Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary.
Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; Department of Laboratory, Grof Tisza Istvan Hospital, Berettyoujfalu, Hungary.
Urol Oncol. 2020 Apr;38(4):191-197. doi: 10.1016/j.urolonc.2019.10.007. Epub 2019 Nov 9.
Thromboembolic complications are present in 0.8%-16.8% of the cases after radical prostatectomy (RP). Association between elevated plasma von Willebrand factor (VWF) levels-as an endothelial activation marker-and increased risk of thrombotic events has been evidenced. We aimed to elicit new data on the VWF after RP in prostate cancer patients and explore the role of it as a thrombotic risk factor. Upon perioperative plasma VWF levels (VWF:Ag) its collagen-binding (CB) activity (VWF:CB), multimerization, and cleaving enzyme (ADAMTS13 [a disintegrin and metalloprotease with thrombospondin type repeats, motif 1, type 13]) of the VWF multimers were quantitated along with Factor VIII and routine laboratory parameters in this observational pilot study.
Plasma samples of 24 prostate cancer patients were collected before (-1 day; D-1) and after RP (1 hour, 6 days, 1 month, and 10 months; H1, D6, M1, and M10). VWF:Ag, VWF:CB, ADAMTS13:Ag were measured by ELISA, and the multimer distribution by electrophoresis and quantitative densitometry. Factor VIII, fibrinogen, D-dimer, and other routine laboratory parameters were determined as well. Preoperative values served as baselines which were compared to controls (24 healthy individuals).
VWF:Ag and CB elevated by 122% and 143% respectively at H1 after RP then plateaued at D6 compared to baseline values. ADAMTS13/VWF:Ag ratio reduced by 41% at H1, and by 46% at D6, meanwhile the ratio of high molecular weight multimers increased as well. Values returned to baseline at M1 and further reduced to the levels of the controls at M10. All of the 24 patients at H1 and D6 and 14 at M10 were in potential prothombotic state according ROC analysis of the VWF parameters as indicators.
Prostate malignancy and then surgical stress, and inflammatory reactions induced release of VWF from the endothelial cells, along with an increasing amount of large multimers and relative reduction of ADAMTS13 level. Because these changes mark a prothrombotic state even at M1 after RP, more than 1 month follow-up and prophylactic targeting through the thrombotic and inflammatory activity of the VWF is proposed. Evaluation of VWF parameters provides new information about the long-term disturbances of primary hemostasis after radical pelvic oncologic surgery like RP and might improve the understanding the physiological and pathological recovery.
根治性前列腺切除术（RP）后，血栓栓塞并发症的发生率为 0.8%-16.8%。已有证据表明，血浆血管性血友病因子（VWF）水平升高（作为内皮细胞激活标志物）与血栓形成事件风险增加之间存在关联。我们旨在获得前列腺癌患者 RP 后 VWF 的新数据，并探讨其作为血栓形成风险因素的作用。在这项观察性初步研究中，我们定量检测了围手术期血浆 VWF 水平（VWF：Ag）、其胶原结合（CB）活性（VWF：CB）、多聚体化和 VWF 多聚体的裂解酶（ADAMTS13[解整合素和金属蛋白酶与血小板反应蛋白 1 型、重复序列 13]），以及因子 VIII 和常规实验室参数。
收集 24 例前列腺癌患者术前（-1 天；D-1）和术后（1 小时、6 天、1 个月和 10 个月；H1、D6、M1 和 M10）的血浆样本。通过 ELISA 测定 VWF：Ag、VWF：CB、ADAMTS13：Ag，通过电泳和定量密度测定法测定多聚体分布。还测定了因子 VIII、纤维蛋白原、D-二聚体和其他常规实验室参数。术前值作为基线，与对照组（24 名健康个体）进行比较。
RP 后 1 小时（H1），VWF：Ag 和 CB 分别升高 122%和 143%，然后在 D6 时达到平台期，与基线值相比。ADAMTS13/VWF：Ag 比值在 H1 时降低 41%，在 D6 时降低 46%，同时高分子量多聚体的比例也增加。在 M1 时，数值恢复到基线，在 M10 时进一步降低到对照组的水平。根据 VWF 参数作为指标的 ROC 分析，所有 24 例患者在 H1 和 D6 时以及 14 例患者在 M10 时均处于潜在的血栓形成状态。
前列腺恶性肿瘤和随后的手术应激、炎症反应诱导内皮细胞释放 VWF，同时大分子量多聚体的含量增加，ADAMTS13 水平相对降低。由于这些变化标志着 RP 后甚至在 M1 时即存在血栓前状态，因此建议进行超过 1 个月的随访，并通过 VWF 的血栓形成和炎症活性进行预防性靶向治疗。VWF 参数的评估提供了关于根治性盆腔肿瘤手术后原发性止血长期紊乱的新信息，如 RP，并可能有助于提高对生理和病理恢复的理解。
