Volume 24, Issue 8 pp. 589-593

Review Article

Free Access

Venous thromboembolism prophylaxis in urology: A review

Manmeet Saluja,

Manmeet Saluja

Department of Urology, Auckland City Hospital, Auckland, New Zealand

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Peter Gilling,

Corresponding Author

Peter Gilling

[email protected]

Department of Urology, Tauranga Hospital, Tauranga, New Zealand

Correspondence: Peter Gilling C.N.Z.M., M.D., F.R.A.C.S., Department of Urology, Tauranga Hospital, 829 Cameron Road, Tauranga South, Tauranga 3112, New Zealand. Email: [email protected]Search for more papers by this author

Manmeet Saluja,

Manmeet Saluja

Department of Urology, Auckland City Hospital, Auckland, New Zealand

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Peter Gilling,

Corresponding Author

Peter Gilling

[email protected]

Department of Urology, Tauranga Hospital, Tauranga, New Zealand

First published: 25 July 2017

https://doi.org/10.1111/iju.13399

Citations: 13

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Abstract

Venous thromboembolism is potentially a lethal problem, and is associated with chronic morbidity. Venous thromboembolism is frequently diagnosed after urological surgery, yet the role of perioperative venous thromboembolism prophylaxis is not clearly defined. Any current recommendations are largely based on evidence derived from other surgical specialties. Even within different guidelines, there remains significant variation, suggesting a consensus is required. The present review aims to define the problem of venous thromboembolism within the urological population, and identifies patients at risk. It evaluates the role of various types of mechanical and pharmacological prophylaxis, along with its timing and duration of administration in common urological operations. The current guidelines are summarized and compared in order to give the reader a better perspective of this vital condition.

Abbreviations & Acronyms

ACCP: American College of Chest Physicians
AUA: American Urological Association
DVT: deep vein thrombosis
LMWH: low molecular weight heparin
NNT: numbers needed to treat
PE: pulmonary embolism
RPLND: retroperitoneal lymph node dissection
UFH: ultrafractionated heparin
VTE: venous thromboembolism

Introduction

VTE is the presence of DVT or PE objectively confirmed on imaging or autopsy. It remains a vital problem, as it is potentially fatal and is associated with significant morbidity.

DVT can either be symptomatic or diagnosed on a screening ultrasound. Although the most of the DVT are subclinical,1 they can develop into post-thrombotic syndrome2 and can lead to chronic edema, pigmentation and ulceration. The majority of symptomatic DVT originates in calf veins, and might extend to the proximal leg.1, 3, 4 If untreated, proximal VTE can develop PE in up to 50% of cases.5 Other early complications include phlegmasia cerulea dolens and venous gangrene. Late complications include post-phlebitic syndrome, chronic venous insufficiency and chronic thromboembolic pulmonary hypertension.6

PE is preceded by a symptomatic DVT in just one-quarter of cases.4 After a PE, 2–4% of patients will develop chronic pulmonary hypertension.7 Between 17% and 25% of PEs are fatal1 and PE remains the most common form of preventable hospital mortality.8

Recommendations regarding VTE prophylaxis in urological surgery are mainly derived from research carried out in other specialties; mainly orthopedics and general surgery. Organizational guidelines are mainly based on expert opinion, and vary in their recommendations (Table 1). The literature remains scarce for urological operations that can range from ambulative to major abdominopelvic surgery, and possess a spectrum of VTE risks. Rates vary within the literature, as some studies measure only clinical VTEs, whereas other studies objectively screen for postoperative VTEs in all patients. There is often confusion as to which prophylaxis is best, and the optimal duration is often debated. Additionally, there is fear that the drive for additional thromboprophylaxis might be driven by pharmaceutical companies. Therefore, we intended to address these issues, and summarize the current evidence base in order to provide a clear and concise guide for our patients.

Table 1. Summary of guidelines – recommendations (risk class and prophylactic recommendation)

Risk class	Very low	Low	Moderate	High	Very high
ACCP (2012) (if low risk of bleeding)	Caprini = 0 Rogers <7 Risk = 0%	Caprini = 1–2 Rogers 7–10 Risk = 1.5%	Caprini = 3–4 Rogers >10 Risk = 3%	>5 NA Risk = 6%	NA
Management	None or mechanical	Mechanical	Mechanical and chemical	Mechanical and chemical (extended if cancer)
AUA Best Practice Statement (2009)a	NA	Minor surgery, <40 years, no risk factors	40–60 years, or minor surgery with risk factors	>60 years, or 40–60 years with risk factors	Presence of multiple risk factors
Management		None	Chemical or pneumatic	Chemical or pneumatic	Chemical and pneumatic (consider extended)

^a Risk scores adapted from Geerts et al.16

Risk factors for VTE

Virchow's triad is commonly used in understanding the etiology of VTE, and comprises “stasis of blood flow, hypercoagulability and endothelial injury.” Risk factors for VTE have been described in Table 2.

Table 2. Risk factors for VTE

Preoperative	History of VTE
	Thrombophilia
	Obesity (BMI >30)
	Pregnancy
	Trauma
	Age >60 years
	Estrogen therapy
	Comorbidities: acute medical illness, congestive cardiac or respiratory failure, nephrotic syndrome, inflammatory bowel disease
	Malignancy (advanced/metastatic > localized)
	Trauma
	Immobility
	Smoking
	Chemotherapy
	Ethnicity: Black > Caucasian > Hispanic > Asian/Pacific Islanders
Intraoperative	Length of surgery >2 h
	Volume of blood loss
	Lack of mechanical thromboprophylaxis
	Type of anesthesiaa
Postoperative	Immobilization >4 days
	Prolonged hospital stay
	Lack of thromboprophylaxis
	Recovery: sepsis, reoperation, nutrition
	Lymphocoeles

^a Epidural and spinal anesthesia are associated with a reduction of DVT and PE by 55%. Modified from Geerts et al.,16 Scarpa et al.,33 Edmonds et al.58 and White et al.59

Urological patients are often aged and have multiple comorbidities. Furthermore, many have an active malignancy, which is associated with a twofold increased risk of postoperative DVT, and a fourfold increase in the risk of VTE compared with the normal population.9, 10 Additional risks in cancer patients include venous occlusion, immobility, smoking history, malnutrition and multiple hospitalizations.11 The risk is increased if they have locally advanced or metastatic disease, or if they are undergoing chemotherapy. This risk is further aggravated if they undergo an operative procedure, especially if it is lengthy (>2 h), associated with a large volume of blood loss or the patient has a prolonged hospital stay.9-11

A few risk stratification models have been described and incorporated within guidelines to guide a prophylactic regime (Table 1).12, 13 The Caprini model assigns a score from >35 known risk factors. Each risk factor is scored between 1 and 5 based on its attributable risk toward VTE. The higher the score, the higher the risk of VTE. Although some of the risk factors have now been disproven, the model is relatively easy to use.14 The score has been validated within the urological literature; however, there are inconsistencies with its correlation to VTE risk in certain urological surgeries.15

The Rogers model is another risk-scoring system that includes variant risk factors and is less comprehensive. It was originally designed for vascular and general surgery patients, and has not been modified or validated for the urological population.14 Therefore, development of improvised or novel models are recommended to assess the risk specific to our population.

Types of thromboprophylaxis

Mechanical thromboprophylaxis

Early mobilization is an essential part of any thromboprophylaxis regime. Mechanical prophylaxis devices are used to reduce venous stasis and release of anti-thrombotic factors from leg muscles.6 They have been shown to decrease DVT rates, but do not decrease the risk of PE- or VTE-related deaths.16 In general, they are safe and easily tolerable.17 There are two main types:

Graduated compression stockings

These generate pressure at the ankle, and gradually decrease the pressure moving up the leg. These should be fitted to every patient and worn continuously until a return to full mobilization. They reduce the risk of DVT by 31–65%18, 19 with NNT of 28 to prevent one DVT.16, 20 No consistent difference has been noted in efficacy between calf-length and thigh-length stockings. Contraindications include peripheral arterial disease, severe peripheral edema, leg cellulitis, diabetic neuropathy, skin graft and severe lower limb deformity.20 Complications are rare, and could include compartment syndrome, skin ulcers and nerve palsy.

Pneumatic calf compressors

Calf compressors reduce the risk of DVT by 60% and proximal DVT by 50%, but do not decrease the rates of PE.21-23 A combination of calf compressors and stockings are more efficacious, as they work by different mechanisms – stockings prevent distention and calf compressors empty veins.24, 25 In a recent Cochrane analysis, calf compressors and anticoagulation were found to be equally effective in reducing DVT; however, the studies had several limitations.25

Pharmacological thromboprophylaxis

Before the initiation of heparin prophylaxis to prevent VTEs after pelvic surgery, the DVT incidence was between 10% and 30%, and the PE incidence was between 1% and 10%.1 There are two main types: UFH and LMWH. Complications include injection site bleeding and wound hematomas; however, rates of major bleeding or spinal/epidural hematoma are very rare.14

UFH is associated with an 18% reduction in the odds of death from any cause, a 47% reduction in the odds of fatal PE and a 41% reduction in the odds of non-fatal PE, along with a 57% increase in the odds of non-fatal major bleeding.14, 26

LMWH appears to be equally efficacious as UFH, and reduces the risk of DVT and PE by 51% and 70%, respectively, compared with a placebo.26, 27 However, it can double the risk of major bleeding and wound hematoma.27 Its once-daily dosing might be preferable to the twice-daily dosing of UFH for an outpatient prophylactic dose.

Aspirin has been shown to decrease symptomatic DVT by 28% and fatal PE by 58% in orthopedic surgical patients.14, 28 However, it is not as effective as heparin in preventing VTE.6, 29 Therefore, major guidelines, such as ACCP, recommend against the use of aspirin unless the use of heparin is contraindicated.14

The addition of mechanical prophylaxis to pharmacological prophylaxis has been shown to decrease the DVT rate by 60% (NNT for high risk patients = 28).4, 30 Initiation of heparin 6–9 h post-surgery is more effective and has less risk of bleeding compared with (<2 h) preoperative dosing.31

Timing of perioperative pharmacological VTE prophylaxis

Meta-analyses and systematic reviews from the orthopedic literature have found no difference in efficacy and safety between initiating VTE pre- versus postoperatively.32 However, postoperative administration allows flexibility in management decisions based on bleeding risk, and might be more feasible. Although evidence is limited, prophylaxis administered 4–6 h postoperatively might be superior to delayed prophylaxis (>12 h postoperatively), and could be associated with less bleeding than immediate prophylaxis (<2 h postoperatively).32

Standard versus extended pharmacological thromboprophylaxis

Various studies have shown that patients who undergo high-risk urological surgery remain at significant risk of a VTE post-discharge.33, 34 Multiple randomized controlled trials and subsequent meta-analysis have shown that extended duration LMWH for 4 weeks reduces the incidence of DVT (distal and proximal) by at least 50% in patients undergoing high-risk abdominopelvic surgery compared with inpatient-only treatment.35-37 Rates of major bleeding, PE and overall survival did not differ between the groups.37 Furthermore, extended prophylaxis in high-risk surgeries might be more cost-effective.38

Thromboprophylaxis in urological surgery

All patients admitted for urological surgery should be assessed for VTE risk. After urological procedures, DVT rates of 0.2–7.8% and PE of 0.2–7% have been reported (Table 3).6 Rates vary, as some studies report subclinical DVT, whereas others report clinically diagnosed VTE. Most of the evidence regarding the efficacy of VTE prophylaxis is extrapolated from studies that have used some urological procedures as part of their cohort. Studies often include a mixed cohort of patients, who may or may not have received prophylactic treatment. Furthermore, as the rates of VTE in general are relatively low, studies are often underpowered to make any definitive conclusions.

ACCP classifies the risk of VTE for the individual patient based on Rogers and Caprini scores, and provides recommendations on prophylaxis. The AUA has published a best practice statement in 2009 and the European Association of Urology guidelines are currently pending. Multiple other regional and organizational guidelines are available, but are mainly based on recommendations from panel experts.39 Overall, most recommendations state that low-risk categories need no prophylaxis or solely mechanical prophylaxis. Moderate-risk categories can either have mechanical or pharmacological prophylaxis. The high-risk category should have both mechanical and pharmacological prophylaxis, and extended prophylaxis should be considered (Table 1).14, 20, 30, 39 Adherence to mechanical prophylaxis ranges from 53.5% to 75% in a meta-analysis.40 However, compliance with pharmacological prophylaxis even in high-risk patients is relatively poor.41

Transurethral surgery/ureterorenoscopy

Rates of VTE are low at 0–0.4%. As transurethral procedures are associated with postoperative bleeding, the benefit of chemical prophylaxis might not outweigh the risk of bleeding. Therefore, apart from early ambulation and use of mechanical prophylaxis, no specific prophylaxis is required unless the patient has other risk factors.10, 33

Table 3. Risk of VTE in common urological procedures

Urological procedure	Risk of VTE (%)
Transurethral/ureterorenoscopic	0–0.410, 33
Nephrectomy (radical/partial)	0.2–2.944
High-risk disease (vascular invasion etc.)	2.6–22.643, 44
Radical prostatectomy	0.2–0.917, 44
Extended lymph node dissection	3.9–15.744
Radical cystectomy	6–24.453
RPLND	0–156, 57

Modified from White,10 Scarpa et al.,33 Sallah et al.,43 Tikkinen et al.,44 Edmonds et al.58 and VanDlac et al.53

Penile/scrotal/inguinal surgery

No specific data is available, but as most patients are ambulant early after surgery, only mechanical prophylaxis is usually required. Invasive penile surgery or inguinal lymph node dissection for malignancy requires mechanical and pharmacological prophylaxis.

Functional urology

Most data regarding VTE rates are derived from gynecological literature. The AUA recommends mechanical and pharmacological prophylaxis for patients undergoing vaginal, paravaginal repairs, vault suspension, sacrospinous ligament fixation and abdominal sacrocolpopexy.30

Nephrectomy

Patients undergoing partial or radical nephrectomy have a risk of DVT and PE of 0.6% and 0.9%, respectively.42 There was no difference in open and laparoscopic surgery.42 However, for patients who had stage 3 or 4 malignancy, rates of VTE were as high as 22.6%.43 ACCP guidelines recommend mechanical and pharmacological prophylaxis in patients undergoing radical nephrectomy if the patient is not at a high risk for bleeding. For partial nephrectomy, routine pharmacological prophylaxis needs to be weighed against the risk of bleeding.

Radical prostatectomy

Rates of clinical VTE in open radical prostatectomy have been reported as 0.2–0.9%17, 44 and 3.9–15.7% in patients with extended pelvic lymph node dissection.44 Laparoscopic and robotic surgery have reported rates of DVT of 0.5% and PE of 0.2%, with higher rates in longer operations.45 There is no definitive evidence to suggest that heparin provides benefit, as many series are underpowered.6 Heparin might slightly increase the risk of bleeding46 and lymphoceles after surgery.47, 48 Conversely, lymphoceles are associated with a higher risk of VTE, likely due to pressure on pelvic veins.49 Recommendations vary from giving only mechanical prophylaxis to giving extended pharmacological prophylaxis for high-risk patients.17, 50 In practice, as few as 10% of urologists use routine pharmacological thromboprophylaxis.51

Radical cystectomy

Radical cystectomy has one of the highest VTE rates (clinical = 6%, subclinical = 24.4%) compared with any surgery of any discipline.1, 52, 53 In one large retrospective study, the average time to VTE was noted to be 15.2 days, with a majority (55%) being diagnosed after discharge.54 Both mechanical and extended duration pharmacological prophylaxis have been recommended for this high-risk group.14, 30, 55

RPLND

RPLND has been associated with a 0–1% risk of VTE in both primary and post-chemotherapy RPLND.56, 57 Perioperative mechanical prophylaxis should be given. Heparin should be considered after the risk of VTE for the individual patient is balanced against the risk of bleeding and the potential risk of lymphocele.48

Conclusion

VTE is often an underrecognized, but nevertheless important problem within the urological patient population. Further trials are required within urology to quantify individual risk of each procedure. Improved prognostic risk models are needed to stratify patients into risk groups. Despite the current use of thromboprophylaxis regimens, rates of VTE still appear to be high. Additional preventative strategies and better compliance need to be implemented within each individual practice. Further evidence-based consensus guidelines are pending, and will hopefully provide better direction for the management of VTE prophylaxis in our patients.

Conflict of interest

None declared.

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Citing Literature

Volume24, Issue8

August 2017

Pages 589-593

Venous thromboembolism prophylaxis in urology: A review

Abstract

Abbreviations & Acronyms

Introduction

Risk factors for VTE

Types of thromboprophylaxis

Mechanical thromboprophylaxis

Graduated compression stockings

Pneumatic calf compressors

Pharmacological thromboprophylaxis

Timing of perioperative pharmacological VTE prophylaxis

Standard versus extended pharmacological thromboprophylaxis

Thromboprophylaxis in urological surgery

Transurethral surgery/ureterorenoscopy

Penile/scrotal/inguinal surgery

Functional urology

Nephrectomy

Radical prostatectomy

Radical cystectomy

RPLND

Conclusion

Conflict of interest

References

Citing Literature

References

Information

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Venous thromboembolism prophylaxis in urology: A review

Abstract

Abbreviations & Acronyms

Introduction

Risk factors for VTE

Types of thromboprophylaxis

Mechanical thromboprophylaxis

Graduated compression stockings

Pneumatic calf compressors

Pharmacological thromboprophylaxis

Timing of perioperative pharmacological VTE prophylaxis

Standard versus extended pharmacological thromboprophylaxis

Thromboprophylaxis in urological surgery

Transurethral surgery/ureterorenoscopy

Penile/scrotal/inguinal surgery

Functional urology

Nephrectomy

Radical prostatectomy

Radical cystectomy

RPLND

Conclusion

Conflict of interest

References

Citing Literature

References

Related

Information