Thalassemia

Introduction

Thalassemia is a blood disorder passed down through families (inherited) in which the
body makes an abnormal form or inadequate amount of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen. The disorder results in large numbers of red blood cells being destroyed, which leads to anemia.
They characterised by varying degrees of ineffective hematopoiesis and increased hemolysis.

There are two basic groups of thalassemia.

❖ Alpha ( α)Thalassemia In alpha-thalassemia, the alpha
genes are deleted; loss of one gene (α-/α) or both genes
(α-/α-) from each chromosome 16 may occur, in
association with the production of some or no alpha
globin chains
❖ Beta (β )Thalassemia In beta-thalassemia defective
production usually results from disabling point mutations
causing no (β0) or reduced (β-) beta chain production

CLINICAL OUTCOMES OF ALPHA THALASSEMIA

o Silent carriers
• asymptomatic
• “normal”
o Alpha Thalassemia trait
• no anemia /mild anemia
• microcytosis
-unusually small red blood cells due to fewer Hb in RBC
o Hb H disease
• microcytosis & hemolysis (breakdown of RBC)
• results in severe anemia
• bone deformities
• Golf ball inclusions on microscopy • splenomegaly (enlargement of spleen)
• “severe and life threatening”
• Hb Bart’s
• fatal hydrops fetalis – fluid build-up in fetal compartments, leads to death occurs in utero

BETA THALASSEMIA

o Beta Thalassemia: deficient/absent beta subunits
Commonly found in Mediterranean, Middle East, Asia, and
Africa
o Three types:
▪ Minor
▪ Intermedia
▪ Major (Cooley anemia)
▪ asymptomatic at birth as HbF functions

CLINICAL OUTCOMES OF BETA THALASSEMIA
❑ Beta Thalassemia minor (trait)
• asymptomatic
• microcytosis
• minor anemia
• Elevated HbA2 >3.4%
❑ Beta Thalassemia intermedia .
• symptoms similar to Cooley Anemia but less severe
❑ Beta Thalassemia major (Cooley Anemia)
• most severe form
• moderate to severe anemia
• intramedullary hemolysis (RBC die before full development)
• peripheral hemolysis & splenomegaly
• skeletal abnormalities (overcompensation by bone marrow)
• congestive heart failure,pulmonary hypertension

CLINICAL OUTCOMES OF BETA THALASSEMIA

❑ Beta Thalassemia minor (trait)
• asymptomatic
• microcytosis
• minor anemia
• Elevated HbA2 >3.4%
❑ Beta Thalassemia intermedia .
• symptoms similar to Cooley Anemia but less severe
❑ Beta Thalassemia major (Cooley Anemia)
• most severe form
• moderate to severe anemia
• intramedullary hemolysis (RBC die before full development)
• peripheral hemolysis & splenomegaly
• skeletal abnormalities (overcompensation by bone marrow)
• congestive heart failure,pulmonary hypertension

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

SIGNS & SYMPTOMS

o Beta Thalassaemia Minor :
Usually no signs or symptoms
except for a mild persistent anemia not responding to hematinics.
o Beta Thalassaemia Major : manifests after 6 months

1. Pallor- fatigue, irritability
2. Growth retardation.
3. Recurrent infections
4. Bony abnormalities specially of the facial bones, hemolytic facies,
   caput quadtratum
5. Enlarged spleen and liver.
6. Delayed sexual development
7. Features of complications .

CLINICAL PRESENTATION

❑ Shortage of red blood cells- Anemia
❑ Pale skin
❑ Weakness
❑ Fatigue
❑ Enlarged liver and spleen- hepatosplenomegaly
❑ Heart defects
❑ Abnormalities of the urinary system or genitalia
❑ Hb Bart syndrome can cause complications in pregnancy
such as
• High blood pressure
• Premature delivery
• Abnormal bleeding
• Jaundice

THALASSEMIA COMPLICATIONS

(1) Transfusion-transmitted infections,
(2) Transfusional iron overload,
(3) Toxicities of iron chelation therapy

Management:

❑ 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
❑ Medications
• FOLIC ACID- ORAL
• FOLIC ACID – INJECTION

Treatment for beta thalassemia involves iron chelation.

1. Deferoxamine
2. Deferasirox
   Surgical Treatment
   ❑ Splenectomy- decrease transfusion requirements
   ❑ Cholecystectomy