Anaemia

A reduction in haemoglobin concentration below the normal range for age and sex, generally below 130 g/L in men and 120 g/L in non-pregnant women, representing a sign requiring a cause rather than a diagnosis in itself.

Classification by mechanism, which structures the entire diagnostic approach:

• Decreased production: nutritional deficiency (iron, B12, folate), bone marrow failure (aplastic anaemia, infiltration, myelodysplasia), chronic disease/inflammation, chronic kidney disease (erythropoietin deficiency), hypothyroidism.
• Increased destruction (haemolysis): intrinsic (membrane, enzyme, haemoglobin defects) or extrinsic (immune, mechanical, infective).
• Blood loss: acute (trauma, haemorrhage) or chronic (occult gastrointestinal, menstrual).

Classification by red cell size (MCV), which is the practical first branch point:

• Microcytic (MCV under 80): iron deficiency, thalassaemia, anaemia of chronic disease (can also be normocytic), sideroblastic anaemia, lead poisoning.
• Normocytic (MCV 80-100): anaemia of chronic disease/inflammation, early iron deficiency, chronic kidney disease, acute blood loss, haemolysis, bone marrow failure, mixed deficiency.
• Macrocytic (MCV over 100): megaloblastic (B12/folate deficiency) versus non-megaloblastic (alcohol, liver disease, hypothyroidism, myelodysplasia, reticulocytosis from haemolysis or bleeding, certain drugs).

• Fatigue, weakness, reduced exercise tolerance, dyspnoea on exertion --- the general symptoms of reduced oxygen delivery, whose severity depends more on the rate of onset than the absolute level (chronic anaemia is tolerated far better than acute).
• Pallor of the conjunctivae, palmar creases and mucous membranes, which correlates poorly with severity but is a useful bedside sign.
• Tachycardia, a flow murmur, and in severe/rapid-onset anaemia, symptoms of high-output cardiac failure.
• Angina in patients with pre-existing coronary disease, precipitated at higher haemoglobin thresholds than in healthy individuals.
• Specific clues by cause: koilonychia and pica in iron deficiency; glossitis and peripheral neuropathy/subacute combined degeneration in B12 deficiency; jaundice and dark urine in haemolysis; bone pain and weight loss suggesting marrow infiltration; melaena, haematochezia or menorrhagia pointing to a bleeding source.

• Full blood count with red cell indices (MCV, MCH, RDW) as the starting point.
• Reticulocyte count (corrected for the degree of anaemia), which is the pivotal early test: an appropriately elevated reticulocyte response indicates the marrow is compensating (haemolysis or blood loss), while an inappropriately low reticulocyte count indicates a production problem.
• Blood film examination, which is frequently more informative than automated indices alone: target cells, spherocytes, schistocytes, sickle cells, hypersegmented neutrophils, basophilic stippling, rouleaux.
• Iron studies (ferritin, transferrin saturation, total iron binding capacity), B12 and folate, renal function, thyroid function, liver function, and inflammatory markers as guided by the MCV and clinical context.
• Haemolysis screen where indicated: LDH, haptoglobin, unconjugated bilirubin, direct antiglobulin test.
• Bone marrow examination where production failure or infiltration is suspected and peripheral testing is unrevealing.
• Investigate the source in blood loss anaemia: gastrointestinal endoscopy (bidirectional) in unexplained iron deficiency in men and postmenopausal women, gynaecological assessment in premenopausal women where menorrhagia does not fully explain the deficit.

• Treat the underlying cause: this is the substance of anaemia management.
• Transfusion thresholds: generally restrictive, transfusing at haemoglobin below 70 g/L in stable patients (below 80 g/L with cardiovascular disease), with a target post-transfusion haemoglobin rather than reflexive multiple-unit transfusion; transfuse based on symptoms and haemodynamic status in acute significant blood loss regardless of a specific threshold.
• Iron, B12 or folate replacement as indicated by deficiency.
• Erythropoiesis-stimulating agents for anaemia of chronic kidney disease and selected chemotherapy-induced anaemia, with careful attention to target haemoglobin (avoiding over-correction, which increases thromboembolic risk) and iron sufficiency before initiation.
• Address anaemia of chronic disease/inflammation by treating the underlying inflammatory condition; iron therapy is generally ineffective and potentially harmful (iron is sequestered by elevated hepcidin) unless true iron deficiency coexists.
• Multidisciplinary referral (haematology) for unexplained anaemia, suspected marrow pathology, or complex haemolytic processes.