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Anaemia. Nov 2010. Overview. Iron deficiency anaemia Macrocytic anaemia Haemolytic anaemia Recognition and management of bleeding disorders. Case history (1). 45yr old female 3 month history of fatigue and shortness of breath on exertion O/E pallor ++ FBC – Hb 6.2g/dl.
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Anaemia Nov 2010
Overview • Iron deficiency anaemia • Macrocytic anaemia • Haemolytic anaemia • Recognition and management of bleeding disorders
Case history (1) • 45yr old female • 3 month history of fatigue and shortness of breath on exertion • O/E pallor ++ • FBC – Hb 6.2g/dl
Case history (1) • What further results are important in the full blood count? • What further details are important in the clinical history and examination? • What further investigations should be carried out? • How should the patient be managed?
Full Blood Count • Hb 6.2 g/dl (12-16) • WCC 7.0 x 109/l (4-11) • Platelets 300 x 109/l (140-440) • MCV 60fl (76-96) • MCH 24 pg (27-32) • WCC differential –N • Blood Film
Some causes of microcytic anaemia….. • Acquired • Iron deficiency • Anaemia of chronic disease • Myelodysplastic syndromes • Lead poisoning
More causes of microcytic anaemia….. • Inherited • Thalassaemia • Sickle cell trait
What further details are important in the clinical history? • Dietary intake of iron • Symptoms of malabsorption / weight loss • Overt GI blood loss • Menorrhagia • Pregnancy • Oral iron therapy • Bleeding history/ family history of bleeding disorder
Iron Requirements • Males 0.5-1mg per day • Menstruating females 1-2mg per day • Pregnant females 1.5-2.5mg per day • Children 1mg per day • An adequate diet contains 15mg of iron, 10% of which is absorbed.
Dietary iron • Red meat , liver, beans • Absorbed in the duodenum and jejunum • Absorption enhanced by ascorbic acid, citrus fruits • Absorption reduced by phytates, alkalis, tea, tetracyclines
Inadequate intake Failure of absorption Increased blood loss Increased requirements Dietary iron Iron supplements Gastrointestinal symptoms Hx of Coeliac disease Overt blood loss from bowel or change of bowel habit Menorrhagia Pregnancy Causes of iron deficiency anaemia
Oesophagus Stomach Small bowel Hiatus hernia Varices Gastritis Ulcer Carcinoma Ulcer Meckels diverticulum Carcinoma Common causes of gastrointestinal bleeding
Colon Rectum Ulcerative colitis Carcinoma Diverticulitis Haemorrhoids Ulceration Carcinoma Common causes of gastrointestinal bleeding
Iron loss in pregnancy • Obligatory iron loss 150-200 mg • Fetal iron 200-370 mg • Iron in placenta and cord 30-170 mg • Iron in blood lost at delivery 90-310 mg • Total iron loss 470-1050mg
What further investigations should be carried out? • Serum ferritin +/- serum iron • B12 / folate • Faecal Occult Blood • +/- Coeliac screen • +/- Gastroscopy and/or colonoscopy • +/- Gynaecology referral
Causes of raised ferritin levels • Acute inflammation • Acute liver disease • Lymphomas • Solid tumours • Haemochromatosis
How should the patient be managed? • Treat the underlying cause • Oral iron supplements • correct anaemia • replenish iron stores • IV iron • malabsorption • intolerance • Is there a role for blood transfusion?
Failure to respond to oral iron • Is the diagnosis correct? • Is the patient taking the iron? • Is there evidence of malabsorption? • Is there evidence of persistent blood loss?
Case (2) • 45yr old female • 3 month history of fatigue and palpitations • O/E pallor ++ • FBC – Hb 5.3 g/dl
Case 2 • What further results are important in the full blood count? • What further details are important in the clinical history and examination? • What further investigations should be carried out? • How should the patient be managed?
Full Blood Count • Hb 6.2 g/dl (12-16) • WCC 7.0 x 109/l (4-11) • Platelets 120 x 109/l (140-440) • MCV120fl (76-96) • MCH 28pg (27-32) • WCC differential –N • Blood Film
Some causes of macrocytosis…... • Megaloblastic anaemia • Vitamin B12 deficiency • Folate deficiency • Myelodysplasia
More causes of macrocytosis…. • Liver disease • Alcohol excess • Hypothyroidism • Cytotoxic drugs
What further details are important in the clinical history? • Diet • Symptoms of malabsorption / weight loss • Family history of anaemia or autoimmune disorders • Thyroid disease • Alcohol intake
What further investigations should be performed? • Blood film • B12, Folate, Ferritin • Liver function tests • Thyroid function tests • Coeliac screen • Intrinsic factor and parietal cell antibodies • ?Bone marrow – only if above normal
Vitamin B12 • Sources – liver meat fish and dairy products • Daily intake 3-30 microgram • Adult daily requirement 1-2 microgram • Body stores 3-5 mg in the liver (2-4 yr supply) • Important for pyrimidine synthesis in the production of DNA
Vitamin B12 absorption • B12 attaches to intrinsic factor (IF) in the stomach • IF – a glycoprotein secreted by the parietal cells • B12/IF passes to the terminal ileum where absorption takes place
Causes of B12 deficiency • Strict vegetarianism • Malabsorption • Pernicious anaemia • Gastrectomy • Coeliac disease • Disease involving the terminal ileum • Resection • Crohn’s disease
Pernicious anaemia • Autoimmune disease • Gastric atrophy • Anti parietal cell antibodies 90% • Anti intrinsic factor antibodies 70% • Often associated with other autoimmune disorders
B12 deficiency – clinical features • Related to anaemia • Neurological • Peripheral neuropathy • Loss of vibration and position sense • Demyelination of the cord • Irreversible
Management • Lifelong replacement with B12 usually required • IM Hydroxocobalamin 1000 microgram every 3 months
Folate • Dietary sources- eggs, green vegetables, liver, nuts • Absorbed in the jejumun • Daily intake 600-700microgram • Daily requirement 100 microgram • Stored in the liver (4-6 months supply) • Important in DNA synthesis
Causes of folate deficiency • Dietary – infancy and old age • Malabsorption – coeliac disease • Increased utilisation – pregancy, lactation, haemolytic anaemia • Antifolate drugs – methotrexate, anticonvulsants
Management of folate deficiency • Treat underlying cause • Correct folate levels : oral folic acid 5-15mg daily • Prophylactic folate to at risk groups eg pregnancy, congenital haemolytic anaemias
Haemolytic anaemia • Normal red cell life span 100-120 days • A haemolytic anaemia occurs if that life span is shortened • Congenital • Acquired
Mrs C • 31 year old female • History of recent “viral illness” • C/O increasing tiredness • Noticed to look jaundiced by her family
Mrs C • What laboratory investigations should be carried out? • How should the patient be managed?
Mrs C –laboratory results • FBC – Hb 7.7 g/dl • Blood film – polychromasia • Raised reticulocyte count • Raised bilirubin • Raised lactate dehydrogenase (LDH)
Haemolytic Anaemia • How would you investigate the patient? • What are the causes of acquired haemolytic anaemia?
Warm Antibody Idiopathic Secondary CLL Connective tissue disorders Lymphomas Drugs eg Methyldopa Cold Antibody Idiopathic Secondary Mycoplasma Infectious mononucleosis Lymphoma Autoimmune haemolytic anaemia
Alloimmune Haemolytic Anaemia • Haemolytic transfusion reactions eg ABO mismatch • Haemolytic disease of the newborn eg Rhesus incompatibility
Red cell fragmentation Infections Chemical/ Physical DIC, Cardiac valves HUS, TTP March haemoglobinuria Malaria, Clostridium Drugs, chemicals Venoms Burns Non immune haemolytic anaemia
Clinical features of haemolytic anaemias • Symptoms related to anaemia • Jaundice • Increased incidence of pigmented gallstones • Splenomegaly • Leg ulcers- sickle cell, hereditary spherocytosis
Warm autoimmune haemolytic anaemia • Antibody usually IgG – maximum activity @370 • Any age, either sex • Splenomegaly common • Blood film – microspherocytes, polychromasia • Direct Coombs test (DCT) positive
Warm autoimmune haemolytic anaemia • Management • Treat the underlying cause • Corticosteroids • Splenectomy • Other immunosuppressants eg azathioprine, cyclosporin • Blood transfusion – if life threatening
Cold autoimmune haemolytic anaemia • Antibody usually IgM – maximum activity @40 • Raynauds Phenomenon • Positive DCT – complement • Cold agglutinins – agglutination on blood film
Cold autoimmune haemolytic anaemia • Management • Treat the underlying cause • Keep the patient warm • Consider immunosuppression
Haemolytic anaemia and infections • Direct damage to cells eg malaria • Toxin production eg clostridium • Oxidant stress in G6PD deficiency • DIC eg meningococcus • Autoantibody formation eg infectious mononucleosis