What are the evidence‑based guideline recommendations for initiating and dosing unfractionated heparin or low‑molecular‑weight heparin, including contraindications and duration of therapy, in an adult patient with non‑ST‑segment elevation myocardial infarction?

Heparin in NSTEMI: Evidence-Based Recommendations

Immediate Anticoagulation Strategy

All patients with NSTEMI should receive parenteral anticoagulation in addition to antiplatelet therapy immediately upon presentation, with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) as first-line options. 1, 2

Agent Selection

UFH Dosing:

• Initial bolus: 60 U/kg (maximum 4,000 U) followed by continuous infusion of 12 U/kg/hour (maximum 1,000 U/hour) 1, 3, 4
• Target aPTT: 1.5 to 2.0 times control (approximately 50-70 seconds) 1, 3, 4
• Check aPTT at 3,6,12, and 24 hours after initiation, then daily 5
• Monitor platelet count daily throughout therapy to detect heparin-induced thrombocytopenia 3, 5

LMWH (Enoxaparin) Dosing:

• 1 mg/kg subcutaneously every 12 hours (maximum 10,000 IU twice daily) 3
• No routine laboratory monitoring required 1, 6
• Equivalent efficacy to UFH with more predictable pharmacokinetics 7, 8, 6

Duration of Anticoagulation

Continue UFH for at least 48 hours or until PCI is performed, whichever comes first. 1, 2, 5 The evidence explicitly does not support prolonging UFH beyond 48 hours in the absence of ongoing indications, as this increases heparin-induced thrombocytopenia risk without additional benefit 5.

For enoxaparin or fondaparinux, continue for the duration of hospitalization, up to 8 days 1, 2.

Management Strategy-Specific Recommendations

Early Invasive Strategy (PCI Planned)

If PCI is performed within 24 hours:

• Continue UFH through PCI with additional boluses to maintain therapeutic ACT 1
• Target ACT: 250-300 seconds (HemoTec) or 300-350 seconds (Hemochron) without GP IIb/IIIa inhibitors 1, 3
• Target ACT: 200 seconds if GP IIb/IIIa inhibitors are used 3, 5
• Discontinue anticoagulant immediately after uncomplicated PCI 1, 2

For enoxaparin:

• No additional dosing if last dose was within 8 hours 1
• Give 0.3 mg/kg IV bolus if last dose was 8-12 hours prior 1
• Continue through PCI 1

Conservative Strategy (No Immediate PCI)

Continue anticoagulation for at least 48 hours with UFH or for duration of hospitalization (up to 8 days) with enoxaparin or fondaparinux 1, 2.

Special Populations and Contraindications

Renal Impairment

Severe renal impairment (CrCl <30 mL/min): UFH is strongly preferred as it does not accumulate with renal dysfunction and does not require dose adjustment 2, 3. Enoxaparin requires dose reduction in moderate renal impairment and should be avoided in severe impairment 2.

Hepatic Impairment

UFH is preferred in severe liver disease as it can be monitored with aPTT and does not undergo hepatic metabolism 2. Avoid enoxaparin and fondaparinux due to unpredictable pharmacokinetics 2.

Active Bleeding

In patients with active gastrointestinal bleeding:

• Heparin may be justified only when ongoing refractory ischemia persists despite optimal anti-ischemic therapy 2
• Withhold anticoagulation if ischemic symptoms are adequately controlled by anti-ischemic medications 2
• If bleeding risk exceeds thrombotic risk, use conservative strategy without anticoagulant 2
• Continue aspirin monotherapy (if tolerated) with beta-blockers, nitrates, and statins 2
• Never administer GP IIb/IIIa inhibitors in active bleeding 2

Pre-CABG Management

• Continue UFH through CABG 1
• Discontinue enoxaparin 12-24 hours before CABG and transition to UFH 1
• Discontinue fondaparinux 24 hours before CABG and transition to UFH 1
• Discontinue bivalirudin 3 hours before CABG and transition to UFH 1

Critical Pitfalls to Avoid

Never switch between anticoagulants during the same admission as this significantly increases bleeding risk 2, 3, 5. If a patient has already received enoxaparin, do not add UFH 3, 5.

Do not use fondaparinux as sole anticoagulant during PCI—it must be supplemented with UFH bolus due to catheter thrombosis risk 2, 5.

Avoid exceeding maximum doses: 4,000 U bolus and 1,000 U/hour infusion for UFH, regardless of weight 3, 5, 4. Excess dosing (>70 U/kg bolus or >15 U/kg/hour infusion) increases major bleeding risk 3.

Do not prolong UFH infusions beyond 48 hours without specific ongoing indications, as this increases heparin-induced thrombocytopenia risk without improving outcomes 5.

Concomitant Antiplatelet Therapy

All patients should receive:

• Aspirin 162-325 mg immediately, then 75-162 mg daily indefinitely 1, 2
• P2Y12 inhibitor (clopidogrel 300-600 mg loading dose, then 75 mg daily) for at least 12 months 1, 2

The combination of aspirin and heparin provides incremental benefit over aspirin alone, though the effect is modest 1. Triple therapy with GP IIb/IIIa inhibitors provides additional benefit in high-risk patients but increases bleeding risk 1.