Anaemia
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Anaemia Prof. A. B. Skotnicki M.D. Ph.D. Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Anaemia Decreased haemoglobin concentration and/or PCV Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Internal iron exchange. Absorption - about 1 mg/d is required from the diet in men, 1.4 mg/d in women transferrin saturation 20 to 60% Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Iron storage and transport Tissue ferritin Serum transferin 20 umol/l Bone Marrow Erythroblasts Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Classification of anaemia Morphological Based on red cell measurement Aetiological Based on cause Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Aetiological classification of anaemia ↓ Hb ↓ ER Excessive blood loss -haemorrhage Haemolitica anaemias Post – haemorrhagic anaemia Inadequate production of red cells Excessive red cell destruction - decreased Aplastic anameia Bone marrow infiltrattion abnormal - Cytoplasmic defect ↓ Fe Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland Nuclear defect ↓ B12 YOUR LOGO HERE Morphological classification of anaemia Acute blood loss Haemolysis Bone marrow aplasia Bone marrow infiltration ↓ Fe ↓ MCV ↓ MCH Microcytic hypochromic anaemia Chronic disease MCV and MCH normal Normocytic normochromic anaemia B12 ↓ fol.ac. ↓ ↑ MCV ↑ MCH Macrocytic hyperchromic Megaloblastic anaemia Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Anaemia – signs and symptoms General signs and symptoms universal for all anaemias Signs and symptoms specific for a particular cause Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE General symptoms of anaemia ↓ Hb ↓ O2 carrying capacity of blood TISSUE HYPOXIA Clinical manifestations Palpitations Tachycardia Heart murmurs dyspnoea pallor Compensatory mechanisms mobilised to contract hypoxia Cardiac overactivity Cadiorespiratory insufficiency Skin vasoconstriction redistribution of blood flow (brain, heart) Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Anaemia – general signs and symptoms CSN: Pale skin & mucous membranes CVS: •Tachycardia •Functional murmur •Stenocardiac pain •Headaches •Tinnitus General: •Shortness of breath •Fatigue •Weakness •Susceptibility to infections Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Anaemia – major types Iron deficiency anaemia Nutritional factor deficiency Megaloblastic anaemia Haemolytic anaemia Aplastic anaemia Anaemia of chronic disease Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Normal erythropoiesis Fe B12 haemoglobinisation RBC production HB N = N E MCV=90 fl MCHC=32 g/l MCH=32 pg Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Erythropoiesis in IDA or after bleeding Fe B12 haemoglobinisation RBC production HB <N = N/>N E MCV=70 fl MCHC=28 g/l MCH=25 pg Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Iron deficiency anaemia (IDA) - causes Inadequate intake Increased requirement Chronic blood loss Iron malabsorbtion • GI • Urinary Tract Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE IDA – causes of chronic blood loss Haematemesis Haemoptysis Gastrointestinal tract bleeding: •Hiatus hernia •Gastritis haemorrhagica •Peptic ulcer •Gastric cancer •Intestinal polyposis •Colonic cancer •Colitis ulcerosa •Haemorrhoidal varices Urinary tract bleeding – haematura: •Renal disorders •Inflammation •Tumour •Urinary tract •Calculosis •Polyps •Urinary bladder tumours Genital tract bleeding: •Menorrhagiae •Metrorrhagiae •Uterine myoma •Melaena Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE IDA - signs and symptoms General signs and symptoms PLUS tissue asiderosis Hair: •Fragility, coming out •Early gray Skin: •Dry, cracked •Cheilitis angularis •rhagades Eyes: •Bluish sclera Nails: •Brittle, spoon nails •Atrophic changes Tongue •Glossitis anaemica Dysphagia Plummer-Vinson syndrome Neurovegetative dystonia Pica Gastric troubles Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Moderately severe iron deficiency anaemia This example of moderately severe iron deficiency anaemia shows anisocytosis, anisochromasia, hypochromia, microcytosis and poikilocytosis. The poikilocytes include several particularly long elliptocytes, sometimes referred to as 'pencil cells'. Elliptocytes are characteristic of iron deficiency but not pathognomonic. Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Severe iron deficiency anaemia Blood film from a patient with severe iron deficiency anaemia. The film shows anaemia, microcytosis, hypochromia, anisocytosis, anisochromasia and poikilocytosis. Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Pallor in iron deficiency anaemia The hand of a patient with iron deficiency anaemia showing pallor. The hand of a nonanaemic person is pictured for comparison. Pallor is a non-specific feature of anaemia. Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Pale conjunctiva in iron deficiency anaemia The best places to check for pallor that may indicate anaemia are the conjunctiva, the nail beds and the palms of the hands. This patient with iron deficiency anaemia has conjunctival pallor. Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Pallor in iron deficiency anaemia Pallor in a patient with iron deficiency anaemia. The patient's hand is pictured together with the hand of a healthy person. (Courtesy of Dr D. Samson.) Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Oral changes in iron deficiency anaemia Angular cheilosis and atrophic glossitis in iron deficiency anaemia. These features are typical of moderately severe iron deficiency anaemia and indicate the effect of iron deficiency on tissues other than the bone marrow. (Courtesy of Dr D. Samson.) Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Cheilitis Angularis in IDA Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Koilonychia in iron deficiency anaemia Koilonychia or spoonshaped nails in iron deficiency anaemia. Koilonychia has a high degree of specificity for iron deficiency but it is a relatively uncommon feature, occurring only in severe chronic iron deficiency. Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Typical changes in blood count in IDA Normal Blood Count Hb 14 g/dl RBC 4,50 x 10^12/l PCV 40 % MCV 90 fl MCH 30 pg Ret 0,5 % WBC 7,5 x 10^9/l Differential normal Platelets 400x10^9/l Blood Count in IDA Hb 7,5 g/dl RBC 4,05 x 10^12/l PCV 26% MCV 64 fl MCH 18,5 pg Ret 2,6% WBC 7,5 x 10^9/l Differential normal Platelets 530x10^9/l Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Iron deficiency is NOT a diagnosis but a symptom Aetiology ? Iron Deficiency anaemia Clinical & laboratory findings Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Iron deficiency anaemia 53 old male Tiredness Hb 7 g/l MCV 69 fl Serum ferritin 8ug/l Occult faecal blood test positive (+) Colonoscopy •Carcinoma of the colon Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE 22 years old patient with ACD (Hodgkin’s lymphoma) 30 25 Fe (umol/l) - normal values 20 Hb (g/l) 15 Hb - norm al values Fe (um ol/l) 10 5 0 XI 2000 XII 2000 IV 2001 V 2002 TIME Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Megaloblastic Anaemia Abnormal changes in blood cell formation leading to macrocytic anaemia and varying degrees of pancytopenia as a result of abnormal DNA synthesis because of single or combined deficiency of folate and/or vitamin B12 Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Normal erythropoiesis Fe B12 haemoglobinisation RBC production HB N = N E MCV=90 fl MCHC=32 g/l MCH=32 pg Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Erythropoiesis in B12 deficiency Fe B12 haemoglobinisation RBC production HB N = <N E MCV=100 fl MCHC=32 g/l MCH=40 pg Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Megaloblastic anaemia - causes Inadequate intake Malabsorbtion Increased requirement Disturbed metabolism Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Megaloblastic anaemia - causes COBALAMIN DEFICIENCY. Inadequate intake: vegetarians (rare) Malabsorption: Defective release of cobalamin from food:Gastric achlorhydria, Partial gastrectomy, Drugs that block acid secretion Inadequate production of intrinsic factor (IF): Pernicious anemia; Total gastrectomy: Congenital absence or functional abnormality of IF Disorders of terminal ileum Competition for cobalamin Other FOLIC ACID DEFICIENCY Inadequate intake: unbalanced diet (common in alcoholics, teenagers, some infants) Increased requirements: Pregnancy, Infancy, Malignancy, Increased hematopoiesis, Chronic exfoliative skin disorders Malabsorption: Tropical sprue, Nontropical sprue, others Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Megaloblastic anaemia - causes Cause 1. Dietary deficiency: 2. Malabsorbtion: •Atrophic gastritis •Hipochlorchydria •Lack of intrisinc factor •Small bowel diseases •Post gastrectomy 3. Increased demands: •Pregnancy B12 deficiency Folic acid deficiency rarely often (alcohol abuse, parenteral nutrition, age) +++ +++ + + − − ++ - − ++ − + + + 4. Disturbed metabolism: •anticonvulsives •cytostatics Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Megaloblastic anaemia– symptoms and signs CSN: •Headaches •Tinnitus •Visual disturbances •Optic nerve disturbances •Psychiatric disturbances •Irritability •Sleepiness •Dementia •Peripheral neuropathy •Paresthesia •Pins and needles •Unsteady gait •Reduced Sensation •Imbalance •Dysuria •Reduced heat and cold sensibility Specific PLUS General signs and symptoms • Average age – 60 Often - women • • • • • • • Glossitis Hunteri • smooth • Reddened • Burning • Reduced in size Loss of appetite Loss of taste Loss of body weight Abdominal pains Atrophic gastritis Diarrhoea Achlorchyrdia Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Blood film in megaloblastic anaemia In megaloblastic anaemia the most characteristic features in the peripheral blood film are hypersegmented neutrophils and macrocytes, particularly oval macrocytes [arrow]. The neutrophil shown has six lobes and is therefore classified as hypersegmented Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Haemolytic anaemia Decrease in the total number of circulating erythrocytes that is caused by premature destruction or removal of red cells from the circulation Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Haemolytic anaemia Classifications of HA according to Type of defect Site of defect Site of haemolisis Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Classification of HA according to Type of defect Hereditary Membrane defect Metabolic defect Hemoglobinopathies Acquired Immunologic defect Mechanical defect Intravascular coagulopathy March hemoglobinuria Infection Membrane abnormality Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Classification of HA according to Type of defect Hereditary Membrane defect Acquired • Drug-induced hemolysis • Isoimmune and alloimniune hemolysis (neonatal and delayed transfusion reactions) • HS • Hereditary elliptocytosis Metabolic defect • GdPD deficiency • PK deficiency Mechanical defect • Rapid turbulent flow of blood, tumors, hypertension, aortic stenosis, Prosthetic valve leaks Hemoglobinopathies • Thalassemias • Sickle cell diseases • Other hemoglobinopathies Immunologic defect Intravascular coagulopathy March hemoglobinuria Infection Membrane abnormality (stem cell abnormality) Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Classifications of HA according to Site of defect Intracorpuscular factors Red cell membrane abnormalities (HS and related abnormalities PNH) Hemoglobinopathies (Thalassemias, Sickle cell disease and related hemoglobinopathies, Methemoglobinemia, Unstable hemoglobin diseases ) Enzymopathies (G6PD deficiency Others) Extracorpuscular factors Antibodies (Autoimmune hemolytic anaemia, transfusion-related haemolytic reactions, Drugrelated hemolytic reactions) Mechanical or traumatic factors (Prosthetic heart valves, High-flow red cell damage, Intravascular coagulopathy) Infections (Bacterial, Parasitic) Cell membrane lipids (Liver disease, Lipid disorders) Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Classifications of HA according to Site of Haemolysis Intravascular hemolysis Traumatic hemolysis Immune hemolysis Infections Extra vascular hemolysis Autoimmune hemolytic anemia Red cell membrane defects Spur cell anaemia Red cell metabolism defect Unstable haemoglobin diseases Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Clinical signs and symptoms of haemolytic anaemia General signs and symptoms universal for all anaemia Signs and symptoms specific haemolysis Jaundice Increased billirubin (unbound) Increased reticulocitosis Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Example of blood film in HA Microangiopathic haemolytic anaemia Blood film showing the features of microangiopathic haemolytic anaemia in haemolytic uraemic syndrome. There are schistocytes including one microspherocyte Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Aplastic anaemia Acellular or hypocellular marrow that Etiology: causes bone marrow failure and lower level of cell production, leading to pancytopenia. Idiopathic Secondary Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Causes of Secondary Aplastic Anaemia Drugs and toxins Chloramphenicol Cancer chmotherapy Chemicals Infections Viral hepatitis CMV Infectious mononucleosis Parvovirus 19 Proleukaemic and leukaemic conditions Paroxysmal nocturnal haemoglobinuria Genetic or constitutional conditions Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Bone marrow in AA Normal Bone marrow WBC PLT Bone marrow in AA Residual haemopoesis RBC Fat cells Fat cells Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Signs and symptoms of AA The results of pancytopenia Anaemia (general signs) Thrombocytopenia (bleeding tendency) Granulocytopenia (infections) Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Normal bone marrow (right) and in aplastic anaemia (left) trephine biopsies normal AA Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Anaemia of chronic disease (ACD) Common type of anaemia that occurs in patients who present with any of several chronic inflammatory and malignant diseases Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Anaemia of chronic disease (ACD) Anaemia of chronic disease caused by a defect in incorporation of iron into haemoglobin as a consequence of infection, inflammation or malignant disease. Bone marrow iron stores are usually normal or increased. The anaemia is initially normocytic and normochromic but when it becomes severe is hypochromic and microcytic. Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Signs and symptoms of ACD General signs and symptoms of anaemia Blood film as in IDA No tissue asiderosis Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE ACD & IDA: clinical & laboratory differences Feature ACD IDA Severity + ++ Tissue asiderosis - +++ Chronic disorder +++ + ++ - Serum iron ↓ ↓↓ Serum ferritin ↑ ↓ Serum transferin ↓ ↑ TIBC ↓ ↑ ↑ ESR: fever; ↑WBC; ↑PLT; pain; lymph nodes ↑ Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Signs and symptoms in anaemia Anaemia Signs and symptoms Aplastic Marrow failure Iron deficiency Tissue asiderosis B12 & follic acid deficiency Neuro & gastrointestinal Chronic disease Without tissue asiderosis Haemolytic Haemolysis Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Anaemia of chronic disease bone marrow Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Comparison of blood films in anaemias Normal Macrocytic IDA Haemolytic Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Fe, TIBC and UIBC TIBC 60 umol/l Fe 20 umol/l UIBC NORMAL Fe overload IDA, pregnancy Infections cancers Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE Oral iron absorbtion test Fe serum concentration (umol/l) 50 upper limit of the normal value lower limit of the normal value impaired absorbtion (flat curve) iron deficiency with increased absorbtion 40 30 20 10 0 1 3 6 hours Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE MCV in anaemia Microcytic (MCV<N) Iron deficiency Fe<N, Ferritin<N, TIBC>N Chronic disease Fe>N, Ferritin=,>N Talasemia Fe >N, Ferritin >N Normocytic (MCV=N) Aplastic Reticulocytes < N Macrocytic (MCV>N) B12 <N Haemolytic Reticulocytes > N Folic acid <N Acute blood loss Reticulocytes > N Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland YOUR LOGO HERE
