Anaemia

Dr Kate Foley

ST5 Haematology

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 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

•Need iron, B12, 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, B12, folatedeficiency

Anaemia ofChronic disease,

CKD,Hypothyroid

Hereditary Ineffective

erythropoesis

Bone marrow failure or infiltration

Increased destruction•Intracorpuscular

•Membrane•Enzyme•Hb

•Extracorpuscular•Mechanical•Chemical•Infection•Antibodies•Splenomegaly

Bleeding

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 85g/L

Tachycardia

Signs Symptoms

Flow murmur

Cardiomegaly

Pulmonary oedema

Pale Mucus membranes

Bruising

Leg ulcers

Koilynichia

Jaundice

Weakness

Headaches

Angina

SOBOE

Palpitations

Intermittent Claudication

Confusion

Back pain

Change in bowel habit

Bleeding

Dyspepsia

Weight loss

Mrs Green....

• On further questioning admits to several months history of dyspepsia and early satiety

• Has lost 10kg 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•LFT•Clotting screen•Group and Save/Crossmatch

Would you wait for these results before referring Mrs Green to hospital?

•Ferritin/Iron studies•B12/folate•GI investigations•Urine dip

•Bone marrow aspirate•Haemoglobin Electrophoresis

NICE Recommends

• Refer all patients with IDA and dyspepsia via 2ww

• Refer all men with Hb < 110 g/L via 2ww• Refer all post menopausal women with Hb

< 100 g/L via 2ww

• Screen all patients for coeliac disease.• Other patients with unexplained IDA will

still need upper and lower GI endoscopy

Parameter Result Normal RangeHaemoglobin 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 72fl 82-98

MCH 25 pg 27.0-34.0

MCHC 300g/L 310-360

Classification of Anaemias

Microcytic, hypochromic

Normocytic, normochromic

Macrocytic

MCV <80 fl

MCH <27pg

MCV 80-95 fl

MCH >27 pg

MCV >95 fl

Iron deficiency Haemolytic Anaemias Megaloblastic

Thalassaemia Anaemia of chronic disease

B12/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

• Blood film-microcytic, hypochromic cells, pencil cells.

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

• H Pylori test

• Urine dip for blood

Treatment

• Treat underlying condition AND

• Trial of oral iron– Ferrous sulphate 200mg 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 test with GP

Parameter Result Normal RangeHaemoglobin 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 108fl 82-98

MCH 29 pg 27.0-34.0

MCHC 360g/L 310-360

Results

• TFTs normal

• B12 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

B12 Metabolism

Dietary B12

B12

Gastric Parietal Cells

Intrinsic factor

Terminal Ileum

Intrinsic factor receptors

Causes B12 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• 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, coeliac disease

• Excess utilisation– Pregnancy, haemolytic anaemias, inflammation

• Drugs– Anticonvulsants, sulfasalazine

• Increased urinary excretion– CCF, liver disease

Treatment B12/Folate Deficiency

• Hydroxycobalamin IM 1000μg od for 5-7 days

• Then 1000μg every 3 months

• Folic acid 5mg daily for 4 months/until cause resolved.

Other Effects

• Neuropathy –SCDC (B12 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 worse than usual

• Widespread lymph nodes, tachycardia, tachypnoea, splenomegaly

• Urgent FBC is sent.....

Parameter Result Normal RangeHaemoglobin 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 95fl 82-98

MCH 29 pg 27.0-34.0

MCHC 360g/L 310-360

Other tests?

• Bilirubin 120μmol/L (3-20)

• Reticulocytes 5% (0.5-2.5)

• LDH 1260U/L (240-480)

• Ferritin, folate and B12 all normal

• DAT-positive

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 G6PD deficiency– Haemoglobin disorder eg HbS, HbC

• 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 to malignancy/infection/drugs

Direct Antiglobulin Test

Blood of patient-antibodies 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

• IgG autoantibody. DAT + (IgG)

• Binds at 37°C

• Any age/gender

• Associated with lymphoid malignancy, drugs (methyldopa), SLE

• When occurs together with ITP = ‘Evans syndrome.’

Treatment

• Prednisolone 60mg 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

• IgM 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

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– 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 laboratory tests.

• Pathophysiology, epidemiology and treatment of common causes for anaemia.

• Interpreting full blood count results.

• Transfusion in anaemic patients.