Use of bivalirudin as a primary anticoagulant in a child during Berlin Heart EXCOR ventricular assist device support

Abstract

We describe our experience of bivalirudin use, a newer direct thrombin inhibitor, in an infant who was supported with Berlin Heart EXCOR VAD (Berlin VAD) as bridge to transplant for 122 days without complications and without need for pump exchange. An 11-month-old girl with dilated cardiomyopathy with acute heart failure was awaiting cardiac transplant. Lack of improvement despite maximizing medical therapy and anticipating a prolonged waitlist time, she was supported with Berlin LVAD as a bridge to transplant. Anticoagulation with bivalirudin was started and titrated with a goal partial thromboplastin time of 60-90 seconds. Therapeutic anticoagulation was achieved with bivalirudin for 50% of the days (61/122 days) on a dose of 2.1 mg/kg/hour and in a narrow dose range of 1.9 to 2.3 mg/kg/hour for 80% of the days (98/122 days). Antiplatelet regimen was started initially with aspirin and clopidogrel added later. She was supported for 122 days on a single pump without any evidence of thrombus or need for pump change. Berlin VAD explant and orthotopic heart transplant with biatrial anastomosis were performed uneventfully. Explanted Berlin VAD had no evidence of clot/fibrin or thrombus formation. The child was discharged to home uneventfully 15 days after cardiac transplant.

A Review of Bivalirudin for Pediatric and Adult Mechanical Circulatory Support

“…Target aPTT variable (range 50–100 s) Major bleeding events occurred in 7 pts with 8 overall bleeding events (6 pts on bivalirudin, 1 on argatroban); all pts were on antiplatelet agent at time of bleeding event. Pump thrombosis event rate of 5.7 per 1000 pt days of support; neurologic event rate of 2.1 per 1000 pt days of support on bivalirudin Campbell et al [ 20 ] 19 pediatric pts on bivalirudin for VAD (9 pts with BiVAD, 5 pts with LVAD, 5 pts with RVAD) Retrospective analysis Initial median (IQR) infusion rate 0.1 (0.1–0.2) mg/kg/h; average infusion rate 0.4 (0.31–1) mg/kg/h; maximum median (IQR) infusion rate of 0.7 (0.41–1.2) mg/kg/h; target aPTT 60–90 s Average percentage of time spent within goal aPTT range was 67.4%; higher average and maximum dose vs. pts on ECMO; similar initial dose used Medar et al [ 29 ] 11-month-old girl with dilated cardiomyopathy utilizing LVAD as bridge to transplant (122 days of support) Case report No bivalirudin bolus reported; initial infusion rate 0.15 mg/kg/h; maintenance rate ranged from 0.15 to 2.3 mg/kg/h; target aPTT 60–90 s No evidence of thrombus or need for pump change; no significant bleeding intraoperatively or postoperatively. Pt discharged home on postoperative day 15 ACT activated clotting time, aPTT activated partial thromboplastin time, BiVAD biventricular assist device, DTI direct thrombin inhibitor, ECLS extracorporeal life support, ECMO extracorporeal membrane oxygenation, FFP fresh frozen plasma, GI gastrointestinal, HIT heparin-induced thrombocytopenia, LVAD left ventricular assist device, PS propensity score, pt(s) patient(s), RBC red blood cells, RVAD right ventricular assist device, SDH subdural hematoma, UFH unfractionated heparin, VAD ventricular assist device, VAP ventilator-associated pneumonia …”

“…The initial infusion rate of 0.3 mg/kg/h utilized by both VanderPluym et al [ 28 ] and Bates et al [ 25 ], case series reports of 43 and 14 pediatric patients, respectively, was identical to that of Nagle et al [ 7 ] and Ezetendu et al [ 17 ]. Meanwhile, in a case report by Medar et al [ 29 ], the authors stated an initial bivalirudin infusion rate of 0.15 mg/kg/h, 50% that of VanderPluym et al [ 28 ] and Bates et al [ 25 ]. Campbell et al [ 20 ] reported that the median initial rate was similar between VAD and ECMO patients, at 0.1 mg/kg/h.…”

“…For example, in the largest study examined, infusion rates began at a median of 0.3 mg/kg/h, yet maximum doses necessary to maintain aPTT goals ranged from 0.1 to 3.9 mg/kg/h [28]. In the case report by Medar et al [29], this high variability was replicated; in one patient alone, maintenance infusion rates ranged from 0.15 to 2.3 mg/kg/h across a full VAD course of 122 days.…”

“…Given the nature of pediatric heart transplant, specifically the limited availability of neonatal and infant donors, and the fact that the majority of patients receive VADs as a bridge to transplant, the duration of therapy in this population is typically extended when compared with that of ECMO. Medar et al [29] reported on a patient who received bivalirudin for 122 days. The authors reported that the patient did not experience any complications throughout this time.…”

“…The authors reported that the patient did not experience any complications throughout this time. Indeed, the patient received a heart transplant, with no major bleeding events throughout surgery, and was successfully discharged at postoperative day 15 [29].…”