Long-lasting prothrombotic state implied by changes of plasma von Willebrand factor parameters after radical prostatectomy for prostate malignancy

• Published in: Urologic oncology Vol. 38; no. 4; pp. 191 - 197
• Main Authors: Harsfalvi, Jolan, Molnar, Zsuzsanna, Csanyi, Maria Cs, Domjan, Istvan, Flasko, Tibor, Kaposi, Andras, Benyo, Matyas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2020
• Subjects: Aged; Cellular haemostasis; Humans; Male; Malignancy; Middle Aged; Plasma - chemistry; Prostate cancer; Prostatectomy - methods; Prostatic Neoplasms - blood; Prostatic Neoplasms - surgery; Radical pelvic surgery; Thromboembolism; Thrombotic event; Von Willebrand factor; von Willebrand Factor - metabolism; Von Willebrand factor; Malignancy; Radical pelvic surgery; Thromboembolism; Thrombotic event; Prostate cancer; Cellular haemostasis
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2019.10.007

•Elevated von Willebrand factor (VWF) level is associated with thrombotic events.•Prostate cancer patients have increased VWF level and activity compared to controls.•VWF and Factor VIII parameters are still elevated 1 month after radical prostatectomy.•Increase of high VWF multimers and low relative ADAMTS13 levels are observed.•Long-lasting postoperative prothrombotic state indicates VWF targeted prophylaxis.
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.
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