Division of Pediatric Cardiology, Le Bonheur Children's Hospital, University of Tennessee Health Sciences Center, Memphis, TN, USA.
Department of Pediatric Cardiothoracic Surgery, Le Bonheur Children's Hospital, University of Tennessee Health Science Center, Memphis, TN, USA.
Artif Organs. 2021 Jan;45(1):38-45. doi: 10.1111/aor.13782. Epub 2020 Aug 19.
Thromboembolic events and bleeding are major sources of morbidity among pediatric patients supported on a ventricular assist device (VAD). Pharmacokinetics and pharmacodynamics of enteral antiplatelet agents are affected and variable due to erratic enteral absorption in end-stage heart failure and VAD circulation. Additionally, 20%-40% of the population are poor metabolizers of clopidogrel, a prodrug, making cangrelor an alternative when antiplatelet therapy is crucial. Cangrelor has been used effectively and safely for short durations in adults during percutaneous coronary interventions, but the use of cangrelor is still under investigation in pediatrics. This case series utilized cangrelor, a novel short-acting, reversible, intravenous P2Y platelet inhibitor in managing pediatric patients supported with a VAD. We performed a retrospective, single-center review of patients admitted to a tertiary medical center with end-stage heart failure requiring mechanical circulatory support and concomitant cangrelor administration between January 2019 and March 2020. Platelet function testing, cangrelor dose, bleeding complications, thromboembolic events, and frequency of circuit interventions during the use of cangrelor were recorded. Optimal platelet reactivity, defined as P2Y < 180 platelet reaction units (PRU), was measured with serial point-of-care testing (VerifyNow). Seven patients, median age of 4.9 years, met the above criteria. Three patients had a diagnosis of complex congenital heart disease. Four patients had dilated or restrictive cardiomyopathy. All patients were on continuous flow VADs. The median VAD duration was 84.5 days (IQR 61.5-103). The median duration on cangrelor was 43 days (IQR 8-70). The median cangrelor dose to reach the therapeutic threshold was 0.75 μg/kg/min with the mean P2Y , while on cangrelor of 164.75 PRU. Bleeding complications included mild gastrointestinal bleeding and hematuria. There was one patient with pump thrombosis requiring intervention. There were no cerebrovascular events while on cangrelor. We report the first successful long-term use of cangrelor in pediatric patients. The reversibility and short half-life of cangrelor make it a feasible antiplatelet agent in selected patients. This data supports the use of cangrelor in children as a viable antiplatelet option; with minimal bleeding complications and no cerebrovascular events demonstrated in this cohort.
在接受心室辅助装置(VAD)支持的儿科患者中,血栓栓塞事件和出血是导致发病率的主要原因。由于终末期心力衰竭和 VAD 循环中肠内吸收不稳定,肠内抗血小板药物的药代动力学和药效动力学受到影响且各不相同。此外,20%-40%的人群是氯吡格雷的代谢不良者,氯吡格雷是一种前体药物,因此当抗血小板治疗至关重要时,坎格雷洛是一种替代药物。坎格雷洛已在成人经皮冠状动脉介入治疗中有效且安全地短期使用,但在儿科中仍在研究坎格雷洛的使用。本病例系列利用坎格雷洛,一种新型的短期、可逆、静脉 P2Y 血小板抑制剂,治疗接受 VAD 支持的儿科患者。我们对 2019 年 1 月至 2020 年 3 月期间因需要机械循环支持而入住三级医疗中心的终末期心力衰竭并同时接受坎格雷洛治疗的患者进行了回顾性单中心研究。记录了血小板功能检测、坎格雷洛剂量、出血并发症、血栓栓塞事件以及使用坎格雷洛期间的回路干预次数。使用即时护理检测(VerifyNow)测量最佳血小板反应性,定义为 P2Y < 180 血小板反应单位(PRU)。7 名患者符合上述标准,中位年龄为 4.9 岁。3 名患者患有复杂先天性心脏病。4 名患者患有扩张型或限制型心肌病。所有患者均接受连续流动 VAD 治疗。VAD 中位持续时间为 84.5 天(IQR 61.5-103)。中位坎格雷洛使用时间为 43 天(IQR 8-70)。达到治疗阈值的中位坎格雷洛剂量为 0.75 μg/kg/min,平均 P2Y 为 164.75 PRU。出血并发症包括轻度胃肠道出血和血尿。有 1 例患者因泵血栓形成需要干预。在使用坎格雷洛期间未发生脑血管事件。我们报告了首例成功在儿科患者中长期使用坎格雷洛的案例。坎格雷洛的可逆性和半衰期短使其成为选定患者中可行的抗血小板药物。该数据支持在儿童中使用坎格雷洛作为一种可行的抗血小板选择;在该队列中未显示出最小的出血并发症和没有脑血管事件。