Results of our study have demonstrated that both anaesthetic techniques seem to increase the risk of TED in prostate cancer patients undergoing LRP, mainly when the robot device was utilized, suggesting, therefore, the utility of a peri-operative thromboembolic prophylaxis. In fact, both TIVA-TCI and BAL patients showed a marked and significant increase in pro-coagulant factors and consequent reduction in haemostatic system inhibitors in the early post operative period (p≤0.004 for each markers). However, this effect could be linked also to surgical stress, although the latter seems to have an independent effect only for p-selectin, as demonstrated by multivariate analysis. Moreover, the significant reduction of p-selectin levels between T0 and T2 (p = 0.001) observed in TIVA patients undergoing LRP, although this group of patients was composed mainly of patients at high-risk prostate cancer (as reported in Table 1), demonstrated that general anaesthetic agents used for TIVA have a better protective effect on the platelet activation in this subgroup of patients.
The evaluation of markers detecting activation of the hemostatic system represents a more sensitive way to assess the risk of thromboembolism as compared to the clinical assessment of TED. In our study, the activation of haemostatic system associated with thromboembolic risk was estimated by measuring levels of thrombin activation markers. TAT, PF1 + 2 and FVIII increased in the immediate post operative period and gradually returned to near baseline levels. The peri-operative activation of coagulation also caused an increased of peri-operative PAI-1 levels, a potent inhibitor of fibrinolysis. The activation state persists during surgery and is independent of the anaesthetic agents used. These results confirm previous studies performed on patients undergoing major abdominal surgery for colon-rectal cancer , hepatic cancer resection , pneumonectomy for lung cancer .
No studies had previously examined whether different intra-operative anaesthetic regimens (TIVA-TCI vs. BAL) could cause different intra-operative profiles of highly sensitive and specific coagulation and fibrinolysis markers in prostate cancer patients undergoing a highly standardized type of surgery (LRP or RALP). In this context, the results of our study seem to provide useful information in reducing the peri-operative trombo-embolic risk and improving the prognosis of cancer patients undergoing LRP and RALP.
Even though cancer patients who undergo surgery are targeted for thromboprophylaxis, widespread use of prophylaxis could determine the risk of intra-operative bleeding , and a detrimental effect rather than a benefit. This problem is evident in prostate cancer patients undergoing surgery, especially in view of the increasingly frequent use of the robotic technique that has resulted in a significant reduction of surgical complications ,. Although the American and European guidelines recommend prophylaxis in patients with prostate cancer -, its use is currently widely debated given the different incidence of TED observed by several authors. A multicentric analysis of a number of institutions from both Europe and the United States showed a very low incidence of TED (about 0.5%) . A similar incidence (0.9%) was reported from the California Cancer Registry . Conversely, Osborne et al.  consider patients with prostate cancer at intermediate risk of TED similar to patients with uterine, rectal, colon and liver cancer.
Prostatectomy significantly increases the incidence of TED up to 2.9% and 3.9%, as reported by Hu JC et al. , irrespective of the surgical approach. Tewari et al.  in a recent meta-analysis on 400 original research articles on surgical treatment for prostate cancer and its complications reported that the rate of deep vein thrombosis was significantly lowest for RALP (0.3%), intermediate for LRP (0.5%) and highest for open surgery (1.0%). More recently, Van Hemelrijck et al.  analysed thromboembolic events following prostatectomy in about 45.000 men collected in the Prostate Cancer Database Sweden. Risk of venous thromboembolism and pulmonary embolism occurred especially in the first 2 months after surgery with the highest risk in patients undergoing open or laparoscopic surgery with pelvic lymph node dissection while laparoscopic procedures without lymph node dissection were at lowest risk. Unfortunately, in this study authors did not created separate categories for LRP and RALP as the majority of laparoscopic surgery was performed with robotic assistance. In our case series, dissection of pelvic lymph node was not an independent risk factor for TED because no significant differences were demonstrated in the values of the markers analyzed among the various subgroups of patients studied. Moreover, it should be noted that in previous studies only the clinical incidence of venous thromboembolism was measured, but not the changes of coagulation factors. In other studies many biomarkers were specifically checked for their capacity to predict venous thromboembolism during the course of cancer disease , but changes in these markers due to different types of surgery, such as LRP or RALP, were not evaluated. Our results are even more surprising when we consider that the anesthetic drugs used both in TIVA-TCI and BAL, in particular propofol  and sevoflurane , act by inhibiting the platelet aggregation, although with different mechanisms.
Patients underwent RALP, compared to LRP group, showed a greater reduction of inhibitors of haemostatic system, such as protein S, and the increase of p-selectin, a cell adhesion molecule on the surface of activated endothelial cells and activated platelets . Data present in the literature regarding the different risk of thrombosis in patients submitted to LRP or RALP are very few. In a recent study Saily et al.  observed that RALP activates coagulation, and thromboprophylaxis for high-risk patients even after minimally invasive surgery may be beneficial. In particular, patients undergoing RALP showed postoperatively increased levels of fibrinogen, factor VIII, d-dimer associated to a thrombocytosis, reflecting a coagulation activity. The greater risk of thrombosis with the RALP could be also related to the surgical stress that leads RALP to a major release of inflammatory mediators  or a greater oxidative stress induced by ischemia–reperfusion , determining the endothelial dysfunction and hypercoagulability . This hypothesis is outlined by the fact that no differences were observed in other factors that may cause an activation of the haemostatic system in the peri-operative period such as anemia, hypoxia, hypothermia, hemodilution, hypotension, peritoneal insufflation, and Trendelenburg position ,. We do not know whether changes in pro-coagulant factors may determine the occurrence of thrombotic complications since an anti-thrombotic prophylaxis was administered for ethical reasons 24 hrs after surgery.
Our results suggest the use of a prophylaxis in all patients undergoing laparoscopic prostatectomy, in particular RALP, regardless of the type of anesthesia. Prophylaxis could not be required only in patients undergoing LRP with TIVA-TCI anaesthesia since a significant reduction in p-selectin levels between T0 and T2 (p = 0.001) was observed in this subgroup of patients. On the contrary, p-selectin did not change in patients undergoing LRP with BAL. Thus, the results we obtained suggest a greater inhibition effect of propofol, as compared to sevofluorane, on platelet aggregation p-selectin mediated. The different effect of propofol and sevofluorane on p-selectin levels observed in our study is in agreement with previous observations reporting that sevofluorane inhibits human platelet aggregation induced by weak antagonists such as adenosine diphosphate, but not by strong agonists like thrombin ,. Propofol, on the contrary, inhibits platelet aggregation mediated by thrombin  that regulates also the expression of p-selectin on platelets.