VTE Prophylaxis in Hospitalized Adults: Current Recommendations
First-Line Pharmacologic Agents and Standard Dosing
For hospitalized medical patients at high risk for VTE (Padua score ≥4 or IMPROVE VTE score ≥2), low-molecular-weight heparin (LMWH) or fondaparinux should be initiated immediately upon admission and continued throughout hospitalization. 1, 2
Preferred Agents (in order of preference):
- Enoxaparin 40 mg subcutaneously once daily 1, 2
- Dalteparin 5,000 IU subcutaneously once daily 1, 2
- Fondaparinux 2.5 mg subcutaneously once daily 1, 2
- Unfractionated heparin 5,000 units subcutaneously every 8 hours (alternative, less preferred due to three-times-daily dosing and higher heparin-induced thrombocytopenia risk) 1, 2
LMWH is preferred over unfractionated heparin because of once-daily dosing, more predictable anticoagulation, lower risk of heparin-induced thrombocytopenia, and superior efficacy in preventing DVT. 2, 3
Duration of Prophylaxis
Pharmacologic prophylaxis should continue for the entire hospital stay or until the patient is fully ambulatory. 1, 2
Extension of prophylaxis beyond hospital discharge is NOT recommended for general medical inpatients—the American Society of Hematology strongly recommends against routine post-discharge continuation. 1
Exceptions requiring extended prophylaxis (up to 4 weeks):
- Major cancer surgery (abdominal/pelvic procedures) 1
- Hip fracture surgery 2
- Patients with restricted mobility, obesity, or history of VTE undergoing major surgery 1, 2
Renal Impairment Adjustments
Severe Renal Impairment (CrCl <30 mL/min):
Enoxaparin must be dose-reduced to 30 mg subcutaneously once daily due to 44% reduction in clearance and significantly increased bleeding risk. 1, 4, 5
Alternatively, switch to unfractionated heparin 5,000 units subcutaneously every 8-12 hours, which is not renally cleared and is preferred by many guidelines for severe renal dysfunction. 1, 2, 4
Fondaparinux is contraindicated when CrCl <30 mL/min. 1, 6
Moderate Renal Impairment (CrCl 30-50 mL/min):
Fondaparinux should be reduced to 1.5 mg once daily. 2, 6, 7
Enoxaparin 40 mg once daily may be continued, but consider anti-Xa monitoring (target 0.2-0.5 IU/mL at 4-6 hours post-dose) after 3-4 doses. 1, 4, 5
Dalteparin may be safer than enoxaparin in moderate renal impairment and can be used at standard prophylactic doses with anti-Xa monitoring if prolonged use (>10 days) is anticipated. 6, 5
Obesity Adjustments
Class 1-2 Obesity (BMI 30-40 kg/m²):
Standard prophylactic doses (enoxaparin 40 mg once daily, dalteparin 5,000 IU once daily) are appropriate. 1
Class 3 Obesity (BMI ≥40 kg/m² or weight >150 kg):
Increase enoxaparin to 40 mg subcutaneously every 12 hours (twice daily) for patients at very high VTE risk (e.g., immobile, septic, multiply injured). 1, 2, 5
Consider anti-Xa monitoring (target 0.2-0.5 IU/mL) in patients weighing >190 kg to ensure adequate anticoagulation without excessive accumulation. 1, 4, 5
Dalteparin may be increased to 5,000 IU twice daily or 7,500 IU once daily in morbidly obese patients at high VTE risk. 1
Do NOT cap doses in obese patients—underdosing occurs in 36% of patients >100 kg when weight-based adjustments are not made. 8
Bleeding Risk Assessment and Mechanical Prophylaxis
Absolute Contraindications to Pharmacologic Prophylaxis:
- Active major bleeding (>2 units transfused in 24 hours) 1, 2
- Severe thrombocytopenia (platelet count <50 × 10⁹/L) 1, 2
- Recent central nervous system bleed or intracranial lesion at high bleeding risk 1, 2
- Coagulopathy (INR >1.5) 1, 6
- Recent neurosurgery (within 24 hours) or spinal anesthesia/lumbar puncture 1, 2
When Pharmacologic Prophylaxis is Contraindicated:
Immediately initiate mechanical prophylaxis with intermittent pneumatic compression (IPC) devices—apply within 24 hours of admission and continue until pharmacologic agents can be safely started. 1, 2
Graduated compression stockings are NOT recommended as they have not demonstrated reduction in pulmonary embolism-related mortality and may cause harm. 1, 2
For very high-risk patients (e.g., critically ill, immobile, septic), combine pharmacologic and mechanical prophylaxis once bleeding risk is controlled. 1, 2
Special Populations
Cancer Patients:
All hospitalized cancer patients with acute medical illness or reduced mobility should receive LMWH prophylaxis (enoxaparin 40 mg once daily or dalteparin 5,000 IU once daily) unless contraindicated by bleeding risk. 1, 2
LMWH is preferred over unfractionated heparin for cancer patients due to superior efficacy and once-daily dosing. 1
Unfractionated heparin is preferred over LMWH for cancer patients with severe renal impairment (CrCl <30 mL/min). 1
COVID-19 Patients:
Standard prophylactic-dose anticoagulation (not intermediate or therapeutic doses) should be used for hospitalized COVID-19 patients in both non-critically ill and critically ill settings. 1, 2
Intermediate or therapeutic-dose anticoagulation in COVID-19 ICU patients increases bleeding without mortality benefit. 2
Critically Ill ICU Patients:
All critically ill patients should receive LMWH or unfractionated heparin prophylaxis unless actively bleeding or at high bleeding risk. 1, 2
Daily reassessment of VTE and bleeding risks is required in ICU patients due to rapidly changing clinical status. 1, 2
Direct oral anticoagulants (DOACs) should NOT be used for VTE prophylaxis in critically ill patients due to hemodynamic instability, drug-drug interaction risk, and high incidence of acute kidney injury. 2
Critical Pitfalls to Avoid
Do not use therapeutic-dose anticoagulation for primary prophylaxis—it increases bleeding without proven benefit in the absence of confirmed VTE. 2
Do not routinely extend prophylaxis beyond hospital discharge for general medical inpatients—only 39.5% of at-risk medical patients receive appropriate prophylaxis during hospitalization, but post-discharge extension is not supported by evidence. 1, 2
Do not use standard obesity-adjusted doses (40 mg every 12 hours) in patients with severe renal impairment—this creates unacceptable bleeding risk. 1, 4
Do not delay mechanical prophylaxis when pharmacologic agents are contraindicated—IPC devices must be applied within 24 hours to mitigate VTE risk. 2
Do not administer fondaparinux earlier than 6 hours post-surgery—this significantly increases major bleeding risk. 1, 2
Do not assume antiplatelet agents (aspirin) provide VTE protection—dedicated anticoagulant prophylaxis is necessary except in low-risk multiple myeloma outpatients. 1, 2
Monitor platelet counts every 2-3 days up to day 14 after initiating heparin to detect heparin-induced thrombocytopenia. 1