Classify anticoagulant, antiplatelet and thrombolytic drugs. Compare heparin with warfarin.

Overview of Haemostasis and Drug Targets

Vessel injury → platelet adhesion (von Willebrand factor, GPIb) and activation → Release of ADP and thromboxane A2 recruits more platelets — the target of aspirin and clopidogrel → GPIIb/IIIa receptors bind fibrinogen and cross-link platelets — the target of abciximab and tirofiban → The coagulation cascade generates thrombin, which converts fibrinogen to fibrin — the target of heparin, warfarin and the direct oral anticoagulants → Fibrin is eventually dissolved by plasmin — the target of thrombolytics and, in the opposite direction, of tranexamic acid

• Arterial thrombi are platelet-rich ("white"), forming under high shear on ruptured plaque — so antiplatelet drugs are used
• Venous thrombi are fibrin-rich ("red"), forming in stasis — so anticoagulants are used. This single distinction dictates the choice of drug throughout

Anticoagulants Compared

Warfarin — Interactions and Management

• Potentiated by — enzyme inhibitors (metronidazole, ciprofloxacin, azoles, amiodarone, cimetidine), displacement from protein binding (aspirin, sulphonamides), reduced vitamin K (broad-spectrum antibiotics), liver disease, and antiplatelet drugs adding to the bleeding risk
• Antagonised by — enzyme inducers (rifampicin, carbamazepine, phenytoin, barbiturates, St John wort) and a high dietary vitamin K intake (green leafy vegetables)
• Patients should keep vitamin K intake consistent rather than avoid it — the dose is titrated to habitual diet
• Management of a high INR — withhold doses; oral vitamin K if the INR is very high or there is minor bleeding; prothrombin complex concentrate with intravenous vitamin K for major bleeding
• Direct oral anticoagulants — dabigatran (direct thrombin inhibitor) and rivaroxaban, apixaban, edoxaban (factor Xa inhibitors); fixed dose, no routine monitoring, fewer interactions, less intracranial bleeding. Reversal — idarucizumab for dabigatran, andexanet alfa for the Xa inhibitors. not used in mechanical heart valves or severe mitral stenosis, where warfarin remains essential

Antiplatelet Drugs

Thrombolytics and Antifibrinolytics

• Thrombolytics convert plasminogen to plasmin, which digests fibrin — streptokinase (antigenic, cannot be repeated within a year), alteplase, tenecteplase, reteplase (fibrin-selective, not antigenic)
• Uses — ST-elevation myocardial infarction where primary angioplasty is unavailable, acute ischaemic stroke within the window, massive pulmonary embolism, and occluded catheters
• "Time is muscle" — benefit falls sharply with delay, and is greatest within the first hour
• Contraindications — active bleeding, recent surgery or trauma, previous intracranial haemorrhage or recent stroke, aortic dissection, severe uncontrolled hypertension, bleeding diathesis
• Antifibrinolytics act in the opposite direction — tranexamic acid and aminocaproic acid block plasminogen binding to fibrin; used in trauma (given early), menorrhagia, dental extraction in haemophilia, and post-partum haemorrhage

Direct Oral Anticoagulants Compared with Warfarin

Applied Aspects

• Match the drug to the clot — antiplatelets for arterial disease (coronary, cerebral, peripheral), anticoagulants for venous thrombosis and for cardioembolic stroke prevention in atrial fibrillation
• Suspect heparin-induced thrombocytopenia if the platelet count falls by more than half after 5 to 10 days; it causes thrombosis, not bleeding, and heparin must be stopped and replaced with a non-heparin anticoagulant
• Warfarin needs patient education above all — a record book, consistent diet, awareness of interactions, and prompt reporting of bleeding; in India, access to reliable INR testing is often the limiting factor and may itself decide between warfarin and a direct oral anticoagulant
• Never assume a herbal preparation is inert — garlic, ginkgo and ginger all affect platelet function and add to bleeding risk
• Stop antiplatelets and anticoagulants appropriately before surgery, balancing bleeding against thrombotic risk; for high-risk patients, bridging with heparin may be needed
• Tranexamic acid given within 3 hours reduces death in trauma and in post-partum haemorrhage — cheap, widely available, and one of the most cost-effective interventions in emergency care
• Low molecular weight heparin accumulates in renal failure, so unfractionated heparin is preferred where clearance is very poor, being cleared by the reticuloendothelial system
• Protamine fully reverses unfractionated heparin but only partly reverses the low molecular weight form, and can itself cause hypotension and anaphylaxis if given rapidly
• Aspirin resistance is more often non-adherence or concurrent NSAID use — ibuprofen competes for the COX-1 site and can block aspirin’s antiplatelet effect if taken first
• Check platelet count before and during heparin therapy, since heparin-induced thrombocytopenia is diagnosed on a falling count and is easily missed without a baseline
• Anticoagulation decisions rest on balancing two risks, and scores exist for both — CHA2DS2-VASc for stroke and has-bled for bleeding; a high bleeding score prompts correction of reversible factors rather than automatic withholding