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Tranexamic Acid

Tranexamic acid (TXA) is a synthetic lysine-analogue antifibrinolytic that can reduce blood loss or transfusion in selected surgical settings; benefits and safety depend on procedure, patient and regimen. For the reconstructive and pelvic surgeon the relevant questions are narrow: when does the blood-loss reduction justify giving it, and when is it dangerous? — and the answer to the second is uniquely urologic.[8][9]

Mechanism — and Why the Urinary Tract Is Special​

TXA competitively blocks the lysine-binding site on plasminogen, preventing its conversion to plasmin and thereby stabilizing fibrin clots.[3] The urinary tract is uniquely rich in plasminogen activators — urokinase and high urinary plasminogen drive local fibrinolysis and clot breakdown.[1][3] TXA's antifibrinolytic action directly counteracts this local fibrinolytic milieu, which is both why it is pharmacologically well-suited to urologic bleeding and why it carries a urology-specific hazard (clot retention in the upper tract — see Safety). TXA is renally excreted, so it concentrates exactly where the fibrinolysis is.[1][14]

Evidence Across Urologic Surgery​

The 2026 POISE-3 prespecified urologic analysis included 1,124 participants with bleeding and cardiovascular risk factors. With 1 g IV at the start and end of surgery, the primary bleeding composite occurred in 8.1% versus 10.9% (HR 0.73, 95% CI 0.50–1.07), which did not reach statistical significance. The major-bleeding component was lower, 6.1% versus 9.5% (HR 0.63, 95% CI 0.41–0.97). The safety composite was 12.1% versus 10.9% (HR 1.12, 95% CI 0.79–1.58); few stroke/VTE events limit precision. No subgroup interaction was detected, which does not prove identical benefit in every operation.[8]

TRACTION, June 2026: a cluster-randomized crossover policy trial across 10 Canadian hospitals, with 8,273 evaluable patients undergoing major noncardiac surgery, found fewer in-hospital red-cell transfusions with TXA (7.4% versus 9.8%; adjusted RR 0.73, 95% CI 0.61–0.86). Ninety-day VTE was 2.1% in both groups (RR 0.96, 95% CI 0.65–1.38), meeting the prespecified noninferiority margin of 1.46. Most operations were oncological. This strengthens broad perioperative evidence but is not a dedicated reconstructive-urology trial or proof of benefit in every procedure. The primary abstract was verified; full trial methods were not accessible in this review.[19]

A 13-RCT urologic meta-analysis (1,814 participants) also reported lower blood loss and transfusion; sparse thrombotic events limit safety conclusions.[9]

The procedure-specific trials that built this base — drawn largely from prostate, cystectomy, and stone surgery — are summarized here as the evidence the general recommendation rests on:

SettingKey finding
Prostate surgeryMeta-analysis (9 RCTs): reduced EBL (SMD −1.93) and transfusion (RR 0.61) without ↑ DVT/PE.[4] Landmark RRP RCT (n=200): transfusion 55% → 34% (NNT 5), no thromboembolism at 6 mo.[5] TURP benefit attributed to urokinase release from prostatic tissue.[2]
Radical cystectomyTACT, a 10-center RCT (353 randomized; 344 analyzed), found no transfusion reduction (37.0% vs 37.4%).[6] A propensity-matched series using a simplified 1 g bolus showed transfusion 47% → 19%.[7] The observational result does not override the randomized null result; an anticoagulation explanation is unproven. TACT does not support routine TXA solely for open cystectomy.
PCNLCochrane review: 10 systemic-TXA RCTs (1,883 participants) and one topical trial (400). Systemic TXA may reduce transfusion; stone-free benefit is uncertain (RR 1.11, 95% CI 0.98–1.27). Thrombotic events were sparse; do not describe risk as absent.[1]

Hematuria Management (Non-Surgical)​

Outside the OR, TXA has been studied off-label for gross hematuria. A review of 7 heterogeneous studies (970 participants) describes possible benefits; it does not establish a preferred route for every bleeding source:[10]

  • IV TXA was studied for postoperative hematuria;
  • oral and intravesical approaches were also reported in non-surgical settings, without a definitive head-to-head route hierarchy;
  • a pilot RCT of intravesical TXA for painless gross hematuria reduced irrigation-volume requirements (without a difference in hemoglobin decline).[11]

Investigate the bleeding source and preserve drainage; TXA must not delay clot evacuation, decompression or treatment of a tumor, infection or vascular injury.

Dosing​

The following are study regimens, not interchangeable prescriptions. US CYKLOKAPRON approval is for short-term bleeding prevention in hemophilia around dental extraction; urologic uses are off-label. Confirm local protocol, renal function and administration rate.[17]

SettingProtocol
General urologic surgery (POISE-3)1 g IV at surgery start + 1 g at end[8]
Radical prostatectomy500 mg IV load + 250 mg/h infusion intraop[5]
Radical cystectomy (TACT)10 mg/kg IV load + 5 mg/kg/h infusion intraop[6]
Radical cystectomy (simplified)1 g IV bolus preoperatively[7]
Intravesical (hematuria)Local instillation via Foley during bladder irrigation[11]

Renal impairment requires dose reduction (renal excretion → accumulation).[14]

Safety and Contraindications​

Thromboembolism. Small urologic trials and meta-analyses generally did not detect an increase, but absence of statistical significance is not proof of safety.[4][8][9][12] The original 2022 POISE-3 trial did not establish noninferiority for its broad cardiovascular composite; TRACTION subsequently met its specified VTE noninferiority margin. These outcomes and margins are different.[18][19]

Upper-tract hematuria and clot obstruction. Stabilized urinary clots can obstruct the renal pelvis or ureter. Avoid reflexive systemic TXA for unexplained renal/ureteral bleeding; make a specialist decision based on source control and drainage. Hemophilia guidance advises against antifibrinolytics for hematuria.[14] This caution is different from asserting that every renal operation is an absolute contraindication: perioperative PCNL trials exist. The Lee review had renal-function documentation in only 28 patients, so it cannot establish a reliable “less than 1%” obstruction rate or rule out injury.[1][15]

Current US injection label: contraindications include active intravascular clotting, subarachnoid hemorrhage, hypersensitivity and neuraxial administration. The boxed warning highlights fatal errors from intrathecal/epidural injection: label syringes and verify the route. Seizure risk is exposure-dependent, particularly with high-dose use or renal accumulation; there is no universal 2 g/day safety boundary. Adjust for renal function and infuse at the product's specified rate to avoid hypotension.[17]

Cancer-surgery meta-analyses support possible reductions in bleeding/transfusion but do not make TXA automatically appropriate for every patient with cancer.[16]

Guideline Status and Reconstructive Relevance​

EAU 2026 urolithiasis guidance acknowledges evidence that perioperative TXA may reduce PCNL bleeding and transfusion.[13] The evidence is strongest for selected perioperative settings, with direct procedure-level findings taking precedence over broad extrapolation. For reconstructive and vaginal operations, weigh expected bleeding, renal function, thrombosis risk and urinary drainage with anesthesia. Local measures such as hydrodissection remain complementary; a generic designation of all urology as “high bleeding risk” is not an indication.

See Also​

References​

1. Cleveland B, Norling B, Wang H, et al. Tranexamic acid for percutaneous nephrolithotomy. Cochrane Database Syst Rev. 2023;10:CD015122. doi:10.1002/14651858.CD015122.pub2

2. Vanderbruggen W, Brits T, Tilborghs S, Derickx K, De Wachter S. The effect of tranexamic acid on perioperative blood loss in transurethral resection of the prostate: a double-blind, randomized controlled trial. Prostate. 2023;83(16):1584–1590. doi:10.1002/pros.24616

3. Mannucci PM. Hemostatic drugs. N Engl J Med. 1998;339(4):245–253. doi:10.1056/NEJM199807233390407

4. Longo MA, Cavalheiro BT, de Oliveira Filho GR. Systematic review and meta-analyses of tranexamic acid use for bleeding reduction in prostate surgery. J Clin Anesth. 2018;48:32–38. doi:10.1016/j.jclinane.2018.04.014

5. Crescenti A, Borghi G, Bignami E, et al. Intraoperative use of tranexamic acid to reduce transfusion rate in patients undergoing radical retropubic prostatectomy: double blind, randomised, placebo controlled trial. BMJ. 2011;343:d5701. doi:10.1136/bmj.d5701

6. Breau RH, Lavallée LT, Cagiannos I, et al. Tranexamic acid during radical cystectomy: a randomized clinical trial. JAMA Surg. 2024;159(12):1355–1363. doi:10.1001/jamasurg.2024.4183

7. Egen L, Keller K, Menold HS, et al. Tranexamic acid reduces perioperative blood transfusions following open radical cystectomy — a propensity-score matched analysis. World J Urol. 2024;42(1):477. doi:10.1007/s00345-024-05168-x

8. Tikkinen KAO, Marcucci M, Halme ALE, et al. Safety and efficacy of tranexamic acid in urologic surgery: results from the international, randomized, placebo-controlled POISE-3 trial. Eur Urol. 2026. doi:10.1016/j.eururo.2026.03.019

9. Lin YH, Lee KC, Hsu CC, Chen KT. Efficacy and safety of intravenous tranexamic acid in urologic surgery: a systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2023;102(25):e34146. doi:10.1097/MD.0000000000034146

10. Naseralallah L, Nasrallah D, Alsheikh R, Assami D, Boudaka R. Tranexamic acid for the management of hematuria: a systematic review. Urology. 2026;210:136–142. doi:10.1016/j.urology.2025.12.035

11. Moharamzadeh P, Ojaghihaghighi S, Amjadi M, Rahmani F, Farjamnia A. Effect of tranexamic acid on gross hematuria: a pilot randomized clinical trial study. Am J Emerg Med. 2017;35(12):1922–1925. doi:10.1016/j.ajem.2017.09.012

12. Fowler H, Law J, Tham SM, et al. Impact on blood loss and transfusion rates following administration of tranexamic acid in major oncological abdominal and pelvic surgery: a systematic review and meta-analysis. J Surg Oncol. 2022;126(3):609–621. doi:10.1002/jso.26900

13. EAU. Urolithiasis Guidelines, 2026: PCNL evidence summary. Current chapter.

14. Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1–e47. doi:10.1111/j.1365-2516.2012.02909.x

15. Lee SG, Fralick J, Wallis CJD, et al. Systematic review of hematuria and acute renal failure with tranexamic acid. Eur J Haematol. 2022;108(6):510–517. doi:10.1111/ejh.13762

16. Soliman A, Azim AAA, Elgarawany A, et al. Efficacy and safety of tranexamic acid in solid cancer surgeries: a systematic review and meta-analysis of randomized controlled trials with GRADE assessment. Ann Surg Oncol. 2026. doi:10.1245/s10434-026-19377-8

17. CYKLOKAPRON. US prescribing information, revised August 2025. Pfizer label.

18. Devereaux PJ, Marcucci M, Painter TW, et al. Tranexamic acid in patients undergoing noncardiac surgery. N Engl J Med. 2022;386:1986–1997. doi:10.1056/NEJMoa2201171.

19. Houston BL, McIsaac DI, Breau RH, et al. Hospital policy of tranexamic acid to reduce transfusion in major noncardiac surgery. N Engl J Med. Published June 2026. doi:10.1056/NEJMoa2515820.