What is the mechanism of action of Clexane (enoxaparin)?

From the Guidelines

Enoxaparin (Clexane) works primarily by enhancing the activity of antithrombin III, which inhibits coagulation factors Xa and IIa (thrombin), with a preferential inhibition of factor Xa over thrombin in a ratio of approximately 4:1, as stated in the 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes 1. The mechanism of action of enoxaparin involves disrupting the coagulation cascade and preventing blood clot formation.

Key Points

• Enoxaparin has a more predictable dose-response relationship, better bioavailability, and longer half-life due to its smaller molecular size compared to unfractionated heparin.
• It allows for once or twice daily subcutaneous dosing without routine monitoring in most patients.
• Enoxaparin does not significantly bind to plasma proteins, endothelial cells, or macrophages, which contributes to its more predictable anticoagulant effect.
• The drug is primarily eliminated through renal clearance, so dose adjustments are necessary in patients with kidney impairment, as recommended by the manufacturer for patients with severe renal insufficiency (creatinine clearance <30 mL/min) 1.
• The anticoagulant effect begins within 1-2 hours after subcutaneous injection and lasts approximately 12 hours, making it effective for both treatment and prevention of thromboembolic disorders. Some studies have shown that enoxaparin is associated with a 2- to 3-fold increased risk of bleeding when administered in standard, unadjusted therapeutic doses to patients with severe renal insufficiency compared with those without severe renal insufficiency 1.

Important Considerations

• Dose reductions are recommended for patients with creatinine clearance values less than 30 mL/min.
• Some evidence supports downward dose adjustments of enoxaparin in the management of patients with creatinine clearance values of 30 to 60 mL/min.
• Monitoring of peak anti-Xa levels is recommended for patients with cancer and creatinine clearance less than 30 mL/min receiving dalteparin for extended treatment of acute VTE.

From the Research

Mechanism of Action of Clexane (Enoxaparin)

The mechanism of action of Clexane (enoxaparin) involves the inhibition of thrombin generation and factor Xa activity. Key points about its mechanism include:

• Enoxaparin binds to and increases the activity of antithrombin III, resulting in the inhibition of prothrombinase-mediated thrombin generation and direct thrombin generation by binding to factor Xa and thrombin factor IIa 2.
• It has a greater anti-Xa activity than unfractionated heparin, which contributes to its antithrombotic effects 3.
• Enoxaparin inhibits tissue factor-mediated prothrombinase assembly and inactivates platelet prothrombinase activity, resulting in reduced thrombin generation 3.
• The anti-Xa activity of enoxaparin is important in determining its overall antithrombotic potential 3.

Comparison with Other Anticoagulants

Comparisons with other anticoagulants, such as fondaparinux, have been made:

• Fondaparinux has a more selective inhibition of activated factor X (FXa) and seems to be superior to enoxaparin in preventing deep vein thrombosis 4.
• Enoxaparin has a supplementary anti-activated factor II activity, which contributes to its more profound inhibition of thrombin generation compared to fondaparinux 4.

Clinical Implications

Clinical implications of the mechanism of action of enoxaparin include:

• The risk of over-anticoagulation when administering intravenous unfractionated heparin to subjects already receiving enoxaparin, which can result in excessive anticoagulation not detected by activated clotting time 5.
• The importance of monitoring anti-Xa and anti-IIa activities, as well as thrombin generation, to assess the anticoagulation effect of enoxaparin 5.