Sickle cell Disorders Sickle cell Disorders 1 1 Sickle Cell Sickle Cell Anemia Anemia
Dec 16, 2015
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Sickle Cell AnemiaSickle Cell Anemia
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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
44
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InheritanceInheritanceHomozygous stateHomozygous stateHeterozygous stateHeterozygous state
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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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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 AnemiaSickle Cell Anemia
Sickle cell dactylitisSickle cell dactylitis (hand-foot syndrome)(hand-foot syndrome)
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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).
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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 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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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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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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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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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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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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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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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
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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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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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
Other HemoglobinopathiesOther Hemoglobinopathies
Hb C diseaseHb C disease Hb D diseaseHb D disease MethemoglobineMethemoglobine
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