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Anemia Diagnostic Workup

Anemia Diagnostic Workup: Anaemia on FBC (adult, not pregnant) → Pregnant or under 15? Use another pathway → Any urgent feature? → Urgent anaemia: stabi...

Pathway Overview

23 steps

Algorithm Steps

23 total

  1. 01Start

    Anaemia on FBC (adult, not pregnant)

    Adults: Hb <130 g/L (men) or <120 g/L (non-pregnant women).

  2. 02Warning

    Pregnant or under 15? Use another pathway

    This pathway uses adult cut-offs.

    • Pregnancy: anaemia is Hb <110 g/L (<105 g/L in 2nd trimester); use a pregnancy anaemia pathway
    • Children: age-specific Hb cut-offs; think of lead in microcytosis; use a paediatric pathway
  3. 03Decision

    Any urgent feature?

    Yes if any: active bleeding or shock; Hb <70 g/L or a fast fall in Hb; chest pain, syncope or breathlessness at rest; low platelets with red cell fragments on the film; blasts or unexplained pancytopenia; low B12 with neurological signs.

  4. If Yes
    1. 04Action

      Urgent anaemia: stabilise and get same-day help

      Act now; continue the work-up when stable. Before transfusion, take a group and screen (in a massive bleed, emergency blood must not wait for it). Take FBC, film, reticulocytes, ferritin, B12 and folate before transfusion if this causes no delay.

      • Bleeding or shock: resuscitate and find and stop the source (use the bleeding pathway)
      • Low platelets with fragments (possible TTP, HUS or DIC): same-day haematology; send ADAMTS13 activity
      • Suspected TTP: avoid platelet transfusion unless serious bleeding (haematology decides); do not delay plasma exchange
      • Blasts or unexplained pancytopenia (possible acute leukaemia): same-day haematology
      • Transfusion in stable inpatients: consider if Hb <70 g/L, or <80 g/L with cardiovascular disease; give 1 unit, then reassess (heart failure: risk of fluid overload)
      • Low B12 with neurological signs: take blood, then start IM hydroxocobalamin the same day (see B12 step)
      • Iron deficiency and stable: IV iron is an alternative to transfusion (not after a previous reaction to IV iron)
    2. 05Action

      First-line tests (all patients; urgent patients once stable)

      Take these samples before you start iron, B12, folate or a non-urgent transfusion.

      • FBC with MCV, MCH and RDW; blood film; reticulocyte count
      • Ferritin, transferrin saturation (TSAT) and CRP
      • B12, folate, UEC/eGFR, LFTs, TSH
      • History: bleeding, diet, alcohol, medicines, family history; urinalysis
    3. 06Decision

      Group by MCV

      Mixed causes are common. Check ferritin and B12 in every group.

      • Microcytic: MCV <80 fL
      • Normocytic: MCV 80-100 fL
      • Macrocytic: MCV >100 fL
    4. MCV <80
    5. 07Action

      Microcytic (MCV <80 fL)

      Read ferritin with CRP and TSAT.

      • Causes: iron deficiency, inflammation, thalassaemia trait; rarely sideroblastic anaemia or lead
    6. 08Decision

      Microcytic: iron studies pattern?

      Ferritin rises with inflammation. Ferritin >150 µg/L makes absolute iron deficiency unlikely. CKD, inflammation or heart failure: ferritin <100 µg/L with TSAT <20% can still be iron deficiency. Heart failure: ferritin 100-299 µg/L with TSAT <20% is also iron deficiency.

      • Ferritin <30 µg/L (or <100 µg/L with TSAT <20% in inflammation, CKD or heart failure; heart failure also 100-299 µg/L with TSAT <20%): iron deficiency
      • Ferritin 30-45 µg/L, or low TSAT without inflammation: possible iron deficiency; treat as iron deficiency and check Hb response
      • Ferritin ≥100 µg/L with TSAT <20% and inflammation or CKD (not heart failure): anaemia of inflammation
      • Normal ferritin and TSAT: test for thalassaemia trait
    7. Iron deficiency
    8. 09Action

      Iron deficiency anaemia: find the cause and replace iron

      Ferritin <30 µg/L, or <100 µg/L with TSAT <20% in inflammation, CKD or heart failure (heart failure: also 100-299 µg/L with TSAT <20%). Equivocal iron studies: a Hb rise of ≥10 g/L after 2 weeks of iron confirms iron deficiency. Investigate and treat at the same time.

      • All: coeliac serology and urinalysis
      • Men and postmenopausal women: gastroscopy and colonoscopy (CT colonography if colonoscopy is unsuitable)
      • Premenopausal women: GI tests if age >50, GI red flags, no periods, or strong family history of GI cancer; gynaecology review if periods are heavy
      • Anticoagulant or antiplatelet use: still investigate the source
      • Oral iron: 1 tablet with 50-100 mg elemental iron once daily (many low-dose products contain much less); if not tolerated, 1 tablet on alternate days
      • IV iron if oral iron fails, is not tolerated or is unsuitable, or fast repletion is needed; heart failure with reduced EF: IV iron. Do not give during active infection or after a previous reaction to IV iron (specialist advice)
      • IV iron: have resuscitation available and observe for 30 minutes after each dose; ferric carboxymaltose can cause hypophosphataemia (ask about bone pain; monitor with repeated doses)
      • Check Hb within 4 weeks (adequate: rise of 20 g/L or normal Hb); continue iron for about 3 months after Hb is normal
    9. 10End

      Review response and cause

      Recheck FBC after treatment. No response or cause not found: refer (haematology, gastroenterology or nephrology).

    10. Inflammation
    11. 11Action

      Ferritin ≥100 µg/L, TSAT <20%: anaemia of inflammation or CKD

      Find and treat the cause. Iron deficiency can coexist.

      • Look for infection, inflammatory disease, cancer and CKD
      • Heart failure: ferritin 100-299 µg/L with TSAT <20% is iron deficiency; IV iron with cardiology
      • CKD: iron and ESA decisions with nephrology (KDIGO 2026)
      • No cause found: serum protein electrophoresis and serum free light chains; refer to haematology
    12. Path rejoins step 10Shared downstream outcome
    13. Normal iron
    14. 12Action

      Microcytic, normal iron studies: check for thalassaemia trait

      Do not give iron unless iron deficiency is proven.

      • Hb electrophoresis or HPLC (HbA2, HbF)
      • Raised HbA2: beta-thalassaemia trait. Normal HbA2 does not exclude alpha-thalassaemia (DNA test)
      • Iron deficiency lowers HbA2: retest after iron repletion
      • Reproductive age: test the partner and offer genetic counselling
      • No cause: consider sideroblastic anaemia or lead; refer to haematology
    15. 13Warning

      Haematology referral

      Same day: blasts, pancytopenia, or red cell fragments with low platelets.

      • Unexplained haemolysis or positive DAT
      • Suspected marrow disease (MDS, myeloma, aplasia) or other cytopenias
      • Unexplained anaemia, no response to treatment, or need for transfusion
    16. Path rejoins step 10Shared downstream outcome
    17. MCV 80-100
    18. 14Action

      Normocytic (MCV 80-100 fL)

      Use the reticulocyte count to separate low output from blood loss or haemolysis.

      • Early or mixed iron, B12 or folate deficiency can be normocytic
      • Also: CKD, inflammation, hypothyroidism, marrow disease
    19. 15Decision

      Normocytic: reticulocyte response?

      Compare with the lab reference range.

      • Low or normal: underproduction
      • High with bleeding: blood loss
      • High with haemolysis markers: haemolysis
    20. Low or normal
    21. 16Action

      Low or normal reticulocytes: underproduction

      Look for a deficiency, CKD, inflammation or marrow disease.

      • Review ferritin, TSAT, B12, folate, eGFR, TSH, LFTs and CRP
      • CKD: iron and ESA decisions with nephrology (KDIGO 2026)
      • No cause: serum protein electrophoresis and serum free light chains
      • Other cytopenias or abnormal film: haematology
    22. Path rejoins step 13Shared downstream outcome
    23. High, bleeding
    24. 17Action

      High reticulocytes with bleeding: blood-loss anaemia

      Active bleeding or a fall in blood pressure: treat as urgent (see the urgent step).

      • Find the source: GI, menstrual, urinary, surgical or trauma
      • Review anticoagulants, antiplatelets and NSAIDs
      • Check ferritin: chronic loss causes iron deficiency (see the iron deficiency step)
    25. Path rejoins step 10Shared downstream outcome
    26. High, haemolysis
    27. 18Action

      High reticulocytes with haemolysis markers: haemolysis

      Red cell fragments with low platelets: same-day haematology (possible TTP, HUS or DIC).

      • Confirm: LDH high, haptoglobin low, unconjugated bilirubin high
      • Direct antiglobulin test (DAT): positive suggests immune haemolysis
      • Film: spherocytes, fragments, bite cells (G6PD deficiency)
      • Review medicines and infections; in G6PD deficiency stop oxidant drugs (for example dapsone, primaquine, rasburicase)
    28. Path rejoins step 13Shared downstream outcome
    29. MCV >100
    30. 19Action

      Macrocytic (MCV >100 fL)

      Check B12 and folate. Review alcohol, liver, thyroid and medicines.

      • Tests: B12 (total or active), serum folate, LFTs, TSH, reticulocytes, film
      • Nitrous oxide use: B12 can be normal; test methylmalonic acid (MMA) or homocysteine
      • Medicines: methotrexate, hydroxyurea, azathioprine, some antiretrovirals and anticonvulsants
    31. 20Decision

      Macrocytic: B12 and folate results?

      Use the lab reference range. Indeterminate B12 with symptoms: test MMA; treat as B12 deficiency if MMA is raised or there are neurological signs.

      • Total B12 <133 pmol/L or active B12 <25 pmol/L: B12 deficiency
      • Total B12 133-258 pmol/L or active B12 25-70 pmol/L: indeterminate
      • Low folate with normal B12: folate deficiency
      • Both normal: other cause of macrocytosis
    32. Low B12
    33. 21Action

      B12 deficiency (or indeterminate B12 with raised MMA)

      Find the cause and replace B12. Neurological signs: start IM hydroxocobalamin now; do not wait for results. Severe anaemia: check potassium in the first days (risk of hypokalaemia).

      • No neurological signs: hydroxocobalamin 250-1000 microgram IM on alternate days for 1-2 weeks, then 250 microgram weekly until the blood count is normal; maintenance 1000 microgram every 2-3 months
      • Neurological signs: hydroxocobalamin 1000 microgram IM on alternate days for 1-2 weeks; maintenance 1000 microgram every 2 months
      • Autoimmune gastritis (pernicious anaemia), total gastrectomy or ileal resection: lifelong IM B12
      • Causes: anti-intrinsic factor antibodies, diet low in animal foods, gastric or ileal surgery, metformin, PPIs, nitrous oxide
      • Do not give folic acid alone
    34. Path rejoins step 10Shared downstream outcome
    35. Low folate
    36. 22Action

      Folate deficiency with normal B12: give folic acid

      Exclude or treat B12 deficiency first: folic acid alone can make B12 nerve damage worse.

      • Folic acid 5 mg orally once daily (PI range 1-5 mg daily)
      • Continue until Hb and folate are normal and the cause is treated; recheck FBC
      • Both B12 and folate low: give B12 before or with folic acid
      • Causes: poor diet, alcohol, malabsorption (coeliac disease), haemolysis, methotrexate, trimethoprim, anticonvulsants
    37. Path rejoins step 10Shared downstream outcome
    38. Normal
    39. 23Action

      B12 and folate normal: other macrocytosis

      Other cytopenias, abnormal film or no cause found: refer to haematology (possible MDS or myeloma).

      • Alcohol, liver disease, hypothyroidism
      • Medicines (see macrocytic step)
      • Reticulocytosis from haemolysis or bleeding
      • Marrow disease (MDS, myeloma, aplastic anaemia)
    40. Path rejoins step 13Shared downstream outcome
    If No
    1. Path rejoins step 05Shared downstream outcome

Guideline Source

British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults (Snook et al., Gut 2021)

Clinical Safety Information

Clinical Decision Support — Not a Substitute for Clinical Judgment

Individual patient factors may require deviation from these recommendations.

Known Limitations

  • Adults only. Not for pregnancy or children: Hb cut-offs and causes differ.
  • Urgent problems (bleeding, TTP, acute leukaemia) are covered only as triggers for same-day action; use their own pathways.
  • Lab cut-offs vary; use the local reference range.
  • Haemoglobinopathy, haemolysis and marrow disease work-up is limited to referral triggers.

Contraindicated Populations

PregnancyChildren under 15 years

Applicable Regions

AUUSEUGlobal

AU: Australian units: Hb g/L, B12 pmol/L, folate nmol/L. Hydroxocobalamin 1000 microgram/mL injection and folic acid 0.5 mg and 5 mg tablets are TGA-registered.

US: US labs may report Hb in g/dL (g/L divided by 10) and B12 in pg/mL (pmol/L x 1.355).

Global: Hb cut-offs follow WHO 2024.

Version 2Next review: 2027-09-30

Frequently Asked Questions

What is the Anemia Diagnostic Workup?

The Anemia Diagnostic Workup is a diagnostic clinical algorithm for Internal Medicine. It provides a structured decision tree to guide clinical decision-making, based on British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults (Snook et al., Gut 2021).

What guideline is the Anemia Diagnostic Workup based on?

This algorithm is based on British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults (Snook et al., Gut 2021) (DOI: 10.1136/gutjnl-2021-325210).

What are the limitations of the Anemia Diagnostic Workup?

Known limitations include: Adults only. Not for pregnancy or children: Hb cut-offs and causes differ.; Urgent problems (bleeding, TTP, acute leukaemia) are covered only as triggers for same-day action; use their own pathways.; Lab cut-offs vary; use the local reference range.; Haemoglobinopathy, haemolysis and marrow disease work-up is limited to referral triggers.. Individual patient factors may require deviation from these recommendations.

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