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

2. Hospital provides laboratory service to primary care

4. Here to help and advise

5. The challenge with haematology results is that there is sometimes just too much information!

6. You want to be confident that you can give informed advice to patient

7. A framework for haematology results will help

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

9. What’s so interesting about red cells?

10. Normal red cells

11. Red blood cells are produced in the bone marrow

12. Bone marrow with active red cell production

13. Red cell production rate is impressive Adult male 70kg 2 000 000 red cells every second !

14. Control systems for red cell production are vital

15. Growth factors Erythropoitin o JAK 2 kinase

16. Anaemia the size of the problem 1.3 billion people with anaemia 600-700m iron deficiency Mainly developing countries

17. Iron deficiency world wide

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

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

20. What’s so interesting about red cells? Size matters

22. Classification of anaemia by red cell size Mean cell volume= MCV 1.Microcytic 2.Normocytic 3.Macrocytic

23. 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

24. Case history Lives with partner No pregnancies Smokes 15 /day 6 units of alcohol - weekends

25. What could be cause of her symptoms?

26. What could be cause of symptoms? Non specific history Respiratory disease – smokes Cardiovascular disease – young Anaemia Depression

27. What type of anaemia – 35y female

28. Most likely cause of anaemia in a 35y female Iron deficiency Female Childbearing age

29. How should her anaemia be assessed clinically?

30. 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

31. Smooth pale tongue

32. Nail changes in iron deficiency

33. what should be done next?

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

35. Blood film Normal blood film Small pale red cells

36. Blood film in iron deficiency

37. what do these result indicate?

38. low MCV Small red cells Commonly iron deficiency

39. what other reasons could there be for small pale red cells?

40. what other reasons could there be for small red cells? Thalassaemia carrier Deficient globin chain synthesis

41. 6what other reasons could there be for small pale red cells? Anaemia of chronic disease

42. What reasons would you give for and against thalassaemia or anaemia of chronic disease?

43. Small red cells thalassaemia Thalassaemia uncommon in Caucasian More common Mediteranean Middle East South east Asia

44. Small red cell chronic disease Chronic disease Chronic inflammation /infection Malignancy

45. what other investigation will help to confirm your diagnosis?

46. Serum ferritin Low in iron deficiency Normal range 20 – 200 micrograms/l

47. 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

48. At what level would you be prepared to accept iron deficiency as diagnosis?

49. Ferritin < 10 micro grams /ml

50. At what level would you be prepared to accept iron deficiency as diagnosis? Care interpreting ferritin Chronic disease Liver disease Old age

51. iron deficiency is likely – what next step? Detailed dietary history to assess iron intake

52. Absorption of iron from food Which is better source of iron ?

53. Iron balance in and out /day are equal

54. bleeding

55. Iron absorption can increase when need Absorption of iron can increase 30% in iron deficiency

56. Site of iron absorption Iron is absorbed from proximal small intestine

57. Is dietary deficiency likely to be the explainaition in Katy? Full time job Steady relationship Appears well nourished

58. what is the commonest mechanism to cause a woman of 35 to become iron deficient?

59. 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

60. what other parts of the physical examination are important to find the cause of iron deficiency?

61. Exclude gastrointestinal blood loss Especially post menopausal female Males

62. 13 what other parts of the physical examination are important to find the cause of iron deficiency? Rectal examination Stool for occult blood

63. Iron deficiency

64. Colon cancer

65. Iron deficiency - causes dietary deficiency blood loss malabsorption

66. Woman with iron deficiency - results ferritin 6  g/l serum folate 0.4  g/l red cell folate 80  g/l

67. Normal jejunum

68. Coeliac disease endomesial antibodies positive predictive value 99%

69. Dermatitis herpetiformis

70. 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

71. 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%

72. Carrier of thalassaemia Reduced Beta globin chains or Reduced alpha chains

73. Carriers of thalassaemia trait risk of thalassaemia major in children

74. Child with untreated thalassaemia major

75. World distribution of haemoglobinopathies

76. Classification of anaemia by red cell size Mean cell volume= MCV 1.Microcytic 2.Normocytic 3.Macrocytic

77. Anaemia of chronic disease Common type of anaemia Mild to moderate anaemia (Hb 10 g/dl) Normocytic normochromic anaemia (normal MCV and MCH).

78. Anaemia of chronic disease

79. Causes Malignancy Inflammation eg rheumatoid arthritis Infection eg leg ulcer

80. Classification of anaemia by red cell size Mean cell volume= MCV 1.Microcytic 2.Normocytic 3.Macrocytic

81. Elderly woman with tingling toes 76yr Tingling toes difficulty doing up buttons breathless and pale friends say “looks yellow”

82. Elderly woman with tingling toes Investigations Hb 8.6g/dl MCV 108fl Hypersegmented neutrophil

83. Elderly woman with tingling toes Investigations Hb 8.6g/dl MCV 108fl Vitamin B12 = 56 ng/l Hypersegmented neutrophil

84. 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

85. Commonest cause of B12 deficiency Pernicious anaemia autoimmune disease antibody to intrinsic factor B12 Intrinsic factor normal

86. Treatment of B12 deficiency Vitamin B 12 Liver!

87. Why is B12 needed ? DNA –folate –vitamin B12 Red cell nucleus

88. Elderly woman with tingling toes Final diagnosis malabsorption of vitamin B12 due to autoimmune disease = pernicious anaemia neurological damage

89. 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?

90. Normal B12 and folate !

91. 78 year old woman macrocytosis and pancytopenia blood film red cells abnormal shaped neutrophils abnormal nucleus, hypogranular platelets abnormal size and granularity  myelodysplasia

92. 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

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

94. Another was to think about anaemia Red cells Reduced production Increased destruction

95. Bone marrow is like a window box!

96. Another was to think about anaemia Reduced production –Empty marrow

97. Bone marrow failure aplastic anaemia

99. Another was to think about anaemia Reduced production –Full marrow

100. 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?

101. Anaemia and backache due to myeloma Plasma cells – mature B lymphocytes

102. Anaemia and backache due to myeloma Plasma cells – mature B lymphocytes X-rays

104. Increased destruction of red cells Intrinsic RBC abnormality Extrinsic RBC abnormality

105. Increased destruction of red cells Intrinsic RBC abnormality Membrane Haemoglobin Enzymes Extrinsic RBC abnormality non immune immune

106. Abnormalities of Red cell causing anaemia Membrane hereditary spherocytosis Haemoglobin sickle cell disease Enzymes G6PD

107. Sickle cell disease

108. A normal red cells needs to be flexible to cross narrow capillary bed

109. Jaundice haemolytic anaemia - Sickle cell disease

110. “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…”

111. G6PD deficiency

112. Heredity spherocytosis

113. Increased destruction of red cells Extrinsic RBC abnormality

114. Fragmented red cells

115. Red cell fragmentation Mechanical heart valves

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