Essentials
Most anticoagulant therapy has failed to demonstrate a survival benefit in the overall sepsis population.
We conducted separate meta‐analyses of anticoagulant therapy in three different ...populations.
Survival benefit was observed only in the septic disseminated intravascular coagulation (DIC) population.
Further randomized controlled trials should focus on specific populations with septic DIC.
Summary
Background
Although many preclinical trials have indicated the effectiveness and safety of anticoagulant therapy as an adjuvant therapy against sepsis, there is little evidence to support its effectiveness to reduce mortality in the overall population with sepsis in clinical situations. However, several studies suggested that specific anticoagulant therapy may potentially reduce mortality in patients with sepsis‐induced disseminated intravascular coagulation (DIC).
Objective
We investigated whether the survival benefit of anticoagulant therapy might pertain to the coagulopathic population with sepsis.
Methods
We conducted separate meta‐analyses of randomized controlled trials for anticoagulant therapy in three different populations: (i) overall population with sepsis, (ii) population with sepsis‐induced coagulopathy, and (iii) population with sepsis‐induced DIC. We searched MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials comparing anticoagulant therapy with placebo or no intervention in sepsis patients. We measured all‐cause mortality as the primary outcome and bleeding complications as the secondary outcome.
Results
We analyzed 24 trials enrolling 14 767 patients. There were no significant reductions in mortality in the overall sepsis population and the population with sepsis‐induced coagulopathy. Otherwise, we observed significant reductions in mortality (risk ratio 0.72, 95% confidence interval 0.62–0.85) in the population with sepsis‐induced DIC. As adverse events, bleeding complications tended to increase similarly with anticoagulant therapy in all three populations.
Conclusion
Although associated with an increased risk of bleeding, anticoagulant therapy resulted in no survival benefits in the overall sepsis population and even the population with sepsis‐induced coagulopathy; beneficial effects on mortality were observed only in the population with sepsis‐induced DIC.
This current article was dedicated to the determination of the composition of phenolic compounds in extracts of four species of the genus
in order to establish a connection between the composition of ...polyphenols and biological effects. A chemical analysis revealed that the composition of the extracts studied depended both on the plant species and its part (leaf or flower) and on the extractant used. All four species of
were rich sources of phenolic compounds and contained hydrolyzable tannins, condensed tannins, phenolic acids and their derivatives, and flavonoids. The activities included data on those that are most important for creating functional foods with
plant components: the influence on blood coagulation measured by prothrombin and activated partial thromboplastin time, and on the activity of the digestive enzymes (pancreatic amylase and lipase). It was established that plant species, their parts, and extraction methods contribute meaningfully to biological activity. The most prominent result is as follows: the plant organ determines the selective inhibition of either amylase or lipase; thus, the anticoagulant activities of
and
hold promise for health-promoting food formulations associated with general metabolic disorders.
Albumin is the most abundant plasma protein. Critical illness is often associated with altered, predominately decreased, serum albumin levels. This hypoalbuminaemia is usually corrected by ...administration of exogenous albumin. This study aimed to track the concentration-dependent influence of albumin on blood coagulation in vitro. Whole blood (WB) samples from 25 volunteers were prepared to contain low (19.3 ± 7.7 g/L), physiological (45.2 ± 7.8 g/L), and high (67.5 ± 18.1 g/L) levels of albumin. Haemostatic profiling was performed using a platelet function analyzer (PFA) 200, impedance aggregometry, a Cone and Platelet analyzer (CPA), calibrated automated thrombogram, and thrombelastometry (TEM). Platelet aggregation-associated ATP release was assessed via HPLC analysis. In the low albumin group, when compared to the physiological albumin group, we found: i) shortened PFA 200-derived closure times indicating increased primary haemostasis; ii) increased impedance aggregometry-derived amplitudes, slopes, ATP release, as well as CPA-derived average size indicating improved platelet aggregation; iii) increased TEM-derived maximum clot firmness and alpha angles indicating enhanced clot formation. TEM measurements indicated impaired clot formation in the high albumin group compared with the physiological albumin group. Thus, albumin exerted significant anticoagulant action. Therefore, low albumin levels, often present in cancer or critically ill patients, might contribute to the frequently occurring venous thromboembolism.
Introduction
The coagulopathy of cirrhosis is complex, placing patients at risk for both bleeding and thrombosis. Direct oral anticoagulants (DOACs) have equivalent or superior efficacy and safety as ...compared to vitamin K antagonists (VKAs); however, their efficacy and safety in liver cirrhosis has not been studied. To better define this, we evaluated outcomes of patients with cirrhosis prescribed DOACs compared to other anticoagulants at our center.
Methods
Retrospective cohort study of patients with cirrhosis prescribed therapeutic anticoagulation over a 3‐year period for thrombosis or prevention of stroke in patients with atrial fibrillation. The primary outcomes of interest were bleeding events and recurrent thrombosis or stroke.
Results
During the study period, 27 patients with cirrhosis were prescribed a DOAC and 18 were prescribed VKA or low molecular weight heparin (LMWH). Both groups had similar total bleeding events (8 DOAC vs 10 other, P=.12). There were significantly less major bleeding episodes in the DOAC group (1 4% vs 5 28%, P=.03). Recurrent thrombosis occurred in one patient receiving a DOAC (4%) and one patient (6%) receiving other anticoagulation (P=1.0).
Conclusions
Direct oral anticoagulant use in patients with cirrhosis may be as safe as traditional anticoagulants. Patients with cirrhosis at our center prescribed DOACs had less major bleeding events, while maintaining efficacy at preventing stroke or thrombosis.
A novel glycosaminoglycan-like sulfated polysaccharide (AAP) from the pleopods of Haliotis discus hannai Ino was purified by DEAE ion exchange chromatography followed with S-300 HR geltrion ...chromatography. Chemical composition analysis indicated that AAP was composed of galactosamine, glucuronic acid, fucose, galactose with a ratio of 2.14:2.37:2.94:1, the content of sulfate was 15.5%. The average molecular weight (Mw) was 56.2kDa in a TSK G4000 column. Further IR, 1D, 2D NMR spectroscopic analysis of the correlation signals of different sugar units gave a proposal repeating structure, as follows: Display omitted
In vitro anticoagulant assay indicated AAP prolonged both the activated partial thromboplastin time (APTT) and thrombin time (TT), with a 22.5U/mg and 72.0U/mg compared with standard heparin, respectively. The anticoagulant property of AAP was mainly attributed to powerful potentiation thrombin by anti-thrombin III.
Acute ischemic stroke (AIS) in patients with non-valvular atrial fibrillation (AF) despite oral anticoagulation (OAC) is a complex and insufficiently investigated setting. Potential strategies range ...from maintaining the current OAC to changing the substance class. We have queried the specific treatment standards on German stroke units (SUs).
By means of a standardized online questionnaire via SurveyMonkey™ (San Mateo, CA, USA), all clinical heads of German SUs were asked about their treatment standards in the following clinical situations: first AIS of an OAC-naïve AF patient, AF patient with AIS despite administration of a vitamin K antagonist (VKA), AF patient with AIS despite administration of direct OAC (DOAC). In addition, the performance of specific coagulation tests in AF patients with AIS despite OAC was queried.
160 (48%) clinical heads of German SU responded. Data from pivotal trials (84%), own experience with substances (71%), and side-effect profiles (66%) determine the initial DOAC prescription. In case of an AIS despite OAC, 83 and 18% would switch from VKA to DOAC under certain conditions and always, respectively. Half of respondents would switch from DOAC to VKA under certain conditions, while the other half would decline. 96% would switch to an alternative DOAC. The vast majority of those who made preconditions considered concomitant diseases (92, 90, and 81%, respectively). Few would consider infarct pattern (<35%). 61% perform initial coagulation tests (only one-third substance-specific assessments); however, the majority do not use these to make further decisions.
In the setting of an OAC-naïve AF patient with AIS, established pivotal data are most respected. In the unclear setting of an AIS despite OAC, most respondents consider concomitant diseases and give preference to switching to a (different) DOAC.
To evaluate the effects of therapeutic heparin compared with prophylactic heparin among moderately ill patients with covid-19 admitted to hospital wards.
Randomised controlled, adaptive, open label ...clinical trial.
28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and US.
465 adults admitted to hospital wards with covid-19 and increased D-dimer levels were recruited between 29 May 2020 and 12 April 2021 and were randomly assigned to therapeutic dose heparin (n=228) or prophylactic dose heparin (n=237).
Therapeutic dose or prophylactic dose heparin (low molecular weight or unfractionated heparin), to be continued until hospital discharge, day 28, or death.
The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation, or admission to an intensive care unit, assessed up to 28 days. The secondary outcomes included all cause death, the composite of all cause death or any mechanical ventilation, and venous thromboembolism. Safety outcomes included major bleeding. Outcomes were blindly adjudicated.
The mean age of participants was 60 years; 264 (56.8%) were men and the mean body mass index was 30.3 kg/m
. At 28 days, the primary composite outcome had occurred in 37/228 patients (16.2%) assigned to therapeutic heparin and 52/237 (21.9%) assigned to prophylactic heparin (odds ratio 0.69, 95% confidence interval 0.43 to 1.10; P=0.12). Deaths occurred in four patients (1.8%) assigned to therapeutic heparin and 18 patients (7.6%) assigned to prophylactic heparin (0.22, 0.07 to 0.65; P=0.006). The composite of all cause death or any mechanical ventilation occurred in 23 patients (10.1%) assigned to therapeutic heparin and 38 (16.0%) assigned to prophylactic heparin (0.59, 0.34 to 1.02; P=0.06). Venous thromboembolism occurred in two patients (0.9%) assigned to therapeutic heparin and six (2.5%) assigned to prophylactic heparin (0.34, 0.07 to 1.71; P=0.19). Major bleeding occurred in two patients (0.9%) assigned to therapeutic heparin and four (1.7%) assigned to prophylactic heparin (0.52, 0.09 to 2.85; P=0.69).
In moderately ill patients with covid-19 and increased D-dimer levels admitted to hospital wards, therapeutic heparin was not significantly associated with a reduction in the primary outcome but the odds of death at 28 days was decreased. The risk of major bleeding appeared low in this trial.
ClinicalTrials.gov NCT04362085.
Abstract Bariatric surgery may alter the absorption, distribution, metabolism and/or elimination (disposition) of orally administered drugs via changes to the gastrointestinal tract anatomy, body ...weight, and adipose tissue composition. As some patients who have undergone bariatric surgery will need therapeutic anticoagulation for various indications, appropriate knowledge is needed regarding anticoagulant drug disposition and resulting efficacy and safety in this population. We review general considerations about oral drug disposition in patients after bariatric surgery, as well as existing literature on oral anticoagulation after bariatric surgery. Overall, available evidence on therapeutic anticoagulation is very limited and individual drug studies are necessary to learn how to safely and effectively use the direct oral anticoagulants. Given the sparsity of presently available data, it appears most prudent to use warfarin with INR monitoring, and not direct oral anticoagulants, when full-dose anticoagulation is needed after bariatric surgery.
Objectives
To determine the effect of new oral anticoagulants (NOACs) on prescribing practices in older adults with atrial fibrillation (AF).
Design
Retrospective observational cohort study.
Setting
...Academic medical center in St. Louis, Missouri.
Participants
Individuals aged 75 and older with AF admitted to the hospital from October 2010 through September 2015 (N = 6,568, 50% female, 15% non‐white).
Measurements
Information on NOACs and warfarin prescribed at discharge was obtained from hospital discharge summaries, and linear regression was used to examine quarterly trends in their use. Multivariable logistic regression was used to assess independent predictors of anticoagulant use.
Results
NOAC use increased over time (correlation coefficient (r) = 0.87, P < .001), warfarin use did not change (r = −0.16, P = .50), and overall anticoagulant use (NOACs and warfarin) increased (r = 0.68, P = .001). NOAC use increased over time in all age groups (75–79, 80–84, 85–89) except aged 90 and older, but increasing age attenuated the rate of NOAC uptake. There was no consistent relationship between age and warfarin or overall anticoagulant use, except that individuals aged 90 and older had consistently lower use. Overall, fewer than 45% of participants were prescribed an anticoagulant. In multivariable analysis, younger age, white race, female sex, higher hemoglobin, higher creatinine clearance, being on a medical service, hypertension, stroke or transient ischemic attack, no history of intracranial hemorrhage, and a modified HAS‐BLED score of less than 3 increased the likelihood of receiving NOACs.
Conclusion
Prescription of anticoagulants for AF increased in older adults primarily because of an increase in the use of NOACs. Nonetheless, fewer than 45% of participants were prescribed an anticoagulant. Additional research is needed to optimize prescribing practices for older adults with AF.
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