Efficacy of a haemostatic matrix for the management of bleeding in patients undergoing liver resection: results from 237 cases

ABSTRACT

Background: The haemostatic matrix (FloSeal) is a topical agent that provides effective haemostasis in a range of surgical applications. We evaluated this sealant for intra-operative haemostatic effectiveness in an observational series of patients undergoing surgery for the resection of primary and metastatic liver tumours.

Methods: A haemostatic matrix was applied directly to areas of bleeding. The severity of bleeding before and after application was graded on a 5-point scale (0 = no bleeding, 1 = oozing, 2 = moderate blood flow, 3 = heavy blood flow, 4 = spurting blood). The time to complete haemostasis was also recorded.

Results: 105 women (age 61 ± 9 years) and 132 men (age 61 ± 12 years) were included in this study. One hundred and seventeen patients (49.36%) had pre-operative coagulopathy resulting from co-existent cirrhosis (67 Child-Pugh Class A; 50 Child-Pugh Class B). Prior to administration of a haemostatic matrix, 93 bleeding sites (24.8%) had a bleeding severity score of 2, 269 bleeding sites (71.7%) had a score of 3 and 13 bleeding sites (3.5%) had a score of 4. Following administration of the haemostatic matrix, bleeding stopped completely (score of 0) at 367 (97.9%) of the 375 sites and was reduced to a score of 1 at the remaining 8 sites (2.1%), of which only 2 were in patients with coagulopathy. The mean time to achieve haemostasis in the overall population was 2.9 ± 1?min; this was significantly increased in patients with coagulopathy versus non-coagulopathic patients (4 ± 1 vs. 2 ± 1?min, p < 0.001).

Conclusions: In this prospective, uncontrolled study of 237 consecutive patients undergoing major hepatic surgery to remove primary or metastatic tumours, application of a haemostatic matrix provided rapid and effective intra-operative control of mild to severe bleeding from the liver edge, even in patients with prolonged bleeding times resulting from cirrhosis. This preliminary evidence warrants a randomised, controlled clinical trial with a larger sample size.     

Management of pharmacotherapy‐related problems in acute coronary syndrome: Role of clinical pharmacist in cardiac rehabilitation unit

Acute coronary syndrome (ACS) is one of the leading causes of mortality worldwide and negatively impacts healthcare costs, productivity and quality of life. Polymorbidity and polypharmacy predispose ACS patients to medication discrepancies between cardiologist‐prescribed medication and drug use by the patient, drug‐related problems (DRPs) and inadequate drug adherence. This study aimed to evaluate the impact of clinical pharmacist–provided services on the outcome of ACS patients. This was a prospective, randomized, controlled study on ACS patients participating in a cardiac rehabilitation programme. Forty ACS patients were randomly assigned to either control group, who received standard medical care, or intervention group, who received standard medical care plus clinical pharmacist–provided services. Services included DRP management, clinical assessment and enforcing the patient education and adherence. For both groups, the following were assessed at baseline and after 3 months: DRPs, adherence (assessed by 8‐item Morisky Adherence Questionnaire), patient's knowledge (assessed by Coronary Artery Disease Questionnaire), 36‐Short Form Health Survey (SF‐36), heart rate, systolic and diastolic blood pressure, low‐density lipoprotein (LDL), total cholesterol (TC) and fasting blood glucose (FBG). After 3 months, there was a significant difference between the intervention and control groups in the per cent change of DRPs (median: ?100 vs 5.882, P = 0.0001), patient's adherence score (median: 39.13 vs ?14.58, P = 0.0001), knowledge score (median: 30.28 vs ?5.196, P = 0.0001), SF‐36 scores, heart rate (mean: ?10.04 vs 6.791, P = 0.0001), diastolic blood pressure (mean: ?17.87 vs 10.45, P = 0.0001), systolic blood pressure (mean: ?16.22 vs 4.751, P = 0.0001), LDL (median: ?25.73 vs ?0.2538, P = 0.0071), TC (median: ?14.62 vs 4.123, P = 0.0005) and FBG (median: ?11.42 vs 5.422, P = 0.0098). Clinical pharmacists can play an important role as part of a cardiac rehabilitation team through patient education and interventions to minimize DRPs.     

Development of haemostatic decontaminants for the treatment of wounds contaminated with chemical warfare agents. 1: Evaluation of in vitro clotting efficacy in the presence of certain contaminants

The treatment of penetrating, haemorrhaging injuries sustained within a hazardous environment may be complicated by contamination with toxic chemicals. There are currently no specific medical countermeasures for such injuries. Haemostats with an absorbent mechanism of action have the potential to simultaneously stop bleeding and decontaminate wounds. However, a primary requirement of a ‘haemostatic decontaminant’ is the retention of clotting function in the presence of chemical contaminants. Thus, the aim of this study was to investigate the haemostatic efficacy of seven commercially available haemostats in the presence of toxic chemicals (soman, VX, sulphur mustard, petrol, aviation fuel and motor oil). Clot viscosity was assessed ex vivo using thrombelastography following treatment of pig blood with: (i) toxic chemical; (ii) haemostat; or (iii) haemostat in combination with toxic chemical. Several contaminants (VX, petrol and GD) were found to be pro‐haemostatic and none had an adverse effect on the rate with which the test products attained haemostasis. However, the total clot strength for blood treated with certain haemostats in the presence of sulphur mustard, soman and petrol was significantly decreased. Three test products failed to demonstrate haemostatic function in this ex vivo (thrombelastography) model; this was tentatively ascribed to the products achieving haemostasis through a tamponade mechanism of action, which can only be replicated using in vivo models. Overall, this study has identified a number of commercial products that may have potential as haemostatic decontaminants and warrant further investigation to establish their decontaminant efficacy. Copyright © 2014 John Wiley & Sons, Ltd.     

Clinical trial: maintenance intermittent therapy with rabeprazole 20 mg in patients with symptomatic gastro‐oesophageal reflux disease – a double‐blind,placebo‐controlled,randomized study

Aliment Pharmacol Ther 31 , 950–960

Summary

Background Optimal long‐term management of symptomatic gastro‐oesophageal reflux disease (sGERD) patients has not been established. Aim To determine the clinical value of maintenance intermittent treatment with rabeprazole 20 mg vs. placebo in patients with sGERD. Methods This multicentre, US study enrolled patients with sGERD (≥3‐month history of GERD symptoms and ≥4 days/week of heartburn during a 2‐week placebo run‐in) without oesophageal erosions. Patients with complete heartburn control after 4 weeks of open‐label rabeprazole 20 mg daily treatment were randomized to 6‐month, double‐blind, maintenance intermittent treatment (7‐ to 14‐day courses when heartburn recurred) with rabeprazole 20 mg or placebo. Results The primary efficacy end point, mean percentage of heartburn‐free days, was significantly greater with rabeprazole vs. placebo: 82.58% and 62.17% (ITT; P < 0.0001) [per protocol 86.74% rabeprazole vs. 74.93% placebo (P < 0.0254)]. Compared with placebo group, the rabeprazole group also experienced a significantly higher percentage of heartburn‐free daytime (84.06% vs. 63.39%; P < 0.0001) and nighttime (95.41% vs. 90.25%; P = 0.0021) periods, had significantly fewer discontinuations because of insufficient heartburn control (6.3% vs. 36.3%; P < 0.0001) and took fewer antacid tablets daily (0.58 vs. 1.16; P = 0.0021). Conclusion Intermittent use of rabeprazole may be an effective maintenance treatment strategy for patients with sGERD and warrants further investigation. This trial was registered with http://clinicaltrials.gov under the number NCT00165841.     

Randomised clinical trial: a 'nudge' strategy to modify endoscopic sedation practice

Aliment Pharmacol Ther 2011; 34: 229–234

Summary

Background In behavioural economics, a ‘nudge’ describes configuration of a choice to encourage a certain action without taking away freedom of choice. Aim To determine the impact of a ‘nudge’ strategy – prefilling either 3 mL or 5 mL syringes with midazolam – on endoscopic sedation practice. Methods Consecutive patients undergoing sedation for EGD or colonoscopy were enrolled. On alternate weeks, midazolam was prefilled in either 3 mL or 5 mL syringes. Preprocedure sedation was administered by the endoscopist to achieve moderate conscious sedation; dosages were at the discretion of the endoscopist. Meperidine was not prefilled. Results Overall, 120 patients received sedation for EGD [59 (5 mL), 61 (3 mL)] and 86 patients were sedated for colonoscopy [38 (5 mL), 48 (3 mL)]. For EGDs, average midazolam dose was significantly higher in the 5‐mL group (5.2 mg) vs. 3‐mL group (3.3 mg), (P < 0.0001); for colonoscopies, average midazolam dose was also significantly higher in the 5‐mL group (5.1 mg) vs. 3‐mL group (3.3 mg), (P < 0.0001). There was no significant difference in mean meperidine dose (42.1 mg vs. 42.8 mg, P = 0.9) administered to both colonoscopy groups. No adverse sedation‐related events occurred; no patient required reversal of sedation. Conclusions These findings demonstrate that ‘nudge’ strategies may hold promise in modifying endoscopic sedation practice. Further research is required to explore the utility of ‘nudges’ in impacting other aspects of endoscopic practice.     

内镜黏膜下剥离术治疗消化道良性肿瘤30例临床分析

目的：探讨内镜黏膜下剥离术（endoscopic submucosal dissection,ESD）在治疗消化道良性肿瘤中的应用价值。方法收集近2年电子胃肠镜发现的30例胃与大肠黏膜及黏膜下良性肿瘤,内镜超声检查和（或）病理活检进一步明确病灶大小、位置及性质。 ESD操作步骤：黏膜下注射液体以抬高病灶,接着预切开病灶周围黏膜,之后使用Hook刀或IT刀沿病灶黏膜下层完整剥离病灶。结果30例患者均顺利完成ESD治疗,病变直径1.0-3.5cm,平均2.3cm,ESD手术时间30-175min,平均73 min,ESD治疗过程中创面均有少量出血,均经电凝或金属钛夹止血,无术后延迟出血发生,穿孔发生率为6.7%（1/15）,术后随访1-8个月,未见肿瘤残留或复发。结论 ESD作为一种内镜微创治疗,能实现较大病灶的完全剥离,为临床提供完整的病理学资料,也为消化道黏膜及黏膜下良性肿瘤的治疗开辟了新的治疗途径。     

The pharmacodynamics and pharmacokinetics of S‐tenatoprazole‐Na 30 mg, 60 mg and 90 mg vs. esomeprazole 40 mg in healthy male subjects

Aliment Pharmacol Ther 31 , 648–657

Summary

Background Racemic tenatoprazole 40 mg/day provides more prolonged acid suppression than esomeprazole 40 mg/day. Aim To compare pharmacodynamic and pharmacokinetic profiles of tenatoprazole and esomeprazole. Methods A single‐centre, double‐blind, double‐dummy, randomized, 4‐way, cross‐over study was conducted in 32 healthy male subjects. S‐tenatoprazole‐Na 30, 60 or 90 mg, or esomeprazole 40 mg was administered once daily for 5 days with 10‐day washout intervals. The 24‐h intragastric pH was recorded at baseline and on day 5 of each period. Results On day 5, median pH (5.34 ± 0.45 and 5.19 ± 0.52 vs. 4.76 ± 0.82, respectively, P < 0.002) and percentage time with pH > 4 (80 ± 11 and 77 ± 12, vs. 63 ± 11 respectively, P < 0.0001) for 24‐h were higher with S‐tenatoprazole‐Na 90 mg and 60 mg than esomeprazole. In nocturnal periods, S‐tenatoprazole‐Na 90 mg, 60 mg and 30 mg were superior to esomeprazole with regard to median pH (5.14 ± 0.64, 4.94 ± 0.65, 4.65 ± 0.86 and 3.69 ± 1.18 respectively, P < 0.0001) and percentage time with pH > 4 (77 ± 12, 73 ± 17, 64 ± 17 and 46 ± 17 respectively, P < 0.0001). Proportion of subjects with nocturnal acid breakthrough with S‐tenatoprazole‐Na 90 mg, 60 mg and 30 mg was significantly less than with esomeprazole (54.8, 43.3, 56.7 and 90.3 respectively, P < 0.04). The proportion of subjects with >16 hrs with pH >4 was significantly higher with S‐tenatoprazole‐Na 90 mg and 60 mg than with esomeprazole (87.1%, 83.3% and 41.9% respectively, P < 0.02). Conclusions S‐tenatoprazole‐Na produced significantly greater and more prolonged dose‐dependent 24‐h and nocturnal acid suppression than esomeprazole. S‐tenatoprazole‐Na may provide greater clinical efficacy compared with current PPIs for patients with ineffective once‐daily therapy.     

The effect of nimesulide versus placebo on hemostasis in healthy volunteers

Objective: The primary objective was to evaluate the effect of 7 days treatment with nimesulide on bleeding time. Blood coagulation, von Willebrand factor and platelet aggregation ex vivo were investigated as a secondary objective. Method: A randomised, double-blind, placebo-controlled, parallel group, single centre study performed on 20 healthy male volunteers who received either placebo or nimesulide 100 mg twice daily for 7 days. Bleeding time, platelet count and platelet aggregation, thromboplastin time (prothrombin time), activated partial thromboplastin time, fibrinogen, Factor VIII:C, vWF:Ag, vWF:RCof and platelet-rich plasma aggregation following stimulation with adenosine 5′-diphosphate, collagen, arachidonic acid, ristocetin, thrombin and thrombin receptor-activating peptide were measured at baseline (day 0), and then 3 h after the first (day 1) and last (day 7) treatment. Results: The bleeding times for all subjects remained within the normal range throughout the study period, with no significant differences between the two treatment groups. There were no significant changes from baseline in platelet aggregation studies or in any of the other haemostasis tests, with no significant differences between the two groups. No clinically significant adverse events were reported or observed. Conclusions: Daily administration of 200 mg nimesulide for 7 days neither prolongs bleeding time nor modifies any of the other haemostasis variables measured. The lack of interactions with important haemostatic mechanisms suggests that nimesulide may also be used in patients with bleeding problems. This expectation has still to be confirmed by clinical experience. Received: 6 October 1997 / Accepted in revised form: 5 March 1998     

Haemostatically active proteins in snake venoms

Snake venom proteins that affect the haemostatic system can cause (a) lowering of blood coagulability, (b) damage to blood vessels, resulting in bleeding, (c) secondary effects of bleeding, e.g. hypovolaemic shock and organ damage, and (d) thrombosis. These proteins may, or may not, be enzymes. We review the data on the most relevant haemostatically active proteinases, phospholipases A₂, l-amino acid oxidases and 5′-nucleotidases from snake venoms. We also survey the non-enzymatic effectors of haemostasis from snake venoms - disintegrins, C-type lectins and three-finger toxins. Medical applications have already been found for some of these snake venom proteins. We describe those that have already been approved as drugs to treat haemostatic disorders or are being used to diagnose such health problems. No clinical applications, however, currently exist for the majority of snake venom proteins acting on haemostasis. We conclude with the most promising potential uses in this respect.     

宫血宁胶囊联合醋酸甲羟孕酮和戊酸雌二醇治疗青春期功能失调性子宫出血的疗效观察

目的探讨宫血宁胶囊联合醋酸甲羟孕酮和戊酸雌二醇治疗青春期功能失调性子宫出血的临床疗效。方法选取2014年1月—2015年1月在海南省第三人民医院接受治疗的青春期功能失调性子宫出血患者76例,随机分为对照组和治疗组,每组各38例。所有患者均给予必要的心理干预。对照组口服醋酸甲羟孕酮片,8 mg/d,止血3 d后开始减量,每3天减量1/3,维持量为1 mg/d;同时口服戊酸雌二醇片,4~6 mg/次,3次/d。治疗组在对照组基础上口服宫血宁胶囊,2粒/次,3次/d。两组患者均连续治疗21 d。观察两组患者的临床疗效,同时比较治疗前后两组患者止血时间、性激素水平和WHOQOL-BREF评分的变化情况。结果治疗后,对照组和治疗组总有效率分别为84.21%、97.37%,两组比较差异有统计学意义(P0.05)。治疗后,治疗组的有效控制出血时间和完全止血时间明显短于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者促卵泡激素(FSH)、黄体生成素(LH)、雌二醇(E2)水平均明显降低(P0.05);且治疗组上述性激素指标水平降低更显著(P0.05)。治疗后,两组患者生理健康评分、心理状态评分、社会关系评分、周围环境评分和总分均较同组治疗前升高(P0.05);治疗组上述各项WHOQOL-BREF评分升高的更明显(P0.05)。结论宫血宁胶囊联合醋酸甲羟孕酮和戊酸雌二醇治疗青春期功能失调性子宫出血疗效确切,可有效提高患者生活质量,具有一定的临床应用推广价值。     

Early symptomatic response and mucosal healing with mesalazine rectal suspension therapy in active distal ulcerative colitis--additional results from two controlled studies

Aliment Pharmacol Ther 2011; 34: 747–756

Summary

Background Rapid resolution of symptoms and endoscopic inflammation in ulcerative colitis (UC) represent important treatment goals. Aims To establish times to bleeding cessation and endoscopic healing for topical and oral mesalazine in active distal UC, a post hoc analysis of two published studies was performed. Methods Study I (Sutherland 1987) compared mesalazine rectal suspension to placebo, while Study II (Safdi 1997) compared topical suspensions, either alone or in combination with oral mesalazine, and oral alone. Cessation of rectal bleeding (RB) was defined as absence of bleeding on four consecutive days. Endoscopic remission was defined as DAI mucosal healing (MH) subscore = 0 and clinical remission as MH subscore = 0–1 and ≥ 1‐point improvement, plus RB subscore = 0. Results Study I: By Day 2, 31.4% of subjects using topical monotherapy reported no RB vs. 5.5% in the placebo arm (P < 0.0006); median time to RB cessation was 8 days. Significantly higher rates of endoscopic (25.0% vs. 7.8%, P < 0.005) and clinical remission (48.6% vs. 9.6%, P < 0.0001) were observed at Week 3. Study II: A significantly higher proportion of subjects achieved RB cessation with combination therapy vs. oral therapy, commencing by Day 8. By Week 3, a significantly higher proportion of subjects using combination therapy achieved clinical remission compared to oral therapy alone (57.9% vs. 18.2%, P < 0.05). Conclusions Topical mesalazine suspension, either alone or in combination with oral mesalazine, led to earlier rectal bleeding cessation and mucosal healing. These data support use of topical therapy for more rapid treatment benefit in active distal ulcerative colitis.     

窄带成像技术在胃黏膜高级别上皮内瘤变内镜黏膜下剥离术中的应用价值

目的 考察窄带成像技术（NBI）在胃黏膜高级别上皮内瘤变内镜黏膜下剥离术（ESD）中的应用价值。方法 选择2011年10月至2017年9月武警河南总队医院收治的221例高级别胃黏膜上皮内瘤变（HGIN）患者，根据术前检查方式不同将患者分为NBI组（113例）与白光内镜（WLE）组（98例），两组患者均接受ESD术治疗。比较两组患者术前内镜图像清晰程度、手术一般情况、围术期并发症及随访复发与生存情况。结果 NBI组对黏膜微血管形态与病变轮廓的图像清晰程度高于WLE组，差异有统计学意义（P<0.01），两组胃小凹形态的图像质量差异无统计学意义（P>0.05）；NBI组手术时间（52.37±20.23）分，少于WLE组的（72.14±19.86）分，差异有统计学意义（P<0.05）；NBI组切除的病灶直径、一次性整块切除率、治愈性切除率均高于WLE组，差异有统计学意义（P<0.05）；术后随访，NBI组复发率0.88%、并发症发生率5.31%，均低于WLE组的11.22%、25.51%，差异均有统计学意义（P<0.05）。结论 对于ESD治疗胃黏膜HGIN患者，WLE可实现病灶范围的精确标记与环切剥离，缩短手术时间，提升病灶切除的有效性及手术安全性。     

Omeprazole‐Mg 20.6 mg is superior to lansoprazole 15 mg for control of gastric acid: a comparison of over‐the‐counter doses of proton pump inhibitors

Aliment Pharmacol Ther 31 , 846–851

Summary

Background Over‐the‐counter (OTC) proton pump inhibitors (PPIs) relieve heartburn by decreasing the production of gastric acid, but may not do so with equal effectiveness. It is important for healthcare professionals to compare the ability of OTC PPIs to control gastric acid when recommending them for patients with frequent heartburn. Aim To compare the effects of omeprazole‐Mg 20.6 mg and lansoprazole 15 mg (OTC doses in the US) on 24‐h steady state gastric acid suppression. Methods This single‐centre, randomized, double‐blind clinical study compared the steady‐state gastric acid control of omeprazole‐Mg 20.6 mg vs. lansoprazole 15 mg, dosed before breakfast. Volunteers were enrolled in a 3‐period, cross‐over design (ABB, BAA) with 24‐h gastric pH monitoring on dosing day 5. The primary efficacy variable was the percentage time intragastric pH was >4.0 over 24 h on day 5 of dosing. Results Forty subjects were enrolled; all completed the study. The mean (SE) percentage time pH was >4.0 was 45.7% (3.45%) for omeprazole‐Mg 20.6 mg and 36.8% (3.45%) for lansoprazole 15 mg, an absolute difference of 8.9% (P < 0.0001), and a relative difference of 24.2%. Both drugs were well tolerated. Conclusion Omeprazole‐Mg 20.6 mg provided a statistically significantly (P < 0.0001) greater acid control than lansoprazole 15 mg.     

Transient elastography and biomarkers for liver fibrosis assessment and follow-up of inactive hepatitis B carriers

Background Non invasive methods for fibrosis evaluation remain to be validated longitudinally in hepatitis B. Aim To evaluate longitudinally transient elastography (TE) and biomarkers for liver fibrosis assessment and follow‐up of hepatitis B virus (HBV) inactive carriers. Methods Three hundred and twenty‐nine consecutive HBeAg‐negative HBV patients (201 inactive carriers) who underwent TE, Fibrotest and aspartate to platelet ratio index (APRI) the same day were studied. Results TE (median 4.8 vs. 6.8 kPa, P < 0.0001), Fibrotest (0.16 vs. 0.35, P < 0.0001) and APRI values (0.28 vs. 0.43, P < 0.0001) were significantly lower in inactive carriers than in the remaining patients whereas they did not differ among inactive carriers according to HBV DNA levels. In 82 inactive carriers with repeated examinations, although differences were observed among individual patients, TE values did not differ significantly over time (median intra‐patient changes at end of follow‐up relative to baseline: ?0.2 kPa, P = 0.12). Conversely, significant fluctuations were observed for Fibrotest (+0.03, P = 0.012) and APRI (?0.01, P < 0.05). Eleven inactive carriers (5.5%) had initial elevated TE values (>7.2 kPa) confirmed during follow‐up in two with significant fibrosis (F2 and F3) on liver biopsy. Conclusion Non‐invasive tools, particularly TE, could be useful, in addition to HBV DNA and transaminase levels, for follow‐up of HBV inactive carriers as well as better selection of patients who require a liver biopsy.     

Prospective randomized trial evaluating ketamine for advanced endoscopic procedures in difficult to sedate patients

Background Adequate patient sedation is mandatory for advanced endoscopic procedures such as ERCP and EUS. Aim To evaluate the effectiveness and safety of ketamine in difficult to sedate patients undergoing advanced endoscopic procedures. Methods This was a prospective, randomized trial of all patients undergoing ERCP or EUS who were not adequately sedated despite administration of meperidine 50 mg, midazolam 5 mg and diazepam 5 mg. Patients during endoscopy were then randomized to receive either intravenous ketamine (20 mg) every 5 min or continue to receive standard sedation using meperidine and diazepam. Results Of 175 patients, 82 were randomized to receive ketamine and 93 standard sedatives. Compared with standard sedation, qualitative physician rating (P < 0.0001) and depth of sedation (P < 0.001) were superior in the ketamine group with shorter recovery times (P < 0.0001). Both patient discomfort and sedation‐related technical difficulty were significantly less among patients randomized to receive ketamine (P < 0.0001). More patients in the standard sedation group were crossed‐over to the ketamine group due to sedation failure (35.5 vs. 3.7%, P < 0.0001). Nine patients who received ketamine, developed adverse events that were managed conservatively. Conclusions Ketamine is a useful adjunct to conscious sedation in patients who are difficult to sedate. Its use results in better quality and depth of sedation with shorter recovery times than patients sedated using benzodiazepines and meperidine alone. Further prospective studies evaluating the effectiveness and safety of ketamine for endoscopic sedation are needed.     

不同剂量奥曲肽联合兰索拉唑治疗肝硬化合并上消化道出血疗效及安全性评价

目的评价不同剂量奥曲肽联合兰索拉唑治疗肝硬化合并上消化道出血疗效及安全性。方法 2013年5月-2016年5月收治的80例肝硬化合并上消化道出血患者均予奥曲肽联合兰索拉唑治疗,根据奥曲肽的剂量不同分为大剂量组（40例）与小剂量组（40例）,治疗前后分别彩超测定门静脉平均流速（PVV）与门静脉内径（PVD）,记录止血时间、输血例数、输血量及再出血例数,观察不良反应。结果治疗后2组PVV与PVD均明显改善（P<0.05）,组间比较无明显差异。大剂量组止血时间、输血率、输血量及再出血率均明显少于小剂量组（P<0.05）。大剂量组总有效率为90.0%,小剂量组为70.0%,两组比较差异显著（P<0.05）。大剂量组不良反应发生率与小剂量组无明显差异。结论大剂量奥曲肽联合兰索拉唑治疗肝硬化合并上消化道出血对止血作用有增益,且不会明显增加不良反应。     

Natural history of acute colonic diverticular bleeding: a prospective study in 133 consecutive patients

Aliment Pharmacol Ther 2010; 32: 466–471

Summary

Background Bleeding recurrence rate after spontaneous haemostasis of colonic diverticular haemorrhage varies in the literature, and a small minority of patients will require endoscopic, radiological or surgical intervention. Aim To study the natural history of colonic diverticular bleeding in consecutive patients. Methods We studied prospectively consecutive patients admitted for colonic diverticular bleeding from 1997 to 2005. Data on age, gender, 30‐day mortality, therapeutic modality for bleeding management and subsequent rebleeding were collected. Results One hundred and thirty‐three patients (mean age 75.7 years) were recruited. Bleeding stopped spontaneously in 123 patients (92.4%). A more interventional approach was necessary in 10 patients. Thirty‐day mortality rate for first bleeding was 2.25%. Out of the 123 patients managed conservatively and submitted to an average follow‐up of 47.5 months, 17 (13.8%) presented at least one recurrent diverticular bleeding. Spontaneous haemostasis was obtained in all recurrent cases except one, who died. The estimated bleeding recurrence rate was 3.8% at 1 year, 6.9% at 5 years and 9.8% at 10 years. Conclusions The low estimated rebleeding rate and the fact that rebleeding can be treated conservatively in most cases suggest that an aggressive approach with intervention is not justified.     

Comparing coagulation activity of Selaginella tamariscina before and after stir-frying process and determining the possible active constituents based on compositional variation

Context: Selaginella tamariscina (P. Beauv.) Spring (Selaginellaceae) (ST) has been widely used in China as a medicine for improving blood circulation. However, its processed product, S. tamariscina carbonisatus (STC), possesses opposite haemostatic activity.

Objective: To comprehensively evaluate the activity of ST and STC on physiological coagulation system of rats, and seek potential active substances accounting for the activity transformation of ST during processing.

Materials and methods: The 75% methanol extracts of the whole grass (fine powder) of ST and STC were prepared, respectively. Male Sprague–Dawley rats were randomly divided into five groups: control group, model group, model?+?ST group, model?+?STC group and positive control group (model?+?Yunnanbaiyao). The duration of intragastric administration was 72?h at 12?h intervals. Haemorheology parameters were measured using an LB-2?A cone-plate viscometer and the existed classic methods, respectively. SC40 semi-automatic coagulation analyzer was employed to determine coagulation indices. Meanwhile, HPLC and LC-MS were applied for chemical analyses of ST and STC extracts.

Results: STC shortened tail-bleeding time, increased whole blood viscosity (WBV) and plasma viscosity (PV), decreased erythrocyte sedimentation rate blood (ESR), reduced activated partial thromboplastin time (APTT) and increased the fibrinogen (FIB) content in the plasma of bleeding model rats. Although ST could shorten APTT and TT, the FIB content was significantly decreased by ST. Dihydrocaffeic acid with increased content in STC vs. ST showed haemostatic activity for promoting the platelet aggregation induced by collagen and trap-6, and reducing APTT and PT significantly with a concentration of 171.7?μM in vitro. Amentoflavone with reduced content in STC vs. ST inhibited ADP and AA-induced platelet aggregation significantly with a concentration of 40.7?μM.

Discussion and conclusions: As the processed product of ST, STC showed strong haemostatic activity on bleeding rat through regulating the parameters involved in haemorheology and plasma coagulation system. Two active compounds, dihydrocaffeic acid and amentoflavone, might be partially responsible for the haemostatic and anticoagulant activity of STC and ST, respectively.     

Modulation of haemostatic function and prevention of experimental thrombosis by red wine in rats: a role for increased nitric oxide production.

1. The effects of ethyl alcohol and wine (red and white) on haemostatic parameters and experimental thrombosis were studied in rats; NO was evaluated as a possible mediator of these effects. 2. We found that red wine (12% alcohol) supplementation (8.4 +/- 0.4 ml d-1 in drinking water, for 10 days) induced a marked prolongation of 'template' bleeding time (BT) (258 +/- 13 vs 132 +/- 13 s in controls; P < 0.001), a decrease in platelet adhesion to fibrillar collagen (11.6 +/- 1.0 vs 32.2 +/- 1.3%; P < 0.01) and a reduction in thrombus weight (1.45 +/- 0.33 vs 3.27 +/- 0.39 mg; P < 0.01). 3. Alcohol-free red wine showed an effect similar to red wine. In contrast, neither ethyl alcohol (12%) nor white wine (12% alcohol) affected these systems. 4. All these effects were also observed after red wine i.v. injection (1 ml kg-1 of 1:4 dilution) 15 min before the experiments. 5. The effects of red wine were prevented by the NO inhibitor, N omega nitro-L-arginine-methyl ester (L-NAME). L-arginine, not D-arginine, reversed the effect of L-NAME on red wine infusion. 6. Red wine injection induced a 3 fold increase in total radical-trapping antioxidant parameter values of rat plasma with respect to controls, while white wine and alcohol did not show any effect. 7. Our study provides evidence that red wine modulates primary haemostasis and prevents experimental thrombosis in rats, independently of its alcohol content, by a NO-mediated mechanism.     

Low‐dose adjunctive cilostazol in patients with complex lesions undergoing percutaneous coronary intervention

Patients with complex coronary lesions undergoing percutaneous coronary intervention (PCI) have more major adverse cardiac events (MACE) than do those with simpler cases. Therefore, intensive antiplatelet therapy might be needed in these patients. A total of 127 patients with complex lesions undergoing PCI in the Second Hospital of Tianjin Medical University from October 2012 to April 2014 were randomized to receive either dual (aspirin plus clopidogrel, DAPT, n = 66), or triple antiplatelet therapy (aspirin plus clopidogrel plus cilostazol; TAPT, n = 61). Patients in the TAPT group received low‐dose cilostazol (100 mg loading, followed with 50 mg twice per day) for 3–6 months. The primary endpoint was composite MACE. The complex coronary target lesions were defined as at least one of the following: left main disease; severe 3‐vessel disease; chronic total occlusion lesions; true bifurcation lesion; ostial lesions; severe calcified lesions; and highly thrombotic lesions. The two groups had similar baseline clinical and angiographic characteristics. One‐year clinical outcomes showed that the TAPT group had significantly lower incidences of myocardial infarction (1.6% vs 13.6%, P = 0.018) and MACE (1.6% vs 16.7%, P = 0.004) than DAPT group. The DAPT group had two cases of stent thrombosis, while the TAPT group did not. Furthermore, adjunctive low‐dose cilostazol didn't significantly increase the incidence of bleeding events (26.2% vs 19.7%, P = 0.381) regardless of major (4.9% vs 4.5%, P = 0.921) or minor (21.3% vs 15.2%, P = 0.368) bleeding events. In conclusion, low‐dose adjunctive cilostazol seems superior to dual antiplatelet therapy in reducing recurrent ischemic events in patients with complex coronary lesions and the two test groups have a similar incidence of bleeding events.