Anaemia

1. Anaemia Dr Kate Foley ST5 Haematology

2. Definitions • Anaemia ‘Reduction in blood haemoglobin concentration below what is considered normal for age and sex.’ • Erythropoiesis (from Greek 'erythro' meaning "red" and 'poiesis' meaning "to make") is the process which produces red blood cells (erythrocytes).

3. Objectives • Perform a competent clinical assessment of a patient with anaemia (including red flags) • Pathophysiology of anaemias • Describe the epidemiology of iron deficiency and macrocytic anaemia and how this affects both the UK population and the global population. • Describe the main investigations used to diagnose anaemia and its causes. • Explain the differing influences of racial, genetic, environmental (e.g. diet and culture) and sex differences in both the development and management of anaemia. • Explain the treatments of anaemia (and its underlying causes) • Synthesise both your history and examination findings to formulate a differential diagnosis of anaemia and its underlying causes and other relevant condition

4. Erythropoesis

5. Need iron, B12, folate and other essential factors • Need stimulating factors (EPO, IL-3, GM-CSF, SCF) • Genes code for red cell structure and function including haemoglobin. • Produced in bone marrow • Lifespan 120 days (travels 300 miles!) • Removed by macrophages of the reticuloendothelial system in marrow, liver and spleen.

6. Hereditary Ineffective erythropoesis Fe, B12, folate deficiency • Increased destruction • Intracorpuscular • Membrane • Enzyme • Hb • Extracorpuscular • Mechanical • Chemical • Infection • Antibodies • Splenomegaly • Bleeding Anaemia of Chronic disease, CKD, Hypothyroid Bone marrow failure or infiltration

7. Case History • Mrs Green, 45 year old female. • Presents to GP with 3 months history of increasing tiredness, shortness of breath and headaches. • History of hypothyroidism-well controlled on treatment. • Found to be anaemic with a Haemoglobin of 85g/L

8. Signs Symptoms Tachycardia SOBOE Bleeding Flow murmur Weakness Koilynichia Change in bowel habit Cardiomegaly Palpitations Pulmonary oedema Back pain Jaundice Headaches Dyspepsia Pale Mucus membranes Angina Intermittent Claudication Weight loss Leg ulcers Bruising Confusion

9. Mrs Green.... • On further questioning admits to several months history of dyspepsia and early satiety • Has lost 10kg in weight without trying in the same time • Has spoon shaped nails, tachycardia and a flow murmur on examination • PR exam reveals melaena.

10. What do you want to do now? • Full blood count • U+E • LFT • Clotting screen • Group and Save/Crossmatch • Ferritin/Iron studies • B12/folate • GI investigations • Urine dip • Bone marrow aspirate • Haemoglobin Electrophoresis Would you wait for these results before referring Mrs Green to hospital?

11. NICE Recommends • Refer all patients with IDA and dyspepsia via 2ww • Refer all men with Hb < 110 g/L via 2ww • Refer all post menopausal women with Hb < 100 g/L via 2ww • Screen all patients for coeliac disease. • Other patients with unexplained IDA will still need upper and lower GI endoscopy

13. Classification of Anaemias

14. Other Results • Ferritin 6 ug/l (15-300) • Serum Iron low • TIBC raised • Blood film-microcytic, hypochromic cells, pencil cells.

16. Causes Iron Deficiency • Blood loss • Menstruation • GI loss • Other chronic blood loss • Dietary • Pregnancy • Coeliac disease • Partial/total gastrectomy • Atrophic Gastritis • Regular blood donation • Hookworm infection-biggest worldwide cause

17. Further investigations • Gynaecological investigations • Upper and lower GI endoscopy • Anti-endomysial antibodies • H Pylori test • Urine dip for blood

18. Treatment • Treat underlying condition AND • Trial of oral iron • Ferrous sulphate 200mg bd 2-4 weeks • Ferrous Gluconate • Intravenous iron • If rapid rise needed or poor oral response • Hypotension and anaphylaxis risk • Avoid in bacteraemia

19. Case 2 • 60 year old female • Hypothyroidism and diabetes • Routine blood test with GP

21. Results • TFTs normal • B12 50 ng/L (120-680) • Serum folate 4.0 ug/L (4-30) • Reticulocytes low • Other tests? • Intrinsic factor and parietal cell antibodies • Gastroscopy (Atrophy)

22. Blood Film

23. B12 Dietary B12 Intrinsic factor Gastric Parietal Cells Intrinsic factor receptors B12 Metabolism Terminal Ileum

24. Causes B12 Deficiency • Nutritional (vegans) • Pernicious anaemia • Total/partial gastrectomy • Intestinal stagnant loop syndrome • Chronic tropical sprue • Ileal resection • Crohns disease • Fish tapeworm • Coeliac disease

25. Pernicious Anaemia • Autoimmune attack on gastric mucosa • Reduced production of IF • 90% abs to parietal cells, 50% abs to IF • Female>male, peak age 60 years • Northern European • Associated with autoimmune disease and autoimmune polyendocrine syndrome • Associated with gastric carcinoma

26. Folate Deficiency Causes • Dietary • Old age, institutions • Malabsorption • Tropical sprue, coeliac disease • Excess utilisation • Pregnancy, haemolytic anaemias, inflammation • Drugs • Anticonvulsants, sulfasalazine • Increased urinary excretion • CCF, liver disease

27. Treatment B12/Folate Deficiency • Hydroxycobalamin IM 1000μg od for 5-7 days • Then 1000μg every 3 months • Folic acid 5mg daily for 4 months/until cause resolved.

28. Other Effects • Neuropathy –SCDC (B12 only) • Sterility • Skin pigmentation • Neural tube defects • Decreased osteoblast activity • Cardiovascular disease

29. Case 3 • 77 year old female • Presents to A+E • Tired, SOBAR, angina worse than usual • Widespread lymph nodes, tachycardia, tachypnoea, splenomegaly • Urgent FBC is sent.....

31. Other tests? • Bilirubin 120μmol/L (3-20) • Reticulocytes 5% (0.5-2.5) • LDH 1260U/L (240-480) • Ferritin, folate and B12 all normal • DAT-positive

32. Haemolytic Anaemia • Increased rate of red cell destruction • Congenital or acquired. • Intravascular or extravascular • Jaundice, splenomegaly, leg ulcers, dark urine, folate deficiency.

33. Classification • Congenital • Membrane disorder eg hered. spherocytosis • Metabolism disorder eg G6PD deficiency • Haemoglobin disorder eg HbS, HbC • Acquired • Autoimmune (warm/cold) • Alloimmune (transfusion/HDFN) • Red cell fragmentation syndomes • Drugs • Infections (malaria) • Burns • Liver and renal disease • Paroxysmal nocturnal haemoglobinuria

34. Autoimmune Haemolytic Anaemia • Antibody against own RBCs • May be idiopathic or seconday to malignancy/infection/drugs

35. Direct Antiglobulin Test Antihuman globulin links the antibodies on the red cells-causing agglutination. Blood of patient-antibodies attached to antigen on the red cell surface Patient’s washed red cells incubated with antihuman globulin

36. Warm Autoimmune Haemolytic Anaemia • IgG autoantibody. DAT + (IgG) • Binds at 37°C • Any age/gender • Associated with lymphoid malignancy, drugs (methyldopa), SLE • When occurs together with ITP = ‘Evans syndrome.’

37. Treatment • Prednisolone 60mg od for 1-2 weeks then taper • IV methylprednisolone • IV Immunoglobulin • Rituximab • Splenectomy • Folic acid • Transfusion if severely unwell/unstable • Look for / treat underlying cause.

38. Cold Autoimmune Haemolytic Anaemia • IgM autoantibody • Optimal at 4°C-binds to red cells in peripheries. • Associated with lymphoid malignancy and infection (mycoplasma pneumoniae). • Exacerbated by cold weather • Purplish discoloration of extremities. • Poor response to steroids/splenectomy • May respond to some chemotherapy agents and monoclonal antibodies.

39. Acrocyanosis

40. Transfusing Anaemic Patients • If no severe or life-threatening symptoms wait until you can treat appropriately • If chronic anaemia patient may be able to tolerate a low Hb • Transfusion is associated with significant risks including over transfusion. • If decision made to transfuse give one unit, reassess patient.

41. BUT.... • No one should die from lack of blood.... • Hypotension/tachycardia • Low saturations • Chest pain or ECG changes • Pulmonary oedema • Children decompensate quickly

42. Summary • How to recognise and classify anaemia based on clinical history, examination and laboratory tests. • Pathophysiology, epidemiology and treatment of common causes for anaemia. • Interpreting full blood count results. • Transfusion in anaemic patients.