Antifibrinolytics for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding (HMB) is an important physical and social problem for women. Oral treatment for HMB includes antifibrinolytic drugs, which are designed to reduce bleeding by inhibiting clot-dissolving enzymes in the endometrium.Historically, there has been some concern that using the antifibrinolytic tranexamic acid (TXA) for HMB may increase the risk of venous thromboembolic disease. This is an umbrella term for deep venous thrombosis (blood clots in the blood vessels in the legs) and pulmonary emboli (blood clots in the blood vessels in the lungs). OBJECTIVES: To determine the effectiveness and safety of antifibrinolytic medications as a treatment for heavy menstrual bleeding. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO and two trials registers in November 2017, together with reference checking and contact with study authors and experts in the field. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing antifibrinolytic agents versus placebo, no treatment or other medical treatment in women of reproductive age with HMB. Twelve studies utilised TXA and one utilised a prodrug of TXA (Kabi). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary review outcomes were menstrual blood loss (MBL), improvement in HMB, and thromboembolic events. MAIN RESULTS: We included 13 RCTs (1312 participants analysed). The evidence was very low to moderate quality: the main limitations were risk of bias (associated with lack of blinding, and poor reporting of study methods), imprecision and inconsistency.Antifibrinolytics (TXA or Kabi) versus no treatment or placeboWhen compared with a placebo, antifibrinolytics were associated with reduced mean blood loss (MD -53.20 mL per cycle, 95% CI -62.70 to -43.70; I² = 8%; 4 RCTs, participants = 565; moderate-quality evidence) and higher rates of improvement (RR 3.34, 95% CI 1.84 to 6.09; 3 RCTS, participants = 271; moderate-quality evidence). This suggests that if 11% of women improve without treatment, 43% to 63% of women taking antifibrinolytics will do so. There was no clear evidence of a difference between the groups in adverse events (RR 1.05, 95% CI 0.93 to 1.18; 1 RCT, participants = 297; low-quality evidence). Only one thromboembolic event occurred in the two studies that reported this outcome.TXA versus progestogensThere was no clear evidence of a difference between the groups in mean blood loss measured using the Pictorial Blood Assessment Chart (PBAC) (MD -12.22 points per cycle, 95% CI -30.8 to 6.36; I² = 0%; 3 RCTs, participants = 312; very low quality evidence), but TXA was associated with a higher likelihood of improvement (RR 1.54, 95% CI 1.31 to 1.80; I² = 32%; 5 RCTs, participants = 422; low-quality evidence). This suggests that if 46% of women improve with progestogens, 61% to 83% of women will do so with TXA.Adverse events were less common in the TXA group (RR 0.66, 95% CI 0.46 to 0.94; I² = 28%; 4 RCTs, participants = 349; low-quality evidence). No thromboembolic events were reported in any group.TXA versus non-steroidal anti-inflammatory drugs (NSAIDs)TXA was associated with reduced mean blood loss (MD -73.00 mL per cycle, 95% CI -123.35 to -22.65; 1 RCT, participants = 49; low-quality evidence) and higher likelihood of improvement (RR 1.43, 95% CI 1.18 to 1.74; 12 = 0%; 2 RCTs, participants = 161; low-quality evidence). This suggests that if 61% of women improve with NSAIDs, 71% to 100% of women will do so with TXA. Adverse events were uncommon and no comparative data were available. No thromboembolic events were reported.TXA versus ethamsylateTXA was associated with reduced mean blood loss (MD 100 mL per cycle, 95% CI -141.82 to -58.18; 1 RCT, participants = 53; low-quality evidence), but there was insufficient evidence to determine whether the groups differed in rates of improvement (RR 1.56, 95% CI 0.95 to 2.55; 1 RCT, participants = 53; very low quality evidence) or withdrawal due to adverse events (RR 0.78, 95% CI 0.19 to 3.15; 1 RCT, participants = 53; very low quality evidence).TXA versus herbal medicines (Safoof Habis and Punica granatum)TXA was associated with a reduced mean PBAC score after three months' treatment (MD -23.90 pts per cycle, 95% CI -31.92 to -15.88; I² = 0%; 2 RCTs, participants = 121; low-quality evidence). No data were available for rates of improvement. TXA was associated with a reduced mean PBAC score three months after the end of the treatment phase (MD -10.40 points per cycle, 95% CI -19.20 to -1.60; I² not applicable; 1 RCT, participants = 84; very low quality evidence). There was insufficient evidence to determine whether the groups differed in rates of adverse events (RR 2.25, 95% CI 0.74 to 6.80; 1 RCT, participants = 94; very low quality evidence). No thromboembolic events were reported.TXA versus levonorgestrel intrauterine system (LIUS)TXA was associated with a higher median PBAC score than TXA (median difference 125.5 points; 1 RCT, participants = 42; very low quality evidence) and a lower likelihood of improvement (RR 0.43, 95% CI 0.24 to 0.77; 1 RCT, participants = 42; very low quality evidence). This suggests that if 85% of women improve with LIUS, 20% to 65% of women will do so with TXA. There was insufficient evidence to determine whether the groups differed in rates of adverse events (RR 0.83, 95% CI 0.25 to 2.80; 1 RCT, participants = 42; very low quality evidence). No thromboembolic events were reported. AUTHORS' CONCLUSIONS: Antifibrinolytic treatment (such as TXA) appears effective for treating HMB compared to placebo, NSAIDs, oral luteal progestogens, ethamsylate, or herbal remedies, but may be less effective than LIUS. There were too few data for most comparisons to determine whether antifibrinolytics were associated with increased risk of adverse events, and most studies did not specifically include thromboembolism as an outcome.

Naftopidil for the treatment of lower urinary tract symptoms compatible with benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common condition in ageing men that may cause lower urinary tract symptoms (LUTS). Treatment aims are to relieve symptoms and prevent disease-related complications. Naftopidil is an alpha-blocker (AB) that has a high affinity for the A1d receptor that may have advantages in treating LUTS in this setting. This is an update of a Cochrane Review first published in 2009. Since that time, several large randomised controlled trials (RCTs) have been reported, making this update relevant. OBJECTIVES: To evaluate the effects of naftopidil for the treatment of LUTS associated with BPH. SEARCH METHODS: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, LILAC, and Web of Science), trials registries, other sources of grey literature, and conference proceedings with no restrictions on the language of publication or publication status up to 31 May 2018 SELECTION CRITERIA: We included all parallel RCTs. We also included cross-over design trials. DATA COLLECTION AND ANALYSIS: Two review authors independently classified and abstracted data from the included studies. We performed statistical analyses using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. Primary outcomes were urological symptom scores, quality of life (QoL) and treatment withdrawals for any reason; secondary outcomes were treatment withdrawals due to adverse events, acute urinary retention, surgical intervention for BPH, and cardiovascular and sexual adverse events. We considered outcomes measured up to 12 months after randomisation as short term, and later than 12 months as long term. We rated the certainty of the evidence according to the GRADE approach. MAIN RESULTS: We included 22 RCTs with 2223 randomised participants across four comparisons for short-term follow-up. This abstract focuses on only two of four comparisons for which we found data since two comparators (i.e. propiverine and Eviprostat (phytotherapy)) are rarely used. One study comparing naftopidil to placebo did not report any relevant outcomes and was therefore excluded. There were no trials that compared to combination therapy with naftopidil or any 5-alpha reductase inhibitors (5-ARIs) to combination therapy with other ABs and any 5-ARIs.All included studies were conducted in Asian countries. Study duration ranged from four to 12 weeks. Mean age was 67.8 years, prostate volume was 35.4 mL, and International Prostate Symptom Score was 18.3. We were unable to perform any of the preplanned subgroup analyses based on age and baseline symptom score.Naftopidil versus tamsulosinBased on 12 studies with 965 randomised participants, naftopidil may have resulted in little or no difference in urological symptom score (mean difference (MD) 0.47, 95% confidence interval (CI) -0.09 to 1.04 measured on a scale from 0 to 35 with higher score representing increased symptoms), QoL (MD 0.11, 95% CI -0.09 to 0.30; measured on a scale from 0 to 6 with higher scores representing worse QoL), and treatment withdrawals for any reason (risk ratio (RR) 0.92, 95% CI 0.64 to 1.34; corresponding to 7 fewer per 1000 participants, 95% CI 32 fewer to 31 more). Naftopidil may have resulted in little to no difference in sexual adverse events (RR 0.54, 95% CI 0.24 to 1.22); this would result in 26 fewer sexual adverse events per 1000 participants (95% CI 43 fewer to 13 more). We rated the certainty of evidence as moderate for urological symptom score and low for the other outcomes.Naftopidil versus silodosinBased on five studies with 652 randomised participants, naftopidil may have resulted in little or no difference in the urological symptom scores (MD 1.04, 95% CI -0.78 to 2.85), QoL (MD 0.21, 95% CI -0.23 to 0.66), and treatment withdrawals for any reason (RR 0.80, 95% CI 0.52 to 1.23; corresponding to 26 fewer per 1000 participants, 95% CI 62 fewer to 32 more). We rated the certainty of evidence as low for all these outcomes. Naftopidil likely reduced sexual adverse events (RR 0.15, 95% CI 0.06 to 0.42; corresponding to 126 fewer sexual adverse events per 1000 participants, 95% CI 139 fewer to 86 fewer). We rated the certainty of evidence as moderate for sexual adverse events. AUTHORS' CONCLUSIONS: Naftopidil appears to have similar effects in the urological symptom scores and QoL compared to tamsulosin and silodosin. Naftopidil has similar sexual adverse events compared to tamsulosin but has fewer compared to silodosin.

Treatment of Persistent Gross Hematuria with Tranexamic Acid in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND/AIMS: In this retrospective study we aimed to compare the effect of tranexamic acid (TXA) vs etamsylate, two hemostatic agents, on hematuria duration in autosomal dominant polycystic kidney disease (ADPKD) patients with persistent gross hematuria. METHODS: This is a retrospective study of 40 patients with ADPKD and macroscopic hematuria. 20 patients receiving TXA and snake venom blood clotting enzyme injection were compared with 20 matched patients receiving etamsylate and snake venom blood clotting enzyme injection. The primary outcome was hematuria duration and the secondary outcomes were blood transfusion requirements and adverse events. RESULTS: The hematuria duration was shorter in the TXA group compared with the etamsylate group (4[3-5] d vs 7[6-10] d, P<0.001). The volume of blood transfusion tended to be less in the TXA group than in the etamsylate group (300±115 ml vs 486±195 ml, P=0.12), and the number of patients needing a blood transfusion also tended to be lower [20% (4/20) vs 35% (7/20), P=0.29]. TXA and etamsylate were equally well tolerated and no serious adverse events were observed in both groups. CONCLUSIONS: Our study indicates that TXA treatment was more effective than etamsylate in stopping bleeding in ADPKD patients with persistent gross hematuria.

Beneficial effects of early hemostasis on spinal cord injury in the rat.

STUDY DESIGN: Experimental study. OBJECTIVES: To investigate the effect of early hemostasis on spinal cord injury (SCI). SETTING: Fourth Military Medical University, Xi'an, China. METHODS: Sprague Dawley rats were used. Hematoxylin and eosin (HE) staining was performed to observe hemorrhage at different time points (2, 6, 12, 24 and 48 h) after SCI to determine the time window of hemostatic drug administration (n=3 per time point). Three different concentrations of Etamsylate (0.025, 0.05 and 0.1 g kg-1) were administered immediately and 5 and 10 h after SCI to evaluate the effective dosage (n=6 per group). Another 82 rats were then randomly divided into two groups, Etamsylate group (0.1 g kg-1, n=41) and glucose control group (n=41). Nissl staining was performed to observe neurons at 10 days post injury. Immunohistochemistry, western blot and quantitative real-time PCR were performed to detect tissue necrosis at 7 d.p.i., the activation of astrocytes and microglia/macrophages and lesion cavity at 10 d.p.i. Basso-Beattie-Bresnahan scoring and rump height index assay were used to examine locomotion recovery. RESULTS: Early hemostasis reduced the lesion area and tissue necrosis, enhanced neuronal survival, alleviated the activation of microglia/macrophages and astrocytes and facilitated functional recovery after spinal cord contusion in rats. Early hemostasis decreased hemorrhage area and lesion area after spinal cord transection in rats. CONCLUSION: The present study demonstrated that early hemostasis has beneficial effects on SCI in the rat. It has the potential to be translated into clinical practice.

Strong negative interference of ethamsylate (Dicynone®) in serum creatinine quantification via enzymatic assay using Trinder reaction.

BACKGROUND: With discrepancies encountered as early as the verification of enzymatic method for quantification of serum creatinine, our research pointed to a later confirmed interference caused by a compound called ethamsylate present in the commonly used antihemorrhagic drug Dicynone. METHODS: We measured concentrations of creatinine of 10 patients with blood taken before and 15 minutes after the intravenous administration of a 500 mg dose of Dicynone. The creatinine concentration was determined using Jaffe method and enzymatic method that utilize Trinder reaction (Roche) in analyzer Cobas c 501 (Roche AG, Basel, Switzerland). We also monitored concentration of blood creatinine in three patients before and 15 minutes after application of Dicynone (500 mg i.v.) and in the following 6th, 12th, 18th, and 24th hours. RESULTS: We discovered a significant negative bias in creatinine results using enzymatic assay with Trinder reaction in blood taken 15 min after i.v. application of 500 mg Dicynone to patients compared to their pre-application values (average decrease of 47%). Unlike this, the results of compensated Jaffe method yielded steady results in all samples (average deviation 0.6% from original values). However, 12 h after the drug administration comparable results were seen as before the administration. CONCLUSION: Considering the strong negative interference of ethamsylate in enzymatic assay using Trinder reaction for creatinine quantification, blood from patients with prescribed Dicynone should be taken at least 12 h after the last application of the drug for obtaining the correct creatinine values.

Suppression of bladder overactivity and oxidative stress by the phytotherapeutic agent, Eviprostat, in a rat model of atherosclerosis-induced chronic bladder ischemia.

OBJECTIVES: To clarify the mechanism by which chronic bladder ischemia causes bladder functional changes, and to investigate the involvement of oxidative stress and pro-inflammatory cytokines, and the effects of the phytotherapeutic drug, Eviprostat, on these biochemical marker levels and bladder function. METHODS: Male Sprague-Dawley rats aged 15 weeks were divided into three groups. Arterial injury was experimentally induced by balloon endothelial injury of the iliac arteries, and a 2% cholesterol diet was given for 8 weeks. Rats in the arterial-injury group were given daily oral vehicle or Eviprostat, whereas sham-operated animals on a regular diet (0.09% cholesterol) were given vehicle for the last 2 weeks. Eight weeks after surgery, the levels of bladder pro-inflammatory cytokines, as well as bladder and urinary oxidative-stress markers, were determined. Cystometrograms were carried out without anesthesia or restraint. RESULTS: Bladder and urinary oxidative-stress markers, and bladder pro-inflammatory cytokine levels were significantly increased in the arterial-injury group, and Eviprostat markedly suppressed these increase. The cystometrograms showed that arterial injury decreased the intermicturition interval without affecting the micturition pressure. This decrease was reversed by Eviprostat treatment. CONCLUSIONS: Oxidative stress and pro-inflammatory cytokines might be involved in the development of overactive bladder by atherosclerosis-induced chronic bladder ischemia. Eviprostat might provide an attractive treatment option for individuals with bladder dysfunction due to chronic bladder ischemia because of its anti-oxidant and anti-inflammatory properties.

Effect of a phytotherapeutic agent, Eviprostat®, on prostatic and urinary cytokines/chemokines in a rat model of nonbacterial prostatitis.

BACKGROUND: Chronic inflammation in the prostate has recently been recognized as an important component of the symptom progression of benign prostatic hyperplasia. The objective of this study was to evaluate a range of cytokines/chemokines in prostate tissue and urine to identify markers of prostate inflammation in a prostatitis model and to investigate the effect of a phytotherapeutic agent, Eviprostat®, on these markers. METHODS: Ten-month-old male Wistar rats were divided into four groups. Nonbacterial prostatitis (NBP) was experimentally induced in groups 2-4 by castration followed by daily subcutaneous injection of 17ß-estradiol for 30 days. Control rats were fed a standard diet, while animals in the Eviprostat groups were fed a diet containing 0.05 or 0.1% Eviprostat for 30 days. The levels of cytokines/chemokines in prostate tissue on the 31st day and in urine collected the day before castration and the day before removal of the prostate were determined. RESULTS: Experimentally induced NBP increased the prostatic levels of the cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). The levels of the chemokines CCL2/monocyte chemoattractant protein-1 (MCP-1), CCL3/macrophage inflammatory protein-1α (MIP-1α), CXCL1/CINC-1, CXCL3/CINC-2, and CXCL5/LIX were elevated in both prostate and urine. Eviprostat significantly suppressed the increases in prostate IL-1ß, TNF-α and CCL3/MIP-1α and prostatic and urinary CCL2/MCP-1 and CXCL1/CINC-1. CONCLUSIONS: Chemokines, including CCL2/MCP-1 and CXCL1/CINC-1, were elevated in the prostate and urine of NBP rats, and Eviprostat potently suppressed the increases in CCL2/MCP-1 and CXCL1/CINC-1. These chemokines are therefore candidate diagnostic biomarkers for nonbacterial chronic prostatic inflammation.

Intraventricular hemorrhage in preterm infants: coagulation perspectives.

It has long been considered that a severe coagulation deficiency in premature newborns could be a major contributing factor in the occurrence of intraventricular hemorrhage (IVH). High-grade IVH has also been shown to coincide with severe derangement of coagulation in extremely low birth weight infants. This review focuses on the relevance of the physiologically developing immature hemostatic system to IVH, and the potential benefit of agents affecting hemostasis for IVH therapy or prevention in preterm infants. The findings of small, open-label interventional studies on the effect of ethamsylate, vitamin K, fresh frozen plasma, recombinant activated factor VII, and prothrombin complex concentrate on the premature coagulation system will be reviewed.

Ethamsylate for the prevention of morbidity and mortality in preterm or very low birth weight infants.

BACKGROUND: Ethamsylate decreases blood loss in certain clinical situations such as menorrhagia and following some surgical procedures. This potential to reduce bleeding has led to the hypothesis that it may have a role to play in reducing intraventricular haemorrhage in preterm infants. OBJECTIVES: To determine if ethamsylate, when compared to placebo or no treatment, reduces morbidity and/or mortality in preterm infants. SEARCH STRATEGY: We searched the Cochrane Neonatal Group Trials Register (24 August 2009), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2009, Issue 2), MEDLINE and EMBASE (January 1966 to July 2009) and the Oxford Database of Perinatal Trials. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised trials comparing ethamsylate with placebo or no treatment. The initial search for trials enrolling infants born less than 32 weeks gestation was subsequently expanded to include trials enrolling preterm infants < 35 weeks gestation or < 2000 grams birth weight. Studies were included if they reported on outcomes of all children until death or discharge home. Data from reports of neurodevelopmental follow-up were only included if at least 80% of participants were followed up. DATA COLLECTION AND ANALYSIS: Both review authors independently assessed trial quality and extracted data. We calculated relative risk (RR) and risk difference (RD) together with 95% confidence intervals (CI) and used a fixed-effect model for meta-analysis. MAIN RESULTS: Eight studies were identified but only seven trials enrolling 1410 preterm infants were located. There was no significant difference detected in neonatal mortality or neurodevelopmental outcome at two years between infants treated with ethamsylate and controls. Infants treated with ethamsylate had significantly less intraventricular haemorrhage than controls at < 31 weeks (typical RR 0.63, 95% CI 0.47 to 0.86) and < 35 weeks gestation (typical RR 0.77, 0.65 to 0.92). There was also a significant reduction in grade 3 and 4 intraventricular haemorrhage when all infants < 35 weeks gestation (typical RR 0.67, 95% CI 0.49 to 0.94) were analysed as a single group, but not for the group of infants < 32 weeks alone. There was a reduction in symptomatic patent ductus arteriosus at < 31 weeks gestation (typical RR 0.32, 95% CI 0.12 to 0.87). There were no adverse effects of ethamsylate identified from this systematic review. AUTHORS' CONCLUSIONS: Preterm infants treated with ethamsylate showed no reductions in mortality or neurodevelopmental impairment despite the reduction in any grade of intraventricular haemorrhage seen in infants < 35 weeks gestation.

Eviprostat suppresses urinary oxidative stress in a rabbit model of partial bladder outlet obstruction and in patients with benign prostatic hyperplasia.

Eviprostat is a phytotherapeutic agent that has been used widely for more than 40 years in the treatment of benign prostatic hyperplasia (BPH) in Japan and Germany, and is known to have antioxidant activity. The present study investigated the effect of Eviprostat on the levels of the urinary oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) in a rabbit model of surgical partial bladder outlet obstruction (PBOO) and in patients with lower urinary tract symptoms (LUTS) associated with BPH. In the rabbit model, 8-OHdG levels in urine collected after 3 weeks of PBOO were 3.8-fold higher than in the urine of sham-operated rabbits. When twice-daily Eviprostat was administered orally throughout the 3-week PBOO period, the increase in urinary 8-OHdG levels was suppressed by 70%. In the clinical study, nine patients who received Eviprostat for 4 weeks showed 2.5-fold lower urinary 8-OHdG levels than before treatment. During Eviprostat treatment, the total International Prostate Symptom Score (IPSS) decreased from 16.56 +/- 2.74 to 13.67 +/- 2.30 and the quality of life score from 4.22 +/- 0.40 to 3.22 +/- 0.46. The findings provide evidence that the antioxidant activity of Eviprostat is responsible for its beneficial effects in the treatment of BPH.

Effect of eviprostat on bladder overactivity in an experimental cystitis rat model.

OBJECTIVE: The purpose of this study was to investigate the effects of eviprostat, a phytotherapeutic drug, on bladder overactivity and inflammation in a cyclophosphamide (CYP)-induced cystitis rat model. METHODS: Female Sprague-Dawley rats received a single intraperitoneal injection of CYP (200 mg/kg) or saline. After the CYP injection, eviprostat (9, 18 or 54 mg/kg per day) or a vehicle was orally given twice each day. Four days after the CYP injection, bladder function was evaluated by cystometrograms under urethane anesthesia. In a separate group, bladder inflammation was compared between the eviprostat- or vehicle-treated animals. Furthermore, the effects of eviprostat on carbachol-induced muscle contraction were evaluated by an in vitro experiment. RESULTS: The intercontraction interval (ICI) significantly decreased in the CYP-injected rats in comparison to the saline-injected rats. In the CYP-injected group, 18 and 54 mg/kg per day of eviprostat treatment significantly increased the ICI, but did not change the maximum voiding pressure in comparison to the vehicle treatment. In the saline-injected group, no significant changes of any parameters in the cystometrograms were observed between the eviprostat- and vehicle-treated groups. CYP-induced bladder inflammation tended to be lower in the eviprostat-treated group in comparison to the vehicle-treated group. An in vitro experiment revealed that eviprostat failed to inhibit carbachol-induced muscle contraction. CONCLUSION: The oral administration of eviprostat suppressed CYP-induced bladder overactivity. The effects of eviprostat on the micturition reflex may be irrespective of antimuscarinic action. The present findings raise the possibility that eviprostat could be an effective treatment for bladder overactivity associated with inflammation.

Poor reproducibility of template bleeding time in horses.

BACKGROUND: Template bleeding time (TBT) is considered to be a useful test for detecting platelet function disorders and the effect of platelet-activating drugs, but studies in human medicine have concluded that the test has poor reproducibility and sensitivity. HYPOTHESIS: TBT has poor reproducibility in horses and has insufficient sensitivity to detect the effect of etamsylate on platelet function. ANIMALS: Twenty healthy horses. METHODS: TBT was determined and repeated 2 hours and 30 days later. TBT was also performed 2 hours after IV administration of etamsylate. RESULTS: Although no statistical differences were seen between the TBT values obtained at different times, the coefficients of variation for TBT replicates ranged from 26.8% to 45.5%. The reference range for TBT was 138.4-860.4 seconds. No statistically significant shortening of the mean TBT value was observed after etamsylate administration. CONCLUSION AND CLINICAL IMPORTANCE: TBT has poor reproducibility, and the reference range is too wide to make TBT useful in a clinical setting. Other tests with higher reproducibility should be considered when assessing platelet function disorders in horses.

[Uso de etamsilato para reducir el sangrado posoperatorio y el índice de transfusión en la artroplastia total de cadera. Ensayo clínico controlado]. / Use of ethamsylate to reduce postoperative bleeding and transfusion index in total hip arthroplasty. A randomized clinical trial.

ANTECEDENTES: El sangrado secundario es una de las principales causas de morbilidad después de la cirugía. El etamsilato se ha utilizado con buenos resultados para disminuir el sangrado en diversas patologías, como metrorragias, sangrado intraventricular, prostatectomías, cirugías de catarata y amigdalectomías. El objetivo de este estudio fue evaluar la efectividad del etamsilato para disminuir el sangrado en la cirugía de reemplazo total de cadera. MÉTODO: La población se dividió en dos grupos. En el grupo control se realizó la hemostasia de manera convencional; en el grupo experimental se administró etamsilato. RESULTADOS: Se incluyeron 34 pacientes, de los cuales 17 fueron aleatorizados al grupo de etamsilato y 17 al grupo control. No hubo diferencias en las características de la población entre los dos grupos. Al comparar los valores de hemoglobina preoperatoria y a las 24, 48 y 72 horas posquirúrgicas entre ambos grupos, no se encontraron diferencias estadísticamente significativas. Tampoco hubo diferencia en el hematocrito ni en la cuantificación del gasto por drenaje a las 24 y 48 horas. Hubo tres pacientes transfundidos en el grupo de etamsilato y siete en el grupo de control, lo cual no difirió significativamente (p = 0.62). CONCLUSIÓN: En este estudio no se demostró un efecto sobre la reducción de la hemorragia en pacientes sometidos a reemplazo total de cadera con el uso de etamsilato. BACKGROUND: Secondary bleeding is one of the leading causes of morbidity after the surgery. Ethamsylate has been used with good results to decrease bleeding in various pathologies such as metrorrhagia, intraventricular bleeding, prostatectomies, cataract surgeries and tonsillectomies. The objective of this study was to evaluate the effectiveness of the hemostatic agent ethamsylate to decrease bleeding in total hip replacement surgery. METHOD: The population were divided into two groups, in the control group was performed the hemostasis conventionally; in the experimental group ethamsylate was administered. RESULTS: A total of 34 patients were included, of whom 17 were randomized to the group of ethamsylate and 17 randomized to the control group. There were no differences in the characteristics of the population between the two groups. Comparing preoperative hemoglobin levels and at 24, 48 and 72 postsurgical hours between the control group and ethamsylate group there was no statistically significant difference. There was also no difference in the levels of hematocrit. In the quantification of expenditure by the drainage there was no difference between the groups at 24 and 48 hours. There were three patients transfused in the ethamsylate group and seven in the control group, which did not differ significantly (p = 0.62). CONCLUSION: An effect on the reduction of bleeding in patients undergoing total hip replacement with the use of hemostatic agent ethamsylate was not demonstrated in this study.

[Hemostatic therapy for hemorrhages during first and second trimesters].

Hemorrhages during pregnancy are the conditions requiring emergency therapy. The aim of the investigation was to study the efficiency of tranexamic acid (the drug Tranexam) in arresting bleeding and prolonging pregnancies in women with a history of threatened abortion and miscarriage. In the group of women taking tranexamic acid as part of pathogenetic treatment, hemostasis occurred more rapidly than in the control group and hence uterine hematomas resolved on shorter notice. Inclusion of tranexamic acid into the treatment regimen for patients with threatened and incipient abortion is effective in rapidly arresting hemorrhage and prolonging pregnancy.

Developmental outcome of the use of etamsylate for prevention of periventricular haemorrhage in a randomised controlled trial.

OBJECTIVE: To compare neurodevelopmental outcome of survivors of the multicentre trial of etamsylate (the iRNN for ethamsylate) for prevention of periventricular haemorrhage in very low birthweight infants. DESIGN: Double blind, single observer, prospective follow up of placebo controlled study. SETTING: Six neonatal intensive care units in the United Kingdom. Neurodevelopmental outcome was assessed in health premises or children's homes. SUBJECTS: 268 of 276 survivors of the original study were seen between 3.5 and 4.2 years of age. All were inborn and weighed 1500 g or less at birth. INTERVENTION: Etamsylate 12.5 mg/kg or placebo six hourly from within one hour of delivery for four days. MAIN OUTCOME MEASURES: McCarthy scales of children's abilities, standardised neurological examination, full physical examination, functional assessment, seven letter Stycar vision test, and audiometry. RESULTS: There was no difference between the groups in neuromotor outcome (cerebral palsy) or in the general cognitive index (GCI) of the McCarthy scales (mean GCI was 93.3 for the etamsylate group (n = 133) and 89.7 for the placebo group (n = 131); p = 0.10). There were more children with GCI < 70 (9 v 19; p = 0.047) or

[Clinical study of Eviprostat for the treatment of benign prostatic hyperplasia].

OBJECTIVE: To study the efficacy and safety of Eviprostat for the treatment of benign prostatic hyperplasia (BPH). METHODS: An open, multicentral clinical trial was conducted in 100 patients with BPH. Patients received a 12-week oral administration of Eviprostat 2 tablets per-time, 3 times a day. The main indexes of efficacy include international prostatic symptom score (IPSS), maximum urinary flow rate (Qmax), residual urine ( Ru) and prostatic volume (V). The additional indexes are quality of life score (QOL) and average urinary flow rate (Qave). RESULTS: After a 12-week therapy, IPSS, QOL score, Qmax and Qave were significantly improved. IPSS was averagely decreased by 5.67 (P < 0.001); QOL score was averagely decreased by 1.44 (P < 0.001); Qmax was averagely increased by 1.70 ml/s (P <0.001); Qave was averagely increased by 1.15 ml/s (P < 0.001); Ru was averagely decreased by 5.07 ml (P = 0.046) , PSA level was averagely decreased by 0.129 microg/L (P < 0.017). The clinical adverse event rate was 1%. CONCLUSION: Eviprostat is a kind of safe, effective and preferable drug for treating BPH. It can improve the subjective symptoms and objective measures of the patients.

Intraventricular haemorrhage in preterm infants--can we improve outcome by addressing coagulation?

During the last few decades, the survival of preterm infants has increased dramatically. Nevertheless, with the increasing number of very young and extremely low birth weight infants, morbidity is still a major problem. Intraventricular Haemorrhage (IVH) is a major complication of preterm birth, and large haemorrhages or haemorrhages associated with parenchymal brain lesions may yield a high rate of future disability. IVH is a complex, multi-factorial disorder. Prematurity and low birth weight remain as its most important risk factors, affecting vulnerability of the germinal matrix as well as the coagulation system. Approximately 80% of IVHs occur by 72 h after birth, but a considerable proportion of IVH is already visible on the first cranial ultrasound scan within a few hours of birth. The hypothesis that a severe coagulation deficiency in the premature newborn could be a major contributing factor to IVH has been suggested, and small open label interventional studies targeting the premature coagulation system have been conducted with ethamsylate, vitamin K, fresh frozen plasma, recombinant activated factor VII and prothrombin complex concentrate. The outcome of these studies will be reviewed.

A study of the effect of ethamsylate (Dicynene) on the bleeding time, von Willebrand factor level and fibrinolysis in patients with von Willebrand's disease.

Nine patients with clinically moderate or severe Type I von Willebrand's disease were treated for 2 weeks with ethamsylate (2 g/day in four equal doses) and with a matched placebo in a randomised double-blind trial. Template bleeding time, von Willebrand factor activity (ristocetin co-factor) and antigen, euglobulin lysis time and type I tissue plasminogen activator inhibitor were determined before and at the end of each treatment period. None of these parameters showed any significant change attributable to ethamsylate. Thus, despite the fact that five patients thought subjectively that their bleeding symptoms improved during ethamsylate treatment compared to only one while on placebo, we obtained no evidence that the drug was of benefit to patients with von Willebrand's disease.