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Platelet Inhibition With IV Glycoprotein IIb/IIIa Inhibitor to Prevent Thrombosis in Pediatric Patients Undergoing
Sirisha Emani1, Luis M Pereira2, Breanna L Piekarski1
1Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA.
Insights
Tirofiban, an IV glycoprotein IIb/IIIa inhibitor, shows promise as a bridge therapy for pediatric patients after aortopulmonary shunting, with low rates of shunt thrombosis and bleeding. Dosing should consider age and renal function.
Area of Science:
- Cardiovascular Surgery
- Pediatric Critical Care
- Pharmacology
Background:
- Shunt thrombosis post-aortopulmonary shunting carries high mortality.
- Oral antiplatelet drugs like aspirin have variable efficacy in critically ill pediatric patients.
- Intravenous glycoprotein IIb/IIIa inhibitors offer rapid, reproducible antiplatelet effects.
Purpose of the Study:
- To evaluate the safety and efficacy of tirofiban as a bridge to oral aspirin therapy in pediatric patients undergoing aortopulmonary shunting.
- To assess pharmacokinetic parameters and platelet inhibition with tirofiban infusion.
- To identify factors influencing tirofiban clearance in this population.
Main Methods:
- Retrospective review of 52 pediatric patients (<18 years) receiving tirofiban infusion post-aortopulmonary shunt.
- Pharmacokinetic analysis in a subset of 15 patients using discarded blood samples.
- Platelet inhibition measured by thromboelastography with platelet mapping.
Main Results:
- Shunt thrombosis occurred in 3.9% of patients, exclusively after tirofiban discontinuation.
- One patient (1.9%) experienced a bleeding complication during tirofiban infusion.
- Tirofiban significantly increased platelet inhibition (p < 0.05); half-life was 142 ± 1.5 minutes.
Conclusions:
- Intravenous glycoprotein IIb/IIIa inhibitor therapy, like tirofiban, is safe as a bridge to oral antiplatelets in pediatric patients post-aortopulmonary shunting.
- Age and renal function are significant factors influencing tirofiban clearance, necessitating individualized dosing.
- Further randomized trials are recommended to confirm efficacy against current anticoagulation practices.
Objectives:
Shunt thrombosis, a potential complication of aortopulmonary shunting, is associated with high mortality. Commonly used oral antiplatelet drugs such as aspirin demonstrate variable absorption and inconsistent antiplatelet effect in critically ill patients early after surgery. IV glycoprotein IIb/IIIa inhibitors are antiplatelet agents with rapid and reproducible effect that may be beneficial as a bridge to oral therapy.
Design:
Retrospective review of pediatric patients undergoing treatment with IV tirofiban. Discarded blood samples were used to determine pharmacokinetic parameters.
Setting:
Pediatric cardiac ICU at a single institution.
Patients:
Fifty-two pediatric patients (< 18 yr) undergoing surgical aortopulmonary shunt procedure who received tirofiban infusion as a bridge to oral aspirin.
Interventions:
None.
Measurements And Main Results:
Primary outcome measures were shunt thrombosis and bleeding events, whereas secondary outcomes included measurement of platelet inhibition by thromboelastography with platelet mapping and pharmacokinetic analysis (performed in a subset of 15 patients). Shunt thrombosis occurred in two of 52 patients (3.9%) after prophylaxis treatment with tirofiban; both thrombosis events occurred after discontinuation of the drug. One patient (1.9%) experienced bleeding complication during the infusion. A tirofiban bolus of 10 µg/kg and infusion of 0.15 µg/kg/min resulted in significantly increased platelet inhibition via adenosine diphosphate pathway (median 66% [43-96] pre-tirofiban compared with 97% [92-99%] at 2 hr; p < 0.05). Half-life of tirofiban in plasma was 142 ± 1.5 minutes, and the average steady-state concentration was 112 ± 62 ng/mL. Age and serum creatinine were significant covariates associated with systemic clearance. Dosing simulations were generated based upon one compartment model.
Conclusions:
IV glycoprotein IIb/IIIa inhibitor as a bridge to oral antiplatelet therapy is safe in pediatric patients after aortopulmonary shunting. Dosing considerations should include both age and renal function. Randomized trials are warranted to establish efficacy compared with current anticoagulation practices.
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