Lüsebrink Enzo, Scherer Clemens, Binzenhöfer Leonhard, Hoffmann Sabine, Höpler Julia, Kellnar Antonia, Thienel Manuela, Joskowiak Dominik, Peterß Sven, Petzold Tobias, Deseive Simon, Hein Ralph, Brunner Stefan, Kääb Stefan, Braun Daniel, Theiss Hans, Hausleiter Jörg, Hagl Christian, Massberg Steffen, Orban Martin
Medizinische Klinik und Poliklinik I, Klinikum der Universität München and DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, 81377 Munich, Germany.
Institut für Medizinische Informationsverarbeitung Biometrie und Epidemiologie, Klinikum der Universität München, 81377 Munich, Germany.
J Clin Med. 2023 Jan 2;12(1):362. doi: 10.3390/jcm12010362.
Background: Heparin-induced thrombocytopenia (HIT) is a serious, immune-mediated adverse drug reaction to unfractionated heparin (UFH) affecting also patients undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO). Although the association between VA-ECMO support and the development of thrombocytopenia has long been known and discussed, HIT as one underlying cause is still insufficiently understood. Therefore, the purpose of this study was to further investigate the epidemiology, mortality, diagnosis, and clinical management of HIT occurring in VA-ECMO patients treated with UFH. Methods: We conducted a retrospective single-center study including adult patients (≥18 years) with VA-ECMO support in the cardiac intensive care unit (ICU) of the University Hospital of Munich (LMU) between January 2013 and May 2022, excluding patients with a known history of HIT upon admission. Differences in baseline characteristics and clinical outcome between excluded HIT (positive anti-platelet factor 4 (PF4)/heparin antibody test but negative functional assay) and confirmed HIT (positive anti-PF4/heparin antibody test and positive functional assay) VA-ECMO patients as well as diagnosis and clinical management of HIT were analysed. Results: Among the 373 patients included, anti-PF4/heparin antibodies were detected in 53/373 (14.2%) patients. Functional HIT testing confirmed HIT in 13 cases (3.5%) and excluded HIT in 40 cases (10.7%), corresponding to a prevalence of confirmed HIT of 13/373 (3.5%) [1.6, 5.3] and a positive predictive value (PPV) of 24.5% for the antibody screening test. The platelet course including platelet recovery following argatroban initiation was similar between all groups. One-month mortality in patients with excluded HIT was 14/40 (35%) and 3-month mortality 17/40 (43%), compared to 5/13 (38%) (p > 0.999), and 6/13 (46%) (p > 0.999) in patients with confirmed HIT. Neurological outcome in both groups measured by the cerebral performance category of survivors on hospital discharge was similar, as well as adverse events during VA-ECMO therapy. Conclusions: With a prevalence of 3.5%, HIT is a non-frequent complication in patients on VA-ECMO and was not associated with a higher mortality rate. HIT was ultimately excluded by functional essay in 75% of VA-ECMO patients with clinical suspicion of HIT and positive anti-PF4/heparin antibody test. Argatroban seems to be an appropriate and safe therapeutic option for confirmed HIT-positive patients on VA-ECMO support.
肝素诱导的血小板减少症(HIT)是一种严重的、免疫介导的对普通肝素(UFH)的药物不良反应,也会影响接受静脉-动脉体外膜肺氧合(VA-ECMO)治疗的患者。尽管VA-ECMO支持与血小板减少症发生之间的关联早已为人所知并被讨论,但作为一个潜在原因的HIT仍未得到充分理解。因此,本研究的目的是进一步调查接受UFH治疗的VA-ECMO患者中发生HIT的流行病学、死亡率、诊断和临床管理情况。方法:我们进行了一项回顾性单中心研究,纳入了2013年1月至2022年5月在慕尼黑大学医院(LMU)心脏重症监护病房(ICU)接受VA-ECMO支持的成年患者(≥18岁),排除入院时已知有HIT病史的患者。分析了排除HIT(抗血小板因子4(PF4)/肝素抗体检测阳性但功能试验阴性)和确诊HIT(抗PF4/肝素抗体检测阳性且功能试验阳性)的VA-ECMO患者之间的基线特征和临床结局差异,以及HIT的诊断和临床管理情况。结果:在纳入的373例患者中,53/373(14.2%)例患者检测到抗PF4/肝素抗体。功能性HIT检测确诊13例(3.5%)HIT,排除40例(10.7%)HIT,确诊HIT的患病率为13/373(3.5%)[1.6, 5.3],抗体筛查试验的阳性预测值(PPV)为24.5%。所有组之间包括阿加曲班开始使用后的血小板恢复情况在内的血小板变化过程相似。排除HIT的患者1个月死亡率为14/40(35%),3个月死亡率为17/40(43%),而确诊HIT的患者分别为5/13(38%)(p>0.999)和6/13(46%)(p>0.999)。两组中通过出院时幸存者的脑功能类别衡量的神经学结局相似,VA-ECMO治疗期间的不良事件也相似。结论:HIT在VA-ECMO患者中的患病率为3.5%,是一种不常见的并发症,且与较高死亡率无关。在临床怀疑HIT且抗PF4/肝素抗体检测阳性的VA-ECMO患者中,75%最终通过功能试验排除了HIT。对于确诊HIT阳性的接受VA-ECMO支持的患者,阿加曲班似乎是一种合适且安全的治疗选择。