Deptula Joseph, Olshove Vincent, Oldeen Molly, Kozik Deborah, Alsoufi Bahaaldin
Pediatric Perfusion, Norton Children's Hospital, Louisville, Kentucky, USA.
Department of Cardiovascular and Thoracic Surgery, School of Medicine and Norton Children's Hospital, University of Louisville, Louisville, Kentucky, USA.
Perfusion. 2025 Mar;40(2):431-439. doi: 10.1177/02676591241239819. Epub 2024 Mar 19.
Over the past decade, there has been an increase in the use of recombinant Anti-Thrombin III (AT-III) administration during neonatal and pediatric short- and long-term mechanical support for the replacement of acquired deficiencies. Recombinant AT-III (Thrombate) administration is an FDA licensed drug indicated primarily for patients with hereditary deficiency to treat and prevent thromboembolism and secondarily to prevent peri-operative and peri-partum thromboembolism. Herein we propose further use of Thrombate for primary AT-III deficiency of the newborn as well as for acquired dilution and consumption secondary to cardiopulmonary bypass (CPB).
All patients undergoing CPB obtain a preoperative AT-III level. Patients with identified deficiencies are normalized in the OR using recombinant AT-III as a patient load, in the CPB prime, or both. Patient baseline Heparin Dose Response (HDR) is assessed using the Heparin Management System (HMS) before being exposed to AT-III. If a patient load of AT-III is given, a second HDR is obtained and this AT-III Corrected HDR is used as the primary goal during CPB. Once CPB is initiated, an AT-III level is obtained with the first patient blood analysis. A subtherapeutic level results in an additional dose of AT-III. During the rewarm period, a final AT-III level is obtained and AT-III treated once again if subtherapeutic. A retrospective, matched analysis review of practice analyzing two groups, a Study Group (Repeat HDR, May 2022 onward) and Matched Group (Without Repeat HDR, July 2019 to April 2022), for age (D), weight (Kg) and operation was conducted. The focus of the study was to determine any change in heparin sensitivity identified post AT-III patient bolus load in the HDR (U/mL), Slope (U/mL/s), ACT (s), and total amount of heparin on CPB (U) and protamine (mg) used in each group.
No significance was seen in Baseline AT-III (%), post heparin load HDR (U/mL), first CPB ACT (s), first CPB HDR (U/mL), or total CPB heparin (u/Kg) between the two groups. Statistical significance was seen in Baseline ACT (s), Baseline HDR (U/mL), Baseline Slope (U/mL/s), Post Heparin Load ACT (s), first CPB AT-III (%), and Protamine (mg/Kg) ( < .05). No statistical significance was seen in the Study Intragroup between pre versus post AT-III patient load baseline sample in ACT (s), however significance was seen in HDR (U/mL) and Slope (U/mL/s) ( < .05).
Implementation of AT-III monitoring and therapy before and during CPB in conjunction with the HMS allows patients to maintain a steady state of anticoagulation with overall less need for excessive heparin replacement and potentially thrombin activation. The result is obtaining a steady state of anticoagulation, a reduced fluctuation in the heparin and ACT levels and a potential for lower co-morbidities associated with prolonged CPB times.
在过去十年中,在新生儿和儿科短期及长期机械支持期间,为弥补获得性缺乏,重组抗凝血酶III(AT-III)的使用有所增加。重组AT-III(血栓形成素)给药是一种获得美国食品药品监督管理局(FDA)许可的药物,主要用于治疗和预防遗传性缺乏患者的血栓栓塞,其次用于预防围手术期和围产期血栓栓塞。在此,我们提议进一步将血栓形成素用于新生儿原发性AT-III缺乏以及体外循环(CPB)继发的获得性稀释和消耗。
所有接受CPB的患者术前均检测AT-III水平。已确定存在缺乏的患者在手术室使用重组AT-III作为患者负荷量、在CPB预充液中或两者兼用,使其恢复正常。在患者接受AT-III治疗前,使用肝素管理系统(HMS)评估患者基线肝素剂量反应(HDR)。如果给予AT-III患者负荷量,则再次获取HDR,且该AT-III校正后的HDR用作CPB期间的主要目标。一旦开始CPB,通过首次患者血液分析获取AT-III水平。如果水平低于治疗剂量,则给予额外剂量的AT-III。在复温期,获取最终AT-III水平,如果低于治疗剂量,则再次给予AT-III治疗。对两组进行回顾性、匹配分析,即研究组(重复HDR,2022年5月起)和匹配组(无重复HDR,2019年7月至2022年4月),分析年龄(岁)、体重(千克)和手术情况。该研究的重点是确定每组中AT-III患者推注负荷后在HDR(单位/毫升)、斜率(单位/毫升/秒)、活化凝血时间(秒)以及CPB中使用的肝素总量(单位)和鱼精蛋白(毫克)方面所确定的肝素敏感性的任何变化。
两组之间在基线AT-III(%)、肝素负荷后HDR(单位/毫升)、首次CPB活化凝血时间(秒)、首次CPB HDR(单位/毫升)或CPB总肝素量(单位/千克)方面未发现显著差异。在基线活化凝血时间(秒)、基线HDR(单位/毫升)、基线斜率(单位/毫升/秒)、肝素负荷后活化凝血时间(秒)、首次CPB AT-III(%)和鱼精蛋白(毫克/千克)方面发现有统计学意义(P<0.05)。在研究组内,患者负荷AT-III前后的基线样本在活化凝血时间(秒)方面未发现统计学意义,但在HDR(单位/毫升)和斜率(单位/毫升/秒)方面有统计学意义(P<0.05)。
在CPB前后实施AT-III监测和治疗并结合HMS,可使患者维持抗凝稳定状态,总体上减少对过量肝素替代的需求以及潜在的凝血酶激活。结果是获得抗凝稳定状态,肝素和活化凝血时间水平波动减小,以及与延长CPB时间相关的潜在合并症减少。