Elevated Microparticle Tissue Factor Activity Differentiates Patients With Venous Thromboembolism in Anti-neutrophil Cytoplasmic Autoantibody Vasculitis
Elevated Microparticle Tissue Factor Activity Differentiates Patients With Venous Thromboembolism in Anti-neutrophil Cytoplasmic Autoantibody Vasculitis
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DOI：
10.1016/j.ekir.2019.07.006
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发表时间：
2019-11-01
影响因子：
6
通讯作者：
Bunch, Donna O'Dell
中科院分区：
文献类型：
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作者：
Mendoza, Carmen E.;Brant, Elizabeth J.;Bunch, Donna O'Dell
前言：静脉血栓栓塞症(VTE)是抗中性粒细胞胞浆抗体(ANCA)型血管炎的一种危及生命的并发症，其发病机制尚不完全清楚。我们验证了微粒子组织因子活性(MPTFa)或抗纤溶酶原抗体(抗-PLG)升高可以识别VTE风险患者的假设。12例VTE患者(VTEpos)与29例无VTE患者(VTEneg，n=29)和70例健康对照组(HC，n=70)进行比较。检测MPTFa、抗-PLG、白介素6、超敏C反应蛋白(hs-CRP)、D二聚体、血肌酐和血清白蛋白。Fisher的精确检验和Wilcoxon检验分别比较了分类变量和连续变量。结果：VTEpos患者的MPTFa(峰值中位数为14.0，四分位数范围为4.3~36.6)明显高于HC患者(0，03.5)和VTEneg患者(0，0~1.4)。在事件发生时间分析中，在疾病活动期(危险比[HR]；95%可信区间[CI]：1.04；1.01-1.08)和缓解期(1.4；1.11-1.77)测量MPTFa时，MPTFa与VTE有关。缓解期抗PLG与VTE相关(1.17；1.03~1.33)。血清白蛋白每降低1 g/dl，VTE风险增加4倍(4.4；1.5-12.9)。调整估计的肾小球滤过率(EGFR)，缓解期抗PLG抗体与VTE显著相关。结论：MPTFa升高和缓解期抗PLG抗体升高是VTE独立于肾功能的强烈指标。缓解期抗-PLG与静脉血栓栓塞症的相关性表明，即使在疾病平静期也存在高凝状态。低蛋白血症强烈预示着静脉血栓栓塞症的风险，这是ANCA血管炎的新发现。血栓征将允许改善对患者的管理，将静脉血栓形成的风险和抗凝并发症降至最低。
Introduction: Venous thromboembolism (VTE) is a life-threatening complication of anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis whose mechanism remains incompletely elucidated. We tested the hypothesis that elevated microparticle tissue factor activity (MPTFa) or anti-plasminogen antibodies (anti-Plg) may identify patients at risk for VTE.Methods: In this prospective study, patients were enrolled during active disease and followed longitudinally. Twelve patients who experienced a VTE (VTEpos) were compared with patients without VTE (VTEneg, n = 29) and healthy controls (HC, n = 70). MPTFa, anti-Plg, interleukin-6, high-sensitivityC-reactive protein (hs-CRP), Ddimer, serumcreatinine, and serumalbuminwere assessed. Fisher's exact tests and Wilcoxon tests compared categorical and continuous variables, respectively. Cox regression for time to VTE or last follow-up was performed.Results: VTEpos patients had higher MPTFa (peak median = 14.0, interquartile range = 4.3-36.6) than HC (0, 03.5) and VTEneg patients (0, 0-1.4). In time-to-event analysis, MPTFa was associated with VTE when measured during both active disease (hazard ratio [HR]; 95% confidence interval [CI]: 1.04; 1.01-1.08) and remission (1.4; 1.11-1.77). Anti-Plg during remission was also associated with VTE (1.17; 1.03-1.33). Each g/dl decrease of serum albumin was associated with a 4-fold increase in VTE risk (4.4; 1.5-12.9). Adjusting for estimated glomerular filtration rate (eGFR), anti-Plg during remission remained significantly associated with VTE.Conclusion: Elevated MPTFa and increased anti-Plg in remission are strong indicators of VTE independent of renal function. Association of anti-Plg during remission with VTE implies hypercoagulability even during disease quiescence. Hypoalbuminemia strongly portends VTE risk, which is a novel finding in ANCA vasculitis. A thrombotic signature would allow improved management of patients to minimize VTE risk and complications of anticoagulation.