Holmium Laser Enucleation of the Prostate in Patients Requiring Anticoagulation

Abstract

Introduction:

Holmium laser enucleation of the prostate (HoLEP) is a well-established technique for the surgical management of benign prostatic hyperplasia (BPH). A significant number of patients who require surgery for BPH are being treated with anticoagulation (AC) or antiplatelet (AP) therapy. We evaluated the efficacy and morbidity of HoLEP in this population.

Materials and Methods:

One hundred sixteen patients who required AC/AP therapy undergoing HoLEP from 1999 to 2014 were compared with 1558 HoLEP patients who were not on AC/AP therapy (no AC/AP). Patients on intermittent vs continuous AC/AP therapy were also compared.

Results:

No significant differences in preoperative characteristics were found between patients who did and did not receive AC/AP therapy. Intraoperative characteristics were similar except for enucleation time (51 minutes vs 65 minutes, AC/AP vs no AC/AP, respectively, p < 0.001) and morcellation rate (5 g/min vs 4.5 g/min, AC/AP vs no AC/AP, respectively, p = 0.02). Postoperative outcomes were comparable in all aspects except for length of hospital stay (27.8 hours vs 24 hours, p < 0.001) and duration of continuous bladder irrigation (15 hours vs 13.5 hours, p < 0.001), both of which were longer in the AC/AP group.

There was no difference between cohorts in the lowest postoperative hemoglobin or transfusion rate. Two patients (1.9%) in the AC/AP cohort required clot evacuation vs 10 patients (0.7%) in the no AC/AP cohort. Pre-, intra-, and postoperative characteristics between patients on continuous vs intermittent AC/AP were not statistically significant, except for specimen weight (55.5 g vs 74.5 g, p = 0.028), which was greater in the intermittent AC group.

Conclusion:

Other than slight prolongation of duration of bladder irrigation and hospital stay, the intermittent or continuous use of anticoagulant therapy did not adversely affect outcomes of HoLEP, suggesting that this approach is an attractive approach for such patients, especially when the prostate is extremely large.

Introduction

Benign prostatic hyperplasia (BPH) is a common disease in men older than 50 years of age. Up to 50% of men in their sixth decade have BPH and this rate increases with age.¹ The prevalence of cardiovascular events also increases with age: 83.6 million people in the United States have cardiovascular disease.² Recent advances in coronary stents have made the stents more popular for selected cases than traditional coronary artery bypass grafts, and this has led to more patients being on antiplatelet (AP) therapy.³ Discontinuation of AP or anticoagulation (AC) therapy can lead to drastic thromboembolic events, especially in high-risk patients such as those with drug-eluting coronary stents, mechanical heart valves, recent pulmonary embolism, or atrial fibrillation with prior cerebral ischemia.⁴ Therefore, patients with concomitant BPH and cardiovascular disease who require some form of AC or AP therapy are prone to more complications, adding to the economic impact of the already huge cost of BPH management, which exceeds 4 billion dollars annually.⁵

Both transurethral resection of the prostate (TURP) and open prostatectomy can be associated with excessive bleeding that may require prolonged catheterization, longer bladder irrigation, and transfusion rates as high as 22% in several TURP meta-analysis studies.^6
–8 These risks will be elevated for patients on AC/AP therapy. Descazeaud and colleagues recognized oral AC as the sole, independent parameter associated with bladder clots and late hematuria following TURP.⁹

Since the introduction of holmium laser enucleation of the prostate (HoLEP) in the late 1990s,¹⁰ HoLEP has increased in popularity for the management of BPH.^11
–13 Evidence suggests that HoLEP provides superior short- and long-term improvement in men with BPH, regardless of prostate size^14,15 and is also associated with a lower risk of bleeding and blood transfusion.¹⁶

As a tertiary referral center, we encounter a significant number of patients with BPH mandating surgical intervention who also require AC or AP therapy. For these patients, withholding AC or AP therapy pre- and perioperatively may not be feasible. The aim of this study is to evaluate the safety and efficacy of HoLEP in men on AC/AP therapy and compare this cohort to our overall database.

Materials and Methods

Patients, outcomes, and variables

After obtaining institutional review board (IRB) approval, we conducted a retrospective cohort analysis using the prospectively collected Indiana University Health Methodist Hospital database to identify patients who underwent HoLEP between 1999 and 2014. Patients who required intermittent or continuous AC/AP therapy were identified and their cases were reviewed and compared with the overall database cohort.

The HoLEP database was used to identify 116 patients who were taking aspirin (325 mg), Plavix, Aggrenox, Pradaxa, Lovenox, or Coumadin. Both chart and database reviews were done on each of the patients to confirm use of AC/AP. Those on a full dose of the aforementioned drugs were considered part of the AC/AP group. Patients on 81 mg of aspirin (the amount in baby aspirin) were excluded from the AC/AP group. The 116 patients who were in the AC/AP cohort were retrospectively compared with the 1558 patients who underwent HoLEP and were not on AC/AP therapy. Patients were also divided into continuous vs intermittent AC/AP groups and compared with each other. The continuous AC/AP group was defined by patients whose AC/AP therapy was not interrupted pre-, peri-, and/or postoperatively. The intermittent AC/AP group was defined by patients who discontinued AC/AP therapy preoperatively and then restarted the therapy, usually 1 week postoperatively. Pre-, intra-, and postoperative variables were analyzed to determine the efficacy, safety, and morbidity. The majority of the surgeries were performed by a single experienced surgeon (JEL).

The methods and HoLEP surgical procedure have been previously described.¹⁷ A 28F continuous flow resectoscope (Karl Storz Endoscopy, Culver City, CA) with a laser bridge that houses a 7F stabilizing catheter (Cook Medical, Spencer, IN) is used to enucleate the prostate by engaging a 100 W Ho:YAG laser source configured with a 550-micron end-fire laser fiber. In all cases, physiologic saline is used as the irrigant. Briefly, the enucleation requires laser settings of 2 J and 40 to 50 Hz for the lateral lobes, 2 J and 20 Hz for the apical dissection, and 2 J and 20 Hz to divide the apical mucosal bridges. At the conclusion of enucleation, tissue morcellation is performed using a Storz nephroscope, which permits the introduction of a prostate morcellation device (PMD) into the bladder. Morcellation is conducted using dual irrigation under endoscopic view that must be adequate to prevent bladder injuries. During this step, the aperture of the PMD needs to be seen at all times to minimize any possible bladder injury.

The postoperative protocol of patient care includes insertion of a 22F, 3-way Foley catheter with or without traction. Continuous bladder irrigation is continued overnight as needed and weaned gradually. The Foley catheter is removed at 4 a.m. the following morning and the patient is discharged after voiding two times.

Results

Comparing AC/AP to no AC/AP cohorts

Pre-, intra-, and postoperative characteristics are summarized in Table 1. Both cohorts were similar in terms of preoperative prostate-specific antigen (PSA), American Urological Association System Score (AUASS), postvoid residual (PVR) urine volume, and preoperative hemoglobin (Hgb) levels. Intraoperative characteristics were also comparable in all aspects except enucleation time, which favored the AC/AP cohort (51 minutes vs 65 minutes, respectively, p < 0.001), and the morcellation rate, which also favored the AC/AP cohort (5 g/min vs 4.5 g/min, respectively, p = 0.022).

Table 1.

Anticoagulated vs Nonanticoagulated Patients

	Anticoagulated		Nonanticoagulated
	n		n		p
Preoperative characteristics
PSA	78	5.5 (0.2–121.0)	1308	5.2 (0.04–1600)	0.751
AUASS	67	19 (4–35)	1163	21 (0–35)	0.480
PVR	58	199.5 (0–1900)	892	134.5 (0–5000)	0.032
Preoperative Hgb	114	13.9 (8.3–17.3)	1233	14.3 (3.8–18.9)	0.007
Intraoperative characteristics
Specimen weight (g)	114	69.5 (1–285)	1514	68 (0.2–532.2)	0.752
Enucleation time (minutes)	116	51 (12–119)	1455	65 (8–350)	<0.001
Enucleation rate (g/min)	114	1.2 (0.1–5.2)	1411	1.0 (0.01–8.1)	0.006
Morcellation time (minutes)	112	13 (2–75)	1326	15 (1–290)	0.107
Morcellation rate (g/min)	110	5 (1.4–18)	1312	4.5 (0.2–31.5)	0.022
Postoperative outcomes
Hospitalization (hours)	116	27.8 (8–192)	1521	24 (2–600)	<0.001
Length of CBI (hours)	110	15 (4–48)	1003	13.5 (0–65)	<0.001
Catheterization (hours)	109	15.5 (6–168)	1075	15 (1–310)	0.337
Lowest postoperative Hgb	113	12.3 (6.3–15.9)	1120	12.6 (3.6–17.0)	0.006
Transfusion	116	4 (3.5%)	1558	25 (1.6%)	0.128
Reoperation (1 month)	107	2 (1.9%)	1475	10 (0.7%)	0.192
Complications	116	2 (1.6%) urosepsis hyponatremia	1558	8 (0.5%) fever, urosepsis (3), pleural effusion, PE, ARF, AF
PVR (1 month)	54	11.7 (0–200)	608	13.8 (0–560)	0.540
PVR (6 months)	5	6 (0–76.4)	228	19.6 (0–550)	0.674
AUASS (1 month)	82	11 (0–25)	1028	7 (0–35)	0.008
AUASS (6 months)	53	5 (0–22)	642	4 (0–31)	0.992
PSA (6 months)	35	0.8 (0.02–3.8)	661	0.7 (0–66)	0.648
Pathology	116		1558		0.612
Benign		104 (89.7%)		1420 (91.1%)
Malignant		12 (10.3%)		138 (8.9%)

Continuous variables summarized using median (min–max) and compared between groups using Wilcoxon rank-sum tests. Categorical variables summarized using count (percent) and compared between groups using Fisher's exact tests.

AF = atrial fibrilation; ARF = acute renal failure; AUASS = American Urological Association System Score; CBI = continuous bladder irrigation; Hgb = hemoglobin; PE = pulmonary embolis; PSA = prostate-specific antigen; PVR = postvoid residual.

Postoperative characteristics were also similar in all aspects except for length of hospital stay (LOS), which favored the no AC/AP cohort (27.8 hours vs 24 hours), and the duration of continuous bladder irrigation (CBI), which also favored the no AC/AP cohort (15 hours vs 13.5 hours); both were statistically significant (p < 0.001). There was no difference in terms of catheterization time or lowest postoperative Hgb level. Transfusion rates were 3.5% vs 1.6%, for the AC/AP and the no AC/AP cohort, respectively (p = 0.128).

Both cohorts were similar in regard to postoperative PSA value, PVR, and AUASS at 1 and 6 months (Table 1). In the AC/AP cohort, 2 patients (1.9%) required clot evacuation vs 10 patients (0.7%) in the no AC/AP cohort.

Comparing continuous to intermittent AC/AP cohorts

Preoperative characteristics were similar, including PSA, AUASS, PVR, and Hgb. Intraoperative characteristics were also similar in all aspects except for specimen weight, which was 55.5 g vs 74.5 g for the continuous and intermittent AC/AP cohort, respectively (p = 0.028). Postoperative characteristics were also similar in all aspects with no statistical significance. Transfusion rates were 6.7% vs 2.32% for the continuous and intermittent AC/AP cohort, respectively (p = 0.27) (Table 2).

Table 2.

Continuous Anticoagulation vs Intermittent Anticoagulation

	Continuous anticoagulation		Intermittent anticoagulation
	n		n		p
Preoperative characteristics
PSA	18	4.3 (1–15.7)	60	5.8 (0.2–121)	0.371
AUASS	16	19.5 (9–29)	51	19 (4–35)	0.866
PVR	13	150 (0–1000)	45	250 (0–1900)	0.213
Preoperative Hgb	29	13.5 (9.7–16.8)	85	14 (8.3–17.3)	0.222
Type of anticoagulation	30		86
Aggrenox		1		1
ASA		9		39
Plavix		10		36
Coumadin		15		35
Pradaxa		3		2
Lovenox		2		0
INR value for Coumadin patients	12	1.47 (1–2.19)^a	32	1.2 (0.9–2.2)	0.008
Intraoperative characteristics
Specimen weight (g)	30	55.5 (1–206)	84	74.5 (5–285)	0.028
Enucleation time (minutes)	30	47.5 (20–105)	86	53.5 (12–119)	0.182
Enucleation rate (g/min)	30	1.1 (0.1–3.8)	84	1.2 (0.1–5.2)	0.120
Morcellation time (minutes)	28	10 (2–42)	84	13.5 (2–75)	0.086
Morcellation rate (g/min)	28	5.3 (1.9–12.2)	82	4.9 (1.4–18)	0.430
Postoperative outcomes
Hospitalization (hours)	30	30.5 (17–156)	86	27 (8–192)	0.052
Length of CBI (hours)	28	15.5 (6–48)	82	14.8 (4–38)	0.458
Catheterization (hours)	28	16.3 (11.5–125)	81	15 (6–168)	0.481
Lowest postoperative Hgb
Transfusion	30	2 (6.7%)	86	2 (2.32%)	0.27
Reoperation (1 month)	27	1 (3.7%)	80	1 (1.3%)	0.443
PVR (1 month)	15	5.3 (0–90)	39	12.9 (0–200)	0.901
PVR (6 months)	1	0 (0–0)	4	40.8 (0–76.4)	0.600
AUASS (1 month)	21	10 (2–25)	61	11 (0–25)	0.790
AUASS (6 months)	10	3.5 (1–9)	40	5 (0–19)	0.536
PSA (6 months)	9	0.7 (0.02–1.1)	26	0.8 (0.2–3.8)	0.254
Pathology	30		86		0.729
Benign		28 (93.3%)		76 (88.4%)
Malignant		2 (6.7%)		10 (11.6%)

Coumadin was not or was held for 1–3 days preoperatively and restarted back immediately or 1–3 days postoperatively.

ASA = acetylsalicylic acid; INR = international normalized ratio.

Discussion

As the patient population ages, the incidence of cardiovascular events will increase and, therefore, AC/AP therapy will become more prevalent. Studying different techniques and their safe use for the surgical treatment of BPH in this population is essential. Our study highlights the safety, efficacy, and outcomes of AC/AP therapy with HoLEP.

When comparing the results of our study to conventional TURP in patients on AC therapy, there is a significant difference in terms of LOS and clot retention, which favored HoLEP. Michielsen and colleagues studied 176 patients who underwent either monopolar or bipolar TURP. The average LOS for the procedures was 4.91 and 4.35 days and average catheterization times were 1.77 and 1.79 days, respectively. Clot retention in this series ranged from 13% to 15%, which is high when compared with our results.¹⁸ Descazeaud and colleagues studied 206 patients who underwent TURP on oral AC therapy and reported an average LOS of 6.4 days with clot retention occurring in 13%.⁹ Chakravarti and MacDermott studied 11 patients on oral AC therapy who underwent TURP and reported an average LOS of 6.7 days and three readmissions secondary to hemorrhage.¹⁹ These data are extremely valuable when calculating healthcare costs, in which each added hospital day results in an additional financial burden to the patient and healthcare system.²⁰ In the studies mentioned earlier, the average weight of resected prostate tissue was 19.4 to 23.2 g. Comparing these results to our own, in which the average weight was 69.5 g, shows the advantages of the HoLEP procedure over conventional and bipolar TURP.

Some reports have studied HoLEP in patients on AC/AP. Tyson and colleagues studied 39 patients who underwent HoLEP on either aspirin (acetylsalicylic acid, ASA) or Coumadin and showed an excellent safety profile. No patients received a blood transfusion and only 8% experienced significant hematuria and readmission. Interestingly, the length of catheterization was longer than in our series (2.6, 2.2, and 1.9 days in the control, Coumadin, and ASA groups, respectively).²¹ Elzayat and colleagues also showed a similar safety and results profile on 83 patients receiving AC therapy. However, there were some postoperative differences when compared with our series: hospital stay (2.5 days), catheterization time (2.2 days), and blood transfusions (8.4%).²² Bishop and colleagues studied 52 patients who underwent HoLEP on antithrombotic therapy. Similar safety and efficacy were achieved with a median LOS of 2 days and a transfusion rate of 7.7%.²³ The reason for this variation in postoperative characteristics is unclear. Likely, our protocol was more aggressive in terms of catheter removal and patient discharge. Regardless, in all studies, hospital stay and catheterization time were significantly decreased when compared with published data for TURP patients on AC/AP therapy.

Clinically, in our population, little difference in intraoperative and postoperative outcomes was seen between the AC/AP and no AC/AP group. Interestingly the AC/AP group had shorter enucleation times than the no AC/AP group. This may be due to greater staff involvement while treating a higher risk patient.

Specimen weight was on average 55.5 g vs 74.5 g in the continuous and intermittent AC/AP cohorts, respectively (p = 0.028); the smaller weight likely accounts for the decreased enucleation and morcellation times. Smaller prostates were seen in the continuous AC group, which may be due to the reluctance of referring physicians to perform TURP on these patients resulting in their referral for HoLEP. The AC/AP cohort did have a slightly higher transfusion rate than the control group but this was not statistically significant. Patients in the AC/AP group had longer hospital stays and increased length of CBI and catheter time on average. However, most of these patients were still able to be discharged on postoperative day 1 with catheterization and CBI times only a few hours longer. Technically, the ability to perform HoLEP on patients with intermittent or continuous AC/AP was feasible and safe with operative time, PVR, and PSA comparable to patients in the no AC/AP group. The 1-month AUASS was higher in the AC group, and this may be secondary to the irritative symptoms associated with the low-level bleeding and passing small blood clots shortly postoperatively; however, the 6-month AUASS is comparable between both cohorts. Recent publications have suggested that bridging AC may be associated with increased risk of significant bleeding events.²⁴ Because of such concerns, it has been our custom to leave patients on their anticoagulants when HoLEP is required rather than doing bridging. We believe that this approach is justified by the data presented herein.

This study is not devoid of limitations. It is retrospective in nature, although the data are collected in a prospective manner to minimize bias. However, because patient information was entered into the database during a span of 15 years, differences in patients and techniques may exist. Despite these limitations, this study is the largest series to date to focus on the safety and efficacy of HoLEP in patients receiving AC/AP therapy.

Conclusions

HoLEP is a safe and effective technique for the surgical treatment of BPH in patients receiving AC or AP therapy, particularly when the prostate is extremely large.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Abbreviations Used

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