In the thalassemias, the synthesis of either the α- or the β-globin chain is defective. Imbalance in α- and β-globin synthesis leads to precipitation of excess goblin chain e.g. α4-tetramers in β-thalassemias                    β4-tetramers(HbH) and γ4-tetramers(Hb Barts) in α-thalassemias 3. (**Click on above image for better view on smartphones) Clinical Features of Thalassemias β-thalassemia minor and α-trait are often asymptomatic with mild microcytic and hypochromic anemia. β-thalassemia major: Decreased synthesis of goblin chain causes microcytic, hypochromic anemia, growth retardation and are sustained by repeated blood transfusions. "Target Cells" (so called because hemoglobin collects in the center of the cell) are common. Precipitation of α4-tetramers causes Extravascular hemolysis of mature RBCs Ineffectiv...

Different types of hemoglobin HbA α2β2 HbA2 α2δ2 HbF     Α2γ2 HbA1c Α2β2-glucose                   HbS             sickle hemoglobin, valine replaces glutamic acid                   HbC             lysine replaces glutamic acid Sickle cell disease occurs primarily in individuals of African descent. HbS is protective against Plasmodium falciparum malaria. Sickle cell disease is caused by a point mutation in the sixth codon of β-globin that leads to the replacement of a glutamate residue with a valine residue. Sickle cell disease is a homozygous, recessive disorder. At low oxygen tension, deoxyhemoglobin S polymerizes inside the red blood cell...

X-linked recessive disorder Diminished G6PD activity impairs the ability of the cell to form the NADPH that is essential for the maintenance of the reduced glutathione pool. This results in a decrease in the cellular detoxification of free radicals and peroxides formed within the cell. Most severe in erythrocytes, where the pentose phosphate pathway provides the only means of generating NADPH. Glutathione also helps maintain the reduced states of sulfhydryl groups in proteins, including hemoglobin. Heinz Bodies Exposure of G6PD-deficient red cells to high levels of oxidants causes the cross-linking of reactive sulfhydryl groups on globin chains, which become denatured and form membrane-bound precipitates known as Heinz bodies . These are seen as dark inclusions within red cells stained with crystal violet. Heinz bodies can damage the membrane sufficiently to cause intravascular hemolysis. As inc...

Hereditary Spherocytosis Inherited defect in the red cell membrane skeleton that renders the cells spheroidal, less deformable, and vulnerable to splenic sequestration and destruction. mutations most frequently involve ankyrin, band 3, and spectrin most commonly autosomal dominant Loss of central pallor, hyperchromic cells Anisocytosis, spherocytes Features of anemia with extravascular hemolysis Extravascular hemolysis takes place within the macrophages of the spleen and liver. Any reduction in red cell deformability leads to splenic sequestration, followed by phagocytosis. not associated with hemoglobinemia and hemoglobinuria often produces jaundice can lead to the formation of gallstones ( pigment stones). Haptoglobin levels are   decreased splenomegaly. Splenectomy is helpful in these patients. Asplenic patients show Howell-Jolly bodies (nuclear remnants)...

Normal red cells have a life span of about 120 days All hemolytic anemias are characterized by      (1) an increased rate of red cell destruction      (2) a compensatory increase in erythropoietin levels and erythropoiesis that            results in reticulocytosis      (3) associated with a marked erythroid hyperplasia within the marrow and an increased reticulocyte count in peripheral blood. Normal M:E ratio in marrow is 3:1. This ratio decreases in hemolytic anemias.      (4) the retention by the body of the products of red cell destruction    (including iron, bilirubin, Hb ) Intravascular hemolysis leads to : Hemoglobinemia, hemoglobinuria Hemosiderinuria unconjugated hyperbilirubinemia and jaundice. Haptoglobin levels are depleted Ext...

Decrease in oxygen carrying capacity of blood. Hb<13.5gm/dl in males Hb<12.5gm/dl in females Symptoms of anemias Pallor - palms, conjunctiva Fatigue Lassitude Weakness Shortness of breath Palpitations Heart failure (high output type) Types of Anemias On the basis of mechanism Blood Loss Acute: trauma Chronic: lesions of gastrointestinal tract, and genitourinary tract in females Increased Destruction (Hemolytic Anemias) Hereditary   Membrane abnormlities : Spherocytosis     Enzyme deficiencies : G6PD deficiency     Deficient globin synthesis: thalassemia syndromes      Structurally abnormal globin synthesis: sickle cell anemia, unstable hemoglobins   Acquired     Membrane defect: paroxysmal nocturnal hemoglobinuria   Antibody mediate...

Red Blood Cell  Normal Indices Diameter 7.5microns Male Female Unit Hemoglobin 13.5 12.5 Gm/dl Hematocrit Hct 39-49 33-43 % RBC count 4.2-5.6 3.8-5.0 Million/microlitre Reticulocyte count 0.5-1.5 % MCV 80-100 femtolitre MCHC 33-35 Gm/dl MCH 28-34 picogram RDW 11.5-14.5 Mean cell volume (MCV): the average volume per red cell, expressed in femtoliters (cubic microns) Mean cell hemoglobin (MCH): the average content (mass) of hemoglobin per red cell, expressed in picograms Mean cell hemoglobin concentration (MCHC): the average concentration of hemoglobin in a given volume of packed red cells, expressed in grams per deciliter Red cell distribution width (RDW): the coefficient of variation of red cell volume. Polychromasia - RBCs of...