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围手术期使用伊洛前列素治疗诊断为肝素诱导的血小板减少症反应性抗体或真正 HIT(HIT 反应性抗体加血小板减少症)的心脏手术患者:11 年经验。

Perioperative use of iloprost in cardiac surgery patients diagnosed with heparin-induced thrombocytopenia-reactive antibodies or with true HIT (HIT-reactive antibodies plus thrombocytopenia): An 11-year experience.

机构信息

3rd Department of Cardiothoracic Surgery, Onassis Cardiac Surgery Center, Athens, Greece.

2nd Department of Cardiothoracic Surgery, Onassis Cardiac Surgery Center, Athens, Greece.

出版信息

Am J Hematol. 2015 Jul;90(7):608-17. doi: 10.1002/ajh.24017.

Abstract

Thrombocytopenia and thromboembolism(s) may develop in heparin immune-mediated thrombocytopenia (HIT) patients after reexposure to heparin. At the Onassis Cardiac Surgery Center, 530 out of 17,000 patients requiring heart surgery over an 11-year period underwent preoperative HIT assessment by ELISA and a three-point heparin-induced platelet aggregation assay (HIPAG). The screening identified 110 patients with HIT-reactive antibodies, out of which 46 were also thrombocytopenic (true HIT). Cardiac surgery was performed in HIT-positive patients under heparin anticoagulation and iloprost infusion. A control group of 118 HIT-negative patients received heparin but no iloprost during surgery. For the first 20 patients, the dose of iloprost diminishing the HIPAG test to ≤5% was determined prior to surgery by in vitro titration using the patients' own plasma and donor platelets. In parallel, the iloprost "target dose" was also established for each patient intraoperatively, but before heparin administration. Iloprost was infused initially at 3 ng/kg/mL and further adjusted intraoperatively, until ex vivo aggregation reached ≤5%. As a close correlation was observed between the "target dose" identified before surgery and that established intraoperatively, the remaining 90 patients were administered iloprost starting at the presurgery identified "target dose." This process significantly reduced the number of intraoperative HIPAG reassessments needed to determine the iloprost target dose, and reduced surgical time, while maintaining similar primary clinical outcomes to controls. Therefore, infusion of iloprost throughout surgery, under continuous titration, allows cardiac surgery to be undertaken safely using heparin, while avoiding life-threatening iloprost-induced hypotension in patients diagnosed with HIT-reactive antibodies or true HIT.

摘要

在肝素免疫介导的血小板减少症(HIT)患者再次暴露于肝素后,可能会发生血小板减少症和血栓栓塞症。在 Onassis 心脏外科中心,在 11 年期间,17000 名需要心脏手术的患者中有 530 名接受了 ELISA 和三点肝素诱导的血小板聚集试验(HIPAG)的术前 HIT 评估。筛选出 110 名具有 HIT 反应性抗体的患者,其中 46 名也伴有血小板减少症(真正的 HIT)。在 HIT 阳性患者中,心脏手术在肝素抗凝和伊洛前列素输注下进行。118 名 HIT 阴性患者作为对照组,在手术期间接受肝素但不接受伊洛前列素。对于前 20 名患者,通过使用患者自身的血浆和供体血小板进行体外滴定,在手术前确定了将 HIPAG 试验降低至≤5%的伊洛前列素剂量。同时,也在手术期间为每位患者确定了伊洛前列素的“目标剂量”,但在给予肝素之前。伊洛前列素最初以 3ng/kg/ml 输注,并在手术期间进一步调整,直到体外聚集达到≤5%。由于术前确定的“目标剂量”与术中确定的剂量之间存在密切相关性,因此其余 90 名患者从术前确定的“目标剂量”开始接受伊洛前列素治疗。这一过程显著减少了确定伊洛前列素目标剂量所需的术中 HIPAG 重新评估次数,并缩短了手术时间,同时保持与对照组相似的主要临床结果。因此,在持续滴定的情况下,整个手术期间输注伊洛前列素可安全地使用肝素进行心脏手术,同时避免对诊断出具有 HIT 反应性抗体或真正 HIT 的患者使用伊洛前列素引起危及生命的低血压。

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