Summary
There has been an explosion of interest in the ability of tranexamic acid to reduce morbidity and mortality in surgical and traumatic bleeding. Tranexamic acid has been shown to reduce ...mortality due to traumatic bleeding by a third, without apparent safety issues. It is now clearly established that intravenous tranexamic acid reduces blood loss in patients with surgical bleeding and the need for transfusion. It can also be used topically to reduce bleeding. Its use is being explored further in large pragmatic trials in traumatic head injury, postpartum haemorrhage and in upper gastro‐intestinal haemorrhage. There are few side effects from the use of tranexamic acid except when administered in high dose where neurological events have been noted, possibly relating to tranexamic acid interfering with cerebral GABA and glycine receptors. However, clinical studies suggest that there is no increased efficacy in using a higher dose, and that a dose of 1 g intravenously in an adult patient has maximal efficacy, which is not increased by higher doses. The CRASH‐2 trauma trial clearly showed no increase in thrombotic events after its use in trauma, indeed there was a significant reduction in myocardial infarction. However, trials of tranexamic acid in surgery have failed to adequately study its effects on the risk of postoperative venous and possible reduction in arterial thrombo‐embolism, and this needs to be the subject of future research.
van der Waals heterostructures constitute a new class of artificial materials formed by stacking atomically thin planar crystals. We demonstrated band structure engineering in a van der Waals ...heterostructure composed of a monolayer graphene flake coupled to a rotationally aligned hexagonal boron nitride substrate. The spatially varying interlayer atomic registry results in both a local breaking of the carbon sublattice symmetry and a long-range moiré superlattice potential in the graphene. In our samples, this interplay between short-and long-wavelength effects resulted in a band structure described by isolated superlattice minibands and an unexpectedly large band gap at charge neutrality. This picture is confirmed by our observation of fractional quantum Hall states at ±5/3 filling and features associated with the Hofstadter butterfly at ultrahigh magnetic fields.
The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and ...presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.
Plasminogen is the proenzyme of plasmin, the key protease of the fibrinolytic system, but its role is not limited to fibrinolysis regulation. Plasminogen binds not only to fibrin, but also to ...different receptors on cell surfaces, including the heterotetrameric complex Annexin A2-S100A10, enolase-1, histone H2B and the plasminogen receptor Plg-R(KT) . These receptors localize plasmin generation to the cell surface and provide a broad spectrum of reactions including proteolytic activity, cell migration and recruitment as well as signaling pathway activation. These plasminogen-binding proteins are involved in both physiologic and pathologic processes such as inflammation, thrombosis and cancer. Thus, plasminogen is at the center of a complex tightly controlled and regulated system where plasminogen-binding proteins have a crucial role, suggesting new therapeutic and diagnostic strategies. This review will discuss currently available information on plasminogen receptors, particularly their mechanisms of action and their roles in inflammatory, autoimmune and malignant disease.
Trauma is a global disease, with over 2.5 million deaths annually from hemorrhage and coagulopathy. Overt hyperfibrinolysis is rare in trauma, and is associated with massive fatal injuries. ...Paradoxically, clinical trials suggest a much broader indication for antifibrinolytics.
To determine the incidence and magnitude of fibrinolytic activation in trauma patients and its relationship to clot lysis as measured by thromboelastometry.
A prospective cohort study of 303 consecutive trauma patients admitted between January 2007 and June 2009 was performed. Blood was drawn on arrival for thromboelastometry (TEM) and coagulation assays. Follow-up was until hospital discharge or death. TEM hyperfibrinolysis was defined as maximum clot lysis of > 15%. Fibrinolytic activation (FA) was determined according to plasmin-antiplasmin (PAP) complex and D-dimer levels. Data were collected on demographics, mechanism, severity of injury, and baseline vital signs. The primary outcome measure was 28-day mortality. The secondary outcome measures were 28-day ventilator-free days and 24-h transfusion requirement.
Only 5% of patients had severe fibrinolysis on TEM, but 57% of patients had evidence of 'moderate' fibrinolysis, with PAP complex levels elevated to over twice normal (> 1500 μg L(-1)) without lysis on TEM. TEM detected clot lysis only when PAP complex levels were increased to 30 times normal (P < 0.001) and antiplasmin levels were < 75% of normal. Patients with FA had increased 28-day mortality as compared with those with no FA (12% vs. 1%, P < 0.001), fewer ventilator-free days, and longer hospital stay.
FA occurs in the majority of trauma patients, and the magnitude of FA correlates with poor clinical outcome. This was not detected by conventional TEM, which is an insensitive measure of endogenous fibrinolytic activity.
Summary
Over the last 10 years, the management of major haemorrhage in trauma patients has changed radically. This is mainly due to the recognition that many patients who are bleeding when they come ...in to the emergency department have an established coagulopathy before the haemodilution effects of fluid resuscitation. This has led to the use of new terminology: acute traumatic coagulopathy, acute coagulopathy of trauma shock or trauma‐induced coagulopathy. The recognition of acute traumatic coagulopathy is important, because we now understand that its presence is a prognostic indicator, as it is associated with poor clinical outcome. This has driven a change in clinical management, so that the previous approach of maintaining an adequate circulating volume and oxygen carrying capacity before, as a secondary event, dealing with coagulopathy, has changed to haemostatic resuscitation as early as possible. While there is as yet no universally accepted assay or definition, many experts use prolongation of the prothrombin time to indicate that there is, indeed, a coagulopathy. Hypoxia, acidosis and hypothermia and hormonal, immunological and cytokine production, alongside consumption and blood loss, and the dilutional effects of resuscitation may occur to varying extents depending on the type of tissue damaged, the type and extent of injury, predisposing to, or amplifying, activation of coagulation, platelets, fibrinolysis. These are discussed in detail within the article.
Derangement of the coagulation system is a common phenomenon in critically ill patients, who may present with severe bleeding and/or conditions associated with a prothrombotic state. Monitoring of ...this coagulopathy can be performed with conventional coagulation assays; however, point-of-care tests have become increasingly attractive, because not only do they yield a more rapid result than clinical laboratory testing, but they may also provide a more complete picture of the condition of the hemostatic system. There are many potential areas of study and applications of point-of-care hemostatic testing in critical care, including patients who present with massive blood loss, patients with a hypercoagulable state (such as in disseminated intravascular coagulation), and monitoring of antiplatelet treatment for acute arterial thrombosis, mostly acute coronary syndromes. However, the limitations of near-patient hemostatic testing has not been fully appreciated, and are discussed here. The currently available evidence indicates that point-of-care tests may be applied to guide appropriate blood product transfusion and the use of hemostatic agents to correct the hemostatic defect or to ameliorate antithrombotic treatment. Disappointingly, however, only in cardiac surgery is there adequate evidence to show that application of near-patient thromboelastography leads to an improvement in clinically relevant outcomes, such as reductions in bleeding-related morbidity and mortality, and cost-effectiveness. More research is required to validate the utility and cost-effectiveness of near-patient hemostatic testing in other areas, especially in traumatic bleeding and postpartum hemorrhage.
Thrombosis is the common pathology underlying ischemic heart disease, ischemic stroke, and venous thromboembolism (VTE). The Global Burden of Disease Study 2010 (GBD 2010) documented that ischemic ...heart disease and stroke collectively caused 1 in 4 deaths worldwide. GBD 2010 did not report data for VTE as a cause of death and disability.
To review the literature on the global burden of disease caused by VTE.
We performed a systematic review of the literature on the global disease burden because of VTE in low-, middle-, and high-income countries. Studies from Western Europe, North America, Australia, and Southern Latin America (Argentina) yielded consistent results with annual incidences ranging from 0.75 to 2.69 per 1000 individuals in the population. The incidence increased to between 2 and 7 per 1000 among those aged ≥70 years. Although the incidence is lower in individuals of Chinese and Korean ethnicity, their disease burden is not low because of population aging. VTE associated with hospitalization was the leading cause of disability-adjusted life-years lost in low- and middle-income countries, and second in high-income countries, responsible for more disability-adjusted life-years lost than nosocomial pneumonia, catheter-related blood stream infections, and adverse drug events.
VTE causes a major burden of disease across low-, middle-, and high-income countries. More detailed data on the global burden of VTE should be obtained to inform policy and resource allocation in health systems and to evaluate whether improved use of preventive measures will reduce the burden.
Rivers (on land) and turbidity currents (in the ocean) are the most important sediment transport processes on Earth. Yet how rivers generate turbidity currents as they enter the coastal ocean remains ...poorly understood. The current paradigm, based on laboratory experiments, is that turbidity currents are triggered when river plumes exceed a threshold sediment concentration of ~1 kg/m3. Here we present direct observations of an exceptionally dilute river plume, with sediment concentrations 1 order of magnitude below this threshold (0.07 kg/m3), which generated a fast (1.5 m/s), erosive, short‐lived (6 min) turbidity current. However, no turbidity current occurred during subsequent river plumes. We infer that turbidity currents are generated when fine sediment, accumulating in a tidal turbidity maximum, is released during spring tide. This means that very dilute river plumes can generate turbidity currents more frequently and in a wider range of locations than previously thought.
Key Points
Here we document for the first time how very dilute (up to 0.07 kg/m3) river plumes can generate powerful turbidity currents
Such low sediment concentrations are 20 times lower than those predicted by past theory and experiments
Therefore, turbidity currents are likely to be much more frequent and occur at a far wider range of locations than previously thought
Using algorithms based on point of care coagulation tests can decrease blood loss and blood component transfusion after cardiac surgery. We wished to test the hypothesis that a management algorithm ...based on near-patient tests would reduce blood loss and blood component use after routine coronary artery surgery with cardiopulmonary bypass when compared with an algorithm based on routine laboratory assays or with clinical judgement.
Patients (n=102) undergoing elective coronary artery surgery with cardiac bypass were randomized into two groups. In the point of care group, the management algorithm was based on information provided by three devices, the Hepcon®, thromboelastography and the PFA-100® platelet function analyser. Management in the laboratory test group depended on rapidly available laboratory clotting tests and transfusion of haemostatic blood components only if specific criteria were met. Blood loss and transfusion was compared between these two groups and with a retrospective case–control group (n=108), in which management of bleeding had been according to the clinician's discretion.
All three groups had similar median blood losses. The transfusion of packed red blood cells (PRBCs) and blood components was greater in the clinician discretion group (P<0.05) but there was no difference in the transfusion of PRBCs and blood components between the two algorithm-guided groups.
Following algorithms based on point of care tests or on structured clinical practice with standard laboratory tests does not decrease blood loss, but reduces the transfusion of PRBCs and blood components after routine cardiac surgery, when compared with clinician discretion. Cardiac surgery services should use transfusion guidelines based on laboratory-guided algorithms, and the possible benefits of point of care testing should be tested against this standard.
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