Anaemia investigation

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Quick Overview

Anaemia investigation requires systematic interpretation of MCV, blood film morphology, and iron studies to identify underlying causes. NICE NG8 provides referral criteria for suspected haematological malignancy. A structured approach distinguishes microcytic, normocytic, and macrocytic patterns, guiding targeted investigation and timely specialist referral when indicated.

Core Facts & Concepts

📊 Anaemia Definitions (WHO criteria)

  • Men: Hb <130 g/L | Women: Hb <120 g/L | Pregnancy: Hb <110 g/L

MCV Classification

  • Microcytic: <80 fL (iron deficiency, thalassaemia, anaemia of chronic disease)
  • Normocytic: 80-100 fL (acute blood loss, haemolysis, chronic disease, renal failure)
  • Macrocytic: >100 fL (B12/folate deficiency, alcohol, hypothyroidism, myelodysplasia)

Iron Studies Patterns

ParameterIron DeficiencyAnaemia Chronic DiseaseThalassaemia Trait
Ferritin↓ (<30 μg/L)Normal/↑ (>100 μg/L)Normal/↑
Serum IronNormal
TIBCNormal
Transferrin Sat↓ (<16%)Normal

Figure 1: Blood film showing microcytic hypochromic red cells with pencil cells and target cells characteristic of iron deficiency anaemia

Key Numbers

  • Reticulocyte count: Normal 50-100 × 10⁹/L (↑ suggests haemolysis/bleeding, ↓ suggests production failure)
  • B12 deficiency threshold: <200 ng/L
  • Folate deficiency: <7 nmol/L

Problem-Solving Approach

Step-by-Step Investigation

  1. Confirm anaemia → Check Hb against age/sex-specific thresholds
  2. Determine MCV category → Microcytic/normocytic/macrocytic
  3. Review blood film → Morphology guides differential diagnosis
  4. Order targeted tests:
    • Microcytic: Ferritin, iron studies, haemoglobin electrophoresis (if ferritin normal)
    • Macrocytic: B12, folate, TFTs, reticulocytes, LFTs (alcohol screen)
    • Normocytic: Reticulocytes, renal function, haemolysis screen if ↑ reticulocytes

Figure 2: Blood film showing macrocytic red cells with hypersegmented neutrophils pathognomonic of megaloblastic anaemia

🚩 NICE NG8 Urgent Referral Criteria (2-week wait)

  • Hb <100 g/L (men) or <90 g/L (women) without obvious cause
  • Unexplained lymphadenopathy + anaemia
  • Splenomegaly + anaemia
  • Persistent unexplained anaemia after investigation

Red Flags Requiring Immediate Action

  • Hb <70 g/L → Consider transfusion
  • Signs of cardiac decompensation
  • Suspected haemolytic crisis (jaundice + dark urine + ↑ reticulocytes)

⚠️ Warning: Always investigate microcytic anaemia in men and post-menopausal women for GI malignancy (colonoscopy + OGD) after confirming iron deficiency

Analysis Framework

Blood Film Morphology: Discriminating Features

FindingPrimary DifferentialKey Associated Tests
Hypochromic microcytic cellsIron deficiency, thalassaemiaFerritin, Hb electrophoresis
Hypersegmented neutrophilsB12/folate deficiencySerum B12, red cell folate
SpherocytesHereditary spherocytosis, AIHADirect Coombs test, osmotic fragility
Target cellsThalassaemia, liver diseaseHb electrophoresis, LFTs
SchistocytesMicroangiopathic haemolysisLDH, haptoglobin, coagulation screen
Rouleaux formationMyeloma, inflammationSerum protein electrophoresis, ESR

B12 vs Folate Deficiency

  • B12: Subacute combined degeneration (posterior columns + corticospinal tracts), glossitis, peripheral neuropathy
  • Folate: Pregnancy-related, no neurological features
  • Both: Macrocytosis, hypersegmented neutrophils, ↑ LDH, ↑ bilirubin (ineffective erythropoiesis)

📌 Remember: TAILS for iron deficiency causes - Tea (tannins), Achlorhydria/PPI, IBD, Loss (menstruation/GI bleeding), Surgery (gastrectomy)

Visual Aid

Reticulocyte Response Interpretation

Clinical ScenarioReticulocyte CountInterpretation
Acute haemorrhage↑↑ (>100 × 10⁹/L)Appropriate marrow response
Iron/B12 deficiency↓ or normalProduction failure
Post-treatment (Fe/B12)↑↑ (peak day 7-10)Confirms diagnosis retrospectively
Aplastic anaemia↓↓ (<20 × 10⁹/L)Marrow failure

Key Points Summary

MCV classification is the first step: microcytic (<80), normocytic (80-100), macrocytic (>100 fL)

Ferritin <30 μg/L confirms iron deficiency; investigate GI source in men/post-menopausal women (mandatory colonoscopy + OGD)

NICE NG8: Refer urgently if Hb <100 g/L (men) or <90 g/L (women) without clear cause

Hypersegmented neutrophils (≥6 lobes) are pathognomonic for megaloblastic anaemia (B12/folate deficiency)

Reticulocyte count distinguishes production failure (↓) from haemolysis/bleeding (↑↑)

Thalassaemia trait: microcytosis with normal/raised ferritin and disproportionately low MCV for degree of anaemia

Never treat B12 deficiency with folate alone - risks precipitating subacute combined degeneration

Practice Questions: Anaemia investigation

Test your understanding with these related questions

A 52-year-old woman presents with progressive dysphagia and weight loss. She has tight skin on her hands and face. ANA shows nucleolar pattern. What is the most concerning systemic complication?

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Flashcards: Anaemia investigation

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D-Dimer is a marker of _____

TAP TO REVEAL ANSWER

D-Dimer is a marker of _____

fibrin degredation

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