What is the recommended protocol for low dose heparin (Unfractionated Heparin (UFH) / Low Molecular Weight Heparin (LMWH)) infusion?

Low Dose Heparin Infusion Protocol

Standard Prophylactic Dosing

For DVT prophylaxis in most clinical settings, UFH 5,000 IU subcutaneously every 8 hours is the recommended regimen, as three times daily dosing has been proven more effective than twice-daily administration in preventing deep vein thrombosis. 1

Subcutaneous Administration (Prophylactic)

• Standard dose: UFH 5,000 IU subcutaneously every 8 hours starting 1-2 hours before surgery and continuing for 7-10 days or until fully ambulatory 2, 3
• Alternative twice-daily dosing: UFH 5,000 IU every 12 hours may be used in medical patients, though this shows less reduction in proximal DVT and PE (p=0.05) but significantly lower major bleeding risk (p<0.001) 1
• Administration technique: Use deep subcutaneous (intrafat) injection with a fine needle (25-26 gauge) in the arm or abdomen, rotating sites to prevent hematoma formation 3

Intravenous Administration (Therapeutic)

For therapeutic anticoagulation, UFH should be administered as a weight-based bolus of 80 U/kg followed by continuous infusion of 18 U/kg per hour, adjusted to maintain aPTT ratio of 1.5-2.5 (corresponding to anti-factor Xa levels of 0.3-0.7 IU/mL). 2, 3

• Initial bolus: 80 U/kg IV (maximum 4000 U for patients >70 kg when used with fibrinolytics) 2
• Continuous infusion: 18 U/kg per hour (maximum 1000 U/hr initial infusion for patients >70 kg when used with fibrinolytics) 2
• Alternative weight-based dosing without fibrinolytics: 60-70 U/kg IV bolus followed by 12-15 U/kg per hour infusion 2
• Monitoring: Adjust infusion using validated institutional nomograms to maintain aPTT ratio of 1.5-2.5, which approximates heparin levels of 0.3-0.7 IU/mL by anti-factor Xa assay 2, 3

Subcutaneous Therapeutic Dosing (Alternative)

• Initial dose: 333 U/kg subcutaneously followed by 250 U/kg twice daily 2
• This regimen has been shown as safe and effective as weight-based LMWH for VTE treatment 2

Special Population Adjustments

Renal Impairment

UFH is the preferred anticoagulant in patients with creatinine clearance <30 mL/min, as it is primarily metabolized by the liver rather than renally excreted. 1, 4

• Standard prophylactic dosing of 5,000 IU every 8 hours can be used without dose adjustment 2, 1
• For therapeutic anticoagulation in renal failure, use standard weight-based IV dosing with aPTT monitoring 4

Elderly Patients (>60 years)

• Patients over 60 years may require lower doses of heparin 3
• Consider starting at the lower end of dosing ranges and titrate based on monitoring 3

Pediatric Patients

• Initial dose: 50 units/kg IV infusion 3
• Maintenance dose: 100 units/kg IV infusion every 4 hours, or 20,000 units/m²/24 hours continuously 3

Cancer Patients

• Surgical prophylaxis: UFH 5,000 IU every 8-12 hours starting 1-2 hours before operation 2
• Higher prophylactic doses (5,000 IU vs 2,500 IU daily) increase efficacy without significantly enhancing bleeding in cancer surgery patients 2
• Extended prophylaxis for up to 4 weeks should be considered for high-risk cancer patients 2

Trauma Patients

• Moderate-high risk elderly trauma patients: UFH 5,000 IU every 8 hours, initiated as soon as possible 2
• Delay initiation by 24 hours in cases of CNS injuries, active bleeding, coagulopathy, hemodynamic instability, or solid organ injury 2
• In traumatic brain injury, hold prophylaxis until CT scan shows no progression 2

Monitoring Requirements

Prophylactic Dosing

• Platelet monitoring: Check platelet counts every 2-3 days from day 4 to day 14 in patients with HIT risk ≥1% 2
• Routine coagulation monitoring is NOT required for standard prophylactic dosing 1, 3
• Periodic hematocrit and occult blood in stool testing recommended throughout therapy 3

Therapeutic Dosing

• aPTT monitoring: Draw samples 4-6 hours after subcutaneous injection or at any time during continuous IV infusion 3
• Target aPTT: 1.5-2.0 times control (approximately 50-70 seconds) 2
• Alternative monitoring: Anti-factor Xa levels (0.3-0.7 IU/mL) may be superior in patients with apparent heparin resistance 4
• Site-specific validation of aPTT therapeutic range is essential, as reagent variability affects results 4

Timing Considerations with Neuraxial Anesthesia

UFH Prophylactic Dosing

• First dose: Administer no sooner than 1 hour after needle/catheter placement 2
• Neuraxial puncture/catheter manipulation: Should not occur within 4-6 hours after UFH administration 2
• Subsequent UFH dosing: May occur no earlier than 1 hour after catheter removal 2

UFH Therapeutic Dosing

• Neuraxial block/catheter removal: Should not occur within 12 hours after therapeutic UFH administration (>15,000 U/24 hours) 2

When to Choose UFH Over LMWH

UFH should be selected over LMWH in the following clinical scenarios:

• Severe renal impairment (CrCl <30 mL/min) 1, 4
• Need for rapid reversibility with protamine sulfate 1
• Patients without reliable IV access who cannot receive monitored therapeutic anticoagulation 1
• Active or history of heparin-induced thrombocytopenia (use direct thrombin inhibitor or fondaparinux instead) 1

However, LMWH is generally preferred when renal function is normal due to more predictable pharmacokinetics, once-daily dosing, no need for routine monitoring, reduced healthcare worker exposure, and lower rates of missed doses 2, 1

Common Pitfalls and How to Avoid Them

Heparin-Induced Thrombocytopenia (HIT)

• Absolute contraindication: Never use UFH in patients with active or history of HIT 1
• Risk: Up to 5% with UFH, particularly high in orthopedic surgery patients 2
• Monitoring: Check platelet counts every 2-3 days from day 4-14 in patients with HIT risk ≥1% 2
• Alternative agents: Use direct thrombin inhibitor or fondaparinux if HIT develops 1

Inadequate aPTT Monitoring

• Critical error: Many clinical trials comparing UFH to LMWH failed to validate aPTT therapeutic ranges, leading to unreliable results 4
• Solution: Ensure your institution has validated the aPTT therapeutic range to correspond with anti-factor Xa levels of 0.3-0.7 IU/mL 2, 4

Inappropriate Dosing in Obesity

• Severe obesity (>150 kg): Anti-factor Xa monitoring is prudent when administering weight-based doses 4
• Standard weight-based dosing may need adjustment based on anti-factor Xa levels 4

Spinal Hematoma Risk

• Never administer anticoagulants too close to neuraxial anesthesia due to spinal hematoma risk 1
• Follow strict timing protocols outlined above for neuraxial procedures 2

Unnecessary Anti-Xa Monitoring

• Do not routinely monitor anti-Xa levels for prophylactic dosing, as this is unnecessary for standard prophylaxis 1
• Reserve anti-Xa monitoring for therapeutic dosing in patients with heparin resistance or extreme body weights 4

Bridging Therapy Errors

• When bridging to warfarin, overlap UFH for minimum 5 days and continue until INR is therapeutic (2.0-3.0) for 2 consecutive days 2
• For perioperative bridging in high thromboembolic risk patients, stop UFH 4 hours before surgery and resume 1-2 days postoperatively depending on hemostatic status 2