Doi:10.1016/j.juro.2007.11.076

Safety and Efficacy of Flexible Ureterorenoscopy and
Holmium:YAG Lithotripsy for Intrarenal Stones in Anticoagulated Cases
Burak Turna, Robert J. Stein, Marc C. Smaldone, Bruno R. Santos, John C. Kefer,
Stephen V. Jackman, Timothy D. Averch and Mihir M. Desai*
From the Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio and Department of Urology, University of
Pittsburgh Medical Center (MCS, SVJ, TDA), Pittsburgh, Pennsylvania
Purpose: We compared perioperative outcomes in patients undergoing ureterorenoscopy and Ho:YAG lithotripsy for renal
calculi with or without anticoagulation.
Materials and Methods: We reviewed the records of all patients undergoing flexible ureterorenoscopy and Ho:YAG
lithotripsy for renal calculi at 2 institutions from 2001 to 2007. We identified 37 patients on anticoagulation with Coumadin®,
clopidogrel or aspirin in whom anticoagulation therapy was not discontinued before surgery. Data on the anticoagulation
group were retrospectively compared to those on a contemporary matched cohort of 37 controls without anticoagulation who
underwent a similar operative procedure. The 2 groups were compared with regard to the stone-free rate, and intraoperative
and postoperative complications with specific reference to bleeding and thromboembolism.
Results: The 2 groups were matched for stone size, stone location, number of stones, bilateral procedures and concomitant
ureteral stones. Anticoagulation group patients were older (58.2 vs 50.4 years, p ϭ 0.0209) and had a greater American
Society of Anesthesiologists score (2.8 vs 1.9, p Ͻ0.0001) compared to the control group. No procedure had to be terminated
in the anticoagulation group due to poor visibility from bleeding. The median postoperative hemoglobin decrease was greater
in the anticoagulation group than in the control group (0.6 vs 0.2 gm/dl, p Ͻ0.0001). The stone-free rate (81.1% vs 78.4%,
p ϭ 0.7725), intraoperative complications (0% vs 3%, p ϭ 0.3140), postoperative complications (11% vs 5%, p ϭ 0.3943) and
hemorrhagic or thromboembolic adverse events were comparable in the 2 groups.
Conclusions: When necessary, ureterorenoscopy and Ho:YAG lithotripsy can be performed safely and efficaciously for renal
calculi in patients on anticoagulation therapy without the need for perioperative manipulation.
Key Words: kidney, kidney calculi, lasers, anticoagulants, endoscopy During the last decade there has been a rapid devel- especially with flexible URS, in patients on AC that is not opment in small caliber flexible URS, Ho:YAG laser discontinued perioperatively. We evaluated the safety and lithotripsy and various ancillary instruments for efficacy of flexible URS and Ho:YAG laser lithotripsy for stone manipulation and Flexible URS is being intrarenal calculi in patients on active oral AC.
increasingly used for a large number of diagnostic and ther-apeutic procedures involving the upper urinary tract, allow-ing the entire renal collecting system to be accessed safely MATERIALS AND METHODS
Stone disease in patients on chronic oral AC therapy Between July 2001 and January 2007, 692 patients were poses a difficult management problem. Many such patients treated with flexible URS and Ho:YAG laser lithotripsy for on chronic AC therapy have multiple associated comorbidi- renal calculi at 2 institutions. Of these patients 37 (5.3%) ties, making perioperative discontinuation of AC therapy were identified who underwent a procedure while on active significantly risky for adverse thromboembolic events. Ther- AC. Chronic AC included Coumadin in 14 patients (37.8%), apeutic modalities, such as extracorporeal shock wave lith- clopidogrel in 5 (13.5%), and 81 and 325 mg oral aspirin in 13 otripsy, percutaneous nephrolithotomy, or laparoscopic or (35.2%) and 5 (13.5%), respectively. Indications for AC were open stone treatment, are contraindicated in patients on coronary artery disease in 8 patients, hyperlipidemia and active AC Flexible URS may be the only surgical hypertension in 7, a mechanical cardiac valve in 5, atrial option available for stone disease. There is a paucity of fibrillation in 4, myocardial infarction in 3, cerebrovascular published information regarding the safety and efficacy, disease in 3, DVT in 2, and lupus anticoagulant, ischemiccolitis, factor V Leiden, total hip replacement and an un-known reason in 1 each The median duration of ACtherapy was 15 months (range 1 to 120).
Submitted for publication August 12, 2007.
Supported by the Scientific and Technological Research Council of Data on the AC group were retrospectively compared to those on a contemporary cohort of 37 control patients not on * Correspondence: Section of Endourology and Stone Disease, AC therapy who underwent flexible URS and Ho:YAG laser Glickman Urological Institute, Cleveland Clinic Foundation, 9500 lithotripsy for intrarenal calculi. Control patients were Euclid Ave. /A100, Cleveland, Ohio 44195 (telephone: 216-445-1185;FAX: 216-445-2267; e-mail:).
matched for stone size, stone location, the number of stones, Copyright 2008 by AMERICAN UROLOGICAL ASSOCIATION DOI:10.1016/j.juro.2007.11.076
FLEXIBLE URETERENOSCOPY FOR INTRARENAL STONES and the chi-square test for categorical data with statistical TABLE 1. Anticoagulation therapy etiology significance considered at p ϭ 0.05.
Compared to the 37 patients in the control group the 37 in the AC group were older (58.2 vs 50.4 years, p ϭ 0.0209) and had a greater American Society of Anesthesiologists score rable in terms of the number of lower pole stones (32% vs 32%, p ϭ 1.0), number of multiple stones (43% vs 46%, p ϭ 0.3636) and concomitant ureteral stones (22% vs 19%, p ϭ 0.7725) requiring simultaneous treatment. The groups were also similar in terms of preoperative flank pain/colic(57% vs 70% of patients), baseline hemoglobin (13.8 vs 13.5gm/dl), baseline serum creatinine (1.0 vs 0.9 mg/dl), a pre- the number of bilateral simultaneous procedures, and the existing Double-J stent (46% vs 35% of patients), renal stone number and size of concomitant ipsilateral ureteral stones.
size (13.2 vs 11.1 mm) and associated ureteral stone size (8.3 Preoperative clotting parameters were available in all pa- vs 6.7 mm) However, clotting parameters, such as tients. Intraoperative and postoperative outcomes were com- prothrombin time (14 vs 10.7 seconds, p ϭ 0.0051), partial pared between the 2 groups. Specifically the groups were thromboplastin time (31.9 vs 28.4 seconds, p ϭ 0.0419) and compared for clotting parameters (normal prothrombin time INR (1.3 vs 0.9, p ϭ 0.0284) were significantly prolonged in less than 13 seconds, normal partial thromboplastin time the AC group compared to those in controls.
less than 34 seconds and normal INR less than 1.1), changes lists perioperative outcomes. A ureteral access in preoperative and postoperative hemoglobin, the stone- sheath was used more frequently (22% vs 3%, p ϭ 0.0128) free rate, and intraoperative and postoperative complica- and mean operative time was significantly longer (69.9 vs tions, including hemorrhagic and thromboembolic adverse 57.8 minutes, p ϭ 0.0146) in the AC group. Intraoperative visibility was satisfactory for allowing successful completion All patients underwent noncontrast computerized tomog- of the procedure in all patients on AC. No patient required raphy before surgery. Any associated ipsilateral ureteral blood transfusion in either group. The median postoperative stones or contralateral renal stones were treated at the same hemoglobin decrease was 0.7, 0.65, 0.3, 0.6 and 0.2 gm/dl in patients on aspirin, Coumadin, clopidogrel and overall AC, All patients underwent flexible URS using a 7.5Fr Karl and in controls, respectively (AC vs control p Ͻ0.0001). The Storz™ 11278 AUA1 Flex-X™, 8.7Fr ACMI™ DUR-8 Elite shows the changes in preoperative and postoperative or 6.9Fr Olympus™ URF-P3 flexible ureterorenoscope. Ure- hemoglobin. No patients in either group experienced major teral balloon dilatation was performed when necessary. A bleeding complications perioperatively. lists detailed ureteral access sheath was used based on individual surgeon hemorrhagic and thromboembolic adverse events.
preference. Lower pole stones were typically relocated to a The single intraoperative complication in the entire more favorable location using a 2.4Fr nitinol basket before series (superficial proximal ureteral perforation) occurred in laser lithotripsy. Ho:YAG laser lithotripsy was performed us- the control group. Four patients in the AC group experi- ing a 200 or 365 ␮m laser fiber set at 10 W (1.0 Joule ϫ 10 Hz).
enced postoperative complications, including macroscopic Stone(s) were completely fragmented into a gravel size of hematuria 3 days or longer in duration in 3 and urinary less than 2 mm. Basket retrieval at the end of laser litho- tract infection in 1, compared to 2 in the control group, tripsy was performed based on individual surgeon prefer- including urinary tract infection and DVT in 1, and severe dysuria in 1. The stone-free rate at 1 month did not differ A systematic inspection of the collecting system was per- significantly among the 4 subgroups or between the 2 groups formed at the end of the procedure to confirm adequate fragmentation. A 6Fr Double-J® stent was routinely in-serted in all patients and removed a minimum of 1 week DISCUSSION
after the procedure. All patients were discharged homewithin 24 hours after the procedure following postoperative Currently there are several alternatives for the surgical hemoglobin determination, urine color assessment and con- treatment of renal and ureteral calculi. Factors such as firmation of stable vital signs. Any residual fragment stone characteristics, anatomical detail, patient factors and greater than 2 mm on postoperative computerized tomogra- surgeon preference typically determine the choice of surgical phy followup at 1 month was considered treatment failure.
Summary statistics are reported using the mean or me- Uncorrected bleeding diathesis is an absolute contraindi- dian for continuous variables and percents for categorical cation to stone treatment with shock wave lithotripsy, per- variables. Statistical comparison of the 2 groups (AC vs cutaneous nephrolithotomy, open surgery or control) was performed using the Wilcoxon rank sum test for Several indications, therapeutic goals and recommended du- continuous data and the chi-square test for categorical data rations of therapy exist for the use of aspirin, clopidogrel and with SPSS® software. For further analysis the 4 subgroups Coumadin. The prevention of thromboembolic complications (Coumadin vs clopidogrel vs aspirin vs control) were also from DVT, atrial fibrillation, valvular heart disease and compared using the Kruskal-Wallis test for continuous data coronary stenting are the main indications for AC therapy, FLEXIBLE URETERENOSCOPY FOR INTRARENAL STONES No. pts with associated ureteral stones (%) * Kruskal-Wallis test for continuous data and chi-square test for categorical data.
† Wilcoxon rank sum test for continuous data and chi-square test for categorical data.
which often requires long-term or indefinite Coumadin The decision to stop/modulate chronic AC therapy preop- and aspirin were shown to dramatically decrease the risk of eratively depends on the etiology requiring AC and the sub- stroke with a pooled relative risk reduction of 68% and 21%, sequent risk of stopping AC therapy. This issue is becoming respectively, compared to that in an untreated group of more relevant in patients who have drug eluting vascular patients with atrial The rate of recurrent DVT stents that necessitate some form of AC therapy, potentially in patients at high risk for DVT without AC is 7.2% per lifelong, to minimize the risk of stent thrombosis.
Arnold et al reported that physicians could have pre- Major concerns of discontinuing and re-initiating AC vented 17.4% of 253 episodes of venous thromboembolism if therapy in patients at high risk are 3-fold. 1) During the they had applied adequate prophylaxis according to the rec- correction of bleeding diathesis patients requiring AC are at ommended Aspirin decreases the risk of death risk for thromboembolic events. 2) Drug therapy need not be after myocardial infarction and decreases mortality in those altered, which provides greater simplicity of the medication at high risk for cardiovascular disease, ie previous angina, regimen and likely improves compliance in elderly patients stroke or a transient ischemic Similarly the oral with common polypharmacy. 3) The expense of bridging antiplatelet agent clopidogrel has been widely used predom- therapy (temporary use of intravenous unfractionated hep- inately as adjunct therapy to prevent subacute thrombosis arin or low molecular weight heparin) is considerable. In our experience referring physicians are increasingly reluctant todiscontinue AC even temporarily.
* Wilcoxon rank sum test for continuous data and chi-square test for FLEXIBLE URETERENOSCOPY FOR INTRARENAL STONES Certain technical details may be of even greater impor- TABLE 4. Hemorrhagic and/or thromboembolic related adverse tance during ureteroscopy in patients on AC. If there is events in patients undergoing flexible URS and Ho:YAG laser lithotripsy on active oral AC vs controls difficulty in inserting the ureteroscope, or accessing orfragmenting a stone, or if there is bleeding that impedes visibility, there should be a lower threshold for placement of an indwelling stent and planning for stage 2 URStreatment. Also, no procedure should be performed with- out having fluoroscopy and a safety guidewire to maintain ureteral access. Lastly, familiarity with and the availabil- ity of appropriate endoscopes and ancillary instruments Ureteral access sheaths were used in 8 patients and ureteral balloon dilatation was done in 1 without anyhemorrhagic complications, confirming their safety in pa- No patients had clot retention, blood transfusion, discharge home with anindwelling stent, reoperation or conversion to open surgery.
tients on AC. Of all intracorporeal lithotriptors the Ho: * Urinary tract infection and DVT in the same patient.
YAG laser provides the ability to fragment stones of anycomposition with minimal The preciseablation, decreased collateral damage and hemostatic ef-fects of laser energy make it an ideal method in patients Flexible URS with laser lithotripsy remains the only on active AC. Nevertheless, special care should be exer- potential surgical treatment alternative in patients on AC in cised while using the Ho:YAG laser in anticoagulated whom therapy cannot be discontinued perioperatively. How- cases and attempts to minimize contact with the mucosa ever, due to the paucity of published data on the safety and efficacy of flexible URS and laser lithotripsy in patients on To our knowledge this is the largest study assessing active AC urologists may be hesitant to proceed with defin- the safety and efficacy of flexible URS in anticoagulated itive treatment. In our study we noted that despite active AC cases. Nevertheless, a sample size of 37 patients may be patients were not at increased risk for associated intraoper- underpowered for detecting clinically significant differ- ative (0% vs 3%) or postoperative (11% vs 5%) complications ences, specifically between the 4 subgroups. As such, there and stone-free rates were comparable to those in patients were 18 patients in the aspirin group, 14 in the Coumadin undergoing flexible URS and laser lithotripsy without AC group and only 5 in the clopidogrel group. This limitation (81.1% vs 78.4%). A concern, especially with flexible ureter- should be considered when interpreting our results.
oscopy due to lower irrigant flow and optical resolution com-pared to those of semirigid ureteroscopy, is the impact of ACtherapy on oozing and intraoperative visibility. In this re- CONCLUSIONS
gard in our study no procedure had to be prematurely ter-minated because of poor visibility from bleeding. Neverthe- URS and Ho:YAG laser lithotripsy can be performed safely less, there was a significant increase in operative time (69.9 and effectively for intrarenal stones in anticoagulated cases.
vs 57.8 minutes) and a greater, though clinically insignifi- Our data suggest no increased risk of hemorrhagic adverse cant decrease in hemoglobin in the AC group compared to events or decreased stone-free rates when compared to those in a matched cohort group undergoing URS and Ho:YAG This comparative study attests to the technical feasibil- laser lithotripsy. Thus, it should be considered the ideal ity, effectiveness and safety of flexible URS and Ho:YAG treatment modality in this setting without discontinuing laser lithotripsy in patients on active AC. Our findings con- and re-initiating AC. This may further increase the already firm the 2 available descriptive studies in the literature in growing popularity of retrograde intrarenal surgery for an objective manner. Kuo et al first reported the safety and efficacy of ureteroscopy and holmium laser treatment in 6patients receiving Coumadin, 2 with thrombocytopenia and1 with von Willebrand’s In the study 8 patients Abbreviations and Acronyms
had upper tract calculi and 1 had transitional cell carci-noma. Only 1 patient had a postoperative bleeding compli- cation, which resolved without surgical intervention. None of the bleeding diatheses were corrected before surgery.
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