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Prevention and management of TURP-related

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REVIEWS
Prevention and management of TURP-related
hemorrhage
Liam E. Kavanagh, Gregory S. Jack and Nathan Lawrentschuk
Abstract | Transurethral resection of the prostate (TURP) is the most common surgical treatment for benign
prostatic hyperplasia (BPH) worldwide, but despite its minimally invasive nature, perioperative bleeding
remains a common morbidity. Anticoagulant and antiplatelet medications are increasingly common in this
patient population and further contribute to the risk of bleeding and extended hospital stay. Preoperative
cessation of anticoagulant and antiplatelet drugs is recommended but requires risk assessment of thrombotic
complications. Pharmacologic maneuvers to reduce hemorrhage include perioperative administration of
5α-reductase inhibitors. Technical considerations include the use of hemostatic energy sources such as laser
and bipolar technologies. Ultimately, no surgical technique is devoid of bleeding risks, and urologists should be
aware of how best to prevent and treat TURP-related hemorrhage.
Kavanagh, L. E. et al. Nat. Rev. Urol. 8, 504–514 (2011); published online 16 August 2011; doi:10.1038/nrurol.2011.106

common complication of the procedure.1,2 Historically,

Continuing Medical Education online
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Released: 16 August 2011; Expires: 16 August 2012
Learning objectives
Upon completion of this activity, participants should be able to:
1 Analyze the use of warfarin in the perioperative period
around TURP.
2 Analyze the use of aspirin in the perioperative period around
TURP.
3 Evaluate preoperative treatment to reduce the risk for TURP-
related hemorrhage.
4 Assess operative factors that might contribute to TURP-
University of related hemorrhage.
Melbourne, Department
of Surgery, Ludwig
Institute for Cancer
Research, Austin Introduction
Hospital, Studley Road, Transurethral resection of the prostate (TURP) is the
Heidelberg, Melbourne,
Vic 3084, Australia
most common surgical option for benign prostatic
(L. E. Kavanagh, hyperplasia (BPH) worldwide. Despite the minimally
G. S. Jack, invasive nature of TURP, bleeding remains the most
N. Lawrentschuk).
Correspondence to:
N. Lawrentschuk Competing interests
lawrentschuk@ The authors, the journal Chief Editor S. Farley and the CME
gmail.com questions author C. P. Vega declare no competing interests.
transfusion rates during TURP were reported to be as
high as 20%.3,4 Improvements in resectoscopes, optics,
anesthesia, and energy sources have caused the trans-
fusion rate to fall, but hemorrhage remains a common
complication. A recent multi-institutional study reported
transfusion rates of up to 2.9% after TURP.5 Other studies
have shown the transfusion rate to be below 2% at major
surgical centers.6,7
Extensive hemorrhage requiring blood transfusion is
rare in the modern TURP era, but moderate perioperative
bleeding is common and can adversely affect outcomes.
Intraoperative bleeding obscures surgical vision, which
can lead to prolonged operative time, capsular perfora­
tion, fluid absorption, and excessive use of irriga­tion
fluids, all of which are ultimately risk factors for TURP
syndrome and sepsis. In the postoperative setting, exces-
sive fossa bleeding results in prolonged hospitalization
for patients and consumes significant hospital resources.
Bladder irrigation is required until bleeding subsides,
which is labor-intensive, costly, requires inpatient hos-
pitalization, and is restrictive for patients. If irrigation is
performed to a low standard or if bleeding is excessive,
blood clots in the bladder can obstruct the catheter and
result in major patient distress owing to clot retention.
Patients with large prostates, concurrent urinary tract
infections, or indwelling urinary catheters have tradition-
ally been at the greatest risk of TURP-related bleeding.1,4,5
However, a contemporary increase in the prescription
of anticoagulant and, particularly, antiplatelet drugs has
created a new high-risk population of patients. Therefore,
it is crucial for treating surgeons to familiarize themselves
with the plethora of blood thinners on the market, in
order to avoid error. Urologists must also be familiar with
the alternative surgical procedures that can be performed
in patients who must remain on active blood thinners.

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In this Review we will describe the common medica­
tions that increase the risk of TURP-related hemorrhage,
as well as the pharmacologic agents that have been shown
to reduce prostatic bleeding in patients undergoing
surgery for BPH. We also discuss surgical techniques that
can be used to minimize prostate blood loss.
Drugs that increase hemorrhage risk
Approximately 4% of patients requiring prostate resec-
tion are on chronic oral anticoagulant medication, such as
warfarin.8 A far greater proportion of patients—up to 37%
in one recent series9—take antiplatelet medicines. Both
classes of medication can cause significant hemorrhage
after TURP.
The coagulation cascade includes two pathways that
lead to fibrin formation—the contact activation pathway
(also known as the intrinsic pathway), and the tissue
factor pathway (also known as the extrinsic pathway).
Anticoagulants, such as warfarin and heparin inhibit
the coagulation cascade at different levels (Figure 1).
Anticoagulants are used for the acute treatment of throm-
boembolic events, such as deep vein thrombosis (DVT)
and pulmonary embolism, or for the chronic prevention
of intracardiac thrombi and stroke related to artificial
heart valves and atrial fibrillation. Historically, anticoag-
ulants did not present a major problem for TURP surgery
because patients taking them prophylactically could have
them withheld during surgery. The action of heparin and
warfarin is reversible.
Antiplatelet medications function via a separate
mechanism to anticoagulants, interfering instead with
platelet aggregation and thrombosis (Figure 2). Platelet
aggregation is a complicated initial response to vessel
trauma and results in clot formation at the traumatic
site. Certain chemicals promote platelet aggregation,
including thromboxane (TXA2) and adenosine diphos-
phate (ADP). Acetylsalicylic acid, or aspirin, is an inhibi-
tor of TXA2 production. After scientific studies first
demonstrated the cardiovascular protective benefits of
aspirin,10 the antiplatelet pharmaceutical class exploded.
Consequently, in the last decade there has been a massive
increase in the availability, diversity, and prescription of
antiplatelet medications.11 The most important indica-
tion for antiplatelet therapy in modern series is metallic
or drug-eluting cardiovascular stenting. Unlike warfarin,
the effect of antiplatelet agents cannot be reversed.
Before stopping anticoagulant or antiplatelet medi-
cines, it is critical that the surgeon and patient consider
the risks and alternatives of such actions. Consultation
with the prescribing doctor and specialist in the field
is recommended for appropriate risk stratification.
In many instances, such as the cessation of warfarin in
a patient with atrial fibrillation, the risks are low.
In other instances, such as cessation of antiplatelet
agents in the setting of cardiac stenting, there is a risk
of a major cardio­vascular event and cessation should
be avoided when possible. Agents that increase hemor-
rhage risk in patients under­going TURP are summa-
rized in Table 1 with recommenda­tions given regarding
their management.
NATURE REVIEWS | UROLOGY VOLUME 8  |  SEPTEMBER 2011  |  505
© 2011 Macmillan Publishers Limited. All rights reserved
REVIEWS
Key points
■■ Traditional factors influencing blood loss during transurethral resection of the
prostate (TURP) include prostate size, weight of resected prostate tissue, type
of instrumentation, surgeon experience, and catheterization
■■ Patient use of anticoagulant or antiplatelet medications can increase the risk of
significant TURP-related hemorrhage
■■ Cessation of such drugs prior to TURP is recommended only after thorough risk
stratification and consultation with the prescribing clinician
■■ Treating surgeons must familiarize themselves with the plethora of novel
pharmaceutical blood thinners on the market today to avoid error
■■ 5α-reductase inhibitors have been shown to decrease prostate microvessel
density and reduce intraoperative blood loss in select studies
■■ Laser and bipolar technologies offer vaporization, enucleation, and resection
alternatives to traditional TURP that involve significantly less blood loss; these
procedures can often be performed in the setting of active anticoagulation or
antiplatelet therapy
FXIIa
FXIa FVIIa Tissue factor
Warfarin FIXa
FVIIIa
Rivaroxaban
FXa Low-molecular-weight heparins
FVa
Unfractionated heparin
Thrombin Dabigatran
Fibrin
Figure 1 | Mechanism of action of anticoagulation therapies. Anticoagulants inhibit
the coagulation cascade at different levels. Warfarin inhibits the vitamin K‑
dependent activation of clotting factors II (thrombin), VII, IX and X. Heparin chiefly
catalyzes inactivation of factors II and X. Low-molecular-weight heparins exert an
inhibitory effect against factor X only. Dabigatran, a thrombin inhibitor, and
rivaroxaban, which inhibits factor Xa, have both been studied in large, double-blind
randomized phase III trials. With permission from Nature Publishing Group.
Anticoagulant medications
Anticoagulants reduce thrombus formation (Figure 1)
and are proven to lower the incidence of stroke in
patients with atrial fibrillation, history of previous stroke,
and thromboembolic complications associated with arti-
ficial heart valves.12,13 Patients at risk of thrombo­embolic
events can be categorized according to their indication
for anticoagulation therapy. High-risk patients include
those with a history of intracardiac thrombus, transient
ischemic attack, stroke, recent or recurrent DVT, pul-
monary embolism or prosthetic valves (especially mitral,
mechanical and caged-ball valves). Lower risk patients
on warfarin, including those with a history of rheu-
matic heart disease, atrial fibrillation or DVT, should
receive appropriate pharmacological and mechanical
prophylaxis.13–15
Warfarin
Warfarin inhibits the vitamin K‑dependent activation of
clotting factors II (thrombin), VII, IX and X (Figure 1).
The half-life of warfarin ranges from 25 h to 60 h, and the
REVIEWS

Activation Aggregation LMWH treatment from 4 days before surgery to 1 day

Coagulation before the operation.14,15,20–22 INR should be checked on
cascade the morning of surgery to ensure it is <1.5, so reversal
can be organized if required.23
Endothelium Thrombin
Thienopyridines
Heparin
PGI2 Heparin, also known as unfractionated heparin, achieves
its effects by binding to antithrombin, and catalyzing
PAR
(thrombin inactivation of factors II, IX, X, XI and XII. Factors II and
receptor) ADP
receptor X are the most responsive to this inhibition (Figure 1).
ADP The half-life of heparin is 1–6 h. Intravenous therapeutic
cAMP Dense
granule
heparin has an immediate onset of action and is used
Platelets
PI as treatment for acute thromboembolic events, such as
5'AMP pulmonary embolism or acute myocardial infarction.16
Such patients are generally not considered for nonurgent
IIb–IIIa IIb–IIIa procedures such as TURP until more-urgent medical
fibrinogen fibrinogen
Arachidonic receptors receptors issues are resolved.
acid GP IIb–IIIa
inhibitors Low-dose subcutaneous heparin is used for prevention
TXA2 of DVT or pulmonary embolism, and inactivates factor X
receptor Aspirin and COX-1
NSAIDs COX-2 without a direct effect on factor II. Preoperative low-dose
Fibrinogen prophylactic heparin, continued postoperatively, makes
cross-linking no difference to intraoperative blood loss.24
TXA2

Figure 2 | Mechanism of action of antiplatelet therapies. Antiplatelet medications Low-molecular-weight heparins

inhibit platelet activation and aggregation. Aspirin acts by irreversibly acetylating
COX‑1, whereas other NSAIDs reversibly acetylate both COX‑1 and COX‑2, which
prevents synthesis of TXA2, a key player in the platelet aggregation process.
Thienopyridines impair platelet aggregation by blocking the interaction of ADP with
its receptor. Phosphodiesterase inhibitors (PI) are thought to act by blocking the
decomposition of cAMP, which inhibits calcium release during platelet activation.
Glycoprotein IIb–IIIa antagonists block the IIb–IIIa fibrinogen receptors, which are
involved in the final step of the platelet aggregation pathway. Abbreviations: ADP,
adenosine diphosphate; cAMP, cyclic adenosine monophosphate; COX,
cyclooxygenase; GP, glycoprotein; NSAID, nonsteroidal anti-inflammatory drug; PGI 2,
prostacyclin; PI, phosphodiesterase inhibitors; TXA2, thromboxane A2.
duration of action of therapeutic levels is 2–5 days, owing
to the long half-lives of some of the coagulation factors,
especially factor II.16
Evidence suggests that low-risk patients can stop war-
farin before TURP and recommence after surgery. Parr
et al.17 performed TURP on 12 patients who remained
on therapeutic warfarin (mean inter­national normalized
ratio [INR] 2.3), four of whom (33%) required blood
transfusion. Katholi et al.18 report two cases of fatal peri-
operative thromboembolism among 10 patients with
mitral valve prostheses who had their warfarin ceased
5 days before noncardiac surgery with no bridging
therapy. Mulcahy et al.19 recommended that warfarin
should be recommenced once hematuria resolves post-
operatively, no sooner than 48 h after surgery.19 Most
urologists believe this period should be much longer.
Wysokinski et al.20 demonstrated that the 3‑month cumu-
lative incidence of thromboembolism was low in patients
with atrial fibrillation whose warfarin was temporarily
ceased for surgery. Higher risk patients received bridg-
ing low-molecular-weight heparin (LMWH) therapy and
there was no increase in bleeding rate.20
Many perioperative anticoagulation guidelines recom-
mend that patients at high risk of thromboembolic events
should stop taking warfarin 5 days before surgery, with
This group of medicines includes agents comprised
of fragments of heparin that exert an inhibitory effect
against factor X only (Figure 1). The half-lives vary but
range between 8 h and 10 h.25 Importantly, dosing should
be halved in patients with a creatinine clearance of less
than 30 ml/min because LMWHs are excreted renally.16
Dotan et al. 26 demonstrated in a small trial that
patients with significant thromboembolic risk who
ceased LMWH treatment the evening before TURP and
recommenced the day after surgery did not experi­ence
increased hemorrhage or thromboembolic risk, com-
pared to patients who did not require anticoagulation.
However, patients treated with LMWH experienced
longer catheterization, requiring a catheter for 3.2 days
after surgery compared to 2.1 days in the control group,
and an increased hospital stay of 4.2 days compared
to 2.1 days.26 High-risk patients should be given low-
dose prophylactic heparin or LMWH the day after
surgery for the first 48 h, then treatment-dose LMWH
be reinstituted.21–23
Other inhibitors
Newer more-costly agents that directly inhibit factors
within the clotting pathway are available in oral forms
for venous thromboembolism prophylaxis (Figure 1).27
Dabigatran, a thrombin inhibitor, and rivaroxaban,
which inhibits factor Xa, have both been studied in
large, double-blind randomized phase III trials for the
prevention of venous thromboembolism and demon-
strated equivalent efficacy to warfarin with lower rates
of major hemorrhage.28,29 There are no data relating to
their use perioperatively in urologic surgery, but for
venous thromboembolism prophylaxis in orthope-
dic surgery, rivaroxaban is commenced 6–8 h after the
operation.29 Furthermore, it has been recommended by
Levy et al.30 that rivaroxaban is ceased 24 h before any

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Table 1 | Agents that increase bleeding during TURP
Drug Effects
Anticoagulant therapy
Warfarin Increased transfusion rate if continued
perioperatively
Heparin Low-dose prophylactic heparin shows no
increased bleeding rate
LMWH No increased bleeding. Delay in catheterization
period and increased hospital stay when
recommenced the day after surgery
Antiplatelet therapy
Aspirin No effect on intraoperative bleeding, but can
increase postoperative bleeding. No effect on
transfusion rates. No increased risk of
bleeding with early re-introduction after surgery
Thienopyridines No literature exists on their use specifically
during urologic surgery
Abbreviation: LMWH, low-molecular-weight heparin.
invasive procedure.30 Importantly, unlike warfarin and
heparin, there is no antidote for these agents in the case
of overdose or need for reversal.
Antiplatelet medications
A number of drugs are available that reduce platelet
adhesion or aggregation (Figure 2). They are used pre-
dominantly for the prevention of athero­t hrombosis
in cardio­v ascular disease. If a patient who contin-
ues antiplatelet therapy through surgery has severe
hemorrhage peri­operatively, platelet transfusion is
the most likely success­ful treatment option, although
considera­tion must be given to time of the last dose of
antiplatelet medication.
Aspirin and NSAIDs
Aspirin and other non-steroidal anti-inflammatory drugs
(NSAIDs) inhibit the production of TXA2 (Figure 2).
Aspirin is used extensively as a cardiovascular protec-
tive medication owing to its antiplatelet effect; it acts by
irreversibly acetylating cyclooxygenase‑1 (COX‑1). Low-
dose aspirin (50–100 mg) is considered to act prefer­
entially on COX‑1, while higher doses are thought to
have a less selective effect on platelet aggregation and
more gastro­intestinal toxicity.31,32 Low-dose aspirin is
widely proven to reduce the incidence and risk of death
associated with myocardial infarction, unstable angina,
transient ischemic attack and stroke.31,33,34 After coronary
stent placement, aspirin is commonly taken to prevent
stent thrombosis, especially if a drug-eluting stent
is inserted.
Bleeding time, after cessation of aspirin, will return
to normal within 48 h,35 which is the time taken for new
platelets to reach sufficient numbers to compensate for
the effects of aspirin. 36 Common historical practice
NATURE REVIEWS | UROLOGY VOLUME 8  |  SEPTEMBER 2011  |  507
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REVIEWS
Recommendations References
Cease warfarin 5 days before surgery in all patients. In high-risk 12–14, 16,
patients, bridge with LMWH treatment before and after surgery (level A 17, 19–23
evidence). Warfarin should be restarted within 48 h if adequate
hemostasis (level B), with LMWH cover depending on the risk status
Give perioperatively to all patients undergoing TURP, especially those in 13–15,
whom warfarin is being withheld (level A). Consider heparin infusion after 19–24
surgery for high-risk patients with concerns about hemostasis and renal
function (level A)
Cease treatment-dose LMWH 24 h before surgery. Recommence 20, 21, 23,
treatment-dose LMWH >24 h after surgery in high-risk patients if 26, 29
bleeding is controlled (level A). Otherwise commence low-dose LMWH
until hemostasis is adequate
High-risk patients should remain on aspirin (level B). Lower-risk patients 31, 33, 34,
should stop taking aspirin 7 days before surgery and restart within 48 h 36–45
given adequate hemostasis (level B)
Continue if patient has recent stent and consider delaying surgery 21, 45–48
(level B). Otherwise cease 1 week before surgery and recommence
within 48 h given adequate hemostasis (level B)
was for aspirin to be discontinued 7–10 days before
surgery,36 although this was not based on any firm evi-
dence and might be inappropriate in high-risk patients.
Given that over 20% of patients undergoing prostate
surgery have a past history of ischemic heart disease or
cerebral vascular accident,1,37,38 and that ischemic heart
disease is the leading cause of death in the perioperative
period for patients undergoing TURP,39 it is impera-
tive that aspirin is only withheld after appropriate
risk stratification.
Data demonstrate that aspirin use is associated with
a slightly increased risk of postoperative bleeding.
Ala-Opas et al.40 found no difference in TURP-related
blood loss between patients on aspirin and nonaspirin
users.40 Nielsen et al.41 performed a randomized con-
trolled trial comparing hemorrhage rates of patients
who continued aspirin during TURP with those who
stopped taking aspirin 10 days before surgery. They
showed no significant difference in intraoperative
blood loss rates, but the aspirin group experienced
significantly greater post­operative blood loss (284 ml
versus 144 ml), although there was no difference in
transfusion requirements or recatheterization rates. 41
Ehrlich et al. 42 compared early recommencement of
aspirin after TURP (once irrigation had been discon-
tinued) with restarting 21 days after surgery and found
that early aspirin recommencement was not associated
with increased postoperative bleeding.42 Donat et al.43
retrospectively analyzed a series of patients who under-
went TURP, over 20% of whom remained on aspirin or
NSAIDs. These patients did not have increased trans­
fusion requirements. 43 In the large meta-analysis of
non­cardiac surgeries carried out by Burger et al.,44 it
was found that periprocedural aspirin increased the
rate of bleeding complications by 1.5%, although it
REVIEWS
did not lead to a higher level of severity of bleeding
complica­tions. Further, it was found that aspirin with-
drawal precedes up to 10.2% of cases of acute cardio-
vascular syndrome and that these events usually occur
within 30 days of aspirin cessation.44
The American College of Chest Physicians suggests
that aspirin should be continued perioperatively in
high-risk patients undergoing noncardiac surgery, but
discontinued in lower-risk patients, such as those taking
aspirin for primary prevention of acute myocardial
infarction or cerebral vascular accident.21 Furthermore,
it has been suggested that patients who discontinue
aspirin perioperatively should start taking it again 24 h
after surgery.45
Other NSAIDs, such as ibuprofen, indomethacin
and naproxen, reversibly acetylate both COX‑1 and
COX‑2, which prevents synthesis of TXA2 within plate-
lets, thereby reducing their aggregation (Figure 2).
Different agents cause transient and incomplete plate-
let dysfunction to varying degrees.31 As a simple rule,
the more COX‑1-specific an NSAID is, the more plate-
let dysfunction and bleeding it causes, whereas COX‑2
specificity implies greater anti-inflammatory properties.
Because the majority of NSAIDs are used for analgesia
or inflamma­tory conditions rather than cardiovascular
protection, they can be withheld a week before surgery
without raising cardiovascular risk. Alternatively,
NSAIDs can be continued through surgery at the
surgeon’s discretion with proper risk assessment.
Thienopyridines
These drugs act to impair platelet aggregation by block-
ing the interaction of ADP with its receptor (Figure 2).
Clopidogrel and prasugrel are commonly used in
patients with cardiac stents, and in those with a history
of ischemic heart disease or cerebral vascular accident as
secondary prevention.
Clopidogrel is the original thienopyridine used widely
in patients with ischemic heart disease. Platelet function
returns to normal 7 days after treatment is stopped.31,46
There are associated problems with substantial patient
intervariability in terms of response to clopidogrel.47
No studies have been performed that specifically assess
clopidogrel use during prostate surgery. The American
College of Chest Physicians suggests that clopidogrel
should be stopped 7 days before prostate surgery,
unless the patient has had a bare metal stent inserted
within 6–12 weeks or a drug-eluting stent inserted within
12 months, then both aspirin and clopidogrel must be
continued,21 and prostate surgery should be postponed.
In one study of 192 patients, the incidence of early drug-
eluting stent thrombosis after noncardiac surgery (13%
urologic) was 31% in patients who had stopped taking
clopidogrel, compared to 0% in those who continued
dual antiplatelet therapy.48
Prasugrel is a newer thienopyridine, recently approved
for patients with acute coronary syndrome undergoing
percutaneous interventions. Prasugrel is associated with
more effective and consistent action than clopidogrel, but
a slightly increased risk of major bleeding.47,49,50
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Other antiplatelet medicines
Dipyridamole is a phosphodiesterase inhibitor normally
used in stroke prevention that impairs platelet aggrega-
tion. Although its mechanism of action is unclear, it is
thought to act by blocking the degradation of cAMP
(Figure  2). The increased levels of cAMP inhibit
calcium release, which occurs during platelet activation.
Dipyridamole has a weak and short-lasting antiplatelet
effect, and is shown to cause no excess risk of bleeding.32
In patients at low risk of a thromboembolic event, it can
be ceased 2 days before TURP. Importantly, extended-
release dipyridamole is often produced in combination
with aspirin, which results in a relative reduction in risk
of cardiovascular events of 20%, compared to aspirin
alone, without increasing risk of hemorrhage.51
Glycoprotein IIb–IIIa antagonists, such as abciximab
and tirofiban, are medications used in the acute setting
of unstable angina and perioperatively for the preven-
tion of acute thrombosis during coronary stent inser-
tion. They antagonize the IIb–IIIa fibrinogen receptors
involved in the final step of the platelet aggregation
pathway (Figure 2).32 A much higher risk of bleeding
would be anticipated if a patient remained on such agents
during surgery, so TURP is contraindicated, although
no studies have been performed to specifically address
this issue. Glycoprotein IIb–IIIa antagonists are typically
stopped 7–10 days before surgery.
Vitamin E is used by an increasing number of the
general population although studies have shown an
equivocal protective effect against cardiovascular
disease.52 Vitamin E can significantly reduce platelet
adhesion, and it is recommended that patients stop
taking this nonessential medication before TURP.53
Treatment of TURP-related bleeding
Many pharmacologic interventions have been tested in
clinical trials for the reduction of TURP-related bleeding,
including medications that reduce prostate vascularity
and others that stabilize the clotting process. Agents that
reduce idiopathic prostate bleeding or hemorrhage risk in
patients undergoing prostate surgery are summarized
in Table 2.
Antiandrogens
Various agents that reduce androgen activity also reduce
intraprostatic vascularity. The most commonly used
drugs are the 5α-reductase inhibitors (5-ARIs), which
block the 5α-reductase enzyme that converts testoster-
one to dihydro­testosterone, the active hormone involved
in growth of the prostate. 5‑ARIs reduce prostatic
blood flow via downregulation of vascular endothelial
growth factor (VEGF), before gland shrinkage occurs.
Dutasteride blocks type I and II 5α-reductase enzymes,
whereas finasteride blocks type II only. Both drugs have
been shown to reduce the amount of dihydro­testosterone
in the bloodstream by about 80% within 1–2 weeks, and
reduce the size of the prostate by about 30% within
6–12 months.54 Subsequently, PSA levels halve owing to
reduction in size of the transition zone where most PSA
is produced.55
 REVIEWS

Table 2 | Medications to reduce prostate bleeding

Drug Regimen Effects Recommendation References
Finasteride 5 mg daily for treatment 77–100% reduction in hematuria grade Effective treatment for idiopathic prostatic 60–65
of hematuria for all patients including those on hemorrhage
anticoagulants
Finasteride 5 mg daily, initiated before In TURP <20–30 g, there is reduction Suggest pretreatment with finasteride for 66–69
TURP in blood loss only. 2–4 weeks before TURP in selected patients with
In TURP >20–30 g, there is reduction large prostate, anemia or ischemic heart disease,
in blood loss and transfusion rates hematuria or those receiving antiplatelet or
anticoagulant therapy (level C)
Dutasteride 0.5 mg daily or 5 mg daily; No reduction in perioperative blood loss Needs further evaluation 70, 71
2–4 weeks before TURP or transfusion rate
Tranexamic 2 g three times daily on day Reduction in perioperative bleeding and Could be administered at 1 g three times daily for 73, 74
acid of surgery and postoperative operative time. Reduction in secondary 3 weeks starting the day before surgery (level C).
day 1 followed by 1 g three bleeding with reduced readmission rate. Needs further study
times daily for 3 weeks after No change in transfusion rate
surgery
Epinephrine Intraprostatic injections Significant reduction in perioperative Needs further evaluation. Could be an appealing 75
plus before microwave TURP bleeding and reduced need for irrigation adjunct to TURP given the possibility of early
mepivicaine after TURP discharge (level C)

Of the two drugs, finasteride has been most closely
examined with regard to bleeding associated with pros-
tate surgery. Donohue et al.56 demonstrated the down-
regulation of VEGF in patients treated with finasteride for
2 weeks before TURP, with an associated reduction in sub-
urethral prostatic microvessel density (MVD).56 Hochberg
et al.57 also reported that finasteride reduces MVD in men
undergoing TURP.57 These observations are important
given that the prostates of men with BPH and hema­
turia have a significantly higher MVD in the sub­urethral
portion than those of men with BPH alone.58
Kashif et al. 59 studied finasteride in a series of 12
patients with recurrent idiopathic prostatic hema­
turia, and found that bleeding resolved in all patients
within 2 weeks.59 Puchner and Miller 60 showed 11 of 12
patients treated with finasteride had an improvement in
their degree of idiopathic hematuria within 3 months.60
Sieber et al.61 described a similar result: 25 of 28 patients
reported resolution of their gross hematuria with finas-
teride treatment.61 Kearney et al.62 demonstrated that
prostate volume correlated with the average time needed
for resolution of hematuria, which was 2.7 days for small
prostates (<40 g) and 19–45 days for extra large glands
(>100 g). Further, they demonstrated resolution of hema-
turia in 31 of 40 patients on aspirin or warfarin treated
with finasteride.62 Foley et al.63 performed a prospective
randomized trial of patients with idiopathic prostatic
hematuria treated with finasteride or placebo. Hematuria
resolved in 86% of finasteride-treated patients, compared
with only 37% of those who received placebo. Surgery
was required in 26% of patients in the control group, and
no patients who took finasteride.63
A survey of British urologists revealed that 98% of
respondents use finasteride for hematuria thought to
be prostate-related. Only 4%, however, use finasteride
in all their patients before TURP, and 51% use it selec-
tively, such as for intermittent hematuria, large prostate,
or bleeding concerns.64 Ozdal et al.65 showed that when
patients were treated with 5 mg finasteride daily for
4 weeks before TURP, the amount of bleeding per gram of
resected tissue was significantly lower in the finasteride
group than controls (7.6 ml versus 14.0 ml).65 Donohue
et al.66 compared finasteride 5 mg daily with placebo for
2 weeks before TURP, and found a significant reduction
in blood loss per gram of resected tissue in the finasteride
group (2.65 g versus 4.65 g of hemoglobin), although
in this study hemoglobin loss was unusually high in
the control group.66 Neither of these studies showed a
signifi­cant difference in blood transfusions required.
Sandfeldt et al.67 studied TURP-related bleeding in
patients pretreated with finasteride for 3 months and
found no significant reduction in blood loss, resection
weight or operating time. However, they did show a
positive correlation between blood loss and resection
weight in finasteride-treated patients, where prostates
weighing more than 18.6 g were associated with signifi-
cantly less blood loss than those weighing less than 18.6 g
(324 ml versus 547 ml).67 Hagerty et al.68 demonstrated a
similar result for patients pretreated with finasteride for
4 weeks before TURP. Postoperative bleeding rates
for patients with more than 30 g of resected tissue were
8.3% and 36.8% in the finasteride and control groups,
respectively. Moreover, this study showed a reduction in
transfusion rates for patients pretreated with finasteride
with resected prostates >30 g (0% compared to 16% for
patients who did not receive finasteride).68
A large randomized controlled trial comparing patients
who received dutasteride or placebo for 2–4 weeks before
TURP found no difference in blood loss or difference
in MVD.69 Similarly, no difference in blood loss was
observed in a smaller randomized controlled where
patients in the treatment arm received dutasteride for
5 weeks before TURP.70
Notably, many studies of 5‑ARIs exclude patients on
anticoagulant or antiplatelet therapy and 5‑ARIs might
be particularly effective in reducing blood loss in these
patients. The 2010 AUA BPH guidelines state there is
insufficient evidence to recommend perioperative 5‑ARI
treatment to reduce hemorrhage.71 Recommended dura-
tion of finasteride therapy to optimize benefit must

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© 2011 Macmillan Publishers Limited. All rights reserved
REVIEWS
be balanced against cost and adverse effect profile.
Decreased libido and impotence occur in 5–10% of
patients, and should resolve following cessation of treat-
ment, although impotence is a potential complication of
the TURP itself. No serious drug-related adverse effects,
particularly thromboembolic events, have been noted in
these studies of short-term finasteride treatment.
Antifibrinolytics
Tranexamic acid is a synthetic derivative of the amino
acid lysine that binds to plasminogen and inhibits
activation of plasmin, which breaks up clots.32 Thus,
tranexamic acid acts to stabilize the clotting process.
Aminocaproic acid works via a similar mechanism, but is
less potent and not as freely commercially available. The
manufacturer’s recommended dose of tranexamic acid
is 1 g taken four times daily, and maximum daily dose is
6 g. Dosage should be reduced in patients with renal
impairment. Tranexamic acid can be given intravenously
0.5–1.0 g three times a day and can also be administered
intravesically during post-TURP washout.
Patients receiving 2 g oral tranexamic acid three times
daily for 72 h starting on the morning of TURP experi­
enced significantly less operative blood loss (128 ml
versus 250 ml), reduced operating time (36 min versus
48 min), and required less irrigating fluid (15 l versus 18 l)
than those who received placebo. However, tranexamic
acid treatment did not influence hospital stay duration
or the number of patients who required blood trans­
fusion.72 Similarly, a randomized controlled trial of 100
patients (52 of whom received 1 g tranexamic acid three
times daily from day 1 post-TURP; 48 patients received
no medical therapy) demonstrated a reduction in inci-
dence of secondary hemorrhage from 56% in the control
group to 24% in the treatment group, with significant
reduction in re-admission rate.73 Several studies have
also shown that high-risk patients treated with short-
term tranexamic acid perioperatively do not experience
more thromboembolic complications.74
Aprotinin is an antifibrinolytic that directly inacti­
vates plasmin. Increased 30-day mortality has been
demonstrated in patients who received aprotinin during
cardiac surgery, compared to tranexamic acid,75 and the
drug was subsequently withdrawn from the market by
the manufacturers.
The use of antifibrinolytics needs more thorough
evalua­t ion. We believe it is a safe and cost-effective
option, and should be considered for patients at risk
of bleeding. Tranexamic acid could be administered
at 1 g three times daily for 3 weeks starting the day
before surgery.
Topical medications
Local administration of epinephrine is a well-­recognized
technique for reducing blood loss during ear, nose and
throat surgery. A novel approach to TURP-related
bleeding was attempted by Schelin et al.,76 who admin-
istered intraprostatic injections of mepivicaine plus
epi­nephrine immediately before microwave TURP, the
objective being to anesthetize the prostate as well as
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© 2011 Macmillan Publishers Limited. All rights reserved
reduce blood flow. This relatively small retrospective
study showed an average blood loss of 108 ml in the
treatment arm compared with 354 ml in patients who
did not receive injections, which equated to an approxi-
mate 70% reduction in blood loss. Furthermore, 10 of
the 11 treated patients did not require bladder irrigation
postoperatively.76 Local epinephrine could potentially be
used as an adjunct treatment before TURP, though more
research is required.
Minimizing TURP-related blood loss
Although the terms ‘classical’ and ‘standard’ are often
used to describe the present day cautery-based TURP,
it is important to remember that frequent progressive
hemostatic advancements have been made to the proce-
dure since its earliest inception in the 1830s. Pioneering
surgeons, including Guthrie, D’Etiolles, Civiale, and
Mercier, used various transurethral cold knives
and punches to resect prostate adenomas with varying
degrees of success.77 Mercier 78 reported on 300 proce-
dures he performed in 1856 and noted that, although
successful, these procedures caused considerable hemor-
rhage.78 Hemostatic improvements were made as early as
1873, when Bottini79 used galvanocautery to perform the
first thermal resections of the prostate.79
Electrocautization technology was further advanced in
the early 1900s with the development of high frequency
unipolar currents that could sharply cut tissue rather
than deeply burn it, resulting in decreased secondary
necrosis and hemorrhage. 80 By 1926 the modern day
resectoscope was in use, which comes equipped with a
tungsten-wire cutting loop that functions under water.81
However, hemostasis remained a problem until the 1930s
when devices were introduced that allowed surgeons to
switch back and forth between undamped electrical
currents for cutting and damped electrical currents for
coagulation, which achieved better hemostasis.77
Over the next 80 years, the ‘traditional’ TURP con-
tinued to evolve and various hemostatic technologies
were incorporated, including electrode advancements,
electrical generator improvements, and alternative
energy sources.
Loop and electrode technology
A variety of resectoscope loops and electrodes are com-
mercially available, some of which have better hemostatic
properties than others. Although the electrosurgical
princi­ples behind these electrodes are similar, the ter-
minology can be confusing when manufacturers employ
terms such as electrofulgaration, tissue desiccation,
vaporizing-resection, and electrovaporization to differ-
entiate their electrodes. Simply, electrode technology can
be divided into: thin-wire loops that resect tissue, solid
electrodes that vaporize tissue, and thick hybrid loops
that do both (known as vapor-resection loops). Thin
loops result in the most intraoperative bleeding, but cause
minimal necrosis. Thicker loops require higher energy
and provide greater coagulation, but cause deeper tissue
necrosis and potential secondary bleeding. Vaporizing
electrodes achieve the deepest coagulation.

Gupta et al.82 performed a randomized comparison
between a commercial monopolar vapor-resection loop
and a standard cutting loop, reporting a significant
decrease in TURP-related blood loss with the former
(median blood loss 52.5 ml versus 150 ml; P <0.0001).82
In a randomized trial comparing electro­cautery TURP
and transurethral electrovaporization of the prostate
(TUVP), a statistically significant improvement in
hemostasis was demonstrated in the TUVP arm. The
mean decrease in hemoglobin was 1.2 g/dl for TURP
and 0.6 g/dl for TUVP; 8% of patients who underwent
a TURP required a blood transfusion compared with
1% of men who received TUVP.83 Meta-analysis of 11
trials comparing TURP to TUVP showed evidence of a
lower rate of blood transfusion after vaporization (rela-
tive risk 0.18; P <0.001) compared to electrocautery, at
the cost of greater urinary retention.84 However, another
meta-analysis of available vapor-resection studies did not
find a statistically significant hemostatic advantage of
vapor-resection with regard to blood transfusions.7
Bipolar electrical generators
Bipolar TURP technology was first employed in the early
1900s, but soon fell out of favor owing to advancements
in monopolar systems. Over the last 10 years, major
modifica­tions of bipolar devices have been reintroduced
to the market. As with monopolar devices, bipolar proce-
dures can also be divided into those designed to resect and
those that vaporize tissue, with the same advantages
and dis­advantages as above.
One of the advantages of bipolar technology is that
it uses lower voltages than monopolar electrodes and
theoretically causes less thermal deep-tissue injury.
Manufacturers report improved hemostasis with bipolar
technologies owing to the additional coagulation that
forms around the bipolar circuit of the electrode. A
random­ized trial comparing bipolar TURP to mono­polar
TURP reported less bleeding in the bipolar cohort. 86
However, there was no difference in terms of blood
transfusion rates in a meta-analysis of three random­ized
studies in the literature (Table 3).84
TUVP can also be performed with bipolar electro-
surgical generators, and although this technology has
been rapidly adopted with general enthusiasm, long-
term data are not yet available. The hemostasis results
are promising and suggest outcomes will be similar to
those reported for monopolar TUVP. Data on whether
these procedures can be peformed on patients receiving
anticoagulation therapy are pending.
Laser technology
Laser energy can be used to resect and vaporize prostate
tissue, with reduced transfusion rates and clot retention
compared to electrocautery.71,86–89 A variety of lasers are
commercially available.
The holmium:yttrium–aluminum–garnet laser can
be used to enucleate (holmium laser enuclea­tion of the
prostate [HoLEP]) or vaporize (holmium laser abla-
tion of the prostate [HoLAP]) the prostate.90 HoLEP is
performed more commonly, with thorough evaluation.
NATURE REVIEWS | UROLOGY VOLUME 8  |  SEPTEMBER 2011  |  511
© 2011 Macmillan Publishers Limited. All rights reserved
REVIEWS
Table 3 | Hemorrhagic complications of transurethral BPH surgery7
Procedure Transfusion (%) Clot Secondary Secondary
retention (%) coagulation hemorrhage (%)
revision (%)
TURP 2.0 4.9 1 0.5
Bipolar TURP 1.9 4.3 0 0.5
Bipolar TUVP 0.5 5.3 0 0.5
HoLEP 0 0 1.4 0
KTP 0 0 0 0.7
Abbreviations: HoLEP, holmium laser enucleation of the prostate; KTP, potassium–titanyl–phosphate; TURP,
transurethral resection of the prostate; TUVP, transurethral electrovaporization of the prostate.
Gilling et al.91 reported their 6‑year follow-up of patients
who underwent HoLEP showing good results in terms
of flow rates and quality of life.91 A meta-analysis per-
formed by Ahyai et al.7 demonstrated HoLEP to be as
effective as TURP, with decreased risk of bleeding and
minimal transfusion (Table 3).7 HoLEP has been shown
to be safe in fully anticoagulated patients.86,89 A retro-
spective review of HoLEP for patients on anti­coagulation
therapy with large prostates showed a much lower blood
trans­f usion rate than TURP with concurrent anti­
coagulant use. The blood transfusion rate was 14.2% in
patients on warfarin and 14.7% in those on LMWHs.
HoLAP is effective in smaller prostates,92 with reduced
transfusion rates.93
Potassium–titanyl–phosphate (KTP) and lithium tri-
borate lasers are used for photovaporization of the pros-
tate (PVP), which is associated with an especially low
rate of bleeding; a 0% transfusion rate has been reported
in studies that include patients on anticoagulants. 94,95
PVP has shown equivalent effectiveness,96 and a 2‑year
functional outcome comparable to TURP.95 In a study
of 500 men who underwent PVP, 45% of whom were
on perioperative anticoagulation, patients experienced
minimal complications and demonstrated a reoperation
rate of 7% at 5 years.97 A meta-analysis of PVP studies
demon­strated that outcomes were equivalent to TURP
for small and medium sized prostate, with minimal blood
loss (Table 3).7 Longer-term follow-up is needed to assess
durability of these results but the fact that PVP can be
performed as a day case admission or overnight stay with
reduced morbidity is appealing in an era where reduction
in morbidity and health costs is essential.
The thulium laser can be used to vaporize or enucle-
ate the prostate and has been shown to be faster than the
KTP laser,98 with excellent hemostasis,98,99 and 2‑year effi-
cacy comparable to HoLEP and TURP.100 Furthermore,
using the tangerine technique described by Xia et al.99
tissue can be sent for histopathology analysis.
Conclusions
TURP remains the most common surgery for BPH.
Anticoagulation and antiplatelet drugs are increasingly
common in this patient population and pose thera­peutic
dilemmas for urologists. Anticoagulants can often be
replaced with short-acting heparin derivatives in the
perioperative period and restarted shortly after surgery.
In patients with coronary artery disease, cessation
REVIEWS

of antiplatelet therapy can increase the risk of cardiac
events, and individual risk assessment is required. Low-
dose aspirin does not pose a significant risk of increased
bleeding from TURP and can often be continued safely,
although individual assessment is recommended.
Guidelines on medications that can reduce prostate
bleeding are lacking, although some key points can be
made. Finasteride is a highly effective treatment for idio-
pathic prostate bleeding. 5‑ARIs are yet to be proven an
effective treatment for reduction of prostate bleeding
related to TURP, although current research suggests they
might reduce the incidence of hemorrhage. Tranexamic
acid and use of local epinephrine are other options for
reducing perioperative bleeding related to TURP.
For additional hemostasis, prostate resection can be
performed with a vapor-resection electrode, bipolar
electrode, or holmium laser. Laser vaporization of the
prostate is an emerging field with intermediate data sug-
gesting that morbidity, in particular hemorrhage, might
be significantly reduced compared to conventional TURP.
Patients can also remain on anticoagulants through-
out the procedure in many instances, which is highly
relevant in an era where such agents are prescribed with
increasing frequency.
Ongoing study is required to improve evidence-based
practice in the field of prostate surgery. A number of
areas need clarification and further evaluation, includ-
ing targeted treatment with 5‑ARIs, especially in patients
on anticoagulant or antiplatelet agents, or patients with
a large prostate; cost-benefit analysis of optimal time
of 5‑ARI treatment before TURP; concomitant use of
5‑ARIs and tranexamic acid; and long-term follow-up
of patients in whom aspirin is ceased perioperatively.
Review criteria
Relevant manuscripts were found by searching MEDLINE,
Embase and Science Direct using, but not exclusively,
the terms “prostate”, “surgery”, “transurethral resection
of prostate”, “laser TURP”, “button TURP”, “neoplasm”,
“hemorrhage”, “operative procedure”, “prostatectomy”,
“finasteride”, “dutasteride”, “tranexamic acid”, “aspirin”,
“antiplatelets” and “anticoagulants”. References in
obtained articles were checked to cascade for further
relevant articles.

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Acknowledgments
C. P. Vega, University of California, Irvine, CA, is the
author of and is solely responsible for the content of
the learning objectives, questions and answers of the
Medscape, LLC-accredited continuing medical
education activity associated with this article.
Author contributions
L. E. Kavanagh and N. Lawrentschuk researched data
for the article. L. E. Kavanagh wrote the article.
L. E. Kavanagh, G. S. Jack and N. Lawrentschuk made
substantial contribution to discussion of content, and
editing the manuscript before submission.