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Yr 3 Haem > macrocytic anaemia > Flashcards

macrocytic anaemia Flashcards

1
Q

definition of macrocytic anaemia

A

Anaemia associated with a high MCV of erythrocytes (>100 fl in adults).

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2
Q

aetiology of macrocytic anaemia

A

megaloblastic

  • drugs - cytotoxic eg hydroxycarbamide
  • folate deficiency
  • vit B12 deficiency

non-megaloblastic:

  • alcohol excess
  • liver disease
  • myelodysplasia
  • multiple myeloma
  • hypothyroidism
  • haemolysis - shift to immature red cells ‘reticulocytosis’
  • drugs eg tyrosine kinase inhibitors: imatinib, sunitinib
  • antifolate drugs - phenytoin
  • marrow infiltration
  • myeloproliferative disorder
  • aplastic anaemia
  • pregnancy
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3
Q

why does folate/B12 deficiency = megaloblastic anaemia

A

deficiency of B12/folate needed for conversion of deoxyuridate to thymidylate, DNA synthesis and nuclear maturation

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4
Q

aetiology of vit B12 deficiency

A

reduced absorption

  • post-gastrectomy,
  • pernicious anaemia,
  • terminal ileal resection or disease eg Crohn’s, bacterial overgrowth, fish tapeworm, tropical sprue, TB, pancreatic insufficiency)
  • metformin,
  • omeprazole

reduced intake - vegans

abnormal metabolism

  • congenital transcobalamin II deficiency,
  • inactivation of B12 by nitrous oxide
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5
Q

aetiology of folate deficiency

A

reduced intake - alcoholics, elderly, anorexia

increased demand - pregnancy, lactation, malignancy, chronic inflammation, chronic haemolysis, exfoliative dermatitis

reduced absorption - jejunal disease (coeliac, tropical sprue, whipple’s disease, small intestinal resection), drugs (phenytoin, trimethoprim, methotrexate, sulphasalazine)

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6
Q

drugs that cause megaloblastic anaemia

A

Methotrexate (inhibition of dihydrofolate reductase),

hydroxyurea (inhibition of ribonucleotide reductase),

azathioprine,

zidovudine

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7
Q

epidemiology of macrocytic anaemia

A

more common in elderly and females

Annual worldwide incidence of pernicious anaemia in those >40 years old is 25 in 100,000 (most common cause of vitamin B12 deficiency in the West).

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8
Q

sx of macrocytic anaemia

A

non-specific signs of anaemia

  • tiredness
  • lethargy
  • dyspnoea

FH of autoimmune disease

previous history of GI surgery

symptoms of cause - weight loss, diarrhoea, steatorrhoea in coeliac

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9
Q

signs of macrocytic anaemia

A

non-specific signs of anaemia

  • pallor
  • tachycardia

signs of cause - malnutrition, jaundice, hypothyroid appearance

signs of pernicious anaemia

signs of B12 deficiency

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10
Q

signs of perncious anaemia

A

lemon-tinted skin (mild jaundice)

glossitis - sore red tongue

angular stomatitis - chelitis

weight loss

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11
Q

signs of B12 deficiency

A

peripheral neuropathy

parasthesiae

ataxia

subacute combined degeneration of the spinal cord

optic atrophy

irritability, depression, psychosis, dementia

sx of anaemia

lemon tinge - from pallor (anaemia) and mild jaundice (haemolysis)

glossitis

angular cheilosis

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12
Q

subacute combined degeneration of the cord

A

sign of B12 deficiency

combination of peripheral sensory neuropathy with both UMN and LMN signs

degeneration of the dorsal columns = sensory (loss of joint and position sense) and LMN

and lateral columns of the spinal cord = ataxia and UMN weakness.

joint position and vibration sense lost 1st -> ataxia -> stiffness and weakness if untreated

spinothalamic tract intact - temp and pain sensation remain

classical triad:

  • extensor plantars (UMN)
  • absent knee jerks (LMN)
  • absent ankle jerks (LMN)

onset is insidious

sign symmetrical

Partially or completely relieved by restoring vitamin B12 levels.

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13
Q

Ix for macrocytic anaemia

A

blood

blood film

schilling’s test

bone marrow biopsy

investigations for the suspected cause

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14
Q

blood results for macrocytic anaemia

A

FBC

  • high MCV,
  • pancytopenia in megaloblastic anaemia,
  • varying degrees of cytopenia in myelodysplasia,
  • exclude reticulocytosis

LFT (include yGT) - high BR from ineffective erythropoeisis or haemolysis.

ESR

TFT
serum B12

red cell folate

Ab against parietal cells or intrinsic factor

serum protein electrophoresis - exclude myeloma

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15
Q

blood film in macrocytic anaemia

A

macrocytes

target cells if liver disease

in megaloblastic anaemia

  • macroovalocytes
  • hypersegmented neutrophol nuclei >5lobes
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16
Q

schilling’s test

A

part 1

  • radiolabelled vitamin B12is given orally and IM non-radioactive B12isgiven to saturate vitamin B12-binding proteins
  • low Radiolabelled vitamin B12 in a 24-h urine collection indicates low absorption

part 2

  • PartI repeated with oral IF.
  • If radiolabelled vitamin B12 is now detected in urine, the cause is likely to be IF deficiency from pernicious anaemia or gastrectomy
17
Q

use of shilling’s test

A

Potential usefulness only when more simple tests (e.g. anti-IF antibodies) are normal and the diagnosis is in doubt

Measurement of the metabolites methylmalonate and total homocysteine have superior sensitivity to Schilling’s test (both increase in vitamin B12 deficiency).

18
Q

bone marrow biopsy in macrocytic anaemia

A

rarely necessary

megaloblasts (nucleated red cells) or myelodysplastic changes

normoblastic marrow - liver disease, hypothyroidism

abnormal erythropoeisis - sideroblastic anaemia, leukaemia, aplasia

increased erythropoiesis - haemolysis

19
Q

Mx of pernicious anaemia

A

IM hydroxycobalamin - thrice weekly for 2 weeks, then every 3mo for life

20
Q

Mx for folate deficiency

A

Oral folic acid: 5 mg/day for 1–4 months, or until complete haematologic recovery occurs.

Vitamin B12 deficiency must be treated first if present (folic acid may worsen neurologic complications of untreated vitamin B12 deficiency).

assess for undelrying cause eg poor diet, malabsorption

in pregnancy - prophylactic dosease of folate (400mcg/day) given from conception until at least 12weeks - prevent spina bifida and anaemia

21
Q

complications of macrocytic anaemia

A

In pernicious anaemia, increased risk of gastric cancer.

In pregnancy, folate deficiency predisposes to spinal cord anomalies.

22
Q

prognosis of macrocytic anaemia

A

Majority are treatable if there are no complications.

23
Q

what is megaloblastic anaemia

A

a megaloblast is a cell in which nuclear maturation is delayed compared with the cytoplasm

caused by B12/folate def and cytotoxic drugs

24
Q

where is folate found

A

green veg

nuts

yeast

liver

25
Q

body’s use of folate

A

synthesised by the gut bacteria

body stores can last 4mo

maternal folate deficiency = fetal neural tube defects

26
Q

where is folate absorbed

A

duodenum, prox jejunum

27
Q

cause of folate deficiency

A

poor diet eg poverty

increased demand - pregnancy, high cell turnover - seen in haemolysis, malignancy, inflammatory disease and renal dialysis

malabsorption - coeliac disease, tropical sprue

alcohol

drugs: anti-epileptics (phenytoin, valproate), mathotrexate, trimethoprim

28
Q

summarise vit B12

A

deficiency is common - occur in 15% of older people

helps synthesise thymidine and hence DNA

= in deficiency RBC production is slow

untreated = megaloblastic anaemia and irreversible CNS complications

body stores are sufficient for 4yrs

29
Q

treating megaloblastic anaemia in unwell patients

A

eg CCF

treat before serum B12 and folate results are known

do tetsst then treat with large dose hydroxyocobalamin and folic acid

30
Q

what is B12 found in

A

meat

fish

dairy products

31
Q

absorption of B12

A

IF in stomach binds to B12 - enabling it to be absorbed in the terminal ileum

32
Q

what is pernicious anaemia

A

autoimmune condition

atrophic gastritis -> lack of IF secretion from parietal cells of the stomach

dietry B12 remains unbound and cannot be absorbed by the terminal ileum

33
Q

epidemiology of pernicious anaemia

A

female slightly more

>40yrs

higher incidence if blood group A

34
Q

associations with pernicious anaemia

A

other autoimmune disease

  • thyroid disease
  • vitiligo
  • addison’s
  • hypoparathyroidism

carcinoma of the stomach is 3 fold more common in pernicious anaemia - low threshold for upper GI endoscopy

35
Q

Ix results for pernicious anaemia

A

low Hb

high MCV

low WCC and platelets if severe

low serum B12

reticulocytes may be low - production impaired

hypersegmented neutrophils

megaloblasts in the marrow

parietal cell Ab

IF Ab - specific, but low specificity

36
Q

Mx of B12 deficiency

A

treat the cause

if malabsorption - hydroxycobalamin (B12) 1mg IM alternate days for 2 wks (or if CNS signs, until improvement stops), then 1mg IM every 3 mo for life

if diet - oral B12 after initial IM course

improvement indicated by transient marked reticulocytosis (high MCV) after 4-5days

37
Q

prognosis of B12 deficiency

A

supplementation improves peripheral neuropathy within 1st 3-6mo - has little effect on cord signs

dont delay treatment

38
Q

epidemiology of folate deficiency

A

common where no fortification of cereal grains

pre-school, pregant, older people most affcected

39
Q

Ix results for folate deficiency

A

film

  • macrocytosis
  • anisocytosis
  • poikilocytosis
  • hypersegmented neutrophils

FBC

  • low Hb
  • high MCV, MCH
  • thrombocytopenia
  • neutropenia

low corrected reticulocyte count

Yr 3 Haem (16 decks)

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