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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
Key points
- Warfarin: vitamin K antagonist, target INR 2–3 (mechanical heart valves 2.5–3.5). Reversed with vitamin K (phytomenadione), prothrombin complex concentrate (PCC), and FFP
- DOACs (apixaban, rivaroxaban, edoxaban, dabigatran): increasingly first-line for AF and VTE. Fewer interactions, no routine monitoring, but renal dosing essential
- Heparin: UFH (IV, APTT monitoring) for inpatient use; LMWH (SC, e.g. dalteparin, enoxaparin) for VTE treatment/prophylaxis. Reversed with protamine
- Major bleeding on warfarin: STOP warfarin + IV vitamin K 5 mg + PCC (Beriplex/Octaplex) — faster than FFP
- Dabigatran reversal: idarucizumab (Praxbind). Factor Xa inhibitor reversal: andexanet alfa (NICE TA697) or PCC if unavailable
Overview
Anticoagulants are used to prevent and treat thromboembolic diseases including atrial fibrillation, deep vein thrombosis, pulmonary embolism, and mechanical heart valves. Warfarin (a vitamin K antagonist) has been the mainstay for decades but requires INR monitoring and has numerous food and drug interactions. Direct oral anticoagulants (DOACs) — apixaban, rivaroxaban, edoxaban (factor Xa inhibitors) and dabigatran (direct thrombin inhibitor) — have largely replaced warfarin for AF and VTE due to predictable pharmacokinetics, fewer interactions, and no routine monitoring requirement. Heparins (UFH and LMWH) are used for inpatient anticoagulation, bridging, and VTE prophylaxis. All anticoagulants increase bleeding risk, and specific reversal agents are essential for managing major haemorrhage.
Epidemiology
Approximately 1.5 million people in the UK take anticoagulants. DOACs now account for the majority of new anticoagulant prescriptions for AF and VTE. Anticoagulant-related bleeding is one of the most common causes of drug-related hospital admissions. Warfarin has a narrow therapeutic index with an INR target of 2–3 for most indications — both sub-therapeutic and supra-therapeutic levels carry significant clinical consequences.
Clinical Features
Symptoms
This topic covers prescribing principles and reversal strategies
Signs
Signs of bleeding: bruising, haematuria, melaena, haematemesis, haemoptysis, intracranial haemorrhage signs
Investigations
First-line
INR (warfarin)Target 2–3 for AF and VTE. Target 2.5–3.5 for mechanical mitral valve. Check regularly (at least monthly when stable)
APTT (UFH)Target ratio 1.5–2.5 times normal. Check 6 hours after starting/changing dose
Renal function (DOACs)All DOACs require renal dose adjustment. Dabigatran contraindicated if CrCl <30 mL/min. Apixaban/rivaroxaban: dose reduce if CrCl 15–29
Second-line
Anti-Xa levelCan monitor LMWH activity in special populations (obesity, renal impairment, pregnancy)
FBC and group & saveBaseline and if bleeding — assess haemoglobin and prepare for transfusion if needed
1
Warfarin reversal
- Major/life-threatening bleeding: STOP warfarin + IV vitamin K 5 mg + 4-factor PCC (Beriplex/Octaplex 25–50 IU/kg) — PCC works within minutes
- INR >8, no bleeding: STOP warfarin, give oral vitamin K 1–5 mg, recheck INR in 24 hours
- INR 5–8, no bleeding: withhold 1–2 doses, consider oral vitamin K 1–2 mg if high bleeding risk
- INR <5 but above target: reduce dose or omit one dose
2
DOAC reversal
- Dabigatran: idarucizumab (Praxbind) 5 g IV — specific monoclonal antibody reversal agent
- Factor Xa inhibitors (apixaban, rivaroxaban, edoxaban): andexanet alfa (NICE TA697) if available, otherwise 4-factor PCC 50 IU/kg
- General measures: stop DOAC, tranexamic acid 1 g IV, direct pressure, surgical haemostasis
- DOACs have short half-lives (12–24 hours) — if bleeding is not life-threatening, withholding and supportive care may suffice
3
Heparin reversal
- UFH: protamine sulphate 1 mg per 100 units of heparin given in previous 1 hour (max 50 mg). Give slowly IV (risk of anaphylaxis)
- LMWH: protamine partially reverses (only ~60% effective). Give 1 mg per 100 units of LMWH
4
Perioperative management
- Warfarin: stop 5 days pre-op, check INR day of surgery (target <1.5), consider LMWH bridging if high thromboembolic risk
- DOACs: stop 24–48 hours pre-op (longer if renal impairment or high bleeding risk surgery). No bridging usually needed
- LMWH: last dose 12–24 hours pre-op
Complications
- Major bleeding: Intracranial, GI, retroperitoneal — can be fatal
- Heparin-induced thrombocytopenia (HIT): Immune-mediated platelet activation — paradoxically causes thrombosis. Stop heparin, start argatroban/fondaparinux
- Warfarin skin necrosis: Rare, occurs in protein C deficiency on warfarin initiation
- Sub-therapeutic anticoagulation: Stroke (in AF), recurrent VTE
UKMLA Exam Tips
- 1Warfarin reversal for major bleeding: IV vitamin K 5 mg + PCC (Beriplex) — NOT FFP as first-line (too slow)
- 2Dabigatran reversal: idarucizumab (Praxbind). Factor Xa inhibitor reversal: andexanet alfa or PCC
- 3Warfarin interactions: levels INCREASED by amiodarone, macrolides, metronidazole, SSRIs, cranberry juice. DECREASED by rifampicin, carbamazepine, St John’s Wort
- 4HIT: platelets fall >50% from baseline 5–10 days after starting heparin → STOP all heparin, start alternative anticoagulant
- 5DOACs do NOT need routine monitoring but DO need renal dose adjustment
- 6Warfarin in pregnancy = teratogenic (use LMWH). Warfarin is safe in breastfeeding
- 7Mechanical heart valve = warfarin ONLY (DOACs are contraindicated)
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