Pilot study of Alteplase (tissue plasminogen activator) for treatment of urinary clot retention in an in vitro model.
BACKGROUND
The management of urinary clot retention and hematuria involves manual irrigation with sterile water or normal saline via a Foley catheter followed by continuous bladder irrigation. Irrigation may become difficult because of the formation of dense blood clots. Tissue plasminogen activator (t-PA/Alteplase) may be a useful pharmacological agent to improve the efficacy of manual irrigation of large, dense clots. The goal of the current study was to compare t-PA to sterile water for clot irrigation in an in vitro model.


METHODS
In vitro models of clot retention were created using 500-cc urinary leg bags each filled with 80 cc of unpreserved whole blood from a healthy volunteer. Each model was incubated at 25 degrees C for 24 hours to allow clot formation. Four models each with 25 mL solution of t-PA at concentrations of 2, 1, 0.5, and 0.25 mg/mL were evaluated and compared to a control (25 mL sterile water). Models were instilled with solution (t-PA or control) and incubated for 30 minutes at 37 degrees C, and then irrigated with sterile water via 18F Foley by a blinded investigator. Three separate experiments were conducted, and statistical analysis was performed comparing various irrigation parameters.


RESULTS
Clot evacuation with 25 mL of t-PA at a concentration of 2 mg/mL (50 mg) was significantly easier (p = 0.05) and faster (p < 0.05) than the sterile water control. The mean time for clot evacuation in this model was 2.7 minutes for t-PA solution 2 mg/mL versus 7.3 minutes for the control (p < 0.05). Compared to the control, irrigation with t-PA solution 2 mg/mL also required less irrigant (180 mL vs. 500 mL) (p < 0.05) for complete evacuation. There was a similar trend in efficacy for the lower doses of t-PA, but this was not statistically significant.


CONCLUSIONS
In this in vitro study, a single 25 mL instillation of t-PA solution 2 mg/mL is significantly better than sterile water alone for clot evacuation. In vivo animal studies are pending.
Ritch
Chad R
CR
Department of Urology, Columbia University Medical Center, New York, NY 10032, USA.
Ordonez
Maria A
MA
Okhunov
Zhamshid
Z
Araujo
Juan
J
Walsh
Rhonda
R
Baudin
Vania
V
Lee
Daniel
D
Badani
Ketan K
KK
Gupta
Mantu
M
Landman
Jaime
J
D006801:Humans; D008954:Models, Biological; D010865:Pilot Projects; D007507:Therapeutic Irrigation; D013927:Thrombosis / Q000188:drug therapy* / Q000652:urine*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D010959:Tissue Plasminogen Activator