Objectives Preeclampsia (PE) is a serious complication of pregnancy. The fibrinolytic system play crucial roles regarding placentation and evolution of PE. Aim To study comprehensively components of the fibrinolytic system and fibrin lysability in women with PE. Design and Methods 117 women with PE and matched controls were included. Tissue type plasminogen activator (t-PA), plasminogen, PAI-1, plasmin inhibitor (PI), D-dimer, the fibrinolytic potential of dextran sulphate euglobulin fraction (DEF), PAI-2, polymere PAI-2, fibrin clot lysability, thrombin activatable fibrinolysis inhibitor (TAFI) and fibrinogen were assessed. Results Women with PE had significantly increased concentrations of t-PA and PAI-1, whereas the plasma concentration of PAI-2 was significantly lower compared to controls, p < 0.0001. Polymere PAI-2 was detected in both groups. DEF, TAFI and fibrinogen were not different between the groups. D-dimer was significantly increased and plasminogen/PI together with fibrin clot lysability time decreased in the PE-group, p = 0.0004 p = 0.04, p = 0.03, p < 0.0001 respectively. Conclusion This study demonstrates that PE is associated with an affected t-PA/PAI-1 system, decreased PAI-2 and increased fibrin lysability. Furthermore, PAI-2 has the potential to polymerize during pregnancy.
ObjectiveThe pathophysiology of preeclampsia is not fully understood. Disturbances in the contact system are associated with preeclampsia. Few studies have investigated the association between preeclampsia and alterations in the contact system in plasma. This study aims to elucidate whether this basic biological system is affected in preeclampsia using new methods focusing on the dynamic interactions and total capacity of the contact system in blood.DesignCross-sectional study matching women with preeclampsia and controls without preeclampsia regarding age, pregestational body mass index, and gestational age at onset of the disease.SettingTwo Danish University hospitals.SampleA cohort of 117 women with preeclampsia and 117 controls.MethodsThe turnover and capacity of the contact system were determined with new methods. Paired t-test, Wilcoxon signed-pairs signed rank test, Mann-Whitney or Chi2-test were applied, as appropriate.Main Outcome MeasurementsKallikrein generation (peak kallikrein concentration and endogenous kallikrein potential), coagulation factor XII, prekallikrein, H-kininogen, cleaved H-kininogen, and complement C1 esterase inhibitor.ResultsThe endogenous kallikrein potential, peak kallikrein concentration, prekallikrein and cleaved H-kininogen were significantly lower in women with preeclampsia compared to the controls, p ≤ 0.005, whereas the concentration of coagulation factor XII, H-kininogen and complement C1 esterase inhibitor was not significantly different, p > 0.05.ConclusionThis study demonstrates significant reduction in kallikrein generating capacity, prekallikrein and cleaved H-kininogen indicating that the contact system is affected in preeclampsia suggesting a link to the pathophysiology of the disease.
The increasing proportion of elderly Americans has brought about an anticipation of 50% rise in prolapse surgeries by 2050. It is anticipated that 25% to 40% of patients undergoing surgeries will develop de novo stress urinary incontinence (SUI) after prolapse repair. The Outcomes Following Vaginal Prolapse Repair with Midurethral Sling (OPUS) found a 36% reduction in the risk for de novo SUI, but also demonstrated increased risk of bladder perforations, urinary tract infections, and incomplete bladder emptying symptoms (N Engl J Med. 2012;366:2358-2367. As a result, pelvic reconstructive surgeons often vary their approach toward prophylactic MUS at the time of vaginal prolapse repair (VPR). Although a cost-effectiveness analysis found universal MUS placement to be the most cost-effective strategy over both selective and staged strategies (J Urol. 2013;190:1306-1312, this analysis did not include an arm for the less-costly option of using a selective approach via a prolapse-reduced cough stress test (CST). In addition, Richardson analysis of patients undergoing sacral colpopexy lacks generalizability for VPR surgeries (which account for two thirds of all prolapse surgeries). The manuscript described here therefore tested the cost-effectiveness of 3 generalizable MUS utilization strategies for preventing de novo SUI within 1 year post-VPR.Three approaches were compared: (1) staged strategy performing VPR with later MUS placement only for de novo SUI;(2) universal sling placement at the time of VPR; and (3) selective sling placement with MUS at the time of VPR when occult SUI was observed at the time of preoperative prolapse-reduced CST. A representative population of women with symptomatic pelvic organ prolapse (at least stage II) was modeled. Included in the VPR model was colpocleisis, apical suspension, or anterior colporrhaphy, with or without hysterectomy. The base assumption was that all VPRs were uncomplicated and anatomically successful. Subsequent treatment pathways were formed based on the 3 aforementioned options if de novo SUI was to occur.A 2017 systematic review by van der Ploeg was used for obtaining literature to gain point estimates concerning the risk for postoperative SUI (Int Urogynecol J. 2016;27:1029-1038). The search was performed via PubMed through January 2017, and exclusionary criteria were as follows: studies examining urodynamics preoperatively, abdominal prolapse repairs, duplicate studies, and studies lacking clear definitions for VPR, MUS, or SUI. Using data from 3 previous studies, for a selective MUS, the authors estimated the rate of de novo SUI after VPR with a negative preoperative CST to be 33.6%. The authors determined the existence of 4 possible adverse outcomes following MUS: (1) persistent SUI, (2) sling lysis required for voiding dysfunction, (3) mesh exposure requiring excision, and (4) anticholinergic medications required for de novo overactive bladder. Information on costs was gathered Physician Fee Schedules from the 2020 Centers for Medicare and Medicaid Services. Incr...
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