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Autoimmune hemolytic anemia
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Hemolytic disease of the newborn
Paroxysmal nocturnal hemoglobinuria
Pyruvate kinase deficiency
Sickle cell disease (NORD)
Folate (Vitamin B9) deficiency
Vitamin B12 deficiency
Anemia of chronic disease
Iron deficiency anemia
Vitamin K deficiency
Langerhans cell histiocytosis
Essential thrombocythemia (NORD)
Polycythemia vera (NORD)
Acute intermittent porphyria
Porphyria cutanea tarda
Disseminated intravascular coagulation
Von Willebrand disease
Monoclonal gammopathy of undetermined significance
Thrombotic thrombocytopenic purpura
Antithrombin III deficiency
Factor V Leiden
Protein C deficiency
Protein S deficiency
Coagulation disorders: Pathology review
Extrinsic hemolytic normocytic anemia: Pathology review
Heme synthesis disorders: Pathology review
Intrinsic hemolytic normocytic anemia: Pathology review
Leukemias: Pathology review
Lymphomas: Pathology review
Macrocytic anemia: Pathology review
Microcytic anemia: Pathology review
Mixed platelet and coagulation disorders: Pathology review
Myeloproliferative disorders: Pathology review
Non-hemolytic normocytic anemia: Pathology review
Plasma cell disorders: Pathology review
Platelet disorders: Pathology review
Thrombosis syndromes (hypercoagulability): Pathology review
0 / 3 complete
allelic heterogeneity p. 55
intron/exon splicing variants p. 41
β -thalassemia and p. 425
in anemia taxonomy p. 423
target cells in p. 421
Beta thalassemia is a genetic disorder where there’s a deficiency in production of the β-globin chains of hemoglobin, which is the oxygen-carrying protein in red blood cells - or RBCs for short. Beta thalassemia is most commonly seen in Mediterranean, African and South East Asian populations.
Normally, hemoglobin is made up of four globin chains, each bound to a heme group. There are four major globin chain types - alpha (α), beta (β), gamma (γ), and delta (δ). These four globin chains combine in different ways to give rise to different kinds of hemoglobin. First, there’s hemoglobin F (or HbF), where F stands for fetal hemoglobin, and it’s made up of two α-globin and two γ-globin chains. Hemoglobin A (or HbA), the major adult hemoglobin form, is made up of two α-globin and two β-globin chains. Finally, hemoglobin A2 (or HbA2)) accounts for a small fraction of adult hemoglobin in the blood, and it’s made up of two α-globin and two δ-globin chains.
With beta thalassemia, there’s either a partial or complete β-globin chain deficiency, due to a point mutation, which is when a single nucleotide in DNA is replaced by another nucleotide, in the beta globin gene present on chromosome 11. And most often, these mutations occur in two regions of the gene called the promoter sequences and splice sites, which affects the way the mRNA is read. The result is either a reduced, or completely absent beta globin chain synthesis.
And since this is an autosomal recessive disease, two mutated copies of this gene, one from each parent, are needed to develop the disease. If the person has just one mutated gene that codes for either a reduced production or absent production of beta globin chains, then they have beta thalassemia minor. If the person has two mutated genes that code for reduced beta globin chain synthesis, then they’re said to have beta thalassemia intermedia. If the person has two β0 mutations then no beta globin chains are produced, and they’re said to have beta thalassemia major.
When there’s a β-globin chain deficiency, free α-chains accumulate within red blood cells, and they clump together to form intracellular inclusions, which damage the red blood cell’s cell membrane. This causes hemolysis, or red blood cells breakdown in the bone marrow; or extravascular hemolysis, when red blood cells are destroyed by macrophages in the spleen. Hemolysis causes hemoglobin to spill out directly into the plasma, where heme is recycled into iron and unconjugated bilirubin. Over time, the excess unconjugated bilirubin leads to jaundice, and excess iron deposits leads to secondary hemochromatosis.
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