Anticoagulation and Antiplatelet Therapy (Physician-Managed)

The answer first

Antithrombotic prescribing is risk arbitration, not drug selection — every decision trades a thrombotic risk you can quantify against a bleeding risk you can modify, and the examiner wants to hear you do the arithmetic aloud. Four rules carry almost every DWE question and every consultant viva [9]:

1. DOACs are the default for atrial fibrillation and for VTE. Across RE-LY, ROCKET AF, ARISTOTLE and ENGAGE AF, the direct oral anticoagulants were non-inferior or superior to warfarin for stroke prevention with roughly half the intracranial haemorrhage — warfarin survives only where DOACs have no evidence or proven harm [1] [2] [3] [4].
2. Warfarin still owns three territories: mechanical heart valves (DOACs are contraindicated — RE-ALIGN), moderate-to-severe rheumatic mitral stenosis, and antiphospholipid syndrome; plus patients whose renal failure puts them below DOAC thresholds [5].
3. Reversal and perioperative management are protocols, not improvisations. Know the antidotes (vitamin K plus PCC, idarucizumab, andexanet alfa, protamine), know that bridging is dead for most AF patients (BRIDGE), and know that device surgery is done ON warfarin (BRUISE CONTROL) [15] [16] [18] [19].
4. Antiplatelets are secondary-prevention drugs. Aspirin has no default role in primary prevention (ASPREE, ASCEND, ARRIVE); DAPT duration after stenting is a bleeding-versus-thrombosis decision; and after PCI in an anticoagulated AF patient, the winning regimen is the shortest one — triple therapy measured in days, not months (AUGUSTUS, PIONEER AF-PCI) [26] [29].

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The agents and their targets

Every antithrombotic question reduces to two pathways: the coagulation cascade (target of warfarin, heparins and DOACs) and platelet activation (target of aspirin, P2Y12 inhibitors and GPIIb/IIIa antagonists). Arterial thrombosis — stroke, myocardial infarction, stent thrombosis — is platelet-driven, which is why antiplatelets dominate there; venous thrombosis and AF-related cardioembolism are fibrin-driven, which is why anticoagulants dominate there. The crossover mistake — aspirin for AF stroke prevention, or warfarin alone for a stent — fails both the biology and the exam [21] [34].

Warfarin — the drug with a century of baggage

Warfarin inhibits VKORC1, blocking regeneration of reduced vitamin K and so depleting functional factors II, VII, IX and X (plus proteins C and S). Three properties explain its entire clinical behaviour [17]:

• Narrow therapeutic window, monitored by INR. Target 2.0–3.0 for AF, VTE and most mechanical aortic valves; some mechanical mitral valves target 2.5–3.5. Quality is measured as time in therapeutic range — below about 65–70% TTR, the case for a DOAC (if the indication permits) strengthens.
• Interactions everywhere. Amiodarone, macrolides, azole antifungals, sulfonamides and metronidazole all raise the INR; rifampicin, carbamazepine and St John's Wort lower it. The exam answer is not to memorise forty drugs but to say: any new prescription or antibiotic course in a warfarin patient triggers an INR check within 3–5 days [17].
• Diet is about consistency, not prohibition. Vitamin K–rich foods (leafy greens) antagonise warfarin; the advice is a stable intake, not avoidance, plus honest limits on alcohol [17].

Warfarin's slow offset (days, not hours) is why acute VTE treatment starts with a parenteral overlap — and why, in HIT, warfarin alone early can precipitate limb gangrene: proteins C and S fall before factor II does, briefly worsening thrombosis [32].

The DOACs — one target each, no monitoring, renal rules

The four DOACs share three features that changed practice: fixed dosing without routine monitoring, rapid onset and offset, and renal clearance that must be respected. The pivotal AF trials are the spine of the evidence [1] [2] [3] [4]:

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Indications — who gets anticoagulated

Atrial fibrillation. Stroke prevention in AF is risk-stratified prescribing: CHA₂DS₂-VASc estimates annual stroke risk, HAS-BLED flags modifiable bleeding factors, and a DOAC is the default agent unless a warfarin-only indication exists [34] [35]. The full discussion — thresholds, rhythm versus rate, valvular versus non-valvular — lives in the atrial fibrillation topic; what this topic owns is the drug logic above and everything below.

Venous thromboembolism. The EINSTEIN, AMPLIFY and Hokusai-VTE trials established DOACs as first-line VTE treatment, non-inferior to the traditional heparin-to-warfarin bridge with less major bleeding [6] [7] [8]. Apixaban and rivaroxaban are started directly at treatment intensity (apixaban 10 mg twice daily for 7 days then 5 mg twice daily; rivaroxaban 15 mg twice daily for 21 days then 20 mg daily); edoxaban and dabigatran require at least 5 days of parenteral anticoagulation first [7] [8]. Diagnostic strategy, Wells scoring and thrombolysis decisions are the pulmonary embolism and thrombophilia/VTE topics' business — the duration question below is yours.

Mechanical valves — warfarin, full stop. RE-ALIGN randomised mechanical valve patients to dabigatran versus warfarin and was stopped early: dabigatran produced more thromboembolism AND more bleeding — a rare double loss that killed the hypothesis for the whole class [5]. Mechanical valves need warfarin with valve-specific INR targets (2.0–3.0 for most modern bileaflet aortic valves, 2.5–3.5 for mitral and higher-risk valves) plus low-dose aspirin in some practices. The same warfarin-only logic extends to moderate-to-severe rheumatic mitral stenosis with AF and to antiphospholipid syndrome (especially triple-positive or arterial events), where DOACs underperform [5].

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VTE duration — the 3-month fork

Duration is where VTE management earns its physician stripes. The CHEST framework (2016, updated 2021) divides treatment into the initial 3 months — during which everyone is anticoagulated — and then a decision at the 3-month fork driven by why the clot happened [9] [10]:

For extended therapy, full-dose is not the only option. AMPLIFY-EXT showed apixaban 2.5 mg twice daily prevents recurrence as well as 5 mg with less bleeding, and EINSTEIN CHOICE showed rivaroxaban 10 mg daily (and 20 mg) beat aspirin for extended prophylaxis without excess major bleeding — aspirin has no role in VTE secondary prevention [11] [12].

Occult malignancy in unprovoked VTE. An unprovoked clot in a patient over 50 carries a real — but modest — risk of occult cancer, and the physician's response is targeted, not a reflex total-body CT. The defensible workup: thorough history (weight loss, change in bowel habit, haemoptysis, night sweats), full examination including breast, prostate and rectal, FBC, chemistry, calcium, urinalysis, chest imaging, and completion of age-appropriate screening programmes. Extensive screening beyond that finds little and harms through incidentalomas [9].

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Antiplatelet therapy — aspirin and the P2Y12 family

Aspirin irreversibly acetylates platelet COX-1, abolishing thromboxane A₂ production for the platelet's 7–10 day lifespan. Its modern role is precise: secondary prevention of established atherosclerotic disease (prior MI, ischaemic stroke, symptomatic PAD) and partner duty in DAPT — and almost nothing else [21].

Primary prevention is dead. Three 2018 trials closed the case. ARRIVE (moderate-risk adults) found no reduction in vascular events with aspirin. ASCEND (diabetes) found a small vascular benefit exactly offset by major bleeding. ASPREE (healthy people over 70) found no benefit in disability-free survival or cardiovascular events, more major haemorrhage, and a troubling all-cause mortality signal — so routine aspirin in healthy elderly patients is now an exam error, not an exam answer [26] [25] [27].

The P2Y12 inhibitors block the platelet ADP receptor that amplifies activation [22]:

DAPT duration after PCI. The default after ACS with stenting is 12 months of aspirin plus a P2Y12 inhibitor — the era defined by CURE and confirmed through the drug-eluting stent trials [21]. The DAPT trial then showed that extending to 30 months reduces stent thrombosis and MI at the cost of more bleeding and a mortality signal — so duration is individualised: shorter (3–6 months) when bleeding risk dominates, longer when ischaemic risk dominates and bleeding has been clean [24].

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Reversal — the antidotes, cold

Reversal is for life-threatening bleeding, critical-site bleeding (intracranial, pericardial, retroperitoneal), or urgent surgery that cannot wait — not for a high INR, a nosebleed, or reassurance. The first moves are agent-agnostic: stop the drug, establish when the last dose was taken, check renal function (it determines how long the drug will linger), apply local haemostatic measures, and resuscitate. Then match the antidote [15] [16]:

Resuming after a major bleed is the mark of a physician answer. AF stroke risk and VTE recurrence risk persist after haemostasis. The framework: treat the bleeding source definitively (endoscopic therapy, surgery, embolisation), wait until haemostasis is secure — typically days to two weeks for GI bleeding, longer after intracranial haemorrhage with neurology input — then restart, and document the shared decision with the patient [10].

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Perioperative management — protocols, not improvisation

The elective-surgery questions collapse into four facts, each backed by a named trial [18] [19] [20]:

[18] [19] [20]

Bridging is dead for most AF patients. BRIDGE randomised warfarin-treated AF patients undergoing procedures to LMWH bridging versus placebo interruption: no difference in thromboembolism, significantly more major bleeding with bridging [18]. The residual candidates for bridging are the exceptions the examiner wants named: mechanical mitral valves, stroke/TIA or VTE within the last 3 months, and very high-risk mechanical valve anatomy — decisions made with haematology, not habit [18].

Device surgery is the mirror image. BRUISE CONTROL showed that pacemaker/ICD surgery on continued warfarin caused markedly less pocket haematoma than interrupting warfarin and bridging with heparin — the bridging, not the warfarin, was the bleeding problem [19]. Most DOAC device cases are done with brief interruption or continuation depending on operator and bleeding risk.

DOAC interruption is clock arithmetic. PAUSE validated the simple schedule: skip doses to create about 1 day (low-bleed-risk) or 2 days (high-bleed-risk) between last dose and procedure — longer for dabigatran in renal impairment — with no bridging and low measured residual drug levels; neuraxial anaesthesia and very high-bleed-risk surgery extend interruption to about 48–72 hours [20].

Urgent surgery on a DOAC flips to the reversal logic above: delay 12–24 hours if the surgery allows (renal function dictates drug persistence), consider antidote for truly emergent high-bleed-risk surgery (idarucizumab for dabigatran; andexanet or PCC for Xa agents) [15] [16].

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Heparin-induced thrombocytopenia — the thrombosis that looks like a side effect

HIT is an immune catastrophe: IgG against platelet factor 4–heparin complexes activates platelets, producing thrombosis with a falling platelet count — classically a 50% platelet fall beginning 5–10 days into heparin exposure (within 24 hours if prior exposure in the last ~100 days). Half the patients present WITH a thrombotic event; the platelet count often never reaches the classic "thrombocytopenia" ranges [31].

Score with the 4Ts before touching the lab: Thrombocytopenia magnitude, Timing, Thrombosis, and oTher causes. A low score (0–3) effectively excludes HIT; intermediate/high scores mandate action before confirmatory testing — immunoassay (sensitive, over-called) then functional assay (serotonin release, specific) [31] [32].

[32]

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Cancer-associated VTE — the DOAC era

Cancer shifts every part of the VTE calculus: higher recurrence, higher bleeding, drug interactions, thrombocytopenia from chemotherapy, and a treatment duration that runs while the cancer is active. For two decades the answer was LMWH (dalteparin) over warfarin; the modern trials have moved the default to DOACs [13] [14].

The prescribing synthesis: a DOAC (usually apixaban) for most cancer-associated VTE; LMWH retained for GI/GU luminal tumours with mucosal bleeding, significant drug–drug interactions with chemotherapy, severe thrombocytopenia (below about 50 × 10⁹/L — use half-dose or hold strategies), or malabsorption concerns; warfarin only when neither is feasible. Duration is at least 6 months and continues while cancer is active or treatment ongoing, reassessed periodically [10] [13].

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Special populations — where physicians earn the fee

The elderly patient who falls. The falls objection is the most common reason anticoagulation is wrongly withheld, and the arithmetic refutes it. Man-Son-Hing's classic analysis found an AF patient would need to fall hundreds of times per year before the subdural haemorrhage risk from falls offset the stroke prevention benefit of warfarin — and DOACs, with their halved intracranial bleeding, only widen the margin [33]. The consultant response is not "stop the anticoagulant" but "treat the falls": review sedation and orthostatic drugs, correct vision, manage postural hypotension, strength-and-balance referral, and choose the agent with the best intracranial safety profile (apixaban) [3] [33]. The falls and syncope topic owns the falls workup; this topic owns the refusal to let falls veto stroke prevention.

Chronic kidney disease. Renal function is the DOAC gatekeeper, measured as creatinine clearance by Cockcroft–Gault (the trial metric), not eGFR. The practical ladder: apixaban retains evidence furthest down the GFR range (usable to CrCl 15–25); rivaroxaban and edoxaban need dose reduction in the 15–50 band; dabigatran — 80% renally cleared — is avoided once CrCl drops below 30; below the DOAC floor (CrCl under 15, dialysis), warfarin remains the default while acknowledging its own vascular-calcification concerns and the thin evidence in dialysis patients [2] [3] [4]. Whatever the agent, renal function is rechecked at least annually, more often in the elderly and the fluctuating.

The multimorbidity patient. Frailty, polypharmacy, intermittent NSAID use, antiplatelet co-prescription, and recurrent hospitalisation each multiply bleeding risk. The physician moves: strip interacting drugs, avoid "triple" combinations without a current indication, add PPI gastroprotection when combined antithrombotic therapy is genuinely required, choose the DOAC with the mildest bleeding profile, dose-reduce by the label criteria (not by instinct), and schedule the review — bleeding risk is re-scored, not assumed static [3] [35].

Pregnancy, briefly. Warfarin is embryopathic (first-trimester exposure) and DOACs are contraindicated — anticoagulation in pregnancy is LMWH, and the detailed management belongs to obstetric medicine. The physician's duty is the pre-pregnancy conversation for every woman of childbearing potential on long-term anticoagulation [9].

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Triple therapy after PCI in AF — shortest wins

The patient with AF who gets a stent concentrates three risks — stroke, stent thrombosis, and bleeding — into one prescription. Triple therapy (anticoagulant + aspirin + P2Y12 inhibitor) suppresses the first two and maximises the third. Three trials rebuilt the strategy around double therapy with the earliest possible aspirin exit [28] [29] [30]:

The working protocol: triple therapy only for the periprocedural window (up to about a week, rarely 30 days in very high ischaemic risk), then an anticoagulant plus a single P2Y12 inhibitor (clopidogrel — not prasugrel or ticagrelor, which were minimally studied here) to 12 months, then the anticoagulant alone [29] [30]. The exam trap is reflexly prescribing a year of triple therapy "because he has a stent AND AF".

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The DCE long case — anticoagulation in multimorbidity

The archetypal long case is the 82-year-old with AF, CKD (CrCl 38), recurrent falls, a GI bleed last year, and apixaban stopped by a well-meaning locum. The examiner's interest is never the drug list — it is the reasoning chain: quantify the stroke risk (CHA₂DS₂-VASc), quantify and modify the bleeding risk (HAS-BLED points you to fixable items — uncontrolled BP, interacting drugs, labile behaviour), choose the agent on renal and bleeding pharmacology, then defend the choice against each objection the family raises [34] [35].

The viva answer that distinguishes a physician: "The falls do not change the answer — the stroke risk dominates the arithmetic — but they change the work. I address the falls themselves, I pick the anticoagulant with the lowest intracranial bleeding rate, I check renal function on schedule, and I revisit the decision after every bleed rather than letting one event silently retire the drug" [33]. The second distinguishing move is anticipating the scenarios: what happens to this regimen at surgery, at a future bleed, if the creatinine worsens, if he develops cancer.

Short-case angles. The AF examination (irregularly irregular pulse, rate control, signs of valve disease, thyroid status, heart failure) ends in an anticoagulation discussion — so examine with the decision in mind: a mechanical valve click or a mitral stenosis murmur changes the drug answer completely. The pre-procedure short case tests the perioperative protocol above. The bleeding short case tests reversal and resumption logic [5] [18].

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Exam traps, collected

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