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Bladder outlet procedures in the setting of anticoagulation therapy

Marien, Tracy; Shah, Ojas

doi: 10.1097/MOU.0b013e32835ac039

Purpose of review To assess the safety and bleeding risk in men on chronic oral anticoagulation, including antiplatelet therapies, undergoing bladder outlet procedures for the treatment of benign prostatic hyperplasia (BPH).

Recent findings There are conflicting findings; however, most recent series show that when treating bladder outlet obstruction from BPH in patients on chronic anticoagulants, there is an increased risk of hemorrhagic complications for these men. There is also an increased risk of cardiovascular and cerebrovascular complications, especially when antithrombotic therapy is used for secondary prevention and is withdrawn perioperatively. Some have found bipolar electrosurgical vaporization of the prostate, laser vaporization, and enucleation of the prostate to provide superior hemostatic outcomes compared to classic monopolar transurethral resection of the prostate.

Summary Extra caution should always be given to patients on chronic anticoagulation undergoing surgical procedures, given increased risk of bleeding and cardiovascular and cerebrovascular complications. For men with BPH undergoing bladder outlet procedures, photoselective vaporization of the prostate, Holmium laser enucleation of the prostate, and vaporization of the prostate with bipolar electrosurgical instruments may result in less bleeding complications. Further prospective randomized studies are needed to elucidate which methods provide better hemostasis and lower postoperative bleeding to best manage men with BPH on chronic antithrombotic therapy, especially when the anticoagulation therapy cannot be discontinued prior to therapy.

Department of Urology, New York University School of Medicine, NYU Langone Medical Center, New York, New York, USA

Correspondence to Ojas Shah, MD, 150 East 32nd Street, 2nd Floor, New York, NY 10016, USA. Tel: +1 646 825 6322; fax: +1 646 825 6385; e-mail:

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The success of medical therapy for benign prostatic hyperplasia (BPH) delays the need for the surgical treatment of bladder outlet obstruction (BOO) in many men. Series have shown that with the widespread use of medical therapy for BPH, the mean age at the time of bladder outlet procedure has significantly increased [1,2]. Some have also shown that the number of medical comorbidities, BMI, and prostate size have also significantly increased in patients undergoing surgical management of the prostate now compared with those cases prior to the advent of medical therapy [2].

Delayed surgical treatment of BPH combined with increased life-expectancy secondary to improved medical therapies has led to increased risk of morbidity with prostate surgeries aimed at treating BOO and BPH. With many elderly patients on chronic oral anticoagulation (OAC) or oral antiplatelet (OAP) medications for history of coronary stent, cardiac valve, arrhythmia, history of deep venous thrombosis or pulmonary embolism, peripheral vascular disease, and cerebrovascular disease, there is a significant concern for increased risk of bleeding and morbidity. Additionally, patients undergoing prostate surgery are already known to be at increased risk for bleeding from local fibrinolysis because of urokinase [3]. The purpose of this review is to assess the safety and bleeding risk in men on chronic OACs and OAPs undergoing bladder outlet procedures.

Box 1

Box 1

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Medical therapy for the purpose of decreasing thrombosis risks targets multiple pathways. OAP therapies target platelets to inhibit the formation of a platelet plug, whereas OAC target coagulation factors to inhibit the coagulation cascade. Aspirin irreversibly inhibits the formation of prostaglandin derivative thromboxane A2, resulting in the inhibition of platelet aggregation. Clopidogrel reduces platelet aggregation by irreversibly blocking a site on the platelet ADP receptor and thus preventing activation of the GPIIb/IIIa receptor complex. Aspirin combined with dipyridamole (which inhibits the uptake of adenosine into platelets, endothelial cells and erythrocytes and inhibits platelet plug formation) is also a commonly used agent for stroke prevention.

Warfarin depletes active vitamin K that is necessary for the hepatic synthesis of coagulation factors II, VII, IX, X, and proteins C and S. Other newer and less commonly employed OAC include dabigatran (an active direct thrombin inhibitor) and rivaroxaban (reversible inhibition of factor Xa). These drugs have the advantage over warfarin in that they do not require monitoring of coagulation tests. For dabigatran, reversal agents are only in experimental phases and the medication is known to have prolonged effects in the elderly and in those with chronic kidney disease [4,5]. Current recommendations for timing of discontinuation of dabigatran are dependent on the patient's renal function and risk of bleeding with the surgical procedure. In the setting of normal renal function, the drug can be withdrawn about 24 h prior to a low-risk procedure versus 2–4 days prior for a procedure that has a higher risk of bleeding [6]. As renal function declines, the half-life of dabigatran increases and the patient will need a longer withdrawal period prior to surgical procedure. Rivaroxaban is cleared less by the kidneys and can be held 1–2 days prior to surgery; however, consideration of a longer withdrawal period should be considered for men with kidney disease [6]. As these drugs are still relatively new with very few studies available to validate their safety in the setting of surgical procedures and none in the setting of prostate surgery for BPH, we recommend extreme caution when performing bladder outlet procedures on these patients, specifically when the anticoagulation cannot be discontinued [7].

The remainder of this section will focus on the most commonly used OAC and OAPs – warfarin, clopidogrel, and aspirin.

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Indications for warfarin therapy include atrial fibrillation, severe myocardial dysfunction, prosthetic heart valves (especially metallic), deep venous thrombosis, and pulmonary embolism. Concerns regarding the management of this medication in the perioperative period include the risk of thromboembolic events if this medication is withdrawn, the risk of rebound hypercoagulability when withdrawn, and risk of bleeding if this medication is continued through the bladder outlet procedure or bridged with heparin therapy. Intravenous heparin or subcutaneous low molecular weight heparin (LMWH) is sometimes used as a bridge between warfarin withdrawal and resumption. These medications allow the patient to be without anticoagulation for a shorter period of time and in theory decrease the risk of thromboembolic events. For atrial fibrillation, the risk of thromboembolic events without anticoagulant therapy is approximately 5% per year [8]. Systemic embolism risk for prosthetic valves is roughly quoted at 1% per year on warfarin, 2% per year on aspirin, and 4% per year with no anticoagulation. For elective noncardiac surgeries, most guidelines recommend bridges in the setting of mitral mechanical valves, multiple mechanical valves, and an aortic mechanical valve with a risk factor (i.e. atrial fibrillation, history of thromboembolism, left ventricular dysfunction, a hypercoagulable state, and older generation thrombogenic valves) [9,10].

In Table 1, several series compare bladder outlet procedures in patients on warfarin to those not on any OCPs and OAPs. Some managed perioperative warfarin therapy with complete cessation, bridging, or continuation through the procedure.

Table 1

Table 1

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Continuation of warfarin

In Table 1, three series describe their experience with continuation of warfarin through bladder outlet procedure. Tyson et al. and Hochreiter et al. performed Holmium enucleation of the prostate (HoLEP) with patients on warfarin, though the average INR in the Tyson series was 1.5 versus 2.7 in the Hochreiter series [12,15]. Of Hochrieter's 19 patients, two experienced clot retention postoperatively. Tyson's series of 13 patients did not experience any hemorrhagic complications, though over half of the patients in this series were subtherapeutic on warfarin at the time of HoLEP. Another series by Ruszat et al.[13] described their experience with photoselective vaporization of the prostate (PVP) using the 80-W potassium titanyl phosphate [KTP, Greenlight (American Medical Systems, Minnetonka, Minnesota, USA)] laser; 36 patients who continued their warfarin therapy through laser prostatectomy versus 92 patients not on any antithrombotic therapy were studied and they found that patients on warfarin required more postoperative continuous bladder irrigation (CBI).

In uncontrolled series, Woo and Hossack [18] reported on 43 patients who were continued on warfarin and underwent PVP with the 120-W lithium triborate (LBO) laser [Greenlight HPS (American Medical Systems, Minnetonka, Minnesota, USA)]. Although no patient required transfusions in this series, two patients experienced prolonged catheterization secondary to bleeding and two patients experienced exacerbation of a medical comorbidity.

Two series reported on their experience with maintaining warfarin therapy on 10–20 patients through neodynium yttrium aluminum garnet (Nd:YAG) laser ablation of the prostate and while one series reported no bleeding or thrombotic complications [19], the other had several complications including three patients requiring transfusions, one patient requiring reversal with fresh frozen plasma (FFP), one patient needing a revision for bleeding, and that same patient having a CVA secondary to FFP and revision of prostate procedure [20]. An older series from the 1980s performed transurethral resection of the prostate (TURP) on 13 patients (one underwent transurethral resection of bladder tumor) while on warfarin and found that four patients needed at least two transfusions, three required reversal, and one went into clot retention [21].

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Bridging warfarin

In theory, bridging patients on warfarin therapy with heparin should provide the best balance of low-risk bleeding and thromboembolic complications. One series of 36 men who were bridged with heparin undergoing TURP had no significant bleeding complications compared to 92 controls (Table 1) [16]. However, two other series had different findings. Dotan et al.[14] performed TURP on 20 patients on warfarin bridged with heparin and 20 control patients, and found a significantly longer catheterization period for those patients bridged with heparin secondary to hematuria. There was not a statistically significant difference for blood transfusions. Descazeaud et al.[11▪] compared patients on any type of antithrombotic (including 42 who were on warfarin and bridged with heparin by stopping warfarin 4 days prior to surgery and 7 days following and 13 patients whose warfarin was stopped) to 406 controls and found statistically significant higher rates of blood transfusions, bladder clots, and late hematuria as well as statistically significant increased rate of thromboembolic events (2.4 versus 0.7%). However, the interpretation of the Descazeaud et al. results regarding warfarin in particular is limited, as all antithrombotic medications were bundled together.

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Warfarin withdrawal

Stopping warfarin altogether should put patients at the same overall risk as any man not taking antithrombotic therapy. Two uncontrolled series reported their experience with PVP [Greenlight (American Medical Systems, Minnetonka, Minnesota, USA)]. Sandhu et al.[22] reported no patient required transfusions, experienced significant blood loss or postoperative bleeding in 24 patients undergoing PVP with the 80-W KTP laser. However, Chung et al.[23▪] reported on 31 patients undergoing PVP with the 120-W Greenlight HPS laser (American Medical Systems, Minnetonka, Minnesota, USA) whose warfarin was held 1–3 days preoperatively and found that two patients required transfusions and one a reoperation for bleeding. Many of these patients were likely to still be therapeutic at the time of PVP given the short interval of time between cessation and PVP, though preoperative INR was not reported in this series. In a series performing TURP on multiple men on antithrombotics, including 11 men on warfarin that was withdrawn perioperatively, one patient with atrial fibrillation experienced a perioperative transient ischemic attack and stroke [24▪].

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When performing bladder outlet procedures on men taking warfarin therapy, it appears laser procedure such as PVP [Greenlight (American Medical Systems, Minnetonka, Minnesota, USA)] or HoLEP have illustrated the least major bleeding complications in the limited available studies. Bleeding risk can be minimized if warfarin therapy can be discontinued perioperatively; however, this will likely increase the risk of thromboembolic events. This decision requires discussion between the treating urologist, consulting physicians, and the patient in order to appropriately weigh the risks against the benefits of the anticoagulation therapy and continuing or discontinuing it prior to surgical intervention.

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Clopidogrel is typically used in patients with previous cerebrovascular accidents, recent acute coronary syndromes, or recent percutaneous coronary interventions with placement of cardiac stents. When drug-eluting coronary stents are placed, clopidogrel should not be stopped for up to 1 year per Food and Drug Administration recommendations [25]. It is generally recommended that elective surgery be postponed until the minimum period of therapy with this platelet inhibitor is completed and the medication can be safely held. For coronary stents, it is typically recommended to continue baby aspirin at a minimum to prevent thrombosis of the stent during the perioperative period.

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Continuation of clopidogrel

One series by Ruszat et al.[13] contained nine patients who continued clopidogrel therapy during PVP with the 80-W KTP laser [Greenlight (American Medical Systems, Minnetonka, Minnesota, USA)] versus 92 controls who were not on any antithrombotic therapy and found no statistically significant difference in bleeding complications except increased postoperative CBI (Table 1). Three other series without control groups with two to 19 patients in which clopidogrel was continued through PVP [Greenlight (American Medical Systems, Minnetonka, Minnesota, USA)] also found no significant bleeding complications [22,23▪,26▪].

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Bridging or withdrawal of clopidogrel

The series by Descazeaud et al.[11▪] with 74 patients on clopidogrel (59 bridged with preventive dosed LMWH and 15 were withdrawn from this medication peri-TURP) again reported increased transfusions, bladder clots, and late hematuria compared with controls, but again these results are combined with patients on all types of antithrombotics and are not specific to clopidogrel. This series performed a subanalysis between OAC and OAPs and found no difference in complication rates between patients on warfarin versus antiplatelet therapies. In another series comparing TURP to transurethral resection in saline (TURis), no major bleeding complications were noted with 25 patients bridged on clopidogrel and three where this medication was withdrawn perioperatively [27▪]. There are reports of patients with a history of symptomatic BPH and cardiovascular disease with percutaneous coronary intervention (details regarding type of or timing of coronary stent were not provided) where clopidogrel was withdrawn at the time of TURP and one patient experienced acute coronary syndrome perioperatively [24▪].

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Clopidogrel is a potent platelet inhibitor and is a critical component in antiplatelet therapy, specifically in cases of coronary drug-eluting stents. Overall, laser therapy with PVP [Greenlight (American Medical Systems, Minnetonka, Minnesota, USA)] appears to provide adequate hemostatic control for men with symptomatic BPH undergoing bladder outlet procedures. Our recommendation would be to wait for elective surgery until clopidogrel therapy can be held perioperatively whenever possible; however, it does appear to be relatively safe to perform PVP BPH surgery if needed while on therapy. More studies on the newer laser and bipolar technologies are needed to better assess the safety profile of these technologies in the setting of clopidogrel.

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Many men take aspirin for primary and secondary prevention of cardiovascular complications. The 2012 guidelines from the American College of Chest Physicians recommend continuing aspirin at the time of surgery for patients at moderate-to-high risk of cardiovascular events undergoing noncardiac surgery and for those at low risk to stop 7–10 days prior to surgery [28]. Additionally, high-dose aspirin is noted to have increased bleeding risk compared with low-dose aspirin [29].

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Aspirin continuation

In Table 1, three series had patients continue aspirin therapy through bladder outlet procedure. Two series with 25 and 71 patients undergoing HoLEP or PVP with KTP [Greenlight (American Medical Systems, Minnetonka, Minnesota, USA)] noted no bleeding complications compared to controls except increased postoperative CBI [12,13]. However, a series by Donat et al.[17] in 2003 conducted a multicenter, prospective, randomized, double-blind, placebo-controlled series on a total of 99 patients with some proportion remaining on aspirin and the rest as controls, and found that at the time of TURP there was no significant difference in blood loss, increased need for bladder washouts, and delayed catheter removal. However, four patients on aspirin required blood transfusions and one patient underwent a reoperation versus zero patients in the control arm. Other studies have reported good hemostasis with PVP on aspirin [22].

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Bridging or withdrawal of aspirin

Descazeaud et al.[11▪] demonstrated in their series that included men with BPH undergoing TURP whose aspirin was bridged or withdrawn at the time of TURP, an increased rate of blood transfusions, bladder clots, late hematuria, and thromboembolic events compared to men not on any OAC and OAP therapy, though again these results are for all antithrombotics and not specific to aspirin. Another series, in which all antithrombotic outcomes (n = 111) were combined and aspirin was withdrawn in most cases, found no significant difference in hemorrhagic or thromboembolic complications compared to 194 control patients [30▪]. However, another series where aspirin was withheld in 40 patients peri-TURP, one patient with a history of cardiovascular disease and an unspecified percutaneous intervention experienced an acute coronary syndrome perioperatively [24▪].

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Similar to the findings with clopidogrel, men with BPH and on aspirin appeared to do well with PVP and HoLEP when maintained on aspirin. Given the risk of permanent damage with thrombotic and embolic disease, it may be more prudent to maintain patients on their antithrombotics and perform the chosen procedure with transfusions if needed. Our recommendation based on the limited data would be to continue baby aspirin whenever feasible in men who have moderate-to-high risk cardiovascular or cerebrovascular disease and to discontinue aspirin therapy in low-risk disease prior to BPH therapy. The laser technologies appear to fare better than standard TURP in the setting of aspirin therapy. Further data on bipolar technology is needed to assess bleeding risk while anticoagulated. Patients who have coronary stents (either drug-eluting or bare metal) should continue on baby aspirin therapy during surgery whenever possible.

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Resection or ablation of the prostate can be performed using electrosurgery, or with laser technology through ablation, vaporization, or enucleation of the prostate. Electrosurgery can be performed with monopolar or bipolar technology. With monopolar surgery, the current goes through the patient to complete the circuit and with bipolar surgery the current only goes through the tissue between the electrodes of the instrument to complete the current. Bipolar technology has the advantage that it can be performed in normal saline and has less risk of transurethral resection syndrome compared to monopolar TURP that must be performed in isotonic irrigation solutions, such as glycine.

Laser technology in BPH therapy has increasingly gained popularity based on its ability to be performed on an outpatient basis with reduced potential morbidities of TUR syndrome, blood loss, retrograde ejaculation, and catheterization time. A Cochrane review comparing laser methods to TURP found a reduced risk of transfusion with laser prostatectomy [31]. The most common lasers employed to treat BPH include Nd:YAG, KTP laser [Greenlight PVP (American Medical Systems, Minnetonka, Minnesota, USA)], the Holmium:yttrium-aluminum-garnet (Ho:YAG), and the lithium triborate (LBO) laser [Greenlight HPS and XPS (American Medical Systems, Minnetonka, Minnesota, USA)].

The Nd:YAG laser emits light at 1064 nm and is poorly absorbed by water and body pigments and thus can penetrate tissues relatively deeply, though this laser is rarely used now for BOO and BPH surgery. The KTP laser emits light at 532 nm providing an intermediate level of coagulation and vaporization with shallower penetration compared to Nd:YAG. The Ho:YAG emits light at 2100 nm and compared to the Nd:YAG, this laser emits energy intermittently with impulses instead of continuous resulting in poorer hemostatic properties. The Holmium laser technology has been used for both ablation procedures similar to the vaporization procedure, likely best for smaller glands, and for enucleation procedures, which is one of the most effective procedures for the removal of prostate adenoma and very useful in larger glands; however, it has not attained popularity secondary to its steep learning curve [32–34]. In a series of 57 men with prostate volumes greater than 175 g undergoing HoLEP, Krambeck et al.[33] reported outcomes equivalent to that of open prostatectomy with low morbidity.

The LBO laser also functions at a wavelength of 532 nm like the KTP laser but offers an increased generator output of 120-W versus the 80-W by the KTP laser. The LBO laser has been noted to have a higher tissue ablation capacity but also higher bleeding rate compared to KTP [35]. This LBO technology has now also changed to an improved 180-W laser [Greenlight (American Medical Systems, Minnetonka, Minnesota, USA)] with the potential benefits of more efficacious vaporization and improved coagulation [36]. The fiber has a built-in cooling system with normal saline and has an automatic safety system [FiberLife (American Medical Systems, Minnetonka, Minnesota, USA)] that detects when the fiber may overheat and briefly disables the laser beam.

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Monopolar transurethral resection of the prostate versus bipolar transurethral resection procedures

Several studies have been performed evaluating patients on antithrombotic medications with BPH undergoing monopolar TURP versus those undergoing bipolar TURis and transurethral vaporization of the prostate in saline (TUVis) (Table 2). In the series by Delongchamps et al.[27▪] of patients with BPH on various antithrombotic medications managed in various ways (i.e. most withdrawn or bridged, some held), 57 men who underwent monopolar TURP were compared to 54 men who underwent TUVis. The men in the TUVis arm were significantly less likely to need bladder washouts, experience late hematuria, and have less blood loss. No patient in the entire series required blood transfusions or needed a reoperation for bleeding.

Table 2

Table 2

In the series by Michielson et al.[37▪], 176 men on chronic anticoagulation with BPH were divided into two groups in which 78 men underwent TURP and 98 underwent TURis. The average gland size for men undergoing TURP and TURis was approximately 55 cc in each group. All 92 patients on warfarin and 84 patients on OAPs were bridged with heparin except for those patients on clopidogrel for cardiac stents (unclear how many patients) which was then continued. This series found no difference in blood loss, need for blood transfusions, or clot retention between patients who underwent monopolar versus bipolar resection of BPH typically when the anticoagulation therapy was discontinued perioperatively.

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Laser vaporization, ablation, and enucleation of the prostate

There are no studies comparing the endoscopic surgical management of BPH for patients on OACs or OAPs to other lasers or other surgical treatment modalities. Overall, laser therapy appears to have low risk of bleeding complications in this patient population, particularly with the KTP and LBO lasers. Other commonly used laser technologies, such as the 2013 nm thulium [Revolix (Lisa Laser, Pleasanton, California, USA)] and the 980 nm lasers [Evolve (Biolitec, Inc, East Longmeadow, Massachusetts, USA)], have not been well studied with regard to anticoagulation. The two series evaluating HoLEP in patients on anticoagulation (warfarin and aspirin that was continued through surgery) reported a high procedure abortion rate at 8% and almost a 10% transfusion rate [12,38].

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Simple prostatectomy

To our knowledge, no studies to date have evaluated the bleeding risks of performing simple prostatectomy (open or laparoscopic and robotic) for large glands on anticoagulant and antithrombotic therapy.

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The effectiveness of medical therapy has led to a delay in the surgical management of BPH. Men undergoing deobstructive prostate surgery are frequently older with more medical comorbidities and more likely to be on chronic antithrombotic therapy. Continuation of these medications through prostate surgery results in increased bleeding complications, whereas withdrawal of these medications results in increased risk for cardiovascular and cerebrovascular complications. From the limited retrospective, noncomparative studies available PVP [Greenlight (American Medical Systems, Minnetonka, Minnesota, USA)] and HoLEP appear to provide superior hemostasis. Bipolar vaporization procedures may provide improved hemostasis; however, further confirmatory studies are needed. Future research with prospective, randomized studies of patients on commonly used oral anticoagulants and OAP therapies comparing various ablative techniques is necessary to draw definitive conclusions on the most effective technique with the fewest complications. The ideal technique would not require cessation of any antithrombotic medication.

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Conflicts of interest

Disclosures: Ojas Shah: Boston Scientific – consultant; Cook Urological – consultant; Covidien – consultant; Watson Pharmaceuticals – study investigator. Tracy Marien: none.

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Papers of particular interest, published within the annual period of review, have been highlighted as:

  • ▪ of special interest
  • ▪▪ of outstanding interest

Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 98–99).

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This multicenter, observational study of 612 men with BPH undergoing TURP, 206 of who were on oral warfarin and platelet inhibitors, showed an increase in bleeding complications on antithrombotics and no difference in complications if on OAC versus OAP.

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This retrospective series on 162 men on various antithrombotic therapies undergoing PVP (Greenlight HPS) reported a 4% delayed bleeding rate with some patients requiring transfusions and one patient needing a reoperation, illustrating still a risk of bleeding even with Greenlight laser vaporization.

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This retrospective series on 480 men (18 on clopidogrel) undergoing Greenlight laser vaporization of the prostate illustrated that this technology allows for the treatment of BPH in men at high risk of bleeding secondary to clopidogrel without any bleeding or cardiovascular complications.

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This retrospective series of 305 patients on various antithrombotic therapies showed that cessation of aspirin, dipyrimadole and aspirin, or warfarin 7 days prior to TURP or clopidogrel 10 days prior to TURP did not result in higher cardiovascular or cerebrovascular complications.

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35. Heinrich E, Wendt-Nordahl G, Honeck P, et al. 120 W lithium triborate laser for photoselective vaporization of the prostate: comparison with 80 W potassium-titanyl-phosphate laser in an ex-vivo model. J Endourol 2010; 24:75–79.
36. Malek RS, Kang HW, Peng YS, et al. Photoselective vaporization prostatectomy: experience with a novel 180 W 532 nm lithium triborate laser and fiber delivery system in living dogs. J Urol 2011; 185:712–718.
37▪. Michielsen DP, Coomans D, Van Lersberghe C, Braeckman JG. Comparison of the haemostatic properties of conventional monopolar and bipolar transurethral resection of the prostate in patients on oral anticoagulants. Arch Med Sci 2011; 7:858–863.

This retrospective series on 176 men on chronic anticoagulation found no difference in bleeding complications for men undergoing TURis versus TURP.

38. Elzayat E, Habib E, Elhilali M. Holmium laser enucleation of the prostate in patients on anticoagulant therapy or with bleeding disorders. J Urol 2006; 175:1428–1432.

anticoagulation; antiplatelet; benign prostatic hypertrophy; bladder outlet procedure; transurethral resection of the prostate

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