Haematology Lecture - Anaemias - University of Fallujah - 2024 PDF

Haematology ”“Anaemias University Of Fallujah College Of Medicine Lecture : L11 Stage : 5th Lecturer : Assistant Professor: Mohammed Ismael Dawood Department: Medicine Date: 29/10/2024 Basic Learning Objectives: 1. Iron Deficiency...

Haematology ”“Anaemias University Of Fallujah College Of Medicine Lecture : L11 Stage : 5th Lecturer : Assistant Professor: Mohammed Ismael Dawood Department: Medicine Date: 29/10/2024 Basic Learning Objectives: 1. Iron Deficiency anaemia. 2. Anaemia of chronic disease. 3. Megaloblastic Anaemia.  ANAEMIAS Around 30% of the world population is anaemic; iron deficiency is the cause in half of these. The physiological response to anaemia is an attempt to maintain adequate oxygenation of the body. The level of 2,3-DPG rises to ensure that oxygen is unloaded at the tissues. The cardiac output increases and the circulation becomes hyperdynamic. This can be detected by a rapid pulse and the appearance of heart.murmurs  Iron deficiency anaemia:  This occurs when iron losses exceed absorption:  Blood loss: The most common explanation in men and postmenopausal women is GI blood loss. This may result from gastric or colorectal malignancy, peptic ulceration, inflammatory bowel disease, diverticulitis and angiodysplasia. Worldwide, hookworm and schistosomiasis are common causes. GI bleeding may be exacerbated by the use of aspirin or NSAIDs. In younger women, menstrual bleeding and pregnancy often contribute to iron deficiency.  Malabsorption: Gastric acid is required to release iron from food and helps keep it in the soluble ferrous state. Hypochlorhydria due to proton pump inhibitor (PPI) treatment or previous gastric surgery may contribute to deficiency. Iron is absorbed actively in the upper small intestine and absorption can be affected by coeliac disease.  Physiological demands: Increased demands for iron during puberty and pregnancy can lead to deficiency. :Features specific to iron deficiency Glossitis (smooth, sore, red tongue).Koilonychia (spoon-shaped nails).Angular stomatitis (sores and cracks at corners of mouth).Alopecia.Pica (unusual dietary cravings, e.g. for clay and ice)  Investigations:  Blood film shows microcytic hypochromic red cells (low MCV, low mean cell Hb (MCH)).  Iron deficiency is confirmed by a low plasma ferritin level; however, ferritin levels may also be raised (up to 100 μg/L) by liver disease and in the acute phase response, even in the presence of iron deficiency.  In these patients, measurement of transferrin saturation (< 16%) and soluble transferrin receptor (raised) may be helpful. :The haematological findings are.A microcytic, hypochromic anaemia Reduced serum iron and ferritin (to.distinguish from thalassaemia traits) Increased serum transferrin and total iron- binding capacity (TIBC) (to distinguish from.anaemia of chronic disease).Reduced plasma transferrin saturation Absence of iron stores demonstrated on bone.marrow smear  The underlying cause of the iron deficiency should be established. Men > 40 years and post-menopausal women should undergo investigation of the upper and lower GI tract by endoscopy or barium studies. If coeliac disease is suspected, anti- endomysium or antitransglutaminase antibodies and duodenal biopsy are indicated. In the tropics, stool and urine should be examined for parasites.  Management:  Unless the patient has angina, heart failure or evidence of cerebral hypoxia, transfusion is not necessary.  Oral iron supplementation (ferrous sulphate 200 mg 3 times daily for 3–6 months) is appropriate, together with treatment of the underlying cause.  The Hb should rise by 10 g/L every 7–10 days.  A failure to respond adequately may be due to non-adherence, continued blood loss, malabsorption or an incorrect diagnosis.  Patients with malabsorption, chronic gut disease or inability to tolerate any oral preparation may need parenteral iron therapy.  Previously, iron dextran or iron sucrose was used, but new preparations of iron isomaltose and iron carboxymaltose have fewer allergic effects and are preferred.  Doses required can be calculated based on the patient’s starting haemoglobin and body weight.  Observation for anaphylaxis following an initial test dose is recommended. Anaemia of chronic disease:  This common type of anaemia occurs in the setting of chronic infections, chronic inflammation and neoplasia.  The anaemia is mild and is usually associated with a normal MCV (normocytic, normochromic), though this may be reduced in long-standing inflammation.  Hepcidin, a key regulatory protein, inhibits the export of iron from cells, resulting in anaemia despite high iron stores.  Raised ferritin and reduced total iron binding capacity (TIBC) and soluble transferrin receptor help to distinguish anaemia of chronic disease from iron deficiency.  Measures that reduce the severity of the underlying disorder generally help to improve the anaemia. Anaemia of CD Fe Deficiency Parameter Low Low Serum Fe Normal or High Low Serum ferritin Decreased or Normal Increased or Normal Serum Transferrin Decreased or Normal Increased Serum Transferrin receptors Reduced Increased TIBC Megaloblastic anaemia:  This results from deficiency of vitamin B12 or folic acid, both of which are required for DNA synthesis.  Deficiency leads to red cells with arrested nuclear maturation but normal cytoplasmic development within the bone marrow (megaloblasts).  There is a macrocytic anaemia with an MCV often > 120 fl, and mature red cells are commonly oval in shape.  Involvement of white cells and platelets can lead to neutrophils with hypersegmented nuclei and, in severe cases, pancytopenia.  Bone marrow examination reveals hypercellularity and megaloblastic changes. Vitamin B12:  The average diet contains well in excess of the 1 μg daily requirement of vitamin B12, mainly in meat, eggs and milk.  In the stomach, gastric enzymes release vitamin B12 from food and it binds to a carrier protein called R protein.  The gastric parietal cells produce intrinsic factor, a vitamin B12-binding protein. As gastric emptying occurs, vitamin B12 released from the diet switches from the R protein to intrinsic factor.  Vitamin B12 is absorbed in the terminal ileum and is transported in plasma bound to transcobalamin II, a transport protein produced by the liver.  The liver stores enough vitamin B12 for 3 years, and deficiency therefore takes many years to become manifest, even if all dietary intake is stopped.  Vitamin B12 deficiency can result in neurological disease, including peripheral neuropathy (glove and stocking paraesthesiae) and subacute combined degeneration of the cord. The latter involves the posterior columns (causing diminished vibration sense and proprioception, leading to sensory ataxia) and corticospinal tracts (resulting in upper motor neuron signs).  Dementia and optic atrophy can also occur. Causes of vitamin B12 deficiency:  Dietary deficiency: This only occurs in strict vegans.  Gastric factors: Gastric surgery (including gastrectomy) can result in vitamin B12 deficiency due to impaired secretion of gastric acid and intrinsic factor. Pernicious anaemia:  The Schilling test, involving measurement of absorption  This is an autoimmune disorder characterised by of radio-labelled vitamin B12 after oral atrophy of the gastric mucosa. administration, before and  Loss of the parietal cells causes intrinsic factor after replacement of intrinsic deficiency, leading to vitamin B12 malabsorption. factor, has fallen out of favour with the availability  Pernicious anaemia has an average age of onset of 60 of autoantibody tests, greater years, and is associated with other autoimmune caution in the use of radioactive tracers and conditions including: limited availability of  Hashimoto’s thyroiditis. intrinsic factor.  Graves’ disease.  Vitiligo.  Addison’s disease.  Antiparietal cell antibodies are present in 90% of cases but also occur in 20% of normal females > 60 yrs.  Small bowel factors:  Terminal ileal disease (e.g. Crohn’s disease) and ileal resection result in vitamin B12 malabsorption.  Motility disorders can cause bacterial overgrowth and the resulting competition for free vitamin B12 leads to deficiency. Clinical features of vitamin B deficiency 12 :include A lemon-yellow colour to the skin (if severe),.due to a combination of pallor and jaundice.Glossitis.Gastrointestinal disturbances.Weight loss Neurological abnormalities (peripheral neuropathy, subacute combined degeneration of the cord (SCDC) involving the posterior and.lateral columns.Psychiatric disturbances Folate:  Leafy vegetables, fruits, liver and kidney provide rich sources of dietary folate.  An average Western diet meets the daily requirement, but total body stores are small, and deficiency can develop within weeks.  Causes of folate deficiency include:  Diet, e.g. poor intake of vegetables.  Malabsorption, e.g. coeliac disease.  Increased demand, e.g. pregnancy, haemolysis.  Drugs, e.g. phenytoin, contraceptive pill, methotrexate.  Serum folate is very sensitive to dietary intake, and red cell folate is therefore a more accurate indicator of the body’s folate stores. :Haematological findings include Macrocytic anaemia (leucopenia and thrombocytopenia in severe megaloblastic anaemia) Hypersegmentation of neutrophil nuclei (right shift) Megaloblasts seen on bone marrow smear Low serum vitamin B levels or reduced 12.red cell folate content Management of megaloblastic anaemia:  If a patient with severe megaloblastic anaemia requires treatment before vitamin B12 and red cell folate results are available, both folic acid and vitamin B12 are given.  Folic acid therapy alone in the presence of vitamin B12 deficiency may result in worsening of neurological defects.  Vitamin B12 deficiency: Treated with IM hydroxycobalamin (1000 μg, 6 doses 2 or 3 days apart, followed by lifelong therapy of 1000 μg every 3 months).  Hb should rise by 10 g/L per week, but neuropathy may take 6–12 months to correct.  Folate deficiency: Treated with oral folic acid 5 mg daily.  Folic acid supplementation in pregnancy may reduce the risk of neural tube defects.  Prophylactic folic acid is also given in chronic haematological disease associated with reduced red cell lifespan (e.g. autoimmune haemolytic anaemia or haemoglobinopathies).