Abstract
BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a potentially devastating immune-mediated complication that occurs in 1-2% of heparin-exposed pediatric patients in the ICU. Thrombosis can occur 5-14 days following heparin initiation and may cause significant morbidity and mortality. The thrombotic risk of HIT is mediated by heparin-platelet factor 4 antibody complexes that trigger platelet and endothelium activation, resulting in increased thrombin production. Argatroban is a direct thrombin inhibitor that is currently approved for use in adults for the prophylaxis or treatment of HIT. There is limited argatroban experience in the pediatric population.
METHODS: A retrospective review of all pediatric patients (age < 18 years) who received argatroban at our institutions (1,2) was performed. Data collected: age, diagnosis, indication for argatroban use, dose, duration, concurrent medications, measures of coagulation, adverse effects, and outcome.
RESULTS: Six pediatric patients who received argatroban anticoagulation were identified (Table 1). Ages ranged from 8 months to 16 years. Indications included HIT or history of HIT on ECMO, HIT with thrombosis, and refractory thrombosis unrelated to HIT. Argatroban was infused at a dosing range of 0.5 to 24 mcg/kg/min with goal PTT at 2X baseline. Duration of therapy ranged from 1–39 days. All cases were successfully anticoagulated on argatroban. Termination of therapy occurred when ECMO was discontinued (cases 1, 2, 4), when HIT was ruled out (case 3), when patient was converted to coumadin (case 5), and at the time of surgery (case 6). There were no significant thrombotic nor bleeding episodes during argatroban therapy.
CONCLUSIONS: Our limited experience demonstrates that Argatroban can be an effective means of anticoagulation in pediatric patients who require alternatives to heparin therapy. An ongoing multi-center study to evaluate the safety and efficacy of argatroban in the pediatric population will help to determine appropriate pediatric dosing.
Table 1. Argatroban in Pediatrics
Case Age/Gender Diagnosis Indication for Argatroban Initial Dose (μ g/kg/min) Dosing Range (μg/kg/min) Therapy Duration (days) Complications ECMO= extracorporeal membrane oxygenation, HPF4= Heparin-Platelet Factor 4, OHT= orthotopic heart transplant, WPW= Wolf-Parkinson-White syndrome, RLE= right lower extremity, DVT= deep vein thrombosis, B-T= Blalock-Taussig. 1 8 yo M Dilated cardiomyopathy, requiring ECMO Thrombus in circuit on day 4 of ECMO, +HPF4 ELISA 0.5 0.5 to 1.5, stabilized at 1.0 6 None 2 16 yo M Complex congenital heart disease, idiopathic cardiomyopathy s/p OHT, acute rejection requiring ECMO History of +HPF4 ELISA 2.0 0.6–2.0, stabilized at 0.6–0.8 10 None 3 8 yo F Complex congenital heart disease, heart failure requiring ECMO Concern for HIT when initiating ECMO, HPF4 ELISA pending 2.0 1.5–2.0 1 None 4 15 mo F Dilated cardiomyopathy,heart failure requiring ECMO Dropping platelets, and +HPF4 ELISA on day #10 ECMO 2.0 2.0–3.5 during 1st week, rate increased to 24 during 2nd week, then stabilized at 13–15 39 None 5 16 yo F History of right femoral osteosarcoma and WPW requiring ablation by cardiac catheterization RLE DVT after cardiac catheterization; DVT refractory to heparin & thrombolytic therapy 2.0 2.0 10 None 6 8 mo F Complex congenital heart disease Thrombosed B-T shunt, +HPF4 ELISA 1.0 0.5–1.0 9 None
Heart Transplantation in Congenital Heart Disease: In Whom to Consider and When?
