Department of Urology, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu Province, 226200, People’s Republic of China

Correspondence: Jian-Gang Chen, Department of Urology, Affiliated Hospital 2 of Nantong University, No. 666 Victory Road, Chongchuan District, Nantong, Jiangsu Province, 226200, People’s Republic of China, 226200, Tel +862115996558081, Email [email protected]

Objective: To compare low- vs high-power HoLEP effects on coagulation in patients on antiplatelet (AP) therapy via thromboelastography (TEG).
Methods: 210 patients was retrospectively analyzed and stratificated into three discrete groups, specifically: Group A (AP therapy, high-power HoLEP, n = 72); Group B (AP therapy, low-power HoLEP, n=73); Group C (no AP therapy, low-power HoLEP, n = 65). Baseline characteristics and coagulation profiles via TEG were compared. Univariate and multivariate analyses were conducted to identify independent risk factors associated with hematuria. Furthermore, parameters such as IPSS, Qmax, post-void residual volume V2 and PSA levels were recorded during 1year follow-up.
Results: No differences in terms of baseline characteristics across all groups. Significant differences were observed in the duration of enucleation, morcellation, bladder irrigation, post-operative catheterization, length of hospital stay and the extent of hemoglobin reduction (F = 54.06, 8.54, 6.68, 9.24, 17.06, 5.97, p 12 = 1.082 ; x22 =  0.197,; x32 =  3.981;x42 =  0.816, p >  0.05). Univariate and multivariate analyses revealed that prostate volume emerged as an independent risk factor for hematuria (OR 1.080, 95% CI: 1.007– 1.158, p =  0.031). Clinical outcomes including Qmax, IPSS, V2, and PSA demonstrated significant enhancement during 1 year follow-up.
Conclusion: Compared to HP-HoLEP, LP-HoLEP effectively reduces surgical and subsequent processing times, decreases hospital stay duration, and diminishes hemoglobin decline, offering a viable option without discontinuing AP therapy.

Introduction

The prevalence of lower urinary tract symptoms attributed to benign prostatic hyperplasia (LUTS/BPH) is on the rise, particularly within the aging demographic.1 This cohort of patients often presents with concomitant cardiovascular diseases, necessitating ongoing antiplatelet (AP) therapy.2 Continuous administration of AP agents has demonstrated efficacy in reducing the incidence of cardiovascular events such as coronary heart disease, stroke, and venous thrombosis.3,4 However, it poses a substantial risk for bleeding complications in the context of standard transurethral resection of the prostate (TURP).5,6 Zheng et al confirmed that persistent use of antithrombotic medications significantly elevates the risk of bleeding, necessitating blood transfusion, bladder tamponade, and acute urine retention.7 Consequently, addressing benign prostatic hyperplasia (BPH) in such patients poses a pertinent challenge for urologists, as discontinuation of AP therapy may heighten the risk of cardiovascular events. Meanwhile, prolonged lithotomy position can increase the probability of lower limb thrombosis.8 Therefore, it is particularly important to find a reference standard for balancing the risk of bleeding and thrombosis.

In recent years, thromboelastography (TEG) has been employed as a reference approach for assessing coagulation throughout all phases of clot formation and evaluating inherited bleeding disorders9, especially for the long-term administration of oral anticoagulants in patients with coronary syndrome,10 as well as for perioperative prevention of lower limb venous thrombosis in trauma patients.11 Jan Hartmann employed thromboelastography for cardiovascular disease management in knowing individual reactivity at these stages when prescribing or when trying to assess risk of bleeding or thrombotic events.12 Lin C et al has also used TEG to monitor the hemocoagulase effects of blood coagulation status in patients after thoracic surgery.13 Therefore, incorporating TEG into clinical practice is of great significance in assessing the risk of bleeding and thrombosis in patients undergoing prostate hyperplasia surgery who are on antiplatelet therapy.

Holmium laser enucleation of the prostate (HoLEP) has emerged as a safe and effective intervention for BPH, and is particularly recommended for patients concurrently on AP medications.14 Notably, transfusion rates in patients undergoing HoLEP while on AP therapy remain below 3%.15 However, despite its proven efficacy, the widespread adoption of HoLEP faces hindrances due to its extended learning curve and the considerably higher cost of high-power holmium laser equipment, which is nearly three times that of low-power alternatives. Additionally, the technical challenges associated with high-power HoLEP (HP-HoLEP), including the risk of capsular perforation and reduced visibility, further limit its broader application.16 In response to these challenges, the use of low-power holmium lasers has gained prominence. Studies conducted by Shah and Becker et al have affirmed the superiority of low-power holmium laser enucleation of the prostate (LP-HoLEP) in terms of hemostasis.17,18 Minagawa demonstrated comparable safety and outcomes with the use of a low-power laser, providing the added benefit of reduced operative time, thus positioning it as a potential alternative treatment for BPH.19

Conventionally, the general recommendation has been to discontinue AP agents prior to surgery. While LP-HoLEP has demonstrated feasibility and safety in general, there is a lack of compelling evidence specific to patients requiring continuous AP therapy.20 Building upon prior research establishing the safety and efficacy of LP-HoLEP, the objective of this study is to compare the results of low- and high-power HoLEP in patients undergoing continuous antiplatelet (AP) therapy through thromboelastography TEG evaluation.

Methods Study Population

The analysis focused on patients with a medium-sized prostate (30–80 grams) who underwent HoLEP and were on aspirin/clopidogrel therapy. The analysis covered the period from March 2019 to March 2022 . For the purposes of this study, AP therapy was defined as the daily intake of aspirin/clopidogrel for a minimum duration of one year.21 This study included a cohort of 220 patients, out of which 10 were lost to follow-up due to discontinuation of antiplatelet therapy before operation. Group A comprised 72 patients receiving AP therapy and undergoing high-power HoLEP; Group B included 73 patients on AP therapy undergoing low-power HoLEP; and Group C consisted of 65 patients not on AP therapy and undergoing low-power HoLEP. The coagulation status of the patients was evaluated using thromboelastography (TEG). The TEG tracings revealed prolonged R times, suggesting factor deficiency and/or the presence of heparin, and reduced maximum amplitude (MA), indicating defects in platelet function.22,23 Clinical data, including age, hemoglobin (HB), prostate volume (V1), International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), prostate-specific antigen (PSA), platelet count (PLT), MA, enucleation time, morcellation time, bladder irrigation, postoperative catheterization time (PCT), length of hospital stay (LOS) and hemoglobin drop (HBD), were collected for analysis.

All operations were performed under general anesthesia by an experienced surgeon (engaged in enucleation of prostate for 5 years and more than 200 cases have been enucleated). Inclusion criteria comprised of a medium-sized prostate, Qmax < 15 m/s, and IPSS >7. Exclusion criteria included the presence of bladder calculus, neurogenic bladder, and prostate cancer. Prostate weight and volume were examined using transrectal ultrasound scan (TRUS) and calculated using the formula—volume = upper and lower diameter x antero-posterior x left and right diameter x 0.52, weight = volume x 1.05). Patients underwent both LP-HoLEP (40 W, 1J x 40 Hz) and HP-HoLEP (100W, 2J x 50 Hz) procedures. A 550 μm laser fiber (SlimLine, Lumenis Ltd, Yokneam, Israel) was used with a 120 W Holmium neodymium: YAG laser (VersaPulse PowerSuite, Lumenis Ltd). Both procedures were conducted using a 26F continuous-flow laser resectoscope with a video system (Karl-Storz, Germany) and a mechanical tissue morcellator (DPM-3-A, Dahwa, China).

Statistical Analysis

SPSS version 22.0 was used for the execution of statistical analyses. Continuous variables were delineated as means ± standard deviation (SD) or as median values with interquartile range (IQR) based on their distribution. The Kruskal–Wallis test and one-way analysis of variance (ANOVA) were used for the analysis of continuous variables, while the chi-squared test was applied for categorical variables. Univariate and multivariate analyses were conducted to ascertain independent risk factors for hematuria. The association of categorical parameters was estimated with a 95% confidence interval. All statistical tests were two-sided, and a significance level of p < 0.05 was set.

Results

Table 1 presents a summary of the basic clinical data. There was no difference in terms of age, HB, V1, IPSS, Qmax, PSA, PLT, MA among all groups. However, there were notable discrepancies in enucleation, morcellation, bladder irrigation, post-operative catheterization time, the LOS, and hemoglobin drop among all groups, with statistical significance (F=54.06, 8.54, 6.68, 9.24, 17.06, 5.97, p < 0.05). As indicated in Table 2, there were no discernible differences in postoperative hematuria, urine retention, the rate of transfusion, and stress urinary incontinence (x2 = 1.082, p = 0.582; x2 = 0.197, p = 0.906; x2 = 3.981, p = 0.137; x2 = 0.816, p = 0.665). Univariate and multivariate analyses, as presented in Table 3, revealed that prostate volume emerged as an independent risk factor for hematuria (odds ratio [OR] 1.080, 95% confidence interval [CI]: 1.007–1.158, p = 0.031 < 0.05) (Figure 1). The clinical outcomes including Qmax, IPSS, V2, PSA were significantly enhanced during the 1-year follow-up (Figure 2).

Table 1 Clinical Basic Data

Table 2 Postoperative Complications

Table 3 Logistic Regression Models Predicting the Occurrence of Hematuria

Figure 1 Forest plot about multivariate logistic regression analyses of factors related to hematuria V1, prostate volume. PLT, Platelet. MA, Maximum amplitude. LP vs HP, LP-HoLEP vs HP-HoLEP. WA/CA, without Aspirin/clopidogrel/continuous Aspirin/clopidogrel.

Figure 2 Clinical outcomes including Qmax, IPSS, V2, and PSA Qmax, maximum urinary flow rate. IPSS, International Prostate Symptom Score. V2, post-void residual volume. PSA, prostate-specific antigen.

Discussion

HoLEP has evolved as a well-established and minimally invasive alternative for patients undergoing AP therapy, particularly those with large prostates.24,25 The feasibility and safety of HoLEP in patients on non-vitamin K antagonist oral anticoagulants (NOAC) or AP therapy have been demonstrated,26,27 with patients exhibiting prostate sizes up to 105.8 ml, albeit with an increased risk of hematuria in cases of very large prostates.10,28 Consequently, we opted for patients with medium-sized prostates as the focus of this study.

Initially, differences in preoperative characteristics between Group B and Group C were identified, highlighting the impact of Aspirin/clopidogrel intake on the surgical context. Subsequently, from our findings, we discovered that LP-HoLEP resulted in decreased enucleation, morcellation, bladder irrigation, postoperative catheterization duration, the length of hospital stays, and hemoglobin drop compared to HP-HoLEP. We attributed this superiority of LP-HoLEP to its efficacy in facilitating efficient vessel coagulation.29

Hematuria emerged as the most prevalent complication, particularly in patients with continuous AP therapy. Persistent or delayed postoperative bleeding, in some cases, correlated with a preoperative hypercoagulable state.30 TEG was used to unveil coagulation defects challenging to detect through routine laboratory tests. Prior studies have associated a TEG MA value above 68 mm with an increased likelihood of postoperative thrombotic events.31 In this study, no disparities in MA were observed among the groups, as antiplatelet therapy exhibited a low inhibitory rate on platelet aggregation. In this study, the MA values for all groups were below 68 mm, and the platelet counts remained within an acceptable range. This further demonstrates that Through the enhancement of the TEG examination, patients who are unsuitable for surgery due to long-term oral antiplatelet therapy can be identified and excluded. Simultaneously, there is no longer a need to discontinue antiplatelet medication in cases where platelet count and aggregation functions remain within normal parameters, as the approach now has greater support evidence.

Furthermore, there were no discernible differences in postoperative hematuria, hemorrhage, and transfusion rates, aligning with reported probabilities in the literature. Logistic regression models predicting hematuria revealed prostate volume as an independent risk factor associated with a higher complication rate. Consequently, we postulated that the thinner vessels of the medium-sized prostate could not be entirely excluded from the risk. Subsequently, 5-alpha reductase inhibitors (5-ARIs) were employed as a suitable and effective alternative treatment for men with refractory hematuria presumably due to prostatic bleeding.32,33

However, this study is not without limitations. It is a single-center study with a relatively short follow-up period, introducing inherent constraints. The patient population was limited to those on antiplatelet therapy medication with medium-sized prostates, inevitably introducing selection bias. Additionally, the study did not include information on the drug dose of aspirin/clopidogrel and other types of NOAC concerning postoperative bleeding complications.34 Further and more detailed studies with great number of patients and a randomized asset should be made in future, based on overcoming limitations.

Conclusion

TEG holds potential utility in informing preoperative strategies, particularly in patients undergoing continuous AP therapy. In contrast to HP-HoLEP, LP-HoLEP demonstrated a capacity to mitigate enucleation requirements, morcellation procedures, bladder irrigation necessity, post-operative catheterization duration, length of hospitalization, and reductions in hemoglobin levels. LP-HoLEP presents a feasible option that may be advocated without interrupting AP therapy, particularly in cases where platelet count and aggregation functions remain within normal parameters.Preoperative management, particularly for patients undergoing continuous AP therapy, could benefit from the use of TEG as a guiding tool.

Abbreviations

BPH, Benign prostatic hyperplasia; TRUS, Transrectal ultrasound; LTUS, Lower urinary tract symptoms; HBD, Haemoglobin drop; HoLEP, Holmium laser enucleation of the prostate; PLT, Platelet; TURP, Transurethral resection of the prostate; MA, Maximum amplitude; LOS, Operative length of hospital stay; PCT, Post catheterisation time; Qmax, Maximum urinary flow rate; SUI, Stress urinary incontinence; NOAC, New oral anticoagulants.

Data Sharing Statement

The datasets during the current study were available from the corresponding author (Jian-Gang Chen) on reasonable request.

Ethics approval and consent to participate

The study was conducted in accordance with the principles of the Declaration of Helsinki, and the study protocol was approved by The Affiliated Hospital 2 of Nantong University’s ethics committee. The need for informed consent was waived by the ethics committee/Institutional Review Board of The Affiliated Hospital 2 of Nantong University, because of the retrospective nature of the study. The requirement of patient consent for inclusion was waived. Patient personal privacy and data confidentiality has been upheld.

Funding

The present study was fund by Nantong Science and Technology Bureau General Project (MSI2020025) and Nantong Fundamental Research Project (JCI2022008).

Disclosure

The authors declare that they have no competing interests.

References

1. Launer BM, McVary KT, Ricke WA, et al.. The rising worldwide impact of benign prostatic hyperplasia. BJU Int. 2021;127(6):722–728. PMID: 33124118; PMCID: PMC8170717. doi:10.1111/bju.15286

2. Descazeaud A, Robert G, Lebdai S, et al.. A Impact of oral anticoagulation on morbidity of transurethral resection of the prostate. World J Urol. 2011;29(2):211–216. PMID: 20577744. doi:10.1007/s00345-010-0561-3.

3. Liu L, Lei H, Hu J, et al.. Direct oral anticoagulants combined with antiplatelet therapy in the treatment of coronary heart disease: an updated meta-analysis. Drugs. 2021;81(17):2003–2016. PMID: 34731462. doi:10.1007/s40265-021-01637-4

4. Polymeris AA, Macha K, Paciaroni M, et al.. Oral anticoagulants in the oldest old with recent stroke and atrial fibrillation. Ann Neurol. 2022;91(1):78–88. PMID: 34747514; PMCID: PMC9300111. doi:10.1002/ana.26267

5. Palmisano F, Boeri L, Fontana M, et al.. Incidence and predictors of readmission within 30 days of transurethral resection of the prostate: a single center European experience. Sci Rep. 2018;8(1):6575. PMID: 29700356; PMCID: PMC5919965. doi:10.1038/s41598-018-25069-5

6. Boeri L, Capogrosso P, Ventimiglia E, et al.. Clinical comparison of holmium laser enucleation of the prostate and bipolar transurethral enucleation of the prostate in patients under either anticoagulation or antiplatelet therapy. Eur Urol Focus. 2020;6(4):720–728. PMID: 30872124. doi:10.1016/j.euf.2019.03.002

7. Zheng X, Peng L, Cao D, et al.. Holmium laser enucleation of the prostate in benign prostate hyperplasia patients with or without oral antithrombotic drugs: a meta-analysis. Int Urol Nephrol. 2019;51(12):2127–2136. PMID: 31494858. doi:10.1007/s11255-019-02278-z

8. Zhou X, Zhang L, Cai J, et al.. Application areas of intermittent pneumatic compression in the prevention of deep vein thrombosis during Dixon surgery: a randomized, controlled trial. Clin Ther. 2023;45(10):977–982. PMID: 37626001. doi:10.1016/j.clinthera.2023.07.022

9. Subramanian M, Kaplan LJ, Cannon JW. Thromboelastography-guided resuscitation of the trauma patient. JAMA Surg. 2019;154(12):1152–1153. PMID: 31596452. doi:10.1001/jamasurg.2019.3136

10. Gue YX, Memtsas V, Kanji R, et al.. Impact of very low dose rivaroxaban in addition to dual antiplatelet therapy on endogenous fibrinolysis in acute coronary syndrome: the VaLiDate-R study. Thromb Res. 2024;236:144–154. PMID: 38447421. doi:10.1016/j.thromres.2024.02.030

11. Teichman AL, Cotton BA, Byrne J, et al.. Approaches for optimizing venous thromboembolism prevention in injured patients: findings from the consensus conference to implement optimal venous thromboembolism prophylaxis in trauma. J Trauma Acute Care Surg. 2023;94(3):469–478. PMID: 36729884; PMCID: PMC9975027. doi:10.1097/TA.0000000000003854

12. Hartmann J, Curzen N. Modified thromboelastography for peri- interventional assessment of platelet function in cardiology patients: a narrative review. Semin Thromb Hemost. 2023;49(2):192–200. PMID: 36252602; PMCID: PMC9894686. doi:10.1055/s-0042-1757545

13. Lin C, Zhang J, Yang X, Cheng J, Sun L, Jiang M. Use of thromboelastography to monitor effects of the hemocoagulase on the blood coagulation in patients after thoracic surgery. Ann Palliat Med. 2020;9(4):2090–2095. PMID: 32762226. doi:10.21037/apm-20-1221

14. Becker B, Netsch C, Hansen J, et al.. Perioperative safety in patient under oral anticoagulation during holmium laser enucleation of the prostate. J Endourol. 2019;33(3):219–224. PMID: 30516393. doi:10.1089/end.2018.0693

15. Netsch C, Herrmann TRW, Bozzini G, et al.. Recent evidence for anatomic endoscopic enucleation of the prostate (AEEP) in patients with benign prostatic obstruction on antiplatelet or anticoagulant therapy. World J Urol. 2021;39(9):3187–3196. PMID: 33721062. doi:10.1007/s00345-021-03647-z

16. Heiman J, Large T, Krambeck A. Best practice in the management of benign prostatic hyperplasia in the patients requiring anticoagulation. Ther Adv Urol. 2018;10(12):431–436. PMID: 30574203; PMCID: PMC6295789. doi:10.1177/1756287218807591

17. Shah HN, Etafy MH, Katz JE, et al.. A randomized controlled trial comparing high and medium power settings for holmium laser enucleation of prostate. World J Urol. 2021;39(8):3005–3011. PMID: 33398423. doi:10.1007/s00345-020-03535-y

18. Becker B, Gross AJ, Netsch C. Safety and efficacy using a low-powered holmium laser for enucleation of the prostate (HoLEP): 12-month results from a prospective low-power HoLEP series. World J Urol. 2018;36(3):441–447. PMID: 29275506. doi:10.1007/s00345-017-2159-5.

19. Minagawa S, Okada S, Morikawa H. Safety and effectiveness of holmium laser enucleation of the prostate using a low-power laser. Urology. 2017;110:51–55. PMID: 28882779. doi:10.1016/j.urology.2017.08.034

20. Scoffone CM, Cracco CM.Prostate enucleation, better with low or high-power holmium laser? A systematic review. Arch Esp Urol. 2020;73(8):745–752. PMID: 33025919.

21. Culkin DJ, Exaire EJ, Green D, et al.. Anticoagulation and antiplatelet therapy in urological practice: ICUD/AUA review paper. J Urol. 2014;192(4):1026–1034. PMID: 24859439. doi:10.1016/j.juro.2014.04.103

22. Karon BS. Why is everyone so excited about thromboelastrography (TEG)?. Clin Chim Acta. 2014;436:143–148. PMID: 24880040. doi:10.1016/j.cca.2014.05.013

23. Mukhopadhyay T, Subramanian A. An overview of the potential sources of diagnostic errors in (classic) thromboelastography curve interpretation and preventive measures. Pract Lab Med. 2020;22:e00193. PMID: 33319008; PMCID: PMC7723805. doi:10.1016/j.plabm.2020.e00193

24. Sun J, Shi A, Tong Z, Xue W. Safety and feasibility study of holmium laser enucleation of the prostate (HOLEP) on patients receiving dual antiplatelet therapy (DAPT). World J Urol. 2018;36(2):271–276. PMID: 29138929. doi:10.1007/s00345-017-2129-y.

25. El Tayeb MM, Jacob JM, Bhojani N. Holmium laser enucleation of the prostate in patients requiring anticoagulation. J Endourol. 2016;30(7):805–809. PMID: 27065437. doi:10.1089/end.2016.0070

26. Habib E, Ayman LM, ElSheemy MS, et al. Holmium laser enucleation vs bipolar plasmakinetic enucleation of a large volume benign prostatic hyperplasia: a randomized controlled trial. J Endourol. 2020;34(3):330–338. doi:10.1089/end.2019.0707

27. Habib EI, ElSheemy MS, Hossam A, et al. Holmium laser enucleation versus bipolar plasmakinetic resection for management of lower urinary tract symptoms in patients with large-volume benign prostatic hyperplasia: randomized-controlled trial. J Endourol. 2021;35(2):171–179. doi:10.1089/end.2020.0636

28. Gild P, Lenke L, Pompe RS, Soave A. Assessing the outcome of holmium laser enucleation of the prostate by age, prostate volume, and a history of blood thinning agents: report from a single-center series of >1800 consecutive cases. J Endourol. 2021;35(5):639–646. PMID: 33040607. doi:10.1089/end.2020.0605

29. Agarwal DK, Large T, Stoughton CL, et al.. Real-world experience of holmium laser enucleation of the prostate with patients on anticoagulation therapy. J Endourol. 2021;35(7):1036–1041. PMID: 33280490. doi:10.1089/end.2020.0886

30. Yuk HD, Oh SJ. Perioperative safety and efficacy of holmium laser enucleation of the prostate in patients receiving antithrombotic therapy: a prospective cohort study. Sci Rep. 2020;10(1):5308. PMID: 32210252; PMCID: PMC7093432. doi:10.1038/s41598-020-61940-0

31. Othman M, Kaur H. Thromboelastography (TEG). Methods Mol Biol. 2017;1646:533–543. PMID: 28804853. doi:10.1007/978-1-4939-7196-1_39

32. Lerner LB, McVary KT, Barry MJ, et al.. Management of lower urinary tract symptoms attributed to benign prostatic hyperplasia: AUA guideline part II-surgical evaluation and treatment. J Urol. 2021;206(4):818–826. PMID: 34384236. doi:10.1097/JU.0000000000002184

33. Yang BY, Jiang CY, Dai CY, et al.. 5-ARI induces autophagy of prostate epithelial cells through suppressing IGF-1 expression in prostate fibroblasts. Cell Prolif. 2019;52(3):e12590. PMCID: PMC6536403. doi:10.1111/cpr.12590

34. Deuker M, Rührup J, Karakiewicz PI, et al.. Holmium laser enucleation of the prostate: efficacy, safety and preoperative management in patients presenting with anticoagulation therapy. World J Urol. 2021;39(4):1219–1226. PMID: 32488362; PMCID: PMC8124040. doi:10.1007/s00345-020-03272-2