What are the current guideline‑recommended weight‑based loading doses for thrombolytic and antiplatelet agents in an adult with acute ischemic stroke (cerebrovascular accident) or acute myocardial infarction, using actual body weight and without renal or hepatic dose adjustment?

Loading Doses for Acute Ischemic Stroke and Acute Myocardial Infarction

Acute Ischemic Stroke: Antiplatelet Loading Doses

For patients with acute ischemic stroke, administer aspirin 160–325 mg as a single loading dose within 24–48 hours after ruling out intracranial hemorrhage on neuroimaging. 1, 2

Standard Acute Stroke Protocol (Moderate-to-Severe Stroke, NIHSS >3)

• Aspirin loading: 160–325 mg orally (or 325 mg rectally if dysphagia) within 24–48 hours of symptom onset 1, 2
• Maintenance: Aspirin 75–100 mg daily beginning day 2, continued indefinitely 1, 2
• Critical timing: If IV alteplase was administered, delay aspirin until 24 hours post-thrombolysis and after repeat imaging confirms no hemorrhagic transformation 1, 3

Minor Stroke or High-Risk TIA Protocol (NIHSS ≤3 or ABCD² ≥4)

For minor stroke or high-risk TIA presenting within 24 hours, dual antiplatelet therapy with loading doses of both aspirin AND clopidogrel provides superior stroke prevention compared to aspirin alone. 2, 3

• Clopidogrel loading: 300 mg (acceptable range 300–600 mg) 2, 3
• Aspirin loading: 160–325 mg 2, 3
• Maintenance phase (days 2–21): Clopidogrel 75 mg daily + aspirin 75–100 mg daily 2, 3
• After day 21: Transition to single antiplatelet therapy (aspirin 75–100 mg daily OR clopidogrel 75 mg daily) indefinitely 2, 3

The 300 mg clopidogrel loading dose used in the CHANCE trial may carry modestly lower bleeding risk than the 600 mg dose used in POINT, while maintaining equivalent efficacy. 2

Critical Exclusions for Dual Antiplatelet Therapy

• NIHSS >3 (use aspirin monotherapy instead) 2
• Presentation >72 hours after symptom onset 2
• Intracranial hemorrhage not ruled out on imaging 2, 3
• IV alteplase within preceding 24 hours 2, 3
• Severe renal impairment (CrCl <30 mL/min) – use aspirin monotherapy only 2

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Acute Ischemic Stroke: Thrombolytic Loading Doses

For patients presenting within 3 hours of clearly defined symptom onset, IV alteplase 0.9 mg/kg (maximum 90 mg) is the only FDA-approved thrombolytic for acute ischemic stroke. 1, 4

Alteplase Dosing Protocol

• Total dose: 0.9 mg/kg actual body weight, maximum 90 mg 1
• Administration: 10% as IV bolus over 1 minute, then 90% as continuous infusion over 60 minutes 1
• Weight-based examples:
  • Patient 65 kg: 15 mg bolus, then 50 mg over 60 minutes 1
  • Patient 67 kg: 15 mg bolus, then 50 mg over 60 minutes 1
  • Patient ≥100 kg: 9 mg bolus, then 81 mg over 60 minutes (ceiling dose 90 mg total) 1, 5

The 90 mg maximum dose ceiling is supported by evidence showing that patients >100 kg who receive lower per-kilogram doses have similar functional outcomes but higher symptomatic intracerebral hemorrhage rates when given higher absolute doses. 5

Tenecteplase (Emerging Alternative)

• Stroke dosing: 0.25 mg/kg IV bolus (single administration) 1
• Maximum dose: 25 mg for patients >100 kg 1
• Advantage: Single bolus administration versus 60-minute alteplase infusion 4

Time Windows for Thrombolysis

• 0–3 hours: Strong recommendation for IV alteplase (Grade 1A) 1
• 3–4.5 hours: Conditional recommendation for IV alteplase (Grade 2C) 1
• >4.5 hours: Recommend against IV alteplase (Grade 1B) 1

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Acute Myocardial Infarction: Antiplatelet Loading Doses

For patients with acute coronary syndrome, administer weight-based loading doses of antiplatelet agents immediately upon diagnosis. 1

Aspirin Loading

• Loading dose: 162–325 mg orally (non-enteric coated for faster absorption) 1
• Rectal alternative: 325 mg if oral route unavailable 1
• Maintenance: 81 mg daily long-term 1

P2Y₁₂ Inhibitor Loading (Choose One)

Clopidogrel:

• Loading dose: 300–600 mg orally 1
• Maintenance: 75 mg daily 1
• Avoid in patients ≥75 years or weight ≤60 kg if using prasugrel instead 1

Prasugrel:

• Loading dose: 60 mg orally 1
• Maintenance: 10 mg daily 1
• Contraindicated: Age ≥75 years, weight <60 kg, prior stroke/TIA 1

Ticagrelor:

• Loading dose: 180 mg orally 1
• Maintenance: 90 mg twice daily 1
• Advantage: Reversible platelet inhibition, no age/weight restrictions 1

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Acute Myocardial Infarction: Anticoagulant Loading Doses

Unfractionated Heparin (UFH)

For patients undergoing coronary angiography, administer weight-based UFH with careful monitoring to avoid both under- and overdosing in extreme body weights. 1

• Before angiography: 60–70 IU/kg IV bolus (maximum 5,000 IU) + 12–15 IU/kg/h infusion (maximum 1,000 IU/h) 1
• During PCI: 70–100 IU/kg IV bolus if not previously anticoagulated; 50–70 IU/kg if receiving concomitant GP IIb/IIIa inhibitor 1
• Monitor: aPTT or ACT frequently 1

Low-Molecular-Weight Heparin (LMWH)

Enoxaparin (preferred for ACS):

• Loading/treatment dose: 1 mg/kg subcutaneous every 12 hours 1
• Renal adjustment: CrCl <30 mL/min: 1 mg/kg every 24 hours 1
• Obesity (BMI >40): Consider dose capping at 150 mg per dose and measure anti-Xa activity 1

Dalteparin:

• ACS dosing: 120 IU/kg subcutaneous every 12 hours (maximum 10,000 IU per dose) 1

Bivalirudin (Direct Thrombin Inhibitor)

• Loading dose: 0.75 mg/kg IV bolus 1
• Maintenance: 1.75 mg/kg/h infusion 1
• Renal adjustment: CrCl <30 mL/min: reduce infusion to 1 mg/kg/h 1

Fondaparinux

• ACS dosing: 2.5 mg subcutaneous once daily (no loading dose) 1
• Contraindicated: CrCl <30 mL/min 1

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Acute Myocardial Infarction: Fibrinolytic Loading Doses

For STEMI patients without access to primary PCI within 120 minutes, fibrinolytic therapy should be administered within 30 minutes of hospital arrival using weight-based dosing. 1

Alteplase (tPA)

• Weight <65 kg: 15 mg IV bolus, then 0.75 mg/kg over 30 minutes (max 50 mg), then 0.5 mg/kg over 60 minutes 1
• Weight 65–67 kg: 15 mg IV bolus, then 50 mg over 30 minutes, then 35 mg over 60 minutes 1
• Weight ≥67 kg: 15 mg IV bolus, then 50 mg over 30 minutes, then 35 mg over 60 minutes (ceiling dose 100 mg total) 1

Tenecteplase (TNK-tPA)

Tenecteplase offers the advantage of single-bolus administration with weight-tiered dosing. 1

• <60 kg: 30 mg IV bolus 1
• 60 to <70 kg: 35 mg IV bolus 1
• 70 to <80 kg: 40 mg IV bolus 1
• 80 to <90 kg: 45 mg IV bolus 1
• ≥90 kg: 50 mg IV bolus 1

Streptokinase

• Dose: 1.5 million IU IV infusion over 30–60 minutes 1
• No weight adjustment required 1
• Caution: Patients >120 kg may have reduced artery patency rates 1

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Common Pitfalls to Avoid

Never use enteric-coated aspirin for loading doses – it delays platelet inhibition by several hours; use immediate-release formulations only. 2

Never continue dual antiplatelet therapy beyond 21–30 days after acute stroke unless a separate cardiac indication exists (e.g., recent coronary stent), as bleeding risk outweighs benefit. 2

Never delay aspirin in acute stroke beyond 48 hours while awaiting specialty consultation – the benefit is time-dependent with maximum efficacy when started early. 2

Never use antiplatelet therapy as a substitute for thrombolysis or thrombectomy in eligible patients – this delays definitive reperfusion and worsens outcomes. 2

Never administer clopidogrel loading doses in severe renal impairment (CrCl <30 mL/min) – use aspirin monotherapy only, as bleeding risk is prohibitive. 2

Never exceed the 90 mg alteplase ceiling dose for stroke even in patients >100 kg – higher absolute doses increase symptomatic intracerebral hemorrhage without improving outcomes. 5