What is the dosing protocol for unfractionated heparin (UFH) in the treatment of limb ischemia?

Unfractionated Heparin Administration for Acute Limb Ischemia

In patients with acute limb ischemia (ALI), administer unfractionated heparin immediately upon diagnosis with an intravenous bolus of 80 units/kg (maximum 5000 units) followed by continuous infusion at 18 units/kg/hour, targeting an aPTT of 1.5-2.5 times control (approximately 60-85 seconds). 1, 2

Initial Bolus and Infusion Protocol

Administer UFH as soon as ALI is diagnosed, regardless of the anatomic level or underlying cause (embolism vs thrombosis), unless contraindicated by active bleeding or high bleeding risk. 1

Standard Weight-Based Dosing:

• Initial IV bolus: 80 units/kg (maximum 5000 units) 2, 3
• Continuous infusion: 18 units/kg/hour (maximum 1000 units/hour initially) 2, 3
• Alternative if no IV access: 333 units/kg subcutaneous loading dose, then 250 units/kg subcutaneously every 12 hours 1, 2

The 80:18 dosing regimen achieves therapeutic anticoagulation significantly faster than lower-dose protocols (60:12), with 36% of patients reaching therapeutic range at 6 hours versus only 16.7% with lower dosing. 3

Monitoring and Dose Adjustment

Measure the first aPTT at 6 hours after initiating therapy, then every 4-6 hours until stable in therapeutic range, followed by daily monitoring. 4, 2

Target aPTT Range:

• Therapeutic goal: aPTT 1.5-2.5 times normal control (approximately 60-85 seconds or 50-70 seconds depending on institutional assay) 1, 4, 2
• Alternative monitoring: Anti-factor Xa level of 0.3-0.7 IU/mL if aPTT monitoring is unreliable 1, 4

Dose Adjustment Nomogram:

• aPTT <35 seconds: Give 80 units/kg bolus, increase infusion by 4 units/kg/hour 4
• aPTT 35-45 seconds: Give 40 units/kg bolus, increase infusion by 2 units/kg/hour 4
• aPTT 46-70 seconds: No change (therapeutic range) 4
• aPTT 71-90 seconds: Decrease infusion by 2 units/kg/hour 4
• aPTT >90 seconds: Hold infusion for 1 hour, then decrease by 3 units/kg/hour 4

Rationale and Mechanism

UFH prevents thrombus propagation and distal embolization while potentially providing anti-inflammatory effects that lessen ischemic injury. 1, 5

The logic behind immediate anticoagulation is universally accepted despite the absence of randomized trials demonstrating improved outcomes, because the high risk of limb loss without intervention has led to widespread adoption of this practice. 1 Heparin may reduce skeletal muscle infarction through both anticoagulant and non-anticoagulant mechanisms, including restoration of endothelial integrity and modulation of inflammatory mediators. 5

Special Populations and Contraindications

Absolute Contraindications:

• Active bleeding or high bleeding risk 1
• History of heparin-induced thrombocytopenia (HIT) - use argatroban, danaparoid, or fondaparinux instead 6, 4, 7
• Recent neuraxial anesthesia (risk of spinal hematoma) 6
• ALI associated with aortic dissection or major vascular trauma 1

Severe Renal Impairment (CrCl <30 mL/min):

UFH is the preferred anticoagulant over LMWH in patients with severe kidney disease because it is primarily metabolized hepatically rather than renally excreted. 6, 4 Use standard weight-based dosing without dose reduction, but monitor aPTT more frequently. 6

Monitoring for Complications:

• Check platelet count every 2-3 days from day 4 to day 14 to screen for HIT, particularly in post-surgical patients where HIT risk may reach 5%. 1, 2
• Monitor for bleeding: Periodically check hematocrit and occult blood in stool throughout therapy 2

Common Pitfalls and How to Avoid Them

Do not use lower-dose "prophylactic" heparin regimens (5000 units subcutaneously every 8-12 hours) for acute limb ischemia - these doses are appropriate only for DVT prophylaxis in immobile patients, not for therapeutic anticoagulation in ALI. 1, 8

Avoid intramuscular administration due to frequent hematoma formation at injection sites. 2

Do not delay heparin administration while awaiting imaging - start anticoagulation immediately upon clinical diagnosis of ALI, as diagnostic imaging should not delay treatment. 1

Recognize heparin resistance (need for >35,000 IU/day to achieve target aPTT), which may occur in hypercoagulable states including COVID-19 patients with ALI. 9, 7 In such cases, consider monitoring anti-factor Xa levels instead of aPTT or switching to alternative anticoagulants. 9

Ensure adequate mixing when adding heparin to IV solutions - invert the container at least six times to prevent pooling of heparin in the solution. 2

Duration and Transition

Continue UFH until definitive revascularization is performed or until transitioning to oral anticoagulation if revascularization is not planned. 1

When converting to warfarin, continue full-dose heparin for several days until INR reaches stable therapeutic range (2-3), then discontinue heparin without tapering. 2 For other oral anticoagulants, stop IV heparin immediately after administering the first dose of the oral agent. 2