RBC3 Hemolytic anemia

"Pleasure in the job puts perfection in the work." -- Aristotle HEMATOLOGY Hemolytic Anemia Dr. Venkatesh M. Shashidhar Senior Lecturer in Pathology Fiji School of Medicine Blood Smear - Normal C.B.C / FBC / Hemogram  Haemoglobin - 15±2.5, 14 ±2.5 - g/dl  PCV - 0.47 ±0.07, 0.42 ±0.05 - l/l (%)  Haematocrit, Total RBC volume - better  RBC count - 5.5 ±1, 4.8 ± 1 x1012/l  MCHC - Hb/PCV - 30-36 - g/dl  Hb synthesis within RBC  MCH - Hb/RBC - 29.5 ± 2.5 pg/l  Average Hb in RBC  MCV - PCV/RBC 85 ± 8 – fl  RBC Maturation RBC disorders (Anemias) : “Anemia is decreased red cell mass affecting tissue oxygenation” * Low Hb <13.5 (males), <11.5 (females)  Acquired / Congenital disorders:  Decreased production / Increased loss Haemolytic An. Introduction  Anemia due to Increased RBC destruction  Decreased life span (<120d)  Breakdown  ↑Bilirubin (Unconj)  Jaundice  Increased RBC production - ↑ reticulocytes  Low Haptoglobins – Hb carrier proteins. Ketabolism of Hb: Polychromasia - Hemolytic An. Blood Film Features:  Abnormal shape  Polychromasia  Nucleated RBC  Plt may be low. Clinical Features:  Pallor mild – mucosal  Jaundice - Mild fluctuating  Splenomegaly  No bile in urine (dark on standing-UBG)  Pigment gall stones – in chronic forms  Crisis – aplastic, hemolytic, vascular  Ankle ulcers Hemolytic Anemia - Types:  Immune lysis • Warm & Cold Ab, Auto & Allo immune  Mechanical Damage • Valve, Microangiopathy (DIC), prosthesis, march  Hereditary Defects • Membrane, Hb & Enzyme defect  Infection induced • Clostridia, malaria, septicemia Clinical Features of Sickle Cell Disease Congenital RBC Disorders:  Membrane Disorders:  Spherocytosis, Elliptocytosis  Hemoglobin Disorders:  Hemoglobinopathies - Sickle cell, HbC etc.  Thalassemia Syndromes - , ,   Enzyme disorders:  G6PD, PK deficiency Laboratory Evaluation:  Features of RBC breakdown:  Hyperbilirubinemia  Increased Urine UBG & Faecal stercobilinogen.  Low or absent Haptoglobins  Features of increased RBC Production:  Reticulocytosis  Marrow erythroid hyperplasia – bone changes  Damaged RBC  Morphology, Osmotic Fragility  Decreased RBC survival – 51Cr labelling.  Hemoglobin electrophoresis, enzyme abnormality Laboratory Evaluation: Intravascular Haemolysis:  Haemoglobinaemia, Haemoglobinuria  Haemosiderinuria – Renal tubular cells  Methhaemalbuminaemia – Schumm’s test. Molecular genetics  Hb Electrophoresis  Globin synthesis studies. CBC Analyzer Report Blood Smear Interpretation: Normal Micro/hypo A Macro Target Sphero Heinz body E Schistocyte nRBC Polychrom Teardrop I B C D F G H J Hb Electrophoresis – New born pH 8.6 _ pH 6.3 C S A F S F A Bart s + “Seeing much, suffering much and studying much are the three pillars of learning.” –Benjamin Disraeli MOLECULAR PATHOLOGY :  Normal adult blood contain 3 types of Hb.  The major component is HbA - α 2ß2.  The minor component fetal Hb (α 2 γ 2) and Hb A2 (α 22) Structure & Synthesis of Haemoglobin: Hb in adult Structure Normal % Hb A α2 ß 2 96-98 Hb F Hb A2 α2 γ2 α2δ2 0.5-0.8 1.5-3.2 Introduction to Haemoglobins: GENE CLUSTER & HB SWITCH EFFECTS OF EXCESS  CHAINS Thalassemia Syndromes:  Group of disorders with decreased production of  or  chains.  Features:       Low Hb – depending on type. Microcytic Hypochromic RBC Unlike IDA, uniform - low RDW Target forms typical. No pencil forms. Heinz bodies – globin deposits HBH inclusions – Golf ball cells Thalassemia Syndromes:  Etiologically , ,  thalassemia, HbH dis.  Clinically classified into  Hydrops fetalis() – IU death  Thalassemia major () – transfusion dep  Thalassemia intermedia () – spleenomegaly, Fe  Thalassemia minor () - symptomless. -Thalassemia:  Decreased production of  chains.  Classification  0 – (four gene deletion) - Hydrops fetalis  + 2/3 gene deletion – Thal. Intermedia, HbH dis.  0 trait, + trait – Thal Minor, HPFH  No  thalassemia major.  HbH inclusions can be demonstrated in some cases. (less in trait, more in intermedia) Hydrops Fetalis: -Thalassemia: Blood Smear & HbH Preparation Thalassemia Trait: Thalassemia Major: ß Thalassemia Major: Sickle Cell Disease: G6PD Def - Heinz bodies: Her. Spherocytosis: Hereditary Elliptocytosis: G6PD Deficiency: G6PD Deficiency Anemia: If you don't stand for something, you will fall for anything…! Hb Barts levels in Cord blood in  thalassemia Phenotype Equivalent No % Barts of Functional Genes 4 0 3 2 1 0 0-1 2-8* 10-40 ~80 Normal  thal trait (mild)  thal trait (severe) Hb H disease Hb Barts Hydrops Higgs DR et al Blood 73, 1081, 1989 * Some references mention upto 15%