背景:ANCA相关性血管炎(AAV)的血栓形成普遍存在,在中国患者中被忽视。这项研究试图描述临床特征,确定风险因素,并通过双样本孟德尔随机(MR)分析研究AAV与静脉血栓栓塞(VTE)之间的因果关系。
方法:在本回顾性研究中,观察性研究,我们纳入了2013年1月至2022年4月在北京协和医院住院的所有AAV患者.我们收集他们的临床数据进行多元回归分析,以确定血栓形成的危险因素。通过应用这些危险因素来预测AAV患者的血栓形成,构建了列线图。至于MR分析,我们从已发表的全基因组关联研究中选择了与AAV相关的单核苷酸多态性(SNP),并从英国生物库提取了包含深静脉血栓形成(DVT)和肺栓塞(PE)的结局数据.
结果:纳入了1203例原发AAV患者,血栓形成发生率为11.3%。多元回归表明,年龄超过65岁,EGPA,神经受累,肺受累,血清肌酐显著升高(>500μmol/L),AAV患者D-二聚体升高与血栓形成有关。该模型显示出满意的区分度,AUC为0.769(95%CI,0.726-0.812)。MR分析显示EGPA可增加发生DVT和PE的风险(OR=1.0038,95CI=1.0035~1.0041,P=0.009)。
结论:中国AAV患者血栓形成并不罕见。肾损害和老年是血栓形成的关键危险因素。EGPA可能与DVT和PE有潜在的因果关系。
BACKGROUND: Thrombosis in ANCA-associated vasculitis (AAV) was prevalent and has been neglected in Chinese patients. This study tried to describe the clinical characteristics, identify the risk factors, and investigate the causal relationship between AAV and venous thromboembolism (VTE) by two-sample Mendelian randomization (MR) analysis.
METHODS: In this retrospective, observational study, we included all hospitalized AAV patients from Jan 2013 to Apr 2022 in Peking Union Medical College Hospital. We collected their clinical data for multivariate regression analysis to determine the risk factors for thrombosis. The nomogram was constructed by applying these risk factors to predict thrombosis in AAV patients. As for MR analysis, we selected single nucleotide polymorphisms (SNPs) related to AAV from published genome-wide association studies and extracted the outcome data containing deep vein thrombosis (DVT) and pulmonary embolism (PE) from the UK biobank.
RESULTS: 1203 primary AAV patients were enrolled, and thrombosis occurred in 11.3%. Multivariate regression suggested that older than 65 years, EGPA, neurological involvement, lung involvement, significantly elevated serum creatinine (> 500µmol/L), and elevated D-dimer were associated with thrombosis in AAV patients. The model demonstrated satisfied discrimination with an AUC of 0.769 (95% CI, 0.726-0.812). MR analysis showed that EGPA could increase the risk of developing DVT and PE (OR = 1.0038, 95%CI = 1.0035-1.0041, P = 0.009).
CONCLUSIONS: Thrombosis was not rare in Chinese patients with AAV. Renal damage and old age emerged as critical risk factors for thrombosis. EGPA might have a potential causal relationship with DVT and PE.