anaemia in primary care march 18 th 2010 dr mary clarke consultant haematologist
TRANSCRIPT
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Anaemia in Primary Care
March 18th 2010Dr Mary Clarke
Consultant Haematologist
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Hospital provides laboratory service to primary care
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Hospital provides laboratory service to primary care
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Hospital provides laboratory service to primary care
• Here to help and advise
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The challenge with haematology results is that there is sometimes just too much information!
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You want to be confident that you can give informed advice to patient
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A framework for haematology results will help
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plan
• What’s so interesting about red cells?
• Size matters
• The forces of Production vs destruction
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• What’s so interesting about red cells?
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Normal red cells
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Red blood cells are produced in the bone marrow
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Bone marrow with active red cell production
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Red cell production rate is impressive
Adult male 70kg
• 2 000 000 red cells every second !
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Control systems for red cell production are vital
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Control systems for red cell production are vital
Growth factors
• Erythropoitin
o JAK 2 kinase
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Anaemia the size of the problem
• 1.3 billion people with anaemia
• 600-700m iron deficiency
• Mainly developing countries
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Iron deficiency world wide
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Definitions of Normal haemoglobin WHO
• Men 13g/dl
• Women 12g/dl
oPregnancy 11g/dl
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Normal haemoglobin WHO
Children
• 6m-6y 11g/dl
• 6-14y 12 g/dl
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• What’s so interesting about red cells?
• Size matters
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Size matters
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Classification of anaemia by red cell size
Mean cell volume= MCV
1. Microcytic
2. Normocytic
3. Macrocytic
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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
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Case history
• Lives with partner
• No pregnancies
• Smokes 15 /day
• 6 units of alcohol - weekends
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• What could be cause of her symptoms?
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What could be cause of symptoms?
Non specific history
• Respiratory disease – smokes
• Cardiovascular disease – young
• Anaemia
• Depression
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• What type of anaemia – 35y female
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Most likely cause of anaemia in a 35y female
Iron deficiency
• Female
• Childbearing age
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• How should her anaemia be assessed clinically?
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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
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Smooth pale tongue
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Nail changes in iron deficiency
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• what should be done next?
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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
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Blood film
Normal blood filmSmall pale red cells
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Blood film in iron deficiency
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• what do these result indicate?
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what do these result indicate?
• low MCV Small red cells
• Commonly iron deficiency
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• what other reasons could there be for small pale red cells?
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what other reasons could there be for small red cells?
• Thalassaemia carrier
• Deficient globin chain synthesis
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6what other reasons could there be for small pale red cells?
• Anaemia of chronic disease
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• What reasons would you give for and against thalassaemia or anaemia of chronic disease?
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Small red cells thalassaemia
• Thalassaemia uncommon in Caucasian
• More common • Mediteranean• Middle East• South east Asia
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Small red cell chronic disease
Chronic disease
• Chronic inflammation /infection
• Malignancy
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• what other investigation will help to confirm your diagnosis?
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what other investigation will help to confirm your diagnosis?
Serum ferritin
• Low in iron deficiency
• Normal range 20 – 200 micrograms/l
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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
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• At what level would you be prepared to accept iron deficiency as diagnosis?
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At what level would you be prepared to accept iron deficiency
as diagnosis?
• Ferritin < 10 micro grams /ml
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At what level would you be prepared to accept iron deficiency
as diagnosis?Care interpreting ferritin
• Chronic disease
• Liver disease
• Old age
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iron deficiency is likely – what next step?
• Detailed dietary history to assess iron intake
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Absorption of iron from food
Which is better source of iron ?
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Iron balance in and out /day are equal
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Iron balance in and out /day are equal
bleeding
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Iron absorption can increase when need
Absorption of iron can increase
• 30% in iron deficiency
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Site of iron absorption
Iron is absorbed from proximal small intestine
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Is dietary deficiency likely to be the explainaition in Katy?
• Full time job
• Steady relationship
• Appears well nourished
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• what is the commonest mechanism to cause a woman of 35 to become iron deficient?
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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
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• what other parts of the physical examination are important to find the cause of iron deficiency?
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Exclude gastrointestinal blood loss
• Especially post menopausal female
• Males
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13 what other parts of the physical examination are important to find the
cause of iron deficiency?
• Rectal examination
• Stool for occult blood
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Iron deficiency
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Colon cancer
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Iron deficiency - causes
• dietary deficiency
• blood loss
• malabsorption
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Woman with iron deficiency - results
• ferritin 6 g/l
• serum folate 0.4 g/l
• red cell folate 80 g/l
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Normal jejunum
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Coeliac disease endomesial antibodies positive predictive value 99%
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Dermatitis herpetiformis
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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
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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%
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• Carrier of thalassaemia
• Reduced Beta globin chains
or
• Reduced alpha chains
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Carriers of thalassaemia trait
risk of thalassaemia major in children
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Child with untreated thalassaemia major
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World distribution of haemoglobinopathies
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Classification of anaemia by red cell size
Mean cell volume= MCV
1. Microcytic
2. Normocytic
3. Macrocytic
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Anaemia of chronic disease
Common type of anaemia
• Mild to moderate anaemia (Hb 10 g/dl)
• Normocytic normochromic anaemia (normal MCV and
MCH).
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Anaemia of chronic disease
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Anaemia of chronic disease
Causes• Malignancy• Inflammation eg rheumatoid arthritis
• Infection eg leg ulcer
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Classification of anaemia by red cell size
Mean cell volume= MCV
1. Microcytic
2. Normocytic
3. Macrocytic
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Elderly woman with tingling toes
• 76yr• Tingling toes• difficulty doing up buttons• breathless and pale• friends say “looks yellow”
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Elderly woman with tingling toes
Investigations
• Hb 8.6g/dl
• MCV 108fl
Hypersegmented neutrophil
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Elderly woman with tingling toes
Investigations
• Hb 8.6g/dl
• MCV 108fl
• Vitamin B12 = 56 ng/l
Hypersegmented neutrophil
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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
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Commonest cause of B12 deficiency
Pernicious anaemia
• autoimmune disease
• antibody to intrinsic factor B12
Intrinsic factor
normal
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Treatment of B12 deficiency
Vitamin B 12
Liver!
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Why is B12 needed ?
• DNA– folate– vitamin B12
Red cell nucleus
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Elderly woman with tingling toes
Final diagnosis
• malabsorption of vitamin B12
• due to autoimmune disease
= pernicious anaemia
• neurological damage
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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?
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• Normal B12 and folate !
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78 year old woman macrocytosis and pancytopenia
blood film
• red cells abnormal shaped
• neutrophils abnormal nucleus, hypogranular
• platelets abnormal size and granularity
myelodysplasia
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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
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• What’s so interesting about red cells?
• Size matters
• The forces of Production vs destruction
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Another was to think about anaemia
Red cells
• Reduced production
• Increased destruction
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Bone marrow is like a window box!
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Another was to think about anaemia
• Reduced production– Empty marrow
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Bone marrow failure aplastic anaemia
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Another was to think about anaemia
• Reduced production– Full marrow
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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?
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Anaemia and backache due to myeloma
Plasma cells – mature B lymphocytes
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Anaemia and backache due to myeloma
Plasma cells – mature B lymphocytesX-rays
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Increased destruction of red cells
• Intrinsic RBC abnormality
• Extrinsic RBC abnormality
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Increased destruction of red cells
• Intrinsic RBC abnormality• Membrane• Haemoglobin• Enzymes
• Extrinsic RBC abnormality• non immune• immune
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Abnormalities of Red cell causing anaemia
Membrane hereditary spherocytosis
Haemoglobin sickle cell disease
EnzymesG6PD
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Sickle cell disease
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A normal red cells needs to be flexible to cross narrow capillary
bed
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Jaundice haemolytic anaemia -Sickle cell disease
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“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…”
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G6PD deficiency
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Heredity spherocytosis
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Increased destruction of red cells
• Extrinsic RBC abnormality
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Fragmented red cells
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Red cell fragmentationMechanical heart valves
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Summary
• What’s so interesting about red cells?
• Size matters
• The forces of Production vs destruction