Anaemia in Primary Care March 18 th 2010 Dr Mary Clarke Consultant Haematologist

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 red cells every second !

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 m iron deficiency Mainly developing countries

Iron deficiency world wide

Definitions of Normal haemoglobin WHO Men 13g/dl Women 12g/dl o Pregnancy 11g/dl

Normal haemoglobin WHO Children 6m-6y 11g/dl 6-14y 12 g/dl

What’s so interesting about red cells? 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?

A full blood count Hb 8.6 gm/dl MCV 62 fl WBC 5.6x10 9 /l Platelets 342 x10 9 /l

Blood film Normal blood film Small pale red cells

Blood film in iron deficiency

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?

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?

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

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 A 2 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

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 lymphocytes X-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 Enzymes G6PD

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 fragmentation Mechanical heart valves

Summary What’s so interesting about red cells? Size matters The forces of Production vs destruction