Definition of Thalassemiax The thalassemias are a diverse group of genetic blood diseases characterized by absent or decreased production of normal hemoglobin, resulting in microcytic anemia of varying degree.
Two Major Forms of Thalassemiax Alpha E Caused by a decrease in production of the alpha-globin genes due to a deletion or mutation of one or more of four alpha-globin genes on chromosome 16.x Beta E Caused by mutations of the beta-globin genes on chromosome 11.
Four Types of Alpha Thalassemiax Silent Carrier - 3 functional genes.x Alpha Thalassemia Trait - 2 functional & 2 non-functional genes.x Hemoglobin H disease - 1 functional gene.x Alpha Thalassemia Major - no functional genes.
Three Types of Beta Thalassemiax Beta Thalassemia Trait - one affected allele of chromosome 11.x Beta Thalassemia Intermedia - one or two affected alleles, but only mild symptoms experienced.x Beta Thalassemia Major - both alleles are affected and require blood transfusions and drug treatments to survive.
History of Thalassemiax Beta Thalassemia was first described by Thomas Cooley, known as Cooley’s anemia in 1925. E Symptoms exhibited: x Anemia x Splenomegaly ( due to increased activity/filtering of the red blood cells) x Enlargement of the Liver x Discoloration of the Skin x Enlargement of the Cranial and Facial Bones
DIAGNOSTIC FEATURES OF BETA-THALASSAEMIAx Majorx Profound hypochromic anaemiax Evidence of severe red cell dysplasiax Erythroblastosisx Absence or gross reduction of the amount of haemoglobin Ax Raised levels of haemoglobin Fx Evidence that both parents have thalassaemia minor
x Minorx Mild anaemiax Microcytic hypochromic erythrocytes (not iron- deficient)x Some target cellsx Punctate basophiliax Raised resistance of erythrocytes to osmotic lysisx Raised haemoglobin A2 fractionx Evidence that one parent has thalassaemia minor
Differences Between Thalassemia and Iron-deficient Anemiax Thalassemia is x Iron-deficient anemia is hereditary. not hereditary.x Iron is present in the x Iron is absent in the bone marrow. bone marrow.x Microcytosis is usually x Microcytosis is mild or very severe. absent.x Basophilic stippling of x Less frequent basophilic red blood cells is stippling of red blood common. cells.x Does not respond to x Responds to iron Iron therapy. therapy.
Similarities Between Thalassemia and Iron-Deficient Anemiax Red Blood Cell fragility is decreased.x Plasma iron may be decreased.x Target cells are present.
Thalassemia and Malaria “Malaria Hypothesis,” “the corpuscles of the anemic heterozygote are smaller than normal, and more resistant to hypotonic solutions. It is at least conceivable that they are also more resistant to attacks by the sporozoa which cause malaria.”x Studies have shown that individuals born with the thalassemia trait can survive malaria and pass the trait onto the next generation.
TREATMENT OF BETA- THALASSAEMIA MAJOR1) Erythropoietic failure: Allogeneic bone marrow transplantation from human leucocyte antigen (HLA)-compatible sibling Transfusion to maintain Hb > 100 g/l Folic acid 5 mg daily 2)Iron overload: Iron therapy forbidden Desferrioxamine therapy 3)Splenomegaly: causing mechanical problems, excessive transfusion needs →Splenectomy
Preventionx It is possible to identify a fetus with homozygous beta-thalassaemia by obtaining chorionic villous material for DNA analysis sufficiently early in pregnancy to allow termination. This examination is only appropriate if both parents are known to be carriers (beta-thalassaemia minor) and will accept a termination.