Mendoza Carmen E, Brant Elizabeth J, McDermott Matthew L, Froment Anne, Hu Yichun, Hogan Susan L, Jennette J Charles, Falk Ronald J, Nachman Patrick H, Derebail Vimal K, Bunch Donna O'Dell
Department of Medicine, Division of Nephrology, UNC Kidney Center, University of North Carolina, Chapel Hill, North Carolina, USA.
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
Kidney Int Rep. 2019 Jul 13;4(11):1617-1629. doi: 10.1016/j.ekir.2019.07.006. eCollection 2019 Nov.
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.
In this prospective study, patients were enrolled during active disease and followed longitudinally. Twelve patients who experienced a VTE (VTE) were compared with patients without VTE (VTE, = 29) and healthy controls (HC, = 70). MPTFa, anti-Plg, interleukin-6, high-sensitivity C-reactive protein (hs-CRP), D-dimer, serum creatinine, and serum albumin were 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.
VTE patients had higher MPTFa (peak median = 14.0, interquartile range = 4.3-36.6) than HC (0, 0-3.5) and VTE 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.
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.
静脉血栓栓塞症（VTE）是抗中性粒细胞胞浆抗体（ANCA）血管炎的一种危及生命的并发症，其发病机制尚未完全阐明。我们检验了这样一个假设，即微粒组织因子活性（MPTFa）升高或抗纤溶酶原抗体（抗-Plg）可能识别出有VTE风险的患者。
在这项前瞻性研究中，患者在疾病活动期入组并进行纵向随访。将12例发生VTE的患者（VTE组）与未发生VTE的患者（非VTE组，n = 29）及健康对照者（HC组，n = 70）进行比较。评估MPTFa、抗-Plg、白细胞介素-6、高敏C反应蛋白（hs-CRP）、D-二聚体、血清肌酐和血清白蛋白。Fisher精确检验和Wilcoxon检验分别比较分类变量和连续变量。对发生VTE的时间或末次随访进行Cox回归分析。
VTE患者的MPTFa水平（峰值中位数 = 14.0，四分位间距 = 4.3 - 36.6）高于HC组（0，0 - 3.5）和非VTE组患者（0，0 - 1.4）。在事件发生时间分析中，无论是在疾病活动期（风险比[HR]；95%置信区间[CI]：1.04；1.01 - 1.08）还是缓解期（1.4；1.11 - 1.77）测量，MPTFa均与VTE相关。缓解期的抗-Plg也与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）。校正估计肾小球滤过率（eGFR）后，缓解期的抗-Plg仍与VTE显著相关。
MPTFa升高和缓解期抗-Plg增加是独立于肾功能的VTE的有力指标。缓解期抗-Plg与VTE的关联意味着即使在疾病静止期也存在高凝状态。低白蛋白血症强烈预示VTE风险，这是ANCA血管炎中的一个新发现。一种血栓形成特征将有助于改善患者管理，以将VTE风险和抗凝并发症降至最低。
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