1. Macrocytic Anaemia Elliot Catchpole PCMD

2. Recap Mean Cell Volume = The size of each RBC Microcytic <76 Normocytic 76-96 MACROCYTIC >96 -IRON deficiency -Thalassaemias -Sideroblastic Chronic Disease Haemolysis B12 and Folate -Alcohol -Liver Disease - MYLODYSPLASIA Megaloblastic Non-Megaloblastic -G6PD Deficiency -Hereditary spherocytosis -Paroxysmal Nocturnal Haemoglobinurea -Autoimmune Haemolysis -Sickle Cell -G6PD Deficiency -Hereditary spherocytosis -Paroxysmal Nocturnal Haemoglobinurea -Autoimmune Haemolysis -Sickle Cell

3. Macrocytic Anaemia So what do we mean by ‘megaloblastic’?

4. B12 and Folate Folate ACTIVE Folate INACTIVE (reduced) Folate Homocysteine Methione B12 Purines/pyrimadines = DNA synthesis

5. ‘Megaloblastic’ anaemia Includes B12 and folate – will show megaloblasts (large and immature cells) due to poor DNA synthesis. These cells are large because B12/folate deficiency result in impaired DNA synthesis, so cells are stuck in the G2 phase of mitosis and carry on growing, so become large and fragile. Cytoplasm/cell contents will be disproportionate to the DNA. This is different from reticulocytes. ALSO will show hypersegmented neutrophils – these have more than 4 nuclei (4 is normal) due to slowed DNA synthesis. They can be seen on a peripheral smear. In contrast, alcohol and liver disease do not fall under this category. Pregnancy and hypothroidism can also cause a mild non- megaloblastic macrocytosis.

6. Common findings in B12/Folate B12/Folate Indirect Bilirubin ?Jaundice? Very mild, not as extreme as true haemolysis LDH MCV = Raised Reticulocyte

7. B12 vs. Folate CAUSES Stores deplete quickly in months Dietary – leaFy green vegetables Cell turnover – e.g. In SCD or psoriasis Stores deplete very very slowly Dietary – Veganism PERNICIOUS ANAEMIA SYMPTOMS ANAEMIA NEUROLOGICAL SYMPTOMS - Most common = peripheral neuropathy NO NEUROLOGICAL SYMPTOMS INVESTIGATIONS B12  Homocysteine Methylmalonic Acid Anti parietal/IF antibodies Folate  Homocysteine Methylmalonic Acid TREATMENT COMPLICATIONS Increased CVS risk (high homocysteine) Coeliac/mal absorption SUBACUTE COMBINED DEGENERATION OF THE CORD Give B12 Folate +Give To prevent... If Low

8. Pernicious Anaemia Parietal cells in Stomach produce Intrinsic Factor (IF) IF is needed to absorb B12 B12 absorbed in terminal ileum Autoimmune Ig attacks: Anti-parietal cell = parietal cells Anti-IF = Intrinsic Factor Look for these autoantibodies in those with suspected pernicious anaemia - E.g. Bariatric surgery (gastric bypass), ileum resection, gastritis If autoantibodies negative, and PA still suspected, perform Schilling’s test Treat with IM B12 (hydroxycobalamine) Stomach Duo. Jej. ILEUM

9. Do you remember your spinal tract anatomy?

10. Subacute Combined Degeneration of the spinal cord Emergency – as irreversible! Loss of: Dorsal column = Sensory loss Corticospinal = Motor UMN signs (extensor plantars) LMN signs (absent knee reflexes) Dorsal Corticospinal Treat with B12

11. CASE A 78 year-old gentleman comes in with numbness and tingling in his hands and feet. He is a chronic alcoholic with no signs of liver disease on examination and no past medical hx. What do you do first?

12. Questions A 42 year old women has been increasingly tired over the past 6 months. She has felt faint upon exertion with palpitations. She is pale. Results of testing show: Hb = 9.2 MCV = 102fL Smear/film = hypersegmented polymorphs. Which is the single most likely cause of her symptoms? 1) Alcholism 2) Liver disease 3) Myxoedema 4) Pernicious anaemia 5) Pregnancy

13. Questions A 45 year-old women presents to her GP with a 4-week history of increasing fatigue. She has noticed that the whites of her eyes are yellowing. She has had flitting joint pain over the last 6 months, which she has put down to ‘growing old’. She is otherwise well with no past medical Hx. On examination, she is mildly jaundiced with an erythematous rash over her cheeks and nose. She has slight splenomegaly but no lymphadenopathy or hepatomegaly. Her blood results are: Hb – 8.9 MCV – 105fL Bilirubin – 75 (3-17) What is the most likely diagnosis? 1) Pernicious Anaemia 2) Cold autoimmune haemolytic anaemia 3) Warm autoimmune haemolytic anaemia 4) Anaemia of chronic disease 5) Sickle Cell disease

14. Questions An African-British man is taking a skydiving course. He is on his first time up in the plane at altitude, about to jump, when he develops severe chest, back, and thigh pain. When the plane returns to the ground for an emergency landing, he feels well. FBC is completely normal, as is his peripheral blood smear. He has no past medical Hx, only occasional dark urine. 1) What is the most likely diagnosis? 2) What is the most accurate diagnostic test?

15. Questions A 54 year-old women presents to her GP with a 2 month Hx of worsening fatigue. She reports no other symptoms. On examination, she is mildly jaundiced, pale, and has a history of rheumatoid arthritis. Blood tests reveal: Hb = 7.9 MCV = 118 Bilirubin = 45 (3 -17) What is the most likely diagnosis? 1) Autoimmune haemolytic anaemia 2) Pernicious Anaemia 3) Iron Deficiency 4) Anaemia of chronic disease 5) Dietary B12 deficiency

16. The Patient is given appropriate therapy (which is????). She returns a month later. Although she noticed improvement, she still doesn't feel back to normal. She is starting to feel tired again and slightly breathless on exertion. Bloods show? Hb = 7.5 MCV = 70 What is the most likely cause of her persistent anaemia? 1) Inadequate B12 replacement 2) Coexisting folate deficiency 3) Iron deficiency 4) Thalassaemia 5) Haemolysis

17. Questions A 52 year-old man has been feeling fatigued over the past year. He complains of foul oily stools and has intermittant abdominal pain. He admits to losing 5kg. His initial blood results are: Hb = 10.6 g/dL (13.5 – 18.0 g/dL) Vit. B12 = 0.35mmol/L (0.13 – 0.68mmol/L) Folate = 1.4 ug/L (~2.1 ug/L) Ferritin = 110 ug/L (12 – 200 ug/L) Which is the single most appropriate further investigation to confirm the diagnosis? 1) Anti-endomysial antibodies 2) Anti-gastric parietal cell antibodies 3) Liver function tests 4) Peripheral blood film 5) Thyroid function tests