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Haematology > Macrocytic Anaemia and Macrocytosis > Flashcards

Macrocytic Anaemia and Macrocytosis Flashcards

1
Q

What is macrocytosis?

A
  • Red cells that are larger than normal
  • raised MCV
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2
Q

What are the two types of macrocytic anaemia?

A
  • megaloblastic (most common)
  • non megaloblastic
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3
Q

What is megaloblastic anaemia?

A
  • 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
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4
Q

What causes megaloblastic anaemia?

A
  • folate deficiency
  • vitamin B12 deficiency
  • drugs which result in the above
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5
Q

Why do we need folate?

A
  • necessary for DNA synthesis
  • adenosine, guanine, thymidine synthesis
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6
Q

Which drugs can interfere with folate metabolism and absorption?

A
  • methotrexate
  • metformin
  • antimicrobials (trimethoprim, sulfasalazine)
  • HIV medication
  • anticonvulsants
  • alcohol
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7
Q

What are the 3 broad causes of folate deficiency?

A
  • increased demand
  • decreased intake
  • decreased absorption
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8
Q

In what cases is there an increased demand for folate, perhaps leading to folate deficiency?

A
  • pregnancy / breast feeding
  • infancy + growth spurts
  • haemolysis + rapid cell turnover: eg. Sickle Cell disease
  • disseminated cancer
  • urinary losses: eg. HF, hepatitis, dialysis
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9
Q

In what cases is there a decreased intake, leading to folate deficiency?

A
  • poor diet
  • elderly
  • chronic alcohol intake
  • starvation
  • poor social conditions
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10
Q

In what cases is there decreased absorption, leading to folate deficiency?

A
  • medication (folate antagonists)
  • coeliac
  • jejunal resection
  • tropical sprue
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11
Q

Where is folate absorbed?

A
  • folate comes from most food with 60-90% lost in cooking :(
  • absorbed in jejunum
  • body has enough stores usually for 3-5 months
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12
Q

What are the blood test findings in megaloblastic anaemia?

A

​

  • low Hb, RBC
  • raised MCV, MCH
  • normal MCHC
  • low reticulocyte count
  • LDH often raised
  • may have reduced WCC + Plts
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13
Q

What would you see on a blood film for megaloblastic anaemia?

A
  • anisopoikilocytosis (change in size + shape of RBCs)
  • macrocytes
  • ovalocytes
  • hypersegmented neutrophils
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14
Q

Even though it is rarely required, what would bone marrow findings show in megaloblastic anaemia?

A
  • hypercellular marrow
  • megaloblastic
  • giant metamyelocytes
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15
Q

What are symptoms of folate deficiency?

A
  • sore mouth, ulcers
  • graying hair
  • general anemia symptoms:
    • fatigue
    • weakness
    • lethargy
    • pale skin
    • SoB
    • irritability
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16
Q

What is the management of folate deficiency?

A
  • 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
17
Q

Who else needs folate?

A
  • prophylaxis for pregnant women
  • 400 mcg/day
  • given from conception until at least 12 weeks
  • helps prevent neural tube defects as well as anaemia
18
Q

What drugs might cause macrocytosis?

A
  • 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
19
Q

Why do we need vitamin B12?

A
  • 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
20
Q

UK intake recommendations are 1.5 mcg/day. What foods contain vitamin B12?

A
  • animal sources
  • fish, meat, dairy, eggs
21
Q

How common is vitamin B12 deficiency?

A
  • 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
22
Q

Where is vitamin B12 absorbed and what does it require?

A
  • 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
23
Q

What are the (5) broad causes of B12 deficiency, listed in the lecture?

A
  • impaired absorption
  • decreased intake
  • congenital causes
  • increased requirements
  • medication
24
Q

What are the causes for impaired absorption, leading to B12 deficiency?

A
  • pernicious anaemia
  • gastrectomy or ileal resection
  • zollinger-ellison syndrome
  • parasites/bacterial overgrowth
25
Q

What causes decreased intake, leading to B12 deficiency?

A
  • malnutrition
  • vegan diet
26
Q

What are the congenital causes of B12 deficiency?

A
  • intrinsic factor receptor deficiency
  • cobalamin mutation C-G-1 gene
27
Q

When is there increased requirement of B12, that can cause B12 deficiency?

A
  • haemolysis
  • HIV infection
  • pregnancy
  • growth spurts
28
Q

What medication can cause B12 deficiency?

A
  • alcohol
  • metformin
  • PPI, H2 antagonists
29
Q

What is pernicious anaemia?

A
  • autoimmune disorder
  • lack of intrinsic factor
  • hence lack of b12 absorption
  • gastric parietal cell antibodies
  • intrinsic factor antibodies
30
Q

What are clinical consequences of B12 deficiency/pernicious anaemia?

A
  • brain: cognition, depression, psychosis
  • neuro: neuropathy, myopathy, sensory changes, ataxia, gait abnormalities, spasticity (SACDC)
  • subfertility
  • cardiac: caridomyopathy
  • tongue: glossitis, taste impairment
  • blood: pancytopenia
31
Q

How do you manage Vit B12 deficiency?

A
  • 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
32
Q

What is SACDC?

A
  • 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
33
Q

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?

A
  • chronic alcoholism
  • hypothyroidisim
  • liver disease
  • myelodysplastic syndromes
  • reticulocytosis (haemolysis)
  • clonal bone marrow disorders

treat the underlying disease!!!!!

34
Q

What are the blood film differences between megaloblastic and non-megaoblastic anaemia?

A
  • megaloblastic changes of blood cells are seen in B12 and folic acid deficiency, characterised on peripheral smear by macroovalocytes and hypersegmented neutrophils

Haematology (16 decks)

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