Anaemia Dr Kate Foley ST 5 Haematology Definitions

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Anaemia Dr Kate Foley ST 5 Haematology

Anaemia Dr Kate Foley ST 5 Haematology

Definitions • • Anaemia ‘Reduction in blood haemoglobin concentration below what is considered normal

Definitions • • Anaemia ‘Reduction in blood haemoglobin concentration below what is considered normal for age and sex. ’ Erythropoiesis (from Greek 'erythro' meaning "red" and 'poiesis' meaning "to make") is the process which produces red blood cells (erythrocytes).

Objectives • Perform a competent clinical assessment of a patient with anaemia (including red

Objectives • Perform a competent clinical assessment of a patient with anaemia (including red flags) • Pathophysiology of anaemias • Describe the epidemiology of iron deficiency and macrocytic anaemia and how this affects both the UK population and the global population. • Describe the main investigations used to diagnose anaemia and its causes. • Explain the differing influences of racial, genetic, environmental (e. g. diet and culture) and sex differences in both the development and management of anaemia. • Explain the treatments of anaemia (and its underlying causes) • Synthesise both your history and examination findings to formulate a differential diagnosis of anaemia and its underlying causes and other relevant condition

Erythropoesis

Erythropoesis

 • Need iron, B 12, folate and other essential factors • Need stimulating

• Need iron, B 12, folate and other essential factors • Need stimulating factors (EPO, IL-3, GM-CSF, SCF) • Genes code for red cell structure and function including haemoglobin. • Produced in bone marrow • Lifespan 120 days (travels 300 miles!) • Removed by macrophages of the reticuloendothelial system in marrow, liver and spleen.

Fe, B 12, folate deficiency Anaemia of Chronic disease, CKD, Hypothyroid Hereditary Ineffective erythropoesis

Fe, B 12, folate deficiency Anaemia of Chronic disease, CKD, Hypothyroid Hereditary Ineffective erythropoesis Increased destruction • Intracorpuscular • Membrane • Enzyme • Hb • Extracorpuscular • Mechanical • Chemical • Infection • Antibodies • Splenomegaly Bleeding Bone marrow failure or infiltration

Case History • Mrs Green, 45 year old female. • Presents to GP with

Case History • Mrs Green, 45 year old female. • Presents to GP with 3 months history of increasing tiredness, shortness of breath and headaches. • History of hypothyroidism-well controlled on treatment. • Found to be anaemic with a Haemoglobin of 85 g/L

Signs Tachycardia Symptoms SOBOE Flow murmur Bleeding Weakness Koilynichia Cardiomegaly Change in bowel habit

Signs Tachycardia Symptoms SOBOE Flow murmur Bleeding Weakness Koilynichia Cardiomegaly Change in bowel habit Palpitations Pulmonary oedema Back pain Jaundice Headaches Dyspepsia Pale Mucus membranes Leg ulcers Bruising Angina Intermittent Claudication Weight loss Confusion

Mrs Green. . • On further questioning admits to several months history of dyspepsia

Mrs Green. . • On further questioning admits to several months history of dyspepsia and early satiety • Has lost 10 kg in weight without trying in the same time • Has spoon shaped nails, tachycardia and a flow murmur on examination • PR exam reveals melaena.

What do you want to do now? • Full blood count • U+E •

What do you want to do now? • Full blood count • U+E • LFT • Clotting screen • Group and Save/Crossmatch • Ferritin/Iron studies • B 12/folate • GI investigations • Urine dip • Bone marrow aspirate • Haemoglobin Electrophoresis Would you wait for these results before referring Mrs Green to hospital?

NICE Recommends • Refer all patients with IDA and dyspepsia via 2 ww •

NICE Recommends • Refer all patients with IDA and dyspepsia via 2 ww • Refer all men with Hb < 110 g/L via 2 ww • Refer all post menopausal women with Hb < 100 g/L via 2 ww • Screen all patients for coeliac disease. • Other patients with unexplained IDA will still need upper and lower GI endoscopy

Parameter Result Normal Range Haemoglobin 85 g/L 130 -175 White Cells 11. 1 x

Parameter Result Normal Range Haemoglobin 85 g/L 130 -175 White Cells 11. 1 x 109/L 4. 0 -11. 0 Platelets 260 x 109/L 150 -450 Neutrophils 6. 5 x 109/L 1. 8 -7. 5 Lymphocytes 4. 0 x 109/L 1. 5 -4. 0 Monocytes 0. 9 x 109/L 0. 2 -0. 8 Eosinophils 0. 0 x 109/L 0. 0 -0. 4 Haematocrit (HCT) 0. 37 0. 4 -0. 52 MCV 72 fl 82 -98 MCH 25 pg 27. 0 -34. 0 MCHC 300 g/L 310 -360

Classification of Anaemias Microcytic, hypochromic Normocytic, normochromic Macrocytic MCV <80 fl MCH <27 pg

Classification of Anaemias Microcytic, hypochromic Normocytic, normochromic Macrocytic MCV <80 fl MCH <27 pg MCV 80 -95 fl MCH >27 pg MCV >95 fl Iron deficiency Haemolytic Anaemias Megaloblastic Thalassaemia Anaemia of chronic disease B 12/folate deficiency Anaemia of chronic disease Acute blood loss Non megaloblastic Lead Poisoning Renal disease Alcohol Sideroblastic Mixed deficiency Liver disease Bone marrow failure MDS/ Aplastic anaemia

Other Results • • Ferritin 6 ug/l (15 -300) Serum Iron low TIBC raised

Other Results • • Ferritin 6 ug/l (15 -300) Serum Iron low TIBC raised Blood film-microcytic, hypochromic cells, pencil cells.

Causes Iron Deficiency • Blood loss – Menstruation – GI loss – Other chronic

Causes Iron Deficiency • Blood loss – Menstruation – GI loss – Other chronic blood loss • Dietary • Pregnancy • Coeliac disease • Partial/total gastrectomy • Atrophic Gastritis • Regular blood donation • Hookworm infection-biggest worldwide cause

Further investigations • • • Gynaecological investigations Upper and lower GI endoscopy Anti-endomysial antibodies

Further investigations • • • Gynaecological investigations Upper and lower GI endoscopy Anti-endomysial antibodies H Pylori test Urine dip for blood

Treatment • Treat underlying condition AND • Trial of oral iron – Ferrous sulphate

Treatment • Treat underlying condition AND • Trial of oral iron – Ferrous sulphate 200 mg bd 2 -4 weeks – Ferrous Gluconate • Intravenous iron – If rapid rise needed or poor oral response – Hypotension and anaphylaxis risk – Avoid in bacteraemia

Case 2 • 60 year old female • Hypothyroidism and diabetes • Routine blood

Case 2 • 60 year old female • Hypothyroidism and diabetes • Routine blood test with GP

Parameter Result Normal Range Haemoglobin 79 g/L 130 -175 White Cells 11. 1 x

Parameter Result Normal Range Haemoglobin 79 g/L 130 -175 White Cells 11. 1 x 109/L 4. 0 -11. 0 Platelets 260 x 109/L 150 -450 Neutrophils 6. 5 x 109/L 1. 8 -7. 5 Lymphocytes 4. 0 x 109/L 1. 5 -4. 0 Monocytes 0. 9 x 109/L 0. 2 -0. 8 Eosinophils 0. 0 x 109/L 0. 0 -0. 4 Haematocrit (HCT) 0. 40 0. 4 -0. 52 MCV 108 fl 82 -98 MCH 29 pg 27. 0 -34. 0 MCHC 360 g/L 310 -360

Results • • • TFTs normal B 12 50 ng/L (120 -680) Serum folate

Results • • • TFTs normal B 12 50 ng/L (120 -680) Serum folate 4. 0 ug/L (4 -30) Reticulocytes low Other tests? – Intrinsic factor and parietal cell antibodies – Gastroscopy (Atrophy)

Blood Film

Blood Film

B 12 Metabolism Terminal Ileum B 12 Dietary B 12 Intrinsic factor Gastric Parietal

B 12 Metabolism Terminal Ileum B 12 Dietary B 12 Intrinsic factor Gastric Parietal Cells Intrinsic factor receptors

Causes B 12 Deficiency • Nutritional (vegans) • Pernicious anaemia • Total/partial gastrectomy •

Causes B 12 Deficiency • Nutritional (vegans) • Pernicious anaemia • Total/partial gastrectomy • Intestinal stagnant loop syndrome • Chronic tropical sprue • Ileal resection • Crohns disease • Fish tapeworm • Coeliac disease

Pernicious Anaemia • • • Autoimmune attack on gastric mucosa Reduced production of IF

Pernicious Anaemia • • • Autoimmune attack on gastric mucosa Reduced production of IF 90% abs to parietal cells, 50% abs to IF Female>male, peak age 60 years Northern European Associated with autoimmune disease and autoimmune polyendocrine syndrome • Associated with gastric carcinoma

Folate Deficiency Causes • Dietary – Old age, institutions • Malabsorption – Tropical sprue,

Folate Deficiency Causes • Dietary – Old age, institutions • Malabsorption – Tropical sprue, coeliac disease • Excess utilisation – Pregnancy, haemolytic anaemias, inflammation • Drugs – Anticonvulsants, sulfasalazine • Increased urinary excretion – CCF, liver disease

Treatment B 12/Folate Deficiency • Hydroxycobalamin IM 1000μg od for 5 -7 days •

Treatment B 12/Folate Deficiency • Hydroxycobalamin IM 1000μg od for 5 -7 days • Then 1000μg every 3 months • Folic acid 5 mg daily for 4 months/until cause resolved.

Other Effects • • • Neuropathy –SCDC (B 12 only) Sterility Skin pigmentation Neural

Other Effects • • • Neuropathy –SCDC (B 12 only) Sterility Skin pigmentation Neural tube defects Decreased osteoblast activity Cardiovascular disease

Case 3 • • 77 year old female Presents to A+E Tired, SOBAR, angina

Case 3 • • 77 year old female Presents to A+E Tired, SOBAR, angina worse than usual Widespread lymph nodes, tachycardia, tachypnoea, splenomegaly • Urgent FBC is sent. . .

Parameter Result Normal Range Haemoglobin 54 g/L 130 -175 White Cells 11. 1 x

Parameter Result Normal Range Haemoglobin 54 g/L 130 -175 White Cells 11. 1 x 109/L 4. 0 -11. 0 Platelets 260 x 109/L 150 -450 Neutrophils 6. 5 x 109/L 1. 8 -7. 5 Lymphocytes 4. 0 x 109/L 1. 5 -4. 0 Monocytes 0. 9 x 109/L 0. 2 -0. 8 Eosinophils 0. 0 x 109/L 0. 0 -0. 4 Haematocrit (HCT) 0. 32 0. 4 -0. 52 MCV 95 fl 82 -98 MCH 29 pg 27. 0 -34. 0 MCHC 360 g/L 310 -360

Other tests? • Bilirubin 120μmol/L (3 -20) • Reticulocytes 5% (0. 5 -2. 5)

Other tests? • Bilirubin 120μmol/L (3 -20) • Reticulocytes 5% (0. 5 -2. 5) • LDH 1260 U/L (240 -480) • Ferritin, folate and B 12 all normal • DAT-positive

Haemolytic Anaemia • • Increased rate of red cell destruction Congenital or acquired. Intravascular

Haemolytic Anaemia • • Increased rate of red cell destruction Congenital or acquired. Intravascular or extravascular Jaundice, splenomegaly, leg ulcers, dark urine, folate deficiency.

Classification • Congenital – Membrane disorder eg hered. spherocytosis – Metabolism disorder eg G

Classification • Congenital – Membrane disorder eg hered. spherocytosis – Metabolism disorder eg G 6 PD deficiency – Haemoglobin disorder eg Hb. S, Hb. C • Acquired – Autoimmune (warm/cold) – Alloimmune (transfusion/HDFN) – – Red cell fragmentation syndomes Drugs Infections (malaria) Burns – Liver and renal disease – Paroxysmal nocturnal haemoglobinuria

Autoimmune Haemolytic Anaemia • Antibody against own RBCs • May be idiopathic or seconday

Autoimmune Haemolytic Anaemia • Antibody against own RBCs • May be idiopathic or seconday to malignancy/infe ction/drugs

Direct Antiglobulin Test Blood of patientantibodies attached to antigen on the red cell surface

Direct Antiglobulin Test Blood of patientantibodies attached to antigen on the red cell surface Patient’s washed red cells incubated with antihuman globulin Antihuman globulin links the antibodies on the red cells-causing agglutination.

Warm Autoimmune Haemolytic Anaemia • • Ig. G autoantibody. DAT + (Ig. G) Binds

Warm Autoimmune Haemolytic Anaemia • • Ig. G autoantibody. DAT + (Ig. G) Binds at 37°C Any age/gender Associated with lymphoid malignancy, drugs (methyldopa), SLE • When occurs together with ITP = ‘Evans syndrome. ’

Treatment • • Prednisolone 60 mg od for 1 -2 weeks then taper IV

Treatment • • Prednisolone 60 mg od for 1 -2 weeks then taper IV methylprednisolone IV Immunoglobulin Rituximab Splenectomy Folic acid Transfusion if severely unwell/unstable Look for / treat underlying cause.

Cold Autoimmune Haemolytic Anaemia • Ig. M autoantibody • Optimal at 4°C-binds to red

Cold Autoimmune Haemolytic Anaemia • Ig. M autoantibody • Optimal at 4°C-binds to red cells in peripheries. • Associated with lymphoid malignancy and infection (mycoplasma pneumoniae). • Exacerbated by cold weather • Purplish discoloration of extremities. • Poor response to steroids/splenectomy • May respond to some chemotherapy agents and monoclonal antibodies.

Acrocyanosis

Acrocyanosis

Transfusing Anaemic Patients • If no severe or life-threatening symptoms wait until you can

Transfusing Anaemic Patients • If no severe or life-threatening symptoms wait until you can treat appropriately • If chronic anaemia patient may be able to tolerate a low Hb • Transfusion is associated with significant risks including over transfusion. • If decision made to transfuse give one unit, reassess patient.

BUT. . • No one should die from lack of blood. . – Hypotension/tachycardia

BUT. . • No one should die from lack of blood. . – Hypotension/tachycardia – Low saturations – Chest pain or ECG changes – Pulmonary oedema – Children decompensate quickly

Summary • How to recognise and classify anaemia based on clinical history, examination and

Summary • How to recognise and classify anaemia based on clinical history, examination and laboratory tests. • Pathophysiology, epidemiology and treatment of common causes for anaemia. • Interpreting full blood count results. • Transfusion in anaemic patients.