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Pathogenesis of Beta Thalassemia

Beta Thalassemia Signs Symptoms Treatment

Alpha Thalassemia Pathogenesis

Hemolytic Anemia - Pathophysiology

Hemolytic Anemia: Pathophysiology behind the Normocytic Anemia Note • Extreme bone marrow compensation for hemolysis (↑ RBC synthesis/reticulocytosis) may result in slightly macrocytic anemia (because reticulocytes have larger volumes than RBCs) Defects in the RBC’s environment Defects in RBC membranes Ex. Hereditary Spherocytosis: mutation causing deficiency of RBC structural proteins like ankyrin or spectrin RBC membranes become weakened and form blebs that break off ↓ RBC surface area while volume remains constantà RBC becomes spherical Spherocytes in spleen trapped and phagocytosed by splenic macrophages (extravascular hemolysis) Defects in RBC internal contents (thalassemia, hemoglobinopathies, and metabolic defects) Ex. Sickle Cell Disease: point mutation in hemoglobin (Hgb) structure (GluàVal) Inappropriate Hgb polymerization in low oxygen environments due to mutationàRBC becomes rigid, forms a sickle shape Inflexible RBCs become trapped in the spleen’s sinusoid membranes àphagocytosed by splenic macrophages (extravascular hemolysis) Infection triggers immune system activation Autoimmune processes TTP/HUS (abnormal platelet aggregation blocking blood vessels) Production of abnormal antibodies and immune complexes targeted against RBC surface antigens Immunoglobulin-bound RBCs are marked for destruction by the immune system (by either the cell- mediated or complement- mediated pathways) DIC (fibrin deposition blocking blood vessels) Artificial heart valve RBCs are sheared when they flow past an abnormal surface Rate of hemolytic RBC destruction > rate of bone marrow RBC synthesis (reticulocytosis) ↓ total number of RBCs in the body (despite normal RBC production/volume) Normocytic anemia Authors: Yan Yu Katie Lin Man-Chiu Poon* Reviewers: Andrew Brack Julia Heighton JoyAnne Krupa Lynn Savoie* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published June 15, 2019 on www.thecalgaryguide.com

beta-thalassemia-minor

Beta Thalassemia Minor: Pathogenesis and clinical findings Authors: Andrew Brack Yan Yu Huneza Nadeem Reviewers: Wendy Yao Katie Lin Liana Martel Ran (Marissa) Zhang Man-Chiu Poon* Lynn Savoie* * MD at time of publication Composition of normal adult hemoglobin (Hb): Ineffective erythropoiesis Excessive free α-chains accumulate, and α-chains precipitate in RBC precursors and RBCs These precipitants (inclusion bodies) give RBCs an abnormal shape Spleen destroys abnormally shaped RBCs Spleen accumulates destroyed red blood cells and enlarges to an abnormal size Splenomegaly (*See Splenomegaly slide for clinical findings) Mild microcytic anemia Hb: ↓ MCV: ↓ • • • 96% HbA (ααββ=2 α chains + 2 β chains) 2% HbA2 (ααẟẟ) 2% HbF (αα!!; fetal hemoglobin) Genetic point mutation on a single allele of the β globin gene on chromosome 11 (heterozygous with one normal alleleà HbA ααββ0 or ααββ+) Mild ↓ of β-chain production relative to ⍺- chain ↓ β-chain available for HbA synthesis Body compensates by ↑ production of non-affected globins (HbA , HbF) 2 ↑ HbF (nonspecific), ↑ HbA2 (hallmark sign specific to Beta Thalassemia Minor) on electrophoresis • • α-chain precipitates form structures visible under the microscope Inclusion bodies Heme from the destroyed RBCs is degraded into bilirubin and iron Excess unconjugated bilirubin is released into the blood Excess bilirubin is deposited in the skin Jaundice Excess iron is stored as ferritin ↑ or normal ferritin Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published June 8, 2022 on www.thecalgaryguide.com