📚 Module Overview
On completion of this module, you will be able to:
- Define anaemia and classify it based on Mean Cell Volume (MCV).
- Describe the initial investigation pathway for microcytic, normocytic, and macrocytic anaemia.
- Identify the key causes for each type of anaemia.
- Understand the role of further tests like reticulocyte counts, haematinics, and coeliac screening.
- Recognise red flag symptoms and referral criteria for suspected cancer.
- Differentiate between true iron deficiency and anaemia of chronic disease.
It is critical to remember that anaemia is not a standalone condition. It is a sign of an underlying disease process. The primary goal of investigation is always to answer the question: "Why is this patient anaemic?"
If a patient is severely symptomatic (e.g., chest pain, shortness of breath at rest), has a very low haemoglobin (e.g., <70-80 g/L), or has pancytopenia (low white cells, red cells, and platelets), they require urgent assessment and potential hospital admission.
🧭 Initial Investigation Pathway
The initial classification of anaemia is based on the Mean Cell Volume (MCV) from the Full Blood Count (FBC), which measures the average size of the red blood cells.
(Low Haemoglobin)
(Low WBC, Hb, and Platelets) → Urgent Haematology Referral/Admission
🔬 Microcytic Anaemia (MCV <80 fL)
Characterised by small red blood cells, most commonly caused by a problem with haemoglobin production (specifically haem synthesis).
Key Causes & Investigations
| Cause | Key Investigation Findings | Clinical Notes |
|---|---|---|
| Iron Deficiency Anaemia (IDA) | Low Ferritin (<30 µg/L strongly suggests IDA, <15 is diagnostic), Low Iron, Low Transferrin Saturation, High Total Iron Binding Capacity (TIBC). | The most common cause. Always investigate the underlying reason for iron loss (e.g., GI bleed, menorrhagia, malabsorption like coeliac disease). Check coeliac serology (tTG IgA). See IDA module for management. |
| Anaemia of Chronic Disease (ACD) | Normal or High Ferritin (>100 µg/L), Low Iron, Low/Normal Transferrin Saturation, Low TIBC. Raised CRP/ESR often present. | Can be microcytic (~30%) or normocytic (~70%). Inflammation blocks iron release from stores & reduces EPO response. Look for underlying chronic inflammatory condition, infection, or malignancy. Often co-exists with true IDA (check ferritin carefully). |
| Thalassaemia Trait | Very low MCV (often <75 fL), disproportionately mild anaemia, normal or high ferritin/iron studies. Often raised red cell count. | A genetic condition affecting globin chain production. Suspect particularly in patients of Mediterranean, Middle Eastern, South East Asian, or African descent. Requires haemoglobin electrophoresis for confirmation. |
| Sideroblastic Anaemia | High Ferritin, High Iron, High Transferrin Saturation. Blood film shows ring sideroblasts. | A rare group of bone marrow disorders (can be congenital or acquired, e.g., due to alcohol, lead, certain drugs) where iron cannot be properly incorporated into haem. Requires specialist haematology investigation. |
| Lead Poisoning (Rare) | Microcytic anaemia with basophilic stippling on blood film. | Consider in specific occupational/environmental exposures. Check lead levels if suspected. |
🔬 Normocytic Anaemia (MCV 80-100 fL)
Characterised by normal-sized red blood cells. This is a very broad category, often considered the "anaemia of everything else." Investigation involves looking for multiple potential causes simultaneously.
Key Causes & Investigations
The reticulocyte count is a particularly key test here. Reticulocytes are immature red blood cells; a high count (reticulocytosis) indicates the bone marrow is appropriately increasing production in response to red cell loss or destruction. A low or normal count suggests a production problem.
| Cause | Typical Reticulocyte Count | Further Clues & Investigations |
|---|---|---|
| Acute Blood Loss | High (after ~3-5 days for marrow to respond) | History of trauma, surgery, major GI bleed (melaena/haematemesis). Initially normocytic as marrow hasn't had time to become iron deficient. |
| Haemolysis (Red cell destruction) | High | Check bilirubin, LDH (Lactate Dehydrogenase), and Haptoglobin (will be raised, raised, and low, respectively). May have jaundice or splenomegaly. Blood film may show specific features (e.g., spherocytes). Requires urgent haematology referral. |
| Anaemia of Chronic Disease (ACD) | Normal or Low | The most common cause of normocytic anaemia overall, especially in hospitalised or chronically unwell patients. Look for underlying inflammation (check CRP/ESR), infection, malignancy. Ferritin usually normal/high, iron low/normal. |
| Chronic Kidney Disease (CKD) | Normal or Low | Due to reduced erythropoietin (EPO) production by the kidneys. Check U&Es (eGFR). Severity usually correlates with degree of renal impairment. |
| Bone Marrow Failure / Infiltration | Low | Often associated with pancytopenia (low WCC/Platelets too). Consider myeloma screen (protein electrophoresis, immunoglobulins, free light chains) especially if >60y or bone pain/high calcium. May be due to leukaemia, lymphoma, MDS, aplastic anaemia, or metastatic cancer. Requires urgent haematology referral. |
| Mixed Deficiency | Normal or Low | A combination of iron deficiency (microcytic tendency) and B12/folate deficiency (macrocytic tendency) can result in a 'normal' average MCV. Always check full haematinics (Ferritin, B12, Folate). |
| Endocrine Disorders | Normal or Low | Hypothyroidism, hypoadrenalism (Addison's), hypopituitarism can cause mild normocytic anaemia. Check TFTs, consider 9am Cortisol if clinically suspected. |
| Early Iron Deficiency | Normal or Low | Before the cells become significantly small, IDA can present as normocytic. Ferritin will be low. |
🔬 Macrocytic Anaemia (MCV >100 fL)
Characterised by large red blood cells. Broadly divided into megaloblastic (impaired DNA synthesis) and non-megaloblastic causes.
Key Causes & Investigations
| Category | Cause | Key Features & Investigations |
|---|---|---|
| Megaloblastic (Impaired DNA Synthesis; often MCV >110 fL, may have hypersegmented neutrophils) |
Vitamin B12 Deficiency | Check serum B12 level. Look for causes (pernicious anaemia [check intrinsic factor/gastric parietal cell Abs], dietary insufficiency [vegans], malabsorption [Crohn's, surgery], metformin use). May have neurological symptoms (peripheral neuropathy, ataxia). |
| Folate Deficiency | Check serum folate level (or red cell folate if available). Look for causes (poor diet, malabsorption [coeliac disease - check tTG IgA], increased demand [pregnancy], certain drugs). | |
| Non-Megaloblastic (Mechanism varies; MCV usually 100-110 fL) |
Alcohol Excess | Very common. Direct marrow toxicity. Check LFTs (esp. GGT). Ask about alcohol intake (AUDIT-C score). MCV often improves with abstinence. |
| Liver Disease | Altered red cell membrane lipids lead to larger size. Check LFTs. Look for signs of chronic liver disease. | |
| Hypothyroidism | Check TFTs. Anaemia usually mild, mechanism unclear. | |
| Reticulocytosis | Reticulocytes are larger than mature red cells. A significantly high count (e.g., post-bleed, haemolysis) can slightly raise the average MCV. Check reticulocyte count result. | |
| Drugs | e.g., Hydroxycarbamide, Azathioprine, Methotrexate, Phenytoin, Zidovudine. Always review medication history. | |
| Myelodysplastic Syndrome (MDS) / Bone Marrow Disorders | A group of clonal bone marrow stem cell disorders, more common in elderly. Often presents with other cytopenias (low WCC/platelets) or abnormal cells on blood film. Requires haematology referral. |
🚀 Referral for Suspected Cancer
Anaemia can be the first sign of an underlying cancer, particularly of the GI tract (causing iron deficiency) or haematological system (causing pancytopenia or specific cell line deficiencies). NICE provides specific referral criteria based on age and anaemia type, alongside other symptoms.
- Patient aged ≥40 years with unexplained iron deficiency anaemia (Hb <110 g/L in men, <100 g/L in non-menstruating women) → Colorectal cancer pathway.
- Patient aged ≥60 years with iron deficiency anaemia OR anaemia + any abdominal symptoms → Colorectal cancer pathway.
- Patient aged ≥55 years with upper abdominal pain AND low haemoglobin (suggestive of anaemia) → Oesophago-gastric cancer pathway.
- Patient with pancytopenia or unexplained persistent macrocytosis → Haematological cancer pathway.
- Patient ≥60 years with bone pain or unexplained fracture AND abnormal protein electrophoresis or Bence Jones protein → Myeloma pathway (NB: anaemia often present too).
Note: This is not exhaustive. Always refer to the full NICE NG12 guideline for specific criteria based on the full clinical picture.
FIT detects small amounts of human blood in the stool and helps risk-stratify patients for colorectal cancer investigation, particularly when they don't meet the urgent 2WW criteria based on symptoms alone.
Consider offering a FIT test to patients with unexplained symptoms but no rectal bleeding, where colorectal cancer is in the differential, including:
- Patients aged 50-59 years with unexplained abdominal pain OR weight loss.
- Patients aged <60 years with a change in bowel habit OR iron deficiency anaemia.
- Patients aged ≥60 years with anaemia (even if not iron deficient).
A positive FIT result in these groups should generally trigger an urgent 2-week wait referral for colorectal cancer investigation (thresholds vary locally).
🎯 OSCE Preparation
Interpreting a Blood Result
Scenario: A 70-year-old man's bloods show: Hb 115 g/L (Low), MCV 95 fL (Normal), Platelets 120 x 109/L (Low), WCC 3.5 x 109/L (Low). Ferritin, B12, and Folate are all within the normal range. His GP asks for your interpretation.
Structured Approach:- Identify the Abnormalities: "Looking at the full blood count, the patient has a mild normocytic anaemia (Hb 115, MCV 95). However, the most striking findings are the mild thrombocytopenia (platelets 120) and the mild leucopenia (WCC 3.5). The combination of low red cells, white cells, and platelets is known as pancytopenia."
- Interpret the Findings: "A normocytic anaemia with normal haematinics (ferritin, B12, folate) suggests the problem isn't a simple nutritional deficiency. The presence of pancytopenia is a significant red flag. It indicates a potential global problem with the bone marrow's ability to produce all three major cell lines."
- Formulate a Differential Diagnosis for Pancytopenia: "Given the patient's age (70), the differential diagnosis for pancytopenia is broad but serious. It includes primary bone marrow failure (like aplastic anaemia, although less common at this age), myelodysplastic syndrome (MDS), haematological malignancies such as leukaemia or myeloma, or infiltration of the bone marrow by metastatic cancer (e.g., prostate, lung). Certain infections or drugs could also cause this, but marrow failure/malignancy needs urgent exclusion."
- State the Plan & Urgency: "This pattern of pancytopenia requires urgent investigation to rule out serious underlying pathology, particularly malignancy. The patient needs an urgent referral to Haematology (likely via the 2-week wait pathway, depending on local guidelines for pancytopenia) for further assessment. This will typically involve a blood film examination and probably a bone marrow biopsy."
- Communicate Key Message: "The key message is that the combination of anaemia with low platelets and white cells warrants urgent specialist haematological assessment."
✅ Test Your Knowledge
You've completed the module. Now, test your understanding with a short quiz!
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