(3) Introduction to Hemolytic anemias and Hereditary spherocytosis (1).pdf

Introduction to Hemolytic anemia and Hereditary spherocytosis 1 Dr.Abdel Rahim Muddathir 02/01/41  By the end of these lectures you should: Define and classify hemolytic anemias Identify mechanism of RBCs hemolysis and Pathophysiology of HA Enumerate red c...

Introduction to Hemolytic anemia and Hereditary spherocytosis 1 Dr.Abdel Rahim Muddathir 02/01/41  By the end of these lectures you should: Define and classify hemolytic anemias Identify mechanism of RBCs hemolysis and Pathophysiology of HA Enumerate red cell membrane disorders and discuss hereditary spherocytosis. Intravascular and Extravascular hemolysis Clinical features of HA Laboratory diagnosis of HA 2 Dr.Abdel Rahim Muddathir 02/01/41  Definition Hemolytic anemias: Group of anemias occur due to shortening of RBCs survival (< 120 days) premature destruction of RBCs (hemolysis). HAs result when rate of destruction exceed BM capacity to produce RBCs. BM can increase it`s rate of production by 6-8 times normal capacity. 3 Dr.Abdel Rahim Muddathir 02/01/41  Pathophysiology 1 ↑breakdown of RBC release larger number of Hb → broken down to haem and globin – globin → amino acids – haem → iron → plasma pool → transferrin ↓ protoporphyrin → catabolized to bile pigments → (hyperbilirubinemia - hemolytic jaundice) with increased indirect bilirubin 4 02/01/41 Dr.Abdel Rahim Muddathir  Formation & Catabolism of Bilirubin 5 Dr.Abdel Rahim Muddathir 02/01/41  2- ↑reticulocytes production – ↓ circulating RBCs → ↑ erythropoietin → ↑ erythropoietic activity → reticulocytosis → normally marrow release reticulocytes within 24-48 hours. erythroid hyperplasia → modify BM → release early reticulocytes and normoblast normal retics 0.5-2% of all RBCs (absolute 10-80x109/l) premature reticulocytes larger with inclusions (Howel-Jolly / basophilic stippling) 6 Dr.Abdel Rahim Muddathir 02/01/41  3-↑ BM activity – increased cellularity → myeloid/erythroid ratio reversed – expansion of marrow space – in severe cases frontal bossing and hair on end appearance (prominent in thalassemia) – extramedullary hemopoiesis is more common in thalassemia 7 Dr.Abdel Rahim Muddathir 02/01/41  Hemolysis mechanisms There are 2 main mechanisms by which red cells are destroyed in HA. 1. Intravascular hemolysis (IVH) : cells are destroyed directly in circulation. Free Hb rapidly saturates haptoglobin & excess is filtered by kidneys resulting in hemoglobinuria & hemosiderinuria. 2. Extravascular hemolysis: excessive removal of RBCs by cells of RES in BM, spleen or liver 8 Dr.Abdel Rahim Muddathir 02/01/41 Prof Dr Asmaa El-Reweny 9 Dr.Abdel Rahim Muddathir 02/01/41  Clinical features of HA pallor mild fluctuation of jaundice splenomegaly pigment stones (↑ bilirubin production) Occurrence of aplastic crises occasionally (parvo-virus19) 10 Dr.Abdel Rahim M0u2d/d0a1t/h4i1r  Gaundice 11 Dr.Abdel Rahim M0u2d/d0a1t/h4i1r  Bilirubin gallstones 12 Dr.Abdel Rahim Muddathir 02/01/41  Classification of HA 13 Dr.Abdel Rahim Muddathir 02/01/41 14 Dr.Abdel Rahim Muddath 02/01/4i1r  Red cell membrane 15 Dr.Abdel Rahim Muddathir 02/01/41  List of RBC membrane disorders 1 Hereditary sherocytosis, inherited as autosomal dominant with spherocytes blood picture. 2 Hereditary elliptocytosis inherited as autosomal dominant with elliptocytes blood picture. 3 Hereditary stomatocytosis inherited as autosomal dominant with stomatocytes blood picture. 4 Hereditary acnthocytosis inherited as autosomal recessive as a result of abetalipoproteinemia or acnthocytosis will be Acquired as in liver disease with acnthocytes blood picture 16 Dr.Abdel Rahim Muddathir 02/01/41  Spherocytes Elliptocytes 17 Dr.Abdel Rahim Muddathir 02/01/41  Stomatocytes 18 Dr.Abdel Rahim Muddathir 02/01/41  Acanthocytosis 19 Dr.Abdel Rahim Muddathir 02/01/41  Target cells 20 Dr.Abdel Rahim Muddathir 02/01/41  Hereditary Spherocytosis Hereditary spherocytoisis Congenital red cell membrane disorder with formation of spherocyes in peripheral blood and increasing red cells hemolysis causing hemolytic anemia. negative coomb's test in the lab test (differential test) Acquired spherocytes Due to presence of antibodies in the surface of the RBCs. positive Direct coomb's test 21 Dr.Abdel Rahim Muddathir 02/01/41  Mechanisms of spherocyte formation 22 Dr.Abdel Rahim Muddathir 02/01/41  Normal RBC Membrane 23 Dr.Abdel Rahim Muddathir 02/01/41 Prof Dr Asmaa El-Reweny  Spherocyte 24 Dr.Abdel Rahim Muddathir 02/01/41 Prof Dr Asmaa El-Reweny  Mechanism of Hereditary spherocytosis (HS) Variety of abnormalities of cytoskeleton proteins Deficiency of Beta Spectrin or Ankyrin  Loss of membrane surface area becomes more spherical during passage through spleen and other RES Destruction in Spleen (trapped) Cells are permeable to Na influx resulting cells fragile Typically jaundice, anemia, 25 splenomegally Dr.Abdel Rahim Muddathir 02/01/41  Causes of HS and HE 26 Dr.Abdel Rahim Muddathir 02/01/41  Laboratory tests Complete blood count - Lower level of Hb, PCV, RBC count. - MCV decreased. - MCHC values usually increased. - High Reticluocytes count Blood cells morphology (PBF) : spherocytosis ,microspherocytes (small round without central pallor)+ polychromasia ↑ Reticluocytes count ( 5-20%) Leukocytes and platelets variable 27 Dr.Abdel Rahim Muddathir 02/01/41  Polychromasia & NRBCs & Spherocytes 28 Dr.Abdel Rahim Muddathir 02/01/41  Spherocytes in PBP 29 Dr.Abdel Rahim Muddathir 02/01/41  Special tests for HS 1- Osmotic fragility test ↑ red cells osmotic fragility and glycerol lysis test. Osmotic fragility test done at room temperature and 24 hours to increase the sensitivity of the test. 2 Autohemolysis; ↑ Autohemolysis (partly corrected by addition of glucose). 3 Direct coomb's test - ve 4Serum bilirubin (Indirect Bilirubin) - high 5- Urine and fecal urobliniogen - high 30 Dr.Abdel Rahim Muddathir 02/01/41  osmotic fragility test : increased Normally hemolysis starts at NaCl concentration 0.45% to 0.50 and hemolysis will be complete at 0.35%. In HS usually it starts hemolysis starts at 0.6% Na cl 31 Dr.Abdel Rahim Muddathir 02/01/41  Osmotic Fragility Test 32 Dr.Abdel Rahim Muddathir 02/01/41  Osmotic fragility curve 33 Dr.Abdel Rahim Muddathir 02/01/41 34 Dr.Abdel Rahim Muddathir 02/01/41  Reticulocytosis 35 Dr.Abdel Rahim Muddathir 02/01/41  Characteristics and Laboratory Profiles of RBC Membrane Disorders 36 Dr.Abdel Rahim Muddathir 02/01/41 37 Dr.Abdel Rahim M0u2d/d0a1t/h4i1r