hirudin and Hypoplastic-Left-Heart-Syndrome

Repeated exposure to unfractionated heparin is the rule in many congenital heart disease patients. Heparin-induced thrombocytopenia occurs in 1% to 3% of adult cardiac surgeries, and carries high thrombotic morbidity (38% to 81%) and mortality (approximately 28%). Although heparin-induced thrombocytopenia appears to be infrequent in pediatric patients, particularly neonates, our evolving experience suggests postcardiopulmonary bypass congenital heart disease patients may be at increased risk. Diagnostic and therapeutic challenges include frequency of thrombocytopenia after cardiopulmonary bypass, imperfect laboratory testing, lack of established dosing of alternative anticoagulants (such as argatroban and lepirudin), and increased anticoagulant-related bleeding in young children.

Topics: Adolescent; Anticoagulants; Arginine; Autoantibodies; Cardiopulmonary Bypass; Child; Child, Preschool; Clinical Trials as Topic; Fatal Outcome; Female; Heart Defects, Congenital; Heparin; Hirudins; Hospitals, University; Humans; Hypoplastic Left Heart Syndrome; Infant; Infant, Newborn; Male; Multicenter Studies as Topic; Pipecolic Acids; Platelet Factor 4; Postoperative Complications; Postoperative Hemorrhage; Recombinant Proteins; Retrospective Studies; Sulfonamides; Thrombocytopenia; Thromboembolism; Treatment Outcome

Infants with heparin-induced thrombocytopenia (HIT) represent a challenging and high-risk group of patients when they require cardiopulmonary bypass (CPB). Bivalirudin offers many potential pharmacologic advantages over other nonheparin anticoagulants for such patients. We describe our protocol for the use of bivalirudin in a 5-month-old infant undergoing stage 2 Norwood for hypoplastic left heart syndrome. The patient was a 5- month-old, 6-kg infant who developed HIT after a bowel resection complicating initial Norwood stage 1. After sternotomy and dissection had been redone, the child received an initial dose of bivalirudin of 1.0 mg/kg and 0.5 mg/kg 5 min later. The CPB circuit was primed with 50 mg/kg bivalirudn/400 cc volume. With the initiation of CPB, a continuous infusion of 2.5 mg/kg bivalirudin was begun. Activated clotting time (ACT) was targeted for over 400 s, with an examination prior to bypass and each 15 min thereafter. Bivalirudin was discontinued with separation from bypass and during modified ultrafiltration (MUF). The ACT was 286 s after the initial 1 mg/kg bolus and 597 s after the second 0.5 mg/kg bolus and initiation of CPB. At a rate of 2.5 mg/kg/min, ACT ranged between 461 and 597 s. At the completion of MUF, the ACT was 316 s. The ACT was 214 s 20 min after MUF. No clots were noted in the CPB circuit, and good hemostasis was achieved within 10 min after MUF was completed. Incision to closure time was 160 min; time from completion of MUF to sternal closure was 30 min. Post-MUF, 60 cc of processed cell saver blood was reinfused, and no clotting factors were required. Chest tube output was 10, 10, 3, and 4 ccs, respectively, at hours 1-4 post operation. Bivalirudin provides effective anticoagulation in infants requiring CPB in the presence of HIT. Bivalirudin's efficacy is effectively monitored by ACT, and, after CPB, its short half-life and ability to be ultrafiltered facilitate the ability to achieve hemostasis in a timely fashion.

Topics: Anticoagulants; Cardiopulmonary Bypass; Clinical Protocols; Heparin; Hirudins; Humans; Hypoplastic Left Heart Syndrome; Infant; Peptide Fragments; Recombinant Proteins; Thrombocytopenia

A 21-month-old boy received anticoagulation with lepirudin for heparin-induced thrombocytopenia (HIT) after undergoing cardiac surgery and receiving extracorporeal membrane oxygenation (ECMO). This report illustrates the significance of HIT in pediatric patients after cardiac surgery and the successful administration of lepirudin in this setting. To our knowledge, this is the first published report of lepirudin administered to treat HIT in a child after cardiac surgery and ECMO. Although guidelines exist that suggest the potential administration of lepirudin as treatment for children with HIT, further studies are needed to determine the safest yet most effective dosage for this population.

Topics: Anticoagulants; Cardiac Surgical Procedures; Child, Preschool; Echocardiography; Extracorporeal Membrane Oxygenation; Fontan Procedure; Heparin; Hirudins; Humans; Hypoplastic Left Heart Syndrome; Male; Platelet Count; Postoperative Complications; Recombinant Proteins; Thrombocytopenia

There are few reports of the management of pediatric patients with heparin-induced thrombocytopenia (HIT) requiring cardiac surgery using currently available anticoagulants. We report a case of an infant with HIT requiring a bidirectional Glenn shunt who was successfully managed using lepirudin (r-hirudin, Refludan; Aventis, Bridgewater, NJ). Dosing and monitoring of anticoagulation were difficult, and we suggest caution in the use of lepirudin for cardiac surgery unless reliable monitoring of the degree of anticoagulation becomes available.

Topics: Anticoagulants; Blood Coagulation Tests; Cardiac Catheterization; Cardiac Surgical Procedures; Hemodynamics; Heparin; Hirudins; Humans; Hypoplastic Left Heart Syndrome; Infant; Male; Monitoring, Intraoperative; Partial Thromboplastin Time; Recombinant Proteins; Thrombocytopenia; Thrombosis