Thalassemia Flashcards
What is Thalassemia?
Group of genetic disorders characterised by reduced globin chain synthesis
Under or no production of 1 globin chain
Unmatched globins precipitate, damaging RBC membranes causing their haemolysis whilst still in the marrow
Describe the inheritance of Thalassemia
Autosomal recessive
Where is the B globin gene located?
Chr11
Where is the A globin gene located?
Chr16
Describe the aetiology of Thalassemia
Imbalance of globin chain production + deposition in erythroblasts+ erythrocytes (membrane damage + cell destruction due to imbalance between globin chains)
What does imbalance in chain production in Thalassemia lead to?
Ineffective erythropoiesis
Haemolysis
Anaemia
Extramedullary haematopoiesis
What is Alpha Thalassemia?
Reduction in alpha-globin chain synthesis.
4 alpha-globin genes on the chromosome.
What are the different types of Alpha Thalassemia according to number of gene deletions?
4= Hb Barts Hydrops Fetalis (intrauterine death) 3= Hb H: microcytic hypochromic anaemia + splenomegaly 2= Alpha 0 thalassemia: microcytic hypochromic red cells, NO ANAEMIA 1 = Alpha+ thalassemia: microcytic hypochromic red cells, NO ANAEMIA
What is Beta Thalassemia major?
Homozygous beta thalassemia
Little or no beta-chain synthesis
What is Beta Thalassemia intermedia?
Mild defect in B-chain synthesis due to e.g. co-inheritance of B thalassemia trait with another haemoglobinopathy like HbC, leads to:
Microcytic anaemia
Reduced alpha-chain synthesis
Increased gamma-chain synthesis
What is Beta Thalassemia trait?
Heterozygous carrier state
ASYMPTOMATIC
Mild microcytic anaemia
Increased red cell count
Describe the epidemiology of Thalassemia
WORLDWIDE
Most common in the MEDITERRANEAN + areas of the Middle-East
List 5 signs of Beta Thalassemia major
Pallor Malaise Severe anaemia Failure to thrive Prone to infection
When do symptoms of Beta Thalassemia present? Why?
3-6 months
Change from HbF (2alpha2gamma) to HbA (2alpha2beta)
Describe symptoms of Alpha Thalassemia
Symptoms of anaemia
Hb H disease: Growth retardation + Sx of gallstones: abdo pain, bloating + wind
How may Alpha or Beta Thalassemia trait present?
May be ASYMPTOMATIC
Detected during routine blood tests or due to FH
List 5 clinical signs of Beta Thalassemia Major
Dyspnoea Mild jaundice Thalassaemia facies Hepatosplenomegaly Osteopenia
List 4 signs of HbH Alpha Thalassemia
Jaundice at birth
Chronic hemolytic anemia
Hepatosplenomegaly
Skeletal deformities (less common)
What is seen on FBC in Thalassemia?
Low Hb Low MCV (microcytic anaemia) Low MCH Normal RDW WBC count + plts elevated due to BM hyperplasia
What is seen on blood film in Alpha Thalassemia?
Hypochromic microcytic anaemia Target cells + basophilic strippling Howell jolly bodies Nucleated red cells High reticulocyte count Teardrop cells Anisopoikilocytosis
What is seen on blood film in Beta Thalassemia?
Hypochromic microcytic anaemia Howell jolly bodies Nucleated red cells High reticulocyte count Teardrop cells Anisopoikilocytosis
What is seen on Hb electrophoreses in Beta Thalassemia?
Absent or reduced HbA
High HbF + HbA2
What is seen on Hb electrophoresis in Alpha Thalassemia?
Will not pick up trait
Extra peak on HPLC due to Hb H
Describe Bone Marrow in Beta Thalassemia
Hypercellular
Erythroid hyperplasia
What other investigations may be used in Thalassemia?
Genetic Testing (rarely) LFTs: raised in B-thalassemia major/ intermedia (high unconjugated BR, high LDH) Skull X-Ray
What is seen on skull x-ray in Beta Thalassemia major?
‘Hair on end’ appearance
Caused by expansion of marrow into the cortex
What causes hepatosplenomegaly in B thalassemia major?
Erythrocyte pooling + extramedullary haematopoiesis
What causes Thalassemia facies? What are these?
Caused by marrow hyperplasia
High forehead
Prominent zygomatic bones, + maxilla “chipmunk”
How do Hb electrophoresis and HPLC differ?
Hb-electrophoresis: qualitative analysis
HPLC: qualitative + quantitative analysis
