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Anaemia:

Anaemia BMLS Year II 2010 Lecture I

Anaemia: General consideration:

Anaemia: General consideration Anaemia exists when a person’s level of circulating Hb is lower than that in healthy persons of the same age and age group in the same environment. The most common kinds of anaemia are due to nutritional deficiencies of iron, and less commonly: - Vitamin B12 and protein Other common causes of anaemia are congenital defects of haemoglobin production: - Sickle cell anaemia - Other haemoglobinopathies including Thalassaemia - Protozoal infections ; malaria and hookworm - bacterial infections 4/5/2011 Aruna Devi Haematology II 2010

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Anaemia: General consideration:

Anaemia : General consideration Anemia is traditionally classified according to either the underlying pathophysiologic process or the RBC size . The pathophysiologic approach begins with 2 broad categories: failure of RBC production,[includes decreased production due to bone marrow failure, impaired erythropoietin production, and disorders of RBC maturation] and increased RBC loss or destruction[includes the hemolytic anemias , red cell membrane and metabolic defects, and direct injury to RBCs. 4/5/2011 Aruna Devi Haematology II 2010

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Anaemia: General consideration:

Anaemia: General consideration The 2 classifications are not mutually exclusive, in that more than one mechanism may be present in some anemias , but typically one functional disorder is the underlying cause for the patient’s anemia. Classification based on pathophysiologic mechanism is coupled with erythrocyte size ( microcytic , normocytic , or microcytic ) and morphology. This, combined with data from the history and physical examination , allows the clinician to narrow the Focus of the initial differential diagnosis. 4/5/2011 Aruna Devi Haematology II 2010

Anaemia: General consideration:

Anaemia: General consideration RBC’s perform the vital physiologic function of oxygen delivery to the tissues. The Hb within the erythrocyte has the capacity to bind oxygen in the lungs and To release it appropriately in the tissues A decrease in the number of RBCs or amount of Hb results in decrease oxygen delivery and subsequent tissue hypoxia[diminished availabity of oxygen to body tissues] 4/5/2011 Aruna Devi Haematology II 2010

Anaemia: General consideration:

Anaemia: General consideration Reduced number of RBC’s results in decreased oxygen delivery Anaemia should not ne thought of as a disease in itself, but rather a manifestation of numerous other underlying disease processes. Anaemia is the most common manifestation of disease worldwide. We will look at the diagnosis, mechanism and classification of anaemia. 4/5/2011 Aruna Devi Haematology II 2010

Anaemia: General consideration:

Anaemia: General consideration Definition: A decrease in RBC’s Hb, and Hct below the previously established reference values for healthy individuals of the same age, gender and race under similar environmental conditions. Clinical Finding: Clinical diagnosis of anaemia includes assessment of the: History and physical examination, signs, symptoms, haemotologic values and other lab procedures. 4/5/2011 Aruna Devi Haematology II 2010

Anaemia: General consideration History and physical examination:

Anaemia : General consideration History and physical examination The classic symptoms assosicated with anaemia are: fatigue and shortness of breath Pallor Jaundice Petechae Eyes, mouth [mucosal bleeding] Cardiac murmurs Splenomegaly heptomegaly Pallor of conjunctivae, nail beds Dyspnea [difficult or painful breathing] Vertigo [dizziness] Headache Muscle weakness lethargy 4/5/2011 Aruna Devi Haematology II 2010

Anaemia: General consideration:

Anaemia : General consideration Anaemia that develops slowly: The body adopts to anaemia over time – few symptoms Increase erythropoietin secretion Increase the oxygen carrying capacity – more rapid delivery of blood with reduced oxygen content Heart rate and respiratory rate are increased Cardiac output is increased Increase in RBC 2,3 bisulphoshoglycerate which shifts the oxygen dissociation curve to the right [decreased oxygen affinity of Hb ] The strain on the heart ultimately can lead to heart failure. 4/5/2011 Aruna Devi Haematology II 2010

Anaemia: General consideration Laboratory procedure::

Anaemia : General consideration Laboratory procedure: FBC and indices [ Hb,Hct , RBC indices WBC and platelet count MCV,MCH, MCHC]. Most important is MCV which measures the RNC in volume in femtoliters [fl] RDW is the mathematical expression of variability within the volume distribution of the RBC population – as %. It indicated the variation of the RBC size [ anisocytosis ] Reticulocytes serves as an important tool to indicate shortened RBC survival and increase RBC production Blood smear peripheral smear- variation in size, shape, color content and inclusions. Also serves as the quality control to verify the results from automated analyzers Bone Marrow Examination Other Laboratory Tests 4/5/2011 Aruna Devi Haematology II 2010

Mechanism of anaemia:

Mechanism of anaemia Life span of RBC is 120 days Approx 1% of the circulating are lost daily, BM continues to produce RBCs to replace those lost. Haematopoietic stem cells must function satisfactorily by maturing the erythroid precursor cells and releasing mature RBCs into peripheral blood RBC production requires several nutrition factors – iron, VitB12 and folic acid Erythropoiesis : marrow erythroid proliferation activity Normal erythropoiesis occurs only in the BM : effective erythropoiesis Ineffective erythropoiesis : production of progenitor cells that are defective and are destroyed before leaving the marrow e.g. Megalobastic anaemia , Thalassaemia and sideroblastic anaemia -Insufficient erythropoiesis is associated with a quantitative lack of erythroid precursors in the marrow. The anaemia is due to decreased in total production of RBCs. Several factors can lead to decreased rbc production- lack of iron, erythropoietin, auto antibodies , infections[parvovirus B19, acute leukaemias etc. 4/5/2011 Aruna Devi Haematology II 2010

Evaluating Anaemias:

Evaluating Anaemias This includes : FBC Reticulocyte count Cell indices [MCV] Examination of blood smear The reticulocyte counts divides the anaemia into decreased production vs shortened RBC survival ↓ retics the anaemia can be further divided into 3 sub groups: Based on the MCV: Normocytic normochromic anaemia Microcytic hypochromic anaeima Macrocytic anaemia 4/5/2011 Aruna Devi Haematology II 2010

Classification of anemia by pathophysiologic mechanism :

Classification of anemia by pathophysiologic mechanism I. Failure of erythrocyte production A. Bone marrow failure 1. Aplastic anemia (congenital or acquired) 2. Pure red cell aplasia a . Diamond- Blackfan anemia (congenital) b . Transient erythroblastopenia of childhood (acquired) 3 . Marrow replacement a . Malignancies b . Osteopetrosis c . Myelofibrosis B. Impaired erythropoietin production 1. Chronic renal disease 2. Hypothyroidism, hypopituitarism 3. Chronic inflammation 4. Protein malnutrition 5. Hb mutation with decreased affinity for oxygen 4/5/2011 Aruna Devi Haematology II 2010

Classification of anemia by pathophysiologic mechanism:

Classification of anemia by pathophysiologic mechanism C . Disorders of erythroid maturation/ineffective erythropoiesis 1 . Abnormalities of cytoplasmic maturation a. Iron deficiency b. Thalassemia syndromes c. Lead poisoning d. Sideroblastic anemia 2. Abnormalities of nuclear maturation a. Vitamin B12 deficiency b. Folic acid deficiency c. Thiamine-responsive megaloblastic anemia d. Hereditary abnormalities in folate metabolism 3. Congenital dyserythropoietic anemia 4. Erythropoietic protoporphyria II. Increased RBC loss or destruction 1. Hemoglobinopathies (including structural and synthetic mutants) 2. Red cell membrane defects 3. Red cell metabolic defects 4. Antibody-mediated 5. Mechanical injury to the erythrocyte 6. Oxidant-induced injury to the erythrocyte 7. Infectious agent-induced red cell injury 8. Paroxysmal nocturnal hemoglobinuria 4/5/2011 Aruna Devi Haematology II 2010

Classification of anemia based on red cell size:

Classification of anemia based on red cell size I . Microcytic anemia (MCV b 70 fL + years of age) 1. Iron deficiency 2. Drug/toxin-mediated (including lead poisoning) 3. Thalassemia syndromes 4. Chronic inflammation 5. Sideroblastic anemias II. Normocytic anemia 1. Congenital hemolytic anemias a. Hemoglobinopathies b. Red cell enzyme defects c. Red cell membrane defects 2. Acquired hemolytic anemias a. Antibody-mediated b. Microangiopathic hemolytic anemias c. Anemia secondary to acute infection 3. Acute blood loss 4. Chronic renal disease 5. Splenic sequestration III. Macrocytic anemia (MCV > 84 fL + 0.6 _ yrs of age) With megaloblastic bone marrow (disturbance of DNA synthesis ) a. Vitamin B12 deficiency b. Folic acid deficiency c. Thiamine-responsive megaloblastic anemia d. Drugs ( eg , methotrexate , certain anticonvulsants) 2 . Without megaloblastic bone marrow a. Aplastic anemia b. Diamond- Blackfan anemia c. Hypothyroidism/ hypopituitarism d. Liver disease e. Bone marrow infiltration f. Congenital dyserythropoietic anemia 4/5/2011 Aruna Devi Haematology II 2010

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Anaemia Decrease production Shortened RBC survival Low[micro] Fe def Thal Sidero Lead poison Chronic infl Normal [ Normo ] Aplastic Renal disease Splenomegaly infection High [macro] Megaloblastic Vit B12 def Folate def MDS Liver disease Haemolysis Immune Hbinopathy Membrane defect Enzyme def Infection [malarial Microangiopathic Haemolytic anaemia Acute Blood loss Absolute retics counts Low High MCV 4/5/2011 Aruna Devi Haematology II 2010

Activity 1 [In pairs]::

Activity 1 [In pairs]: Draw a flow chart for the morhological classification of anaemia [ on basis of MCV ] 4/5/2011 Aruna Devi Haematology II 2010