Is it ok to give streptokinase (fibrinolytic agent) now to a patient who received enoxaparin (low molecular weight heparin) 30 minutes ago?

Streptokinase Administration After Recent Enoxaparin

No, you should NOT give streptokinase now—wait at least 8 hours after the last enoxaparin dose, or proceed with the established protocol of administering enoxaparin concurrently with streptokinase rather than sequentially. 1

The Critical Issue: Timing and Protocol

The question presents a scenario that deviates from established protocols. Guidelines consistently recommend administering enoxaparin and streptokinase together as a coordinated regimen, not sequentially with only 30 minutes separation. 2, 1

Recommended Approach

If fibrinolysis with streptokinase is indicated, you should follow the established concurrent administration protocol:

• Administer enoxaparin 30 mg IV bolus immediately before or with streptokinase (not 30 minutes prior in isolation) 1, 3
• Follow with enoxaparin 1 mg/kg subcutaneously every 12 hours starting after the streptokinase infusion 2, 1
• For patients ≥75 years: use 0.75 mg/kg subcutaneously every 12 hours WITHOUT the initial IV bolus 2, 1
• For severe renal impairment (CrCl <30 mL/min): reduce to 1 mg/kg once daily 2, 1

Evidence Supporting Combined Use

The combination of streptokinase with enoxaparin is well-established and superior to streptokinase with unfractionated heparin:

• The ExTRACT-TIMI 25 trial demonstrated that enoxaparin with fibrinolytics (including streptokinase) reduced death and reinfarction at 30 days compared to UFH, though with increased non-cerebral bleeding 2, 4
• The OASIS-6 trial specifically showed fondaparinux superiority with streptokinase, but enoxaparin remains the most extensively studied anticoagulant with this fibrinolytic 2
• Multiple studies confirm the safety and efficacy of accelerated streptokinase regimens (0.75 MU boluses) combined with enoxaparin 5, 3

Why the 30-Minute Gap is Problematic

The scenario described—giving enoxaparin alone 30 minutes before streptokinase—does not match any validated protocol:

• Standard protocols call for enoxaparin IV bolus immediately before or concurrent with streptokinase, not as isolated pretreatment 1, 3
• The 30-minute interval creates unnecessary anticoagulation without the synergistic fibrinolytic effect 3
• This approach may increase bleeding risk without optimizing reperfusion 2

Critical Safety Considerations

If enoxaparin was already given 30 minutes ago without streptokinase:

• Do NOT switch to UFH—this "stacking" of anticoagulants significantly increases bleeding risk (Class III: Harm recommendation) 2
• Continue with the enoxaparin-based protocol if proceeding with fibrinolysis 1
• Consider whether primary PCI might be preferable if available within appropriate time windows 2

Monitoring Requirements

Once the combined regimen is initiated:

• Continue enoxaparin for at least 48 hours, preferably for the duration of hospitalization (up to 8 days) or until revascularization 2, 1
• Monitor for signs of successful reperfusion: rapid chest pain cessation, >50% ST-segment resolution, early CK/CK-MB peak 5, 6
• Watch for bleeding complications, particularly in elderly patients and those with renal impairment 2, 1

Common Pitfalls to Avoid

• Never administer the IV bolus to patients ≥75 years—the ASSENT-3 PLUS trial showed increased intracranial hemorrhage with standard dosing in elderly patients 2, 1
• Never switch between enoxaparin and UFH—this increases bleeding risk substantially 2, 7
• Always calculate creatinine clearance before dosing—renal impairment requires dose adjustment to prevent drug accumulation 2, 1
• Do not use fondaparinux as sole anticoagulant if PCI is planned—it requires additional anti-IIa activity to prevent catheter thrombosis 2