80, Hb S/A:100/0, Hb F:1–10% S/A:100/0, Hb F:1–10%

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Sickle Cell AnemiaSickle Cell Anemia

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Sickle Cell AnemiaSickle Cell Anemia

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Sickle Cell AnemiaSickle Cell Anemia

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Sickle Cell AnemiaSickle Cell Anemia

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Hemoglobin SC diseaseHemoglobin SC disease

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TherapyTherapy Folic acidFolic acid Blood transfusionBlood transfusion Cold & high altitude avoidanceCold & high altitude avoidance AntibioticsAntibiotics HydrationHydration Keeping warmKeeping warm

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Sickle cell DisordersSickle cell Disorders 2828

TherapyTherapy Splenectomy & exchange transfusion in Splenectomy & exchange transfusion in

sequestration crisissequestration crisis Regular transfusion to maintain HbS ~ Regular transfusion to maintain HbS ~

30% in stroke30% in stroke Cholecystectomy for symptomatic gall - Cholecystectomy for symptomatic gall -

stonestone Joint replacementJoint replacement BMTBMT HydroxyureaHydroxyurea

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Sickle Cell TraitSickle Cell Trait

Heterozygous stateHeterozygous state HbS<50% in RBCsHbS<50% in RBCs HbS<HbA( in S-HbS<HbA( in S-ßß thal. thal.

HbS>HbA )HbS>HbA ) Lab. findingsLab. findings Clinical features Clinical features

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Other HemoglobinopathiesOther Hemoglobinopathies

Hb C diseaseHb C disease Hb D diseaseHb D disease MethemoglobineMethemoglobine

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