Key Facts

Anticoagulation therapy is fundamental to the prevention and treatment of arterial and venous thromboembolism. The choice of agent depends on the indication, patient characteristics, renal function, and the balance of thrombotic versus bleeding risk.

Epidemiology

• Approximately 1.4 million people in the UK take anticoagulants
• AF affects ~1.5 million people in the UK; anticoagulation reduces stroke risk by ~65%
• VTE affects ~1 in 1,000 per year in the UK
• DOAC prescribing has overtaken warfarin since ~2018

Aetiology

Anticoagulation is used in:

• Atrial fibrillation: stroke prevention
• Venous thromboembolism: treatment and secondary prevention of DVT/PE
• Mechanical heart valves: lifelong warfarin
• Antiphospholipid syndrome: warfarin preferred
• Post-ACS: short-term in combination with antiplatelet therapy
• Perioperative thromboprophylaxis: LMWH

Pathophysiology

• Warfarin: inhibits vitamin K-dependent clotting factors (II, VII, IX, X) and proteins C and S
• DOACs: directly inhibit thrombin (dabigatran) or factor Xa (apixaban, rivaroxaban, edoxaban)
• Heparins: potentiate antithrombin III activity — UFH inhibits thrombin + Xa; LMWH primarily inhibits Xa
• Fondaparinux: selective factor Xa inhibitor via antithrombin

Indications for Anticoagulation

• Atrial fibrillation with CHA₂DS₂-VASc ≥2 (men) or ≥3 (women)
• VTE: acute DVT or PE, and secondary prevention
• Mechanical heart valves: lifelong warfarin
• Post-ACS: short-term anticoagulation
• Thromboprophylaxis: post-surgical, immobility, medical inpatients

Complications of Anticoagulation

• Bleeding: GI, intracranial, urogenital, retroperitoneal
• HIT: platelet drop >50%, paradoxical thrombosis (day 5–14 of heparin)
• Warfarin skin necrosis: protein C deficiency; typically day 3–5 of initiation
• Warfarin teratogenicity: contraindicated in first trimester

Red Flags

• Major bleeding: haemodynamic instability, intracranial haemorrhage, GI haemorrhage
• HIT: platelet count drop >50% with thrombosis
• Supratherapeutic INR >8 with or without bleeding
• Unexplained bruising or petechiae on anticoagulation

Bedside

• INR: warfarin monitoring (target 2.0–3.0 for most indications)
• APTT: UFH monitoring (target ratio 1.5–2.5)
• Point-of-care INR: self-monitoring for warfarin patients

Bloods

• FBC: baseline platelet count; monitor for HIT
• U&Es/eGFR: renal function critical for DOAC dosing (dabigatran contraindicated if CrCl <30 mL/min)
• LFTs: hepatic function for warfarin/DOAC metabolism
• Coagulation screen: PT, APTT, fibrinogen
• Anti-Xa levels: LMWH/fondaparinux monitoring in renal impairment, extremes of body weight, pregnancy
• HIT antibodies: ELISA for PF4/heparin antibodies if HIT suspected

Imaging

• Imaging guided by suspected bleeding site (CT head, CT abdomen, endoscopy)

Special Tests

• CHA₂DS₂-VASc score: AF stroke risk
• HAS-BLED score: bleeding risk assessment
• 4Ts score: pre-test probability for HIT
• Thrombin time: screen for dabigatran effect
• Ecarin clotting time: quantify dabigatran level

Non-pharmacological

• Patient education on anticoagulant therapy, bleeding risks, and drug interactions
• Anticoagulation clinic follow-up (warfarin) or structured annual review (DOACs)
• Medical alert bracelet/card
• Dietary advice for warfarin users (consistent vitamin K intake)

Pharmacological

AF stroke prevention (NICE NG196):

• First-line: DOAC — apixaban 5mg BD, rivaroxaban 20mg OD, edoxaban 60mg OD, or dabigatran 150mg BD
• Dose reduction criteria: apixaban 2.5mg BD if ≥2 of: age ≥80, weight ≤60kg, creatinine ≥133 µmol/L
• Warfarin if DOAC contraindicated or mechanical valve

VTE treatment:

• Apixaban 10mg BD for 7 days then 5mg BD, or rivaroxaban 15mg BD for 21 days then 20mg OD
• Alternative: LMWH (enoxaparin 1.5mg/kg OD) for ≥5 days then warfarin (target INR 2.0–3.0)

Reversal agents:

• Warfarin: vitamin K 1–5mg IV (non-urgent) or PCC (Beriplex 25–50 IU/kg) for major bleeding
• Dabigatran: idarucizumab 5g IV (REVERSE-AD trial)
• Factor Xa inhibitors: andexanet alfa (NICE TA697) or PCC if unavailable
• UFH: protamine sulphate 1mg per 100 units heparin

Landmark trials:

• RE-LY: dabigatran vs warfarin in AF
• ROCKET-AF: rivaroxaban vs warfarin in AF
• ARISTOTLE: apixaban vs warfarin in AF — lower bleeding and mortality
• ENGAGE AF-TIMI 48: edoxaban vs warfarin in AF

Surgical/Interventional

• Left atrial appendage occlusion (LAAO): for AF patients who cannot take long-term anticoagulation
• Bridging anticoagulation peri-operatively: LMWH for high-risk patients (mechanical valves)

Referral Criteria

• Haematology referral for recurrent VTE on anticoagulation, HIT, or complex bleeding
• Anticoagulation clinic for warfarin initiation and monitoring
• Cardiology for LAAO consideration

• Anticoagulation in AF reduces ischaemic stroke risk by ~65% and all-cause mortality by ~25%
• VTE recurrence rate: ~5% per year on anticoagulation; ~10% per year after stopping
• Major bleeding risk on DOACs: ~2-3% per year (lower than warfarin ~3-4%)
• HIT mortality: ~20-30% if unrecognised; <5% with prompt treatment
• Warfarin time in therapeutic range (TTR) >65% associated with good outcomes

CHA₂DS₂-VASc Score

HAS-BLED Score

DOAC Dose Adjustments