Anticoagulation

Introduction

Anticoagulants reduce the blood's capacity to form thrombus, and are among the most widely prescribed and most frequently implicated drugs in serious adverse events in the NHS. Understanding which agent, at what dose, for how long, and how to reverse it is core clinical knowledge rather than specialist territory.¹

A useful framing: anticoagulants act principally on the coagulation cascade (secondary haemostasis, preventing fibrin formation), whereas antiplatelet agents such as aspirin and clopidogrel act on primary haemostasis (platelet adhesion and aggregation). This is why anticoagulants are the drugs of choice for venous thrombosis and cardioembolic stroke prevention, while antiplatelets dominate in arterial atherothrombotic disease.

The drug classes

Heparins

Both heparins work by potentiating antithrombin, the body's natural inhibitor of thrombin and factor Xa - they accelerate its activity dramatically rather than inhibiting clotting factors directly. This has an important consequence: patients with antithrombin deficiency exhibit apparent heparin resistance, since the drug has less substrate to work through.

Low molecular weight heparin

• Examples: enoxaparin, dalteparin, tinzaparin
• Predictable pharmacokinetics allow weight-based, once- or twice-daily subcutaneous dosing without routine monitoring - the reason it has largely replaced unfractionated heparin
• Anti-Xa monitoring is reserved for specific situations: pregnancy, extremes of body weight, and renal impairment
• Renally cleared - reduce the dose or switch to unfractionated heparin in significant renal impairment
• Lower risk of heparin-induced thrombocytopenia than unfractionated heparin, though the risk is not zero

Unfractionated heparin

• Given as an IV infusion with a loading bolus, titrated against the APTT ratio
• Short half-life and complete reversibility with protamine make it the agent of choice where anticoagulation may need to be stopped or reversed rapidly - high bleeding risk, imminent surgery, or an unstable patient
• Preferred in severe renal impairment, as it is not principally renally cleared
• Requires more intensive nursing and laboratory input, and carries a higher risk of HIT

Warfarin

Warfarin inhibits vitamin K epoxide reductase, preventing regeneration of reduced vitamin K needed for gamma-carboxylation of factors II, VII, IX and X and of the natural anticoagulants protein C and protein S. Despite the availability of DOACs, warfarin remains essential for several indications.

Practical prescribing

• Monitored by INR, with a target of 2.5 (range 2-3) for most indications including AF and VTE, and 3.5 (range 3-4) for mechanical mitral valves and recurrent VTE on treatment
• Slow onset - therapeutic anticoagulation takes several days, so heparin/LMWH cover is required when treating acute thrombosis, continued for at least 5 days and until the INR is in range on two consecutive readings
• Narrow therapeutic index with substantial inter-individual variability, requiring regular INR monitoring and dose titration for life
• Long half-life (~40 hours) means dose changes take days to be reflected in the INR

Interactions

• Enzyme inhibitors increase the INR (raising bleeding risk) - including many antibiotics (ciprofloxacin, clarithromycin, metronidazole, co-trimoxazole), fluconazole, amiodarone, SSRIs, omeprazole and cranberry juice
• Enzyme inducers decrease the INR (raising thrombotic risk) - including rifampicin, carbamazepine, phenytoin, St John's wort and chronic alcohol excess
• Dietary vitamin K (green leafy vegetables) reduces the INR - patients should aim for consistent intake rather than avoidance
• Always check interactions before adding any new drug to a patient on warfarin, and arrange an earlier INR check

Managing a high INR

Direct oral anticoagulants

DOACs act directly on a single clotting factor rather than through antithrombin or vitamin K metabolism. They have become first line for most indications because they offer fixed dosing, no routine monitoring, rapid onset and offset, and far fewer food and drug interactions than warfarin, with comparable or better efficacy and less intracranial haemorrhage.²

Practical cautions

• Check renal function before starting and at least annually (more often if impaired or the patient is elderly) - all DOACs require dose adjustment and are contraindicated below certain thresholds
• Interactions still exist, particularly with strong P-glycoprotein and CYP3A4 inhibitors/inducers - rifampicin, carbamazepine, certain antifungals and HIV protease inhibitors
• Adherence matters more than with warfarin - the short half-life means missing doses rapidly leaves the patient unprotected, and there is no INR to reveal non-adherence
• Caution with DOACs in luminal gastrointestinal and genitourinary cancers, where gastrointestinal bleeding rates are higher

Choosing an anticoagulant

Managing bleeding and reversal

• Stop the anticoagulant and apply standard resuscitation - ABCDE, direct pressure where accessible, IV access, cross-match, and correction of hypothermia and acidosis
• Establish which drug, the last dose taken, and renal function - this determines both the expected duration of effect and the correct reversal agent
• Unfractionated heparin: protamine sulfate provides complete reversal; it only partially reverses LMWH
• Warfarin: IV vitamin K plus prothrombin complex concentrate (PCC) for major bleeding - PCC replaces factors II, VII, IX and X within minutes, while vitamin K restores endogenous synthesis over hours. Both are needed, since PCC alone wears off before warfarin does
• Dabigatran: idarucizumab, a monoclonal antibody fragment giving rapid, specific reversal; dabigatran is also dialysable
• Factor Xa inhibitors: andexanet alfa where available, otherwise PCC
• Tranexamic acid as an adjunct in major haemorrhage per local protocols
• Involve haematology early in any major bleed on anticoagulation, and consider whether the drug should be restarted once haemostasis is secure - stopping permanently carries its own thrombotic risk

Red flags

Monitoring and follow-up

Every patient on long-term anticoagulation needs structured review, not simply repeat prescribing. This includes an annual reassessment of the indication (is it still needed?), renal and liver function, full blood count, medication reconciliation for new interactions, and a fresh look at bleeding risk as the patient ages and accumulates comorbidity and falls risk.¹

Patients should carry an anticoagulant alert card, understand what to do if a dose is missed, know which symptoms warrant urgent attention, and be advised about dental and surgical procedures. For warfarin, this extends to consistent dietary vitamin K intake and prompt INR checks after any medication change. It is worth noting that falls risk alone is rarely a sufficient reason to withhold anticoagulation in atrial fibrillation, since the stroke risk usually outweighs the bleeding risk by a considerable margin.