What is the recommended alteplase (recombinant tissue‑type plasminogen activator) dosing for a patient weighing less than 60 kg with a high risk of bleeding for acute ischemic stroke, pulmonary embolism, or myocardial infarction?

Alteplase Dosing in Low-Weight Patients (<60 kg) with High Bleeding Risk

For patients weighing less than 60 kg receiving alteplase for acute myocardial infarction, the dose should be weight-adjusted to reduce bleeding risk: 15 mg IV bolus, then 0.75 mg/kg over 30 minutes (maximum 50 mg), followed by 0.5 mg/kg over 60 minutes, with a total maximum dose not exceeding 100 mg. 1

Weight-Based Dosing Thresholds

For STEMI patients specifically under 60 kg:

• The 2024 European Society of Cardiology consensus explicitly addresses this population, noting that patients <65 kg should receive the standard weight-adjusted regimen with careful consideration of bleeding risk 1
• The accelerated alteplase protocol uses: 15 mg bolus, then 0.75 mg/kg over 30 minutes (up to 50 mg), then 0.5 mg/kg over 60 minutes (up to 35 mg) 1
• Total dose ceiling remains 100 mg regardless of weight 2

Critical distinction from tenecteplase:

• Tenecteplase uses fixed weight-band dosing: 30 mg for patients <60 kg as a single bolus 1, 3
• This represents a simpler alternative with equivalent efficacy in the low-weight population 4, 3

Bleeding Risk Mitigation in Underweight Patients

The evidence demonstrates that underweight status independently increases bleeding risk:

• Patients >100 kg receiving lower per-kilogram doses (due to the 90 mg cap for stroke) showed higher symptomatic intracranial hemorrhage rates (2.6% vs 1.7%, OR 1.6) despite receiving less drug per kilogram 5
• This paradox suggests that absolute body weight affects bleeding risk through mechanisms beyond simple drug concentration 5
• Underweight patients (<60 kg) face similar heightened bleeding vulnerability and require strict dose adherence to weight-based calculations 1

Specific precautions for low-weight, high-bleeding-risk patients:

• Avoid overdosing by ensuring accurate weight measurement before administration 1
• The 2024 ESC guidelines emphasize that appropriate body weight measurement is critical to prevent underdosing in normal-weight patients but equally important to prevent relative overdosing in underweight patients 1
• Consider half-dosing (reduced from standard) only in patients >75 years with stroke indications, not for STEMI 4

Adjunctive Anticoagulation Adjustments

Heparin dosing must be weight-capped in low-weight patients:

• UFH: 60 U/kg IV bolus with maximum 4000 U, then 12 U/kg/h infusion with maximum 1000 U/h 1
• This capping is specifically designed to prevent excessive anticoagulation in lighter patients 1
• Target aPTT 50-70 seconds, monitored at 3,6,12, and 24 hours 1

Enoxaparin considerations:

• Standard dose: 30 mg IV bolus, then 1 mg/kg subcutaneously every 12 hours for patients <75 years 1, 3
• For patients with body weight 10-30 kg (pediatric range), use 110% of internal lumen volume for catheter applications 6
• The 2024 ESC guidelines note limited data for dose capping in underweight adults but recommend careful monitoring 1

Clinical Context: When Bleeding Risk is "High"

Relative contraindications that elevate bleeding risk in low-weight patients:

• Recent surgery within 3 weeks 1
• Non-compressible vascular punctures 1
• Traumatic resuscitation 1
• Active peptic ulcer disease 1
• Pregnancy or within 1 week postpartum 1

In these scenarios with weight <60 kg:

• The weight-adjusted dose should still be used (not reduced further) to maintain efficacy 1
• Consider tenecteplase 30 mg as a single bolus alternative, which may simplify administration and reduce cumulative thrombolytic exposure 4, 3
• Ensure meticulous blood pressure control (systolic <180 mmHg, diastolic <110 mmHg) before and during infusion 1, 3

Alternative Thrombolytic Strategy

Tenecteplase offers practical advantages in low-weight, high-bleeding-risk patients:

• Single 30 mg IV bolus over 5 seconds for patients <60 kg 4, 3
• Eliminates infusion-related dosing errors 3
• The 2024 ESC consensus confirms this fixed dose for underweight patients with consideration of bleeding risk 1
• Can be re-administered if needed (unlike streptokinase) without antibody concerns 3

Monitoring Requirements

Post-administration surveillance for bleeding complications:

• Assess ST-segment resolution at 60-90 minutes to confirm reperfusion success 4, 3
• Monitor for symptomatic intracranial hemorrhage (defined as NIHSS deterioration ≥4 points within 24 hours) 5
• Check fibrinogen levels: nadir typically 3.6 mg/mL after standard dosing 7
• Approximately 22% of patients experience some bleeding; 3.5% require transfusion even with appropriate dosing 7

Common Pitfall to Avoid

**Do not arbitrarily reduce the weight-based dose below the calculated amount in patients <60 kg simply because they are small.** The weight-adjusted formula already accounts for body size, and further reduction compromises reperfusion efficacy without proven bleeding benefit 1, 5. The paradoxical finding that heavier patients (>100 kg) receiving lower per-kg doses had worse outcomes underscores that the established weight-based calculations represent optimized risk-benefit ratios 5.