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Phys Topicshaematological

Phys · haematological

Anaemia — Systematic Workup

Also known as anaemia investigation · low haemoglobin workup · microcytic anaemia · macrocytic anaemia · normocytic anaemia · iron deficiency anaemia · IDA · pernicious anaemia · vitamin B12 deficiency · folate deficiency · haemolytic anaemia · autoimmune haemolytic anaemia · AIHA · hereditary spherocytosis · G6PD deficiency · thalassaemia trait · anaemia of chronic disease · aplastic anaemia · reticulocyte count · iron studies · transfusion threshold · direct antiglobulin test · DAT · Coombs test

Consultant-physician-depth guide to the systematic investigation of anaemia. Covers MCV-based classification (microcytic, normocytic, macrocytic), the reticulocyte count as kinetic discriminator, iron-studies interpretation, the iron deficiency workup in adults (mandatory GI source search), haemolytic anaemia classification, blood-film morphology, transfusion thresholds, and the management of each major cause. Structured for FRACP DWE and DCE preparation.

high8 referencesUpdated 11 July 202624 min readVerification in progress

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Red flags

  • Hb < 70 g/L in a stable adult, or any Hb with haemodynamic instability — assess for transfusion
  • Anaemia with chest pain, ischaemic ECG changes, or new heart failure — transfuse to keep Hb above 80 g/L
  • Pancytopenia on FBC — marrow failure, aplastic anaemia, acute leukaemia, or megaloblastic anaemia; urgent blood film and marrow biopsy
  • B12 deficiency treated with folate alone — risk of precipitating subacute combined degeneration of the spinal cord
  • Iron deficiency anaemia in a man or postmenopausal woman — always investigate for GI malignancy unless an obvious other cause is found
  • Acute haemolysis with falling Hb and rising LDH — immune, drug-induced or microangiopathic; urgent DAT, blood film and haemostasis screen
  • Methylene blue must not be given to a patient with suspected G6PD deficiency — it is an oxidant and worsens haemolysis
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  • MCQ practice1
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Target exams

FRACP DWEFRACP DCEMRCP Part 1MRCP Part 2MRCP PACESABIM Internal Medicine

Red flags

  • Hb < 70 g/L in a stable adult, or any Hb with haemodynamic instability — assess for transfusion
  • Anaemia with chest pain, ischaemic ECG changes, or new heart failure — transfuse to keep Hb above 80 g/L
  • Pancytopenia on FBC — marrow failure, aplastic anaemia, acute leukaemia, or megaloblastic anaemia; urgent blood film and marrow biopsy
  • B12 deficiency treated with folate alone — risk of precipitating subacute combined degeneration of the spinal cord
  • Iron deficiency anaemia in a man or postmenopausal woman — always investigate for GI malignancy unless an obvious other cause is found
  • Acute haemolysis with falling Hb and rising LDH — immune, drug-induced or microangiopathic; urgent DAT, blood film and haemostasis screen
  • Methylene blue must not be given to a patient with suspected G6PD deficiency — it is an oxidant and worsens haemolysis

Anaemia — Systematic Workup

The answer first

Anaemia is investigated by a reproducible, two-axis system: the morphological axis (the mean cell volume — microcytic, normocytic, macrocytic) and the kinetic axis (the reticulocyte count — is the marrow responding or not). The registrar who applies these two axes to every low haemoglobin will reach the cause; the one who chases a scatter of tests will miss the GI cancer hiding behind a "simple" iron deficiency. [1]

The mandate in three steps: [1]

  1. Confirm anaemia and classify by MCV. Take a full blood count and look at the MCV. Is the cell small, normal or large? This is the first branch point.
  2. Apply the reticulocyte count as the kinetic discriminator. Is the marrow trying to replace the lost cells (reticulocytes high — think haemolysis or bleeding or recovery) or failing to produce them (reticulocytes low — think iron/B12/folate deficiency, marrow failure, chronic disease)?
  3. Target the cause with the right panel. Iron studies for the microcytic anaemias; B12 and folate for macrocytosis; DAT, LDH and haptoglobin for haemolysis; a blood film for morphology; and a bone marrow biopsy when the marrow itself is suspect. [1]

The single most important principle for the exam: never treat anaemia as the diagnosis. Anaemia is a sign. Iron deficiency anaemia in a man or a postmenopausal woman is GI malignancy until proven otherwise — the iron studies confirm the deficiency, but the endoscopy and colonoscopy find the cause [1].


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References8ShowHide
  1. [1]Goddard AF, James MW, McIntyre AS, Scott BB Guidelines for the management of iron deficiency anaemia Gut, 2011.PMID 21561874
  2. [2]Stabler SP Clinical practice. Vitamin B12 deficiency N Engl J Med, 2013.PMID 23301732
  3. [3]Hébert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group N Engl J Med, 1999.PMID 9971864
  4. [4]Carson JL, Terrin ML, Noveck H, et al. Liberal or restrictive transfusion in high-risk patients after hip surgery N Engl J Med, 2011.PMID 22168590
  5. [5]Carson JL, Grossman BJ, Kleinman S, et al. Red blood cell transfusion: a clinical practice guideline from the AABB* Ann Intern Med, 2012.PMID 22751760
  6. [6]Jäger U, Barcellini W, Broome CM, et al. Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting Blood Rev, 2020.PMID 31839434
  7. [7]Luzzatto L, Ally M, Notaro R Glucose-6-phosphate dehydrogenase deficiency Blood, 2020.PMID 32702756
  8. [8]Manciu S, Matei E, Trandafir B Hereditary Spherocytosis - Diagnosis, Surgical Treatment and Outcomes. A Literature Review Chirurgia (Bucur), 2017.PMID 28463670

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