An anticoagulant, or “blood thinner”, prevents thrombus (blood clot) formation. A thrombus consists of a fibrin web that entraps platelets and red blood cells. Anticoagulants are particularly effective in venous thrombi which are fibrin-rich. In contrast, in the faster flowing arteries, thrombi are primarily platelet-rich, and an antiplatelet medication would be more effective. Common indications for anticoagulant therapy include: Treatment and prophylaxis of venous thromboembolism (VTE): deep vein thrombosis (DVT) or pulmonary embolism (PE) Treatment of myocardial infarction. This article provides an overview of parenteral anticoagulants, including their mechanisms of action, clinical uses, adverse effects, contraindications and drug interactions. Heparins Unfractionated heparin (UH) UH acts by inhibiting thrombin and potentiating naturally occurring inhibitors of factor Xa. Pharmacokinetics: UH is rapid acting and has a short duration of action, which is useful when termination of the anticoagulation effect is beneficial. Administration: UH given by a continuous IV infusion or subcutaneous injection every 8-12 hours. It should not be given by intramuscular injection due to risk of haematoma. Monitoring: When given by a continuous IV infusion, the dose is adjusted based on the activated partial thromboplastin time (APTT) value. Low molecular weight heparins (LMWH) Examples: dalteparin, tinzaparin and enoxaparin Mechanism of action: act mainly through potentiation of the inhibition of factor Xa, and to a lesser extent, thrombin. Indications: LMWH are usually preferred in prophylaxis and treatment of VTE as they are effective and there is a lower chance of Heparin induced thrombocytopenia (HIT). Pharmacokinetics: LMWH have a longer duration of action than UH so can be given once daily; the T ½ of dalteparin following IV and SC administration is 2 hours and 3.5-4 hours respectively, which is twice that of UH. Monitoring: Anti-xa levels can be taken to monitor for efficacy or toxicity in special circumstances such as renal impairment, extremes of body weight or at increased risk of bleeding/rethrombosis. Heparins: Adverse effects Heparin induced thrombocytopenia (HIT) Can occur with UH or LMWH Signs: ≥30% reduction in platelet count, thrombosis or skin allergy. Thrombocytopenia usually occurs within the first 3 weeks of treatment with LMWH and can occur several weeks after the discontinuation of UH. Management: stop heparin and switch to danaparoid or another alternative. Platelet counts should be measured at baseline and regularly if therapy is given for >4 days. If patients experience HIT, further use of heparin compounds is not recommended, as circulating antibodies can persist for several years. Hyperkalaemia Caused by inhibition of adrenal aldosterone secretion Risk factors: diabetes, chronic renal failure, acidosis or taking potassium sparing drugs such as spironolactone are more likely to experience hyperkalaemia. Monitoring: Patients at risk should have baseline serum potassium level and be monitored regularly thereafter. Caution when administering heparins with medications that also cause hyperkalaemia. Danaparoid sodium Mechanism of action: enhances antithrombin mediated inactivation of factor Xa, through enhancing the binding of factor Xa to antithrombin. To a lesser extent, possesses a small amount of antithrombin activity. Both of which result in inhibition of thrombin generation and thrombus formation. Indications: Danaparoid is used in HIT Administration: subcutaneous or intravenous Pharmacokinetics: Renally excreted: caution in chronic kidney disease or acute kidney injury due to an extended elimination half life. Peak plasma anti-xa activity levels are reached after approximately 4-5 hours. Steady state levels of plasma anti-xa levels are reached within 4-5 days dosing. Fondaparinux Mechanism: Synthetic pentasaccharide that selectively inhibits factor Xa via binding to antithrombin III. Fondaparinux does not inhibit thrombin. Administration: subcutaneous or intravenous routes (avoid intramuscular due to risk of haematoma) Pharmacokinetics: Half life is longer than UH, ranging from 17-21 hours, therefore dosing is generally once daily. Renally excreted: dose adjustments are recommended in patients with chronic kidney disease or acute kidney injury. Cautions: rare spontaneous reports of HIT in patients receiving fondaparinux have been received. Created in BioRender. Boucher, M. (2025) https://BioRender.com/w7hteooFig 1: the clotting cascade and actions of anticoagulants Anticoagulants: cautions for use Haemorrhage can occur with anticoagulants, therefore anticoagulants should be used with caution in conditions with increased potential for bleeding such as: Impaired haemostasis History of peptic ulcer disease Recent ischemic stroke or ophthalmic surgery Severe arterial hypertension Concomitant use with antiplatelets, NSAIDs, anticoagulants, thrombolytics, corticosteroids or SSRIs. Severe hepatic impairment, which reduces coagulation factors synthesis Summary Table: Drug/Class Mechanism of Action Route(s) of Administration Half-life Monitoring Key Adverse Effects / Notes Unfractionated Heparin (UFH) Inhibits thrombin and potentiates inhibitors of factor Xa IV infusion, SC (⚠️ avoid IM) Short (~1–2 hrs) aPTT monitoring required HIT, bleeding, hyperkalaemia; rapid onset, reversible quickly Low Molecular Weight Heparins (LMWHs)(e.g., dalteparin, tinzaparin, enoxaparin) Mainly inhibit factor Xa (less effect on thrombin) SC (once daily common) Longer than UFH (e.g., dalteparin SC: 3.5–4 hrs) Monitoring not routine; anti-Xa levels in renal impairment, obesity, pregnancy HIT (lower risk vs UFH), bleeding, hyperkalaemia Danaparoid Sodium Enhances antithrombin-mediated factor Xa inactivation, minor thrombin inhibition IV, SC Prolonged in renal impairment (steady state 4–5 days) Anti-Xa activity if prolonged use Alternative in HIT; caution in renal disease Fondaparinux Sodium Synthetic pentasaccharide → selectively inhibits factor Xa via antithrombin III SC, IV (⚠️ avoid IM) Long (17–21 hrs) Not routine; consider in renal impairment Rare HIT, bleeding; dose adjust in CKD References Parenteral anticoagulants | Treatment summaries | BNF | NICE accessed 11/9/24 Heparin (unfractionated) | Drugs | BNF | NICE accessed 11/9/24 Heparin 5,000 I.U./ml Solution for injection (with preservative) – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 11/9/24 Fragmin 5000 IU solution for injection – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 12/9/24 tinzaparin sodium Syringe 10,000 IU/ml Solution for injection in pre-filled syringe – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 17/9/24 Clexane Forte Syringes – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 17/9/24 Arixtra Fondaparinux sodium solution for injection 2.5 mg/ 0.5 ml – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 17/9/24 Epoprostenol 0.5 mg Powder and Solvent for Solution for Infusion – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 19/9/24 Danaparoid Sodium 750 anti-Xa units/0.6 ml, solution for injection – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 24/9/24 Do you think you’re ready? 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