PHAY0085
Anaemia- Part 2
Dr Nicola Tyers
Updated and delivered by Mrs Tasneem Kapadia
Learning Outcomes
• Recap roles of red blood cells
• Understand and recognise the
epidemiology, aetiology, symptoms and
treatment of different types of anaemia
• Be able to apply knowledge to case studies
Recap: Anaemia
• Microcytic (low MCV)
• Iron deficiency – most common cause
• Chronic diseases
• Sideroblastic (rare)
• Megaloblastic (high MCV)
• Folate deficiency
• Vit B12 deficiency
• Haemolytic
• Autoimmune
• Sickle cell
• Thalassaemia
• G6PD deficiency
We need to treat the underlying cause
Microcytic Anaemias:
Anaemia of chronic disease
Anaemia of renal disease
Anaemia of chronic disease
• Second most common type of anaemia
• Associated with inflammatory diseases (anaemia of inflammation)
• Impaired response to EPO and inflammatory cytokines → reduction in
circulating iron
• Normal iron stores, but iron is not in circulation (reduced erythropoiesis)
• Cytotoxic agents may also reduce erythropoiesis
Note: RBC may be
normocytic or microcytic
Iron metabolism
Diagnosis and Treatment
• Risk factors: autoimmune disorders, malignancy, acute/ chronic infection,
critical illness, major trauma, chronic disease
• Findings consistent with disease states
• Rule out other causes (including bleed, drugs associated with anaemia
risk)
• Treat the underlying condition- anaemia should resolve
• Do NOT treat with iron – functional disorder, not actual deficiency (and
reduced absorption of iron)
• Exception: IV iron with EPO in patients CKD
Focus: Anaemia of renal disease (CKD)
• Anaemia in CKD is usually due to EPO deficiency as a result of damage
to kidney cells
• Some CKD patients also have inflammation or infection so anaemia of
chronic disease may be part of anaemia
https://www.niddk.nih.gov/news/media-library/18304
Anaemia of renal disease (CKD)
• Hb falls to <10-11g/dL and patient develops symptoms attributable to
anaemia
• Offer treatment with ESAs (erythropoietic stimulating agents) to those
who would benefit - Epoetin
• Do not initiate in presence of absolute iron deficiency without also
managing iron deficiency
• Usually seen in severe CKD; dose may depend on dialysis
• IV iron therapy if indicated (iron deficiency)
• Serum ferritin levels should not rise above 800mcg/L – dose should
be reviewed
• Supplements of vit C, folic acid, carnitine should not be prescribed as
adjuvants specifically for anaemia of CKD
• Determine individual aspirational Hb ranges
Microcytic Anaemias:
Sideroblastic anaemia
Sideroblastic anaemia
• Anaemia caused by abnormal utilisation of iron during erythropoiesis
(during heme production)
• Presence of ring sideroblasts in bone marrow (erythroblasts with iron
granules surrounding nucleus)
• Normal to high iron levels
• Hereditary (rare) – hypochromic, microcytic
• Acquired (impaired haem synthesis may be associated with
myeloproliferative disorders or secondary to ingestion of drugs) –
hypochromic, normo/microcytic
Causes
Treatment
• Discontinuation of known drugs/ toxins (should improve anaemia)
• X-linked sideroblastic anaemia
• Trial pyridoxine 50-200mg daily
• Response slow and partial – takes several months to see results
• Severe: Blood transfusion may be required
• Idiopathic sideroblastic anaemia
• Pyridoxine high dose 100-400mg daily in divided doses
• Do not buy OTC iron or vitamin supplements especially ascorbic acid
and pyridoxine
Megaloblastic Anaemias
Megaloblastic anaemias
• Macrocytic – raised MCV >100fL
• Abnormality in maturation of haematopoietic cells in bone marrow –
defective DNA synthesis
• WBC and platelets may also be affected
• Two main causes:
• Folate deficiency
• Vit B12 deficiency
• Pernicious anaemia:
autoimmune disease affecting
gastric mucosa → atrophy
• Fewer parietal cells which
secrete intrinsic factor
(essential for B12
absorption) →
malabsorption of vit B12
• Occurs in 120/100000
• Associated with thyroid
disease, vitiligo
Role of Vit B12 and Folate in DNA synthesis
• Megaloblastic anaemia can be caused
by:
• Medications which modulate
purine metabolism (e.g.
azathioprine, MMF, allopurinol) or
interfere with pyrimidine synthesis
(e.g. hydroxyurea, trimethoprim),
or both (e.g. MTX)
• Meds which affect folate or B12
absorption
• Don’t need to remember specifics
• Both are required for purine and pyrimidine synthesis
Blood tests in megaloblastic anaemia
•
•
•
•
•
Hb
MCV
Bilirubin
Serum B12 (cobalamin)
One or both
Folate
• Can also consider:
• Serum autoimmune antibodies (parietal cell and IF)
• Bone marrow examination
• LFTs, TFTs to identify underlying cause
Features- megaloblastic anaemias
• Main clinical features are similar regardless of underlying cause (B12 or
folate deficiency), except that severe neuropathy does not occur with
folate deficiency
• Onset of anaemia is usually insidious
• Also cognitive changes, dyspnoea, headache, loss of appetite, lethargy,
anorexia, brown pigment in nail beds and skin creases
Features- megaloblastic anaemias
• Neurological complications associated with B12 deficiency include:
• Loss of cutaneous sensation
• Loss of mental and physical drive
• Muscle weakness
• Optic neuropathy
• Psychiatric disturbances
• Symmetrical neuropathy (esp in legs)
• Urinary or faecal incontinence
Megaloblastic Anaemias:
Folate Deficiency
Folate deficiency (<3mcg/L)
• Marginal dietary intake – body stores low
• Readily available in diet, but still deficient
• Folate converted in gut to eventually act as co-enzyme in several
reactions including DNA and RNA synthesis
• Deficiency → defective DNA synthesis → affects cells with rapid turnover
(e.g. RBC, GI)
• Co-enzyme also needs reactivating in DNA synthesis by dihydrofolate
reductase (inhibited by MTX, trimethoprim)
• Causes include:
• Diet deficient in folate-rich foods
• Alcoholism
• GI disorders (coeliac disease)
• Pregnancy (preferential delivery to foetus- deficiency in utero
increases risk of neural tube defects in child)
• Haematological disorders
• Medications
Drug causes- folate deficiency
Managing folate deficiency
• Assess dietary folic acid intake (and advise)
• Check for coeliac disease (if malabsorption suspected)
• Replace with folic acid 5mg daily
• Treat for 4 months – recheck levels
• Check B12 levels in all patients with low folate
• Treating with folic acid while B12 still low can improve wellbeing,
mask underlying deficiency, and allow neurological disease to
develop – risk of precipitating neuropathy
• If B12 is also low – replace B12 first or concurrently
Megaloblastic Anaemias:
Vit B12 Deficiency
Vitamin B12 deficiency (<200ng/L)
• B12 combines with IF to form IF-B12 complex → binds to surface
receptors in distal ileum → absorption of B12
• Pernicious anaemia is the most common cause of severe deficiency
• Similar symptoms to folate deficiency PLUS progressive neuropathy
• Other causes:
• Drugs (see next slide)
• Gastric (gastrectomy, congenital IF deficiency)
• Inherited
• Intestinal (malabsorption, ileal resection, Crohn’s, parasites)
• Nutritional (malnutrition, vegan diet- B12 found in meat)
• Need 1-3mcg daily; stores last for 2-5 years so slow onset
Drug causes- B12 deficiency
Managing B12 deficiency
•
•
•
•
IM hydroxocobalamin or PO cyanocobalamin
Initial replacement and maintenance doses
MHRA/ CHM advice in known cobalt allergy
Neurological involvement?
• Seek urgent specialist advice
• Meanwhile, IM hydroxocobalamin 1mg alt days until no further
improvement, then 1mg every 2 months
• No neurological involvement? Look at underlying cause
• Medicine-induced
• Replace with IM or PO vit B12 while taking the causative medicine, or
see if an alternative medicine can be used
• Choice of IM vs PO depends on clinical judgement/ pt preference
• Dietary cause- see next slide
• Unknown cause
• Consider initial PO replacement (otherwise IM)
• Maintenance
• IM hydroxocobalamin 1mg every 2-3m for life
• PO cyanocobalamin large doses 500-1000mcg daily
Managing B12 deficiency
• Suspected dietary cause
• Explore current diet
• Consider further investigations to rule out other causes
• Advice on improving dietary intake: eggs, foods fortified with
B12, meat, dairy, salmon, cod
• Consider PO cyanocobalamin 50-150mcg OD between meals
• Pregnancy or breastfeeding: 1mg OD between meals
• If concerns about adherence, initially IM hydroxocobalamin 1mg
3x/wk for 2 weeks
• Maintenance dose:
• PO cyanocobalamin 50-150mcg OD
• IM hydroxocobalamin 1mg twice a year
• Treatment may be lifelong for vegan diet (otherwise can stop
when B12 corrected and diet improved)
Haemolytic Anaemias
Haemolytic anaemias
•
•
•
•
Approximately 5% of all anaemias
Reduced life span of erythrocytes
Rate of destruction > rate of production
Genetic and acquired disorders
• Normochromic/ normocytic- may look
normal but bursting
Symptoms may include
• Malaise
• Fever
• Abdominal pain
• Dark urine, jaundice (high bilirubin)
Sickle cell anaemia
• Structural abnormality of Hb, resulting in deformed, less flexible RBC
• Nearly all people with sickle cell disease have anaemia (low Hb)
• Few anaemia symptoms- can get worse if infected with parvovirus
(slapped cheek syndrome)
• Can lead to sudden drop in RBCs and may cause headaches, rapid
heartbeat, dizziness, fainting
• Usually treated with blood transfusion
• In young children, swelling of spleen can also cause sudden anaemia
requiring blood transfusion
• Associated with sickle cell crises, frequent infection
Sickle cell anaemia
• Sickle cell crises- blood vessels to part of body become blocked
• Extremely severe pain lasting days or weeks
• Can affect any part of body – most common in limbs or back
• May occur once a week or less than once a year
• Usually requires hospitalisation – IV fluids, analgesia, treatment of
concurrent infection
• Other complications include:
• Skin ulceration
• Renal failure
• Increased susceptibility to infection
Treatment and counselling
• Increased erythropoiesis (overactive bone marrow) → increased demand
for folate → patients may be started on folic acid
• If anaemia particularly severe or persistent, may require blood
transfusions or hydroxycarbamide
• Risk of iron overload with regular transfusions
• Chelation therapy (deferasirox, desferrioxamine)
• Infection risk – may receive prophylactic antibiotics e.g.
phenoxymethylpenicillin
G6PD deficiency
• Glucose 6-phosphate dehydrogenase deficiency common in individuals
originating from Africa, Asia, Mediterranean region, and Middle East
• Recessive hereditary disease
• G6PD is an enzyme helps protect RBC from damage and premature destruction
• Deficiency → susceptibility to developing acute haemolytic anaemia when taking
certain drugs, when they have an infection, or when eating fava beans
• Drugs are split into those with a:
• Definite risk
• Possible risk
• Lists available in BNF
G6PD deficiency – drugs with definite risk
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•
•
•
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•
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Dapsone
Fluoroquinolones (e.g. ciprofloxacin)
Quinolones
Nitrofurantoin
Primaquine
Rasburicase
Sulfonamides (including co-trimoxazole)
G6PD deficiency – drugs with possible risk
•
•
•
•
•
Aspirin – acceptable up to dose 1g daily in most
Chloroquine – acceptable for malaria
Menadione (vit K3)
Quinine – acceptable in acute malaria
Sulfonylureas
Thalassaemia
• Inherited autoimmune recessive disorder
• Mediterranean, North/ West Africa, Middle East, Indian subcontinent
• Produce little or no Hb → can’t carry O2 around body → symptoms of
anaemia
• Beta thalassaemia is the most severe type and can cause serious organ
damage/ life-threatening complications
• Manage with regular blood transfusions
• Risk of iron overload: administer chelation therapy to remove excess
iron
• Only cure- stem cell or bone marrow transplant
Learning Outcomes
• Recap roles of red blood cells
• Understand and recognise the
epidemiology, aetiology, symptoms and
treatment of different types of anaemia
• Be able to apply knowledge to case studies
Post-Work Optional Case Studies
Case 1
• A 4-year-old child has been seen by the GP and diagnosed with irondeficiency anaemia. The GP has prescribed an oral dose of elemental
iron of 3mg/kg daily in 2-3 divided doses. The child weighs 17kg. Ferrous
sulfate is available as oral drops with strength 125mg (25mg iron)/mL.
• What is the total daily dose in mL needed for this child?
Case 2
• A 48-year-old female asks for advice as she is feeling tired all the time
(for about 10 months) and is irritable. She is generally well and healthy
but leads a stressful life with a couple of children and works long hours.
She was diagnosed with COPD a few years ago. She occasionally drinks
alcohol and has a BMI of 27.
• What Qs would you ask?
• What investigations should be carried out?
• What is your differential diagnosis?
Case 3
• A 74-year-old female sees her visiting paramedic as she is housebound
and feeling tired all the time. She tries to exercise by walking from room
to room, but she is struggling to continue this and is experiencing tingling
in her fingers. She is worried that this is angina.
• On questioning, she explains that she doesn’t have regular meals. She
drinks a lot of tea, and her diet consists mainly of the occasional ready
meal and beans on toast. Her sister had pernicious anaemia.
• What Qs would you ask?
• What investigations should be carried out?
• What is your differential diagnosis?
References
https://www.nice.org.uk/guidance/ng203
https://rarediseases.org/rare-diseases/anemia-of-chronicdisease/#%3A~%3Atext%3DAnemia%20of%20chronic%20disease%2C%20also%2Cas
%20rheumatoid%20arthritis%20or%20lupus
https://www.nhs.uk/conditions/sickle-cell-disease/symptoms/
https://patient.info/doctor/anaemia-in-chronic-kidney-disease
https://ukkidney.org/sites/renal.org/files/Updated-130220-Anaemia-of-ChronicKidney-Disease-1-1.pdf
https://bestpractice.bmj.com/topics/en-gb/95
https://www.slideshare.net/faheemjavedpagal/rbc-morphology-and-disease-thatmay-be-associated-with-abnormal-morphologies
https://www.ncbi.nlm.nih.gov/books/NBK538287/
https://cks.nice.org.uk/topics/anaemia-b12-folate-deficiency
https://geekymedics.com/haematinics-interpretation/
References
https://www.nhs.uk/conditions/sickle-cell-disease/symptoms/
https://bnf.nice.org.uk/treatment-summaries/iron-overload/
https://www.nhs.uk/conditions/thalassaemia/
https://bnf.nice.org.uk/treatment-summaries/anaemia-megaloblastic/
https://www.nejm.org/doi/10.1056/NEJMra1508861
Further reading:
BNF and NICE CKS summaries