What are the mechanisms of action of antithrombotic (anti-clotting) medications?

From the Guidelines

Antithrombotic medications prevent or treat blood clots through several distinct mechanisms, including anticoagulants, antiplatelet medications, and thrombin inhibitors, with the most recent and highest quality evidence supporting the use of direct oral anticoagulants (DOACs) and P2Y12 inhibitors in specific clinical scenarios. The mechanisms of action of antithrombotic medications can be categorized into several groups:

• Anticoagulants, such as warfarin, which inhibit vitamin K-dependent clotting factors 1
• Direct oral anticoagulants (DOACs), including apixaban, rivaroxaban, dabigatran, and edoxaban, which directly target specific clotting factors like thrombin or factor Xa 1
• Heparins, including unfractionated heparin and low molecular weight heparins like enoxaparin, which enhance antithrombin activity 1
• Antiplatelet medications, which prevent platelet aggregation:
  • Aspirin, which inhibits thromboxane A2 production through COX-1 inhibition 1
  • P2Y12 inhibitors, such as clopidogrel, prasugrel, and ticagrelor, which block ADP-mediated platelet activation 1
  • Glycoprotein IIb/IIIa inhibitors, such as tirofiban and eptifibatide, which block the final common pathway of platelet aggregation and are used in acute coronary syndromes 1 The choice of antithrombotic medication and duration of treatment depend on the individual patient's risk factors, clinical characteristics, and specific clinical scenario, with the goal of minimizing the risk of thrombotic events while also reducing the risk of bleeding complications 1. In clinical practice, the selection of an antithrombotic agent should be based on shared decision making, taking into account the patient's risk factors, cost, tolerability, and potential for drug interactions, as well as the specific clinical scenario, such as acute coronary syndrome or atrial fibrillation 1. Regular monitoring of complete blood counts, renal function, and specific coagulation parameters is necessary to minimize the risk of bleeding complications, particularly in patients with renal impairment, low body weight, or advanced age 1. Dosing adjustments may be necessary in these patients to minimize the risk of bleeding complications while still providing effective antithrombotic therapy 1.

From the FDA Drug Label

Apixaban is a selective inhibitor of FXa. It does not require antithrombin III for antithrombotic activity. Apixaban inhibits free and clot-bound FXa, and prothrombinase activity. Warfarin sodium tablets and other coumarin anticoagulants act by inhibiting the synthesis of vitamin K dependent clotting factors, which include Factors II, VII, IX and X, and the anticoagulant proteins C and S.

The mechanisms of action of antithrombotic medications are:

• Inhibition of FXa: Apixaban inhibits FXa, which decreases thrombin generation and thrombus development 2.
• Inhibition of vitamin K dependent clotting factors: Warfarin inhibits the synthesis of vitamin K dependent clotting factors, including Factors II, VII, IX, and X, and the anticoagulant proteins C and S 3. The antithrombotic effects of these medications are achieved through different mechanisms, with apixaban targeting the coagulation cascade directly and warfarin interfering with the synthesis of clotting factors.

From the Research

Mechanisms of Action of Antithrombotic Medications

The mechanisms of action of antithrombotic medications involve the inhibition of platelet function and the prevention of blood clot formation.

• Aspirin inhibits platelet function through irreversible inhibition of cyclooxygenase (COX) activity 4.
• P2Y12 receptor inhibitors, such as clopidogrel, prasugrel, and ticagrelor, prevent platelet activation and aggregation by blocking the P2Y12 receptor 5, 6.
• Oral anticoagulants, such as warfarin and non-vitamin K antagonist oral anticoagulants (NOACs), prevent blood clot formation by inhibiting the production of vitamin K-dependent clotting factors or by directly inhibiting factor Xa or thrombin 7, 5, 6, 8.

Antithrombotic Regimens for Atrial Fibrillation Patients

For patients with atrial fibrillation undergoing percutaneous coronary intervention or with acute coronary syndrome, the recommended antithrombotic regimen is a dual antithrombotic therapy (DAT) consisting of a NOAC and a P2Y12 inhibitor, with aspirin administered during the periprocedural period 7, 8.

• The use of triple antithrombotic therapy (TAT) is associated with a significantly increased risk of bleeding, and its treatment duration should be as short as possible 7, 8.
• The choice of antithrombotic regimen depends on the individual patient's risk of stroke, bleeding, and coronary events, and should be guided by current international guidelines 7, 5, 6, 8.

Prevention and Treatment of Arterial and Venous Thromboembolism

Aspirin is effective in the prevention and treatment of arterial thromboembolism, including acute coronary syndrome, myocardial infarction, and ischemic stroke 4.

• Aspirin is also effective in the prevention of recurrent venous thromboembolism (VTE) in patients with unprovoked VTE who were treated with vitamin K antagonists (VKAs) or NOACs 4.
• Low doses of aspirin are suitable for long-term therapy in patients recovering from orthopedic or other surgeries, and have a reduced risk of bleeding compared to VKAs and NOACs 4.