平均血小板体积预测初发霍奇金淋巴瘤患者发生症状性静脉血栓栓塞的临床价值

Clinical value of mean platelet volume in predicting symptomatic venous thromboembolism in patients with newly diagnosed Hodgkin lymphoma

摘要目的探讨平均血小板体积(MPV)预测初发霍奇金淋巴瘤(HL)患者发生症状性静脉血栓栓塞(VTE)的临床价值。方法选择2011年1月至2014年12月,67例于西安高新医院血液科和100例于空军军医大学唐都医院血液科接受一线化疗方案治疗的初发HL患者为研究对象。其中,男性患者为77例,女性为90例;年龄为(42±15)岁。根据患者出院后随访1年内是否发生症状性VTE,将本研究167患者分为VTE组(n=12)和未发生VTE组(n=155);根据患者化疗前MPV预测发生症状性VTE风险的临界值(MPV=6.8 fl),将其分为MPV<6.8 fl组(n=21)和MPV≥6.8 fl组(n=146)。所有患者均接受标准一线化疗方案ABVD(多柔比星+博莱霉素+长春新碱+达卡巴嗪)方案治疗。采用回顾性研究方法收集本研究167例初发HL患者的一般临床资料和疾病相关资料,包括Lugano分级、症状体征、纵隔受累、国际预后评分(IPS)和Khorana风险评分(KRS),以及实验室相关检查结果,包括化疗前血红蛋白(Hb)值、血小板计数及白细胞计数(WBC)等。本研究所有初发HL患者均通过门诊或电话进行随访,并且记录患者出院后第1年内症状性VTE发生情况。呈正态分布的计量资料年龄,采用±s表示,2组比较采用成组t检验;呈非正态分布的计量资料,如化疗前MPV、血小板计数和WBC等,采用M(P25~P75)表示,2组比较采用Mann-Whitney U检验。患者性别、结外器官累及、全身症状、纵隔淋巴结直径≥10 cm、IPS为3~7分、KRS为3~4分、Hb值<100 g/L、化疗前血小板计数>350×109/L和化疗前WBC>11×109/L的患者所占比例等计数资料,采用率(%)表示,2组比较采用χ2检验或连续性校正χ2检验。患者化疗前MPV预测初发HL患者接受化疗后1年内发生症状性VTE的风险,采用受试者工作特征(ROC)曲线法,计算ROC-曲线下面积(AUC),并且通过约登指数最大原则确定最佳临界值。采用Kaplan-Meier法及Log-rank检验,对不同MPV分组初发HL患者的无症状性VTE生存率和总体生存(OS)率分别进行比较。采用多因素Cox比例风险回归模型分析影响初发HL患者症状性VTE发生率的影响因素(结外器官累及情况和化疗前MPV)。本研究遵循的程序符合2013年修订的《世界医学会赫尔辛基宣言》要求,并由患者本人或其家属签署临床研究知情同意书。结果①本研究167例初发HL患者在第1年随访期内,症状性VTE发生率为7.2%(12/167)。VTE组患者中,结外器官累及(Lugano分期为Ⅳ期)的患者比例为66.7%(8/12),高于未发生VTE组的27.7%(43/155),并且差异有统计学意义(χ^2=7.955,P=0.005);VTE组患者的中位MPV为6.7 fl(6.3~7.0 fl),低于未发生VTE组的7.4 fl(7.1~7.8 fl),并且差异亦有统计学意义(U=3.489,P=0.001)。② ROC曲线分析结果显示,化疗前MPV对初发HL患者发生症状性VTE的风险具有预测价值,其ROC-AUC为0.697 (95%CI:0.476~0.884,P=0.022),化疗前MPV预测初发HL患者发生VTE风险的最佳临界值为6.8 fl,特异度为91.6%,灵敏度为66.7%。③本研究MPV<6.8 fl组患者症状性VTE发生率为38.1%(8/21),高于MPV≥6.8 fl组的2.7%(4/146),并且差异有统计学意义(χ^2=38.757,P<0.001)。④ Kaplan-Meier生存曲线分析结果显示,MPV<6.8 fl组患者的无症状性VTE生存率低于MPV≥6.8 fl组患者,OS率亦低于MPV≥6.8 fl组患者,并且差异均有统计学意义(χ^2=40.220、44.443,P<0.001)。⑤多因素Cox比例风险回归模型分析结果显示,MPV<6.8 fl为影响初发HL患者症状性VTE发生的独立危险因素(OR=1.673, 95%CI:1.434~3.218,P=0.012)。结论MPV降低能够有效预测初发HL患者的症状性VTE发生风险增加,为临床预防、治疗初发HL患者的VTE提供有效指导。

Objective To investigate the clinical value of mean platelet volume (MPV) in predicting sympomatic venous thromboembolism (VTE) in patients with newly diagnosed Hodgkin lymphoma (HL). Methods From January 2011 to December 2014, a number of 67 patients in the Department of Hematology, Xi′an High-tech Hospital and 100 patients in Department of Hematology, Tangdu Hospital, Air Force Military Medical Universityhwith who were newly diagnosed HL and treated with first-line chemotherapy were enrolled in this study. There were 77 male patients and 90 females, with the age of (42±15) years old. According to the diagnosis of symptomatic VTE within 1 year after discharging from hospital, the 167 patients were divided into VTE group (n=12) and non-VTE group (n=155). According to the cut-off value (MPV=6.8 fl) of pre-chemotherapy MPV in predicting risk of symptomatic VTE, the patients were divided into MPV<6.8 fl group (n=21) and MPV≥6.8 fl group (n=146). All patients were treated with standard first-line chemotherapy regimen of ABVD (doxorubicin+ bleomycin+ vincristine+ dacarbazine). A retrospective method was performed to collect general clinical data and disease-related data from all HL patients, including Lugano classification, symptoms and signs, mediastinal involvement, international prognostic score (IPS), and Khorana risk score (KRS), as well as laboratory-related examination results, including hemoglobin (Hb) value, platelet count, and white blood cell count (WBC) before chemotherapy. All HL patients in this study were followed up by clinic or telephone, and the incidences of sympomatic VTE in the first year after discharging from hospital were recorded. The normal distributed data, such as age, was present as Mean±SD, and compared by independent-samples t test between 2 groups. The non-normal distributed data, such as pre-chemotherapy MPV, platelet count and WBC were presented as M (P25-P75), and compared by Mann-Whitney U test between 2 groups. The ratio of patient with different gender, extranodal organ involvement, systemic symptoms, mediastinal lymph node diameter≥10 cm, 3-7 scores of IPS, 3-4 scores of KRS, Hb value<100 g/L, pre-chemotherapy platelet count>350×109/L, pre-chemotherapy WBC>11×109/L were presented as percentage (%), and compared by chi-square test or continuous correction chi-square test between 2 groups. Predict value of pre-chemotherapy MPV for the risk of symptomatic VTE in patients with newly diagnosed HL within 1 year after receiving chemotherapy was assessed by the receiver operating characteristic (ROC) curve, ROC-area under curve (AUC) was calculated, and the optimal threshold was determined when the Youden index reaching the maximum value. The Kaplan-Meier method and Log-rank test were used to compare the non-symptomatic VTE survival rate and overall survival (OS) rate of all patients in different MPV groups. Multivariate Cox proportional hazard regression model was used to analyze the risk factors (exceptional organ involvement and pre-chemotherapy MPV) affecting the incidence of symptomatic VTE in patients with newly diagnosed HL. The procedure of this study was accordance with the requirement of the revised World Medical Association Declaration of Helsinki in 2013. And the informed consent form of the clinical study was signed by the patient or its guardian. Results ① Among 167 patients with newly diagnosed HL, the incidence of symptomatic VTE was 7.2%(12/167) within the first year of follow-up. In the VTE group, the proportion of patients with extranodal involvement (stage Lugano stage Ⅳ) was 66.7%(8/12), which was higher than that of 27.7%(43/155) in the non-VTE group, and the difference was statistically significant (χ^2=7.955, P=0.005). Median MPV was 6.7 fl (6.3-7.0 fl) in VTE group, which was lower than that of 7.4 fl (7.1-7.8 fl) in non-VTE group, and the difference was statistically significant (U=3.489, P=0.001).② ROC curve analysis results showed that pre-chemotherapy MPV had predictive value for the risk of symptomatic VTE in patients with newly diagnosed HL, and its ROC-AUC was 0.697 (95%CI: 0.476-0.884, P=0.022), and the optimal cut-off value of pre-chemotherapy MPV for symptomatic VTE risk in patients with newly diagnosed HL was 6.8 fl, with specificity of 91.6% and sensitivity of 66.7%.③ The incidence of symptomatic VTE in the MPV<6.8 fl group was 38.1%(8/21), which was higher than that of 2.7%(4/146) in the MPV≥6.8 fl group, and the difference was statistically significant (χ^2=38.757, P<0.001).④ Kaplan-Meier survival curve analysis results showed that the non-symptomatic VTE survival rate of patients in MPV<6.8 fl group was significantly lower than that of patients with MPV≥6.8 fl (χ^2=40.220, P<0.001), and the OS rate was significantly lower than that of MPV≥6.8 fl group (χ^2=44.443, P<0.001).⑤ Multivariate Cox proportional hazard regression model analysis results showed that MPV<6.8 fl was an independent risk factor for the incidence of symptomatic VTE in patients with newly diagnosed HL (OR=1.673, 95%CI: 1.434-3.218, P=0.012). Conclusions The decrease MPV could effectively predict the increased risk of symptomatic VTE in patients with newly diagnosed HL, and provide effective guidance for clinical prevention and treatment of symptomatic VTE in patients with newly diagnosed HL.