title: Pilot study of Alteplase (tissue plasminogen activator) for treatment of urinary clot retention in an in vitro model.
abstract: 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.
authors: Department of Urology, Columbia University Medical Center, New York, NY 10032, USA.
authors: Chad R
authors: CR
authors: Ritch
authors: Maria A
authors: MA
authors: Ordonez
authors: Zhamshid
authors: Z
authors: Okhunov
authors: Juan
authors: J
authors: Araujo
authors: Rhonda
authors: R
authors: Walsh
authors: Vania
authors: V
authors: Baudin
authors: Daniel
authors: D
authors: Lee
authors: Ketan K
authors: KK
authors: Badani
authors: Mantu
authors: M
authors: Gupta
authors: Jaime
authors: J
authors: Landman
mesh_terms: 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*
chemical_list: D010959:Tissue Plasminogen Activator