What are the Venous Thromboembolism (VTE) prophylaxis medications, their doses, and rationale for use?

From the Guidelines

Venous thromboembolism (VTE) prophylaxis should be initiated with low molecular weight heparin (LMWH) or unfractionated heparin (UFH) for hospitalized patients at risk of VTE, with enoxaparin 40mg subcutaneously once daily being a standard LMWH regimen, as recommended by the most recent guidelines 1. The choice of VTE prophylaxis medication and dose depends on various factors, including the patient's renal function, bleeding risk, and type of surgery or medical condition.

• For most hospitalized patients at risk of VTE, enoxaparin 40mg subcutaneously once daily is the standard LMWH regimen, with dose reduction to 30mg daily for patients with renal impairment (CrCl <30ml/min) 1.
• Alternatively, UFH 5000 units subcutaneously every 8-12 hours can be used, particularly in patients with renal dysfunction 1.
• For extended prophylaxis after hospital discharge, rivaroxaban 10mg daily for 31-39 days is effective for high-risk orthopedic or cancer patients, as supported by recent studies 1.
• Apixaban 2.5mg twice daily is another DOAC option for extended prophylaxis, although its use may be limited by renal function and other factors 1. These medications work by inhibiting different points in the coagulation cascade - LMWH and UFH enhance antithrombin activity to inhibit factor Xa and thrombin, while DOACs directly inhibit factor Xa. Mechanical prophylaxis with intermittent pneumatic compression devices should be used when anticoagulants are contraindicated due to bleeding risk, as recommended by recent guidelines 1. Prophylaxis should generally continue throughout hospitalization and potentially beyond discharge for high-risk patients, with the goal of reducing the risk of deep vein thrombosis and pulmonary embolism, which carry substantial morbidity and mortality if not prevented 1.

From the FDA Drug Label

XARELTO is a factor Xa inhibitor indicated: ... for the prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery ( 1.5) for prophylaxis of venous thromboembolism (VTE) in acutely ill medical patients ( 1. 6) Prophylaxis of DVT Following Hip or Knee Replacement Surgery: 10 mg orally once daily with or without food ( 2.1) Prophylaxis of VTE in Acutely Ill Medical Patients at Risk for Thromboembolic Complications Not at High Risk of Bleeding: 10 mg once daily, with or without food, in hospital and after hospital discharge for a total recommended duration of 31 to 39 days ( 2.1)

The rationale for use of rivaroxaban for VTE prophylaxis is to prevent deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients at risk. The recommended doses for VTE prophylaxis are:

• 10 mg orally once daily for patients undergoing knee or hip replacement surgery
• 10 mg once daily for acutely ill medical patients at risk for thromboembolic complications, for a total recommended duration of 31 to 39 days 2

From the Research

VTE Prophylaxis Medications and Doses

• Low-dose unfractionated heparin or low-molecular-weight heparin (LMWH) are recommended for VTE prophylaxis in acutely ill medical patients 3
• Fixed doses of LMWH are customarily used for VTE prophylaxis regardless of body weight or body mass index, but weight-based dosing with larger doses for obese patients may be more effective than fixed doses 3
• Reducing LMWH doses for patients with severe renal impairment may offer a safety advantage 3
• Subcutaneous heparin or low-molecular-weight heparin are recommended for VTE prophylaxis in critically ill patients without contraindication 4
• Enoxaparin, a LMWH, appears to be as effective as unfractionated heparin for the treatment of patients with acute pulmonary thromboembolism 5

Rationale for Use

• The risk for VTE increases as the number of risk factors increases, so the aggressiveness of VTE prophylaxis in medical and surgical patients increases as the risk of VTE increases 3
• VTE prophylaxis is underutilized in medical patients despite the fact that DVT is common and guidelines for prophylaxis are available 3
• Obesity and the receipt of vasopressors are risk factors consistently identified in observational studies that may require more aggressive prophylaxis strategies 4
• Non-vitamin K antagonist oral anticoagulants (NOACs) provide Factor Xa inhibition to prevent the thrombin generation essential in thromboembolism development, but evidence for the efficacy and safety of most NOACs is conflicting regarding extended-duration prophylaxis 6

Specific Medications and Doses

• Enoxaparin: 1 mg/kg/dose given subcutaneously twice daily 5
• Fondaparinux: a new alternative for VTE prophylaxis and treatment, but specific doses not mentioned in the studies 3
• Rivaroxaban and apixaban: have shown increased risks of major bleeding in extended-duration prophylaxis 6
• Betrixaban: the only NOAC approved in the USA for extended-duration VTE prophylaxis, and it demonstrates efficacy with fewer adverse effects than other NOACs 6