? Chief Complaint: Anemia and jaundice.
? History of Present Il ness: At the time of presentation, He had been
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chronical y jaundiced and anemic since childhood, with multiple
episodes of severe anemia requiring transfusion. He reported
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receiving more than 30 units of blood prior to age 17.Brit S. Shackley, Thomas A. Drake, Anthony W. Butch. Chronic Microcytic Anemia and Jaundice in a 36-Year-Old Male
of Burmese Descent. Lab medicine.2010; 41:78-82
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? Past Medical History: The patient contracted hepatitis C secondary toblood transfusions he received in Burma. Folic acid was his only
medication. He has no history of tobacco or alcohol abuse.
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? Family History: The patient is married with 1 child and works as an
accountant. His mother and 1 sister both have thalassemia, although
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they are not as severely affected as he is. His father and 3 brothershave no known hematologic disorders.
? Physical Examination: Upon presentation, the patient was a well-
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nourished, well-developed male appearing jaundiced.
? Non-tender splenomegaly was noted extending to the level of the
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umbilicus.? There were no other abnormal findings on physical examination.
? The following vital signs were recorded: blood pressure, 130/75 mm
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Hg; pulse, 72; and respiration rate, 16.Hematological Report
PBF
Basophilic stippling
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Biochemistry Report
HPLC
Thalassemia
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? Thalassemias are a common cause of hypochromic microcytic anemia
which arises from the reduced or absent synthesis of the globin chain
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of hemoglobin.? a quantitative defect of hemoglobin synthesis.
1. Thalessemia
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2. ThalessemiaOrganization of Globin genes
Thalassemia
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? Deletions in the -globin genecluster account for most of the
mutations.
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? 1 or 2 alleles deleted: Thal Trait
? 3 alleles deleted: HbH Disease
? All 4 deleted: Hb Bart/Hydrops
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Fetalis ( Fatal at Birth)Thalassemia
? Inherited mutation of the beta-globin gene,
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? Reduced synthesis of the beta globin chain of hemoglobin.? The highest prevalence is in people of Mediterranean, Middle Eastern,
and Asian descent
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+
0
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? Beta-thalassemia minor, also called carrier or trait, heterozygous statethat is usually asymptomatic with mild anemia
? Homozygosity or compound heterozygosity for beta-thalassemia
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mutations cause a more severe spectrum of anemias called beta
thalassemia intermedia and beta-thalassemia major.
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? These two are distinguished clinically by transfusion dependence.? Beta-thalassemia major requires routine transfusions, and intermedia
does not
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Beta Thalassemia - StatPearls - NCBI BookshelfMolecular Mechanisms
? -thalassemia: deletions in the -globin gene cluster account for
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most of the mutations,? -thalassemia : mutations involving one (or a limited number of
nucleotides) within the gene or its immediate flanking regions
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Point Mutations in Thalassemia
Clinical Features
? Beta-thalassemia minor is typically discovered incidentally on routine
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CBC. Patients may have mild symptoms of anemia without significant
physical exam findings.
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? Beta-thalassemia intermedia encompasses a wide range of clinicalpresentations but no transfusion required
? can present in children as young as two years of age with growth and
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developmental delay
? Milder forms of beta thalassemia intermedia may first present in
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adults as fatigue and pallor? Beta-thalassemia major present between 6 and 24 months of age
when hemoglobin production transitions from fetal (HbF) to adult
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(HbA).
? Severe anemia ensues and presents as feeding problems, irritability,
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failure to thrive, pal or, and abdominal enlargement fromhepatosplenomegaly
? Frontal bossing, maxillary hypertrophy, and long bone deformities are
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common skeletal findings.
Pathophysiological Mechanisms of Thal
Major
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1. Decreased hemoglobin synthesis causing anemia and an increase in
HbF and HbA2 as there are decreased beta chains for HbA formation
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2. the relative excess alpha chains form insoluble alpha chain inclusionsthat cause marked intramedullary hemolysis
? This ineffective erythropoiesis leads to severe anemia and erythroid
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hyperplasia with bone marrow expansion and extramedullary
hematopoiesis
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? The bone marrow expansion leads to bony deformities, characteristical y ofthe facial bones which cause frontal bossing and maxil ary protrusion
? Hepatosplenomegaly from extramedullary hematopoiesis and ongoing
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hemolysis also causes thrombocytopenia and hepatic dysfunction.
? Complications of beta-thalassemia include iron overload and bone-
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deforming marrow expansion with extramedullary hematopoiesis.Laboratory Findings
? Microcytic anemia
? Reference range or increased red blood cell count
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? Reference range red cell distribution width.? Peripheral smear, red blood cells are hypochromic with increased
target cells.
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? There may be significant anisopoikilocytosis (variation of size andshape) in cases of beta-thalassemia major.
? Confirmation: Hemoglobin electrophoresis/ HPLC
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PBF
Peripheral blood, beta-thalassemia (clinically intermedia)
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showing anisopoikilocytosis, a nucleated red cell, andbasophilic stippling.
David T. Lynch, MD and Todd R. Needs, DO
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Hb Electrophoresis? Abnormal percentages of HbA, HbA2, and sometimes HbF.
? Decreased HbA percentage
? Mildly increased HbA2; less than 10%
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? Variably increased HbF.? Patients with beta(+) alleles will have variably decreased HbA levels,
and those that are homozygous beta(0) will produce no HbA.
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? Beta thalassemia minor characteristically has increased HbA2 (4-8%)
with variably normal-to-low elevations of HbF.
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? Beta-thalassemia major typically shows markedly elevated HbF (30-to-greater than 95%) with normal to mildly elevated HbA2.
Treatment
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? Thalassemia minor is a carrier state, it is typically asymptomatic.Genetic counseling and prenatal diagnosis might be indicated when
carriers are detected.
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? Thalassemia major is treated with red blood cell transfusion. The aim
of transfusion is mainly to suppress erythroid expansion. It also serves
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to mitigate symptoms of anemia and to inhibit gastrointestinal ironabsorption.
? The iron status of routinely transfused patients must be monitored.
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Clinical signs of iron overload and serial serum ferritin remain the
most reliable method to evaluate iron overload
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? Iron chelation therapy is general y started after patients have received10 to 20 transfusions or have serum ferritin levels > 1000 ng/mL.
Thank You!
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