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ST-Genesia 分析仪检测到新诊断多发性骨髓瘤患者的增强型凝血酶生成。

Enhanced thrombin generation detected with ST-Genesia analyzer in patients with newly diagnosed multiple myeloma.

机构信息

Department of Hematology, Hospital Universitario Fundación Jiménez Díaz, IIS-FJD, Madrid, Spain.

Department of Hematology, Hospital Universitario Fundación Jiménez Díaz, Avenida Reyes Católicos 2, 28040, Madrid, Spain.

出版信息

J Thromb Thrombolysis. 2023 Apr;55(3):464-473. doi: 10.1007/s11239-022-02765-8. Epub 2023 Jan 11.

DOI:10.1007/s11239-022-02765-8
PMID:36630029
Abstract

The issue of how to identify newly diagnosed multiple myeloma (NDMM) patients requiring thromboprophylaxis remains unsolved. Several changes in thrombin generation (TG)-derived parameters have been described in multiple myeloma (MM) patients recently. Assessment of prothrombotic risk with a fully automated TG analyzer could reduce interlaboratory variability. Our objective was to determine whether ST-Genesia could reveal a hypercoagulable state in NDMM compared to healthy controls. We conducted a multicenter observational study of NDMM requiring initial treatment to compare TG parameters obtained with ST-Genesia analyzer and ST-ThromboScreen reagent with a control group. Clinical data were obtained from medical records and blood samples were collected before initial anti-myeloma therapy. A thrombophilia panel was performed in all patients. Compared to age- and sex-matched controls (n = 83), NDMM patients (n = 83) had significantly higher peak height, higher velocity index, shorter time-to-peak and lower percentage of endogenous thrombin potential (ETP) inhibition after adding thrombomodulin (TM) (ETP%inh). NDMM on prophylactic low molecular weight heparin (LMWH) showed reduced both peak height and velocity index compared to NDMM who had not yet started VTE prophylaxis, similar to that of controls. Moreover, partial correction of ETP%inh was observed in MM patients on LMWH. The presence of a thrombophilia did not modify the TG phenotype. Untreated NDMM patients showed an enhanced TG, regardless of their thrombophilia status. They generate a higher peak of thrombin, take less time to produce it, and exhibit resistance to TM inhibition. Our findings suggest that standard prophylactic dose of LMWH may reduce TG at levels of healthy controls.

摘要

如何识别新诊断的多发性骨髓瘤(NDMM)患者需要进行血栓预防仍然未得到解决。最近,在多发性骨髓瘤(MM)患者中描述了几种凝血酶生成(TG)衍生参数的变化。使用全自动 TG 分析仪评估血栓形成风险可以减少实验室间的变异性。我们的目的是确定 ST-Genesia 是否可以揭示 NDMM 与健康对照组相比是否存在高凝状态。我们进行了一项多中心观察性研究,对需要初始治疗的 NDMM 患者进行了研究,以比较 ST-Genesia 分析仪和 ST-ThromboScreen 试剂获得的 TG 参数与对照组。临床数据来自病历,在初始抗骨髓瘤治疗前采集血液样本。对所有患者进行血栓形成倾向分析。与年龄和性别匹配的对照组(n=83)相比,NDMM 患者(n=83)的峰值高度、速度指数更高,达到峰值的时间更短,添加血栓调节蛋白(TM)后内源性凝血酶潜能(ETP)抑制百分比(ETP%inh)更低。与尚未开始 VTE 预防的 NDMM 相比,正在接受预防性低分子量肝素(LMWH)治疗的 NDMM 患者的峰值高度和速度指数均降低,与对照组相似。此外,在接受 LMWH 治疗的 MM 患者中观察到 ETP%inh 部分纠正。血栓形成倾向的存在并未改变 TG 表型。未经治疗的 NDMM 患者表现出增强的 TG,无论其血栓形成倾向如何。他们产生更高的凝血酶峰值,产生它所需的时间更少,并且对 TM 抑制具有抗性。我们的发现表明,标准预防性 LMWH 剂量可能会降低 TG 水平,使其达到健康对照组的水平。

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