Macrocytic Anaemia Flashcards
What is Macroctyic Anaemia?
large Mean Corpuscular Volume indicating large RBCs
What is the normal range of MCV?
80-100 femtolitres
Macrocytic anaemia can be divided into what two categories?
megaloblastic bone marrow and those with a normoblastic bone marrow
How does megaloblastic anaemia arise?
impaired DNA synthesis preventing the cell from deciding normally
Rather than dividing it keeps growing into a larger, abnormal cell
What are megaloblastic causes?
vitamin B12 deficiency
folate deficiency
What are normoblastic causes?
alcohol
liver disease
hypothyroidism
drugs: cytotoxics
pregnancy
reticulocytosis (from hemolytic anaemia or blood loss)
myelodysplasia
Vitamin B12 is mainly used in the body for?
red blood cell development and also maintenance of the nervous system
How is Vitamin B12 absorbed?
It is absorbed after binding to intrinsic factor (secreted from parietal cells in the stomach)
is actively absorbed in the terminal ileum
A small amount of vitamin B12 is passively absorbed without being bound to intrinsic factor.
true
Causes of vitamin B12 deficiency?
pernicious anaemia: most common cause
vegan diet or a poor diet
post gastrectomy
disorders/surgery of terminal ileum
Crohn’s: either diease activity or following ileocaecal resection
metformin (rare)
What type of anaemia do you get in B12 deficit?
macrocytic anaemia
What symptoms do you get in B12 deficiency?
sore tongue and mouth
neurological symptoms
the dorsal column is usually affected first (joint position, vibration) prior to distal paraesthesia
neuropsychiatric symptoms: e.g. mood disturbances
What factors determine management in B12 deficiency:?
neurological involvement
if a patient is also deficient in folic acid
Outline management of B12 deficiency?
if no neurological involvement 1 mg of IM hydroxocobalamin 3 times each week for 2 weeks
then once every 3 months
if a patient is also deficient in folic acid then it is important to treat the B12 deficiency first to avoid precipitating subacute combined degeneration of the cord
What should you do in B12 deficiency with neurological involvement
Seek urgent specialist advice from a hematologist.
if specialist advice is not immediately available, consider the following:
Initially administer hydroxocobalamin 1 mg intramuscularly on alternate days until there is no further improvement
then administer hydroxocobalamin 1 mg intramuscularly every 2 months.
What is Pernicious Anaemia?
autoimmune disorder affecting the gastric mucosa that results in vitamin B12 deficiency.
What does pernicious mean
pernicious means ‘causing harm, especially in a gradual or subtle way’ - the symptoms of signs are often subtle and diagnose is often delayed.
Is pernicious anaemia the commonest cause of B12 deficit?
YES
Is pernicious anaemia the ONLY cause of B12 deficit?
NO
Other causes include atrophic gastritis (e.g. secondary to H. pylori infection), gastrectomy, malnutrition (e.g. alcoholism).
What antibodies are assoc with pernicious anaemia?
antibodies to intrinsic factor +/- gastric parietal cells
What do intrinsic factor antibodies do?
bind to intrinsic factor blocking the vitamin B12 binding site
What do gastric parietal antibodies do?
Cause reduced acid production and atrophic gastritis
Cause reduced intrinsic factor production → reduced vitamin B12 absorption
vitamin B12 is important in both the production of blood cells and the myelination of nerves
true
→ megaloblastic anaemia and neuropathy
Describe the aetiology of Pernicious anaemia
more common in females (F:M = 1.6:1)
typically develops in middle to old age
more common if blood group A
associated with other autoimmune disorders: thyroid disease, type 1 diabetes mellitus, Addison’s, rheumatoid and vitiligo
List the neurological features that may arise with PA
peripheral neuropathy: ‘pins and needles’, numbness. Typically symmetrical and affects the legs more than the arms
subacute combined degeneration of the spinal cord: progressive weakness, ataxia and paresthesias that may progress to spasticity and paraplegia
neuropsychiatric features: memory loss, poor concentration, confusion, depression, irritabiltiy
List the symptoms of PA (other than neurological)
anaemia features: lethargy, pallor, dyspnoea
mild jaundice: combined with pallor results in a ‘lemon tinge’
glossitis → sore tongue
Schilling test is the diagnostic test for PA
False
Schilling test is no longer routinely done
What tests should you do for PA?
full blood count
vitamin B12 and folate levels
antibodies
What would FBC show in PA?
macrocytic anaemia
macrocytosis may be absent in around of 30% of patients
low WCC and platelets may also be seen
What would blood film show in PA?
hypersegmented polymorphs on blood film
a vitamin B12 level of what is generally considered to be normal
> = 200 nh/L
Describe the sensitivity and specifiity of anti intrinsic factor antibodies for PA
sensivity is only 50% but highly specific for pernicious anaemia (95-100%)
Is gastric parietal cell antibodies useful in diagnosing PA? why?
anti gastric parietal cell antibodies in 90% but low specificity so often not useful clinically
Outline the managemet of PA
vitamin B12 replacement
usually given intramuscularly
no neurological features: 3 injections per week for 2 weeks
followed by 3 monthly treatment of vitamin B12 injections
more frequent doses are given for patients with neurological features
folic acid supplementation may also be required
People with PA have an increased risk of what?
increased risk of gastric cancer
What is Myelodysplastic syndrome?
acquired neoplastic disorder of hematopoietic stem cells
What is the sequelae of Myelodysplastic syndrome?
pre-leukaemia, may progress to AML
Myelodysplastic syndrome is more common with age
YES
How would Myelodysplastic syndrome present?
presents with bone marrow failure (anaemia, neutropaenia, thrombocytopenia)
