Macrocytic Anaemia and Macrocytosis Flashcards
What is macrocytosis?
- Red cells that are larger than normal
- raised MCV
What are the two types of macrocytic anaemia?
- megaloblastic (most common)
- non megaloblastic
What is megaloblastic anaemia?
- bone marrow manufactures erythroblasts
- enlarged erythroblasts with delayed nuclear maturation
- due to defective DNA synthesis
- these megaloblasts spill into circulation
- other cells, WBC may also be affected
- both RBC + WCC types appear abnormal down microscope
What causes megaloblastic anaemia?
- folate deficiency
- vitamin B12 deficiency
- drugs which result in the above
Why do we need folate?
- necessary for DNA synthesis
- adenosine, guanine, thymidine synthesis
Which drugs can interfere with folate metabolism and absorption?
- methotrexate
- metformin
- antimicrobials (trimethoprim, sulfasalazine)
- HIV medication
- anticonvulsants
- alcohol
What are the 3 broad causes of folate deficiency?
- increased demand
- decreased intake
- decreased absorption
In what cases is there an increased demand for folate, perhaps leading to folate deficiency?
- pregnancy / breast feeding
- infancy + growth spurts
- haemolysis + rapid cell turnover: eg. Sickle Cell disease
- disseminated cancer
- urinary losses: eg. HF, hepatitis, dialysis
In what cases is there a decreased intake, leading to folate deficiency?
- poor diet
- elderly
- chronic alcohol intake
- starvation
- poor social conditions
In what cases is there decreased absorption, leading to folate deficiency?
- medication (folate antagonists)
- coeliac
- jejunal resection
- tropical sprue
Where is folate absorbed?
- folate comes from most food with 60-90% lost in cooking :(
- absorbed in jejunum
- body has enough stores usually for 3-5 months
What are the blood test findings in megaloblastic anaemia?
- low Hb, RBC
- raised MCV, MCH
- normal MCHC
- low reticulocyte count
- LDH often raised
- may have reduced WCC + Plts
What would you see on a blood film for megaloblastic anaemia?
- anisopoikilocytosis (change in size + shape of RBCs)
- macrocytes
- ovalocytes
- hypersegmented neutrophils
Even though it is rarely required, what would bone marrow findings show in megaloblastic anaemia?
- hypercellular marrow
- megaloblastic
- giant metamyelocytes
What are symptoms of folate deficiency?
- sore mouth, ulcers
- graying hair
- general anemia symptoms:
- fatigue
- weakness
- lethargy
- pale skin
- SoB
- irritability
What is the management of folate deficiency?
-
REPLACE folate
- improve diet: broccoli, brussels, sprouts, asparagus, peas, chickpeas, brown rice
- give folic acid - 5 mg/day (4 months)
- find the underlying cause + treat it
Who else needs folate?
- prophylaxis for pregnant women
- 400 mcg/day
- given from conception until at least 12 weeks
- helps prevent neural tube defects as well as anaemia
What drugs might cause macrocytosis?
- treatments for HIV: reverse transcriptase inhibitors (stavudine, lamivudine, ziovudine)
- anticonvulsants: (valproic acid, phenytoin)
- folate antagonists: (methotrexate)
- chemotherapeutics: (azathioprine, hydroxyurea)
- antibiotics: (trimethoprim/sulfamethoxazole)
- other: biguanides (metformin), cholestyramine (questran), nitrous oxide
Why do we need vitamin B12?
- essential co-factor for methylation in DNA + cell metabolism
- vit B12 combines w/ methylmalonic acid (MMA) and produces coenzyme A, which is needed for normal cellular function
- so if there is vit B12 def, level of MMA goes up
- homocysteine is another substance found in small quantities in body
- it is metabolised by Vit b12 and therefore in def states, homocysteine levels are increased
UK intake recommendations are 1.5 mcg/day. What foods contain vitamin B12?
- animal sources
- fish, meat, dairy, eggs
How common is vitamin B12 deficiency?
- UK/USA: 6% ppl <60y, 20% >60y
- latin america: 40% children + adults
- 70% kenyan school children
- 80% indian preschool
- 11% uk vegans
- 62% ethiopian pregnant women
Where is vitamin B12 absorbed and what does it require?
- requires presence of intrinsic factor
- for absorption in terminal ileum
- intrinsic factor made in parietal cells in stomach
- transcobalamin II and transcobalamin I transport vitb12 to tissues
What are the (5) broad causes of B12 deficiency, listed in the lecture?
- impaired absorption
- decreased intake
- congenital causes
- increased requirements
- medication
What are the causes for impaired absorption, leading to B12 deficiency?
- pernicious anaemia
- gastrectomy or ileal resection
- zollinger-ellison syndrome
- parasites/bacterial overgrowth
What causes decreased intake, leading to B12 deficiency?
- malnutrition
- vegan diet
What are the congenital causes of B12 deficiency?
- intrinsic factor receptor deficiency
- cobalamin mutation C-G-1 gene
When is there increased requirement of B12, that can cause B12 deficiency?
- haemolysis
- HIV infection
- pregnancy
- growth spurts
What medication can cause B12 deficiency?
- alcohol
- metformin
- PPI, H2 antagonists
What is pernicious anaemia?
- autoimmune disorder
- lack of intrinsic factor
- hence lack of b12 absorption
- gastric parietal cell antibodies
- intrinsic factor antibodies
What are clinical consequences of B12 deficiency/pernicious anaemia?
- brain: cognition, depression, psychosis
- neuro: neuropathy, myopathy, sensory changes, ataxia, gait abnormalities, spasticity (SACDC)
- subfertility
- cardiac: caridomyopathy
- tongue: glossitis, taste impairment
- blood: pancytopenia
How do you manage Vit B12 deficiency?
- diet: fortified cereals, milk, eggs, chicken, red meat, shellfish
- injections: 5 x 1mg given over 2 weeks, then maintenance 1-3 monthly
- look for underlying cause + treat
What is SACDC?
- subacute combined degeneration of spinal cord
- peripheral sensory-motor symptoms
- strongly suggests vit b12 deficiency
- excess MMA remains in myeloid sheath, causing fragility
- homocysteine which can’t be converted into methionine, may lead to dementia + depression
- replacing folate may mask a Vit B12 deficiency, therefore check before treating
Large, mature red cells not related to defective DNA synthesis are less common and referred to as non-megaloblastic anaemia. What are causes of this?
- chronic alcoholism
- hypothyroidisim
- liver disease
- myelodysplastic syndromes
- reticulocytosis (haemolysis)
- clonal bone marrow disorders
treat the underlying disease!!!!!
What are the blood film differences between megaloblastic and non-megaoblastic anaemia?
- megaloblastic changes of blood cells are seen in B12 and folic acid deficiency, characterised on peripheral smear by macroovalocytes and hypersegmented neutrophils
