Macrocytosis and Macrocytic Anaemia 2 Flashcards
What is the most common cause of Vitamin B12 deficiency ?
Pernicious anaemia
What are the 2 main things which parietal cells secrete ?
HCL and intrinsic factor
Explain what pernicious anaemia is
It is an autoimmune condition in which there is atrophic gastritis (chronic inflammation of the stomach mucosa which leads to loss of gastric glandular cells) with loss of parietal cells, resulting in a consequent failure of intrinsic factor (IF) production ==> vitamin B12 malabsorption due to the function of IF
What is pernicious anaemia associated with ?
Other autoimmune conditions:
- Atrophic gastiritis
- Fam history of other autoimmune disorders (eg. Hypothyroidism, vitiligo, Addison’s disease)
Answer the following for both B12 and folate:
- What are their food source
- Where are they absorbed
- How long does the body store them for
- What is there daily requirement to maintain normal levels
What are the causes of folate deficiency ?
Inadequate intake - dietary cause this is more likely than in B12 as the body requires more folate daily and stores it for less time than B12
Malabsorption:
- Coeliac disease, Crohn’s disease
Excess utilisation:
- Haemolysis
- ¨Exfoliating dermatitis
- ¨Pregnancy
- ¨Malignancy
Drugs - anticonvulsants
Recap the general symptoms ad signs of anaemia in general
Symptoms: (general anemaia ones covered in previous flashcards)
- Fatigue and lethargy.
- Dyspnoea.
- Faintness.
- Palpitations.
- Headache.
- Tinnitus.
- Anorexia.
- Angina (if the person has pre-existing coronary artery disease).
General signs of anaemia: (again covered in previous flashcards)
- Pallor
- Tachycardia
- Murmurs
- Sometimes progresses to heart failure
What are the clinical features of both B12 and folate ?
- Symptoms/signs of anaemia
- Weight loss, iarrhoea,
- Infertility
- Sore tongue (glossitis)
- Oropharyngeal ulceration
- Jaundice (due to the increased apoptosis in megaloblastic anaemia)
- Developmental problems
What are the presenting features which would make you think more B12 deficiency ?
- Suspect vitamin B12 deficiency if the person reports unexplained neurological symptoms (for example paraesthesia, numbness, cognitive changes, or visual disturbance).
- Neurological: impaired responses to vibration, touch, pain, and position; visual disturbance; and abnormal gait
- Cognitive changes dementia, psychiatric manifestations
Does neuropathy occur in folate deficiency ?
No - Peripheral neuropathy, a result of damage to your peripheral nerves, often causes weakness, numbness and pain, usually in your hands and feet
What can happen to the spinal cord in B12 deficiency ?
Subacute combined degeneration of the cord - involving the dorsal (posterior column) initially then then progressing to the lateral columns
This is why early loss of vibration and proprioception occurs with this feature
What are the initial investigations for B12 and folate deficiency and the results of these investigations?
1st check FBC – if low Hb and MCV high
2nd check serum B12 and serum folate concentrations (if low Hb and High MCV)
- Note if the Hb low but MCV normal then check the serum ferritin, B12 and folate +/- red cell folate
3rd can look at a blood film if has a B12 or folate deficiency which in these conditions can show:
- oval macrocytes and hypersegmented nuclei in neutrophils (six or more lobes, my note in the lecture is wrong go with this).
- Recticulocyte count may be low
- Low WBC and platelets along with the low RBC’s = pancytopenia (pancytopenia occurs if deficiency is severe)
What feature is shown and what is it associated with ?
macrovalocytes - B12 and folate deficiency
What feature is shown and what is it associated with ?
Hypersegmented neutrophils - B12 and folate
What further investigations are done for folate and B12 deficiency after the intial ones ?
For B12 - Check for auto-antibodies (anti gastric-parietal cell (GPC) and anti-intrinsic factor (IF) - problems are anti-GPC sensitive, not specific; anti-IF: more specific, not sensitive
IF think is the better one to check
For folate - If folate levels are low, and the history suggests malabsorption, check for coeliac disease with anti-endomysial or anti-transglutaminase antibodies
What is the treatment for folate and B12 deficiency ?
B12 deficiency treat with:
- IM Hydroxocobalamin for 3-4 weeks, with lifelong 3 monthly top ups
- Dietary recommendations
Folate deficiency treat with:
- Give dietary advice: good sources of folate are broccoli, Brussels sprouts, asparagus, peas, chickpeas, and brown rice.
- Prescribe oral folic acid 5 mg daily.
- Make sure B12 levels have been checked as if low treat for B12 as well
How is response to B12 and folate deficiency treatment done ?
- A full blood count and reticulocyte count should be performed:
- After approximately 10 days of treatment, to document the response. Then after 8 weeks to confirm normal blood count and then on completion of folic acid treatment.
What are the non-megaloblastic causes of macrocytosis ?
Not the may be associated with anaemia so they may or may not be associated
What are the causes of spurious macrocytosis ?
- When there is an increase in reticulocyte numbers as a marrow response to acute blood loss or red cell breakdown (haemolysis). Reticulocytes are bigger than mature red cells and are analysed along with these for the MCV measurement
- Cold-agglutinins - Cold agglutinin disease is an autoimmune disease characterized by the presence of high concentrations of circulating antibodies, usually IgM, directed against red blood cells. It can result in clumps of ‘agglutinated’ red cells are registered as 1 ‘giant’ cell
What is shown in the pic and what can it result in ?
Cold aggulitins - can result in a spurious macrocytosis
Appreicate these points:
Patients with pernicious anaemia can appear mildly jaundiced due to intramedullary haemolysis
Megaloblastic anaemia results in Ineffective erythropoiesis:
- Red cells die prematurely in the marrow
- Haemoglobin and lactate dehydrogenase (LDH) are released from dead red cells
- Haemoglobin converted to bilirubin (this is why you can potentially get jaundiced with B12 and folate deficiency)
Pancytopenia can complicate severe megaloblastic anaemia
Nuclear maturation defects can affect multiple lineages
