Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study).

OBJECTIVE: To assess the effect of tranexamic acid (which reduces bleeding in surgical patients and reduces mortality due to bleeding in trauma patients) on intracranial haemorrhage in patients with traumatic brain injury. METHODS: A nested, randomised, placebo controlled trial. All investigators were masked to treatment allocation. All analyses were by intention to treat. Patients 270 adult trauma patients with, or at risk of, significant extracranial bleeding within 8 hours of injury, who also had traumatic brain injury. INTERVENTIONS: Patients randomly allocated to tranexamic acid (loading dose 1 g over 10 minutes, then infusion of 1 g over 8 hours) or matching placebo. MAIN OUTCOME MEASURES: Intracranial haemorrhage growth (measured by computed tomography) between hospital admission and then 24-48 hours later, with adjustment for Glasgow coma score, age, time from injury to the scans, and initial haemorrhage volume. RESULTS: Of the 133 patients allocated to tranexamic acid and 137 allocated to placebo, 123 (92%) and 126 (92%) respectively provided information on the primary outcome. All patients provided information on clinical outcomes. The mean total haemorrhage growth was 5.9 ml (SD 26.8) and 8.1 mL (SD 29.2) in the tranexamic acid and placebo groups respectively (adjusted difference -3.8 mL (95% confidence interval -11.5 to 3.9)). New focal cerebral ischaemic lesions occurred in 6 (5%) patients in the tranexamic acid group versus 12 (9%) in the placebo group (adjusted odds ratio 0.51 (95% confidence interval 0.18 to 1.44)). There were 14 (11%) deaths in the tranexamic acid group and 24 (18%) in the placebo group (adjusted odds ratio 0.47 (0.21 to 1.04)). CONCLUSIONS: This trial shows that neither moderate benefits nor moderate harmful effects of tranexamic acid in patients with traumatic brain injury can be excluded. However, the analysis provides grounds for further clinical trials evaluating the effect of tranexamic acid in this population. Trial registration ISRCTN86750102

Impact of Modifiable Bleeding Risk Factors on Major Bleeding in Patients With Atrial Fibrillation Anticoagulated With Rivaroxaban.

Background Reducing major bleeding events is a challenge when managing anticoagulation in patients with atrial fibrillation. This study evaluated the impact of modifiable and nonmodifiable bleeding risk factors in patients with atrial fibrillation receiving rivaroxaban and estimated the impact of risk factor modification on major bleeding events. Methods and Results Modifiable and nonmodifiable risk factors associated with major bleeding events were identified from the XANTUS (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation) prospective registry data set (6784 rivaroxaban-treated patients). Parameters showing univariate association with bleeding were used to construct a multivariable model identifying independent risk factors. Modeling was used to estimate attributed weights to risk factors. Heavy alcohol use (hazard ratio [HR]=2.37; 95% CI 1.24-4.53); uncontrolled hypertension (HR after parameter-wise shrinkage=1.79; 95% CI 1.05-3.05); and concomitant treatment with antiplatelets, nonsteroidal anti-inflammatory drugs, or paracetamol (HR=1.80; 95% CI 1.24-2.61) were identified as modifiable, independent bleeding risk factors. Increasing age (HR=1.25 [per 5-year increment]; 95% CI 1.12-1.38); heart failure (HR=1.97; 95% CI 1.36-2.86); and vascular disease (HR=1.91; 95% CI 1.32-2.77) were identified as nonmodifiable bleeding risk factors. Overall, 128 (1.9%) patients experienced major bleeding events; of these, 11% had no identified bleeding risk factors, 50% had nonmodifiable bleeding risk factors only, and 39% had modifiable bleeding risk factors (with or without nonmodifiable risk factors). The presence of 1 modifiable bleeding risk factor doubled the risk of major bleeding. Conclusions Elimination of modifiable bleeding risk factors is a potentially effective strategy to reduce bleeding risk in atrial fibrillation patients receiving rivaroxaban. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01606995

Access and non–access site bleeding after percutaneous coronary intervention and risk of subsequent mortality and major adverse cardiovascular events:Systematic review and meta-analysis

Background: The prognostic impact of site-specific major bleeding complications after percutaneous coronary intervention (PCI) has yielded conflicting data. The aim of this study is to provide an overview of site-specific major bleeding events in contemporary PCI and study their impact on mortality and major adverse cardiovascular event outcomes. Methods and Results: We conducted a meta-analysis of PCI studies that evaluated site-specific periprocedural bleeding complications and their impact on major adverse cardiovascular events and mortality outcomes. A systematic search of MEDLINE and Embase was conducted to identify relevant studies and random effects meta-analysis was used to estimate the risk of adverse outcomes with site-specific bleeding complications. Twenty-five relevant studies including 2 400 645 patients that underwent PCI were identified. Both non–access site (risk ratio [RR], 4.06; 95% confidence interval [CI], 3.21–5.14) and access site (RR, 1.71; 95% CI, 1.37–2.13) related bleeding complications were independently associated with an increased risk of periprocedural mortality. The prognostic impact of non–access site–related bleeding events on mortality related to the source of anatomic bleeding, for example, gastrointestinal RR, 2.78; 95% CI, 1.25 to 6.18; retroperitoneal RR, 5.87; 95% CI, 1.63 to 21.12; and intracranial RR, 22.71; 95% CI, 12.53 to 41.15. Conclusions: The prognostic impact of bleeding complications after PCI varies according to anatomic source and severity. Non–access site-related bleeding complications have a similar prevalence to those from the access site but are associated with a significantly worse prognosis partly related to the severity of the bleed. Clinicians should minimize the risk of major bleeding complications during PCI through judicious use of bleeding avoidance strategies irrespective of the access site used

Topical use of antifibrinolytic agents reduces postoperative bleeding: a double-blind, prospective, randomized study

Objective: Postoperative bleeding is still one of the most common complications of cardiac surgery. Antifibrinolytic agents successfully reduce bleeding, but there are controversies concerning adverse effects after their systemic use. By topical application of antifibrinolytic agents in pericardial cavity, most of these effects are avoided. We compared the effects of topically applied aprotinin, tranexamic acid and placebo on postoperative bleeding and transfusion requirements. - - - - - Methods: In this single-center prospective, randomized, double-blind trial, 300 adult cardiac patients were randomized into three groups to receive one million IU of aprotinin (AP group), 2.5g of tranexamic acid (TA group) or placebo (PL group) topically before sternal closure. Groups were comparable with respect to all preoperative and intraoperative variables. Postoperative bleeding, transfusion requirements and hematologic parameters were evaluated. - - - - - Results: Postoperative bleeding within first 12-h period (AP group 433+/-294 [350; 360]ml, TA group 391+/-255 [350; 305]ml, PL group 613+/-505 [525; 348]ml), as well as cumulative blood loss within 24h (AP group 726+/-432 [640; 525]ml, TA group 633+/-343 [545; 335]ml, PL group 903+/-733 [800; 445]ml), showed statistically significant inter-group differences (both p<0.001). Bleeding rates values were significantly higher in placebo group compared to the groups treated with antifibrinolytic agents (AP and TA groups) concerning both variables. Although TA group showed the lowest values, no statistical differences between TA and AP groups were found. Inter-group difference of blood product requirements was not statistically significant. - - - - - Conclusions: Topical use of either tranexamic acid or aprotinin efficiently reduces postoperative bleeding. TA seems to be at least as potent as aprotinin, but potentially safer and with better cost-effectiveness ratio

1, 2, 3, Stop the Bleed: Analysis of a Bleeding Control Educational Course

Hemorrhaging, or uncontrolled bleeding, accounts for 40% of preventable deaths in the United States that occur after a traumatic injury. The Stop the Bleed campaign was launched in 2015 by the White House National Security Council to educate the public about methods to control and stop bleeding as well as empower individuals to take action if a traumatic accident occurs. The goal of this study was to evaluate the effectiveness of the “Stop the Bleed” bleeding control course to increase knowledge about the topic as well as increase confidence to take action and use the techniques that were taught during the course appropriately. Data was collected via a cross sectional pre-post survey design. At baseline, the participants were asked basic knowledge questions about bleeding control and techniques to use as well as how confident they felt using those skills. After being presented the bleeding control material and practicing the techniques in the hands-on portion of the course, the participants were asked to complete a post-test with similar questions to that of the pre-test. De-identified responses were collected to analyze the changes in the overall knowledge scores and overall confidence scores with the use of the paired-t statistical test on SPSS. The participants (N=32) were employees within the Thomas Jefferson University Campus Security department. The overall score for the knowledge-based questions were analyzed from pre to post and showed that the changes were statistically significant (8.163,

A Fibreoptic Endoscopic Study of Upper Gastrointestinal Bleeding at Bugando Medical Centre in Northwestern Tanzania: a Retrospective Review of 240 Cases.

Upper gastrointestinal (GI) bleeding is recognized as a common and potentially life-threatening abdominal emergency that needs a prompt assessment and aggressive emergency treatment. A retrospective study was undertaken at Bugando Medical Centre in northwestern Tanzania between March 2010 and September 2011 to describe our own experiences with fibreoptic upper GI endoscopy in the management of patients with upper gastrointestinal bleeding in our setting and compare our results with those from other centers in the world. A total of 240 patients representing 18.7% of all patients (i.e. 1292) who had fibreoptic upper GI endoscopy during the study period were studied. Males outnumbered female by a ratio of 2.1:1. Their median age was 37 years and most of patients (60.0%) were aged 40 years and below. The vast majority of the patients (80.4%) presented with haematemesis alone followed by malaena alone in 9.2% of cases. The use of non-steroidal anti-inflammatory drugs, alcohol and smoking prior to the onset of bleeding was recorded in 7.9%, 51.7% and 38.3% of cases respectively. Previous history of peptic ulcer disease was reported in 22(9.2%) patients. Nine (3.8%) patients were HIV positive. The source of bleeding was accurately identified in 97.7% of patients. Diagnostic accuracy was greater within the first 24 h of the bleeding onset, and in the presence of haematemesis. Oesophageal varices were the most frequent cause of upper GI bleeding (51.3%) followed by peptic ulcers in 25.0% of cases. The majority of patients (60.8%) were treated conservatively. Endoscopic and surgical treatments were performed in 30.8% and 5.8% of cases respectively. 140 (58.3%) patients received blood transfusion. The median length of hospitalization was 8 days and it was significantly longer in patients who underwent surgical treatment and those with higher Rockall scores (P < 0.001). Rebleeding was reported in 3.3% of the patients. The overall mortality rate of 11.7% was significantly higher in patients with variceal bleeding, shock, hepatic decompensation, HIV infection, comorbidities, malignancy, age > 60 years and in patients with higher Rockall scores and those who underwent surgery (P < 0.001). Oesophageal varices are the commonest cause of upper gastrointestinal bleeding in our environment and it is associated with high morbidity and mortality. The diagnostic accuracy of fibreoptic endoscopy was related to the time interval between the onset of bleeding and endoscopy. Therefore, it is recommended that early endoscopy should be performed within 24 h of the onset of bleeding

Liver cirrhosis-epidemiological and Clinical Aspects

Liver cirrhosis is the end-stage of many different chronic liver diseases. Limited data exists on the epidemiology, natural history and complications of liver cirrhosis such as esophageal varices and malignancies in the Nordic countries after the discovery of hepatitis C (HCV). Most hepatocellular carcinomas (HCC) develop in patients with liver cirrhosis but data on the occurrence of other malignancies than HCCs in these patients are scarce. Gastrointestinal (GI) symptoms such as nausea, vomiting, abdominal pain, and diarrhea are common in patients with advanced liver disease but the importance of portal hypertension for these symptoms is unexplored. The aims of the present study were to evaluate the incidence, outcome and complications of liver cirrhosis in a Swedish population and in Iceland and the effects of portal hypertension on small bowel motility and small intestinal bacterial overgrowth (SIBO) in patients with liver cirrhosis. The annual incidence of liver cirrhosis in Gothenburg was 15.3 ±2.4/100.000 compared to 3.3 ±1.2/100.000 in Iceland, p<0.0001. In Gothenburg 50% of the patients had alcoholic cirrhosis compared to 29% in Iceland (p<0.0001). Only 9% of patients died in their first variceal bleeding, that is within one week of their first bleeding episode. Of the patients diagnosed with esophageal varices after a bleeding episode, 55% had a bleeding episode during follow-up compared to only 13% of the patients diagnosed without a bleeding episode. Variables predicting mortality in a multivariate analysis were: Child-Pugh class, bleeding before diagnosis, age and bilirubin levels. Causes of death were in 26% of cases liver failure, 19% variceal bleeding and the rest other causes. Patients with liver cirrhosis had 267 times increased risk of hepatocellular cancer. Among patients with HCV cirrhosis, 19% developed HCC and 20% of those with HCV and alcoholic liver disease (ALD). We observed 13 times increased risk of cholangiocarcinoma and also increased risk for esophageal, pancreatic, pulmonary and colorectal cancer than in the general population. Patients with liver cirrhosis and portal hypertension had more motility disturbances in the small intestine compared to those without portal hypertension and seemed to have a higher risk of small intestinal bacterial overgrowth. Conclusions: The incidence of liver cirrhosis is low in Iceland, 24% of the incidence in Gothenburg. The difference is due to lower incidence of alcoholic liver disease and HCV cirrhosis in Iceland. In patients with liver cirrhosis and esophageal varices a bleeding is still a strong risk factor for recurrent bleeding. The mortality is high but mainly from other causes than variceal bleeding and few die in the first bleeding. The risk of HCC in cirrhosis is mostly associated with HCV and is the same in HCV patients with and without alcohol overconsumption. Other malignancies than HCC are more common in patients with cirrhosis than in the general population. Abnormal small bowel motility and SIBO is common in patients with liver cirrhosis with concomitant portal hypertension. Portal hypertension per se might be significantly related to small bowel abnormalities observed in patients with liver cirrhosis

Natural history of patients with non cirrhotic portal hypertension: Comparison with patients with compensated cirrhosis

Background. The knowledge of natural history of patients with portal hypertension (PH) not due to cirrhosis is less well known than that of cirrhotic patients. Aim. To describe the clinical presentation and the outcomes of 89 patients with non-cirrhotic PH (25 with non-cirrhotic portal hypertension, INCPH, and 64 with chronic portal vein thrombosis, PVT) in comparison with 77 patients with Child A cirrhosis. Methods. The patients were submitted to a standardized clinical, laboratory, ultrasonographic and endoscopic follow-up. Variceal progression, incidence of variceal bleeding, portal vein thrombosis, ascites and survival were recorded. Results. At presentation, the prevalence of varices, variceal bleeding and ascites was similar in the 3 groups. During follow-up, the rate of progression to varices at risk of bleeding (p<0.0001) and the incidence of first variceal bleeding (p=0.02) were significantly higher in non-cirrhotic then in cirrhotic patients. A PVT developed in 32% of INCPH patients and in 18% of cirrhotics (p=0.02). Conclusions. In the patients with non–cirrhotic PH variceal progression is more rapid and bleeding more frequent than in cirrhotics. Patients with INCPH are particularly prompt to develop PVT. This observational study suggests that the management of patients with non-cirrhotic PH should take into consideration the natural history of portal hypertension in these patients and cannot be simply derived by the observation of cirrhotic patients

Coil-Assisted Retrograde Transvenous Obliteration (CARTO) for the Treatment of Portal Hypertensive Variceal Bleeding: Preliminary Results.

ObjectivesTo describe the technical feasibility, safety, and clinical outcomes of coil-assisted retrograde transvenous obliteration (CARTO) in treating portal hypertensive non-esophageal variceal hemorrhage.MethodsFrom October 2012 to December 2013, 20 patients who received CARTO for the treatment of portal hypertensive non-esophageal variceal bleeding were retrospectively evaluated. All 20 patients had at least 6-month follow-up. All patients had detachable coils placed to occlude the efferent shunt and retrograde gelfoam embolization to achieve complete thrombosis/obliteration of varices. Technical success, clinical success, rebleeding, and complications were evaluated at follow-up.ResultsA 100% technical success rate (defined as achieving complete occlusion of efferent shunt with complete thrombosis/obliteration of bleeding varices and/or stopping variceal bleeding) was demonstrated in all 20 patients. Clinical success rate (defined as no variceal rebleeding) was 100%. Follow-up computed tomography after CARTO demonstrated decrease in size with complete thrombosis and disappearance of the varices in all 20 patients. Thirteen out of the 20 had endoscopic confirmation of resolution of varices. Minor post-CARTO complications, including worsening of esophageal varices (not bleeding) and worsening of ascites/hydrothorax, were noted in 5 patients (25%). One patient passed away at 24 days after the CARTO due to systemic and portal venous thrombosis and multi-organ failure. Otherwise, no major complication was noted. No variceal rebleeding was noted in all 20 patients during mean follow-up of 384±154 days.ConclusionsCARTO appears to be a technically feasible and safe alternative to traditional balloon-occluded retrograde transvenous obliteration or transjugular intrahepatic portosystemic shunt, with excellent clinical outcomes in treating portal hypertensive non-esophageal variceal bleeding