thalassemia alpha and beta

1. Thalassemia Syndrome
- Dr Rahul Arya
- Assistant Professor
- Department of Medicine

2. • Are a group of inherited hematologic disorders caused by defects in
the synthesis of one or more of the hemoglobin chains.
• Alpha thalassemia is caused by reduced or absent synthesis of alpha
globin chains.
• Beta thalassemia is caused by reduced or absent synthesis of beta
globin chains.

3. Epidemiology
• Thalassemia affects men and women equally and occurs in
approximately 4.4 of every 10,000 live births.
• Alpha thalassemia occurs most often in persons of African and
Southeast Asian descent.
• Beta thalassemia is most common in persons of Mediterranean,
African, and Southeast Asian descent.

4. Pathophysiology
• The composition of the four globin chains determines the hemoglobin
type.

5. • The transition from gamma globin synthesis (Hgb F) to beta globin
synthesis (Hgb A) begins before birth.
• By approximately six months of age, healthy infants will have
transitioned to mostly Hgb A, a small amount of Hgb A2, and
negligible Hgb F.

6. • Adult hemoglobin A (Hgb A) has two alpha and two beta chains
(alpha2 beta2).

7. • Hemoglobin A2 (HgbA2) has two alpha and two delta chains
(alpha2delta2).

8. Alpha Thalassemia
• Alpha thalassemia is the result of deficient or absent synthesis of
alpha globin chains, leading to excess beta globin chains.
• Alpha globin chain production is controlled by two genes on each
chromosome 16.
• Each of the four alpha globin genes contribute to the synthesis of the
alpha globin protein.

9. Prototypical Forms of Alpha Thalassemia
Variant of alpha thalassemia Chromosome 16 Signs and symptoms
Silent carrier One of four gene deletions Asymptomatic
Trait Two of four gene deletions Asymptomatic
Intermedia with significant Hgb H
(Hgb H disease)
Three of four gene deletions •Moderate to severe hemolytic
anemia
• Modest degree of ineffective
Erythropoiesis
• Splenomegaly
• Variable bone changes
Major with significant Hgb Bart's Four of four gene deletions Causes nonimmune hydrops fetalis,
usually fatal

10. Chromosome 16 gene deletions

11. Beta Thalassemia
• Beta thalassemia is the result of deficient or absent synthesis of beta
globin chains, leading to excess alpha chains.
• Beta globin synthesis is controlled by one gene on each chromosome
11.
• The two gamma globin genes are active during fetal growth and
produce Hgb F.
• The "adult" gene, beta, takes over after birth.

12. • Beta thalassemia occurs from any of more than 200 point mutations
and (rarely) deletions of the two genes.
• Beta globin chain production can range from near normal to
completely absent, leading to varying degrees of excess alpha globin
to beta globin chain production.

13. Prototypical Forms of Beta Thalassemia
Variant of Beta
thalassemia
Chromosome 11 Signs and Symptoms
Trait One gene defect Asymptomatic
Intermedia Two genes defective (mild to
moderate decrease in beta
globin synthesis)
Variable degrees of severity of
symptoms of thalassemia major
Major Two genes defective (severe
decrease in beta globin
synthesis)
•Abdominal swelling
• Growth retardation
•Irritability
• Jaundice, pallor
•Skeletal abnormalities
• Splenomegaly
• Requires lifelong blood
transfusions

14. Chromosome 11 gene defect

15. • The one gene defect, beta thalassemia trait (minor) is asymptomatic
and results in microcytosis and mild anemia.
• If the synthesis from both genes is severely reduced or absent, the
person has beta thalassemia major.
• If the synthesis of beta chains is less severely reduced , the person has
beta thalassemia intermedia.

16. • Persons with beta thalassemia major are almost never symptomatic
at birth because of the presence of Hgb F, but symptoms begin to
develop by six months of age.
• Most persons with thalassemia trait are found incidentally when their
complete blood count shows a mild microcytic anemia.

17. PATHOPHYSIOLOGY
• Disturbance of ratio between Alpha & non alpha globin chain
synthesis then absent or decrease production of one or more globin
chains
• Formation of abnormal Hb structures
• Ineffective erythropoiesis
• Excessive RBCs Destruction
• Iron Overload
• Extra-medullary hematopoiesis

19. SIGNS & SYMPTOMS
• Beta Thalassaemia Minor :
• Usually no signs or symptoms except for a mild persistent anemia
not responding to hematinics.
• BetaThalassaemia Major :
1. Pallor- fatigue, irritability
2. Growth retardation.
3. Recurrent infections
4. Bony abnormalities specially of the facial bones, hemolytic facies
5. Enlarged spleen and liver.
6. Delayed sexual development
7. Features of complications .

21. New bone formation can be
seen in the diploë, producing
a "hair-on-end“
appearance.

22. Investigations
1. Complete Blood Count- microcytic anemia
2. Peripheral Blood Smear
3. S. Iron, S. Ferritin
4. Hemoglobin electropheresis

23. • Microcytic anemia can be caused by:
1. Iron deficiency
2.Thalassemia
3. Lead poisoning
4.Sideroblastic anemia
5.Anemia of chronic disease.

24. Test Iron deficiency Beta thalassemia
MCV Low Low
Ferritin Low Normal
RDW Increased Normal
Hb electrophoresis Normal Abnormal

25. The peripheral smear of Thalassemia major

26. • The hemoglobin electrophoresis with beta thalassemia trait usually
has:
- Reduced or absent Hgb A
- Elevated levels of Hgb A2
- Increased Hgb F
• A normal concentration of HbA2 does not rule out beta thalassemia
trait, especially if there was coexistent iron deficiency.

27. MANAGEMENT OF THALASSEMIA
 Comprehensive management includes the following:
• Confirmation of the diagnosis
• Correction of anemia– Packed red cell transfusions
• Removal of excess iron– Chelation Therapy
• Management of complications – Endocrine and Cardiac
complications
• Curative Treatment– Stem Cell Transplantation
• Future treatment– Gene replacement therapy.

28. TRANSFUSION THERAPY IN THALASSEMIA
 Transfusion therapy in thalassemia has two goals:
• To prevent anemia
• To suppress endogenous erythropoiesis.
• Regular Blood Transfusions are Presently the Mainstay of Treatment
of Thalassemia Major.

29. • Leukoreduced packed red cell transfusion is desired type of blood for
thalassemic children.
• It helps in prevention of transfusion reactions and is achieved by
centrifugation;/saline washing/filtration.

30. WHEN TO START THE TRANSFUSION
• Blood transfusion is started as soon as diagnosis firmly established
(Except in children > 18 months of age).
• If age is > 18 months, these children are observed to r/o Thalassemia
Intermedia and if Hb drops < 7 gms%, regular transfusion started.
• The most ideal way to transfuse thalassemics is using group and type
specific saline washed packed red cells (HCT - 65 to 75%) that are
compatible by direct antiglobulin test (Coomb’s crossmatched).

31. THALASSEMIA COMPLICATIONS
• Complications can be grouped as
(1) transfusion-transmitted infections,
(2) transfusional iron overload,
(3) toxicities of iron chelation therapy, and
(4) bacterial infections

32. • Cardiac complications- arrhythmias, systolic and diastolic dysfunction
• Liver complications- hepatitis
• Endocrine complications- short stature, delayed puberty,
hypothyroidism, impaired glucose tolerence
• Bone complications- pathological fractures
• Infections: Yersinia , parvovirus B19
• Dental Complications
• Leg ulcers

33. HYPERSPLENISM- SPLENECTOMY
• Indications of splenectomy
An increase in the yearly requirement of packed cells more than 1.5 times the
basal requirement, i.e. packed cell 200 to 220 cc per kg/ year.
Massive splenic enlargement posing risk of splenic rupture, or when it is
associated with left upper quadrant pain or early satiety.
Presence of leukopenia or thrombocytopenia due to hyperspleenism.
 Splenectomy should be delayed till the patient is of 5 years of age as there is risk
of overwhleming sepsis below this age.

34. • IMMUNIZATION PRIOR TO SPLENECTOMY- Pneumococcal, Meningococal vaccine
and HIB vaccine.

35. IRON OVERLOAD AND CHELATION THERAPY
• Iron Overload Occurs in Thalassemic Patients due to treatment with
multiple transfusions.
• INITIATION OF CHELATION THERAPY:-
Serum ferritin >1000ng/dl
Patient has received 15-20 transfusions
Hepatic iron concentration exceeds 3.2mg/ g dry weight

36. CHELATING AGENTS
• Deferoxamine(DFO)
Route:SC/IV
Dose: 25-50 mg/kg/day
Adverse effects:- Local skin reaction, ototoxicity, infections,
ophthalmic toxicity, skeletal impairment

37. • Deferasirox
oral iron-chelating agent.
Single daily doses of 20–30 mg/kg.
Side effects :- elevations in liver enzymes and slight but persistent
increases in serum creatinine.

38. STEM CELL TRANSPLANTATION
• This is only the curative therapy available today.
• Sources of stem cells -: Bone Marrow, Peripheral Blood, Cord Blood,
Fetal Liver.
• Most success has been in children
1. younger than 15 yr of age
2. without excessive iron stores and hepatomegaly
3. who undergo sibling HLA-matched allogeneic transplantation.

39. Prevention
• Blood tests and family genetic studies can show whether an individual
has thalassemia or is a carrier.

40. ANTENATAL DIAGNOSIS
• When both partners, who are thalassemia minors, plan to have their
baby, they are told to report to their hematologist as soon as possible
after pregnancy is confirmed.
• Chorionic villous sampling (CVS) done between 9th and 11th week of
pregnancy.
• amniocentesis or cordocentesis-16 to 18 weeks of pregnancy.

41. World Thalassemia Day- May 8
Thank You..

42. • Test result:
‘Affected’ which means the fetus has thalassemia major, or
‘Unaffected’ meaning that the fetus is either thalassemia minor or
normal.
• Affected fetuses are advised to be terminated and unaffected fetuses
to be continued