Cards (68)

  • Anaemia
    Reduction in haemoglobin concentration with a concomitant decrease in oxygen carrying capacity of the blood
  • Anaemia is not a diagnosis, it is an abnormal clinical finding
  • The cause of anaemia must be found and treated appropriately
  • Red cell
    • 8 μm in diameter
    • Oval, flexible, enucleate biconcave disc
    • Made in the bone marrow
    • 10^12 per day (erythropoiesis)
    • 120 day lifespan
    • Destroyed by macrophages in the spleen
    • Function: Gas exchange - To carry O2 from the lungs and return CO2 from the tissues to the lungs
  • Haemoglobin (Hb)
    • Tetrameric structure: 2 different pairs of polypeptide chains - globin. Each attached to a haem molecule
    • Haem = Protoporphyrin + Iron
    • Globin permits variation in oxygen affinity, protects haem from oxidation, renders the molecule soluble
    • Haem Fe containing, transports oxygen
  • Symptoms of anaemia
    • Tiredness & lethargy
    • Shortness of breath
    • Palpitations
    • Headache
    • In older patients: Cardiac failure, Angina, Intermittent claudication, Confusion
  • Signs of anaemia
    • General: Pallor of mucous membranes (if Hb < 9-10 g/dl), Hyperdynamic circulation, Tachycardia, Bounding pulse, Cardiomegaly, Systolic flow murmur, Signs of heart failure
    • Specific: Koilonychia (spoon nails) - iron deficiency, Jaundice - haemolytic/megaloblastic anaemia, Leg ulcers - sickle cell disease, Bone deformities - thalassaemia major, Associated infections/bruising - bone marrow failure
  • Investigations
    • Essential in all cases: Full blood count, Red cell indices, White cell and platelet counts, Blood film
    • Depending on FBC/Film: Reticulocyte count, Haematinics, Ferritin, Iron studies, Vitamin B12, Folate, Hb Electrophoresis, Bilirubin/LDH/haptoglobin, Bone marrow
  • Classification of anaemia
    • Microcytic: MCV<80fl (Iron deficiency, Thalassaemia)
    • Normocytic: MCV 80-95fl (After acute blood loss, Anaemia of chronic disease, Bone marrow failure)
    • Macrocytic: MCV>95fl (Megaloblastic: vitamin B12, folate deficiency, Non-megaloblastic: Alcohol, Liver disease, Myelodysplasia)
  • Hb Electrophoresis
    1. Electrophoresis on cellulose acetate at alkaline pH
    2. Proteins applied to a membrane are exposed to a charge gradient and separate from each other, then visualised by either a protein or haem stain
  • High Performance Liquid Chromatography (HPLC)
    1. Adsorption: A mixture of molecules (such as normal and variant Hbs) with a net positive charge separated into its components by adsorption on to a negatively charged stationary phase in chromatography column
    2. Elution: Mobile phase (liquid) with an increasing concentration of cations compete with the adsorbed proteins for their anionic binding sites. Therefore the adsorbed proteins are eluted at a rate related to their affinity for the stationary phase.
    3. Detection: Molecules detected optically in the eluate, provisionally identified by elution time and quantified by computing the area under the corresponding peak in the elution profile
  • Microcytic Anaemias
    • Iron deficiency
    • Anaemia of Chronic Disease
    • Thalassaemia (later!)
  • Microcytic Anaemia - Iron deficiency
    • Most common cause of anaemia affecting 500 million people worldwide
    • 5-10% pre-menopausal women
    • 2-5% adult men / post-menopausal women
  • Microcytic Anaemia - Iron deficiency
    • Limited ability to absorb iron
    • Excess loss due to bleeding is common
  • Distribution of Body Iron
    • Haemoglobin (65%)
    • Ferritin and haemosiderin (30%)
    • Myoglobin (3.5%)
    • Haem enzymes (eg cytochromes etc) (0.4%)
    • Transferrin - bound iron (0.1%)
  • Daily iron requirement goes up in pregnancy, adolescence and in menstruating females
  • Microcytic Anaemia - Iron deficiency
    • Reticuloendothelial stores (haemosiderin and ferritin) completely depleted first before anaemia develops
    • General signs and symptoms of anaemia
    • Painless glossitis
    • Angular stomatitis
    • Koilonychia
    • Brittle, ridged or spoon-shaped nails
    • In children: Irritability, Poor cognitive function, Decline in psychomotor development
  • Microcytic Anaemia - Iron deficiency: causes
    • Chronic blood loss (Uterine, Gastrointestinal, Peptic ulcer disease, Aspirin/NSAIDs, Malignancy, Inflammatory bowel disease, Hookworm, Haematuria)
    • Increased demands (Prematurity, Growth, Pregnancy)
    • Malabsorption (Coeliac disease, Gastrectomy)
    • Poor diet
  • Rarely the sole cause in the developed world except in infants and children
  • Microcytic Anaemia - Iron deficiency: investigations
    1. History (Diet, Bleeding symptoms, Medication, Family history)
    2. Examination (Abdominal mass, Rectal examination)
    3. FBC and blood film
    4. Serum iron studies (Ferritin, Iron, Total iron-binding capacity (TIBC), Transferrin saturation (TS))
    5. Consider: Upper and lower GI endoscopies, Transvaginal ultrasound, Urine dipstick
  • Blood film in iron deficiency
    • Pencil cells
    • Hypochromic, microcytic anaemia with aniso/poikilocytosis
  • Bone marrow iron assessed by Perls' stain
  • Microcytic Anaemia - Differential diagnosis
    • Iron deficiency
    • Anaemia of Chronic Disease
    • Thalassaemia Trait (a or b)
  • Differences in investigations between the differential diagnoses
    MCV, Ferritin, Serum iron, TIBC, TS, Bone marrow iron stores, Hb electrophoresis
  • Microcytic Anaemia - Iron deficiency: treatment
    1. Treat underlying cause
    2. Oral iron (Ferrous sulphate 200mg TDS on empty stomach, If side-effects then give with food or use lower iron content preparation)
    3. Hb should rise by 2g/dl every 3 weeks, Continue for 3 months once FBC normal to replenish iron stores
    4. Parenteral iron (IV venofer/monofer), Side-effect: hypersensitivity/anaphylaxis, Haematological response no faster than with oral iron but stores replenished faster
  • Microcytic anaemia - Anaemia of Chronic Disease (ACD)
    • Due to chronic inflammatory and malignant diseases
    • Decreased release of iron from macrophages to plasma
    • Reduced red cell lifespan
    • Inadequate erythropoietin response to anaemia
  • Microcytic anaemia - Anaemia of Chronic Disease (ACD)
    • Normocytic or mildly microcytic anaemia (MCV rarely < 75fl)
    • Mild, non-progressive anaemia
    • Serum ferritin normal or raised
    • Serum iron, TIBC and TS all low
    • Bone marrow storage iron normal but erythroblast iron reduced
  • Diagnosis of ACD: Careful history and examination, Elevated inflammatory markers (ESR/CRP), Treat the underlying cause
  • Megaloblastic anaemia
    Erythroblasts in the bone marrow show a characteristic abnormality: Maturation of the nucleus is delayed relative to the cytoplasm
  • Megaloblastic anaemia is associated with delayed maturation of the nucleus relative to the cytoplasm in erythroblasts in the bone marrow
  • Haemolytic anaemias
    Anaemia resulting from an increase in the rate of red cell destruction
  • Haemolytic anaemias
    • Bone marrow compensates by increasing production of red cells to 6-8 x normal rate
    • Marked reticulocytosis
    • Anaemia may not become apparent until red cell lifespan < 30 days
  • Classification of haemolytic anaemias
    • Hereditary
    • Acquired
    • Immune
    • Non-immune
    • Intravascular
    • Extravascular
  • Hereditary haemolytic anaemias
    • Red cell membrane defects (Hereditary spherocytosis, Hereditary elliptocytosis)
    • Red cell enzyme deficiencies (G6PD deficiency, Pyruvate kinase deficiency)
    • Abnormal haemoglobins (HbS, HbC, unstable Hb)
  • Acquired non-immune haemolytic anaemias
    • Red cell fragmentation syndromes (Heart valves, Microangiopathic - TTP, HUS, DIC, Pre-eclampsia, meningococcal sepsis)
    • March haemoglobinuria
    • Infections (Malaria, clostridia)
    • Chemical and physical agents
    • Secondary (Liver and renal disease)
    • Paroxysmal nocturnal haemoglobinuria (PNH)
  • Acquired immune haemolytic anaemias
    • Alloimmune (Haemolytic transfusion reactions, ABO incompatible blood, Haemolytic disease of the newborn)
    • Autoimmune (Warm antibody type, Cold antibody type)
  • Causes of intravascular haemolysis
    • Mismatched blood transfusion
    • G6PD deficiency with oxidant stress
    • Red cell fragmentation syndromes
    • Some autoimmune, drug-induced, infection-induced haemolytic anaemias
    • PNH
    • March haemoglobinuria
    • Unstable haemoglobin
  • Investigations for haemolytic anaemias
    • Proof of haemolysis (Decreased Hb, Increased unconjugated bilirubin and LDH, Decreased haptoglobins, Urinary haemoglobin and haemosiderin)
    • Features of increased red cell production (Increased reticulocytes)
    • Blood film
    • Specific tests (Direct antiglobulin test, HPLC and Hb electrophoresis, Red cell enzyme assays, Flow cytometry for CD55 and CD59)
  • Mutations in the globin genes are the most prevalent monogenic disorders worldwide
  • Hb disorders represent a significant health problem in 71% of 229 countries