Download MBBS Biochemistry PPT 16 Thalassemia Lecture Notes

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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