Key Facts

Anticoagulants are essential drugs in modern medicine. The introduction of DOACs has simplified management for many patients, but understanding the differences between agents, appropriate patient selection, and bleeding management remains critical.

Epidemiology

• AF affects ~1.4 million people in UK — anticoagulation prevents ~70% of strokes
• VTE (DVT/PE): ~1 per 1,000/year; anticoagulation is mainstay of treatment
• ~5 million anticoagulant prescriptions/year in England (DOACs now outnumber warfarin)

Classification

Heparins:

• UFH: potentiates antithrombin III → inhibits thrombin (IIa) and Xa; IV/SC; monitored by APTT
• LMWH (enoxaparin, dalteparin, tinzaparin): preferentially inhibits Xa; SC; predictable PK, no routine monitoring

Vitamin K Antagonists:

• Warfarin: inhibits vitamin K-dependent clotting factor synthesis (II, VII, IX, X, protein C, protein S); monitored by INR

DOACs:

• Factor Xa inhibitors: apixaban, rivaroxaban, edoxaban
• Direct thrombin (IIa) inhibitor: dabigatran

Pathophysiology

• Coagulation cascade: intrinsic and extrinsic pathways converge at factor X → common pathway → thrombin → fibrin
• Anticoagulants interrupt this cascade at various points → prevent thrombus formation/extension
• All anticoagulants increase bleeding risk — balancing thrombosis prevention vs bleeding risk is the key clinical decision

Indications

• AF stroke prevention: CHA₂DS₂-VASc ≥2 (men) / ≥3 (women) → anticoagulate
• VTE treatment: DVT and PE — initial and extended treatment
• VTE prophylaxis: post-operative (THR, TKR), medical inpatients
• Mechanical heart valves: warfarin ONLY (DOACs contraindicated — RE-ALIGN trial)
• Antiphospholipid syndrome: warfarin (DOACs inferior — TRAPS trial)

Major Complications

• Bleeding: GI, intracranial, retroperitoneal — most serious complication
• HIT (heparin-induced thrombocytopenia): type II — immune-mediated; paradoxically causes thrombosis; stop heparin, start argatroban/fondaparinux
• Warfarin skin necrosis: rare; protein C deficiency → early thrombosis before anticoagulation achieved
• Warfarin embryopathy: teratogenic in 1st trimester — use LMWH in pregnancy

Red Flags

• Major bleeding on anticoagulant — stop drug, resuscitate, reverse if available
• INR >8 on warfarin — vitamin K, consider PCC; assess for bleeding
• Suspected HIT: platelet drop >50% from baseline + thrombosis → 4T score, stop heparin
• DOAC in patient with CrCl <15 mL/min → contraindicated

Before Starting

• FBC: baseline platelet count (HIT monitoring for heparin)
• U&Es, creatinine: renal function — essential for DOAC dosing
• LFTs: hepatic function
• Coagulation screen: PT, APTT, INR — baseline
• CHA₂DS₂-VASc and HAS-BLED scores: AF risk stratification

Monitoring

• Warfarin: INR (target 2.0–3.0 for AF/VTE; 2.5–3.5 for mechanical valves) — initially twice-weekly, then at least monthly
• UFH: APTT ratio (target 1.5–2.5) every 6 hours initially
• LMWH: no routine monitoring; anti-Xa levels in renal impairment, extremes of weight, pregnancy
• DOACs: no routine coagulation monitoring; annual renal function; more frequently if CKD

Special Tests

• Anti-Xa levels: LMWH monitoring in special populations; also detects factor Xa inhibitor levels in emergency
• Thrombin time: prolonged by dabigatran — useful in emergency to confirm drug presence
• 4T score: if HIT suspected (Thrombocytopenia, Timing, Thrombosis, oTher causes excluded)

DOAC Prescribing

• Apixaban: 5 mg BD (AF); reduce to 2.5 mg BD if ≥2 of: age ≥80, weight ≤60 kg, Cr ≥133 μmol/L
• Rivaroxaban: 20 mg OD with food (AF); 15 mg BD for 21 days then 20 mg OD (VTE)
• Edoxaban: 60 mg OD; reduce to 30 mg if CrCl 15–50, weight ≤60 kg, or P-gp inhibitor
• Dabigatran: 150 mg BD (AF); reduce to 110 mg BD if age ≥80 or concurrent verapamil; avoid CrCl <30

Warfarin Prescribing

• Loading: typically 5 mg days 1–2 (lower in elderly, hepatic impairment); adjust based on INR
• Maintenance: variable (1–10+ mg/day); guided by INR
• Bridging with LMWH: when starting warfarin (takes 3–5 days for full effect; continue LMWH until INR >2 for 2 days)

Bleeding Management

Warfarin:

• INR 5.0–8.0 (no bleeding): withhold warfarin; recheck INR in 2–3 days
• INR >8.0 (no bleeding): vitamin K 1–5 mg PO; withhold warfarin
• Major bleeding: IV vitamin K 5 mg + PCC (Beriplex — 25–50 IU/kg based on INR)

DOACs:

• Minor bleeding: hold dose; supportive
• Major bleeding: hold DOAC; PCC 25–50 IU/kg; tranexamic acid 1 g IV
• Dabigatran reversal: idarucizumab (Praxbind) 5 g IV — specific reversal
• Xa inhibitor reversal: andexanet alfa (if available); otherwise PCC

HIT:

• Stop ALL heparin (including flushes, lines); start alternative anticoagulant (argatroban IV or fondaparinux SC)

Referral Criteria

• Haematology: complex anticoagulation decisions, HIT, thrombophilia
• Anticoagulation clinic: warfarin management, patient education
• Cardiology: mechanical valve anticoagulation

• AF anticoagulation: reduces stroke risk by ~70%
• VTE treatment: recurrence rate ~5% at 1 year on anticoagulation
• Major bleeding on anticoagulants: ~1–3%/year for DOACs; ~3–4%/year for warfarin
• Intracranial haemorrhage: DOACs have ~50% lower risk than warfarin
• HIT: if unrecognised, thrombosis risk ~30–50%; mortality ~10–20%
• DOACs vs warfarin: non-inferior or superior for efficacy with better safety profile in most trials (ARISTOTLE, RE-LY, ROCKET-AF, ENGAGE)

DOAC Comparison

CHA₂DS₂-VASc Score