Ureteroscopy in Patients with Bleeding Diatheses,Anticoagulated,and on Anti-Platelet Agents: A Systematic Review and Meta-Analysis of the Literature

Abstract

Introduction:

Ureteroscopy (URS) is the most common surgical treatment of urolithiasis and can be problematic in patients with a bleeding diathesis. The intent of this review is to systematically review the literature to assess the safety and efficacy of ureteroscopic procedures in these groups of patients.

Methods:

The systematic review was performed according to the Cochrane diagnostic accuracy review guidelines. The search strategy was conducted to perform a comprehensive database search (1990–2017). A cumulative analysis was done and where applicable a comparative analysis between bleeding diathesis patients and those without.

Results:

Eight studies included were all published between 1998 and 2016 with the total number of participants with bleeding diatheses being 1109 with an age range of 18–97. Overall stone-free rate across the studies was 90.8% vs 86.2% in the control group. There was no significant difference in complications between the bleeding diathesis group and control group (N = 12,757, p = 0.07, 95% confidence interval [CI] 0.92, 6.02, I₂ = 78%). Pooled analysis for bleeding-related complications shows a statistically significant difference favoring the control arm (N = 12,757, p ≤ 0.0001, 95% CI 1.81, 5.73, I₂ = 0%). Pooled analysis for thrombosis shows no statistically significant difference between the bleeding diathesis group and the control arm (N = 118, p = 0.67, 95% CI 0.23, 9.86, I₂ = 48%).

Conclusion:

The use of URS with or without the holmium laser is a safe and efficient modality for treating patients with urolithiasis who also have a bleeding diathesis or are anticoagulated or on antiplatelet agents. However, this review would suggest that the increased risk of procedure related bleeding is not insignificant and a patient-centered approach should be taken with regards to continuing these agents or not correcting bleeding diatheses.

Introduction

Ureteroscopy (URS) is the most common surgical treatment of urolithiasis and has also become an instrumental component in the diagnosis and management of upper tract urothelial carcinoma.^1,2 The lifetime risk of urolithiasis is 13% in men and 7% in women with a peak incidence around the third to fourth decade of life.^1,2 URS stone treatment is currently recommended as the first line treatment for many stones owing to its higher stone-free rate compared with shockwave lithotripsy (SWL).^3,4

Despite the evolution in optics and miniaturization of ureteroscopes, many urologists still tend to correct any coagulopathy before upper tract endourologic procedures.⁵ This tendency can be problematic in some patients, where coagulopathy correction is not an option (i.e., metallic heart valves, high risk of deep vein thrombosis [DVT], and pulmonary embolism). Such patients are often not suitable for other treatments such as percutaneous nephrolithotomy (PCNL) or SWL. Another challenging cohort of patients are ones with a bleeding diathesis in whom an endourologic procedure needs to be done in the emergent setting.⁶

Elkoushy and coworkers summarize the dilemma succinctly; anticoagulated patients often have multiple comorbidities, which in addition to the thrombogenic nature of surgery further increases their risk of thromboembolic episodes.⁷ Surgeons must therefore balance the need to reduce the risk of thrombosis with the need to reduce the risk of bleeding by continuing antiplatelet (APT) or anticoagulation therapy or not correcting coagulopathies.

A previous systematic review on this topic has shown that it was safe to proceed with URS procedures in these groups of patients. However, the evidence was derived from only three available studies of low quality comprising 73 procedures.⁵ This article formed a part of recent American Urological Association (AUA) guidelines on the topic “URS can be performed with continuing oral anticoagulation and APT therapy”.⁸ Since then, further studies have emerged on this topic on the viability of URS in patients with bleeding diatheses. The intent of this review is to systematically review the literature to assess the safety and efficacy of ureteroscopic procedures in patients with bleeding diatheses.

Methodology

Search strategy and study selection

The systematic review was performed according to the Cochrane diagnostic accuracy review guidelines. The search strategy was conducted to find relevant studies from MEDLINE (1990–March 2017), EMBASE (1990–March 2017), Cochrane Central Register of Controlled Trials—CENTRAL (in The Cochrane Library—Issue 1, 2017), CINAHL (1990–March 2017), Clinicaltrials.gov, Google Scholar, and Individual urologic journals.

Terms used included: “ureteroscopy”, “coagulopathy”, “anticoagulant”, “warfarin”, “bleeding”, “urolithiasis”, “aspirin”, “coumarin”, “clopidogrel”, “thrombocytopenia”, and “calculi”. Mesh phrases included: (“Ureteroscopy”[Mesh]) AND “Blood Coagulation Disorders”[Mesh], (“Anticoagulants”[Mesh]) AND “Ureteroscopy”[Mesh], (“Ureteroscopy”[Mesh]) AND “Hemorrhage”[Mesh], (“Anticoagulants”[Mesh]) AND (“Lasers”[Mesh] OR “Laser Therapy”[Mesh]), ((“Lasers”[Mesh]) AND “Calculi”[Mesh]) AND “Anticoagulants”[Mesh], (“Anticoagulants”[Mesh]) AND “Calculi”[Mesh], (“Ureteroscopy”[Mesh]) AND “Aspirin”[Mesh], (“Ureteroscopy”[Mesh]) AND “clopidogrel” [Supplementary Concept], (“Ureteroscopy”[Mesh]) AND “Coumarins”[Mesh], and (“Ureteroscopy”[Mesh]) AND “Thrombocytopenia”[Mesh], (“Kidney Calculi”[Mesh] OR “Ureteral Calculi”[Mesh]) AND “Aspirin”[Mesh], (“Coumarins”[Mesh]) AND (“Kidney Calculi”[Mesh] OR “Ureteral Calculi”[Mesh]), (“Kidney Calculi”[Mesh] AND “Ureteral Calculi”[Mesh]) AND “Coumarins”[Mesh], and (“Thrombocytopenia”[Mesh]) AND (“Kidney Calculi”[Mesh] OR “Ureteral Calculi”[Mesh]).

Reference lists of included studies were analyzed for suitable articles. Articles in languages other than English were included. Authors of the included studies were contacted whenever the data were not available or not clear.

Three reviewers (O.M.A., A.S., T.A.) identified all articles matching the inclusion criteria for full review. Each reviewer independently selected studies for inclusion in the review. Disagreement between them was resolved by consensus.

Data extraction and analysis

Studies reporting on the treatment of patients with a bleeding diathesis with both semirigid and flexible URS with or without laser lithotripsy were included. The authors assessed all patients having URS and not simply those with urolithiasis. Patients included were adults with a bleeding diathesis who had urinary stones. The following variables were extracted from each study: period and location of the study; all study population demographics; type of anticoagulant used or coagulopathy; pre or postop stent insertion; stone-free rates; and major and minor complications. The data of each study were grouped into excel tables to allow a numerical representation of the results.

Results

The literature search yielded 199 studies, of which 165 were excluded after abstract review. Thirty-four studies were then retrieved for further assessment with eight articles eventually included. One previously excluded study was included on closer interrogation; although the authors looked at various treatment modalities for stones, eight patients were ureteroscopically treated (six through Swiss LithoClast and two using the holmium laser).⁹ The study is limited by the authors not providing specific demographic or coagulopathy data for these patients. The previous review process was unsuccessful in contacting the authors.⁵ However, the outcomes of the intervention are relevant to this title. Thus, eight articles were included in the current review.^{4,6,7,9

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Characteristics of the included studies

Seven of the eight included studies were retrospective,^{4,6,7,9,11
–13} with one being a worldwide prospective study from Clinical Research Office of the Endourological Society database (Fig. 1).¹⁰ All the included studies were published between 1998 and 2016 with the total number of participants with bleeding diatheses being 1109 with an age range of 18–97. Four studies were performed in the United States, two in Canada, and one a piece in Argentina and Austria.

FIG. 1.

Pooled analysis of total complications.

Bleeding diatheses or anticoagulation or APT agent

Of 1109 participants, 643 underwent URS while on Aspirin, 153 on Warfarin, and 121 on Clopidogrel. Seven patients had thrombocytopenia, two von Willebrand disease, and three liver dysfunction. Other agents included tinzaparin (n = 1), dual agent therapy (n = 27), calcium carbasalate (n = 47), nadroparin (n = 33), and unknown (n = 77) (Table 1).

Table 1.

Included Articles and Complications

					Antiplatelet or anticoagulant or bleeding diathesis
Name (country)	Journal, article type	Year (research period)	No.	Age range/(mean)/sex/ASA	Aspirin	Warfarin/acenocoumarol/phenprocoumon	Clopidogrel	Bleeding diathesis	Complications
Kuo and coworkers¹³ (United States)	Urology, retrospective over 11 month period	1998 (1997–1998)	9	42–74 (58.3)	0	Six warfarin	0	3 (2 × thrombocytopenia (corrected in 1)	One ureteral bleeding causing clot retention
Kuo and coworkers¹³ (United States)	Urology, retrospective over 11 month period	1998 (1997–1998)	9	42–74 (58.3)	0	Mean INR 2.1	0	1 von Willebrand disease (VWD)	Epistaxis × 1, 1 × failed trial of void
Watterson and coworkers⁶ (Canada)	Journal of Urology, retrospective in two centers over 5.5 years	2002 (1996–2001)	25	42–48	0	17 Warfarin	0	8 (Liver dysfunction × 3, Thrombocytopenia × 4), VWD × 1.	Retroperitoneal hemorrhage × 1, required transfusion
				M 19: F 6		Mean INR 2.3			2 × Renal colic, AF × 1
				Mean ASA 2.8		Mean INR 2.3			2 × Renal colic, AF × 1
Klingler and associates⁹ (Austria)	European Urology, retrospective over 6 years	2003 (1996–2002)	8 (13 Controls)	x	x	x	x	x	2 × Hematuria with clots requiring earlier removal of stents
									Inpatient stay 2.8 vs 2.1 days in control group
									Average cost for bleeding diathesis patients $4611 vs $2342 control
									13 Control patients with similar characteristics (no complications)
Turna and associates¹² (United States)	Journal of Urology, retrospective review in two centers over 7 years	2008 (2001–2007)	37 (37 Controls)	35–86 (58.2 ± 12.5 years)	13 × 81 mg	14	5	0	3 × Hematuria vs 0 (control) UTI: One vs one control
					5 × 325 mg				One DVT in control group vs 0 in control
									Control group 1 × superficial proximal ureteral perforation
									Total four complications in anticoagulated group vs three control (NS)
				ASA 2.8 ± 0.6 vs 1.9 ± 0.8 (p = 0.004)
Daels and coworkers¹⁰ (Argentina)	World Journal of Urology, prospective over 1 year, multiple centers	2015 (2010–2012)	762 (10,896 Controls)	18–97	426	47 Acenocoumarol/41 phenprocoumon	94	154 Calcium carbasalate	Postoperative bleeding higher in patients on anticoagulants (1.1% vs 0.4%; p < 0.01) [8/762 vs 44/10,896]
								47 Nadroparin/fondaparinux
								33 Dipyridamole/aspirin + dipyridamole 5	Patients with risk factors for stone formation had more complications than those without (4.9 vs 3.0%, p < 0.001).
								Other 69
Elkoushy and coworkers⁷ (Canada)	International Brazilian Journal of Urology, retrospective over 18 months	2013 (2009–2011)	12 (32 Control patients)	60 (median)	3	Six warfarin	One Aspirin and clopidogrel	One tinzaparin, One thrombocytopenia	Two bleeding requiring readmission and CBI, one requiring embolization
				78% Male					0 complications in control group
				78% Male					1 × Patient (4%) developed DVT with PE, needed IVC filter since he had developed hemorrhage when anticoagulation was initiated
Toepfer and coworkers¹¹ (United States)	Journal of Urology, retrospective over 5 years in one center	2013 (2005–2010)	176 (470 Control patients)	64.6	137	22 Warfarin	17	0	Unplanned repeat surgery 8% aspirin, 5.9% clopidogrel
							Age 66.0 (61.0, 69.0)		Unplanned repeat surgery 8% aspirin, 5.9% clopidogrel
									ED visit 14% in 30 days vs 11.7% control (NS)
									Readmissions 2.3% control, aspirin 8% (0.04), warfarin 4.6% (NS), clopidogrel 0%
									Clot retention 1 AC group vs 2 control group (NS)
									UTI 13 AC group (9.5%) vs 25 control group


									(5.3%) (NS)
									Poorly controlled pain 15 (6.8%) vs 78 (16.6%) control (NS)
									Controls death 2 (urosepsis day 0, mi day 29) (0.4%), MI 1 (0.2%)
					Age 61.0 (55.0, 70.0)	Age 67.0 (62.0, 73.0) INR 1.65
Westerman and associates⁴ (United States)	Journal of Endourology, retrospective over 7 years	2016 (2009–2016)	80 (234 Control patients)	70.1	Single antiplatelet 63	0	Four Single P2Y12 receptor antagonist	17 on dual APT	Two fever/bacteremia. 1 abdominal pain.
				73.2% Male				11 Aspirin 81 mg	Five bleeding episodes in control group, five in AC group (p = 0.256)
								11 Aspirin 81 mg	Dual APT more likely to be readmitted for any reason at 30 days vs those who held APT/on a single APT (12% vs 0%, p ≤ 0.001).
					13 Aspirin 81 mg			6 Aspirin 325 mg	No difference in overall/significant bleeding events across groups (p = 0.6, p = 0.5)
					46 Aspirin 325 mg			17 P2y12 dual receptor antagonist
		Total	1109 Bleeding diathesis group, controls 11,650	Range 18–86	643	153	121	184	Retention of urine 1, UTI/sepsis 16
				Range 18–86					Uncontrolled pain 18, AF 1, Epistaxis 1
				Mean 62.8					DVT 1
									Total complications in bleeding group 55/1109 (5%), bleeding-related complications 24/1109 (2.5%)
									Total complications in controls 157/11,650 (1.34%). Bleeding-related complications in control group 50/11,650 (0.42%)

AC = anticoagulation; AF = atrial fibrillation; APT = activated partial thromboplastin; ASA = american society of anaesthesiologists; CBI = continuous bladder irrigation; DVT = deep vein thrombosis; ED = emergency department; INR = international normalized ratio; IVC = inferior vena cava; MI = myocardial infarction; NS = non-steroidal; PE = pulmonary embolism; UTI = urinary tract infection; VWD = von Willebrand disease; x = not reported.

Stone characteristics

For those articles which characterized stone burden, the range was 3–25 mm in diameter. Of those articles supplying mean stone burden, this was 11.9 mm,⁷ 6.8 mm,⁹ and 13.2 mm,¹² giving an aggregate mean of 10.5 mm. Several articles had control arms where the aggregate mean of stone diameter was 10.1 mm.^7,11,12 Two articles performed statistical analysis on the size of stones between bleeding diathesis groups and control groups, one found no difference¹² and another found that the control group had significantly smaller stones (p = 0.01).⁷ Stone density was not commented on in any of the included articles (Table 2).

Table 2.

Perioperative Parameters

Name	Year	N	Procedure type	Access sheath used	Stent use	Op duration	Stone size (mm) (mean)Stone location	Post op Hb	Stone-free rate
Kuo and coworkers¹³ (United States)	1998	9	Six FURS and laser stone fragmentation (FURSL)	x	9/9 100%	x	3–15 mm	No significant change	86% (6/7).1 × 2 mm residual fragment1/8 stone patients had no stone on URS
			Six FURS and laser stone fragmentation (FURSL)				Proximal ureter: 1	No significant change
			Two Semirigid URS and stone fragmentation				Middle ureter: 1
			1 × FURS for UTTCC				Distal ureter: 1
			1 × FURS for UTTCC				Renal: 5
Watterson and associates⁶ (Canada)	2002	25	30 URS for 29 stones	Dilation of ureteral orifice, 11/30 (37%) cases	26/30 86%	x	11.9 (6–25)	x	96% (27/28)Concomitant electrohydraulic lithotripsy in two patients93% (26 of 28 cases if including only single ureteroscopic procedures)
			9 × 6.9F semirigid ureteroscopy and laser stone fragmentation for calculi below the iliacs	Dilation of ureteral orifice, 11/30 (37%) cases			Ureteral: Proximal ureter: 9
			21 × 7.5F FURSL for ureteral stones proximal to iliacs and renal stones.	Using 8/10F coaxial sheath × 8			Middle ureter: 3;
				Using 8/10F coaxial sheath × 8			Distal ureter: 7
				Balloon dilation catheter × 2			Renal: 9 (six lower pole)
				Access sheath × 1			Renal: 9 (six lower pole)
Klingler and coworkers⁹ (Austria)	2003	8	Wolf semirigid 7/8.5F Swiss LithoClast/laser fragmentation	x	8/8 100%	x	Mean 6.8 mm (5–8 mm).	x	100%
Turna and associates¹² (United States)	2008	37	37 FURSL	8 (22% vs 3% for control group p = 0.0128)	Prestent 46% vs 35%	69.9 ± 25.4 AC	13.2 mm (5–35 mm)	13.2 ± 1.7 AC group
							Control 11.1 ± 6.6 (0.15)	13.3 ± 1.9 (NS) control
							Ureteral: 8	13.3 ± 1.9 (NS) control
						57.8 ± 15.9 (0.0146)	Renal: 29		100%
						57.8 ± 15.9 (0.0146)	Renal: 29		81.1% (AC) vs 78.4% (control), p = 0.7725
Daels and coworkers¹⁰ (Argentina)	2015	702	Ureteroscopy (no further detail provided)	x	x		x	x	x
Elkoushy and associates⁷ (Canada)	2013	12	16 procedures	9/9 FURS	100%	NS vs controls	14.0 mm bleeding diathesis group vs control 9.2 vs p = 0.01	Median post-op Hb significantly decreased in AC patients vs controls (0.8 vs 0.2 g/dL; p = 0.001).	69.2% (8/12) vs 94.1% (control) p = 0.04)
			Three ureteral biopsies semirigid URS						After second URS, stone-free rates were comparable in both groups (92.3% vs 100%, p = 0.9)
			Nine FURSL
			Two repeat stone procedures
			One third URS				Renal stones 57% Ureteral 43%
			One re biopsy				Renal stones 57% Ureteral 43%
Toepfer and coworkers¹¹ (United States)	2013	176	152/176 FURS (check figure)	77 (44%)	67% vs 46% (control) pre-stented	NS vs controls	6–16 mm (9 mm), control 10.5 mm	x	97% (171/176)
			13 × semirigid URS. Seven both				86 Ureteral
			13 × semirigid URS. Seven both				80 Renal
Westerman and associates⁴ (United States)	2016	80	69 stone cases (69.6%)	80 (100%)	60% vs 35% (control) pre-stented	NS vs control	7.2 (single agent)		94.2% Single agent
			11 diagnostic				7.2 (single agent)		Dual agent 87.5% (Mean 91%)
			Laser used in 66/80 (83%)				8.1 mm (dual agents)		Dual agent 87.5% (Mean 91%)
			FURSL 225	175/327 (53%)	55/59 93% Pre-stented		3–25 mm		90.8% AC/86.2% control
			URS + stone fragmentation 19				Mean 10.5 mm vs 10.1 mm control group
			Diagnostic URS/FURS 29
			Unclear 776		182/293 (62%)
			Total: 1049		182/293 (62%)

FURS = flexible ureteroscopy; FURSL = flexible ureteroscopy and laser lithotripsy; NS = non-steroidal; URS = ureteroscopy; UTTCC = upper-tract transitional-cell carcinoma; x = not reported.

Procedure details

Of those included participants, 225 had flexible ureteroscopy (FURS) and laser stone fragmentation, 19 had URS and stone fragmentation, and 29 had diagnostic URS/FURS with the remaining 779 being unclear whether the patients received semirigid or FURS or both. An access sheath was used in 53% of procedures, and in the three articles assessing the outcome 62% of patients were pre-stented with 67%–100% of patients being stented post procedure. In two of three articles there was no significant change in Hemoglobin (Hb)^12,13 post procedure, but in one the Median postop Hb significantly decreased in anticoagulated patients vs controls (0.8 vs 0.2 g/dL; p = 0.001) (Table 2).⁷

Stone-free rate

Overall stone-free rate across the seven articles which looked at this variable is 90.8% vs 86.2% in the control group (Table 2).

Complications

All articles reported complications as described below.

Major complications

There were two major complications in this series; Watterson and colleagues⁶ reported one case of a large retroperitoneal hemorrhage in a patient who needed concomitant electrohydraulic lithotripsy for stone clearance. Another patient in the series by Elkoushy and coworkers required embolization⁷ (Table 2).

Bleeding-related complications

There were 25 bleeding-related complications in the pooled cohort of patients. This represents a bleeding rate of 2.2%. Of these there were 4 cases of clot retention, 2 cases of clot colic requiring earlier removal of stents, and 16 cases of mild hematuria. There was one case of epistaxis and the above two mentioned cases of major hemorrhage (Table 2).

Intraoperative complications

There were no intraoperative complications in the bleeding diathesis group and one in the control group (proximal ureteral perforation) (Table 2).

Minor complications

There were 16 cases of urinary tract infection or sepsis (1.4%), 18 cases of poorly controlled pain (1.6%), and 1 case (0.09%) each of urinary retention and atrial fibrillation (Table 2).

Thromboembolic episodes

There was one case each of DVT⁷ in the bleeding diathesis group in the control arm¹² (Table 2).

Pooled analysis of total complications

Meta-analysis of six articles with a control arm should prove that overall, there was no significant difference in complications between the bleeding diathesis group and control group (N = 12,757, p = 0.07, 95% confidence interval [CI] 0.92, 6.02, I₂ = 78%) (Fig. 1).

Pooled analysis of bleeding-related complications

Pooled analysis for bleeding-related complications shows a statistically significant difference favoring the control arm (N = 12,757, p ≤ 0.0001, 95% CI 1.81, 5.73, I₂ = 0%) (Fig. 2).

FIG. 2.

Pooled analysis of bleeding-related complications.

Pooled analysis of thrombosis events

Pooled analysis for thrombosis shows no statistically significant difference between the bleeding diathesis group and the control arm (N = 118, p = 0.67, 95% CI 0.23, 9.86, I₂ = 48%) (Fig. 3).

FIG. 3.

Pooled analysis of thrombosis events.

Discussion

Findings of our study

This review has found that the use of URS in patients with anticoagulated or those on APT agents or who have bleeding diathesis is generally safe with comparable stone-free rates to matched controls. While meta-analysis shows no significant difference in overall complication rates, there is a significantly increased bleeding risk. Cumulative analysis shows that the risk of bleeding is more than five times that of controls (2.5% vs 0.42%). There is no difference in the risk of thrombosis.

Current practice

Normalizing coagulopathy before surgery is currently standard practice among surgeons. However, the risk of thromboembolic events during perioperative bridging with heparin is 1%–2%.¹⁴ Furthermore, treating the coagulopathy is significantly more costly compared with patients without coagulopathy undergoing similar procedures; the average cost for URS in patients with bleeding diathesis in one unit in Austria is $4611 vs $2342 control.⁹

Level of evidence and limitations of this review

Only one of the articles in this review is prospective, with the remaining seven being retrospective reports. Therefore, at most this review has a level 2a Levels of Evidence according to Centre for Evidence-Based Medicine.¹⁵ Most of the articles are from single centers with small numbers of patients. A further limitation is the heterogeneity of study population; the majority of patients were on Aspirin with several studies providing insufficient detail on the nature of the bleeding diathesis. Whether such heterogeneity would impact outcomes is not known. All included studies may incur bias as recruitment of patients was from databases in seven of the eight included studies, possibly promoting selection and reporting bias. No studies were randomized. Despite these limitations, the aspiration of this study is to add weight to a previous review based on only 70 patients with a much larger study population of more than 11,000 cases.

Comparison of different studies

Since the previous systematic review on this topic in 2012,⁵ several relevant studies have been published on this topic. Most recently, Westerman and associates retrospectively reviewed 4799 URS procedures, of which 314 were on APTs. The patients were divided into three groups: patients who held APT (234), patients who continued on a single APT (63), and patients who continued on dual APT (17). This review showed that there was no increased risk of bleeding in patients who continued APT; however, patients on dual therapy were more likely to be readmitted within 30 days of discharge than those who withheld APT or were on a single APT.⁴

Daels and colleagues¹⁰ conducted a prospective study which included 11,179 patients who underwent URS for nephrolithiasis. Seven hundred sixty-two of these patients had a coagulopathy; 426 patients were on aspirin, 94 were on clopidogrel, 47 were on acenocoumarol, 41 were on phenprocoumon, and 154 were on other anticoagulants, including calcium carbasalate and nadroparin. Forty-nine (7%) patients on anticoagulants suffered from complications with this group having the highest rate of complication compared with patients with diabetes (5.5%), cardiovascular disease (5%), and obesity (4.9%). Complications included bleeding in eight patients (1.1%). This study found that postoperative bleeding was significantly higher in patients on anticoagulants (1.1% vs 0.4%; p < 0.01) [8/762 vs 44/10,896]. They also found that patients with risk factors for stone formation had more complications than those without (4.9% vs 3.0%, p < 0.001).¹⁰

Toepfer and coworkers¹¹ conducted a retrospective study comprising 646 patients, 176 of whom were on an anticoagulant. One hundred thirty-seven patients were on aspirin, 22 were on warfarin, and 17 were on clopidogrel. Eleven of the patients on warfarin were also on aspirin. These groups were compared with each other and to 470 patients who were not on anticoagulation. Stone sizes were similar between groups with the median size for the control group being 9 mm and for the anticoagulant group being 10.5 mm. Perioperative complications were uncommon, and the frequency was not statistically different among the groups. Of the patients on anticoagulation, 6.8% required repeat surgery compared with 7.2% in the control group. Patients on aspirin were more likely to be admitted within the first 30 days compared with all other groups. Clot retention occurred in only one patient on aspirin (0.56%) compared with two in the control group (0.4%). The study found no difference in bleeding complications among the groups.¹¹

Elkoushy and coworkers⁷ performed a retrospective study, which included 12 patients on anticoagulation undergoing URS and nephrolithiasis. Six patients were on warfarin, three were on aspirin, one was on a combination of aspirin and clopidogrel, one on tinzaparin, and one patient who had cirrhosis with thrombocytopenia. They were compared with a control group of 32 patients. Nine patients underwent nephrolithiasis, and three patients had biopsies. The median stone size was 14 mm. Due to significant stone burden, two of the nine patients had a staged procedure. Therefore, 17 URSs were performed. Two patients developed significant postoperative hemorrhage with one requiring angioembolization. One other patient developed a DVT with pulmonary embolization.⁷

The previous review on this topic had excluded an article by Klingler and associates.⁹ On interrogation, it was felt suitable for inclusion. The authors found no complications in the control arm vs two patients in the anticoagulated group experiencing bleeding necessitating earlier removal of stents.⁹

Recommendations and areas of future research

Overall, this article has added to the previous review by highlighting that the bleeding risk in this cohort of patients is higher than previously documented. While the overall risk of complications is equivalent between patients with bleeding diatheses and controls, the increase in bleeding risk is not insignificant (being fivefold). Fortunately, the vast majority of these events were not significant events with only one reported case of major hemorrhage in a cohort of 1109 patients (0.09%). Until further work is done in this area, a fair conclusion would corroborate that of Jóhann P. Ingimarsson cited in Urology news that the decision to continue anticoagulation or APT agents should be tailored to the patient's risk of a thromboembolic event vs the risk of bleeding associated with URS.^4,16 Indeed, the associated editorial by Brian Matalaga highlights that this trend will continue for the foreseeable future, particularly for those stone patients who must remain anticoagulated meaning they cannot receive PCNL or SWL thereby limiting their treatment options to URS. Matalaga highlights recommendations in the AUA Surgical Management of Stones guidelines, including steps which can be taken to reduce the risk of bleeding, reducing intrarenal pressure through use of an access sheath, nonpressurized irrigation, and bladder decompression with a Foley catheter if an access sheath is not utilized.^8,16

Conclusion

The use of URS with or without the holmium laser is generally a safe and efficient modality for treating patients with urolithiasis who also have a bleeding diathesis or are anticoagulated and or on APT agents. However, this updated review would suggest that in contrast to the previous review in this domain, the increased risk of procedure related bleeding is not insignificant and a patient-centered approach should be taken regarding continuing anticoagulation or APT agents or not correcting bleeding diatheses. While no intraoperative complications were reported in this cohort, higher quality ideally multicenter research is still required to inform future guidelines on this challenging group of patients.

Footnotes

Author's Contributions

A.S. performed literature search and data collection and wrote first draft. T.A. performed literature search, data collection, and meta-analysis and edited first and subsequent drafts. B.K.S. provided academic oversight and edited all drafts. O.M.A. commissioned the article, performed the systematic review of the literature, and edited all drafts. Members of EAU Young Academic Urologists—Endourology and Urolithiasis Working Group are O.M.A. and B.K.S.

Author Disclosure Statement

No competing financial interests exist.

Abbreviations Used

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