Macrocytic Anaemia PDF - MLS 3009SEF Lecture Notes

HONG KONG METROPOLITAN UNIVERSITY MLS 3009SEF Haematology & Transfusion Science I H.LEE Macrocytic Anaemia 27-1-2025 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 1 ...

HONG KONG METROPOLITAN UNIVERSITY MLS 3009SEF Haematology & Transfusion Science I H.LEE Macrocytic Anaemia 27-1-2025 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 1  Macrocytic Anaemia - Macrocytic anaemia are characterized by large RBC with normal haemoglobin content - Characterized by large erythrocytes(MCV> 100) - Macrocytic anaemia are classified as : i. Megaloblastic ii. Non-megaloblatic 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 2  Macrocytic Anaemia Megaloblastic – Results in delayed nuclear development, causing abnormal RBC maturation in the bone marrow i.e. nuclear maturation defect causing macrocytes. – Abnormal DNA synthesis, usually due to vitamin B12 or folate deficiencies and drugs interfering DNA metabolism – Drugs that interfere with DNA metabolism – Inherited disorder that affects DNA synthesis 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 3  Macrocytic Anaemia Non-megaloblastic – Mechanism not well defined – Increase in membrane lipids – DNA synthesis unimpaired 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 4  Megaloblastic Anaemia “Megaloblast”is large abnormal marrow erythrocyte precursor Group of disorders characterized by defective nuclear maturation caused by impaired DNA synthesis. Impairment is a result of a substitution in the nucleic acid chain, causing DNA replication to be fragmented. Nuclear replication is slowed down or stopped resulting in maturation delays, prolonging the premitotic interval – Cellular observation Large nucleus Cytoplasm development normal Hb synthesis normal- because RNA strands are not affected 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 5  Macrocytic Anaemia Macrocytic, normochromic anemia – Increased MCH: due to large cell volume – Normal MCHC RBC, HGB decreased Reticulocytopenia Granulocytes and Thrombocytes are affected as well. – Granulocytes are hypersegmented as a result of impaired DNA synthesis – Megakaryoctyes are abnormal resulting in thrombocytopenia 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 6  Macrocytic Anaemia Triad of: – oval macrocytes – Howell-Jolly bodies-DNA fragments – hypersegmented neutrophils Anisocytosis is moderate Poikilocytosis with nRBC and cabot rings RBC’s are fragile, lifespan is shortened and many die in the bone marrow which causes ↑ LDH 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 7  LaboratoryTests.org 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 8  Medical Laboratories 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 9  Macrocytic Anaemia Causes on Megaloblastic Anaemia Vitamin B12 deficiency Folate deficiency Drugs Myelodysplastic syndromes Acute leukemia 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 10  Megaloblastic Anaemia Primary defect of DNA replication due to depletion of thymidine triphosphate (TTP) leads to retarded nuclear maturation Vit B12 and folic acid are 2 main causes of TTP depletion Vit B12 is due the deficiency of intrinsic factor (IF), binds vitamin B12 so that it can be absorbed in the intestines. IF is released by cells in the stomach. When the stomach does not make enough intrinsic factor, the intestine cannot properly absorb vitamin B12. 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 11  Megaloblastic Anaemia 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 12  Macrocytic Anaemia Inadequate dietary intake Malabsorption – Pernicious anemia – Gastrectomy – Blind loop syndrome – Fish tapeworm – Helicobacter pylori Drugs Increased need 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 13  Malabsorption Pernicious anemia Caused by gastric parietal cell atrophy which causes decreased secretion of intrinsic factor (IF). IF is necessary for B12 absorption. Atrophy due to immune destruction of the acid- secreting portion of the gastric mucosa Onset is usually after age 40, primarily women Affects people of Northern European backgrounds Neurologic problems Schilling test used for diagnosis 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 14  Folic Acid Deficiency Inadequate Dietary Update Malabsorption may due to diseases of upper small intestine Increased Need e.g. pregnancy, hemolytic anaemia, leukemia Drugs e.g. oral contraceptives, alcohol and anticoagulant drugs 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 15  Folic Acid Deficiency Malabsorption – Ileitis/Crohn’s disease – Tropical sprue – Blind loop syndrome – Nontropical sprue Gluten-sensitive enteropathy Childhood celiac disease 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 16  Folic Acid Deficiency Drugs – Methotrexate (chemotherapy drug that is a folate antagonist) – Alcohol – Oral contraceptives – Long term anticoagulant drugs 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 17  Folic Acid Deficiency Chronic liver disease Alcoholism – alcohol has toxic effect on RBC’s Stimulated Erythropoiesis – Newborns 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 18  Folic Acid Deficiency Alcoholism: –Ethanol has a toxic effect on precursor cells –Red cells are macrocytic Stimulated erythropoiesis: –Increased EPO, adequate iron –Release of stress reticulocytes 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 19  Non-Megaloblastic Anaemia DNA synthesis not impaired MCV doesn’t go as high as in megaloblastic Macrocytes are round NOT oval No hypersegmented neutrophils Leukocytes and platelets are normal Jaundice, glossitis and neuropathy are absent 27/1/2025 Henry Lee MLS 3009SEF Macrocytic Anaemia 20