01Purpose and principlesWhat the assessment is for and the core concepts behind it.
Anaemia is a reduction in circulating haemoglobin below the appropriate reference interval. Symptoms arise from reduced oxygen carriage and the cardiovascular response, so chronic slow anaemia may be tolerated at a lower value than an acute fall. History should establish bleeding, diet, gastrointestinal symptoms, menstrual and obstetric history, surgery, medicines, alcohol, infection, inflammation, renal disease, family and ethnic background. Examination tests severity and mechanism through pallor, tachycardia, heart failure, jaundice, glossitis, neuropathy, bruising, lymphadenopathy, splenomegaly and signs of chronic systemic disease.
The laboratory approach combines morphology and physiology. MCV divides microcytic, normocytic and macrocytic patterns, while reticulocytes distinguish an appropriate marrow response from underproduction. Red-cell distribution width and the film can reveal mixed populations hidden within a normal average. Microcytosis with low ferritin supports iron deficiency; microcytosis with preserved stores and a relatively high red-cell count raises haemoglobinopathy. Macro-ovalocytes and hypersegmented neutrophils support megaloblastosis, whereas round macrocytes, target cells or marked reticulocytosis suggest liver, alcohol or regeneration pathways.
Aetiology must be pursued in parallel with replacement. Iron deficiency can arise from blood loss, inadequate intake, malabsorption or increased need; B12 deficiency can cause neurological injury without anaemia; chronic inflammation traps iron and suppresses erythropoiesis; kidney disease reduces erythropoietin; haemolysis may be immune or non-immune; marrow disease may affect one or several lineages. The useful final statement names acuity, severity, MCV, reticulocyte response, leading mechanism, evidence, urgency and the next action.
Key points
- Confirm anaemia against the laboratory's age-, sex- and pregnancy-appropriate reference interval, then compare prior haemoglobin and ask whether the change is acute, chronic or acute on chronic.
- Grade urgency from symptoms, haemodynamics, ongoing bleeding, cardiac or respiratory reserve and speed of fall rather than using a universal transfusion trigger for every patient.
- Use mean cell volume as an organising clue, not a diagnosis. Mixed iron and B12 deficiency, transfusion, reticulocytosis or thalassaemia can make the average cell size deceptively normal.
- Absolute reticulocytes provide the crucial production branch: an appropriate rise suggests bleeding or haemolysis, while a low response suggests nutrient, renal, inflammatory, endocrine or marrow limitation.
- Microcytosis most often reflects iron restriction or haemoglobinopathy; macrocytosis directs B12, folate, alcohol, liver, thyroid, reticulocyte, medicine and marrow assessment; normocytosis includes early forms of both.
- Prove iron deficiency and seek its cause. In adult men and postmenopausal women, gastrointestinal blood loss and cancer require explicit consideration rather than indefinite iron without investigation.
- Confirm haemolysis through a concordant pattern of reticulocytes, bilirubin, LDH, haptoglobin and film, then use the direct antiglobulin test and morphology to separate immune, enzyme, membrane and mechanical causes.
- Transfusion treats oxygen-delivery risk but does not diagnose or correct the underlying process. Record the reason, alternatives, target and reassessment after each transfusion decision.
02Indications, selection and cautionsWhen it is useful, when urgency changes and important limitations.
Resting dyspnoea, chest pain, syncope, heart failure, shock or neurological symptoms with a rapid haemoglobin fall indicate compromised oxygen delivery and urgent support needs.
Low MCV and MCH with high RDW supports iron deficiency, while longstanding microcytosis with preserved stores and a relatively high red-cell count raises thalassaemia trait.
Macro-ovalocytes, hypersegmented neutrophils, glossitis or neurological findings suggest B12 or folate deficiency; alcohol, liver disease, medicines, reticulocytosis and myelodysplasia remain alternatives.
Raised absolute reticulocytes with polychromasia point towards recent bleeding, haemolysis or recovery after effective treatment rather than primary underproduction.
Low reticulocytes, additional cytopenias, blasts, teardrops, dysplasia, constitutional symptoms or organ enlargement raises aplasia, infiltration, myelodysplasia or leukaemia.
Iron deficiency with dysphagia, abdominal symptoms, change in bowel habit, weight loss, visible blood or no menstrual explanation requires source-directed gastrointestinal or cancer assessment.
03Method and interpretationA systematic approach to the test and its findings.
Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.
- 01
Repeat FBC, indices and peripheral filmFirst step - Why
- Confirm anaemia, identify mixed populations and detect urgent marrow or haemolytic morphology.
- Interpretation and limitations
- Compare baseline and all lineages. A normal MCV can conceal opposing microcytic and macrocytic processes; blasts, fragmentation or multilineage cytopenia changes urgency.
- 02
Absolute reticulocyte count - Why
- Decide whether marrow output is appropriate for severity and duration.
- Interpretation and limitations
- A raised response supports blood loss or destruction; a low response directs nutrient, renal, inflammatory, endocrine and marrow investigation. Very early bleeding may precede the rise.
- 03
Ferritin and transferrin saturation - Why
- Assess iron stores and iron availability for erythropoiesis.
- Interpretation and limitations
- Low ferritin supports absolute deficiency. Inflammation can elevate ferritin, so transferrin saturation, CRP, treatment response and the full phenotype help identify iron restriction.
- 04
Vitamin B12 and folate pathway - Why
- Detect megaloblastic deficiency and prevent neurological progression.
- Interpretation and limitations
- Use NICE NG239 thresholds and functional testing for indeterminate B12 or nitrous-oxide-related disease. Treat neurological B12 promptly and do not give folate alone before B12 safety is established.
- 05
Haemolysis profile and DAT - Why
- Confirm destructive anaemia and identify immune coating.
- Interpretation and limitations
- Reticulocytosis, indirect bilirubin, LDH, low haptoglobin and film should align. DAT interpretation requires transfusion, medicine and complement context and does not alone prove active haemolysis.
- 06
Renal, liver, thyroid and inflammatory tests - Why
- Identify common systemic underproduction and macrocytic mechanisms.
- Interpretation and limitations
- Relate severity and chronology. Mild renal or thyroid abnormality may contribute without fully explaining a marked progressive anaemia, and multiple causes often coexist.
- 07
Bleeding and source-directed investigation - Why
- Find menstrual, gastrointestinal, urinary or other blood loss and underlying pathology.
- Interpretation and limitations
- Use history, examination, coeliac testing and age- and symptom-appropriate endoscopic, gynaecological or urological pathways; faecal testing does not replace investigation when guideline indications exist.
04Clinical next stepsHow the result changes management or prompts escalation.
01UnstableSupport oxygen delivery and stop lossFirst stepAnaemia accompanies shock, active bleeding, ischaemic symptoms, syncope, heart failure or rapid clinical deterioration.+
- 1Use ABCDE, identify and control bleeding, obtain FBC, coagulation, group and screen or crossmatch, renal, liver, blood gas and cause-directed samples, and activate major-haemorrhage support when indicated.
- 2PreferredPreferred transfusion practice is individualised, component appropriate and reassessed after each step; alternatives such as haemostasis, iron or B12 cannot replace immediate red-cell support when oxygen delivery is failing.
- 3EscalationEscalate ongoing bleeding, cardiovascular compromise, severe haemolysis or pregnancy-related instability to the relevant surgical, obstetric, haematology and critical-care teams.
02ClassifyUse MCV and reticulocytes togetherAnaemia is confirmed and the patient is stable enough for a structured causal assessment.+
- 1Review tempo, blood loss, diet, medicines, alcohol, family and ethnic history and all lineages, then obtain film, absolute reticulocytes, ferritin, transferrin saturation, B12 and folate.
- 2First linePreferredFor low reticulocytes, the first-line pathway is substrate, renal, inflammatory, thyroid and marrow assessment; for high reticulocytes, the preferred route is bleeding and haemolysis testing.
- 3If MCV conflicts with the phenotype, use RDW, film, haemoglobin analysis and recent transfusion or treatment history rather than forcing the anaemia into one size category.
03Cause and responseTreat, investigate and prove recoveryA likely deficiency, systemic cause, haemolysis or marrow disorder has been identified.+
- 1Treat the confirmed mechanism with the national or specialist regimen while investigating why it occurred; replacement without source investigation is an incomplete plan.
- 2Set the expected early endpoint, such as reticulocyte or haemoglobin response, and monitor tolerance, adherence, ongoing bleeding and organ symptoms at a defined interval.
- 3EscalationEscalate absent response to check diagnostic error, mixed deficiency, malabsorption, continued loss, inflammation, renal disease, haemolysis and marrow pathology before simply increasing treatment.
05Risks, monitoring and follow-upComplications, safety checks and further assessment.
- Trend haemoglobin against symptoms, haemodynamics, bleeding and treatment rather than chasing a normal range without understanding the cause.
- Use reticulocyte and early haemoglobin response to confirm effective replacement or marrow recovery, then monitor replenishment and recurrence according to the diagnosis.
- For active haemolysis, follow bilirubin, LDH, haptoglobin, renal function, potassium and cause-specific immune or mechanical markers.
- For iron deficiency, confirm that gastrointestinal, menstrual, dietary or malabsorptive source investigation is completed and documented, not merely requested.
- For B12-related neurological disease, record objective sensory, gait and cognitive change because serum concentration after replacement does not measure neural recovery.
- Reassess transfusion need after each unit or episode using clinical response and the current national threshold framework.
06Special situationsVariants, exceptions and circumstances that change the usual approach.
MCV is an average
Opposing cell populations can produce a normal mean. RDW and film expose mixed iron and B12 deficiency or donor and patient cells after transfusion.
Reticulocytes link marrow to mechanism
Size describes cells; reticulocytes describe production. Combining both is more discriminating than either result alone.
Ferritin follows inflammation
A normal or raised ferritin during inflammatory illness does not guarantee adequate available iron. Transferrin saturation and context refine interpretation.
Neurology can precede anaemia
B12 deficiency may injure peripheral nerves, posterior columns and cognition before haemoglobin or MCV changes, so clinical suspicion should trigger the NICE pathway.
Transfusion is not closure
A post-transfusion haemoglobin increase treats immediate oxygen carriage. It does not locate bleeding, replace iron stores or explain haemolysis and marrow disease.
07Common pitfallsFrequent interpretation and management errors.
- 01
Using MCV as a diagnosis and ignoring mixed deficiencies.
- 02
Ordering ferritin alone during inflammation and declaring iron sufficiency.
- 03
Giving folic acid before assessing B12 in a patient with neurological symptoms.
- 04
Transfusing a stable chronic anaemia without defining symptoms, alternatives and reassessment.
- 05
Replacing iron indefinitely without investigating an adult source of deficiency.
- 06
Calling a high LDH haemolysis without reticulocytes, bilirubin, haptoglobin and film.
- 07
Failing to escalate low-reticulocyte anaemia with additional cytopenias or abnormal cells.