Thalassemia, a group of inherited blood disorders, presents a complex interplay of genetic mutations and clinical manifestations. This presentation delves into the intricacies of thalassemia, exploring its genetic underpinnings, clinical spectrum, diagnostic modalities, and therapeutic approaches. Through comprehensive analysis and case studies, attendees will gain a deeper understanding of thalassemia's impact on patients' lives and the latest advancements in management strategies. Keywords: Thalassemia Genetic Disorders Hemoglobinopathies Blood Disorders Anemia Genetic Mutations Clinical Spectrum Diagnosis Treatment Modalities Transfusion Therapy Iron Chelation Therapy Genetic Counseling Patient Care Hematological Disorders Research Advancements

1. THALASEMIA

2. INTRODUCTION
• Thalassemia is an inherited autosomal recessive blood disorder
results in excessive destruction of red blood cells and further lead
to anemia.
• It is caused by variant or missing genes that affect how the body
make hemoglobin.
• People with thalassemia make less hemoglobin and fewer
circulating red blood cells than normal resulting in mild or severe
anemia.

3. Definition
• Thalassemia describes a group of inherited disorders characterized
by reduced or absent amount of hemoglobin, the oxygen carrying
protein inside the red blood cells.

4. Epidemiology
A- World Wide
• There are about 240 million carriers of beta thalassemia world wide
• Americas: 0-3% of the population is affected by a gene mutation
• Eastern Mediterranean: 2-18% of the population is affected by a gene
mutation
• Europe: 0-19% of the population is affected by a gene mutation
• Southeast Asia: 0-11% of the population is affected by a gene mutation
• Sub-Saharan Africa: 0-12% of the population is affected by a gene
mutation
• Western Pacific: 0-13% of the population is affected by a gene mutation

5. Cont..

6. Cont..

7. B- Pakistan
• In Pakistan β-thalassemia (β-thal) trait frequency ranges between
5.0-7.0%, thus, there are more than 10 million carriers in the
country; and every year, around 5000 children are diagnosed to
carry β-thal major (β-TM) in Pakistan.

8. Symptoms of thalassemia
• Slow growth in children
• Wide or brittle bones
• Enlarged spleen (an organ in your abdomen that filters blood and fights disease)
• Fatigue
• Weakness
• Pale or yellow skin
• Dark urine
• Poor appetite
• Heart problems
• In some people, symptoms show up at birth. In others, it can take a couple of years
to see anything. Some people who have thalassemia will show no signs at all.

9. Types of thalassemia
Thalassemia
Alpha
thalassemia
Beta
thalassemia

10. Alpha thalassemia
• Alpha thalassemia is a result of changes in the genes for the alpha
globin component in hemoglobin
• The worldwide distribution of inherited Alpha Thalassemia is
corresponding to areas of Malaria exposure

11. ETIOLOGY
• Mutation in the DNA of cell that produce hemoglobin
• It is a form of thalassemia involving the genes HB1 and HB2
• It is most commonly inherited in a Mendelian recessive fashion

12. Pathophysiology
• Alpha thalassemia results when there is disturbance in production
of alpha globin from any or all four of the alpha globin genes.
• Genes are responsible for the regulating the synthesis and
structure of different globin which are divided into 2 clusters.
• The alpha globin genes are encoded on chromosome 16 and the γ
,δ and β-globin genes are encoded on chromosome 11.
• A normal person carries a linked pair of alpha globin genes,2 each
from maternal and paternal chromosomes.

13. Continue
• Therefore alpha thalassemia occurs when there is a disturbance in
production of alpha globin from any or all four of the alpha globin genes
• When functional point mutations ,frame shift mutation , nonsense
mutation ,and chain termination mutations occur within or around the
coding sequences of the alpha globin gene cluster hemoglobin is
impaired.
• When that occurs, protein synthesis may be inhibited

14. Clinical Presentation
• Shortage of red blood cells-Anemia
• Pale skin
• Weakness
• Fatigue
• Enlarged liver and spleen hepatosplenomegaly
• Heart defects
• Abnormalities of urinary system or genitalia

15. Treatment of alpha thalassemia
• Treatment for thalassemia often involves regular blood
transfusions and folate supplements.
• If you receive blood transfusions , you should not take iron
supplements. Doing so can cause a high amount of iron to build up
in the body which can be harmful.
• Persons who receive significant numbers of blood transfusion need
a treatment called chelation therapy to remove excess iron from
the body
• Bone marrow transplant may help treat the disease in some
patients, especially children

16. SURGICAL TREATMENT
• Perform splenectomy if transfusion requirements are increasing.
• Surgical or orthodontic correction may be necessary to correct
skeletal deformities of the skull and maxilla caused by erythroid
hyperplasia
• DEFEROXAMINE-INJECTION

17. MEDICATIONS
• FOLIC ACID – ORAL
• FOLIC ACID -INJECTION

18. FOLIC ACID -ORAL
BRAND NAME(S):FA-8
USES
• Folic acid is the man made form of folate which is B6-VITAMIN
naturally found in some foods
• It is needed to form healthy cells, especially red blood cells
• Active forms of folic acid are :L-methyl folate and levomefolate
• Folic acid supplements are used to treat or prevent low folate
levels

19. Side Effects
• FOLIC ACID usually has very few side effects
• Possible side effects include:
• Serious allergic reaction, including :rash ,itching/swelling
(especially of the face/tongue/throat),dizziness, trouble
breathing

20. Beta thalassemia
• Specifically , it is characterized by a genetic deficiency in the
synthesis of beta-globin chains
• Beta-globin is a component (subunit)of hemoglobin

21. Types
A. THALASSEMIA
MAJOR(COOLEY’S ANEMIA)
1. Severe form of beta
thalassemia
2. Presence of two abnormal
genes that cause either a
severe decrease or complete
lack of beta globin production
B- THALASSEMIA MINOR
1. Presence of one normal
gene and one with mutation
2. Cause mild to moderate
anemia

22. Etiology
• Beta thalassemia is caused by a deficiency of beta globin inherited
in an autosomal recessive pattern , which means both copies of
the HBB(Hemoglobin beta)gene in each cell have mutations.
• The parents of an individual with an autosomal recessive condition
each carry one copy of the mutated gene , but they typically do
not show signs and symptoms of the condition

23. • A lack of beta globin leads to a reduced amount of functional
hemoglobin. Without sufficient hemoglobin ,RBCS do not develop
normally , causing a shortage of mature RBCS
• The low number of mature RBCS leads to anemia and other
associated health problems in people with beta thalassemia

24. CLINICAL PRESENTATION
Thalassemia minor characterized by mild anemia
Symptoms of beta thalassemia major appear in the first two years of life
Fatigue and weakness
Pale skin or jaundice (yellowing of the skin)
Protruding abdomen with enlarged spleen and liver
Dark urine
Abnormal facial bones and poor growth
A poor appetite

25. Pathophysiology
• In beta thalassemia major, patients have severe anemia ,ineffective
erythropoiesis, extra medullary hematopoiesis and iron overload
resulting from transfusion and increased iron absorption
• The skin may show pallor from anemia and jaundice from
hyperbilirubinemia
• The skull and other bones may be deformed secondary to erythroid
hyperplasia with intramedullary expansion and cortical bone thinning
• Heart examination may reveal findings of cardiac failure and arrhythmia
, related to either severe anemia or iron overload

26. • Abdominal examination may reveal changes in the liver,
gallbladder and spleen
• Patients who have received blood transfusion may have
hepatomegaly or chronic hepatitis due to iron overload
• Transfusion associated viral hepatitis resulting in cirrhosis portal
hypertension also may be seen

27. SURGICAL TREATMENT
• Splenectomy decrease transfusion requirements
• Cholecystectomy patients with thalassemia minor may have
bilirubin stones in their gallbladder and, if symptomatic, may
require treatment. Perform a cholecystectomy using a laparoscope
or carry out the procedure at the same time as the splenectomy

28. Treatment
• Treatment for beta thalassemia involves iron chelation.
i. Deferoxamine
ii. deferasirox

29. Diagnosis
• Most children with moderate to severe thalassemia show signs and
symptoms within their first two years of life. If your doctor
suspects your child has thalassemia, he or she can confirm a
diagnosis with blood tests.
• Blood tests can reveal the number of red blood cells and
abnormalities in size, shape or color. Blood tests can also be used
for DNA analysis to look for mutated genes

30. Prenatal testing
• Testing can be done before a baby is born to find out if he or she
has thalassemia and determine how severe it might be. Tests used
to diagnose thalassemia in fetuses include:
• Chorionic villus sampling. Usually done around the 11th week of
pregnancy, this test involves removing a tiny piece of the placenta
for evaluation.
• Amniocentesis. Usually done around the 16th week of pregnancy,
this test involves examining a sample of the fluid that surrounds
the fetus

31. Treatment
• Mild forms of thalassemia trait don't need treatment.
• For moderate to severe thalassemia, treatments might include:
• Frequent blood transfusions. More severe forms of thalassemia often require frequent blood transfusions,
possibly every few weeks. Over time, blood transfusions cause a buildup of iron in your blood, which can
damage your heart, liver and other organs.
• Chelation therapy. This is treatment to remove excess iron from your blood. Iron can build up as a result
of regular transfusions. Some people with thalassemia who don't have regular transfusions can also develop
excess iron. Removing the excess iron is vital for your health.
• To help rid your body of the extra iron, you might need to take an oral medication, such as deferasirox
(Exjade, Jadenu) or deferiprone (Ferriprox). Another drug, deferoxamine (Desferal), is given by needle.
• Stem cell transplant. Also called a bone marrow transplant, a stem cell transplant might be an option in
some cases. For children with severe thalassemia, it can eliminate the need for lifelong blood transfusions
and drugs to control iron overload.
• This procedure involves receiving infusions of stem cells from a compatible donor, usually a sibling.

32. Prognosis
• Alpha-thalassemia
• Alpha-thalassemia silent carrier: The prognosis for silent carriers of alpha-thalassemia
(loss of 1 alpha-globin chain) is excellent. This patient lives normal lives with no
significant transfusion requirements. Life expectancy is similar as persons with no
thalassemia.
• Alpha-thalassemia trait: Patients with alpha-thalassemia trait (loss of 2 alpha-globin
chains) have an excellent prognosis. In rare cases, patients with the alpha-thalassemia
traits require transfusions, but their life expectancy is similar as persons without
thalassemia.
• HbH disease: Patients with HbH disease (loss of 3 alpha-globin chains) have a somewhat
poor prognosis, as these patients can have significant transfusion requirements. One
major causes of death include iron overload leading to cardiac failure.
• Hb Barts: Patients with Hb Barts (loss of 4 alpha-globin chains) have the worst prognosis
amongst all thalassemias. These patients typically die in utero from hydrops fetalis.

33. Cont..
• Beta-thalassemia
• Beta-thalassemia minor: These patients are usually asymptomatic. Prognosis is favorable and
is excellent compared to all other forms of beta-thalassemia.
• Beta-thalassemia intermedia: The prognosis for beta-thalassemia intermedia is fairly good.
Iron accumulation in organs is less common since they do not receive many blood transfusions.
These patients generally do not develop hypothyroidism or hypogonadism. Women with beta-
thalassemia intermedia can have normal pregnancies. Given that cardiac systolic function is
usually preserved, the cardiac disease does not usually contribute towards a poor prognosis
for patients with beta-thalassemia intermedia.
• Beta-thalassemia major (Cooley's anemia): The prognosis for beta-thalassemia major is
generally poor, as patients have severe defects in beta-globin production and thus are
susceptible to treatment-related complications. These patients typically die from iron
deposition in the heart (infiltrative cardiomyopathy) due to repeated blood transfusions. In
71% of patients with beta-thalassemia major, cardiovascular etiology will be the cause of
death.[8] Other common complications that contribute to a poor prognosis are development of
hepatitis B, hepatitis C, and HIV from blood transfusions. Venous thrombosis contributes to
morbidity and sometimes mortality

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