Anaemia in Primary Care
March 18th 2010Dr Mary Clarke
Consultant Haematologist
Hospital provides laboratory service to primary care
Hospital provides laboratory service to primary care
Hospital provides laboratory service to primary care
• Here to help and advise
The challenge with haematology results is that there is sometimes just too much information!
You want to be confident that you can give informed advice to patient
A framework for haematology results will help
plan
• What’s so interesting about red cells?
• Size matters
• The forces of Production vs destruction
• What’s so interesting about red cells?
Normal red cells
Red blood cells are produced in the bone marrow
Bone marrow with active red cell production
Red cell production rate is impressive
Adult male 70kg
• 2 000 000 red cells every second !
Control systems for red cell production are vital
Control systems for red cell production are vital
Growth factors
• Erythropoitin
o JAK 2 kinase
Anaemia the size of the problem
• 1.3 billion people with anaemia
• 600-700m iron deficiency
• Mainly developing countries
Iron deficiency world wide
Definitions of Normal haemoglobin WHO
• Men 13g/dl
• Women 12g/dl
oPregnancy 11g/dl
Normal haemoglobin WHO
Children
• 6m-6y 11g/dl
• 6-14y 12 g/dl
• What’s so interesting about red cells?
• Size matters
Size matters
Classification of anaemia by red cell size
Mean cell volume= MCV
1. Microcytic
2. Normocytic
3. Macrocytic
Case history
• Kate is 35 years old
• Caucasian
• Works in IT
• 1 year decrease in energy worse in last 2 months
• Gym and running – too tired
Case history
• Lives with partner
• No pregnancies
• Smokes 15 /day
• 6 units of alcohol - weekends
• What could be cause of her symptoms?
What could be cause of symptoms?
Non specific history
• Respiratory disease – smokes
• Cardiovascular disease – young
• Anaemia
• Depression
• What type of anaemia – 35y female
Most likely cause of anaemia in a 35y female
Iron deficiency
• Female
• Childbearing age
• How should her anaemia be assessed clinically?
3. How should her anaemia be assessed clinically?
History and examination for clues• Palmar creases
• Conjunctiva• Side of mouth ( angular stomatitis)• Severe anaemia – nails (koilonychia)• Dysphagia due to pharangeal web
……..But may be no symptoms or signs
Smooth pale tongue
Nail changes in iron deficiency
• what should be done next?
what should be done next?
A full blood count
• Hb 8.6 gm/dl
• MCV 62 fl
• WBC 5.6x109/l
• Platelets 342 x109/l
Blood film
Normal blood filmSmall pale red cells
Blood film in iron deficiency
• what do these result indicate?
what do these result indicate?
• low MCV Small red cells
• Commonly iron deficiency
• what other reasons could there be for small pale red cells?
what other reasons could there be for small red cells?
• Thalassaemia carrier
• Deficient globin chain synthesis
6what other reasons could there be for small pale red cells?
• Anaemia of chronic disease
• What reasons would you give for and against thalassaemia or anaemia of chronic disease?
Small red cells thalassaemia
• Thalassaemia uncommon in Caucasian
• More common • Mediteranean• Middle East• South east Asia
Small red cell chronic disease
Chronic disease
• Chronic inflammation /infection
• Malignancy
• what other investigation will help to confirm your diagnosis?
what other investigation will help to confirm your diagnosis?
Serum ferritin
• Low in iron deficiency
• Normal range 20 – 200 micrograms/l
what other investigation will help to confirm your diagnosis?
Serum ferritin
• Low in iron deficiency
• Normal in thalassaemia
• Raised in chronic disease
• Normal range 20 – 200 micrograms/l
• At what level would you be prepared to accept iron deficiency as diagnosis?
At what level would you be prepared to accept iron deficiency
as diagnosis?
• Ferritin < 10 micro grams /ml
At what level would you be prepared to accept iron deficiency
as diagnosis?Care interpreting ferritin
• Chronic disease
• Liver disease
• Old age
iron deficiency is likely – what next step?
• Detailed dietary history to assess iron intake
Absorption of iron from food
Which is better source of iron ?
Iron balance in and out /day are equal
Iron balance in and out /day are equal
bleeding
Iron absorption can increase when need
Absorption of iron can increase
• 30% in iron deficiency
Site of iron absorption
Iron is absorbed from proximal small intestine
Is dietary deficiency likely to be the explainaition in Katy?
• Full time job
• Steady relationship
• Appears well nourished
• what is the commonest mechanism to cause a woman of 35 to become iron deficient?
what is the commonest cause of iron deficiency in a 35 y old woman?
• Heavy menstrual blood loss
• > 80 mls /month = menorrhagia
• Difficult to assess
• High risk menarche and peri menopause
• what other parts of the physical examination are important to find the cause of iron deficiency?
Exclude gastrointestinal blood loss
• Especially post menopausal female
• Males
13 what other parts of the physical examination are important to find the
cause of iron deficiency?
• Rectal examination
• Stool for occult blood
Iron deficiency
Colon cancer
Iron deficiency - causes
• dietary deficiency
• blood loss
• malabsorption
Woman with iron deficiency - results
• ferritin 6 g/l
• serum folate 0.4 g/l
• red cell folate 80 g/l
Normal jejunum
Coeliac disease endomesial antibodies positive predictive value 99%
Dermatitis herpetiformis
Other causes of a microcytic anaemia
28 yr. old woman• booking in antenatal clinic• investigations
– Hb 10.1g/dl– MCV 62fl– ferritin 60 g/l
Other causes of a microcytic anaemia
28 yr. old woman• booking in antenatal clinic• investigations
– Hb 10.1g/dl– MCV 62fl– ferritin 60 g/l
– Hb A2 5.6%
• Carrier of thalassaemia
• Reduced Beta globin chains
or
• Reduced alpha chains
Carriers of thalassaemia trait
risk of thalassaemia major in children
Child with untreated thalassaemia major
World distribution of haemoglobinopathies
Classification of anaemia by red cell size
Mean cell volume= MCV
1. Microcytic
2. Normocytic
3. Macrocytic
Anaemia of chronic disease
Common type of anaemia
• Mild to moderate anaemia (Hb 10 g/dl)
• Normocytic normochromic anaemia (normal MCV and
MCH).
Anaemia of chronic disease
Anaemia of chronic disease
Causes• Malignancy• Inflammation eg rheumatoid arthritis
• Infection eg leg ulcer
Classification of anaemia by red cell size
Mean cell volume= MCV
1. Microcytic
2. Normocytic
3. Macrocytic
Elderly woman with tingling toes
• 76yr• Tingling toes• difficulty doing up buttons• breathless and pale• friends say “looks yellow”
Elderly woman with tingling toes
Investigations
• Hb 8.6g/dl
• MCV 108fl
Hypersegmented neutrophil
Elderly woman with tingling toes
Investigations
• Hb 8.6g/dl
• MCV 108fl
• Vitamin B12 = 56 ng/l
Hypersegmented neutrophil
How is vitamin B12 absorbed?
• Synthesised only by microrganisms - – food of animal origin
• needs intrinsic factor– made by parietal cells in stomach
• absorbed in terminal ileum
Commonest cause of B12 deficiency
Pernicious anaemia
• autoimmune disease
• antibody to intrinsic factor B12
Intrinsic factor
normal
Treatment of B12 deficiency
Vitamin B 12
Liver!
Why is B12 needed ?
• DNA– folate– vitamin B12
Red cell nucleus
Elderly woman with tingling toes
Final diagnosis
• malabsorption of vitamin B12
• due to autoimmune disease
= pernicious anaemia
• neurological damage
78 year old woman macrocytosis and
pancytopenia
• Hb 10 gm/dl
• MCV 109fl
• WBC 3.3 x109/l
• platelets 87 x 109/l
what next?
• Normal B12 and folate !
78 year old woman macrocytosis and pancytopenia
blood film
• red cells abnormal shaped
• neutrophils abnormal nucleus, hypogranular
• platelets abnormal size and granularity
myelodysplasia
Myelodysplasia
• stem cell disorder– affects RBCs, WBCs and platelets
• causes bone marrow failure
• no effective treatment
• may progress to acute myeloid leukaemia
• ? Bone marrow transplant in young
• What’s so interesting about red cells?
• Size matters
• The forces of Production vs destruction
Another was to think about anaemia
Red cells
• Reduced production
• Increased destruction
Bone marrow is like a window box!
Another was to think about anaemia
• Reduced production– Empty marrow
Bone marrow failure aplastic anaemia
Another was to think about anaemia
• Reduced production– Full marrow
Woman with raised ESR
54 year old woman with confusion and malaise, backache and constipation
• Hb 8g/dl
• WBC 9x10/l
• platelets 342 x109/l
• ESR 110 mm/h
what next?
Anaemia and backache due to myeloma
Plasma cells – mature B lymphocytes
Anaemia and backache due to myeloma
Plasma cells – mature B lymphocytesX-rays
Increased destruction of red cells
• Intrinsic RBC abnormality
• Extrinsic RBC abnormality
Increased destruction of red cells
• Intrinsic RBC abnormality• Membrane• Haemoglobin• Enzymes
• Extrinsic RBC abnormality• non immune• immune
Abnormalities of Red cell causing anaemia
Membrane hereditary spherocytosis
Haemoglobin sickle cell disease
EnzymesG6PD
Sickle cell disease
A normal red cells needs to be flexible to cross narrow capillary
bed
Jaundice haemolytic anaemia -Sickle cell disease
“My killer dinner” Nick Kettles
“How a vegetable diet led to organ malfunction
At first I dismissed my pale red urine as the result of a large beetroot salad I had eaten the night
before….
Perhaps the fact that the short walk to the toilet was leaving me progressively breathless should
have been the red flag…”
G6PD deficiency
Heredity spherocytosis
Increased destruction of red cells
• Extrinsic RBC abnormality
Fragmented red cells
Red cell fragmentationMechanical heart valves
Summary
• What’s so interesting about red cells?
• Size matters
• The forces of Production vs destruction
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