Thalassemia

Thalassemia : A Blood Disorder that makes an abnormal form of hemoglobin

Its Is genetically Inherited
Apart from Changing the Hemoglobin structure ,it also Cause severe destruction of RBC
and thus it is a major cause of Anemia
Cause : Either By Mutation
Deletion of Specific Genes
Types Of Thalassemia :
Alpha Thalassemia : Atleast One Alpha gene has mutation/abnormality : Low Alpha
Beta Thalassemia : Beta globin genes are affected: Low Beta
Both Alpha and Beta are an important Constituent of Hemoglobin Molecule.
They are the Building blocks of hemoglobin which are not made enough in case of
thalassemia
Risk Factors :
If only one of your parents is a carrier for thalassemia, you may develop a form of the
disease called thalassemia minor.

If this occurs, you will probably not have symptoms, but you will be a carrier of the
disease
Some people with thalassemia minor do develop minor symptoms.

Patho-Physiology :


Symptoms :
Thalassemia Minor : Cause Minor Anemia
Beta Thalassemia :Two Types
Thalassemia Major:Cooleys Anemia
Thalassemia Intermedia

Apart from these , other symptoms includes the following

Shortness of breath, fatigue, and weakness (anemia)
Hepatomegaly
Bone pain and fragility fractures
Cardiac failure and arrhythmias
Splenomegaly
Gallstones
Malnutrition
Bronze skin

Shortness of breath, fatigue, and weakness (anemia)

Secondary to anemia
Deficient synthesis of the beta chain of hemoglobin causes red cells have low
HbA levels, thus explaining their phenotype and impaired ability to transport
oxygen

Imbalance between alpha and beta globin production leads to a precipitation of

the relatively overabundant alpha globin chain within the RBCs their precursors

Hepatomegaly
Ineffective erythropoiesis leads to activation of extramedullary erythropoiesis in
areas such as the spleen, liver, lymph nodes, and the thorax.
Hepatomegaly can result from a number of mechanisms;
extramedullaryerthyropoiesis, hepatitis due to chronic transfusion associated
infections, and iron overload.

Bone pain and fragility fractures

Caused by two major mechanisms:
Destruction of the cortex leading to weakening of the bone
Secondary to Osteopenia/osteoporosis (mechanism above)

Cardiac failure and arrhythmias

Secondary to anemia and iron overload

Splenomegaly
Secondary to extramedullaryhemotopoiesis
Can also be due to extravascular hemolysis causing a hypertropic response in
the spleen.

Gallstones
Bilirubin stones
Lifelong hemolytic state causes increased bilirubin deposition in the gallbladder

Malnutrition
Rapidly growing erythrocyte precursors compete for nutrients and can cause
malnutrition

Bronze skin
Cutaneous iron deposition damages the skin and enhances melanin production
by the melanocytes.

Examination :
The doctor will do a physical exam to look for an enlarged spleen.
A blood sample will be sent to a laboratory to be tested.
Red blood cells will appear small and abnormally shaped when looked at under a
microscope.
A complete blood count (CBC) reveals anemia.
A test called hemoglobin electrophoresis shows the presence of an abnormal form of
hemoglobin.

 A test called mutational analysis can help detect alpha thalassemia.

Treatment :

Regular blood transfusions to ensure non-anemic states

Iron chelation: Deferoxamine/Deferiprone
Endocrine Therapy
Splenectomy and cholecystectomy

Transfusions:
Regular blood transfusions to ensure non-anemic states and prevent some of the
disease complications (Target Hb 90-100 g/L)
Leukodepletion techniques are used to ensure less alloimmunization and nonhemolytic transfusion reactions.
Testing for viruses is done to reduce transfusion transmitted infections

Iron chelation:
Deferoxamine/deferiprone work by binding serum iron and clearing it via the urine.
Deferiprone has been shown to improve cardiac functioning (left ventricular ejection
fraction; LVEF) in patients with thalassemia major.

Endocrine therapy:
Administration of the deficient hormones (sex hormones and thyroid hormones)
Use of fertility agents to induce spermatogenesis and achievement of pregnancy
osteoclast inhibitors (bisphosphonates) to prevent osteopenia and osteoporosis.

Splenectomy and cholecystectomy:

Splenectomies often assist with reducing transfusion requirements
Cholecystectomies are often required to the presence of bilirubin stones in the
gallbladder.

Outlook (Prognosis) :
Severe thalassemia can cause early death (between ages 20 and 30) due to heart failure.
Getting regular blood transfusions and therapy to remove iron from the body helps improve
the outcome.
Less severe forms of thalassemia often do not shorten lifespan.
You may want to seek genetic counseling if you have a family history of the condition and
are thinking of having children.

 Possible Complications:
Iron overload
A combination of factors, including ineffective erythropoiesis and tissue hypoxia, lead to
increased iron absorption via the GI tract; via hepcidin inhibition.
This Iron is usually transferrin bound, however, when the total amount of iron exceeds the
transferrin binding limits, reactive oxygen species are produced through the fenton reaction
Compounded by life long transfusions
Iron deposition occurs in visceral organs (mainly in the endocrine glands, the heart, and the
liver) causing failure.
Endocrinopathies
Due to iron deposition in multiple endocrine glands inducing damage to those glands.
Hypogonadism, hypothyroidism, hypoparathyroidism, hypopituitarism, testicular/ovarian
failure, diabetes are among the complications
Hemolysis
Alpha globin precipitation leads to cell membrane damage
Mature red cells with alpha precipitate inclusions and membrane damage are more prone
to sequestration and extravascular hemolysis within the spleen
Cortical destruction and impaired bone growth
Uncompensated anemia creates a strong stimulus through erythropoietin (EPO) signalling
to ramp up erythropoiesis. This causes erythroid hyperplasia within the bone marrow, which
expands and destroys adjacent areas of bone such as the cortex, impairing bone growth
and creating malformations
Arterial and venous thromboembolism
RBC membrane dysfunction increases the expression of negatively charged
phosphatidylserines, which have been shown to induce platelet activation.
Deformed RBCs may directly induce vascular damage
RBCs and platelets carry higher levels of ROS (fenton reaction, described above)
Further hypothesis include a chronic hypercoaguable state, due to abnormal levels of
coagulation factors in thalassemia patients.