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Preoperative predictors of postsurgical adhesion formation and the Prevention of Adhesions with Plasminogen Activator (PAPA-study): results of a clinical pilot study

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Author: Hellebrekers, B.W.J. · Trimbos-Kemper, T.C.M. · Boesten, L. · Jansen, F.W. · Kolkman, W. · Trimbos, J.B. · Press, R.R. · Poelgeest, M.I.E. van · Emeis, S.J. · Kooistra, T.
Institution: TNO Kwaliteit van Leven
Source:Fertility and Sterility, 4, 91, 1204-1214
Identifier: 241462
doi: doi:10.1016/j.fertnstert.2008.01.052
Keywords: Health · Biomedical Research · CRP · early second-look laparoscopy · fibrinolytic system · Myomectomy · predictors of adhesion formation · prevention of adhesions · reteplase · C reactive protein · fibrin degradation product · plasminogen activator inhibitor 1 · reteplase · Ringer lactate solution · tissue plasminogen activator · adult · article · clinical article · clinical trial · controlled study · drug efficacy · drug safety · female · human · myomectomy · peritoneal fluid · plasma · priority journal · second look surgery · uterus synechia · Adult · Ascitic Fluid · Female · Gynecologic Surgical Procedures · Humans · Incidence · Infertility, Female · Leiomyoma · Myometrium · Pilot Projects · Plasminogen Activators · Postoperative Complications · Preoperative Care · Prognosis · Risk Factors · Tissue Adhesions · Uterine Neoplasms · Young Adult


Objective: To identify predictors of postsurgical adhesion formation in peritoneal fluid and plasma, and assess efficacy and safety of reteplase (recombinant plasminogen activator [r-PA]). Design: Prospective randomized study. Setting: University Medical Center. Patient(s): Twenty-six abdominal myomectomy patients with early second-look laparoscopy (ESL). Intervention(s): Randomization to IP treatment with 1 mg reteplase in 300 mL Ringer's lactate or 300 mL Ringer's lactate only. Scoring of adhesions and collecting peritoneal fluid during both surgical procedures and collecting plasma samples at ten time points. Main Outcome Measure(s): Incidence, severity, and extent of adhesions at ESL. Concentrations of C-reactive protein (CRP), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1), and fibrin degradation products (FbDPs). Result(s): Significant correlation between the extent of uterine adhesion formation and preoperative plasma levels of CRP (rs = 0.558), PAI-1 (rs = 0.413), and the change in tPA concentration in peritoneal fluid from initial surgery to ESL (Δ+PA: rs = -0.636). No significant differences in adhesion scores between treatment and control groups. Conclusion(s): Our finding that preoperative plasma CRP and PAI-1-levels are significantly correlated with extent of adhesion formation points to a role of chronic inflammation in the disease process. Results are highly indicative for the paradigm that adhesions are caused by an insufficiency in peritoneal fibrinolytic capacity. For successful adhesion prevention therapy relatively high amounts of r-PA are required. © 2008 American Society for Reproductive Medicine.