Is there literature for using aminocaproic acid as a continuous bladder irrigation in pediatrics?

Comment by InpharmD Researcher

Literature specifically evaluating aminocaproic acid administered via continuous bladder irrigation in pediatric patients was not identified. A single pediatric conference abstract describes successful hemostasis following intravesical aminocaproic acid administration for hemorrhagic cystitis, although the treatment involved a defined dwell time rather than continuous irrigation. An older narrative review also mentions intravesical use without providing pediatric outcomes or dosing recommendations. Overall, evidence is insufficient to establish the safety, efficacy, or optimal dosing of continuous bladder irrigation with aminocaproic acid in pediatric patients.

A search was conducted using PubMed and Google Scholar to identify studies evaluating aminocaproic acid administered via continuous bladder irrigation in pediatric patients. Search terms included “aminocaproic acid,” “intravesical,” “continuous bladder irrigation,” “bladder irrigation,” “hemorrhagic cystitis,” “bladder hemorrhage,” “pediatric,” “children,” and “adolescent,” alone and in various combinations. Reference lists of relevant publications were also reviewed to identify additional studies.

Background

A 2019 Canadian Urological Association best practice report reviewed the management of hemorrhagic cystitis in pediatric patients, particularly following bone marrow or hematopoietic stem cell transplantation. The report recommends continuous bladder irrigation as a supportive and preventive measure and discusses various intravesical agents, including alum, hyaluronic acid, prostaglandins, and formalin, for refractory bleeding. However, aminocaproic acid is not discussed, and no recommendations regarding its use in pediatric continuous bladder irrigation are provided. [1]

A dated 1996 narrative review discusses the management of hemorrhagic cystitis in children, including aminocaproic acid as a hemostatic treatment. The authors describe aminocaproic acid as an antifibrinolytic agent that concentrates in the bladder and inhibits local fibrinolysis by urokinase, promoting hemostasis and reducing small-vessel bleeding. For oral or intravenous administration, a loading dose of 4-5 g followed by 1-1.25 g/hour is described, with maximal response generally occurring within 8-12 hours. The review also notes that aminocaproic acid has been administered intravesically following clot evacuation; however, no specific intravesical dosing regimen, continuous bladder irrigation protocol, or pediatric efficacy outcomes are provided. Potential complications include ureteral obstruction and renal failure due to clot formation, as well as potentially fatal thrombosis in patients with disseminated intravascular coagulation. [2]

The only directly relevant pediatric literature identified was a 2013 conference abstract of a case series describing intravesical aminocaproic acid in pediatric patients with hemorrhagic cystitis following hematopoietic stem cell transplantation (Table 1). Patients initially received intravesical recombinant activated factor VII (rFVIIa) at approximately 50 mcg/kg in 50-100 mL of normal saline following bladder irrigation until clear outflow was achieved, with a dwell time of 1-2 hours. Although rFVIIa achieved hemostasis, bleeding took several days to resolve; therefore, aminocaproic acid 4 g in 50-100 mL of normal saline was subsequently instilled after drainage of rFVIIa and allowed to dwell for 1-2 hours. The authors reported effective hemostasis and intravesical clot formation following the addition of aminocaproic acid, describing the combination as safe and effective. However, the abstract does not report the number of patients treated or detailed safety outcomes, and although aminocaproic acid was administered intravesically, the described administration method does not appear to involve continuous bladder irrigation; therefore, these findings should be interpreted cautiously. [3]

Background References: [1] Hannick JH, Koyle MA. Canadian Urological Association Best Practice Report: Pediatric hemorrhagic cystitis. Can Urol Assoc J. 2019;13(11):E325-E334. doi:10.5489/cuaj.5993
[2] Strand WR, Canning DA. Treatment and prevention of acute hemorrhagic cystitis. Dialogues Pediatr Urol. 1996;19(10). https://spuonline.org/Dialogues/archive/19_10.cgi
[3] Douglas JR, Willumsen S, Andreansky M. Can intravesical instillation of recombinant activated factor vii (Rfviia) and aminocaproic acid (Aa) stop bleeding in hemorrhagic cystitis? Biology of Blood and Marrow Transplantation. 2013;19(2):S304. doi:10.1016/j.bbmt.2012.11.446
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Is there literature for using aminocaproic acid as a continuous bladder irrigation in pediatrics?

Level of evidence

D - Case reports or unreliable data  Read more→


Please see Table 1 for your response.

 

Can Intravesical Instillation of Recombinant Activated Factor VII (rFVIIa) and Aminocaproic Acid (AA) Stop Bleeding in Hemorrhagic Cystitis?

Design

 Case series; abstract only 

Case presentation

The authors describe treating pediatric patients with hemorrhagic cystitis following hematopoietic stem cell transplantation using intravesical recombinant activated factor VII (rFVIIa) followed by aminocaproic acid. Initially, the bladder was irrigated with normal saline until clear outflow was achieved, followed by intravesical instillation of rFVIIa at approximately 50 mcg/kg diluted in 50-100 mL of normal saline and retained for 1-2 hours. Although rFVIIa achieved hemostasis, bleeding took several days to resolve completely. To enhance hemostasis, aminocaproic acid 4 g diluted in 50-100 mL of normal saline was instilled immediately after drainage of rFVIIa and retained for an additional 1-2 hours. The authors reported effective hemostasis and intravesical clot formation following the addition of aminocaproic acid, describing the combination as safe and effective. However, the abstract does not report the number of patients treated or detailed safety outcomes, and although aminocaproic acid was administered intravesically, the described administration method does not appear to involve continuous bladder irrigation.

Study Author Conclusions

 The addition of AA led to effective hemostasis and development of intravesical clot. Intravesical instillation and dwelling of rFVIIa, followed by instillation and dwelling of AA, safely and effectively stops HC post-HSCT. Based on this experience, we are developing a standardized protocol to treat post-transplant HC in the early stages of its development.
Table 1 References:
[4] Douglas JR, Willumsen S, Andreansky M. Can intravesical instillation of recombinant activated factor vii (Rfviia) and aminocaproic acid (Aa) stop bleeding in hemorrhagic cystitis? Biology of Blood and Marrow Transplantation. 2013;19(2):S304. doi:10.1016/j.bbmt.2012.11.446