What is the recommended protocol for initiating intravenous unfractionated heparin in a patient with acute limb ischemia, including dosing, aPTT monitoring, and contraindications?

Initiating Intravenous Unfractionated Heparin for Acute Limb Ischemia

Administer unfractionated heparin immediately upon clinical diagnosis of acute limb ischemia with a bolus of 60-80 IU/kg (maximum 4000-5000 IU) followed by continuous infusion of 12-18 IU/kg/hour (maximum 1000 IU/hour), targeting an aPTT of 60-80 seconds or aPTT ratio of 1.5-2.5. 1

Immediate Bolus Dosing

• Give 60-80 IU/kg IV bolus (capped at 4000-5000 IU maximum) as soon as acute limb ischemia is clinically diagnosed 1
• Do not delay heparin administration for imaging studies—clinical diagnosis alone (pain, pallor, pulselessness, paresthesias, paralysis, poikilothermia) is sufficient to initiate therapy 1, 2
• Heparin prevents thrombus propagation and provides anti-inflammatory effects that mitigate ischemia, making every minute critical since skeletal muscle tolerates ischemia for only 4-6 hours 1, 2

Continuous Infusion Protocol

• Start continuous infusion at 12-18 IU/kg/hour (maximum 1000 IU/hour) immediately after the bolus 1
• Target therapeutic aPTT range of 60-80 seconds or aPTT ratio of 1.5-2.5 (corresponding to anti-factor Xa levels of 0.3-0.7 IU/mL) 1
• Check aPTT at 3,6,12, and 24 hours after initiation, then daily once therapeutic 2
• Use a validated, institution-specific dose-adjustment nomogram to titrate the infusion based on aPTT results 1

Alternative Subcutaneous Dosing

If IV access is problematic or the patient requires transfer:

• Give 333 IU/kg subcutaneous bolus, then 250 IU/kg subcutaneously twice daily 1
• This weight-based unmonitored subcutaneous regimen provides effective anticoagulation comparable to IV administration 1

Monitoring Requirements

Activated Partial Thromboplastin Time (aPTT)

• Draw baseline aPTT before initiating heparin 1
• Recheck aPTT at 3,6,12, and 24 hours after starting infusion 2
• Once therapeutic range (60-80 seconds or ratio 1.5-2.5) is achieved, monitor aPTT daily 1
• Adjust infusion rate using your institution's validated nomogram to maintain therapeutic range 1

Platelet Count Surveillance

• Obtain baseline platelet count before heparin initiation 1
• Monitor platelet count every 2-3 days from day 4 through day 14 of heparin therapy to screen for heparin-induced thrombocytopenia (HIT) 1
• HIT occurs in up to 5% of patients receiving unfractionated heparin and presents with a ≥50% drop in platelet count typically 5-10 days after starting heparin (earlier if prior exposure) 1, 3, 4
• If HIT is suspected (thrombocytopenia with or without new thrombosis), immediately stop all heparin and switch to a direct thrombin inhibitor such as argatroban 1, 5

Clinical Assessment

• Use handheld Doppler (not pulse palpation alone) to assess arterial signals at baseline and serially 1, 2
• Loss of arterial Doppler signal indicates threatened limb; absence of both arterial and venous signals suggests irreversible damage 1, 2
• Monitor for signs of compartment syndrome after revascularization (tense compartments, pain out of proportion, progressive motor/sensory deficits) 1

Absolute Contraindications

Do not administer heparin if:

• Active bleeding or high bleeding risk is present 1
• Acute limb ischemia is associated with aortic dissection 1
• Acute limb ischemia is due to major vascular trauma 1
• Known history of HIT (use direct thrombin inhibitor instead) 1

Critical Timing Considerations

• Rutherford Category I (viable limb): Requires urgent revascularization within 6-24 hours; heparin is temporizing but does not replace definitive intervention 6, 2
• Rutherford Category IIa/IIb (threatened limb): Requires emergent revascularization within 6 hours; heparin must be started immediately while arranging intervention 6, 2
• Rutherford Category III (irreversible ischemia): Consider primary amputation; heparin may still be given to prevent propagation but limb salvage is unlikely 1

Transition to Long-Term Anticoagulation

• Continue therapeutic unfractionated heparin until definitive revascularization is performed 1, 6
• After revascularization, maintain anticoagulation with either continued IV heparin or transition to subcutaneous low-molecular-weight heparin (enoxaparin 1 mg/kg twice daily) 1, 6
• Investigate the underlying cause (cardiac embolism, atrial fibrillation, aortic source, prothrombotic disorder) before discharge to guide long-term anticoagulation strategy 1, 6
• If cardiac embolic source is identified, initiate oral anticoagulation 6
• If atherosclerotic thrombotic etiology, start statin therapy which improves post-revascularization outcomes 1, 6

Common Pitfalls to Avoid

• Do not wait for vascular consultation or imaging before starting heparin—both anticoagulation and specialist evaluation are Class I recommendations that must occur simultaneously 1, 2
• Do not assume clinical improvement on heparin alone is sufficient—heparin is temporizing and does not restore arterial flow; definitive revascularization is still required 6, 2
• Do not rely on pulse palpation alone—use handheld Doppler for accurate vascular assessment 1, 2
• Do not overlook HIT surveillance—failure to monitor platelets can result in catastrophic thrombotic complications 1, 3, 4
• Do not use fondaparinux as initial therapy—it is contraindicated for supporting PCI due to catheter thrombosis risk and is not recommended for acute limb ischemia 1

Special Circumstances

Renal Impairment

• If creatinine clearance <30 mL/min, unfractionated heparin is preferred over low-molecular-weight heparin due to accumulation risk with LMWH 1
• Dose adjustment of unfractionated heparin is not required for renal dysfunction; continue aPTT-guided dosing 1

Heparin Resistance

• Rare phenomenon requiring >35,000 IU/day to achieve therapeutic aPTT, more commonly observed in hypercoagulable states including COVID-19 4
• Consider measuring anti-factor Xa levels (target 0.3-0.7 IU/mL) if aPTT remains subtherapeutic despite high-dose heparin 1, 4
• May require antithrombin supplementation or transition to alternative anticoagulant 4

Facility Limitations

• If your facility cannot administer IV heparin or lacks vascular specialist availability, arrange emergent transfer to a facility with both capabilities 2
• The urgency of transfer is proportional to the degree of limb threat (Category IIa/IIb requires transfer within hours) 2