Abstract:

Objective　To investigate the clinical value of plasma von Willebrand factor antigen (VWF:Ag) and activity (VWF:Ac) levels in the prediction of venous thromboembolic events in patients with cancers. Methods　A total of 167 patients with cancers who were treated in Nanyang Central Hospital from June 2020 to December 2021 were selected as a caner group, including 97 males and 70 females who were (52.53±10.58) years old. While 135 healthy volunteers matched with the cancer group during the same period were selected as a healthy control group, including 91 males and 44 females who were (47.56±8.09) years old. Their plasma vWF:Ag and vWF:Ac levels were measured. The differences of vWF were analyzed in the cancer group overall and between each subgroup and the healthy control group by Mann-Whitney U test. Spearman rank correlation was used to analyze the correlation between vWF:Ag and vWF:Ac. Cox proportional risk regression model was used to screen the prognostic influencing factors in the patients. The value of vWF:Ag and vWF:Ac in the prediction of the occurrence of VTE events was assessed by receiver operator characteristic curve (ROC) during the 90 d follow-up. Survival analysis was performed using the Kaplan-Meier method. Results　The plasma vWF:Ag and vWF:Ac levels in the case group were significantly higher than those in the healthy control group [197.38% (143.54%, 328.97%) vs. 117.00% (97.70%, 147.40%) and 191.87% (130.85%, 265.69%) vs. 117.90% (99.50%, 153.00%); Z=8.76 and 7.91; both P<0.001]. The correlation analysis revealed that there was a positive correlation between vWF:Ag and vWF:Ac in the case group (r=0.783, P<0.001). During the follow-up, the vWF:Ag and vWF:Ac levels in the group with VTE events were higher than those in the group without VTE events [432.38% (248.14%, 539.55%) vs. 183.00% (126.96%, 246.02%) and 258.38% (174.11%, 373.84%) vs. 175.42% (122.05%, 251.00%); Z=5.65 and 3.89; both P<0.001]. The Cox multifactorial regression analysis showed that vWF:Ag was an independent influencing factor on the occurrence of VTE events during the 90 d follow up in the patients (hazard rate=1.03, P<0.001). In assessing the diagnostic efficacy for the occurrence of venous thrombotic events in the patients, the areas under the curves (AUC) of vWF:Ag and vWF:Ac were 0.818 and 0.719; the sensitivities were 78.8% and 69.7%; the specificities were 75.4% and 67.9%; for predicting the occurrence of VTE events in the patients, the predictive value of the combined test was higher (AUC=0.825). The patients with vWF:Ag≥244.98% occurred VTE events earlier than the patients with vWF:Ag<244.98% (χ²=20.49, P<0.001). Conclusions　Plasma vWFvWF:Ag and vWF:Ac levels are significantly elevated in patients with cancers, and there is a high concordance between the increases. vWF:Ag is an independent influencing factor in the occurrence of VTE events in patients with cancers; vWF may be a potential marker for predicting venous thrombosis associated with VTE events in patients with cancers.

Key words:

von Willebrand factor, Activity, Cancers, Venous thrombosis

摘要：

目的　探讨恶性肿瘤患者血管性血友病因子（von Willebrand factor antigen，vWF）的抗原（vWF antigen，vWF：Ag）、活性（vWF activity，vWF：Ac）水平预测恶性肿瘤患者发生静脉血栓栓塞（venous thromboembolism，VTE）事件的临床价值。方法　选取2020年6月至2021年12月在南阳市中心医院就诊的恶性肿瘤患者167例作为恶性肿瘤组，其中男97例，女70例，年龄（52.53±10.58）岁；选取同期体检正常、与恶性肿瘤组相匹配的135例志愿者作为健康对照组，其中男91例，女44例，年龄（47.56±8.09）岁。检测两组vWF：Ag和vWF：Ac水平。采用非参数Mann-Whitney U检验分析恶性肿瘤组与健康对照组之间vWF的差异性，采用Spearman秩相关分析vWF：Ag与vWF：Ac之间的相关性。Cox比例风险回归模型筛选恶性肿瘤患者的预后影响因素。随访90 d，通过受试者工作特征曲线（ROC）评估vWF：Ag、vWF：Ac对患者发生VTE事件的预测价值。用Kaplan-Meier法进行生存分析。结果　与健康对照组相比，恶性肿瘤组血浆vWF：Ag和vWF：Ac水平均显著升高［197.38%（143.54%，328.97%）比117.00%（97.70%，147.40%）、191.87%（130.85%，265.69%）比117.90%（99.50%，153.00%），Z=8.76、7.91，均P<0.001］，且vWF：Ag与vWF：Ac呈正相关（r=0.783，P<0.001）。随访期间，VTE事件发生组的vWF：Ag、vWF：Ac水平高于未发生VTE事件组［432.38%（248.14%，539.55%）比183.00%（126.96%，246.02%）、258.38%（174.11%，373.84%）比175.42%（122.05%，251.00%），Z=5.65、3.89，均P<0.001］。Cox多因素回归分析显示，vWF：Ag是恶性肿瘤患者90 d随访期间发生VTE事件的独立影响因素（风险比=1.03，P<0.001）。vWF：Ag和vWF：Ac预测恶性肿瘤患者发生VTE事件的曲线下面积（area under the curve，AUC）分别为0.818、0.719，灵敏度分别为78.8%、69.7%，特异度分别为75.4%、67.9%，两者联合检测的预测价值更高（AUC=0.825）。vWF：Ag≥244.98%的恶性肿瘤患者的总体VTE事件发生时间早于vWF：Ag<244.98%的患者（χ²=20.49，P<0.001）。结论　恶性肿瘤患者血浆vWF：Ag、vWF：Ac水平均显著升高，且两者之间的增长具有较高的一致性。vWF：Ag是恶性肿瘤患者发生VTE事件的独立影响因素，vWF可能是预测恶性肿瘤患者VTE事件的潜在标志物。

关键词:

血管性血友病因子, 活性, 恶性肿瘤, 静脉血栓