thalassemia major minor & other subtypes soumaditya

THALASSEMIA MAJOR MINOR

& OTHER SUBTYPESSOUMADITYA BANERJEE, 5TH SEMESTER STUDENT

Moderator: Dr Santosh Kumar Mondal

Assoc.Professor, Pathology

CASE STUDY:

A four years old male child suffering from growth retardation, irritability ,anorexia till infancy.

O/E :1. pallor marked, huge enlargement of liver & spleen

2.no marked lymphadenopathy, 3. depressed nasal bridge

Classification of beta thalassemia:

Clinical Nomenclature Genotype Disease Molecular Genetics

β- Thalassemias

Thalassemia major Homozygous β0-thalassemia (β0/β0)

Severe; requires blood transfusions

Rare gene deletions in β0/β0 Defects in transcription, processing, or translation of β-globin mRNA

  Homozygous β+-thalassemia (β+/β+)  

Thalassemia intermedia β0/βSevere, but does not require regular blood transfusions

  β+/β+  

Thalassemia minor β0/βAsymptomatic with mild or absent anemia; red cell abnormalities seen

  β+/β

BETA THALASSEMIA MAJOR:

Highest incidence in south east asia , Mediterranean countries & parts of africa..

types of genetic mutations seen:Homozygous β0-thalassemia (β0/β0)

Homozygous β+-thalassemia (β+/β+)

Clinical features:

family history anemia appear during 6-8 months of

age mild icterus history of repeated blood transfusion hepatosplenomegaly dilatation of heart with feature of heart

failure facial & other bony anomalies.

Family history!!

CLINICAL FINDINGS AT DIAGNOSIS:

Clinical manifestation emerge during second sixth month of life.

Diagnosis always evident by 2nd yr. Pallor , irritability , abdominal

swelling ,jaundice are usual symptoms.

.

Thalassemic facies:

Radiograph shows:

Additional skeletal changes are observed in the metacarpals, metatarsals, and phalanges, where expanded medullary cavities produce a rectangular and then a convex shape .

Irregular fusion of the epiphyses of the proximal humerus results in characteristic shortening of the upper arms.

Figure

Hypercoaguable state: A chronic hypercoagulable state has been

observed even in childhood . It has been demonstrated that procoagulant phospholipids are exposed on the surface of the red cells and that platelets and the hemostatic system are activated in thalassemia major.

In addition, vascular endothelial cell injury and the peroxidative status due to iron overload have been proposed as possible mechanism.

Hepato spleenomegaly:

Causes: 1.prior to transfusion d/t

extramedullary hematopoeisis . 2. with transfusion iron overload

add a new reason to this. 3.this also increase chance of

hepatocellular carcinoma.

Heart:

Cardiac abnormalities are important causes of morbidity and mortality .

Cardiac enlargement secondary to anemia is almost always present.

myocardial hemosiderosis and serious iron-induced cardiac diseases were inevitable .

Lungs:

Patients exhibit primarily restrictive defects ; others experience mild to moderate small-airway obstruction and hyperinflation.

Most patients have a decreased maximal oxygen uptake and anaerobic threshold; these do not normalize after transfusion.

Beta thalassemia minor:

CLINICAL FEATURES: Asymptomatic spleen may be palpable mostly detected in adults as a

case of chronic anaemia

:

important feature:

This occurs mainly in endemic areas of malaria.

Thalassemia intermedia:

Clinical features: symptomatic with moderate anemia may have splenomegaly, bone

deformity recurrent leg ulcers ,gall

stones ,infections pt. may be iron overloaded.

Alpha thalassemia:

α- Thalassemias genetic abnormality clical feature

Hydrops fetails -/- -/- Lethal in utero without transfusions

Mainly gene deletions

HbH disease -/- -/α Severe; resembles β-thalassemia intermedia

α-Thalassemia trait -/- α/α (Asian) Asymptomatic, like β-thalassemia minor

  -/α -/α (black African)  

Silent carrier -/α α/α Asymptomatic; no red cell abnormality

Clinical manifestations:

Silent carrier: α+-Thalassemia trait has no consistent

hematologic manifestations. The red blood cells are not microcytic, and Hb

A2 and Hb F are normal. During the newborn period, small amounts

(≤3%) of Hb Bart (γ4) can be seen by electrophoresis or other techniques.

This condition is most often recognized when an apparently normal individual becomes the parent of a child with Hb H disease after mating with a person with α°-thalassemia trait.

α-Thalassemia Trait (α°-Thalassemia Trait) Levels of Hb A2 in the low to low

normal range (1.5%–2.5%) β/α synthetic ratios averaging 1.4 : 1

characterize α°-thalassemia trait. During the perinatal period, elevated

amounts of Hb Bart are noted (3%–8%).

Microcytosis is present in cord blood erythrocytes.

HbH disease:

HbH disease is common in Southeast Asia and relatively frequent in Mediterranean countries and parts of the Middle East,

Subjects with HbH disease may develop complications including hypersplenism, leg ulcers, and gallstones.

Hypersplenism has been reported in 10% of Thai patients with HbH disease, but seems to be rare elsewhere .

Iron overload is not common and has been reported only in some older patients and as a result of repeated blood transfusions

Hydrops fetalis: Hb Bart hydrops fetalis syndrome is the most

severe α-thalassemia clinical condition, often associated with the absent function of all four α-globin genes

A fetus homozygous for α0-thalassemia produces mainly Hb Bart (γ4), which is functionally useless for oxygen transport, and his or her survival to late pregnancy is due to the presence of small amounts of embryonic hemoglobins Portland 1 (ζ2γ2) and Portland 2 (ζ2β2

severe anemia (Hb level range, 3 to 8 g/dl) marked

hepatosplenomegaly, generalized edema, signs of cardiac failure, extensive extramedullary erythropoiesis in

many organs . Other congenital abnormalities: particularly

of the skeletal, cardiovascular, and urogenital system

Complication during pregnanacy:

Complications during pregnancy are common mild pre-eclampsia (hypertension, fluid

retention with or without proteinuria), polyhydramnios or oligohydramnios antepartum hemorrhage. Postpartum complications include :placenta

retention, eclampsia (fits and coma), hemorrhage, anemia, and sepsis.

Th thank you