Antiplatelets

Foundations and mechanisms

Platelet biology and thrombus formation

Antiplatelet drugs act on primary haemostasis, particularly arterial thrombosis where high shear favours platelet adhesion, activation and aggregation over fibrin-rich coagulation. Normal platelet count is approximately 150–400 × 10⁹/L; platelet lifespan is 7–10 days, with daily replacement of about 10–15%. Clinically relevant recovery after irreversible inhibition therefore depends on marrow production rather than plasma drug clearance.

Vascular injury exposes subendothelial collagen and von Willebrand factor. Platelet adhesion is mediated predominantly by GPIb-IX-V binding to vWF, with collagen engagement via GPVI and α₂β₁. Activation then amplifies through thromboxane A₂, ADP, thrombin, adrenaline and intracellular calcium mobilisation. Final common pathway aggregation occurs when activated GPIIb/IIIa receptors bind fibrinogen and vWF, cross-linking adjacent platelets.

Pharmacological targets

Class	Principal target	Effect on platelet function	Key pharmacological feature
Aspirin	COX-1 inhibition	↓ thromboxane A2 synthesis	Irreversible; effect lasts platelet lifespan
P2Y12 inhibitors	ADP receptor blockade	↓ GPIIb/IIIa activation and aggregation	Irreversible thienopyridines; reversible ticagrelor/cangrelor
GPIIb/IIIa inhibitors	Final common aggregation receptor	Prevents fibrinogen-mediated platelet cross-linking	Potent parenteral agents used mainly in PCI
PDE inhibitors	PDE3 and/or adenosine uptake	↑ platelet cAMP; ↓ activation	Dipyridamole and cilostazol; vasodilator properties
PAR-1 antagonist	Thrombin receptor PAR-1	↓ thrombin-induced platelet activation	Vorapaxar; prolonged offset and bleeding liability

Arachidonic acid pathway and aspirin

Aspirin acetylates serine 529 of platelet cyclo-oxygenase-1, irreversibly preventing conversion of arachidonic acid to prostaglandin H₂ and therefore thromboxane A₂, a potent vasoconstrictor and platelet agonist. Platelets cannot resynthesise COX-1 because they are anucleate. Low-dose aspirin preferentially inhibits platelet COX-1 in the portal circulation before systemic dilution; typical antiplatelet maintenance dosing is 75–100 mg orally once daily in UK/European practice, with loading doses of 150–300 mg orally or 250–500 mg IV in acute coronary syndromes. Plasma half-life is short, approximately 15–20 minutes, but pharmacodynamic effect persists for days.

Meta-analysis by the Antithrombotic Trialists’ Collaboration demonstrated approximately 22% proportional reduction in serious vascular events in high-risk patients, establishing aspirin as foundational secondary prevention. In primary prevention, benefit is smaller and offset by major bleeding; contemporary guidelines are more restrictive.

ADP-P2Y₁₂ signalling

ADP activates P2Y₁ and P2Y₁₂ receptors; sustained aggregation depends on P2Y₁₂-mediated Gi signalling, inhibition of adenylate cyclase, reduced cAMP and increased GPIIb/IIIa expression. P2Y₁₂ inhibitors are central to dual antiplatelet therapy after acute coronary syndrome and coronary stenting.

Drug	Usual loading / maintenance dose	Reversibility	Onset and offset	Important science
Clopidogrel	300–600 mg load; 75 mg daily	Irreversible	Maximal effect 4–24 h depending on load; recovery 5–7 days	Prodrug; CYP2C19-dependent; reduced response with loss-of-function alleles
Prasugrel	60 mg load; 10 mg daily, or 5 mg if <60 kg/elderly selected	Irreversible	Rapid, potent; recovery 7 days	Contraindicated after previous stroke/TIA; caution age ≥75 years or weight <60 kg
Ticagrelor	180 mg load; 90 mg twice daily	Reversible	Onset 30–60 min; functional recovery 3–5 days	Non-prodrug; increases adenosine; dyspnoea and bradyarrhythmia recognised
Cangrelor	30 microgram/kg IV bolus then 4 microgram/kg/min infusion	Reversible	Immediate; half-life 3–6 min; recovery within 60 min	Useful when oral absorption is impossible or very rapid offset is required

Landmark comparative data include CAPRIE, showing an 8.7% relative risk reduction in ischaemic stroke, myocardial infarction or vascular death with clopidogrel versus aspirin; CURE, demonstrating benefit of aspirin plus clopidogrel in non-ST elevation ACS; TRITON-TIMI 38, showing prasugrel superiority over clopidogrel with increased major bleeding; and PLATO, showing ticagrelor superiority over clopidogrel in ACS, including mortality reduction.

Final common pathway and adjunctive agents

GPIIb/IIIa antagonists block the final receptor-mediated aggregation step. Abciximab is a monoclonal antibody fragment with prolonged platelet-bound effect; eptifibatide and tirofiban are shorter-acting small molecules requiring renal dose adjustment. They may reduce periprocedural ischaemic complications during high-risk PCI but substantially increase bleeding, particularly when combined with anticoagulants.

Dipyridamole inhibits phosphodiesterase and adenosine uptake, increasing platelet cAMP and causing vasodilatation; modified-release dosing is commonly 200 mg twice daily, often with aspirin after ischaemic stroke or TIA. Cilostazol, a PDE3 inhibitor dosed 100 mg twice daily, is used for intermittent claudication and selected cerebrovascular indications but is avoided in heart failure. Vorapaxar antagonises thrombin PAR-1 signalling; its long half-life of about 8 days and excess intracranial bleeding risk limit use, particularly after prior stroke.

Clinical assessment and investigations

Clinical assessment: defining antiplatelet exposure and competing risks

Assessment of a patient receiving antiplatelet therapy is fundamentally a balance between haemorrhagic risk from platelet inhibition and thrombotic risk from interruption. For anaesthetic and perioperative practice, the history must identify the exact agent, dose, formulation, timing of the last dose, indication, coronary anatomy/intervention history, and whether therapy is single or dual antiplatelet therapy.

Drug/class	Usual dose	Platelet effect	Functional recovery after cessation	Key assessment point
Aspirin; irreversible COX-1 inhibitor	75–300 mg daily	Irreversible inhibition of thromboxane A2	Approximately 7–10 days for full platelet turnover; partial recovery 3–5 days	Usually continued perioperatively except selected closed-space surgery
Clopidogrel; irreversible P2Y12 antagonist	75 mg daily; loading 300–600 mg	Variable inhibition due to CYP2C19 activation	5–7 days	Non-response and CYP2C19 loss-of-function alleles are clinically relevant after PCI
Prasugrel; irreversible P2Y12 antagonist	10 mg daily; loading 60 mg	Potent, consistent platelet inhibition	7–10 days	Higher bleeding risk; avoid if previous stroke/TIA
Ticagrelor; reversible P2Y12 antagonist	90 mg twice daily after 180 mg loading	Direct, reversible inhibition	3–5 days	Dyspnoea and bradyarrhythmia may mimic cardiopulmonary pathology
Cangrelor; intravenous reversible P2Y12 antagonist	30 microgram/kg bolus then 4 microgram/kg/min infusion during PCI	Immediate inhibition	Platelet function returns within 60–90 min; terminal half-life 3–6 min	Potential bridging agent in very high thrombotic risk patients
GPIIb/IIIa inhibitors	Abciximab, eptifibatide, tirofiban regimens	Block final common pathway of aggregation	Abciximab 24–48 h; eptifibatide/tirofiban 4–8 h	Profound bleeding risk, especially with renal dysfunction for small-molecule agents

Presentation may be overt haemorrhage, occult bleeding, or concern before procedures. Typical bleeding is mucocutaneous, epistaxis, gastrointestinal bleeding, haematuria, excessive wound ooze, or intracranial haemorrhage. Antiplatelet-associated bleeding is often disproportionate to platelet count and routine coagulation tests. Conversely, withdrawal may present as acute coronary syndrome, stent thrombosis, ischaemic stroke, mesenteric ischaemia, or acute limb ischaemia. Stent thrombosis is uncommon but catastrophic, with reported mortality approximately 20–45%; risk is greatest within the first month after PCI and remains high after acute coronary syndrome.

Differential diagnosis of bleeding in a patient receiving antiplatelets

Category	Examples	Clues
Drug-related haemostasis impairment	Anticoagulants, NSAIDs, SSRIs/SNRIs, valproate, chemotherapy, herbal agents such as ginkgo/garlic	Normal PT/APTT may coexist with severe platelet dysfunction
Quantitative platelet disorders	ITP, marrow failure, sepsis, massive transfusion, hypersplenism, HIT	Platelet count <100 × 109/L increases procedural bleeding; <50 × 109/L usually unsafe for major surgery
Qualitative platelet disorders	Uraemia, myeloproliferative disease, inherited platelet disorders	Bleeding time historically abnormal but obsolete; consider platelet function testing
Coagulation factor or vascular pathology	DIC, liver disease, vitamin K deficiency, von Willebrand disease, acquired haemophilia	Abnormal PT/APTT, low fibrinogen, raised D-dimer, low factor levels
Local structural lesion	Peptic ulcer, malignancy, surgical source, aneurysm, AVM	Bleeding site-specific symptoms; imaging/endoscopy required

Investigations and interpretation

Initial tests should define anaemia, platelet number, global coagulation, end-organ dysfunction, and the suspected bleeding site. A full blood count identifies haemoglobin and platelet count; the normal platelet count is approximately 150–400 × 10⁹/L. For major surgery, a platelet count <50 × 10⁹/L is generally inadequate; neurosurgery, posterior eye surgery, and neuraxial techniques commonly target >80–100 × 10⁹/L, depending on context and trajectory. PT/INR, APTT, fibrinogen, renal profile, liver function, group and screen/crossmatch, and blood gas/lactate are required in significant bleeding. Antiplatelet drugs usually leave PT and APTT normal.

Cardiac assessment is mandatory when antiplatelets are prescribed for coronary disease: ECG, troponin if symptomatic or perioperative myocardial injury is suspected, echocardiography when ventricular or valvular status is unknown, and review of PCI records. Key details are stent type, vessel, complexity, date, and indication. Contemporary ACC/AHA and ESC guidance generally recommends delaying elective non-cardiac surgery after drug-eluting stent implantation for 6 months where possible, and 12 months after acute coronary syndrome or complex PCI; time-sensitive surgery may be considered after 3 months in selected stable patients. The DAPT Study demonstrated fewer stent thromboses with prolonged dual therapy but increased bleeding; this underpins individualised risk assessment rather than automatic discontinuation.

Platelet function testing

Routine platelet function testing is not recommended for most elective anaesthetic decisions because correlation with surgical bleeding is imperfect, pre-test probability is often low, and thresholds are assay-specific. It may be useful in urgent surgery after P2Y₁₂ exposure, suspected treatment failure, recurrent stent thrombosis, or high-risk neurosurgical/cardiac surgery.

Test	Principle	Interpretation and limitations
Light transmission aggregometry	Gold-standard optical aggregation response to agonists: ADP, arachidonic acid, collagen, ristocetin	Detailed but slow, operator-dependent, platelet-rich plasma required; poor emergency utility
VerifyNow	Point-of-care turbidimetric assay; reports PRU for P2Y12, ARU for aspirin	High on-treatment platelet reactivity often PRU >208–230; aspirin non-response often ARU ≥550; bleeding risk increases with very low PRU, commonly <85–95
Multiplate impedance aggregometry	Whole-blood platelet aggregation by electrical impedance	Useful perioperatively; affected by platelet count, haematocrit, hypothermia, and pre-analytical error
TEG/ROTEM platelet mapping	Viscoelastic clot strength with arachidonic acid or ADP pathways	Assesses whole-blood haemostasis; standard TEG/ROTEM may be normal despite antiplatelet effect
PFA-100/200	Closure time through collagen/ADP or collagen/epinephrine cartridges	Sensitive to von Willebrand disease and aspirin, but nonspecific; affected by anaemia and thrombocytopenia

Procedure-specific thresholds

For neuraxial and deep plexus regional anaesthesia, current ASRA/ESAIC principles are pharmacology-based. Aspirin alone requires no additional delay. Suggested discontinuation intervals are clopidogrel 5–7 days, prasugrel 7–10 days, ticagrelor 3–5 days depending on guideline and bleeding risk, cangrelor at least 3 h, dipyridamole modified release 24 h, abciximab 24–48 h, and eptifibatide/tirofiban 4–8 h, with longer intervals in renal impairment. These intervals assume normal haemostasis; thrombocytopenia, renal failure, traumatic needle placement, or concomitant anticoagulation substantially changes risk.

Management, pharmacology and procedures

Clinical use and treatment strategies

Antiplatelet therapy is central to secondary prevention of arterial thrombosis, particularly acute coronary syndromes (ACS), percutaneous coronary intervention (PCI), ischaemic stroke/TIA, and peripheral arterial disease. Platelet-rich thrombi predominate in high-shear arterial beds; hence antiplatelets, rather than anticoagulants, are the principal long-term therapy after plaque rupture or stent implantation. Management is determined by thrombotic risk, bleeding risk, indication, timing of surgery, and whether neuraxial or deep plexus regional anaesthesia is planned.

Drug/class	Mechanism	Typical dose	Onset/duration	Key anaesthetic relevance
Aspirin	Irreversible COX-1 inhibition → ↓ thromboxane A2	Loading 150–300 mg PO; maintenance 75–100 mg daily	Effect within 30–60 min; platelet effect 7–10 days	Usually continued perioperatively; acceptable for neuraxial blockade
Clopidogrel	Irreversible P2Y12 ADP receptor antagonist; prodrug via CYP2C19	Loading 300–600 mg; maintenance 75 mg daily	Onset 2–6 h after loading; platelet recovery 5–7 days	Stop 5–7 days before neuraxial/deep block
Prasugrel	Irreversible P2Y12 antagonist; more potent than clopidogrel	Loading 60 mg; maintenance 10 mg daily, or 5 mg if <60 kg/elderly	Rapid onset ~30 min; recovery 7–10 days	Stop 7 days before neuraxial; avoid previous stroke/TIA
Ticagrelor	Reversible direct P2Y12 antagonist	Loading 180 mg; maintenance 90 mg twice daily	Onset ~30 min; t1/2 7–12 h; effect 3–5 days	Stop 5 days before neuraxial; may cause dyspnoea/bradyarrhythmia
GPIIb/IIIa inhibitors	Block final common pathway of platelet aggregation	Abciximab, eptifibatide, tirofiban IV in PCI/high-risk ACS	Immediate; recovery: abciximab 24–48 h, small molecules 4–8 h	Major bleeding/thrombocytopenia; avoid neuraxial until effect resolved

Acute coronary syndromes and PCI

In ACS, aspirin should be given immediately unless contraindicated, followed by dual antiplatelet therapy (DAPT) with a P2Y₁₂ inhibitor. Current ESC/ACC practice generally favours ticagrelor for medically managed ACS and ticagrelor or prasugrel for PCI, with prasugrel preferred in selected PCI patients after coronary anatomy is known. Landmark evidence includes CURE, which showed clopidogrel plus aspirin reduced cardiovascular death, MI or stroke in non-ST elevation ACS; TRITON-TIMI 38, where prasugrel reduced ischaemic events compared with clopidogrel but increased major bleeding; and PLATO, where ticagrelor reduced vascular death, MI or stroke compared with clopidogrel without a significant increase in overall major bleeding.

After drug-eluting stent implantation, standard DAPT duration is usually 6 months for stable coronary disease and 12 months after ACS, modified by bleeding risk. Shorter courses, e.g. 1–3 months followed by single antiplatelet therapy, may be used in high bleeding risk patients with contemporary stents. Premature discontinuation, particularly within the first month, carries a high risk of stent thrombosis, often presenting as catastrophic MI with mortality up to 20–45% in historical series.

Perioperative and procedural management

The anaesthetist must balance surgical haemorrhage against arterial thrombosis. Aspirin is commonly continued for most non-intracranial procedures because withdrawal may precipitate MI or stroke; exceptions include surgery where minor bleeding has severe consequences, such as intracranial, posterior eye chamber or some spinal canal surgery. P2Y₁₂ inhibitors are usually interrupted for elective surgery when bleeding risk is significant: clopidogrel 5 days, ticagrelor 5 days, prasugrel 7 days. If recent PCI mandates ongoing DAPT, elective surgery should be deferred where possible: ideally at least 1 month after bare-metal stent and 3–6 months after contemporary drug-eluting stent, longer after ACS where feasible.

Agent	Neuraxial/deep plexus block: minimum discontinuation	Restart after block/catheter removal
Aspirin/NSAID alone	No additional delay required	Immediately acceptable
Clopidogrel	5–7 days	Usually ≥6 h if no loading dose; avoid catheter with therapy
Prasugrel	7–10 days	≥6 h; avoid loading dose with catheter in situ
Ticagrelor	5 days	≥6 h; catheter should not remain during treatment
Eptifibatide/tirofiban	4–8 h and normal platelet count/function	After catheter removal if haemostasis secure
Abciximab	24–48 h	Specialist discussion

For urgent surgery, multidisciplinary discussion with cardiology, surgery, anaesthesia and haematology is essential. Bridging is not routine, but in exceptional very high stent-thrombosis risk, short-acting intravenous cangrelor may be considered: infusion 0.75 micrograms/kg/min, stopped 1–6 h preoperatively, with platelet function returning within approximately 60 min owing to a 3–6 min half-life.

Bleeding, reversal and monitoring

There is no reliable specific reversal for aspirin, clopidogrel, prasugrel or ticagrelor in routine practice. Management of major bleeding is supportive: stop the drug, local haemostasis, surgical/radiological control, tranexamic acid 1 g IV followed by 1 g over 8 h when appropriate, correction of hypothermia, acidosis and hypocalcaemia, and red cell/fibrinogen replacement guided by major haemorrhage protocols. Platelet transfusion may improve haemostasis after irreversible inhibitors once active metabolites have cleared, but is less effective for ticagrelor because circulating drug inhibits transfused platelets. Desmopressin 0.3 micrograms/kg IV may be considered in uraemic platelet dysfunction or antiplatelet-associated intracranial bleeding, although evidence is limited.

Routine coagulation tests are usually normal. Platelet count detects thrombocytopenia, particularly with GPIIb/IIIa inhibitors. Platelet function tests include VerifyNow, Multiplate impedance aggregometry, light transmission aggregometry, and thromboelastography/ROTEM platelet mapping; they may help in complex cardiac surgery or uncertain compliance but are not universally recommended to determine neuraxial safety.

Complications and follow-up

• Bleeding: gastrointestinal bleeding is reduced by proton-pump inhibitor co-prescription in high-risk patients; omeprazole may attenuate clopidogrel activation via CYP2C19, so pantoprazole is often preferred.
• Aspirin hypersensitivity/bronchospasm: relevant in aspirin-exacerbated respiratory disease; consider desensitisation if aspirin is essential after PCI.
• Clopidogrel non-response: associated with CYP2C19 loss-of-function alleles and drug interactions; alternative P2Y₁₂ agents may be required.
• Prasugrel bleeding risk: avoid previous stroke/TIA; caution age ≥75 years or body weight <60 kg.
• Ticagrelor adverse effects: dyspnoea, ventricular pauses, hyperuricaemia; twice-daily dosing affects adherence.
• GPIIb/IIIa inhibitors: profound thrombocytopenia can occur within hours; platelet count should be checked 2–4 h after initiation and if bleeding occurs.

Long-term follow-up focuses on adherence, bleeding surveillance, planned DAPT stop date, gastroprotection, cardiovascular risk modification, and explicit perioperative documentation. In patients with coronary stents, antiplatelet interruption should not occur without assessing stent type, implantation date, indication for PCI, and current ischaemic versus bleeding risk.

Exam controversies and advanced synthesis

Perioperative antiplatelet decisions: thrombotic versus bleeding risk

Primary FRCA vivas frequently test the ability to integrate pharmacology with perioperative risk. The key error is to regard antiplatelet therapy as a binary “stop or continue” decision. The correct synthesis requires assessment of: indication for therapy, time since coronary event or stent, bleeding consequences of surgery, and feasibility of haemostatic rescue. Premature discontinuation of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention is a major predictor of stent thrombosis, which carries mortality of approximately 20–45%.

Clinical context	Typical recommendation	FRCA pitfall
Secondary prevention aspirin after MI/stroke	Usually continue aspirin 75–100 mg daily unless bleeding risk is prohibitive	Stopping aspirin for low-risk surgery may increase thrombotic risk with little bleeding benefit
Primary prevention aspirin	Usually stop 5–7 days pre-operatively	Confusing primary prevention with established vascular disease
Recent drug-eluting stent	Delay elective surgery: ideally ≥6 months; time-sensitive surgery may be considered after 3 months in selected cases	Assuming modern DES require only a few weeks of DAPT in all patients
High bleeding-risk neurosurgery, posterior eye surgery	Individualised multidisciplinary plan; interruption often necessary	Underestimating consequences of confined-space bleeding

Guideline timings for neuraxial and deep regional anaesthesia

For examinations, quote timings rather than vague statements. Aspirin and NSAIDs alone are not considered contraindications to neuraxial block because they do not usually produce clinically significant spinal haematoma risk in isolation. P2Y₁₂ inhibitors are different: their irreversible or potent receptor blockade mandates an interval before neuraxial puncture and catheter manipulation. Contemporary ASRA/ESRA-style recommendations are broadly as follows:

Drug	Mechanism	Minimum interval before neuraxial block	Restart after catheter removal
Aspirin	Irreversible COX-1 inhibition; ↓TXA2	No mandatory delay	May continue
Clopidogrel	Irreversible P2Y12 antagonist; prodrug	5–7 days	Usually immediately after removal if no loading dose; delay 6 h if loading dose planned
Prasugrel	Irreversible P2Y12 antagonist	7–10 days	After catheter removal; avoid indwelling catheter during therapy
Ticagrelor	Reversible P2Y12 antagonist	5 days	After catheter removal; avoid catheter while anticoagulant effect active
Cangrelor	Intravenous reversible P2Y12 antagonist; t1/2 3–6 min	Approximately 3 h after stopping	May restart after catheter removal, institution-dependent

These timings apply particularly to neuraxial and deep plexus/deep peripheral blocks. Superficial compressible blocks may be considered with greater flexibility, but the viva answer should emphasise local policy, ultrasound guidance, compressibility, and consequences of bleeding.

Landmark trials and how they changed practice

• CAPRIE: clopidogrel 75 mg daily produced a modest relative risk reduction versus aspirin in composite vascular events in atherosclerotic disease; absolute benefit was small, but it established clopidogrel as an alternative antiplatelet.
• CURE: in non-ST elevation ACS, clopidogrel plus aspirin reduced cardiovascular death, MI or stroke compared with aspirin alone, at the cost of increased major bleeding. This underpins DAPT after ACS.
• TRITON-TIMI 38: prasugrel reduced ischaemic events and stent thrombosis versus clopidogrel in PCI-treated ACS but increased major bleeding; avoid or use caution in prior stroke/TIA, age ≥75 years, or body weight <60 kg.
• PLATO: ticagrelor reduced vascular death, MI or stroke versus clopidogrel in ACS, with more non-CABG bleeding and adverse effects including dyspnoea and bradyarrhythmias.
• POISE-2: perioperative aspirin did not reduce death or non-fatal MI in an unselected non-cardiac surgical population but increased major bleeding; however, it should not be simplistically extrapolated to very high-risk recent stent patients.

Reversal, rescue and platelet function testing

There is no simple “antidote” for most antiplatelets. Aspirin and clopidogrel irreversibly inhibit exposed platelets, so recovery depends on platelet turnover: approximately 10% of platelet mass per day, with platelet lifespan 7–10 days. Platelet transfusion may help after irreversible agents, particularly if given after active metabolites have cleared; it is less effective for ticagrelor because circulating drug and active metabolite can inhibit transfused platelets. Desmopressin 0.3 micrograms/kg IV may improve platelet adhesion through von Willebrand factor release, but evidence is variable and tachyphylaxis occurs. Tranexamic acid, typically 1 g IV followed by infusion or repeat dosing depending on context, treats fibrinolysis rather than platelet inhibition but is often part of haemorrhage management.

Platelet function testing remains controversial. Light transmission aggregometry is the historical reference method but is slow and laboratory-dependent. Point-of-care tests such as VerifyNow, Multiplate and thromboelastography/ROTEM platelet mapping may detect residual P2Y₁₂ effect, but thresholds predicting surgical bleeding are inconsistent. Routine testing to shorten recommended neuraxial intervals is not generally endorsed; targeted use may be reasonable when thrombotic risk is extreme or drug timing is uncertain.

High-yield viva synthesis

A polished answer states that antiplatelet management is a multidisciplinary risk decision involving anaesthesia, surgery, cardiology and the patient. In urgent surgery after recent PCI, the usual strategy is to continue aspirin, stop the P2Y₁₂ inhibitor only if bleeding risk demands it, minimise interruption, and consider specialist bridging with cangrelor in exceptional high-risk cases. Do not confuse anticoagulants with antiplatelets, do not site neuraxial catheters during active P2Y₁₂ blockade, and do not reassure yourself falsely with a normal platelet count: antiplatelet toxicity is a disorder of function, not platelet number.