What is the recommended protocol for managing acute limb ischemia with a heparin (unfractionated heparin) drip and monitoring Activated Partial Thromboplastin Time (APTT)?

Management Protocol for Acute Limb Ischemia with Heparin Drip and APTT Monitoring

For acute limb ischemia, unfractionated heparin should be administered intravenously with an initial bolus of 80 U/kg followed by 18 U/kg/hour continuous infusion, with APTT monitoring targeting a ratio of 1.5-2.5 times normal (corresponding to anti-factor Xa levels of 0.3-0.7 IU/mL). 1, 2

Initial Management

1. Immediate anticoagulation:

   • Administer intravenous unfractionated heparin (UFH) without delay when ALI is suspected 1
   • Initial dosing: 80 U/kg IV bolus, followed by 18 U/kg/hour continuous infusion 1
   • Use weight-based dosing algorithm to achieve therapeutic anticoagulation quickly

2. APTT monitoring protocol:

   • First APTT measurement: 4-6 hours after initiating heparin infusion 1
   • Target APTT ratio: 1.5-2.5 times normal control 1
   • This corresponds to heparin levels of 0.3-0.7 IU/mL by anti-factor Xa assay

Heparin Dose Adjustment

Weight-Based Nomogram for Heparin Dosing 1:

APTT Result	Action
<35 seconds (<1.2× control)	80 U/kg bolus, then increase infusion by 4 U/kg/h
35-45 seconds (1.2-1.5× control)	40 U/kg bolus, then increase infusion by 2 U/kg/h
46-70 seconds (1.5-2.3× control)	No change
71-90 seconds (2.3-3× control)	Decrease infusion rate by 2 U/kg/h
>90 seconds (>3× control)	Hold infusion for 1 hour, then decrease rate by 3 U/kg/h

Monitoring Schedule

• After initial APTT at 4-6 hours, repeat APTT:
  • Every 6 hours until stable in therapeutic range
  • Then daily once stable
• Monitor platelet count every 2-3 days from day 4 to day 14 to screen for heparin-induced thrombocytopenia (HIT) 1
• Consider anti-factor Xa levels in patients with heparin resistance or abnormal baseline APTT 1

Special Considerations

1. Heparin resistance:

   • May occur in ALI patients, particularly those with COVID-19 3
   • If unable to achieve therapeutic APTT despite high doses (>35,000 IU/day)
   • Consider measuring anti-factor Xa levels
   • May need alternative anticoagulants (direct thrombin inhibitors) 1

2. Timing considerations:

   • For marginally or immediately threatened limbs (Category IIa/IIb ALI): revascularization within 6 hours 1
   • For viable limbs (Category I ALI): revascularization within 6-24 hours 1
   • Heparin therapy should continue during this period

3. Heparin-induced thrombocytopenia (HIT):

   • Risk up to 5% with UFH 1
   • Monitor for platelet count drop of ≥50% between days 5-10 of therapy
   • If HIT suspected, switch to direct thrombin inhibitor 1

Transition to Oral Anticoagulation

• When transitioning to oral anticoagulants:
  • Begin oral anticoagulant while continuing heparin
  • Continue full heparin therapy until INR reaches therapeutic range (usually INR >2.0 for at least 24 hours) 1, 2
  • Measure prothrombin time when heparin effect is minimal (approximately 5 hours after IV bolus) 2

Common Pitfalls to Avoid

1. Inadequate initial dosing: Subtherapeutic anticoagulation increases risk of recurrent thromboembolism by up to 15-fold 1

2. Delayed monitoring: Failure to check APTT within 4-6 hours may lead to prolonged subtherapeutic or supratherapeutic anticoagulation

3. Ignoring institutional APTT reagent variability: Each laboratory should calibrate their APTT reagent to correspond to therapeutic heparin levels (0.3-0.7 IU/mL anti-Xa) 1

4. Overlooking HIT: Failure to monitor platelet counts may result in missing this potentially fatal complication

5. Premature discontinuation: Heparin should be continued until definitive treatment (surgical or endovascular) is performed or until transition to oral anticoagulation is complete 1