What dose and duration of prophylactic anticoagulation should be used in an average adult patient without contraindications?

Prophylactic Anticoagulation: Dose and Duration

For hospitalized adult patients requiring VTE prophylaxis, use enoxaparin 40 mg subcutaneously once daily, dalteparin 5000 IU subcutaneously once daily, fondaparinux 2.5 mg subcutaneously once daily, or unfractionated heparin 5000 units subcutaneously three times daily, continued throughout hospitalization (minimum 7-10 days for acute medical illness). 1, 2

Standard Prophylactic Dosing Regimens

Medical Inpatients

• Low-molecular-weight heparin (LMWH) is the preferred agent over unfractionated heparin due to more predictable pharmacokinetics and once-daily dosing convenience 1
• Enoxaparin: 40 mg subcutaneously once daily 1, 2
• Dalteparin: 5000 IU subcutaneously once daily 1, 2
• Fondaparinux: 2.5 mg subcutaneously once daily 1, 2
• Unfractionated heparin (UFH): 5000 units subcutaneously three times daily 1, 2

Surgical Patients

• Enoxaparin: 40 mg subcutaneously once daily starting preoperatively 1, 2
• Dalteparin: 2500 IU once daily for low-risk patients, or 2500 IU 12 hours after surgery then 5000 IU once daily for high-risk patients 2
• UFH: 5000 units subcutaneously twice or three times daily 2

Orthopedic Surgery (Hip/Knee Replacement)

• Enoxaparin: 30 mg subcutaneously twice daily starting 12 hours before or after surgery 1, 2, 3
• Rivaroxaban: 10 mg orally once daily starting 6-10 hours after surgery once hemostasis established 2, 3
• Duration for hip replacement: 35 days 3
• Duration for knee replacement: 12 days 3

Duration of Prophylaxis

Hospitalized Medical Patients

• Standard-dose prophylaxis: Continue throughout hospitalization until discharge 1
• Acute medical illness with reduced mobility: 7-10 days minimum 1
• High-risk outpatients (BMI >30 kg/m², age >70 years, active cancer, personal history of VTE, major surgery within 3 months): 7-14 days 1

Post-Discharge Extended Prophylaxis

• Acutely ill medical patients: Total duration of 31-39 days (including hospitalization and post-discharge) for patients at continued VTE risk 3
• Post-discharge prophylaxis should be decided case-by-case, with age >75 years and prior VTE history being strong indicators for extended therapy 1

Cancer Patients

• Hospitalized cancer patients: Continue prophylaxis throughout hospitalization 1, 4
• Major abdominal/pelvic cancer surgery: Consider extending prophylaxis up to 4 weeks post-operatively in high-risk patients 4
• Ambulatory cancer patients on chemotherapy: Extended prophylaxis with LMWH for high-risk features 4

Severe/Critically Ill Patients (e.g., COVID-19)

• Increased-dose prophylaxis (intermediate or therapeutic): 7-10 days total duration 1
• Very high thrombotic risk patients: Systematic screening for thrombosis before de-escalation at days 7-10 1

Special Dosing Considerations

Renal Impairment

• Creatinine clearance <30 mL/min: Avoid fondaparinux and adjust LMWH dosing 1, 3
• Enoxaparin with CrCl <30 mL/min: Reduce to 1 mg/kg once daily (for therapeutic dosing) 1, 5
• Severe renal impairment: Prefer UFH or tinzaparin/dalteparin (less renal-dependent elimination) 1

Obesity

• Weight >120 kg: Consider weight-based dosing (0.5 mg/kg enoxaparin every 12 hours) to avoid underdosing 2, 6
• Weight-based twice-daily enoxaparin (0.4-0.5 mg/kg) achieves therapeutic anti-Xa levels more reliably than fixed dosing in obese patients 7, 6

Monitoring

• Standard prophylactic doses: No routine anti-Xa monitoring required 1
• Intermediate or therapeutic doses: Monitor peak anti-Xa level (4 hours after third injection) to avoid overdose 1
• Target anti-Xa for prophylaxis: 0.2-0.4 IU/mL 6
• Overdose threshold: >1.5 IU/mL for enoxaparin and tinzaparin 1

Critical Pitfalls to Avoid

• Do not use rivaroxaban for VTE prophylaxis in acutely ill general medical patients due to increased bleeding risk without clear benefit 2
• Do not prematurely discontinue prophylaxis before minimum duration is met, as this significantly increases thrombotic risk 2
• Do not underdose obese patients with fixed-dose regimens; use weight-based dosing (0.5 mg/kg enoxaparin) 2, 6
• Do not use fondaparinux or LMWH in severe renal impairment (CrCl <15-30 mL/min); switch to UFH 1, 2, 3
• Do not use mechanical prophylaxis alone unless pharmacologic prophylaxis is contraindicated by active bleeding or high bleeding risk 2
• Do not delay initiation of prophylaxis in surgical patients; start preoperatively when possible 1, 2