Anaemia
Summary
Anaemia is defined as haemoglobin concentration below the normal range for age and sex. It is not a diagnosis but a sign of underlying disease. Classification by mean corpuscular volume (MCV) provides a practical diagnostic framework: microcytic (MCV less than 80 fL), normocytic (MCV 80-100 fL), and macrocytic (MCV greater than 100 fL). Iron deficiency is the most common cause worldwide. Investigation should identify the cause - in older patients with iron deficiency, GI malignancy must be excluded. Treatment is directed at the underlying cause plus replacement therapy where appropriate.
Key Facts
- Definition: Hb less than 130 g/L (men), less than 120 g/L (women) (WHO criteria)
- Prevalence: 25% of world population; most common haematological abnormality
- Demographics: More common in women (menstruation, pregnancy), elderly, developing countries
- Classification: Microcytic, normocytic, macrocytic (by MCV)
- Gold Standard Investigation: FBC, blood film, reticulocytes, iron studies, B12/folate
- First-line Treatment: Treat underlying cause + replacement if deficient
- Prognosis: Depends on underlying cause
Clinical Pearls
MCV Pearl: MCV is your first branch point. Microcytic = think iron. Macrocytic = think B12/folate/liver/alcohol/drugs.
Iron Deficiency Pearl: In men and postmenopausal women with iron deficiency, GI investigation (OGD + colonoscopy) is MANDATORY to exclude malignancy.
B12 Pearl: Neurological damage from B12 deficiency can be irreversible. Subacute combined degeneration affects dorsal columns and corticospinal tracts.
Reticulocyte Pearl: Reticulocytes are high if marrow is responding (haemolysis, bleeding, treatment response). Low reticulocytes = production problem.
Ferritin Pearl: Ferritin is an acute phase reactant. May be "normal" in iron deficiency with concurrent inflammation. Check transferrin saturation.
Why This Matters Clinically
Anaemia is extremely common and the underlying cause must be found. Missing GI cancer as a cause of iron deficiency is a serious diagnostic failure. Systematic investigation using MCV and indices identifies the cause in most cases.
Prevalence
| Population | Prevalence |
|---|---|
| Global | 25% (1.6 billion people) |
| Pregnant women | 40% |
| Children under 5 | 40% |
| Elderly | 20% |
Causes by Frequency
| Cause | Contribution |
|---|---|
| Iron deficiency | 50% (most common globally) |
| Anaemia of chronic disease | 30% (in hospitalised patients) |
| Thalassaemia | Common in Mediterranean, Asian, African populations |
| B12/folate deficiency | 5-10% |
| Haemolytic anaemias | 5% |
Normal Erythropoiesis
- Erythropoietin (kidney) → bone marrow → red cell production
- Requires: iron, B12, folate, functioning marrow
- RBC lifespan: 120 days
Classification by MCV
Microcytic (MCV less than 80 fL):
- Iron deficiency (most common)
- Thalassaemia
- Anaemia of chronic disease (may be normocytic)
- Sideroblastic anaemia
- Lead poisoning
Normocytic (MCV 80-100 fL):
- Anaemia of chronic disease
- Acute blood loss
- Chronic kidney disease
- Bone marrow failure/infiltration
- Mixed deficiencies (iron + B12)
- Haemolysis
Macrocytic (MCV greater than 100 fL):
- B12 deficiency (megaloblastic)
- Folate deficiency (megaloblastic)
- Alcohol/liver disease
- Hypothyroidism
- Myelodysplasia
- Drugs (methotrexate, azathioprine, hydroxyurea)
- Reticulocytosis (larger cells)
Iron Deficiency Anaemia
Causes:
- Blood loss (GI, menstrual) - most common
- Reduced absorption (coeliac, gastrectomy)
- Increased requirements (pregnancy, growth)
- Poor dietary intake (rare in developed countries alone)
Pathophysiology:
- Depleted iron stores → impaired haem synthesis → reduced Hb
B12 Deficiency
Causes:
- Pernicious anaemia (autoimmune gastritis, anti-IF antibodies)
- Gastric surgery
- Ileal disease/resection
- Dietary (strict vegans)
- Medications (metformin, PPIs)
Pathophysiology:
- B12 needed for DNA synthesis → megaloblastic erythropoiesis
- Also causes neurological damage (subacute combined degeneration)
General Symptoms of Anaemia
| Symptom | Mechanism |
|---|---|
| Fatigue | Reduced oxygen delivery |
| Dyspnoea on exertion | Compensatory response |
| Palpitations | Tachycardia |
| Dizziness/light-headedness | Cerebral hypoperfusion |
| Headache | Hypoxia |
| Pallor | Reduced haemoglobin |
Cause-Specific Features
| Cause | Features |
|---|---|
| Iron deficiency | Pica, koilonychia, angular stomatitis, glossitis |
| B12 deficiency | Glossitis, neurological (paraesthesia, ataxia, dementia) |
| Folate deficiency | Similar to B12 but NO neurological signs |
| Haemolysis | Jaundice, dark urine, splenomegaly |
| Chronic disease | Features of underlying condition |
Red Flags
[!CAUTION]
- Hb less than 70 g/L or symptomatic at rest
- Signs of active bleeding (melaena, haematemesis)
- Haemodynamic instability
- Neurological symptoms (B12)
- Suspicious features for malignancy (weight loss, mass)
General
- Pallor (conjunctivae, palms, nail beds)
- Tachycardia
- Systolic flow murmur (hyperdynamic circulation)
- Signs of cardiac failure (if severe)
Specific Signs
| Sign | Suggests |
|---|---|
| Koilonychia (spoon nails) | Iron deficiency |
| Angular stomatitis | Iron or B12 deficiency |
| Glossitis | Iron or B12 deficiency |
| Jaundice + pallor | Haemolysis |
| Splenomegaly | Haemolysis, haematological malignancy |
| Peripheral neuropathy | B12 deficiency |
| Petechiae/bruising | Bone marrow failure |
First-Line
| Test | Value |
|---|---|
| FBC | Hb, MCV, MCH, MCHC, RDW, WCC, platelets |
| Blood film | Morphology (microcytic, macrocytic, hypersegmented neutrophils) |
| Reticulocyte count | Production vs destruction |
| Iron studies | Ferritin, iron, TIBC, transferrin saturation |
| B12 and folate |
Iron Studies Interpretation
| Condition | Ferritin | Iron | TIBC | Transferrin Sat |
|---|---|---|---|---|
| Iron deficiency | Low | Low | High | Low (less than 16%) |
| Chronic disease | Normal/High | Low | Low/Normal | Low/Normal |
| Thalassaemia trait | Normal | Normal | Normal | Normal |
Additional Tests (as indicated)
| Test | Indication |
|---|---|
| Haemolysis screen | Suspected haemolysis (LDH, bilirubin, haptoglobin, Coombs) |
| Haemoglobin electrophoresis | Suspected thalassaemia/haemoglobinopathy |
| Bone marrow biopsy | Unexplained cytopenias, suspected marrow pathology |
| Parietal cell/IF antibodies | Suspected pernicious anaemia |
| TFTs | Macrocytosis |
| LFTs | Liver disease |
| GI investigations | Iron deficiency in men/postmenopausal women |
| Coeliac serology | Unexplained iron deficiency |
Management Algorithm
ANAEMIA CONFIRMED (Hb LOW)
↓
┌────────────────────────────────────────────────────────────┐
│ CLASSIFY BY MCV │
├──────────────────┬─────────────────┬──────────────────────┤
│ MICROCYTIC │ NORMOCYTIC │ MACROCYTIC │
│ (MCV less than │ (MCV 80-100) │ (MCV greater than │
│ 80) │ │ 100) │
│ Iron studies │ Reticulocytes │ B12, folate │
│ Ferritin first │ Renal function │ LFTs, TFTs │
│ │ Haemolysis │ Blood film │
│ │ screen │ │
└──────────────────┴─────────────────┴──────────────────────┘
↓
┌────────────────────────────────────────────────────────────┐
│ IRON DEFICIENCY │
│ 1. Find the cause (GI investigation if male/postmeno) │
│ 2. Oral iron (ferrous sulfate 200mg TDS) x 3 months │
│ 3. Recheck Hb at 2-4 weeks (should rise 10-20 g/L/month) │
│ 4. IV iron if intolerant, non-compliant, malabsorption │
└────────────────────────────────────────────────────────────┘
↓
┌────────────────────────────────────────────────────────────┐
│ B12 DEFICIENCY │
│ 1. Identify cause (pernicious anaemia, dietary, ileal) │
│ 2. IM hydroxocobalamin: 1mg on alternate days x 2 weeks │
│ Then 1mg every 3 months for life (if pernicious) │
│ 3. Oral B12 may be effective for dietary deficiency │
│ 4. Urgent treatment if neurological symptoms │
└────────────────────────────────────────────────────────────┘
↓
┌────────────────────────────────────────────────────────────┐
│ FOLATE DEFICIENCY │
│ 1. Rule out B12 deficiency first (can mask/worsen neuro) │
│ 2. Folic acid 5mg daily for 4 months │
│ 3. Address cause (diet, malabsorption, drugs) │
└────────────────────────────────────────────────────────────┘
Iron Replacement
| Route | Regimen | Notes |
|---|---|---|
| Oral | Ferrous sulfate 200mg TDS | Take on empty stomach if tolerated; vitamin C helps absorption |
| IV | Ferric carboxymaltose (Ferinject) | If oral fails, malabsorption, or rapid correction needed |
B12 Replacement
| Cause | Treatment |
|---|---|
| Pernicious anaemia | IM hydroxocobalamin lifelong |
| Dietary | Oral cyanocobalamin 50-150mcg daily OR IM |
| Neurological involvement | IM loading (alternate days x 3 weeks), then maintenance |
Blood Transfusion
- Consider if Hb less than 70 g/L or symptomatic at higher levels
- In elderly/cardiac patients, transfuse slowly (diuretic cover)
- Aim to correct symptoms, not normalise Hb acutely
| Complication | Features |
|---|---|
| Cardiac failure | High-output failure in severe anaemia |
| Angina | May precipitate in CAD |
| Subacute combined degeneration | B12 deficiency; irreversible if delayed |
| Growth retardation | Chronic childhood anaemia |
| Pregnancy complications | Iron deficiency; low birth weight, prematurity |
- Iron deficiency: excellent with replacement and cause treated
- B12 deficiency: haematological recovery good; neurological may be incomplete if delayed
- Depends on underlying cause (malignancy, haematological disease)
Key Guidelines
-
BSH Guidelines on Iron Deficiency Anaemia — Goddard AF et al. Gut. 2011
-
BSH Guidelines on Cobalamin and Folate — Devalia V et al. Br J Haematol. 2014
-
NICE Guideline NG24. Blood transfusion — 2015
Key Evidence
- Oral iron: raises Hb 10-20 g/L per month
- IV iron superior to oral for CKD, IBD, post-surgical
- PMID: 21054451
What is anaemia?
Anaemia means you don't have enough red blood cells or haemoglobin to carry oxygen around your body. This makes you feel tired and breathless.
What causes it?
The most common cause is iron deficiency, often from blood loss or poor diet. Other causes include vitamin deficiencies (B12, folate) or chronic diseases.
Treatment
Depends on the cause:
- Iron tablets (may cause dark stools and constipation)
- B12 injections
- Treating the underlying condition
When to seek help
- Very tired, short of breath at rest
- Black stools or blood in stools
- Numbness or tingling (B12)
-
Goddard AF et al. Guidelines for the management of iron deficiency anaemia. Gut. 2011;60(10):1309-1316. PMID: 21561874
-
Devalia V et al. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166(4):496-513. PMID: 24942828
-
Camaschella C. Iron-Deficiency Anemia. N Engl J Med. 2015;372(19):1832-1843. PMID: 25946282
-
Green R. Vitamin B12 deficiency from the perspective of a practicing hematologist. Blood. 2017;129(19):2603-2611. PMID: 28360040
-
NICE Guideline NG24. Blood transfusion. 2015.
Viva Points
"Anaemia is classified by MCV: microcytic (iron, thalassaemia), normocytic (chronic disease, CKD, haemolysis), macrocytic (B12, folate, liver, drugs). Iron deficiency in men/postmenopausal women needs GI investigation for malignancy. Treat with oral iron for 3 months. B12 deficiency can cause irreversible neurological damage - treat urgently."
Common Mistakes
- ❌ Not investigating cause of iron deficiency (missing GI cancer)
- ❌ Treating folate before excluding B12 deficiency
- ❌ Forgetting ferritin is acute phase reactant
- ❌ Not recognising subacute combined degeneration
Last Reviewed: 2026-01-01 | MedVellum Editorial Team