Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st year (First Year) Biochemistry ppt lectures Topic 16 Thalassemia Notes. - biochemistry notes pdf, biochemistry mbbs 1st year notes pdf, biochemistry mbbs notes pdf, biochemistry lecture notes, paramedical biochemistry notes, medical biochemistry pdf, biochemistry lecture notes 2022 ppt, biochemistry pdf.
Thalassemia
Case
? Patient: A 36-year-old male of Burmese descent.
? Chief Complaint: Anemia and jaundice.
? History of Present Il ness: At the time of presentation, He had been
chronical y jaundiced and anemic since childhood, with multiple
episodes of severe anemia requiring transfusion. He reported
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
? Past Medical History: The patient contracted hepatitis C secondary to
blood transfusions he received in Burma. Folic acid was his only
medication. He has no history of tobacco or alcohol abuse.
? Family History: The patient is married with 1 child and works as an
accountant. His mother and 1 sister both have thalassemia, although
they are not as severely affected as he is. His father and 3 brothers
have no known hematologic disorders.
? Physical Examination: Upon presentation, the patient was a well-
nourished, well-developed male appearing jaundiced.
? Non-tender splenomegaly was noted extending to the level of the
umbilicus.
? There were no other abnormal findings on physical examination.
? The following vital signs were recorded: blood pressure, 130/75 mm
Hg; pulse, 72; and respiration rate, 16.
Hematological Report
PBF
Basophilic stippling
Biochemistry Report
HPLC
Thalassemia
? Thalassemias are a common cause of hypochromic microcytic anemia
which arises from the reduced or absent synthesis of the globin chain
of hemoglobin.
? a quantitative defect of hemoglobin synthesis.
1. Thalessemia
2. Thalessemia
Organization of Globin genes
Thalassemia
? Deletions in the -globin gene
cluster account for most of the
mutations.
? 1 or 2 alleles deleted: Thal Trait
? 3 alleles deleted: HbH Disease
? All 4 deleted: Hb Bart/Hydrops
Fetalis ( Fatal at Birth)
Thalassemia
? Inherited mutation of the beta-globin gene,
? Reduced synthesis of the beta globin chain of hemoglobin.
? The highest prevalence is in people of Mediterranean, Middle Eastern,
and Asian descent
+
0
? Beta-thalassemia minor, also called carrier or trait, heterozygous state
that is usually asymptomatic with mild anemia
? Homozygosity or compound heterozygosity for beta-thalassemia
mutations cause a more severe spectrum of anemias called beta
thalassemia intermedia and beta-thalassemia major.
? These two are distinguished clinically by transfusion dependence.
? Beta-thalassemia major requires routine transfusions, and intermedia
does not
Beta Thalassemia - StatPearls - NCBI Bookshelf
Molecular Mechanisms
? -thalassemia: deletions in the -globin gene cluster account for
most of the mutations,
? -thalassemia : mutations involving one (or a limited number of
nucleotides) within the gene or its immediate flanking regions
Point Mutations in Thalassemia
Clinical Features
? Beta-thalassemia minor is typically discovered incidentally on routine
CBC. Patients may have mild symptoms of anemia without significant
physical exam findings.
? Beta-thalassemia intermedia encompasses a wide range of clinical
presentations but no transfusion required
? can present in children as young as two years of age with growth and
developmental delay
? Milder forms of beta thalassemia intermedia may first present in
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
(HbA).
? Severe anemia ensues and presents as feeding problems, irritability,
failure to thrive, pal or, and abdominal enlargement from
hepatosplenomegaly
? Frontal bossing, maxillary hypertrophy, and long bone deformities are
common skeletal findings.
Pathophysiological Mechanisms of Thal
Major
1. Decreased hemoglobin synthesis causing anemia and an increase in
HbF and HbA2 as there are decreased beta chains for HbA formation
2. the relative excess alpha chains form insoluble alpha chain inclusions
that cause marked intramedullary hemolysis
? This ineffective erythropoiesis leads to severe anemia and erythroid
hyperplasia with bone marrow expansion and extramedullary
hematopoiesis
? The bone marrow expansion leads to bony deformities, characteristical y of
the facial bones which cause frontal bossing and maxil ary protrusion
? Hepatosplenomegaly from extramedullary hematopoiesis and ongoing
hemolysis also causes thrombocytopenia and hepatic dysfunction.
? Complications of beta-thalassemia include iron overload and bone-
deforming marrow expansion with extramedullary hematopoiesis.
Laboratory Findings
? Microcytic anemia
? Reference range or increased red blood cell count
? Reference range red cell distribution width.
? Peripheral smear, red blood cells are hypochromic with increased
target cells.
? There may be significant anisopoikilocytosis (variation of size and
shape) in cases of beta-thalassemia major.
? Confirmation: Hemoglobin electrophoresis/ HPLC
PBF
Peripheral blood, beta-thalassemia (clinically intermedia)
showing anisopoikilocytosis, a nucleated red cell, and
basophilic stippling.
David T. Lynch, MD and Todd R. Needs, DO
Hb Electrophoresis
? Abnormal percentages of HbA, HbA2, and sometimes HbF.
? Decreased HbA percentage
? Mildly increased HbA2; less than 10%
? Variably increased HbF.
? Patients with beta(+) alleles will have variably decreased HbA levels,
and those that are homozygous beta(0) will produce no HbA.
? Beta thalassemia minor characteristically has increased HbA2 (4-8%)
with variably normal-to-low elevations of HbF.
? Beta-thalassemia major typically shows markedly elevated HbF (30-
to-greater than 95%) with normal to mildly elevated HbA2.
Treatment
? Thalassemia minor is a carrier state, it is typically asymptomatic.
Genetic counseling and prenatal diagnosis might be indicated when
carriers are detected.
? Thalassemia major is treated with red blood cell transfusion. The aim
of transfusion is mainly to suppress erythroid expansion. It also serves
to mitigate symptoms of anemia and to inhibit gastrointestinal iron
absorption.
? The iron status of routinely transfused patients must be monitored.
Clinical signs of iron overload and serial serum ferritin remain the
most reliable method to evaluate iron overload
? Iron chelation therapy is general y started after patients have received
10 to 20 transfusions or have serum ferritin levels > 1000 ng/mL.
Thank You!
This post was last modified on 05 April 2022