Thalassemia minor is an inherited form of hemolytic anemia that is less severe than thalassemia major. This blood smear from an individual with thalassemia shows small (microcytic), pale (hypochromic), variously-shaped red blood cells. These small red blood cells (RBCs) are able to carry less oxygen than normal RBCs.
an inherited form of hemolytic anemia red blood cell (hemoglobin) abnormalities the most severe form of anemia the oxygen depletion in the body becomes apparent within the first 6 months of life Thalassemia major
If untreated, death usually results within a few years Note the small, pale (hypochromic), abnormally-shaped red blood cells associated with thalassemia major The darker cells likely represent normal RBCs from a blood transfusion
Diesease Autosomal recessive Deficiency: Synthesis of α/ - globin Origin: Mediteranean, African, Iranian, Indian, Southeast Asian Resistant to malaria
Prevalence of α-Thalassemia 0.01 % in non malarial areas ig. UK, Japan ig. UK, Japan ~ 49 % in Soutwest Pasific Islands
Prevalence of -Thalassemia ~ 1.5 % in Africans and African Americans ~ 30 % in Sardinia
Pathogenesis of -Thalassemia In adequate Hb production Reduced MCV/MCH Unbalanced accumulation of globin subunits Ineffective Erythrocyt 200 different mutations In Iran about 60 mutations
-Thalassemia Trait - –Hemoglobin is with in the reference range. –Reticulocyte count is within the reference range. –Mean corpuscular volume (MCV) is 75-85 fL. –Mean corpuscular hemoglobin (MCH) is 26 pg.
a-Thalassemia Alpha1 thalassemia minor (--/ ) –Hemoglobin is within the reference range. –Reticulocyte count is within the reference range. –MCV is 65-75 fL. –MCH is 22 pg.
Hemoglobin H disease Peripheral smear from a patient with hemoglobin H disease showing target cells, microcytosis and hypochromia. Morphological abnormalities are similar to those observed in beta thalassemia. In alpha2 thalassemia (silent trait) only mild microcytosis is observed.
HbH disease Hemoglobin H disease –Hemoglobin is 7-10 g/dL. –Reticulocyte count is 5-10%. –MCV is 55-65 fL. –MCH is 20 pg. –The peripheral blood smear shows small misshapen red cells, hypochromia, microcytosis, and targeting. –Brilliant cresyl blue stain demonstrates hemoglobin H inclusion bodies.
Hydrops fetalis –Hemoglobin is 4-10 g/dL. –MCV is 110-120 fL. –The peripheral blood smear shows severe hypochromia, and nucleated red blood cells.
Hydrops fetalis Functional α globin : 0 α: globin ratio : 0.0 Genotype: --/-- HbH Inclusion (Heinz body): Present Severe anemia Heart defect/fatal in utero/ shortly after birth
Treatment Avoid iron supplementation. It contributes to iron overload Administer folate supplementation to provide adequate amounts of the vitamin for increased utilization resulting from the hemolytic process and high bone marrow turnover rate. Provide prompt attention to infection, especially in children who have had a splenectomy. Administer blood transfusions only if necessary. If chronic transfusion is needed (hemoglobin H disease), iron chelation therapy should be considered to avoid iron overloading.
Surgical Care Hemoglobin H disease –Perform a splenectomy if transfusion requirements are increasing. –Surgical or orthodontic correction may be necessary to correct skeletal deformities of the skull and maxilla due to erythroid hyperplasia.
globin mutations Cryptic splice sites in Introns ( + ) IVSI-110 IVSII-745 Cryptic splice sites in exons Cd 26 (HbE) Cd 121 (HbD panjab/O Arab)
-Thalassemia major Onset: 6 months Severe hemolytic anemia Hb level< 7 g/dl Skin: pale Growth retardation don’t eat or sleep well Hepatosplenomegaly Bone marrow expansion: Make more red cells Expantion in face and skull Spleen: destroy of young red cell 80% of untreated patients: † by 5 y. Treatment: Cardiac/Hepatic: † by 30 y. Transfusion +Chelation > 30y.
Treatment Blood transfusion (3-4 weeks for life) Iron accumulation in body Remove the iron: Desferal: Infused under the skin (8-12 h/6 times a week) Bone marrow transplantation A sib brother or sister HLA matched
Stuck the red cell in the vessels In children: Spleen, chest, wrists,ankles In adults: hips and shoulders Anemia (Hb 7-8 g/dl) Infections (take antibiotics) Painful crises (6-18 months) Swollen and inflamed (hand/food syndrome)
What are the Complications? pain episodes increased infections bone damage yellow eyes or jaundice early gallstones lung blockage kidney damage and loss of body water in urine painful erections in men (priapism) blood blockage in the spleen or liver (sequestration) eye damage low red blood cell counts (anemia) delayed growth
Prenatal diagnosis I. ARMS-PCR (22 common mut.) II. PCR-RFLP (9 inf. RFLPs) III. RDB (60 mut.) IV. Sequencing