macrocytic anaemia Flashcards
definition of macrocytic anaemia
Anaemia associated with a high MCV of erythrocytes (>100 fl in adults).
aetiology of macrocytic anaemia
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
why does folate/B12 deficiency = megaloblastic anaemia
deficiency of B12/folate needed for conversion of deoxyuridate to thymidylate, DNA synthesis and nuclear maturation
aetiology of vit B12 deficiency
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
aetiology of folate deficiency
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)
drugs that cause megaloblastic anaemia
Methotrexate (inhibition of dihydrofolate reductase),
hydroxyurea (inhibition of ribonucleotide reductase),
azathioprine,
zidovudine
epidemiology of macrocytic anaemia
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).
sx of macrocytic anaemia
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
signs of macrocytic anaemia
non-specific signs of anaemia
- pallor
- tachycardia
signs of cause - malnutrition, jaundice, hypothyroid appearance
signs of pernicious anaemia
signs of B12 deficiency
signs of perncious anaemia
lemon-tinted skin (mild jaundice)
glossitis - sore red tongue
angular stomatitis - chelitis
weight loss
signs of B12 deficiency
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
subacute combined degeneration of the cord
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.
Ix for macrocytic anaemia
blood
blood film
schilling’s test
bone marrow biopsy
investigations for the suspected cause
blood results for macrocytic anaemia
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
blood film in macrocytic anaemia
macrocytes
target cells if liver disease
in megaloblastic anaemia
- macroovalocytes
- hypersegmented neutrophol nuclei >5lobes
schilling’s test
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
use of shilling’s test
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).
bone marrow biopsy in macrocytic anaemia
rarely necessary
megaloblasts (nucleated red cells) or myelodysplastic changes
normoblastic marrow - liver disease, hypothyroidism
abnormal erythropoeisis - sideroblastic anaemia, leukaemia, aplasia
increased erythropoiesis - haemolysis
Mx of pernicious anaemia
IM hydroxycobalamin - thrice weekly for 2 weeks, then every 3mo for life
Mx for folate deficiency
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
complications of macrocytic anaemia
In pernicious anaemia, increased risk of gastric cancer.
In pregnancy, folate deficiency predisposes to spinal cord anomalies.
prognosis of macrocytic anaemia
Majority are treatable if there are no complications.
what is megaloblastic anaemia
a megaloblast is a cell in which nuclear maturation is delayed compared with the cytoplasm
caused by B12/folate def and cytotoxic drugs
where is folate found
green veg
nuts
yeast
liver
