What data exists to support aminocaproic acid or tranexamic acid given intravesically for hematuria?

What data exists to support aminocaproic acid or tranexamic acid given intravesically for hematuria?

Comment by InpharmD Researcher

Available data evaluating the use of intravesical epsilon aminocaproic acid (EACA) or tranexamic acid (TXA) for hematuria is scarce. One case series evaluating intravesical instillation of EACA reported improvements in hematuria, but noted lack of replication in recent studies. Additionally, a randomized controlled trial (RCT) assessing intravesical EACA for post-transurethral resection of the prostate (TURP) bleeding found no significant difference in blood loss between EACA and placebo. In contrast, a retrospective study of intravesical TXA demonstrated reductions in emergency department (ED) length of stay (LOS), Foley catheter duration, and revisits for continuous bladder irrigation; however, current evidence is insufficient to establish definitive conclusions regarding the efficacy and safety of intravesical EACA or TXA for hematuria.

Background

A 2019 Best Practice Report by Canadian Urological Association performed a comprehensive narrative synthesis on the diagnosis and management of radiation-induced hemorrhagic cystitis, with specific emphasis on treatment options, clinical outcomes, and grading of evidence. The panel states that several intravesical options have been trialed in limited case series, but require replication, etiology-specific assessment, or comparative data before they can be formally included as recommendations. Intravesical instillation of epsilon aminocaproic acid (EACA), was evaluated in a case series from 1992 involving 37 patients with intractable bladder hemorrhage. The study reported improvement in hematuria in 34 of these patients, the majority of whom suffered from cystitis induced by radiation or cyclophosphamide treatment. Despite these promising results, similar studies have not been replicated in recent years to confirm the efficacy of EACA for this condition. Available review articles note that intravesical aminocaproic acid is still anecdotally used in clinical practice despite its sparse evidence of utility. [1], [2], [3]

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

What data exists to support aminocaproic acid or tranexamic acid given intravesically for hematuria?

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-2 for your response.

Safety and efficacy of intravesical aminocaproic acid for bleeding after transurethral resection of prostate
Design	Prospective, randomized, double-blind, controlled clinical trial N= 82
Objective	To determine the safety and efficacy of intravesical administration of aminocaproic acid in patients with post-TURP bleeding
Study Groups	Aminocaproic acid group (n= 40) Placebo group (n= 40)
Inclusion Criteria	Male patients aged 45-95 years admitted for presumed benign prostatic hypertrophy and scheduled to undergo TURP
Exclusion Criteria	Symptomatic congestive heart failure, uncontrolled arrhythmia, past history of thromboembolic or hemorrhagic disease, renal disease with serum creatinine >3.0 mg/dl, hepatic disease with elevated liver enzymes, concurrent administration of warfarin, platelet count <150,000/mm3, prothrombin time or partial thromboplastin time >1.5 times control, known sensitivity to aminocaproic acid
Methods	Patients were randomized to receive either aminocaproic acid or placebo irrigation solution post-TURP. Continuous bladder irrigation was administered at 100 ml/hour for up to three days. Blood loss was assessed by hemoglobin determination in irrigation fluid and urine. Serum samples were collected to check for systemic absorption of aminocaproic acid
Duration	Up to three days post-TURP
Outcome Measures	Post-TURP blood loss
Baseline Characteristics	Characteristic	Aminocaproic Acid Group (n= 40)	Placebo Group (n = 40)
	Age, years	65.1 + 8.5	67.0 + 13.7
	Race White Black Hispanic	10 25 5	15 24 1
	Hemoglobin, gm/dl	13.5 + 1.7	13.6 + 1.8
	Hematocrit, %	40.7 + 5.0	41.3 + 5.3
	Platelets, x 103/mm³	254.4 + 75.9	262.0 + 85.9
	Prothrombin time, sec	11.8 + 0.7	11.8 + 0.6
	Partial thromboplastin time, sec	29.9 + 4.4	30.2 + 5.0
Results	Group	Day 1	Day 2	Day 3
	Aminocaproic acid group Mean blood loss, ml Median blood loss, ml Range	23.6 16.9 0.4-81.4	14.0 8.4 2.1-81.3	19.3 8.1 3.5-26.2
	Placebo group Mean blood loss, ml Median blood loss, ml Range	29.9 11.7 0.4-218.9	20.0 13.8 0.3-91.4	28.2 14.4 0.1-83.9
Adverse Events	Adverse effects occurred in 5 aminocaproic acid patients and 5 placebo patients. Transient biochemical abnormalities such as eosinophilia, monocytosis, and elevated LDH and uric acid levels were observed but were not associated with clinical symptoms. Clot retention occurred in one patient from each group.
Study Author Conclusions	There appears to be no clinically significant difference in blood loss or transfusion requirements between intravesical aminocaproic acid and sodium chloride irrigation post-TURP. Intravesical aminocaproic acid might be a useful alternative to systemic antifibrinolytic therapy for delayed, recurrent post-prostatectomy bleeding.
Critique	The study was well-designed as a prospective, randomized, double-blind, controlled trial, which strengthens the validity of the findings. However, the small sample size and the lack of significant differences in outcomes between groups limit the conclusions that can be drawn. Additionally, the study did not specifically evaluate the efficacy of aminocaproic acid in cases of delayed bleeding, which is a potential limitation.

References:

Sharifi R, Lee M, Ray P, Millner SN, Dupont PF. Safety and efficacy of intravesical aminocaproic acid for bleeding after transurethral resection of prostate. Urology. 1986;27(3):214-219. doi:10.1016/0090-4295(86)90277-3

Impact of Intravesical Administration of Tranexamic Acid on Gross Hematuria in the Emergency Department: A Before-and-After Study
Design	Single-center, before-and-after, retrospective study N= 159
Objective	To evaluate the impact of intravesical tranexamic acid injection before continuous bladder irrigation on the length of stay in the emergency department and duration of Foley catheter placement
Study Groups	Before (control) group (n= 73) After (intervention) group (n= 86)
Inclusion Criteria	Patients older than 18 years who visited the ED with gross hematuria and received CBI via a 3-way Foley catheter
Exclusion Criteria	Patients with hematuria grade ≤5, initial urinary obstruction, or who rejected Foley catheter insertion
Methods	The intervention involved the administration of 1000 mg of TXA diluted in 100 mL of normal saline through a three-way Foley catheter, which was then clamped for 15 minutes to allow direct contact of the TXA solution with the bladder mucosa. Following this dwell time, the Foley catheter was declamped, and continuous bladder irrigation (CBI) with cold saline (4°C) was initiated.
Duration	March 2021 to August 2021 (before group) March 2022 to August 2022 (after group)
Outcome Measures	Primary: Length of stay in the ED, duration of Foley catheter placement Secondary: Admissions, revisits for CBI within 48 hours after discharge
Baseline Characteristics	Characteristic	Before group (n= 73)	After group (n= 86)
	Age, years	80.4 ± 6.8	78.4 ± 7.5
	Male	66 (90%)	83 (97%)
	Comorbidities DM Hypertension Cerebrovascular disease HD CKD	33 (45%) 57 (78%) 18 (25%) 20 (27%) 19 (26%)	45 (52%) 63 (73%) 20 (23%) 32 (37%) 21 (24%)
	Vital signs SBP, mmHg DBP, mmHg HR, beats/min RR, cycles/min Body temperature, °C	142 ± 31 81 ± 19 87 ± 18 19 ± 2 36.5 ± 0.3	143 ± 25 82 ± 14 85 ± 16 19 ± 2 36.7 ± 0.5
	Antithrombotic agents Anticoagulants Antiplatelets	12 (16%) 27 (37%)	8 (9%) 42(49%)
	Laboratory findings BUN Creatinine, mg/dL Hemoglobin, g/dL Platelets, ×10³/μL Prothrombin time, seconds INR	23.0 ± 10.4 1.35 ± 0.80 11.9 ± 2.3 219 ± 66 12.5 ± 1.91 1.08 ± 0.18	24.5 ± 12.6 1.44 ± 0.94 11.8 ± 2.2 215 ± 73 12.3 ± 1.83 1.08 ± 0.17
	Abbreviations: DM, diabetes mellitus; HD, heart disease; CKD, chronic kidney disease; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; RR, respiratory rate; BUN, blood urea nitrogen; INR, international normalized ratio
Results	Endpoint	Before group (n= 73)	After group (n= 86)	p-value
	Length of stay (IQR)	411 (280 to 792)	274 (168 to 373)	<0.001
	Duration of Foley catheter placement (IQR)	308(201 to 725)	145 (81 to 293)	<0.001
	Revisits	9 (12.3%)	2 (2.3%)	0.030
	Admissions	33 (45.2%)	25 (29.1%)	0.052
	Abbreviations: IQR, interquartile range
Adverse Events	No significant adverse effects reported.
Study Author Conclusions	After the TXA intervention, reduction in the length of stay in the ED, the duration of Foley catheter placement, and the revisits after ED discharge was observed.
InpharmD Researcher Critique	The study demonstrates a significant reduction in ED length of stay and Foley catheter duration with TXA administration, but its retrospective design and single-center setting may limit generalizability. The subjective grading of hematuria and potential confounding factors not accounted for are limitations. Further multicenter prospective studies are needed to confirm these findings.

References:

Choi H, Kim DW, Jung E, et al. Impact of intravesical administration of tranexamic acid on gross hematuria in the emergency department: A before-and-after study. Am J Emerg Med. 2023;68:68-72. doi:10.1016/j.ajem.2023.03.020