Anticoagulants

Anticoagulants reduce fibrin formation by inhibiting coagulation factors, preventing thrombus growth and embolism. They prevent stroke in atrial fibrillation, treat and prevent venous thromboembolism, protect mechanical heart valves and support treatment of acute coronary syndrome. Bleeding is the main risk. Choice depends on indication, kidney and liver function, interactions, pregnancy, access to monitoring and cost.

Classification. Parenteral: unfractionated heparin, low molecular weight heparins, fondaparinux, direct thrombin inhibitors (argatroban, bivalirudin). Oral: vitamin K antagonists (warfarin, acenocoumarol) and direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, edoxaban).

Mechanism. Heparins and fondaparinux act through antithrombin to inhibit factor Xa (and thrombin for unfractionated heparin). Vitamin K antagonists reduce synthesis of factors II, VII, IX and X. Direct oral anticoagulants inhibit thrombin (dabigatran) or factor Xa (the others) directly.

Regional context. Rheumatic mitral stenosis with atrial fibrillation remains frequent in sub-Saharan Africa, and warfarin is the anticoagulant of choice. Warfarin is also relied on where direct oral anticoagulants are costly, and INR monitoring capacity differs between facilities. Strokes in younger patients with rheumatic valve disease are a recurrent presentation.

• Unfractionated heparin: short acting, reversible, safe in renal failure; infusion and monitoring needed.
• Low molecular weight heparins: subcutaneous, predictable, little monitoring.
• Fondaparinux: once-daily subcutaneous; no reversal agent.
• Warfarin and acenocoumarol: oral, cheap, reversible, need INR monitoring and have many interactions.
• Direct oral anticoagulants: fixed dosing, no routine monitoring, fewer interactions; avoided in mechanical valves, moderate to severe mitral stenosis and severe renal impairment.
• Direct thrombin inhibitors (argatroban, bivalirudin): heparin-induced thrombocytopenia and percutaneous coronary intervention.

• Non-valvular atrial fibrillation: anticoagulate when CHA2DS2-VASc is 2 or over in men and 3 or over in women, and consider at 1 or 2 respectively. A direct oral anticoagulant is preferred to warfarin. Aspirin alone is not adequate stroke prevention.
• Atrial fibrillation with moderate to severe rheumatic mitral stenosis or a mechanical valve: warfarin, not a direct oral anticoagulant.
• Venous thromboembolism: initial treatment with a direct oral anticoagulant, or a parenteral agent then warfarin or a direct oral anticoagulant. Duration at least 3 months. Provoked events stop at 3 months. Unprovoked events are reviewed for extended treatment.
• Cancer-associated thrombosis: direct oral anticoagulant or low molecular weight heparin, with care in gastrointestinal and genitourinary cancers.
• Pregnancy: low molecular weight heparin. Warfarin and direct oral anticoagulants are avoided.
• Antiphospholipid syndrome: warfarin; avoid direct oral anticoagulants in triple-positive disease.
• Heparin-induced thrombocytopenia: stop heparin and use a non-heparin anticoagulant.
• Reversal agents: vitamin K and four-factor prothrombin complex concentrate for warfarin; idarucizumab for dabigatran; andexanet alfa or prothrombin complex concentrate for factor Xa inhibitors; protamine for heparins.
• Selection: assess bleeding risk (HAS-BLED), correct modifiable factors, and do not withhold anticoagulation solely because of a high score.

Contraindications. Active major bleeding, severe thrombocytopenia, recent intracranial haemorrhage or neurosurgery, and uncontrolled severe hypertension. Exclusions differ by drug group, such as mechanical valves for direct oral anticoagulants and pregnancy for warfarin.

Adverse effects. Bleeding, anaemia, heparin-induced thrombocytopenia, osteoporosis with long heparin use, skin necrosis with warfarin, and teratogenicity of warfarin.

Interactions. Antiplatelet drugs, NSAIDs, SSRIs, amiodarone, azole antifungals, macrolides, rifampicin, antiepileptic enzyme inducers, antiretrovirals with ritonavir or cobicistat, and herbal products.

Monitoring. Full blood count, kidney and liver function at baseline and at least yearly (every 3 to 6 months in older adults or reduced function), INR for warfarin, anti-Xa for heparin where needed, and adherence.

Peri-procedural management. Stop and restart on a procedure-specific plan. Bridging with heparin is not routine.

Referral and escalation. Major bleeding, thrombosis despite treatment, pregnancy on anticoagulants, or a mechanical valve needing a procedure require specialist advice.

Special groups. Pregnancy: low molecular weight heparin. Breastfeeding: warfarin and heparin are compatible. Kidney disease: heparin or warfarin, with dose reduction for others. Older adults: reduced-dose strategies and falls review. Children: specialist dosing.