• •Onset and duration: Acute vs chronic fatigue, breathlessness on exertion, exercise tolerance
• •Bleeding history: Menorrhagia (heavy periods), GI blood loss (melaena, haematochezia, haematemesis), epistaxis
• •Dietary history: Vegetarian/vegan diet, poor nutrition, alcohol excess, tea consumption with meals
• •GI symptoms: Dyspepsia, change in bowel habit, abdominal pain, weight loss (consider malignancy)
• •Medications: NSAIDs, aspirin, anticoagulants, PPIs (reduce iron absorption), metformin (B12 deficiency)
• •Past medical history: Previous anaemia, GI disease (coeliac, IBD), chronic kidney disease, autoimmune conditions
• •Family history: Inherited anaemias (thalassaemia, sickle cell), GI malignancy, coeliac disease
• •Systemic symptoms: Fever, night sweats, weight loss, bone pain (consider malignancy)

• •General appearance: Pallor (conjunctivae, palmar creases), jaundice, cachexia
• •Cardiovascular: Tachycardia, flow murmur, signs of heart failure (if severe anaemia)
• •Abdominal: Hepatosplenomegaly, abdominal masses, epigastric tenderness
• •Neurological: Peripheral neuropathy, ataxia, cognitive impairment (B12 deficiency)
• •Skin and nails: Koilonychia (spoon nails), angular stomatitis, glossitis (iron/B12 deficiency)
• •Lymph nodes: Generalised lymphadenopathy (consider haematological malignancy)

• •ICE exploration: Many patients fear cancer when they hear "blood test" — explore concerns early
• •Explain investigations: "We'll check your blood count and iron levels, and look for any underlying causes"
• •Set expectations: "Most causes of anaemia are treatable, and we can usually manage them in primary care"
• •Document clearly: Record severity, impact on function, red flag symptoms checked and excluded

• •Bleeding pattern: Spontaneous vs traumatic, mucosal bleeding (epistaxis, gum bleeding, menorrhagia)
• •Bruising: Size, location, frequency, relationship to trauma, easy bruising with minor knocks
• •Petechiae/purpura: Non-blanching rash, distribution, associated symptoms (fever, joint pain)
• •Medications: Anticoagulants, antiplatelets, NSAIDs, steroids, SSRIs (increase bleeding risk)
• •Past medical history: Liver disease, renal disease, previous bleeding episodes, easy bruising since childhood
• •Family history: Bleeding disorders (haemophilia, von Willebrand disease)
• •Alcohol history: Chronic liver disease, thrombocytopenia
• •Systemic symptoms: Fever, weight loss, night sweats, bone pain (consider malignancy)
• •Safeguarding context: In children, consider non-accidental injury if bruising pattern inconsistent with history

• •Skin examination: Petechiae (pinpoint), purpura (larger), ecchymoses (bruises), distribution pattern
• •Mucosal bleeding: Gum bleeding, oral petechiae, conjunctival haemorrhage
• •Lymph nodes: Generalised lymphadenopathy (consider haematological malignancy)
• •Hepatosplenomegaly: Liver disease, portal hypertension, haematological malignancy
• •Joint examination: Haemarthrosis (haemophilia), vasculitic arthritis
• •Vital signs: Fever (infection, vasculitis), tachycardia (significant bleeding)

• •Reassurance when appropriate: "Easy bruising is common and often benign, but we need to check your blood count and clotting to be sure"
• •Medication review: Always check for anticoagulants, antiplatelets, NSAIDs, SSRIs
• •Safeguarding awareness: In children or vulnerable adults, consider non-accidental injury if pattern inconsistent
• •Document clearly: Size, location, colour of bruises; presence/absence of petechiae; systemic symptoms

• •Node characteristics: Duration, size, location, single vs multiple, painful vs painless
• •Associated symptoms: Sore throat, cough, skin lesions, recent infections
• •B symptoms: Fever, drenching night sweats, weight loss >10% in 6 months (lymphoma)
• •Alcohol-induced pain: Lymph node pain after alcohol consumption (Hodgkin lymphoma)
• •Pruritus: Generalised itching without rash (lymphoma)
• •Travel history: TB, HIV, tropical infections
• •Occupational/animal exposure: Cat scratch disease, toxoplasmosis
• •Medications: Phenytoin, allopurinol (drug-induced lymphadenopathy)
• •Sexual history: HIV, syphilis (if appropriate)

• •Lymph node examination: Size (measure in cm), consistency (soft/firm/hard), mobility (fixed vs mobile), tenderness
• •Distribution: Localised (cervical, axillary, inguinal) vs generalised
• •Supraclavicular nodes: Always significant — high risk of malignancy, urgent referral
• •Spleen examination: Palpable spleen (start in RIF, percuss), measure cm below costal margin
• •Liver examination: Hepatomegaly (haematological malignancy, chronic liver disease)
• •ENT examination: Tonsils, pharynx (infectious mononucleosis, tonsillitis)
• •Skin examination: Rashes, lesions, scratch marks (pruritus)

• •Explain referral criteria: "We refer urgently if nodes are in certain locations, very large, or not settling — this is a precaution to rule out serious causes"
• •Document clearly: Size in cm, location, consistency, mobility, duration, associated symptoms
• •Axillary nodes in women: Always examine breasts — refer via breast pathway if breast lump present

• •Thrombosis history: DVT, PE, stroke, TIA, MI — age at first event, provoked vs unprovoked
• •Recurrent thrombosis: Multiple events, unusual sites (mesenteric, cerebral venous sinus)
• •Hyperviscosity symptoms: Headaches, visual disturbance, dizziness, confusion, tinnitus
• •Family history: Thrombophilia, recurrent miscarriage, young-onset thrombosis
• •Cancer history: Active malignancy (high thrombotic risk)
• •Pregnancy/OCP: Thrombosis during pregnancy, on combined oral contraceptive
• •Autoimmune disease: Antiphospholipid syndrome, SLE

• •Cardiovascular: BP, heart rate, signs of heart failure
• •Respiratory: Respiratory rate, oxygen saturation, signs of PE
• •Neurological: Focal neurology (stroke/TIA), visual fields, fundoscopy (hyperviscosity retinopathy)
• •Limb examination: Swelling, erythema, tenderness (DVT), peripheral pulses
• •Abdominal: Splenomegaly (myeloproliferative disorders)
• •Skin: Plethora (ruddy complexion in polycythaemia), livedo reticularis (antiphospholipid syndrome)

• •Thrombophilia testing: Only test if it will change management (e.g., duration of anticoagulation, family screening)
• •Document clearly: Date, site, provoked/unprovoked, treatment duration, family history

• •Jaundice: Onset, duration, associated symptoms (dark urine, pale stools)
• •Dark urine: Cola-coloured urine (haemoglobinuria in intravascular haemolysis)
• •Triggers: Infection, drugs (dapsone, antimalarials), cold exposure, fava beans (G6PD deficiency)
• •Gallstones: Previous biliary colic, cholecystectomy (chronic haemolysis)
• •Family history: Inherited haemolytic anaemias (sickle cell, thalassaemia, hereditary spherocytosis, G6PD deficiency)
• •Ethnicity: Sickle cell (African, Caribbean), thalassaemia (Mediterranean, Asian), G6PD (Mediterranean, African, Asian)
• •Autoimmune disease: SLE, rheumatoid arthritis (autoimmune haemolytic anaemia)

• •Jaundice: Scleral icterus, skin jaundice (unconjugated hyperbilirubinaemia)
• •Pallor: Anaemia (chronic haemolysis)
• •Splenomegaly: Chronic haemolysis, hereditary spherocytosis
• •Hepatomegaly: Chronic liver disease, haemochromatosis (secondary to transfusions)
• •Leg ulcers: Sickle cell disease
• •Vital signs: Fever (infection trigger), tachycardia (anaemia)

• •Step 1: Confirm anaemia with FBC — check Hb, MCV, MCH, MCHC
• •Step 2: Classify by MCV — microcytic (<80 fL), normocytic (80–100 fL), macrocytic (>100 fL)
• •Step 3: Request haematinics — ferritin, B12, folate, CRP (inflammation marker)
• •Step 4: Identify likely source of loss — GI, menstrual, dietary, chronic disease
• •Step 5: Investigate underlying cause — don't just treat, find the reason

• •Microcytic anaemia: Ferritin, CRP, coeliac screen (if unexplained). For GI investigation, use FIT-based triage (see NICE NG12 below).
• •Normocytic anaemia: Reticulocyte count, renal function, CRP, TFTs. Consider chronic disease, renal failure, haemolysis.
• •Macrocytic anaemia: B12, folate, TFTs, LFTs, reticulocyte count. Consider alcohol, liver disease, hypothyroidism, haemolysis.
• •Mixed picture: Check all haematinics — combined deficiencies common (e.g., iron + B12)

• •Low ferritin (<30): Iron deficiency — investigate cause (GI loss, menorrhagia, dietary)
• •Normal ferritin + microcytosis: Consider thalassaemia trait, chronic disease
• •High ferritin (>300 men, >200 women): Inflammation, liver disease, alcohol, haemochromatosis, malignancy
• •Always check CRP: If CRP raised, ferritin may be falsely elevated — iron deficiency can coexist

• •Low transferrin saturation (<20%): Iron deficiency — even if ferritin normal
• •High transferrin saturation (>45%): Iron overload — check for haemochromatosis
• •Haemochromatosis screening: Ferritin >300 (men) or >200 (women) + transferrin saturation >45% → HFE genetic testing
• •Fasting sample preferred: Iron levels vary throughout day — fasting sample more reliable

• •B12 deficiency causes: Pernicious anaemia (most common), vegan diet, malabsorption (Crohn's, coeliac), metformin, PPIs
• •Folate deficiency causes: Poor diet, alcohol, malabsorption, pregnancy, haemolysis, drugs (methotrexate, trimethoprim)

• •Raised reticulocytes + anaemia: Haemolysis, acute bleeding, response to treatment
• •Low reticulocytes + anaemia: Iron deficiency, B12 deficiency, bone marrow failure, chronic disease
• •Use in haemolysis: Raised reticulocytes + raised bilirubin + low haptoglobin = haemolysis

• •FBC: Check platelets, Hb, WCC
• •Clotting screen: PT, APTT, fibrinogen
• •LFTs: Liver disease affects clotting factor synthesis
• •Renal function: Uraemia affects platelet function
• •Medication review: Anticoagulants, antiplatelets, NSAIDs, SSRIs, steroids

• •Exclude dehydration: Repeat FBC when well hydrated
• •Smoking history: Heavy smoking causes secondary polycythaemia
• •Symptoms: Pruritus after bathing, headaches, visual disturbance, thrombosis (polycythaemia vera)

• •Repeat FBC: Confirm persistent elevation on two occasions 2–4 weeks apart
• •JAK2 mutation: Check if Hb/Hct persistently raised — positive in 95% polycythaemia vera
• •Oxygen saturation: If <92%, consider hypoxic cause
• •Ferritin and CRP: For thrombocytosis — reactive if raised CRP or low ferritin

• •High-risk ethnicities: African, Caribbean, Mediterranean, Middle Eastern, Asian — higher carrier rates
• •Partner testing: If mother is carrier, test partner urgently
• •Genetic counselling: If both parents carriers, refer for prenatal diagnosis and counselling

• •Iron deficiency: Most common cause — ferrous sulfate 200mg once daily or alternate days (NICE CKS 2025)
• •Folate supplementation: All pregnant women should take folic acid 400 micrograms daily (5mg if high risk)
• •Monitoring: Check Hb at booking, 28 weeks, and if symptomatic

• •Sickle cell disease: High-risk pregnancy — shared care with haematology and obstetrics, increased monitoring
• •VTE in pregnancy: LMWH throughout pregnancy and 6 weeks postpartum, specialist-led care

• •FBC findings: Low Hb, low MCV (<80 fL), low MCH, microcytic hypochromic red cells
• •Ferritin: <30 μg/L diagnostic. If CRP raised, ferritin <100 μg/L may indicate deficiency
• •Common causes: GI blood loss (peptic ulcer, malignancy, angiodysplasia), menorrhagia, dietary (vegetarian/vegan), malabsorption (coeliac)
• •Prevalence: 1 in 20 UK adults have iron deficiency anaemia — most common anaemia in primary care

• •Baseline tests: FBC, ferritin, CRP, B12/folate (if mixed picture)
• •Coeliac screen: Tissue transglutaminase (tTG) antibodies — check in all unexplained IDA
• •GI investigation (NICE NG12, 2026): Offer FIT to all adults with IDA; also offer FIT to those aged ≥60 with any anaemia. Refer via suspected cancer pathway if FIT ≥10 µg Hb/g. Do not delay if strong clinical concern despite FIT result.
• •Gynaecology assessment: Pre-menopausal women — assess menstrual loss, consider pelvic ultrasound if menorrhagia
• •Medication review: NSAIDs, aspirin, anticoagulants (GI bleeding risk), PPIs (reduce iron absorption)

• •Oral iron: First-line treatment — ferrous sulfate 200mg once daily (NICE CKS Oct 2025)
• •Dietary advice: Iron-rich foods (red meat, dark green vegetables, fortified cereals), vitamin C aids absorption
• •Avoid: Tea/coffee with meals (reduce absorption), calcium supplements at same time as iron
• •Monitoring: Recheck Hb at 2–4 weeks — expect rise of 10–20 g/L if adherent and correct diagnosis
• •Duration: Continue for 3 months after Hb normalises to replenish stores (check ferritin)

• •FBC findings: Macrocytic anaemia (MCV >100 fL), hypersegmented neutrophils on blood film
• •B12 deficiency causes: Pernicious anaemia (most common), vegan diet, malabsorption (Crohn's, coeliac), gastric surgery, metformin, PPIs
• •Neurological complications: Subacute combined degeneration of the cord (B12 deficiency) — irreversible if untreated

• •Baseline tests: FBC, B12, folate, blood film, LFTs, TFTs
• •Pernicious anaemia: Intrinsic factor antibodies (specific, 50% sensitive), gastric parietal cell antibodies
• •Coeliac screen: tTG antibodies — check in unexplained B12/folate deficiency
• •Medication review: Metformin (B12 malabsorption), PPIs, methotrexate (folate antagonist)

• •INR <1.5: Subtherapeutic — increase dose, recheck in 3–5 days
• •INR 2.0–3.0: Therapeutic (AF/VTE) — continue current dose
• •INR 5.1–8.0: Very high — omit 2 doses, reduce weekly dose, consider oral vitamin K 1–2mg if bleeding risk
• •INR >8.0: Dangerous — stop warfarin, give oral vitamin K 5mg, recheck next day, urgent haematology advice
• •Drug interactions: Always check BNF before prescribing. Common culprits: metronidazole, clarithromycin, ciprofloxacin, amiodarone, azoles

• •Annual checks: Renal function (eGFR), liver function, FBC, weight
• •Renal function: Check eGFR annually (more frequently if CKD or elderly). Dose reduction needed in renal impairment.
• •Adherence: DOACs have short half-life — missing doses increases stroke risk
• •Bleeding risk: HAS-BLED score ≥3 = high risk — optimise modifiable factors (BP, avoid NSAIDs, PPI if GI risk)

• •Indication check: AF — recalculate CHA₂DS₂-VASc score. VTE — duration appropriate?
• •Patient education: Recognise bleeding signs, importance of adherence, carry anticoagulant card
• •Medication review: New drugs with interactions? NSAIDs? Antiplatelets?

• •Clinical features: Often asymptomatic until organ damage. Fatigue, arthralgia (especially hands), bronze skin, diabetes, liver disease, cardiomyopathy, hypogonadism.
• •Screening criteria: Ferritin >300 μg/L (men) or >200 μg/L (women) + transferrin saturation >45% → screen for haemochromatosis

• •Diagnostic pathway: Raised ferritin + raised transferrin saturation → HFE genetic testing → if C282Y homozygous, confirm with liver MRI or biopsy
• •Exclude other causes: Alcohol excess, chronic liver disease, inflammation (raised CRP), repeated transfusions
• •Liver assessment: LFTs, liver MRI (iron quantification), consider liver biopsy if cirrhosis suspected
• •Family screening: First-degree relatives of confirmed cases should be offered ferritin, transferrin saturation, and HFE genetic testing

• •Dietary advice: Avoid iron supplements, vitamin C supplements, excessive alcohol. Normal diet otherwise.
• •Monitoring: Ferritin every 3 months initially, then 6–12 monthly. LFTs annually. Screen for diabetes, cardiomyopathy.
• •Prognosis: Normal life expectancy if treated before organ damage. Cirrhosis → 6-monthly ultrasound surveillance for hepatocellular carcinoma.

• •Vaso-occlusive crisis: Severe pain (bones, chest, abdomen), triggered by infection, dehydration, cold, stress. Requires hospital admission.
• •Infection risk: Functional asplenia — increased risk of encapsulated organisms. Lifelong penicillin prophylaxis essential.
• •Chronic complications: Stroke, pulmonary hypertension, renal disease, retinopathy, avascular necrosis, leg ulcers
• •When to admit: Vaso-occlusive crisis, acute chest syndrome, stroke symptoms, splenic sequestration, severe infection

• •Thalassaemia major: Severe anaemia requiring lifelong blood transfusions every 2–4 weeks. Iron chelation for overload.
• •Diagnosis: FBC (microcytosis), Hb electrophoresis (raised HbA2 in beta thalassaemia trait), genetic testing

• •Vaccinations: PCV13 + PPV23, Haemophilus influenzae type b, meningococcal ACWY, annual influenza
• •Annual review: Adherence to penicillin/folic acid, vaccination status, screen for complications (renal function, retinopathy)
• •Crisis prevention: Avoid dehydration, cold exposure, high altitude, excessive exercise. Prompt treatment of infections.

CRAB Criteria — the classic presentation (NICE NG35):

• •C — Hypercalcaemia: Serum calcium >2.75 mmol/L (or above upper limit of normal). Symptoms: thirst, polyuria, constipation, confusion, nausea.
• •R — Renal impairment: Creatinine >177 µmol/L or eGFR <40 mL/min. Often from cast nephropathy (Bence Jones protein) or hypercalcaemia.
• •A — Anaemia: Hb <100 g/L (normocytic normochromic). Rouleaux on blood film is a classic finding. May also cause fatigue and breathlessness.
• •B — Bone lesions: Lytic lesions, pathological fracture, or osteoporosis. Persistent back pain or rib pain — especially in older adults — is a key presenting symptom.

Other presentations to recognise:

• •Recurrent infections: Immunoparesis (suppressed normal immunoglobulins) leads to bacterial infections, especially pneumonia and UTIs.
• •Incidental paraprotein: Found on SPEP requested for other reasons (high ESR, raised total protein, unexplained anaemia). All paraproteins require further investigation — some are MGUS, some are myeloma.
• •Hyperviscosity (rare): Headache, visual disturbance, confusion, bleeding tendency. More common in Waldenström's macroglobulinaemia than myeloma but can occur.
• •Spinal cord compression: Vertebral collapse causing back pain with neurological symptoms (leg weakness, sensory change, sphincter dysfunction). This is a medical emergency — see When to Refer.

First-line blood tests:

• •FBC: Normocytic normochromic anaemia; rouleaux on blood film (red cells stacking like coins due to paraprotein).
• •U&E: Renal impairment (creatinine, eGFR).
• •Calcium: Corrected calcium — hypercalcaemia in up to 30% at diagnosis.
• •Total protein and albumin: Raised total protein with normal or low albumin raises suspicion of paraprotein.
• •ESR: Often markedly elevated. Non-specific but a useful trigger for further investigation.
• •LDH: Prognostic marker — usually ordered once referral has been made.

Targeted further tests (same consultation if clinical suspicion high):

• •Serum protein electrophoresis (SPEP): Detects a paraprotein (M-band). Any paraprotein detected = urgent referral to haematology.
• •Serum free light chains (kappa and lambda): Sensitive test; detects light-chain-only myeloma (which may not show a band on SPEP).
• •Serum immunoglobulins (IgG, IgA, IgM): Elevated in one class with suppression of others is characteristic.
• •Urine for Bence Jones protein: Useful if light-chain myeloma suspected; ideally an early-morning specimen.
• •Blood film: Request specifically — rouleaux, plasma cells on film (rare but diagnostic if present).

Specialist-initiated treatment (for awareness):

• •Induction chemotherapy: Typically bortezomib-based regimens (e.g. VTd, VRd). Thalidomide and lenalidomide-based regimens are also used. All initiated by haematology.
• •Autologous stem cell transplantation (ASCT): Offered to fit younger patients after induction. Leads to prolonged remission in suitable candidates.
• •Bisphosphonates: Zoledronic acid IV monthly (hospital) or ibandronic acid oral monthly — reduce skeletal complications. Initiated by haematology; GP may continue oral bisphosphonate under shared care agreement.
• •Maintenance therapy: Lenalidomide post-ASCT — specialist-initiated and monitored.

GP supportive care:

• •Analgesia: Paracetamol first-line. Avoid NSAIDs (renal impairment risk). Opioids per WHO analgesic ladder if required — seek palliative care input early for complex pain.
• •Avoid NSAIDs: Contraindicated due to renal impairment risk and myeloma nephropathy.
• •Infection management: Immunoparesis increases infection risk. Low threshold to treat and review. If neutropenic: see neutropenic sepsis protocol.
• •Vaccinations: Annual influenza vaccine. Pneumococcal (PCV13 + PPV23). Confirm haematology have advised on vaccine timing relative to treatment.
• •Hydration: Encourage adequate fluid intake — reduces renal cast formation and hypercalcaemia symptoms.
• •VTE prophylaxis: High VTE risk (especially on thalidomide/lenalidomide). Haematology will advise; GP may be asked to continue LMWH or DOAC.
• •Psychological support: Myeloma is currently incurable for most. Early psychological support and carer involvement is important.

What a GP may prescribe (supportive care only):

• •Analgesia: Paracetamol (preferred). Opioids via WHO ladder for bone pain if required. Avoid NSAIDs. Check BNF for renal dose adjustments of opioids in renal impairment (common in myeloma).
• •Antibiotics for infections: Treat per sensitivity and local guidance — amoxicillin or clarithromycin for community-acquired pneumonia, trimethoprim or nitrofurantoin for UTI (check eGFR first — nitrofurantoin contraindicated if eGFR <30). Source: BNF; verify doses before prescribing.
• •Oral ibandronic acid (shared care): 50mg once monthly, taken 30–60 minutes before food/drink. Only if haematology have initiated and shared care agreement is in place. Source: BNF — verify before prescribing.
• •Anticoagulation (shared care): Thalidomide/lenalidomide-associated VTE — haematology will specify LMWH or DOAC regimen; GP may continue under shared care agreement. Source: BNF/SPC — verify before prescribing.

• •Reversal (warfarin overdose): INR 5–8, no bleeding → oral vitamin K 1–2mg. INR >8 → oral vitamin K 5mg. Major bleeding → IV vitamin K 5mg + prothrombin complex concentrate (PCC). Source: BNF.