Macrocytic Anaemia Flashcards
Definition
Anaemia associated with a high MCV of erythrocytes (> 100 fl in adults)
Aetiology (megaloblastic)
• Megaloblastic - when the bone marrow produces unusually large, structurally abnormal, immature red cells
o Caused by deficiency of B12 or FOLATE required for the conversion of deoxyuridate to thymidylate, DNA synthesis and nuclear maturation
o Drugs • Methotrexate (dihydrofolate reductase inhibitor) • Hydroxyurea • Azathioprine • Zidovudine
Aetiology (causes of B12 deficiency)
- Reduced absorption (e.g. post-gastrectomy, pernicious anaemia (autoimmune cause leading to anti-IF antibodies?) terminal ileal resection or disease (classically Crohn’s disease affects the terminal ileum so can lead to b12 deficiency))
- Reduced intake (vegans)
- Abnormal metabolism (congenital transcobalamin II deficiency)
Aetiology (causes of folate deficiency)
- Reduced intake (alcoholics, elderly, anorexia)
- Increased demand (pregnancy, lactation, malignancy, chronic inflammation)
- Reduced absorption
- Jejunal disease (e.g. coeliac disease!! - folic acid is absorbed in the jejunum)
- Drugs (e.g. phenytoin)
Aetiology (non-megaloblastic/normoblastic)
o Alcohol excess o Liver disease o Myelodysplasia o Multiple myeloma o Hypothyroidism - autoimmune? o Haemolysis (shift to immature red cell form - reticulocytosis) o Drugs (e.g. tyrosine kinase inhibitor)
Epidemiology
- More common in ELDERLY FEMALES
* Pernicious anaemia is the MOST COMMON cause of B12 deficiency in the West
Presenting symptoms
• Non-specific symptoms of anaemia:
o Tiredness
o Lethargy
o Dyspnoea
- Family history of autoimmune disease
- Previous GI surgery
- Symptoms of the CAUSE (e.g. weight loss, diarrhoea)
Signs on physical examination (anaemia)
o Pallor
o Tachycardia
o Breathlessness
Signs on physical examination (pernicious anaemia)
o Mild jaundice
o Glossitis
o Angular stomatitis
o Weight loss
Signs on physical examination (B12 deficiency)
o Peripheral neuropathy o Ataxia o Subacute combined degeneration of the spinal cord o Optic atrophy o Dementia
Investigations (bloods)
o FBC • High MCV • Pancytopaenia in megaloblastic anaemia • Different degrees of cytopaenia in myelodysplasia • Exclude reticulocytosis
o LFT
• High bilirubin (due to ineffective erythropoiesis or haemolysis)
o ESR
o TFT
o Serum vitamin B12
o Red cell folate
o Anti-parietal cell and anti-intrinsic factor antibodies
o Serum protein electrophoresis - looking for a dense band in myeloma
Investigations (other)
• Blood Film o Large erythrocytes o In megaloblastic anaemia: • Megaloblasts • Hypersegmented neutrophil nuclei
• Schilling Test
o Method of testing for pernicious anaemia
o B12 will only be absorbed when given with intrinsic factor
- Bone Marrow Biopsy (rarely needed)
- Investigations for the cause
Management plan
• Pernicious Anaemia
o IM hydroxycobalamin for life
• Folate Deficiency
o Oral folic acid
o If B12 deficiency is present, it must be treated before the folic acid deficiency
Possible complications
- Pernicious anaemia –> increased risk of gastric cancer
* Pregnancy - folate deficiency increases the risk of neural tube defects
Prognosis
• Majority are treatable if there are no complications
Pernicious anaemia
Lack intrinsic factor
Stop absorbing b12
DNA replicates poorly
Thus cell grows but fails to divide
Macrocytosis results from vitamin b12 and folate deficiency
Hypersegmented neutrophils is a feature of pernicious anaemia
Mneumonic for causes
Alcoholics May Have Liver Failure
Alcohol Myelodysplasia Hypothyroidism Liver disease Folate/B12 deficiency
