Rupa-Matysek Joanna, Gil Lidia, Wojtasińska Ewelina, Kanduła Zuzanna, Nowicki Adam, Matuszak Magdalena, Komarnicki Mieczysław
Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznań, Poland.
Oncotarget. 2017 Jun 15;8(35):60001-60014. doi: 10.18632/oncotarget.18499. eCollection 2017 Aug 29.
Hepatic sinusoidal obstruction syndrome (previously named veno-occlusive disease, SOS/VOD) is a serious complication of allogeneic stem cell transplantation (HSCT). Early identification of patients at risk of SOS/VOD may possibly improve the outcome and reduce mortality. Rotation thromboelastometry (ROTEM) is global assay allowing for the precise assessment of both bleeding and thrombotic conditions, however, its usefulness in patients undergoing HSCT for acute leukaemia has not been studied. We evaluated the thromboelastometry parameters in patients undergoing allogeneic HSCT for acute leukaemia to identify candidate biomarkers of SOS/VOD occurrence. ROTEM assays (INTEM, EXTEM, FIBTEM, APTEM) were performed on day -10, on the day of stem cell infusion (day 0) and on days +12 and +28 post-HSCT. The diagnosis of SOS/VOD was based on the Baltimore criteria. Seven patients (26%) developed SOS/VOD. On day +12, the patients with SOS/VOD had statistically significant longer INTEM-CT (clotting time, 199 ± 33.41vs166 ± 23.65s, = 0.0033), EXTEM-CT (69.5 ± 6.39vs.52 ± 3.42s, = 0.0139) and FIBTEM-CT (69.5 ± 22.75vs. 50.8 ± 14.31s, = 0.0124) compared to SOS/VOD (-). ROC curve on day +12 indicated a cut-off value of 179s in INTEM-CT (AUC = 0.91), 69s in EXTEM-CT (AUC = 0.90) and 102s in FIBTEM-CT (AUC = 0.82) for the prediction of SOS/VOD. This is the first study evaluating the usefulness of ROTEM assays in the early detection of haemostasis abnormalities predictive of SOS/VOD development in patients undergoing HSCT for acute leukemia. Patients with SOS/VOD had a significant delay in the initiation of thrombin formation in the analysed ROTEM assays. The utility of ROTEM assays in the optimal management of patients undergoing HSCT should be clarified in further prospective studies.
肝窦阻塞综合征（先前称为静脉闭塞性疾病，SOS/VOD）是异基因干细胞移植（HSCT）的一种严重并发症。早期识别有SOS/VOD风险的患者可能会改善预后并降低死亡率。旋转血栓弹力图（ROTEM）是一种全面的检测方法，可精确评估出血和血栓形成情况，然而，其在接受急性白血病HSCT患者中的应用尚未得到研究。我们评估了接受急性白血病异基因HSCT患者的血栓弹力图参数，以确定SOS/VOD发生的候选生物标志物。在移植前10天、干细胞输注当天（第0天）以及HSCT后第12天和第28天进行ROTEM检测（INTEM、EXTEM、FIBTEM、APTEM）。SOS/VOD的诊断基于巴尔的摩标准。7名患者（26%）发生了SOS/VOD。在第12天，与未发生SOS/VOD的患者相比，发生SOS/VOD的患者INTEM-CT（凝血时间，199±33.41对166±23.65秒，P = 0.0033）、EXTEM-CT（69.5±6.39对52±3.42秒，P = 0.0139）和FIBTEM-CT（69.5±22.75对50.8±14.31秒，P = 0.0124）在统计学上有显著延长。第12天的ROC曲线表明，INTEM-CT的截断值为179秒（AUC = 0.91），EXTEM-CT为69秒（AUC = 0.90），FIBTEM-CT为102秒（AUC = 0.82），用于预测SOS/VOD。这是第一项评估ROTEM检测在早期发现预测接受急性白血病HSCT患者SOS/VOD发生的止血异常方面有用性的研究。在分析的ROTEM检测中，发生SOS/VOD的患者凝血酶形成起始明显延迟。ROTEM检测在接受HSCT患者的最佳管理中的效用应在进一步的前瞻性研究中加以阐明。
