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invasive procedure.30 Importantly, unlike warfarin and was for aspirin to be discontinued 7–10 days before
heparin, there is no antidote for these agents in the case surgery,36 although this was not based on any firm evi-
of overdose or need for reversal. dence and might be inappropriate in high-risk patients.
Given that over 20% of patients undergoing prostate
Antiplatelet medications surgery have a past history of ischemic heart disease or
A number of drugs are available that reduce platelet cerebral vascular accident,1,37,38 and that ischemic heart
adhesion or aggregation (Figure 2). They are used pre- disease is the leading cause of death in the perioperative
dominantly for the prevention of atherot hrombosis period for patients undergoing TURP,39 it is impera-
in cardiov ascular disease. If a patient who contin- tive that aspirin is only withheld after appropriate
ues antiplatelet therapy through surgery has severe risk stratification.
hemorrhage perioperatively, platelet transfusion is Data demonstrate that aspirin use is associated with
the most likely successful treatment option, although a slightly increased risk of postoperative bleeding.
consideration must be given to time of the last dose of Ala-Opas et al.40 found no difference in TURP-related
antiplatelet medication. blood loss between patients on aspirin and nonaspirin
users.40 Nielsen et al.41 performed a randomized con-
Aspirin and NSAIDs trolled trial comparing hemorrhage rates of patients
Aspirin and other non-steroidal anti-inflammatory drugs who continued aspirin during TURP with those who
(NSAIDs) inhibit the production of TXA2 (Figure 2). stopped taking aspirin 10 days before surgery. They
Aspirin is used extensively as a cardiovascular protec- showed no significant difference in intraoperative
tive medication owing to its antiplatelet effect; it acts by blood loss rates, but the aspirin group experienced
irreversibly acetylating cyclooxygenase‑1 (COX‑1). Low- significantly greater postoperative blood loss (284 ml
dose aspirin (50–100 mg) is considered to act prefer versus 144 ml), although there was no difference in
entially on COX‑1, while higher doses are thought to transfusion requirements or recatheterization rates. 41
have a less selective effect on platelet aggregation and Ehrlich et al. 42 compared early recommencement of
more gastrointestinal toxicity.31,32 Low-dose aspirin is aspirin after TURP (once irrigation had been discon-
widely proven to reduce the incidence and risk of death tinued) with restarting 21 days after surgery and found
associated with myocardial infarction, unstable angina, that early aspirin recommencement was not associated
transient ischemic attack and stroke.31,33,34 After coronary with increased postoperative bleeding.42 Donat et al.43
stent placement, aspirin is commonly taken to prevent retrospectively analyzed a series of patients who under-
stent thrombosis, especially if a drug-eluting stent went TURP, over 20% of whom remained on aspirin or
is inserted. NSAIDs. These patients did not have increased trans
Bleeding time, after cessation of aspirin, will return fusion requirements. 43 In the large meta-analysis of
to normal within 48 h,35 which is the time taken for new noncardiac surgeries carried out by Burger et al.,44 it
platelets to reach sufficient numbers to compensate for was found that periprocedural aspirin increased the
the effects of aspirin. 36 Common historical practice rate of bleeding complications by 1.5%, although it
did not lead to a higher level of severity of bleeding Other antiplatelet medicines
complications. Further, it was found that aspirin with- Dipyridamole is a phosphodiesterase inhibitor normally
drawal precedes up to 10.2% of cases of acute cardio- used in stroke prevention that impairs platelet aggrega-
vascular syndrome and that these events usually occur tion. Although its mechanism of action is unclear, it is
within 30 days of aspirin cessation.44 thought to act by blocking the degradation of cAMP
The American College of Chest Physicians suggests (Figure 2). The increased levels of cAMP inhibit
that aspirin should be continued perioperatively in calcium release, which occurs during platelet activation.
high-risk patients undergoing noncardiac surgery, but Dipyridamole has a weak and short-lasting antiplatelet
discontinued in lower-risk patients, such as those taking effect, and is shown to cause no excess risk of bleeding.32
aspirin for primary prevention of acute myocardial In patients at low risk of a thromboembolic event, it can
infarction or cerebral vascular accident.21 Furthermore, be ceased 2 days before TURP. Importantly, extended-
it has been suggested that patients who discontinue release dipyridamole is often produced in combination
aspirin perioperatively should start taking it again 24 h with aspirin, which results in a relative reduction in risk
after surgery.45 of cardiovascular events of 20%, compared to aspirin
Other NSAIDs, such as ibuprofen, indomethacin alone, without increasing risk of hemorrhage.51
and naproxen, reversibly acetylate both COX‑1 and Glycoprotein IIb–IIIa antagonists, such as abciximab
COX‑2, which prevents synthesis of TXA2 within plate- and tirofiban, are medications used in the acute setting
lets, thereby reducing their aggregation (Figure 2). of unstable angina and perioperatively for the preven-
Different agents cause transient and incomplete plate- tion of acute thrombosis during coronary stent inser-
let dysfunction to varying degrees.31 As a simple rule, tion. They antagonize the IIb–IIIa fibrinogen receptors
the more COX‑1-specific an NSAID is, the more plate- involved in the final step of the platelet aggregation
let dysfunction and bleeding it causes, whereas COX‑2 pathway (Figure 2).32 A much higher risk of bleeding
specificity implies greater anti-inflammatory properties. would be anticipated if a patient remained on such agents
Because the majority of NSAIDs are used for analgesia during surgery, so TURP is contraindicated, although
or inflammatory conditions rather than cardiovascular no studies have been performed to specifically address
protection, they can be withheld a week before surgery this issue. Glycoprotein IIb–IIIa antagonists are typically
without raising cardiovascular risk. Alternatively, stopped 7–10 days before surgery.
NSAIDs can be continued through surgery at the Vitamin E is used by an increasing number of the
surgeon’s discretion with proper risk assessment. general population although studies have shown an
equivocal protective effect against cardiovascular
Thienopyridines disease.52 Vitamin E can significantly reduce platelet
These drugs act to impair platelet aggregation by block- adhesion, and it is recommended that patients stop
ing the interaction of ADP with its receptor (Figure 2). taking this nonessential medication before TURP.53
Clopidogrel and prasugrel are commonly used in
patients with cardiac stents, and in those with a history Treatment of TURP-related bleeding
of ischemic heart disease or cerebral vascular accident as Many pharmacologic interventions have been tested in
secondary prevention. clinical trials for the reduction of TURP-related bleeding,
Clopidogrel is the original thienopyridine used widely including medications that reduce prostate vascularity
in patients with ischemic heart disease. Platelet function and others that stabilize the clotting process. Agents that
returns to normal 7 days after treatment is stopped.31,46 reduce idiopathic prostate bleeding or hemorrhage risk in
There are associated problems with substantial patient patients undergoing prostate surgery are summarized
intervariability in terms of response to clopidogrel.47 in Table 2.
No studies have been performed that specifically assess
clopidogrel use during prostate surgery. The American Antiandrogens
College of Chest Physicians suggests that clopidogrel Various agents that reduce androgen activity also reduce
should be stopped 7 days before prostate surgery, intraprostatic vascularity. The most commonly used
unless the patient has had a bare metal stent inserted drugs are the 5α-reductase inhibitors (5-ARIs), which
within 6–12 weeks or a drug-eluting stent inserted within block the 5α-reductase enzyme that converts testoster-
12 months, then both aspirin and clopidogrel must be one to dihydrotestosterone, the active hormone involved
continued,21 and prostate surgery should be postponed. in growth of the prostate. 5‑ARIs reduce prostatic
In one study of 192 patients, the incidence of early drug- blood flow via downregulation of vascular endothelial
eluting stent thrombosis after noncardiac surgery (13% growth factor (VEGF), before gland shrinkage occurs.
urologic) was 31% in patients who had stopped taking Dutasteride blocks type I and II 5α-reductase enzymes,
clopidogrel, compared to 0% in those who continued whereas finasteride blocks type II only. Both drugs have
dual antiplatelet therapy.48 been shown to reduce the amount of dihydrotestosterone
Prasugrel is a newer thienopyridine, recently approved in the bloodstream by about 80% within 1–2 weeks, and
for patients with acute coronary syndrome undergoing reduce the size of the prostate by about 30% within
percutaneous interventions. Prasugrel is associated with 6–12 months.54 Subsequently, PSA levels halve owing to
more effective and consistent action than clopidogrel, but reduction in size of the transition zone where most PSA
a slightly increased risk of major bleeding.47,49,50 is produced.55
Of the two drugs, finasteride has been most closely resected tissue was significantly lower in the finasteride
examined with regard to bleeding associated with pros- group than controls (7.6 ml versus 14.0 ml).65 Donohue
tate surgery. Donohue et al.56 demonstrated the down- et al.66 compared finasteride 5 mg daily with placebo for
regulation of VEGF in patients treated with finasteride for 2 weeks before TURP, and found a significant reduction
2 weeks before TURP, with an associated reduction in sub- in blood loss per gram of resected tissue in the finasteride
urethral prostatic microvessel density (MVD).56 Hochberg group (2.65 g versus 4.65 g of hemoglobin), although
et al.57 also reported that finasteride reduces MVD in men in this study hemoglobin loss was unusually high in
undergoing TURP.57 These observations are important the control group.66 Neither of these studies showed a
given that the prostates of men with BPH and hema significant difference in blood transfusions required.
turia have a significantly higher MVD in the suburethral Sandfeldt et al.67 studied TURP-related bleeding in
portion than those of men with BPH alone.58 patients pretreated with finasteride for 3 months and
Kashif et al. 59 studied finasteride in a series of 12 found no significant reduction in blood loss, resection
patients with recurrent idiopathic prostatic hema weight or operating time. However, they did show a
turia, and found that bleeding resolved in all patients positive correlation between blood loss and resection
within 2 weeks.59 Puchner and Miller 60 showed 11 of 12 weight in finasteride-treated patients, where prostates
patients treated with finasteride had an improvement in weighing more than 18.6 g were associated with signifi-
their degree of idiopathic hematuria within 3 months.60 cantly less blood loss than those weighing less than 18.6 g
Sieber et al.61 described a similar result: 25 of 28 patients (324 ml versus 547 ml).67 Hagerty et al.68 demonstrated a
reported resolution of their gross hematuria with finas- similar result for patients pretreated with finasteride for
teride treatment.61 Kearney et al.62 demonstrated that 4 weeks before TURP. Postoperative bleeding rates
prostate volume correlated with the average time needed for patients with more than 30 g of resected tissue were
for resolution of hematuria, which was 2.7 days for small 8.3% and 36.8% in the finasteride and control groups,
prostates (<40 g) and 19–45 days for extra large glands respectively. Moreover, this study showed a reduction in
(>100 g). Further, they demonstrated resolution of hema- transfusion rates for patients pretreated with finasteride
turia in 31 of 40 patients on aspirin or warfarin treated with resected prostates >30 g (0% compared to 16% for
with finasteride.62 Foley et al.63 performed a prospective patients who did not receive finasteride).68
randomized trial of patients with idiopathic prostatic A large randomized controlled trial comparing patients
hematuria treated with finasteride or placebo. Hematuria who received dutasteride or placebo for 2–4 weeks before
resolved in 86% of finasteride-treated patients, compared TURP found no difference in blood loss or difference
with only 37% of those who received placebo. Surgery in MVD.69 Similarly, no difference in blood loss was
was required in 26% of patients in the control group, and observed in a smaller randomized controlled where
no patients who took finasteride.63 patients in the treatment arm received dutasteride for
A survey of British urologists revealed that 98% of 5 weeks before TURP.70
respondents use finasteride for hematuria thought to Notably, many studies of 5‑ARIs exclude patients on
be prostate-related. Only 4%, however, use finasteride anticoagulant or antiplatelet therapy and 5‑ARIs might
in all their patients before TURP, and 51% use it selec- be particularly effective in reducing blood loss in these
tively, such as for intermittent hematuria, large prostate, patients. The 2010 AUA BPH guidelines state there is
or bleeding concerns.64 Ozdal et al.65 showed that when insufficient evidence to recommend perioperative 5‑ARI
patients were treated with 5 mg finasteride daily for treatment to reduce hemorrhage.71 Recommended dura-
4 weeks before TURP, the amount of bleeding per gram of tion of finasteride therapy to optimize benefit must
be balanced against cost and adverse effect profile. reduce blood flow. This relatively small retrospective
Decreased libido and impotence occur in 5–10% of study showed an average blood loss of 108 ml in the
patients, and should resolve following cessation of treat- treatment arm compared with 354 ml in patients who
ment, although impotence is a potential complication of did not receive injections, which equated to an approxi-
the TURP itself. No serious drug-related adverse effects, mate 70% reduction in blood loss. Furthermore, 10 of
particularly thromboembolic events, have been noted in the 11 treated patients did not require bladder irrigation
these studies of short-term finasteride treatment. postoperatively.76 Local epinephrine could potentially be
used as an adjunct treatment before TURP, though more
Antifibrinolytics research is required.
Tranexamic acid is a synthetic derivative of the amino
acid lysine that binds to plasminogen and inhibits Minimizing TURP-related blood loss
activation of plasmin, which breaks up clots.32 Thus, Although the terms ‘classical’ and ‘standard’ are often
tranexamic acid acts to stabilize the clotting process. used to describe the present day cautery-based TURP,
Aminocaproic acid works via a similar mechanism, but is it is important to remember that frequent progressive
less potent and not as freely commercially available. The hemostatic advancements have been made to the proce-
manufacturer’s recommended dose of tranexamic acid dure since its earliest inception in the 1830s. Pioneering
is 1 g taken four times daily, and maximum daily dose is surgeons, including Guthrie, D’Etiolles, Civiale, and
6 g. Dosage should be reduced in patients with renal Mercier, used various transurethral cold knives
impairment. Tranexamic acid can be given intravenously and punches to resect prostate adenomas with varying
0.5–1.0 g three times a day and can also be administered degrees of success.77 Mercier 78 reported on 300 proce-
intravesically during post-TURP washout. dures he performed in 1856 and noted that, although
Patients receiving 2 g oral tranexamic acid three times successful, these procedures caused considerable hemor-
daily for 72 h starting on the morning of TURP experi rhage.78 Hemostatic improvements were made as early as
enced significantly less operative blood loss (128 ml 1873, when Bottini79 used galvanocautery to perform the
versus 250 ml), reduced operating time (36 min versus first thermal resections of the prostate.79
48 min), and required less irrigating fluid (15 l versus 18 l) Electrocautization technology was further advanced in
than those who received placebo. However, tranexamic the early 1900s with the development of high frequency
acid treatment did not influence hospital stay duration unipolar currents that could sharply cut tissue rather
or the number of patients who required blood trans than deeply burn it, resulting in decreased secondary
fusion.72 Similarly, a randomized controlled trial of 100 necrosis and hemorrhage. 80 By 1926 the modern day
patients (52 of whom received 1 g tranexamic acid three resectoscope was in use, which comes equipped with a
times daily from day 1 post-TURP; 48 patients received tungsten-wire cutting loop that functions under water.81
no medical therapy) demonstrated a reduction in inci- However, hemostasis remained a problem until the 1930s
dence of secondary hemorrhage from 56% in the control when devices were introduced that allowed surgeons to
group to 24% in the treatment group, with significant switch back and forth between undamped electrical
reduction in re-admission rate.73 Several studies have currents for cutting and damped electrical currents for
also shown that high-risk patients treated with short- coagulation, which achieved better hemostasis.77
term tranexamic acid perioperatively do not experience Over the next 80 years, the ‘traditional’ TURP con-
more thromboembolic complications.74 tinued to evolve and various hemostatic technologies
Aprotinin is an antifibrinolytic that directly inacti were incorporated, including electrode advancements,
vates plasmin. Increased 30-day mortality has been electrical generator improvements, and alternative
demonstrated in patients who received aprotinin during energy sources.
cardiac surgery, compared to tranexamic acid,75 and the
drug was subsequently withdrawn from the market by Loop and electrode technology
the manufacturers. A variety of resectoscope loops and electrodes are com-
The use of antifibrinolytics needs more thorough mercially available, some of which have better hemostatic
evaluat ion. We believe it is a safe and cost-effective properties than others. Although the electrosurgical
option, and should be considered for patients at risk principles behind these electrodes are similar, the ter-
of bleeding. Tranexamic acid could be administered minology can be confusing when manufacturers employ
at 1 g three times daily for 3 weeks starting the day terms such as electrofulgaration, tissue desiccation,
before surgery. vaporizing-resection, and electrovaporization to differ-
entiate their electrodes. Simply, electrode technology can
Topical medications be divided into: thin-wire loops that resect tissue, solid
Local administration of epinephrine is a well-recognized electrodes that vaporize tissue, and thick hybrid loops
technique for reducing blood loss during ear, nose and that do both (known as vapor-resection loops). Thin
throat surgery. A novel approach to TURP-related loops result in the most intraoperative bleeding, but cause
bleeding was attempted by Schelin et al.,76 who admin- minimal necrosis. Thicker loops require higher energy
istered intraprostatic injections of mepivicaine plus and provide greater coagulation, but cause deeper tissue
epinephrine immediately before microwave TURP, the necrosis and potential secondary bleeding. Vaporizing
objective being to anesthetize the prostate as well as electrodes achieve the deepest coagulation.
Gupta et al.82 performed a randomized comparison Table 3 | Hemorrhagic complications of transurethral BPH surgery7
between a commercial monopolar vapor-resection loop Procedure Transfusion (%) Clot Secondary Secondary
and a standard cutting loop, reporting a significant retention (%) coagulation hemorrhage (%)
decrease in TURP-related blood loss with the former revision (%)
(median blood loss 52.5 ml versus 150 ml; P <0.0001).82 TURP 2.0 4.9 1 0.5
In a randomized trial comparing electrocautery TURP Bipolar TURP 1.9 4.3 0 0.5
and transurethral electrovaporization of the prostate
Bipolar TUVP 0.5 5.3 0 0.5
(TUVP), a statistically significant improvement in
hemostasis was demonstrated in the TUVP arm. The HoLEP 0 0 1.4 0
of antiplatelet therapy can increase the risk of cardiac relevant in an era where such agents are prescribed with
events, and individual risk assessment is required. Low- increasing frequency.
dose aspirin does not pose a significant risk of increased Ongoing study is required to improve evidence-based
bleeding from TURP and can often be continued safely, practice in the field of prostate surgery. A number of
although individual assessment is recommended. areas need clarification and further evaluation, includ-
Guidelines on medications that can reduce prostate ing targeted treatment with 5‑ARIs, especially in patients
bleeding are lacking, although some key points can be on anticoagulant or antiplatelet agents, or patients with
made. Finasteride is a highly effective treatment for idio- a large prostate; cost-benefit analysis of optimal time
pathic prostate bleeding. 5‑ARIs are yet to be proven an of 5‑ARI treatment before TURP; concomitant use of
effective treatment for reduction of prostate bleeding 5‑ARIs and tranexamic acid; and long-term follow-up
related to TURP, although current research suggests they of patients in whom aspirin is ceased perioperatively.
might reduce the incidence of hemorrhage. Tranexamic
acid and use of local epinephrine are other options for Review criteria
reducing perioperative bleeding related to TURP.
Relevant manuscripts were found by searching MEDLINE,
For additional hemostasis, prostate resection can be Embase and Science Direct using, but not exclusively,
performed with a vapor-resection electrode, bipolar the terms “prostate”, “surgery”, “transurethral resection
electrode, or holmium laser. Laser vaporization of the of prostate”, “laser TURP”, “button TURP”, “neoplasm”,
prostate is an emerging field with intermediate data sug- “hemorrhage”, “operative procedure”, “prostatectomy”,
gesting that morbidity, in particular hemorrhage, might “finasteride”, “dutasteride”, “tranexamic acid”, “aspirin”,
be significantly reduced compared to conventional TURP. “antiplatelets” and “anticoagulants”. References in
Patients can also remain on anticoagulants through- obtained articles were checked to cascade for further
relevant articles.
out the procedure in many instances, which is highly
1. Mebust, W. K., Holtgrewe, H. L., Cockett, A. T. & a critical assessment. Clin. Ther. 22, 500–548 22. Ansell, J. et al. Managing oral anticoagulant
Peters, P. C. Transurethral prostatectomy: (2000). therapy. Chest 119, 22S–38S (2001).
immediate and postoperative complications. 12. Petty, G. W. et al. Ischemic stroke subtypes: 23. Dunn, A. Perioperative management of oral
Cooperative study of 13 participating a population-based study of functional outcome, anticoagulation: when and how to bridge.
institutions evaluating 3,885 patients. 1989. survival, and recurrence. Stroke 31, 1062–1068 J. Thromb. Thrombolysis 21, 85–89 (2006).
J. Urol. 167, 999–1003 (2002). (2000). 24. Wilson, R. G., Smith, D., Paton, G., Gollock, J. M.
2. Wendt-Nordahl, G. et al. New bipolar resection 13. Mant, J. et al. Warfarin versus aspirin for stroke & Bremner, D. N. Prophylactic subcutaneous
device for transurethral resection of the prevention in an elderly community population heparin does not increase operative blood loss
prostate: first ex-vivo and in-vivo evaluation. with atrial fibrillation (the Birmingham Atrial in transurethral resection of the prostate. Br. J.
J. Endourol. 19, 1203–1209 (2005). Fibrillation Treatment of the Aged Study, BAFTA): Urol. 62, 246–248 (1988).
3. Wendt-Nordahl, G. et al. Improvement in mortality a randomised controlled trial. Lancet 370, 25. Wittkowski, A. K. in Applied Therapeutics: The
and morbidity in transurethral resection of the 493–503 (2007). Clinical Use Of Drugs 6th edn (eds Young, L. Y. &
prostate over 17 years in a single center. 14. Heit, J. A. Perioperative management of the Koda-Kimble, M. A.) 12.1–12.5 (Applied
J. Endourol. 21, 1081–1087 (2007). chronically anticoagulated patient. J. Thromb. Therapeutics, Inc., Vancouver, 1995).
4. Uchida, T. et al. Factors influencing morbidity in Thrombolysis 12, 81–87 (2001). 26. Dotan, Z. A. et al. The efficacy and safety of
patients undergoing transurethral resection of 15. Salem, D. N., O’Gara, P. T., Madias, C. & perioperative low molecular weight heparin
the prostate. Urology 53, 98–105 (1999). Pauker, S. G. Valvular and structural heart substitution in patients on chronic oral
5. Reich, O. et al. Morbidity, mortality and early disease: American College of Chest Physicians anticoagulant therapy undergoing transurethral
outcome of transurethral resection of the Evidence-Based Clinical Practice Guidelines (8th prostatectomy for bladder outlet obstruction.
prostate: a prospective multicenter evaluation of Edition). Chest 133, 593S–629S (2008). J. Urol. 168, 610–613 (2002).
10,654 patients. J. Urol. 180, 246–249 (2008). 16. Majerus, P. W. & Tollegsen, T. M. in Goodman & 27. Verma, A. K. New agents for orthopaedic
6. Descazeaud, A. et al. Impact of oral Gilman’s The Pharmacological Basis of thromboprophylaxis: caution essential, but time
anticoagulation on morbidity of transurethral Therapeutics 11th edn (eds Brunton, L. L. will tell. ANZ J. Surg. 79, 773–774 (2009).
resection of the prostate World J. Urol. 29, Lazo, J. S. & Parker, K. L.) 1467–1488 (The 28. Connolly, S. J. et al. Dabigatran versus warfarin
211–216 (2010). McGraw-Hill Companies, New York, 2006). in patients with atrial fibrillation. N. Engl. J. Med.
7. Ahyai, S. A. et al. Meta-analysis of functional 17. Parr, N. J., Loh, C. S. & Desmond, A. D. 361, 1139–1151 (2010).
outcomes and complications following Transurethral resection of the prostate and 29. Eriksson, B. I. et al. Rivaroxaban versus
transurethral procedures for lower urinary tract bladder tumour without withdrawal of warfarin enoxaparin for thromboprophylaxis after hip
symptoms resulting from benign prostatic therapy. Br. J. Urol. 64, 623–625 (1989). arthroplasty. N. Engl. J. Med. 358, 2765–2775
enlargement. Eur. Urol. 58, 384–397 (2010). 18. Katholi, R. E., Nolan, S. P. & McGuire, L. B. Living (2008).
8. Go, A. S. et al. Prevalence of diagnosed atrial with prosthetic heart valves. Subsequent 30. Levy, J. H., Key, N. S. & Azran, M. S. Novel oral
fibrillation in adults: national implications for noncardiac operations and the risk of anticoagulants: implications in the perioperative
rhythm management and stroke prevention: thromboembolism or hemorrhage. Am. Heart J. setting. Anesthesiology 113, 726–745 (2010).
the AnTicoagulation and Risk Factors in Atrial 92, 162–167 (1976). 31. Patrono, C., Coller, B., FitzGerald, G. A., Hirsh, J.
Fibrillation (ATRIA) Study. JAMA 285, 2370–2375 19. Mulcahy, J. J., Bradenburg, R. O., Pluth, J. R. & & Roth, G. Platelet-active drugs: the
(2001). Greene, L. F. Transurethral prostatic resection in relationships among dose, effectiveness, and
9. Lebdai, S. et al. Management of patients under patients with prosthetic cardiac valves. J. Urol. side effects: the Seventh ACCP Conference on
anticoagulants for transurethral resection of the 113, 642–643 (1975). Antithrombotic and Thrombolytic Therapy. Chest
prostate: a multicentric study by the CTMH-AFU 20. Wysokinski, W. E. et al. Periprocedural 126, 234S–264S (2004).
[French]. Prog. Urol. 19, 553–557 (2009). anticoagulation management of patients with 32. Rang, H. P., Dale, M. M., Ritter, J. M. &
10. Lewis, H. D. Jr et al. Protective effects of aspirin nonvalvular atrial fibrillation. Mayo Clin. Proc. 83, Flower, R. J. (eds) Rang and Dale’s
against acute myocardial infarction and death in 639–645 (2008). Pharmacology 6th edn (Elsevier, Philadelphia,
men with unstable angina. Results of a Veterans 21. Douketis, J. D. et al. The perioperative 2007).
Administration Cooperative Study. N. Engl. J. management of antithrombotic therapy: 33. [No authors listed] Randomised trial of
Med. 309, 396–403 (1983). American College of Chest Physicians Evidence- intravenous streptokinase, oral aspirin, both, or
11. Hersh, E. V., Moore, P. A. & Ross, G. L. Based Clinical Practice Guidelines (8th Edition). neither among 17,187 cases of suspected
Over‑the‑counter analgesics and antipyretics: Chest 133, 299S–339S (2008). acute myocardial infarction: ISIS‑2. ISIS‑2
(Second International Study of Infarct Survival) 49. Montalescot, G. et al. Prasugrel compared with 67. Sandfeldt, L., Bailey, D. M. & Hahn, R. G. Blood
Collaborative Group. Lancet 2, 349–360 (1988). clopidogrel in patients undergoing percutaneous loss during transurethral resection of the
34. Aguilar, M. & Hart, R. Antiplatelet therapy for coronary intervention for ST‑elevation myocardial prostate after 3 months of treatment with
preventing stroke in patients with non-valvular infarction (TRITON-TIMI 38): double-blind, finasteride. Urology 58, 972–976 (2001).
atrial fibrillation and no previous history of randomised controlled trial. Lancet 373, 68. Hagerty, J. A., Ginsberg, P. C., Harmon, J. D. &
stroke or transient ischemic attacks. Cochrane 723–731 (2009). Harkaway, R. C. Pretreatment with finasteride
Database Syst. Rev. Issue 4. Art. No.: 50. Eberli, D. et al. Urological surgery and decreases perioperative bleeding associated
CD001925. doi:10.1002/14651858. antiplatelet drugs after cardiac and with transurethral resection of the prostate.
CD001925.pub2 (2005). cerebrovascular accidents. J. Urol. 183, Urology 55, 684–689 (2000).
35. Sonksen, J. R., Kong, K. L. & Holder, R. 2128–2136 (2010). 69. Hahn, R. G. et al. Blood loss and postoperative
Magnitude and time course of impaired primary 51. Halkes, P. H. et al. Aspirin plus dipyridamole complications associated with transurethral
haemostasis after stopping chronic low and versus aspirin alone after cerebral ischaemia of resection of the prostate after pretreatment with
medium dose aspirin in healthy volunteers. Br. arterial origin (ESPRIT): randomised controlled dutasteride. BJU Int. 99, 587–594 (2007).
J. Anaesth. 82, 360–365 (1999). trial. Lancet 367, 1665–1673 (2006). 70. Tuncel, A. et al. Effects of short-term dutasteride
36. Enver, M. K., Hoh, I. & Chinegwundoh, F. I. The 52. de Gaetano, G. Low-dose aspirin and vitamin E and Serenoa repens on perioperative bleeding
management of aspirin in transurethral in people at cardiovascular risk: a randomised and microvessel density in patients undergoing
prostatectomy: current practice in the UK. Ann. trial in general practice. Collaborative Group of transurethral resection of the prostate. Scand. J.
R. Coll. Surg. Engl. 88, 280–283 (2006). the Primary Prevention Project. Lancet 357, Urol. Nephrol. 43, 377–382 (2009).
37. Wasson, J. H. et al. A comparison of 89–95 (2001). 71. McVary, K. T. et al. Update on AUA Guideline on
transurethral surgery with watchful waiting for 53. Petry, J. J. Surgically significant nutritional the Management of Benign Prostatic
moderate symptoms of benign prostatic supplements. Plast. Reconstr. Surg. 97, Hyperplasia. J. Urol. 185, 1793–1803 (2011).
hyperplasia. The Veterans Affairs Cooperative 233–240 (1996). 72. Rannikko, A., Petas, A. & Taari, K. Tranexamic
Study Group on Transurethral Resection of the 54. McConnell, J. D. et al. Finasteride, an inhibitor of acid in control of primary hemorrhage during
Prostate. N. Engl. J. Med. 332, 75–79 (1995). 5 alpha-reductase, suppresses prostatic transurethral prostatectomy. Urology 64,
38. Doll, H. A. et al. Mortality, morbidity and dihydrotestosterone in men with benign prostatic 955–958 (2004).
complications following transurethral resection hyperplasia. J. Clin. Endocrinol. Metab. 74, 73. Miller, R. A., May, M. W., Hendry, W. F.,
of the prostate for benign prostatic hypertrophy. 505–508 (1992). Whitfield, H. N. & Wickham, J. E. The prevention
J. Urol. 147, 1566–1573 (1992). 55. Guess, H. A., Gormley, G. J., Stoner, E. & of secondary haemorrhage after prostatectomy:
39. Gyomber, D., Lawrentschuk, N., Ranson, D. L. & Oesterling, J. E. The effect of finasteride on the value of antifibrinolytic therapy. Br. J. Urol. 52,
Bolton, D. M. An analysis of deaths related to prostate specific antigen: review of available 26–28 (1980).
urological surgery, reviewed by the State data. J. Urol. 155, 3–9 (1996). 74. Ruel, M. A. et al. Is tranexamic acid safe in
Coroner: a case for cardiac vigilance before 56. Donohue, J. F., Hayne, D., Karnik, U., patients undergoing coronary endarterectomy?
transurethral prostatectomy. BJU Int. 97, Thomas, D. R. & Foster, M. C. Randomized, Ann. Thorac. Surg. 71, 1508–1511 (2001).
758–761 (2006). placebo-controlled trial showing that finasteride 75. Fergusson, D. A. et al. A comparison of aprotinin
40. Ala-Opas, M. Y. & Grönlund, S. S. Blood loss in reduces prostatic vascularity rapidly within and lysine analogues in high-risk cardiac surgery.
long-term aspirin users undergoing 2 weeks. BJU Int. 96, 1319–1322 (2005). N. Engl. J. Med. 358, 2319–2331 (2008).
transurethral prostatectomy. Scand. J. Urol. 57. Hochberg, D. A. et al. Decreased suburethral 76. Schelin, S. Transurethral resection of the
Nephrol. 30, 203–206 (1996). prostatic microvessel density in finasteride prostate after intraprostatic injections of
41. Nielsen, J. D. et al. The effect of low-dose treated prostates: a possible mechanism for mepivacain epinephrine: a preliminary
acetylsalicylic acid on bleeding after reduced bleeding in benign prostatic communication. Scand. J. Urol. Nephrol. 43,
transurethral prostatectomy—a prospective, hyperplasia. J. Urol. 167, 1731–1733 (2002). 63–67 (2009).
randomized, double-blind, placebo-controlled 58. Foley, S. J. & Bailey, D. M. Microvessel density in 77. Herr, H. W. The enlarged prostate: a brief history
study. Scand. J. Urol. Nephrol. 34, 194–198 prostatic hyperplasia. BJU Int. 85, 70–73 of its surgical treatment. BJU Int. 98, 947–952
(2000). (2000). (2006).
42. Ehrlich, Y. et al. Early initiation of aspirin after 59. Kashif, K. M. Haematuria associated with BPH- 78. Mercier, L. Recherches sur le traitement des
prostate and transurethral bladder surgeries is Natural history and a new treatment option. maladies des organs urinaires. (Kessinger
not associated with increased incidence of Prostate Cancer Prostatic Dis. 1, 154–156 publishing, Paris, 1856).
postoperative bleeding: a prospective, (1998). 79. Bottini, E. La galvanocaustica nella practica
randomized trial. J. Urol. 178, 524–528 (2007). 60. Puchner, P. J. & Miller, M. I. The effects of chirurgica. (Novara, 1873).
43. Donat, R., McNeill, A. & Brame, K. Anti-platelet finasteride on hematuria associated with benign 80. Beer, E. Landmark article May 28, 1910.
and non-steroidal anti-inflammatory drugs in prostatic hyperplasia: a preliminary report. Removal of neoplasms of the urinary bladder. By
transurethral surgery of the prostate and J. Urol. 154, 1779–1782 (1995). Edwin Beer. JAMA 250, 1324–1325 (1983).
bleeding complications [abstract]. BJU Int. 77 61. Sieber, P. R. et al. The treatment of gross 81. Stern, M. Resection of obstruction at the vesicle
(Suppl. 1), 31 (1996). hematuria secondary to prostatic bleeding with orifice; new instruments resectotherm;
44. Burger, W., Chemnitius, J. M., Kneissl, G. D. & finasteride. J. Urol. 159, 1232–1233 (1998). resectoscope and new method. JAMA 87,
Rücker, G. Low-dose aspirin for secondary 62. Kearney, M. C., Bingham, J. B., Bergland, R., 1726–1730 (1926).
cardiovascular prevention—cardiovascular Meade‑D’Alisera, P. & Puchner, P. J. Clinical 82. Gupta, N., Sivaramakrishna, Kumar, R.,
risks after its perioperative withdrawal versus predictors in the use of finasteride for control of Dogra, P. N. & Seth, A. Comparison of standard
bleeding risks with its continuation—review and gross hematuria due to benign prostatic transurethral resection, transurethral vapour
meta-analysis. J. Intern. Med. 257, 399–414 hyperplasia. J. Urol. 167, 2489–2491 (2002). resection and holmium laser enucleation of the
(2005). 63. Foley, S. J. et al. A prospective study of the prostate for managing benign prostatic
45. Hall, R. & Mazer, C. D. Antiplatelet drugs: natural history of hematuria associated with hyperplasia of >40 g. BJU Int. 97, 85–89 (2006).
a review of their pharmacology and benign prostatic hyperplasia and the effect of 83. Fowler, C., McAllister, W., Plail, R., Karim, O. &
management in the perioperative period. finasteride. J. Urol. 163, 496–498 (2000). Yang, Q. Randomised evaluation of alternative
Anesth. Analg. 112, 292–318 (2011). 64. Donohue, J. F. & Barber, N. J. How do we electrosurgical modalities to treat bladder
46. Weber, A. A. et al. Recovery of platelet function investigate haematuria and what role has outflow obstruction in men with benign prostatic
after discontinuation of clopidogrel treatment in finasteride? BJU Int. 93, 3–4 (2004). hyperplasia. Health Technol. Assess. 9, iii–iv,
healthy volunteers. Br. J. Clin. Pharmacol. 52, 65. Ozdal, O. L. et al. Effect of short-term finasteride 1–30 (2005).
333–336 (2001). therapy on peroperative bleeding in patients who 84. Lourenco, T. et al. Minimally invasive treatments
47. Wiviott, S. D. et al. Prasugrel versus clopidogrel were candidates for transurethral resection of for benign prostatic enlargement: systematic
in patients with acute coronary syndromes. the prostate (TUR‑P): a randomized controlled review of randomised controlled trials. BMJ 337,
N. Engl. J. Med. 357, 2001–2015 (2007). study. Prostate Cancer Prostatic Dis. 8, 215–218 966–973 (2008).
48. Schouten, O. et al. Noncardiac surgery after (2005). 85. Bhansali, M., Patankar, S., Dobhada, S. &
coronary stenting: early surgery and 66. Donohue, J. F. et al. Transurethral prostate Khaladkar, S. Management of large (>60 g)
interruption of antiplatelet therapy are resection and bleeding: a randomized, placebo prostate gland: PlasmaKinetic Superpulse
associated with an increase in major adverse controlled trial of role of finasteride for (bipolar) versus conventional (monopolar)
cardiac events. J. Am. Coll. Cardiol. 49, decreasing operative blood loss. J. Urol. 168, transurethral resection of the prostate.
122–124 (2007). 2024–2026 (2002). J. Endourol. 23, 141–145 (2009).
86. Tan, A. H. & Gilling, P. J. Holmium laser prostate 60 cc or less: short-term results of a 98. Wendt-Nordahl, G. et al. Systematic evaluation of
prostatectomy: current techniques. Urology 60, prospective randomized trial. J. Urol. 182, a recently introduced 2‑microm continuous-wave
152–156 (2002). 133–138 (2009). thulium laser for vaporesection of the prostate.
87. Vavassori, I., Hurle, R., Vismara, A., Manzetti, A. 93. Okamura, K. et al. Perioperative management of J. Endourol. 22, 1041–1045 (2008).
& Valenti, S. Holmium laser enucleation of the transurethral surgery for benign prostatic 99. Xia S. J. et al. Thulium laser versus standard
prostate combined with mechanical hyperplasia: A nationwide survey in Japan. Int. J. transurethral resection of the prostate:
morcellation: two years of experience with 196 Urol. 18, 304–310 (2011). a randomized prospective trial. Eur. Urol. 53,
patients. J. Endourol. 18, 109–112 (2004). 94. Ruszat, R. et al. Safety and effectiveness of 382–389 (2008).
88. Hoffman, R. M., MacDonald, R., Slaton, J. W. & photoselective vaporization of the prostate 100. Bach, T. et al. Thulium: YAG 2 mum cw laser
Wilt, T. J. Laser prostatectomy versus (PVP) in patients on ongoing oral prostatectomy: where do we stand? World J. Urol.
transurethral resection for treating benign anticoagulation. Eur. Urol. 51, 1031–1038 28, 163–168 (2010).
prostatic obstruction: a systematic review. (2007).
J. Urol. 169, 210–215 (2003). 95. Ruszat, R. et al. Comparison of
89. Pedraza, R., Samadi, A. & Eshghi, M. Holmium potassium‑titanyl‑phosphate laser vaporization Acknowledgments
laser enucleation of the prostate in critically ill of the prostate and transurethral resection of C. P. Vega, University of California, Irvine, CA, is the
patients with technique modification. J. Endourol. the prostate: update of a prospective non- author of and is solely responsible for the content of
18, 795–798 (2004). randomized two-centre study. BJU Int. 102, the learning objectives, questions and answers of the
90. Lee, J. & Gianduzzo, T. R. Advances in laser 1432–1438 (2008). Medscape, LLC-accredited continuing medical
technology in urology. Urol. Clin. North Am. 36, 96. Bouchier-Hayes, D. M., Anderson, P., education activity associated with this article.
189–198 (2009). Van Appledorn, S., Bugeja, P. & Costello, A. J.
91. Gilling, P. J., Aho, T. F., Frampton, C. M., KTP laser versus transurethral resection:
King, C. J. & Fraundorfer, M. R. Holmium laser early results of a randomized trial. J. Endourol. Author contributions
enucleation of the prostate: results at 6 years. 20, 580–585 (2006). L. E. Kavanagh and N. Lawrentschuk researched data
Eur. Urol. 53, 744–749 (2008). 97. Ruszat, R. et al. GreenLight laser vaporization of for the article. L. E. Kavanagh wrote the article.
92. Elzayat, E. A., Al-Mandil, M. S., Khalaf, I. & the prostate: single-center experience and long- L. E. Kavanagh, G. S. Jack and N. Lawrentschuk made
Elhilali, M. M. Holmium laser ablation of the term results after 500 procedures. Eur. Urol. 54, substantial contribution to discussion of content, and
prostate versus photoselective vaporization of 893–901 (2008). editing the manuscript before submission.