Objectives: 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.
Methods: 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).
Results: 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.
Conclusions: 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.
2019 Elsevier Inc. All rights reserved.
