For a STEMI patient receiving alteplase, should anticoagulation be given concomitantly or after alteplase completion?

Anticoagulation Timing with Alteplase in STEMI

For STEMI patients receiving alteplase, anticoagulation must be administered concomitantly with fibrinolytic therapy, not after completion.

Mandatory Concomitant Administration

Anticoagulation should be initiated simultaneously with alteplase administration as part of mandatory adjunctive therapy. 1 The evidence is clear that anticoagulants are not optional add-ons but essential components of the fibrinolytic regimen that must be given together with the thrombolytic agent.

Specific Anticoagulation Options and Timing

When administering alteplase for STEMI, you must choose one of the following anticoagulation strategies, all initiated with or immediately before the fibrinolytic:

• Enoxaparin (preferred): Give 30 mg IV bolus, followed 15 minutes later by 1 mg/kg subcutaneous every 12 hours 2, 3

  • For patients ≥75 years: Omit the IV bolus and reduce subcutaneous dose to 0.75 mg/kg every 12 hours 3
  • For severe renal insufficiency (CrCl <30 mL/min): Reduce to 1 mg/kg every 24 hours 3
  • Continue until revascularization or hospital discharge, up to 8 days 2

• Unfractionated heparin (alternative): Give weight-adjusted IV bolus (60 U/kg, maximum 4,000 U) followed by infusion (12 U/kg/hour, initial maximum 1,000 U/hour) adjusted to maintain aPTT 1.5-2 times control 2, 3

  • Continue for at least 48 hours 2

• Fondaparinux: Single IV bolus followed 24 hours later by subcutaneous dosing 2

Critical Timing Rationale

The concomitant administration is essential because:

• Alteplase creates a prothrombotic state during fibrinolysis that requires immediate anticoagulation coverage 1
• Delaying anticoagulation until after alteplase completion increases reocclusion risk of the infarct-related artery
• The evidence base for fibrinolytic efficacy in STEMI assumes concomitant anticoagulation—this is how the trials demonstrating benefit were conducted 3, 4

Complete Adjunctive Therapy Protocol

Along with concomitant anticoagulation, simultaneously administer:

• Aspirin: 150-325 mg oral (chewable, non-enteric coated) or 250-500 mg IV if unable to swallow 2, 1
• Clopidogrel: Loading dose of 300 mg (or 75 mg if age >75 years) 2, 1

Common Pitfall to Avoid

Do not wait for alteplase infusion to complete before starting anticoagulation. This outdated approach increases the risk of early reocclusion and negates the benefits of fibrinolytic therapy. The anticoagulant must be on board during the fibrinolytic process to prevent rethrombosis as the clot dissolves. 1, 3