What is the recommended protocol for low molecular weight heparin (enoxaparin) after tenecteplase in an adult ST-elevation myocardial infarction (STEMI) patient, including timing, dosing, renal adjustment, bleeding‑risk modifications, and concomitant dual antiplatelet therapy?

LMWH Protocol After Tenecteplase for STEMI

Primary Recommendation

For patients <75 years old with normal renal function receiving tenecteplase for STEMI, administer enoxaparin as a 30 mg IV bolus followed by 1.0 mg/kg subcutaneous every 12 hours until hospital discharge (up to 8 days), as this regimen demonstrates superior reduction in death and reinfarction compared to unfractionated heparin. 1, 2, 3

---

Standard Enoxaparin Dosing Protocol

Age <75 Years with Normal Renal Function

• Initial dose: 30 mg IV bolus administered immediately with or after tenecteplase 1, 2, 4
• Maintenance dose: 1.0 mg/kg subcutaneous every 12 hours, starting within 15 minutes of the IV bolus 1, 2, 3
• Maximum single dose: First two subcutaneous doses should not exceed 100 mg 5
• Duration: Continue throughout index hospitalization, up to 8 days or until revascularization 1, 2, 3

Critical Age-Based Modification (≥75 Years)

• Contraindication: Enoxaparin should NOT be used as an alternative to UFH in patients ≥75 years receiving fibrinolytic therapy (Class III recommendation) 1, 4
• If enoxaparin must be used in elderly patients: Omit the 30 mg IV bolus entirely and reduce subcutaneous dose to 0.75 mg/kg every 12 hours 5
• Rationale: Prehospital administration in patients ≥75 years resulted in significant increase in intracranial hemorrhage 1

---

Renal Dose Adjustments

Significant Renal Dysfunction

• Definition: Serum creatinine >2.5 mg/dL in men or >2.0 mg/dL in women 1, 4
• Recommendation: Enoxaparin is contraindicated (Class III); use UFH instead 1, 4

Moderate Renal Impairment

• Creatinine clearance <30 mL/min: Reduce dose to 1.0 mg/kg subcutaneous every 24 hours (instead of every 12 hours) 5
• Maintain the 30 mg IV bolus if patient is <75 years old 5

---

Alternative: Unfractionated Heparin Protocol

When UFH is Preferred Over Enoxaparin

• Patients ≥75 years old 1, 4
• Significant renal dysfunction (Cr >2.5 mg/dL men, >2.0 mg/dL women) 1, 4
• Patients likely to require urgent PCI where switching anticoagulants should be avoided 4

UFH Dosing with Tenecteplase

• Initial bolus: 60 U/kg IV (maximum 4,000 U) 1, 2, 6
• Maintenance infusion: 12 U/kg/hour (maximum 1,000 U/hour for patients >70 kg) 1, 2, 6
• Target aPTT: 1.5-2.0 times control (approximately 50-70 seconds) 1, 2, 6
• Duration: Minimum 48 hours, preferably throughout hospitalization up to 8 days 2, 4

UFH Monitoring Requirements

• Check aPTT at 3,6,12, and 24 hours after initiation 2, 4, 6
• Recheck aPTT 4-6 hours after any dose adjustment 2, 4
• Monitor platelet count daily to detect heparin-induced thrombocytopenia 1, 2, 6

---

Concomitant Antiplatelet Therapy

Dual Antiplatelet Therapy (DAPT)

• Aspirin: 162-325 mg loading dose, then 75-162 mg daily indefinitely 1
• P2Y12 inhibitor: Should be administered according to contemporary STEMI guidelines, though not specifically addressed in the fibrinolytic-era guidelines 1

Glycoprotein IIb/IIIa Inhibitor Considerations

• If GP IIb/IIIa inhibitors are planned: Reduce UFH bolus to 50-70 U/kg and target ACT 200-250 seconds (instead of standard 60 U/kg and ACT 250-300 seconds) 2, 4
• Enoxaparin with GP IIb/IIIa inhibitors: Limited data; combination therapy with abciximab showed increased bleeding in ASSENT-3 1

---

Evidence Supporting Enoxaparin Superiority

Mortality and Reinfarction Benefits

• The ExTRACT-TIMI 25 trial (20,506 patients) demonstrated enoxaparin reduced the composite endpoint of death or nonfatal MI by 17% compared to UFH (9.9% vs 12.0%, P<0.001) 3
• Nonfatal reinfarction was reduced by 33% with enoxaparin (3.0% vs 4.5%, P<0.001) 3
• Net clinical benefit (death, nonfatal MI, or intracranial hemorrhage) favored enoxaparin (10.1% vs 12.2%, P<0.001) 3

Bleeding Risk Trade-off

• Major bleeding was higher with enoxaparin (2.1% vs 1.4%, P<0.001) 3
• However, the net clinical benefit still favored enoxaparin when balancing efficacy and safety 3, 5
• The ENTIRE-TIMI 23 trial showed similar major hemorrhage rates with full-dose tenecteplase (1.9% enoxaparin vs 2.4% UFH) 7

---

Critical Pitfalls to Avoid

Do Not Switch Between Anticoagulants

• Avoid switching from enoxaparin to UFH or vice versa during the acute phase, as this increases bleeding risk 4
• If patient on enoxaparin requires urgent PCI, continue enoxaparin rather than switching to UFH 4

Do Not Use Standard Dosing in High-Risk Groups

• Never give the 30 mg IV bolus to patients ≥75 years 5
• Never use standard 12-hourly dosing in patients with CrCl <30 mL/min 5
• Never use enoxaparin if creatinine >2.5 mg/dL (men) or >2.0 mg/dL (women) 1, 4

Do Not Discontinue Prematurely

• Continue anticoagulation for minimum 48 hours, preferably throughout hospitalization 2, 4
• High-risk patients (large anterior MI, atrial fibrillation, known LV thrombus) may require extended duration 1

Do Not Fail to Monitor Platelets

• Daily platelet counts are mandatory with UFH to detect heparin-induced thrombocytopenia 1, 2, 6
• While less common with LMWH, monitoring is still prudent 8

---

Special Populations

Heparin-Induced Thrombocytopenia (HIT)

• Alternative anticoagulant: Bivalirudin 0.25 mg/kg bolus, then 0.5 mg/kg/hour for 12 hours, then 0.25 mg/kg/hour for 36 hours 1, 2, 4
• Monitoring: Reduce infusion rate if PTT >75 seconds within first 12 hours 1

Patients Proceeding to PCI

• If on enoxaparin: Continue enoxaparin; do not switch to UFH 4
• If on UFH: Administer additional UFH bolus to achieve target ACT 250-350 seconds (or 200-250 seconds with GP IIb/IIIa inhibitors) 4, 6