Argatroban therapy in pediatric patients requiring nonheparin anticoagulation: an open-label, safety, efficacy, and pharmacokinetic study.

BACKGROUND: An increasing number of pediatric patients suffer from thrombotic events necessitating anticoagulation therapy including heparins. Some such patients develop heparin-induced thrombocytopenia (HIT) and thus require alternative anticoagulation. As such, studies evaluating the safety, efficacy, and dosing of alternative anticoagulants are required. PROCEDURE: In this multicenter, single arm, open-label study, 18 patients ≤ 16 years old received argatroban for either a suspicion of or being at risk for HIT, or other conditions requiring nonheparin anticoagulation. Endpoints included thrombosis, thromboembolic complications, and bleeding. RESULTS: Patients (ages, 1.6 weeks to 16 years) received argatroban usually for continuous anticoagulation (n = 13) or cardiac catheterization (n = 4). One catheterization patient received a 250 µg/kg bolus only; 17 patients received argatroban continuous infusion (median (range)) 1.1 (0.3-12) µg/kg/min (of whom four received a bolus) for 3.0 (0.1-13.8) days. In patients without bolus dosing, typically argatroban 1 µg/kg/min was initiated, with therapeutic activated partial thromboplastin times (aPTTs) (1.5-3× baseline) achieved within 7 hr. Within 30 days, thrombosis occurred in five patients (two during therapy). No one required amputation or died due to thrombosis during therapy. Two patients had major bleeding. Pharmacometric analyses demonstrated the optimal initial argatroban dose to be 0.75 µg/kg/min (if normal hepatic function), with dose reduction necessary in hepatic impairment. CONCLUSIONS: In pediatric patients requiring nonheparin anticoagulation, argatroban rapidly provides adequate levels of anticoagulation and is generally well tolerated. For continuous anticoagulation, argatroban 0.75 µg/kg/min (0.2 µg/kg/min in hepatic impairment), adjusted to achieve therapeutic aPTTs, is recommended.

Hemodynamic effects and long-term outcome of percutaneous balloon valvuloplasty in patients with mitral stenosis and atrial fibrillation.

BACKGROUND: The presence of atrial fibrillation (AF) has been identified as a predictor of a suboptimal result in some patients undergoing percutaneous balloon valvuloplasty in the treatment of symptomatic rheumatic mitral stenosis. HYPOTHESIS: Atrial fibrillation adversely affects the short- and long-term outcome of patients with mitral stenosis undergoing percutaneous balloon valvuloplasty. METHODS: A retrospective chart review of 104 consecutive patients with rheumatic mitral stenosis undergoing percutaneous balloon valvuloplasty was performed. A successful procedure was defined as a final mitral valve area > or = 1.5 cm2 and the absence of a complication. Endpoints included freedom from mitral valve replacement, death, and repeat balloon valvuloplasty at 5 years. RESULTS: A successful procedure was obtained in 89% of patients with sinus rhythm and in 78% of patients with AF (p = NS). Patients in sinus rhythm had a greater cardiac output resulting in a larger final valve area than patients in AF (1.8 vs. 1.6 cm2, p < 0.05). Freedom from valve replacement, death, and repeat balloon valvuloplasty at 5 years was 75% for patients in AF and 76% for patients in sinus rhythm (p = NS). Lower postprocedure mitral regurgitation grade and absence of prior commissurotomy were the only independent predictors of event-free survival. CONCLUSIONS: Patients with mitral stenosis and AF have lower cardiac outputs and gradients than patients with sinus rhythm, despite similar valve areas. The long-term outcome of balloon valvuloplasty is independent of the initial cardiac rhythm.