Anaemia Flashcards
What does anaemia mean and how is it measured?
Reduced total red cell mass (not easy to measure)
Hb concentration + haematocrit (Hct) are surrogate markers
What is Hct?
Ratio/% of the whole blood that is red cells if the sample was left to settle
In which situations might Hb and Hct not be a good marker of anaemia?
Rapid bleeding –> massively reduced blood volume –> plasma expansion
Haemodilution
How does the body respond to anaemia?
Increase in RBC production –> reticulocytosis
What are reticulocytes and what do they look like?
Red cells that have just left the bone marrow
- larger than mature red cells
- still have remnants of RNA so stain purple/deeper red
- -> blood film appears ‘polychomatic’
How can anaemias be calculated by pathophysiology and how can they be differentiated?
Reduced production of RBCs –> low reticulocyte count
vs
Increased loss or destruction of RBCs –> high reticulocyte count
How can ‘reduced production of RBCs’ be further classified?
Hypoproliferation (reduced amount of erythropoeisis) Maturation abnormality (ineffective erythropoeisis) - cytoplasmic defects (impaired Hb) - nuclear defects (impaired cell division)
What are the causes of increased loss or destruction of RBCs –> increased reticulocytes?
Bleeding
Haemolysis
How is anaemia classified by MCV and which problems should be considered?
If MCV low –> microcytic –> problem with haemoglobinisation
If MCV high –> macrocytic –> problem with maturation
What is the pathophysiology behind microcytic anaemias?
Hb synthesised in cytoplasm with:
- globins
- haem = porphyrin ring + Fe2+
Shortage of any of these results in small red cells with low Hb content
How would the cells be described in microcytic anaemia?
Microcytic (small) and hypochromic (lacking in colour)
What is the differential for a hypochromic microcytic anaemia?
Haem deficiency:
- lack of iron (iron deficiency or sometimes anaemia of chronic disease)
- problems with porphyrin synthesis (lead poisioning, pyridoxine responsive anaemias)
- congenital sideroblastic anaemia (very rare)
Globin deficiency:
- thalassaemia
How is iron deficiency anaemia confirmed?
Anaemia - low Hb (reduced functional iron)
Low serum ferritin (reduced storage iron)
What are the causes of iron deficiency?
Insufficient intake Blood loss - menorrhagia (>60ml) - occult GI blood loss - haematuria Malabsorption (uncommon)
If reticulocytosis is seen, how would you determine whether it is caused by bleeding or haemolysis?
Look for red cell breakdown products
- raised in haemolysis
- not in bleeding
What is the differential for macrocytic anaemia?
Nuclear maturation defects (failure of cell division):
- B12/folate deficiency (megaloblastic anaemia)
- myelodysplasia
- drugs e.g. chemotherapy
Apparent:
- agglutination
- reticulocytosis
Which conditions may cause macrocytosis without significant anaemia?
Hypothyroidism
Alcohol
Liver disease
What are the causes of normochromic normocytic anaemia?
- -> hypoproliferative
- marrow failure: drug induced, aplastic anaemia
- hypometabolic
- marrow infiltration: metastatic malignancy, fibrosis
- renal impairment –> reduced Epo production
- chronic disease: infective, inflammatory, malignant
What is the pathophysiology behind anaemia of chronic disease?
Multifactorial:
- blunted Epo response by kidney
- impaired iron availability to erythroid precursors
- inhibition of proliferation
- reduced red cell survival
How to the following parameters differ in iron deficiency anaemia and anaemia of chronic disease?
- serum iron
- transferrin
- % transferrin saturation
- ferritin
- MCV
Iron deficiency:
- serum iron LOW
- transferrin NORMAL or HIGH
- % transferrin saturation LOW
- ferritin LOW
- MCV LOW
Anaemia of chronic disease:
- serum iron LOW
- transferrin NORMAL or LOW
- % transferrin saturation LOW
- ferritin NORMAL or HIGH
- MCV NORMAL (can be low)
How is macrocytosis classified?
Genuine (true):
- megaloblastic
- non-megaloblastic
Spurious (false)
What is a megaloblast?
An abnormally large nucleated red cell precursor with an IMMATURE nucleus
What is the pathophysiology of megaloblastic anaemia?
Lack of red cells due to defects in DNA synthesis and nuclear maturation
RNA + Hb synthesis are preserved –> bigger cell (macrocyte)
–> larger cell size due to failure to become smaller
What are the causes of megaloblastic anaemia?
B12 deficiency
Folate deficiency
Others: drugs, rare inherited abnormalities
What are the causes of B12 deficiency, classified by site of problem?
Mouth: vegan diet Stomach: (intrinsic factor produced) - pernicious anaemia - atrophic gastritis - PPIs/H2 receptor antagonists - gastrectomy/bypass Chronic pancreatitis Jejunum: bacterial overgrowth, Coeliac Duodenum: resection, Crohn's Ilium (B12 absorbed): inherited defect of Cubulin receptors
What is pernicious anaemia?
Autoimmune destruction of gastric parietal cells
What are the causes of folate deficiency?
Inadequate intake Malabsorption: Coeliac, Crohn's Excess utilisation: - haemolysis - exfoliating dermatitis - pregnancy - malignancy Drugs e.g. phenytoin (anticonvulsants)
How long would body stores of B12 and folate last?
B12 –> 2-4 years
Folate –> 4 months
What are the clinical features of B12/folate deficiency?
Tiredness, fatigue Sore red tongue Weight loss Diarrhoea Infertility Jaundice (intramedullary haemolysis) Neurological and psychiatric symptoms --> B12 - paraesthesia - depression, confusion - memory problems
How should a suspected B12/folate deficiency be investigated?
FBC: macrocytic anaemia
Blood film: macrovalocytes + hypersegmented neutrophils
Serum B12 and folate (not always reliable)
Check anti-IF and anti-gastric parietal cell (GPC) antibodies
What are the causes of non-megaloblastic macrocytosis?
Alcohol Liver disease Hypothyroidism Marrow failure (likely associated anaemia); - myelodysplasia - myeloma - aplastic anaemia
What does spurious macrocytosis mean?
The volume of mature RBCs is normal but MCV is measured as high
What are the causes of spurious macrocytosis?
Reticulocytosis (increased number of reticulocytes makes the MCV appear larger) Cold agglutinins (clumps of agglutinated red cells are registered as 1 giant cell)
What are the signs/symptoms of anaemia?
SOB fatigue pallor (skin + conjunctiva) angina tachycardia
What are the signs/symptoms of iron deficiency?
Same as for anaemia +
- angular chelitis
- glossitis
- brittle nails
- koilonychia (spoon-shaped nails)
- pica: appetite for non food items e.g. clay, paper
- restless leg syndrome
How should suspected iron deficiency anaemia be investigated?
Low ferritin + low Hb
Low iron, raised TIBC, low transferrin saturation
Blood film: poikilocytes (abnormal shaped RBCs)
Investigate cause e.g. endoscopy
What are the cancer referral guidelines for iron deficiency anaemia?
2 week urgent referral if:
- > 60 years old or
- > 55 with post-menopausal bleeding or
- > 50 with PR bleeding
How is iron deficiency anaemia managed?
Oral ferrous sulphate/fumarate
200mg 2-3 times daily
Take on an empty stomach
Or IV iron
How long does oral iron take to have an effect and when should bloods be checked?
Takes 3-6 months to normalise ferritin
Check Hb after 2-4 weeks
What are the side effects of oral iron?
Nausea and vomiting
Constipation
Black stools
What are the indications for IV iron?
Failure of oral therapy
Impaired absorption e.g. IBD, gastrectomy
Taking Epo stimulating agents for CKD
Alternative to red cell transfusion e.g. if rejected for religious reasons
How is B12 deficiency treated?
Hydroxycobalamin 1mg IM
- initially 3x a week for 2 weeks (more in neurological symptoms)
- then once every 3 months for life
How is folate deficiency treated?
Oral folic acid 5mg daily for 4 months
- may be required for life if cause is persistent
- dietary advice
