Membership of the Royal College of Physicians (MRCP UK) Haematology and Oncology Syllabus

What is Waldenström macroglobulinaemia and its characteristic complication?

A lymphoplasmacytic lymphoma producing a monoclonal IgM paraprotein. The large IgM causes hyperviscosity syndrome (visual disturbance, headache, confusion, mucosal bleeding). Treated acutely with plasmapheresis. Unlike myeloma it does NOT typically cause lytic bone lesions.

List the BCR-ABL-negative myeloproliferative neoplasms and the mutation common to them.

Polycythaemia vera, essential thrombocythaemia, and primary myelofibrosis. The JAK2 V617F mutation is found in nearly all polycythaemia vera and around half of ET and myelofibrosis cases. They share a risk of thrombosis and transformation to AML.

What are the diagnostic clues to polycythaemia vera versus secondary polycythaemia?

Polycythaemia vera: raised haematocrit, JAK2 mutation, LOW erythropoietin, splenomegaly, aquagenic pruritus, raised WCC/platelets. Secondary polycythaemia: HIGH erythropoietin (hypoxia, EPO-secreting tumour). Management of PV: venesection to keep haematocrit $<0.45$, aspirin, and hydroxycarbamide.

What characterises myelodysplastic syndromes and what is the main risk?

MDS is a clonal stem-cell disorder with ineffective haematopoiesis causing cytopenias with a hypercellular dysplastic marrow ($<20\%$ blasts). Film shows dysplasia (e.g. Pelger-Huet cells, ring sideroblasts). The main risk is transformation to AML; prognosis is graded by the IPSS-R score.

Contrast haemophilia A and B, including inheritance and the clotting screen.

Both are X-linked recessive. Haemophilia A = factor VIII deficiency; haemophilia B (Christmas disease) = factor IX deficiency. Both cause prolonged APTT with normal PT, normal platelets, and normal bleeding time. Clinically: haemarthroses and deep muscle bleeds. Treated with factor replacement.

What is von Willebrand disease and how does its bleeding pattern and lab profile differ from haemophilia?

The commonest inherited bleeding disorder, usually autosomal dominant deficiency of von Willebrand factor (which mediates platelet adhesion and carries factor VIII). Causes mucocutaneous bleeding (epistaxis, menorrhagia), prolonged bleeding time/PFA and APTT, with a normal PT and platelet count. Treated with desmopressin (DDAVP) or vWF concentrate.

What is immune thrombocytopenic purpura (ITP) and how is it managed?

Autoimmune destruction of platelets by antiplatelet antibodies, causing isolated thrombocytopenia with otherwise normal blood counts and a normal/increased megakaryocyte marrow. Presents with petechiae, purpura, and mucosal bleeding. First-line treatment: corticosteroids $\pm$ IV immunoglobulin; severe bleeding may need platelets.

What is the classic pentad of thrombotic thrombocytopenic purpura (TTP) and its cause?

Pentad: microangiopathic haemolytic anaemia, thrombocytopenia, neurological signs, renal impairment, and fever. Caused by deficiency of ADAMTS13 (which cleaves vWF multimers). Treatment is urgent plasma exchange; platelet transfusion is contraindicated. Film shows schistocytes.

Describe the laboratory findings in disseminated intravascular coagulation (DIC).

Consumption of clotting factors and platelets: prolonged PT and APTT, low fibrinogen, low platelets, and raised D-dimer/fibrin degradation products. Film shows schistocytes (microangiopathic haemolysis). It is always secondary — treat the underlying cause and support with FFP, cryoprecipitate, and platelets.

List common triggers of DIC.

Sepsis (especially Gram-negative), major trauma, obstetric emergencies (amniotic fluid embolism, placental abruption, pre-eclampsia), malignancy (especially APML and adenocarcinomas), severe burns, and massive haemolytic transfusion reactions. DIC reflects systemic activation of coagulation.

List the inherited thrombophilias and the commonest one.

Factor V Leiden (commonest — causes activated protein C resistance), prothrombin G20210A mutation, and deficiencies of protein C, protein S, and antithrombin III. They increase venous thromboembolism risk. Antithrombin deficiency causes heparin resistance.

What is antiphospholipid syndrome and its key associations?

An acquired thrombophilia with antibodies (lupus anticoagulant, anticardiolipin, anti-$\beta_2$-glycoprotein I) causing arterial and venous thrombosis and recurrent miscarriage. Paradoxically prolongs APTT in vitro but is prothrombotic in vivo. May cause thrombocytopenia; associated with SLE. Treated with lifelong warfarin.

What is the well-established two-level Wells score used for, and what does a positive D-dimer add?

The Wells score risk-stratifies probability of DVT or pulmonary embolism. If the score makes VTE likely, proceed to imaging (Doppler ultrasound for DVT, CTPA for PE). If unlikely, a negative D-dimer excludes VTE; D-dimer is sensitive but not specific (raised in infection, malignancy, pregnancy).

What is the mechanism and laboratory monitoring of unfractionated heparin versus low-molecular-weight heparin?

Both potentiate antithrombin III. Unfractionated heparin inhibits thrombin (IIa) and Xa, monitored by APTT, reversed by protamine. LMWH (e.g. enoxaparin) preferentially inhibits factor Xa, given subcutaneously with predictable dosing, monitored by anti-Xa levels only if needed (renal failure, pregnancy).

What is heparin-induced thrombocytopenia (HIT), its timing, and its paradoxical risk?

An immune reaction (antibodies to platelet factor 4-heparin complexes) typically arising 5–10 days after starting heparin, causing a $>50\%$ fall in platelets. Despite thrombocytopenia it causes THROMBOSIS, not bleeding. Stop all heparin and anticoagulate with a non-heparin agent (e.g. argatroban, fondaparinux).

Compare the mechanism and reversal of warfarin and the DOACs.

Warfarin inhibits vitamin K epoxide reductase, reducing factors II, VII, IX, X (and proteins C and S), monitored by INR, reversed by vitamin K and prothrombin complex concentrate. DOACs: dabigatran (direct thrombin inhibitor, reversed by idarucizumab); apixaban/rivaroxaban/edoxaban (factor Xa inhibitors, reversed by andexanet alfa).

Why must warfarin be co-covered with heparin when initiated in a thrombotic state?

Warfarin initially lowers proteins C and S (short half-lives) faster than the procoagulant factors, creating a transient prothrombotic state that can cause warfarin-induced skin necrosis. Therefore overlap with heparin/LMWH until the INR is therapeutic for at least 2 days.

Compare the mechanisms of aspirin, clopidogrel, and the GPIIb/IIIa inhibitors.

Aspirin irreversibly inhibits cyclo-oxygenase (COX-1), reducing thromboxane $A_2$. Clopidogrel/prasugrel/ticagrelor block the platelet $\text{P2Y}_{12}$ ADP receptor. GPIIb/IIIa inhibitors (abciximab, tirofiban) block the final common pathway of platelet aggregation (fibrinogen cross-linking).

What does TNM staging denote, and how do staging and grading differ?

TNM: T = size/extent of primary Tumour, N = regional lymph Node involvement, M = distant Metastasis. Staging describes anatomical spread of the cancer; grading describes the histological differentiation/aggressiveness of the tumour cells. Both guide prognosis and treatment.

Define neoadjuvant and adjuvant therapy.

Neoadjuvant therapy is given BEFORE the primary (usually surgical) treatment to shrink the tumour and improve resectability. Adjuvant therapy is given AFTER the primary treatment to eradicate micrometastatic disease and reduce recurrence risk.

What are the features and emergency management of neutropenic sepsis?

Temperature $>38^{\circ}\text{C}$ (or signs of sepsis) with neutrophils $<0.5\times10^{9}/\text{L}$, usually within weeks of chemotherapy. It is a medical emergency: take cultures and give empirical broad-spectrum IV antibiotics (e.g. piperacillin-tazobactam) within 1 hour, without waiting for results.

What are the features and management of malignant spinal cord compression?

Back pain (often worse on lying/coughing), limb weakness, sensory level, and bladder/bowel dysfunction. It is an oncological emergency. Give high-dose dexamethasone immediately, arrange urgent whole-spine MRI within 24 hours, and refer for radiotherapy or surgical decompression.

What is tumour lysis syndrome, its biochemical hallmarks, and its prevention?

Massive tumour cell breakdown (often after chemotherapy of bulky/high-turnover tumours) releasing intracellular contents: HIGH potassium, HIGH phosphate, HIGH urate, and LOW calcium, causing acute kidney injury and arrhythmias. Prevented with IV hydration and rasburicase (or allopurinol in lower risk).

What are the features and emergency treatment of malignant hypercalcaemia?

"Stones, bones, groans, moans": polyuria, thirst, constipation, confusion, and abdominal pain. Usually due to PTHrP secretion or bone metastases. Treatment: aggressive IV $0.9\%$ saline rehydration first, followed by IV bisphosphonate (e.g. zoledronate) to inhibit osteoclasts.

What is superior vena cava obstruction, its commonest cause, and its management?

Compression of the SVC causing facial/upper-limb swelling, distended neck veins, dyspnoea, and Pemberton's sign. Commonest cause is lung cancer (or lymphoma). Management: assess airway, corticosteroids, and urgent endovascular stenting; radiotherapy/chemotherapy depending on tumour type.

How is cancer of unknown primary (CUP) defined and approached?

Histologically confirmed metastatic malignancy with no identifiable primary after standard investigation. Work-up: history/examination, CT chest-abdomen-pelvis, tumour markers, and immunohistochemistry to identify treatable subtypes (e.g. germ cell, lymphoma, breast, prostate). Treatment is tailored to likely tissue of origin or given as empirical chemotherapy.

Which tumour markers point to potentially treatable causes within cancer of unknown primary?

Raised AFP and/or beta-hCG suggest germ cell tumour (potentially curable); PSA suggests prostate (hormone-responsive); CA-125 suggests ovarian; immunohistochemistry such as TTF-1 (lung/thyroid), CK7/CK20 patterns, and oestrogen receptor (breast) help localise origin.

What are the WHO analgesic ladder steps for cancer pain?

Step 1: non-opioid (paracetamol $\pm$ NSAID). Step 2: weak opioid (e.g. codeine) plus non-opioid. Step 3: strong opioid (e.g. morphine) plus non-opioid. Adjuvants (e.g. amitriptyline, gabapentin for neuropathic pain; bisphosphonates for bone pain) may be added at any step.

When converting oral morphine to subcutaneous morphine and to diamorphine, what conversion factors are used?

Oral to subcutaneous morphine: divide by 2. Oral morphine to subcutaneous diamorphine: divide by 3. The breakthrough (PRN) dose is approximately $\frac{1}{6}$ of the total 24-hour dose. Always prescribe a regular laxative and an as-needed antiemetic with opioids.

What medications are typically prescribed for symptom control at the end of life (anticipatory "just in case" drugs)?

Subcutaneous PRN drugs: an opioid (e.g. morphine) for pain/breathlessness, an antiemetic (e.g. levomepromazine, haloperidol, cyclizine), an anxiolytic/sedative (midazolam) for agitation, and an antisecretory (hyoscine butylbromide or glycopyrronium) for respiratory secretions/"death rattle".

List the ABO and Rh compatibility rules for red cell transfusion, including the universal donor and recipient.

Group O red cells are the universal donor (no A/B antigens); group AB is the universal recipient (no anti-A/anti-B). RhD-negative females of childbearing potential must receive RhD-negative blood to avoid anti-D sensitisation. ABO incompatibility causes acute intravascular haemolysis.

Distinguish an acute haemolytic transfusion reaction from a febrile non-haemolytic reaction.

Acute haemolytic (ABO incompatibility) reaction: fever, loin/back pain, hypotension, haemoglobinuria, DIC within minutes — STOP transfusion immediately, resuscitate, return blood. Febrile non-haemolytic reaction: isolated fever/chills from cytokines/anti-leucocyte antibodies — slow/stop transfusion, give paracetamol; it is benign.

Compare TACO and TRALI as causes of transfusion-related breathlessness.

TACO (transfusion-associated circulatory overload): hypertension, raised JVP, pulmonary oedema from volume overload; treat with oxygen and diuretics. TRALI (transfusion-related acute lung injury): non-cardiogenic pulmonary oedema with hypotension within 6 hours, caused by donor anti-leucocyte antibodies; supportive/ventilatory care, normal JVP.