UKMLA Haematology Essentials: High-Yield Revision Guide

Haematology is the UKMLA topic where the stems look deceptively simple and the answers reward shallow pattern-matching only to a point. "Microcytic anaemia — next investigation?" reads like a one-line question but hides a three-step mental tree (iron studies → cause → treatment route). "Neutropenic sepsis" is a five-word phrase that triggers an immediate antibiotic algorithm where every minute of delay matters. And the transfusion-reaction stems are some of the most heavily represented in the AKT — because spotting an ABO-incompatible reaction versus TRALI versus TACO is a safety-critical decision.

This guide is the pillar for UKMLA haematology. We cover the four discrete topic groups the GMC content map lists — anaemias, haematological malignancies, coagulation and anticoagulation, and transfusion medicine — and finish with neutropenic sepsis as the emergency everyone must land perfectly. Use it alongside our cardiology masterclass for AF anticoagulation, our respiratory guide for PE diagnosis and management, our infectious diseases guide for the overlap on sepsis and antimicrobial choice, and our prescribing safety guide for anticoagulation reversal protocols.

1. Why Haematology SBAs Punish Shallow Reading

Haematology stems are rich with numbers — MCV, platelet count, INR, reticulocyte count, LDH, haptoglobin, ferritin — and each is a pattern key. A 70 y/o with microcytic anaemia and ferritin 8 is iron deficiency until proven otherwise → colonoscopy. A 70 y/o with normocytic anaemia + rouleaux + hypercalcaemia is myeloma → electrophoresis. A 20 y/o with macrocytic anaemia + glossitis + peripheral neuropathy is B12 deficiency → intramuscular hydroxocobalamin.

The trap is the candidate who memorises "microcytic = iron" without checking ferritin, transferrin saturation, and GI investigation — and who gives oral iron to the post-gastrectomy patient who cannot absorb it.

The AKT rewards three habits in haematology: (1) read the full blood count plus reticulocytes plus film plus ferritin/B12/folate before committing, (2) treat coagulation questions as two separate clocks — thrombosis (clot risk) and haemorrhage (bleeding risk), (3) treat every febrile neutropenic patient as a medical emergency whose first antibiotic dose should have been given ten minutes before you finished reading the stem.

2. Iron-Deficiency Anaemia — Causes, Oral vs IV Iron

Iron deficiency is the most common cause of anaemia worldwide and in the UK. The MCV falls as iron stores deplete; ferritin is low (acute-phase reactant, so can mislead in inflammation — use transferrin saturation and soluble transferrin receptor if CRP elevated).

UK causes by age/sex:

• Men and postmenopausal women: GI blood loss until proven otherwise — refer urgently for OGD + colonoscopy (2WW if anaemia meets NICE NG12 criteria: men Hb <110 g/L, postmenopausal women Hb <100 g/L).
• Premenopausal women: menstrual loss first; investigate GI if heavy periods excluded or ferritin profoundly low.
• Pregnancy: physiological plus dietary — treat with oral iron from early pregnancy.
• Malabsorption: coeliac disease (anti-TTG), post-gastrectomy, IBD, bariatric surgery, H. pylori gastritis.

Management (NICE NG8/CG31):

• Oral iron first line — ferrous sulfate 200 mg OD (not TDS — recent BSH evidence shows alternate-day dosing improves absorption and reduces side effects). Warn about GI side effects, black stools, take on empty stomach with vitamin C, avoid with tea/coffee/dairy/calcium. Response: Hb should rise 20 g/L over 3–4 weeks; continue for 3 months after Hb normalises to replenish stores.
• IV iron (ferric derisomaltose, ferric carboxymaltose) if oral intolerance, malabsorption, CKD, IBD flare, or need for rapid correction. Warn about hypersensitivity; monitor during infusion.

SBA trap: anaemic post-gastrectomy patient started on oral iron with no response → switch to IV iron (malabsorption). Do not repeat the oral course.

3. B12 and Folate Deficiency — Schilling, Neurology

Both cause macrocytic megaloblastic anaemia with hypersegmented neutrophils on film. The clinical discriminator is the neurology of B12 — subacute combined degeneration of the cord (dorsal column loss, corticospinal tract signs), peripheral neuropathy, cognitive changes.

Causes of B12 deficiency:

• Pernicious anaemia — autoimmune gastric parietal cell destruction, anti-IF antibodies, anti-parietal cell antibodies. Most common UK cause.
• Dietary (vegans), post-gastrectomy, ileal disease/resection (B12 absorbed in terminal ileum), metformin (mild), PPI therapy.

Causes of folate deficiency:

• Dietary (alcohol, poor diet), malabsorption (coeliac), increased demand (pregnancy, haemolysis), drugs (methotrexate, trimethoprim, phenytoin).

Investigation: serum B12 + folate. Intrinsic factor antibodies if B12 low. If borderline, active B12 (holotranscobalamin) is more sensitive. Schilling test is historical — rarely performed now.

Management:

• B12 deficiency with neurology: hydroxocobalamin 1 mg IM alternate days until no further improvement, then 1 mg every 2 months for life (PA) or until cause resolved.
• B12 deficiency without neurology: hydroxocobalamin 1 mg IM three times a week for 2 weeks, then 1 mg every 3 months (PA).
• Folate deficiency: folic acid 5 mg OD for 4 months. Always replace B12 first if both deficient — folate alone in B12-deficient state precipitates or worsens subacute combined degeneration.

UKMLA trap: patient with macrocytic anaemia + peripheral neuropathy started on folic acid → worsening neurology → should have had B12 replaced first.

4. Haemolytic Anaemias — Classification, Coombs

Haemolysis = increased RBC destruction. Hallmarks: elevated LDH, elevated unconjugated bilirubin, low haptoglobin, reticulocytosis, urinary haemosiderin, polychromasia on film.

Coombs (direct antiglobulin test) splits into:

Coombs-positive (immune-mediated):

• Warm AIHA — IgG antibodies, splenomegaly, idiopathic / secondary to SLE, CLL, drugs (methyldopa, penicillins). Treatment: steroids ± rituximab ± splenectomy.
• Cold AIHA — IgM antibodies, acrocyanosis in cold, post-Mycoplasma pneumonia or EBV, CLL. Treatment: keep warm, treat cause, rituximab.
• Paroxysmal cold haemoglobinuria — Donath-Landsteiner antibody, post-viral in children.

Coombs-negative:

• Hereditary: spherocytosis (autosomal dominant, Heinz bodies absent, spherocytes on film, splenectomy after age 6), elliptocytosis, G6PD deficiency (X-linked, Heinz bodies, bite cells, triggered by fava beans, sulphonamides, primaquine, dapsone, moth balls, infection), pyruvate kinase deficiency.
• Haemoglobinopathies: sickle cell, thalassaemia (see below).
• Microangiopathic (MAHA): DIC, TTP, HUS, malignant hypertension, HELLP. Schistocytes on film.
• Mechanical: prosthetic heart valves.
• Paroxysmal nocturnal haemoglobinuria (PNH) — acquired, CD55/59 deficiency, complement-mediated, eculizumab treatment.

SBA trap: child with anaemia + jaundice + splenomegaly + spherocytes → hereditary spherocytosis → osmotic fragility or eosin-5-maleimide binding, not Coombs (negative).

5. Sickle Cell Disease — Crises, Management

Sickle cell is autosomal recessive mutation (β-globin Glu6Val), HbS polymerises in deoxygenated state, RBCs sickle → haemolysis + vaso-occlusion. UKMLA relevance is crisis recognition and management.

Crises:

1. Vaso-occlusive (painful) crisis — most common. Triggers: cold, dehydration, infection, hypoxia, stress. Management: analgesia within 30 minutes (opioids — morphine or diamorphine, not pethidine), hydration, oxygen if sat <95%, warmth, VTE assessment.
2. Chest crisis (acute chest syndrome) — leading cause of death. Fever, chest pain, new infiltrate on CXR. Management: O₂, analgesia, broad-spectrum antibiotics (cover atypicals), bronchodilators, exchange transfusion if severe.
3. Splenic sequestration — children; splenomegaly, shock, profound anaemia. Urgent transfusion.
4. Aplastic crisis — parvovirus B19; reticulocytopenia, deep anaemia. Transfusion.
5. Stroke — screen high-risk children with transcranial Doppler; treat with exchange transfusion + hydroxycarbamide.

Chronic management: folic acid 5 mg OD, penicillin V prophylaxis from diagnosis, immunisations (pneumococcal, Hib, meningococcal, annual influenza), hydroxycarbamide (HbF induction — reduces crises and chest syndrome), regular transfusion or exchange transfusion programmes, allogeneic stem cell transplant (potentially curative), gene therapy (approved on specialist use).

SBA trap: sickle cell patient + fever + unilateral chest pain + new CXR infiltrate — answer is acute chest syndrome, manage with exchange transfusion, not just antibiotics.

6. Thalassaemias — α vs β, Transfusion-Dependent

Thalassaemias are reduced synthesis of α or β globin chains, producing microcytic anaemia with normal or raised iron stores (distinguishing from iron deficiency).

α-thalassaemia (chromosome 16, four genes):

• 1 deletion: silent carrier.
• 2 deletions: α-thal trait — microcytosis, asymptomatic.
• 3 deletions: HbH disease — moderate haemolytic anaemia.
• 4 deletions: Hb Barts hydrops fetalis — lethal in utero.

β-thalassaemia (chromosome 11, two genes):

• Minor (heterozygous): microcytic anaemia, usually asymptomatic.
• Major (homozygous, Cooley's anaemia): transfusion-dependent from 6 months of age. Skull X-ray "hair-on-end." Iron overload from transfusions → chelation (desferrioxamine IV, deferasirox oral, deferiprone oral). Cardiac failure is leading cause of death. Consider HSCT in children.
• Intermedia: variable severity.

Diagnosis: Hb electrophoresis or HPLC. β-thal shows raised HbA2 and HbF.

UKMLA trap: microcytic anaemia + normal/raised ferritin + Mediterranean/South Asian family — think thalassaemia → Hb electrophoresis, not more iron.

7. Leukaemias Overview: ALL, AML, CLL, CML

SBA traps:

• AML with DIC + coagulopathy → acute promyelocytic leukaemia (APML, M3) → give ATRA before chemotherapy to avoid fatal DIC.
• Elderly with massive splenomegaly + lymphocytosis + smear cells → CLL.
• Middle-aged with leucocytosis, splenomegaly, Philadelphia+ → CML, start imatinib.
• Child with bone pain, tiredness, bruising, CNS features → ALL; treat with paediatric oncology protocol.

8. Lymphomas — Hodgkin vs Non-Hodgkin, Staging

Hodgkin lymphoma:

• Bimodal age distribution (20s and 60s).
• Painless cervical lymphadenopathy, alcohol-induced nodal pain (classic exam feature), B symptoms (fever, weight loss, night sweats), pruritus.
• Reed-Sternberg cells on biopsy.
• Subtypes: nodular sclerosing (most common), mixed cellularity, lymphocyte-rich, lymphocyte-depleted, nodular lymphocyte-predominant.
• Management: ABVD chemotherapy ± radiotherapy. High cure rates (>80% early stage).

Non-Hodgkin lymphoma:

• Heterogeneous group. 85% B-cell, 15% T-cell.
• Diffuse large B-cell lymphoma (DLBCL) — commonest NHL, aggressive, R-CHOP chemotherapy.
• Follicular — indolent, t(14;18), BCL-2.
• Burkitt — t(8;14), MYC, extranodal (African jaw), fastest growing human tumour, tumour lysis syndrome risk.
• MALT — H. pylori gastric lymphoma, treat with eradication therapy.
• Mantle cell — t(11;14), CCND1.

Ann Arbor staging (I–IV) + A (no B symptoms) or B (B symptoms: fever, night sweats, >10% weight loss over 6 months).

SBA traps:

• Young patient + painless cervical lymphadenopathy + pain in nodes after alcohol → Hodgkin.
• Gastric lymphoma + H. pylori positive → MALT, treat with triple therapy before chemotherapy.

9. Multiple Myeloma — CRAB, Serum Electrophoresis

Myeloma is clonal plasma cell proliferation producing monoclonal immunoglobulin (paraprotein). Median age 70.

CRAB features:

• Calcium elevated (hypercalcaemia of malignancy)
• Renal dysfunction (light-chain cast nephropathy)
• Anaemia (normocytic, rouleaux)
• Bone lesions (lytic, pathological fractures, back pain)

Investigation:

• FBC (anaemia), U&E, bone profile (Ca²⁺), CRP.
• Serum protein electrophoresis — M-band (monoclonal paraprotein).
• Serum free light chains (κ/λ ratio).
• 24-hour urine Bence-Jones protein.
• Bone marrow aspirate (>10% clonal plasma cells).
• Whole-body MRI or low-dose CT (preferred over skeletal survey per NICE NG35).

Diagnostic criteria (IMWG): >10% clonal plasma cells OR biopsy-proven plasmacytoma PLUS one or more SLiM-CRAB features (SLiM = ≥60% plasma cells, involved:uninvolved free-light-chain ratio ≥100, >1 focal MRI lesion).

Management:

• Induction chemotherapy (bortezomib + thalidomide/lenalidomide + dexamethasone — VTD/VRD).
• Autologous stem cell transplant if fit (<70, good performance status).
• Maintenance lenalidomide.
• Supportive: bisphosphonates for bone disease, radiotherapy for painful lytic lesions, VTE prophylaxis (thalidomide/lenalidomide pro-thrombotic), treat hypercalcaemia and renal failure.

SBA trap: elderly + back pain + hypercalcaemia + anaemia + raised ESR + normal CRP → myeloma until proven otherwise.

10. MGUS vs Smouldering Myeloma

MGUS (monoclonal gammopathy of undetermined significance):

• Paraprotein <30 g/L, clonal plasma cells <10%, no CRAB.
• 1% per year risk of progression to myeloma.
• Management: annual monitoring (FBC, U&E, Ca²⁺, protein electrophoresis).

Smouldering myeloma:

• Paraprotein ≥30 g/L OR clonal plasma cells 10–60%, no CRAB.
• 10% per year risk of progression in first 5 years.
• Management: 3–6 monthly monitoring; treat if high-risk features.

Active (symptomatic) myeloma: any CRAB or SLiM feature → treat.

UKMLA framing: the SBA asks you to distinguish MGUS (monitor) from myeloma (treat) based on the presence or absence of CRAB.

11. DVT / PE — Wells, D-dimer, Imaging, Anticoagulation

DVT:

• Wells score ≥2 → likely → proximal leg ultrasound. If ultrasound negative but D-dimer positive, repeat scan at 6–8 days.
• Wells <2 → unlikely → D-dimer. If negative, DVT excluded. If positive, ultrasound.
• Treatment: DOAC first-line (apixaban or rivaroxaban, no lead-in needed). LMWH for pregnancy or cancer-associated. Duration: 3 months for provoked DVT, 3–6 months with reassessment for unprovoked, lifelong for recurrent or ongoing risk.

PE:

• PE rule-out criteria (PERC) in low-risk patients can avoid D-dimer testing.
• Wells ≥4 → likely → CTPA (or V/Q if contraindicated — pregnancy, CKD).
• Wells <4 → unlikely → D-dimer. If negative, PE excluded.
• Haemodynamic instability → thrombolysis (alteplase) or embolectomy.
• Treatment: same DOAC regimens as DVT. IVC filter if anticoagulation contraindicated.

Full algorithm in our respiratory high-yield guide.

12. Anticoagulation (Warfarin + DOACs) and Reversal

Warfarin:

• Target INR: 2.5 (range 2–3) for most indications; 3.5 (range 3–4) for mechanical mitral valves and recurrent thromboembolism on warfarin.
• Slow onset (needs LMWH cover for VTE), narrow therapeutic window, multiple interactions (see prescribing safety).
• Reversal:
  • INR 5–8, no bleeding → withhold 1–2 doses, restart lower dose.
  • INR >8, no bleeding → withhold warfarin, oral vitamin K 1–5 mg.
  • Minor bleeding → withhold, IV vitamin K 1–3 mg.
  • Major bleeding → IV vitamin K 5 mg + prothrombin complex concentrate (PCC, Beriplex) 25–50 units/kg. FFP only if PCC unavailable.

DOACs:

• Apixaban, rivaroxaban (factor Xa inhibitors), dabigatran (thrombin inhibitor).
• Advantages: no INR monitoring, fewer interactions, rapid onset.
• Contraindications: severe renal impairment (variable thresholds — apixaban most forgiving), mechanical valves (warfarin only), severe hepatic impairment, pregnancy.
• Reversal:
  • Dabigatran: idarucizumab (Praxbind) — rapid, near-complete reversal.
  • Apixaban/rivaroxaban: andexanet alfa — expensive, limited availability. PCC (25–50 units/kg) remains standard in UK emergency departments.

UKMLA trap: major bleeding on apixaban → activated charcoal if recent ingestion (<2 hours) + PCC. Not FFP, not vitamin K.

13. DIC — Causes, Labs, Management

Disseminated intravascular coagulation is systemic activation of coagulation → widespread fibrin deposition + consumption of clotting factors and platelets → bleeding.

Causes:

• Sepsis (gram-negative most common)
• Obstetric (amniotic fluid embolism, placental abruption, severe pre-eclampsia/HELLP)
• Malignancy (APML M3, adenocarcinomas)
• Trauma, burns
• Snake venom

Labs:

• Prolonged PT and APTT
• Low fibrinogen
• Low platelets
• Elevated D-dimer (hallmark)
• Schistocytes on film

Management: treat the underlying cause. Supportive: FFP for coagulopathy + bleeding, platelets if <50 + bleeding, cryoprecipitate if fibrinogen <1.5 g/L. Heparin only in chronic DIC with thrombosis (e.g. Trousseau's syndrome).

14. Transfusion Reactions — Acute and Delayed

Acute (during or within 24 hours):

Delayed:

• Delayed haemolytic (5–10 days) — anamnestic response to minor antigen (Kidd, Duffy). Management: supportive.
• Transfusion-associated GvHD — rare, fatal. Prevention: irradiated components in immunocompromised, Hodgkin's, intrauterine, neonatal.
• Post-transfusion purpura (5–10 days) — anti-HPA-1a antibodies in platelet-negative recipients. IV immunoglobulin.
• Iron overload — long-term transfused (thalassaemia, SCD). Chelation.

SBA traps:

• Immediate fever + loin pain + dark urine during transfusion → ABO incompatibility → stop, supportive, investigate.
• Fluid overload picture in frail elderly after 2 units → TACO → furosemide.
• Acute breathlessness + hypoxia + bilateral infiltrates within hours of transfusion → TRALI → supportive; diuretics don't help (and may worsen hypotension).

15. Neutropenic Sepsis — Emergency Protocol

Neutropenic sepsis is fever ≥38°C (or other signs of sepsis) + neutrophils ≤0.5 ×10⁹/L (or ≤1.0 expected to fall). It is a medical emergency — mortality rises with each hour of antibiotic delay.

NICE CG151 protocol:

1. Recognise: temperature ≥38°C in a patient with neutropenia (or cancer patient within 6 weeks of chemotherapy — treat as neutropenic until proven otherwise).
2. Empirical antibiotics within 1 hour — IV piperacillin-tazobactam (Tazocin) 4.5 g before any microbiology results. Do NOT wait for cultures, do NOT wait for CXR.
3. Blood cultures (peripheral + central line if present), FBC, U&E, LFT, CRP, lactate, urinalysis, CXR, sputum/wound/stool/throat swab as clinically appropriate. Sepsis Six bundle as for any sepsis.
4. Admit under haematology/oncology with infectious diseases input as needed.
5. Review at 24–48 hours — if ongoing fever, consider adding gentamicin (if local policy), vancomycin (for line sepsis or MRSA), antifungal therapy (if persistent fever >4–5 days or specific suspicion).
6. G-CSF (filgrastim) for severe or prolonged neutropenia per local protocol.

Don't forget:

• Check for line infection (remove or lock lines per policy).
• Consider PCP in haematology patients (septrin prophylaxis standard).
• HSV/VZV in prolonged immunosuppression.
• Tumour lysis syndrome in rapidly lysing tumours.

UKMLA trap: cancer patient on day 10 post-chemo presents with shivers, fever 38.2°C, BP 90/60, HR 110 — give IV Tazocin before ordering CXR or waiting for FBC. Delayed antibiotics kill.

Cross-link: this is the same emergency covered under "neutropenic sepsis" in our infectious diseases guide and emergency presentations masterclass.

The UKMLA Haematology Pattern Library

Twelve stems worth owning:

1. Microcytic anaemia + low ferritin, 70 y/o man → iron deficiency → urgent 2WW OGD + colonoscopy.
2. Macrocytic anaemia + peripheral neuropathy + glossitis → B12 deficiency → IM hydroxocobalamin (replace B12 before folate).
3. Sickle cell + new infiltrate + chest pain → acute chest syndrome → exchange transfusion + antibiotics.
4. Microcytic anaemia + normal ferritin + Mediterranean family → thalassaemia → Hb electrophoresis.
5. Elderly + massive splenomegaly + lymphocytosis + smear cells → CLL → watch-and-wait or BTK inhibitor.
6. Middle-aged + basophilia + Philadelphia chromosome → CML → imatinib.
7. Cervical lymphadenopathy + alcohol-induced node pain → Hodgkin → biopsy for Reed-Sternberg.
8. Elderly + back pain + hypercalcaemia + rouleaux + normal CRP → myeloma → electrophoresis + whole-body MRI.
9. Major bleeding on apixaban → PCC 25–50 units/kg (andexanet if available).
10. Warfarin INR 9 with no bleeding → withhold + oral vitamin K 1–5 mg.
11. Loin pain + haemoglobinuria during transfusion → ABO incompatibility → stop, resuscitate, report.
12. Febrile + neutropenia day 10 post-chemo → IV Tazocin within 1 hour, blood cultures simultaneously.

Putting It All Together

Haematology rewards readers who hold four separate mental maps in parallel: the anaemia map (micro/normo/macrocytic with reticulocyte and haemolysis overlays), the malignancy map (cell line + cytogenetics + characteristic clinical feature + treatment), the coagulation map (bleeding versus clotting; warfarin versus DOAC; reversal agents), and the transfusion map (timing of reaction versus mechanism). Each map is a short hierarchy you can render in seconds.

Pair this pillar with the cardiology masterclass for AF stroke prevention and anticoagulation decision trees, our respiratory guide for PE pathways, the infectious diseases guide for neutropenic sepsis and sepsis bundles, and prescribing safety for warfarin and DOAC reversal. Emergency presentations are collected in the emergency presentations masterclass.

If a haematology stem reads smoothly on the first pass — the numbers line up with one of the twelve patterns above — trust the match and move on. If the numbers conflict (low ferritin but also high CRP, microcytic but normal Fe studies), pause and re-read: haematology stems are built around the conflict. Ready to practice? Start with an MLA Prep haematology mini-mock and see which patterns you close on the first read.