真性红细胞增多症患者静脉血栓栓塞危险因素分析及预测模型的建立  

Analysis of risk factors for venous thromboembolism in patients with polycythemia vera and establishment of a prediction model

作　　者：马金玉 张宇卉 滕广帅[1] 杜晨霄 张会勤 王艳 李艳旗 段依璠 周圆 邵宗鸿 白洁 Ma Jinyu;Zhang Yuhui;Teng Guangshuai;Du Chenxiao;Zhang Huiqin;Wang Yan;Li Yanqi;Duan Yifan;Zhou Yuan;Shao Zonghong;Bai Jie(Department of Hematology,the Second Hospital of Tianjin Medical University,Tianjin 300211,China;State Key Laboratory of Experimental Hematology,Institute of Hematology&Blood Diseases Hospital,National Clinical Research Center for Blood Diseases,Haihe Laboratory of Cell Ecosystem,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China)

机构地区：[1]天津医科大学第二医院血液科,天津300211 [2]中国医学科学院血液病医院,中国医学科学院血液学研究所,实验血液学国家重点实验室,国家血液系统疾病临床医学研究中心细胞生态海河实验室,天津300020

出　　处：《中华医学杂志》2024年第25期2336-2341,共6页National Medical Journal of China

基　　金：国家自然科学基金(82170117);天津市教委科研计划(2022ZD072、2022KJ253、2023KJ021);中国医学科学院医学与健康科技创新工程(2022-I2M-2-003)

摘　　要：目的探讨真性红细胞增多症(PV)患者发生静脉血栓的危险因素,并建立静脉血栓预测模型。方法回顾性纳入2017年9月至2023年11月天津医科大学第二医院JAK2^(V617F)基因突变阳性的PV患者,根据患者是否发生静脉血栓进行分组,采用倾向性评分匹配年龄、性别因素后,最终静脉血栓组纳入102例[男46例,女56例,年龄M(Q_(1),Q_(3))为52(44,60)岁],无静脉血栓组纳入204例[男92例,女112例,年龄为52(44,59)岁]。比较两组PV患者的临床及实验室特征、疾病进展、基因突变发生率等。随访截止日期为2023年11月20日,中位随访时间[M(Q_(1),Q_(3))]为11(1,53)年。采用多因素Cox风险模型对PV患者发生静脉血栓的影响因素进行分析,建立PV患者静脉血栓危险因素预测模型评分系统。采用受试者工作特征(ROC)曲线对该模型进行预测效能评估。结果静脉血栓组血红蛋白浓度、红细胞压积≥55%比例、中性粒细胞与淋巴细胞比率≥5比例、高血压比例、脾肋下≥5 cm比例、继发骨髓纤维化比例均高于无静脉血栓组(均P<0.05)。且静脉血栓组发生既往血栓栓塞史比例、JAK2^(V617F)基因突变负荷≥50%比例、糖尿病比例、携带ASXL1突变比例、继发网状纤维银染色≥3级比例均高于无静脉血栓组(均P<0.05)。静脉血栓组PV患者发生3个及以上基因突变比例为44.1%(45/102),高于无静脉血栓组的29.9%(61/204)(P=0.014)。静脉血栓组发生ASXL1基因突变比例为17.6%(18/102),高于无静脉血栓组的4.9%(10/204)(P<0.001)。多因素Cox风险模型分析结果表明,既往血栓栓塞史(HR=2.031,95%CI:1.297~3.179,P=0.002)、JAK2^(V617F)基因突变负荷≥50%(HR=2.141,95%CI:1.370~3.347,P=0.001)、ASXL1突变(HR=4.632,95%CI:1.497~14.336,P=0.008)、脾肋下≥5 cm(HR=1.771,95%CI:1.047~2.996,P=0.033)是PV患者发生静脉血栓栓塞的危险因素。建立PV患者静脉血栓危险因素预测模型评分系统:既往血栓栓塞史、JAK2^(V617F)基因�Objective To investigate the risk factors of venous thrombosis in patients with polycythemia vera(PV)and establish a prediction model for venous thrombosis.Methods PV patients with JAK2^(V617F)gene mutation positive in the Second Hospital of Tianjin Medical University from September 2017 to November 2023 were retrospectively included.The patients were divided into groups according to whether they had venous thrombosis.After matching age and gender factors with propensity scores,102 patients were included in the venous thrombosis group[46 males,56 females,with a median age M(Q_(1),Q_(3))of 52(44,60)years]and 204 cases were included in the group without venous thrombosis[92 males,112 females,with a median age of 52(44,59)years].The clinical and laboratory characteristics,disease progression and incidence of gene mutation were compared between the two groups.The follow-up cohort ended on November 20,2023,with a median follow-up[M(Q_(1),Q_(3))]of 11(1,53)years.Multivariate Cox risk model was used to analyze the influencing factors of venous thrombosis in PV patients,and establish a scoring system for the venous thrombosis risk factor prediction model of PV patients.Receiver operating characteristic(ROC)curve was used to evaluate the predictive efficiency of the model.Results Hemoglobin concentration,the ratio of hematopoietic volume≥55%,neutrophil to lymphocyte ratio≥5,hypertension,subcostal spleen≥5 cm and secondary myelofibrosis in venous thrombosis group were higher than those in non-venous thrombosis group(all P<0.05).In addition,the proportion of history of thromboembolism,V617F gene mutation load(V617F%)≥50%,diabetes mellitus,ASXL1 mutation and secondary reticular silver staining≥3 in the venous thrombosis group were higher than those in the non-venous thrombosis group(all P<0.05).The proportion of PV patients with 3 or more gene mutations was 44.1%(45/102)in venous thrombosis group,which was higher than that of PV patients without venous thrombosis 29.9%(61/204)(P=0.014).The proportion of ASXL1 gene

关 键 词：红细胞增多症 真性 静脉血栓栓塞 危险因素 预测模型 

分 类 号：R543.6[医药卫生—心血管疾病] R555.1[医药卫生—内科学]