What is the recommended dose of heparin (unfractionated heparin) for thromboprophylaxis in ICU patients, including dose adjustments for impaired renal function?

Heparin Dosing for Thromboprophylaxis in ICU Patients

For ICU patients with normal renal function, use unfractionated heparin (UFH) 5000 units subcutaneously every 8 hours, which is superior to twice-daily dosing and provides more consistent anticoagulation. 1, 2

Standard Prophylactic Dosing in ICU

The recommended regimen is UFH 5000 units subcutaneously every 8 hours for critically ill patients. 3, 1, 2 This three-times-daily dosing provides more effective VTE prophylaxis than twice-daily administration, with more consistent anticoagulant effect and greater reduction in DVT incidence. 2

• The American College of Chest Physicians supports using either LMWH or UFH thromboprophylaxis over no prophylaxis in critically ill patients (Grade 2C recommendation). 3
• Low molecular weight heparin (LMWH) may reduce pulmonary embolism compared to UFH (risk ratio 0.62,95% CI 0.39-1.00), though both agents are acceptable. 4
• Any heparin prophylaxis reduces DVT (risk ratio 0.51) and pulmonary embolism (risk ratio 0.52) compared to placebo without significantly increasing major bleeding. 4

Alternative Standard Dosing Options

• UFH 5000 units subcutaneously every 12 hours is acceptable for moderate-risk medical patients but provides less robust protection than every-8-hour dosing. 2
• LMWH alternatives: Enoxaparin 40 mg daily, dalteparin 5000 units daily, or tinzaparin 4500 units daily for patients with normal renal function. 1

Dose Adjustments for Renal Failure

Creatinine Clearance 15-30 mL/min

For patients with BMI <30 kg/m²:

• UFH bolus followed by 200 IU/kg/24h continuous infusion for standard prophylaxis 3
• Alternative: LMWH (enoxaparin) 2000 IU every 24 hours 3

For patients with BMI >30 kg/m²:

• LMWH (enoxaparin) 2000 IU every 12 hours 3

Creatinine Clearance <15 mL/min (Severe Renal Impairment)

For patients with BMI <30 kg/m²:

• UFH 5000 units subcutaneously every 12 hours OR continuous infusion 3

For patients with BMI >30 kg/m²:

• UFH 5000 units subcutaneously every 8 hours OR continuous infusion 3

UFH is the preferred agent in severe renal impairment (CrCl <30 mL/min) because it is primarily metabolized by the liver and does not require dose adjustment for renal function. 1, 2, 5

Creatinine Clearance >30 mL/min

For patients with BMI <30 kg/m²:

• LMWH (enoxaparin) 4000 IU every 24 hours 3

For patients with BMI >30 kg/m²:

• LMWH (enoxaparin) 4000 IU every 12 hours 3

Weight-Based Dosing Considerations

Obesity (BMI >30 kg/m²) requires dose adjustment to prevent VTE breakthrough. 3

• For obese patients with normal renal function, consider enoxaparin 40 mg subcutaneously every 12 hours or weight-based dosing at 0.5 mg/kg every 12 hours. 1
• The French Working Group on Perioperative Haemostasis recommends a 50% increase in prophylactic dose for obese patients. 3
• Weight-adjusted thromboprophylaxis reduces VTE in obese hospitalized patients compared to standard dosing. 3

Monitoring Recommendations

Anti-Xa monitoring targets vary by indication: 3

• Standard prophylaxis with LMWH: Avoid overdose (anti-Xa <1.5 IU/mL for enoxaparin) 3
• Intermediate prophylaxis with UFH: Detectable activity and <0.5 IU/mL 3
• Therapeutic prophylaxis with UFH: 0.5-0.7 IU/mL 3

Routine anti-Xa monitoring is not required for most patients on prophylactic doses, but should be considered in patients with extreme body weights or renal impairment. 1

Duration of Prophylaxis

Continue thromboprophylaxis for at least 7-10 days or until the patient is fully ambulatory, whichever is longer. 1, 2, 6

• In COVID-19 or hypercoagulable critically ill patients, consider a sequential strategy: increased prophylactic anticoagulation for 7-10 days (when thrombotic risk peaks), then decrease to standard dose. 3
• Extended prophylaxis beyond 10 days should be considered for high-risk patients with ongoing immobility or risk factors. 2

Critical Pitfalls to Avoid

Do not use UFH in patients with active or history of heparin-induced thrombocytopenia (HIT). 2 Use argatroban, danaparoid, or fondaparinux instead. 3, 5

• Monitor platelet counts every 2-3 days from day 4 to day 14 in patients with HIT risk ≥1%. 2
• Avoid administering anticoagulants within 10-12 hours of neuraxial anesthesia due to spinal hematoma risk. 2
• In severe renal impairment, avoid LMWH accumulation by switching to UFH or reducing LMWH dose significantly. 3, 1
• Heparin resistance may occur in inflammatory states (including COVID-19) due to elevated acute phase reactants; consider measuring both aPTT and anti-Xa levels if therapeutic effect is questioned. 3

Continuous Intravenous Infusion Alternative

For patients requiring precise anticoagulation control or with absorption concerns, UFH can be given as continuous IV infusion at 625 IU/hour (15,000 IU/24h) for prophylaxis. 7

• This method showed equivalent safety to subcutaneous administration in surgical ICU patients. 7
• Continuous infusion may be preferred in hemodynamically unstable patients or those with peripheral edema affecting subcutaneous absorption. 7