Antifactor Xa activity in critically ill patients receiving antithrombotic prophylaxis with standard dosages of certoparin: a prospective, clinical study

INTRODUCTION: Deep venous thrombosis with subsequent pulmonary embolism or post-thrombotic syndrome is a feared complication in the intensive care unit. Therefore, routine prophylactic anticoagulation is widely recommended. Aside from unfractionated heparin, low molecular weight heparins, such as certoparin, have become increasingly used for prophylactic anticoagulation in critically ill patients. In this prospective study, we evaluated the potency of 3,000 IU certoparin administered once daily to reach antithrombotic antifactor Xa (aFXa) levels of 0.1 to 0.3 IU/ml in 62 critically ill patients. METHODS: AFXa levels were determined 4, 12 and 24 h after injection of certoparin. Prothrombin time, activated partial thromboplastin time, antithrombin, fibrinogen, hemoglobin, platelet count, serum urea and creatinine concentrations were documented before and 12 and 24 h after injection of certoparin. RESULTS: Four hours after certoparin injection (n = 32), 28% of patients were within the antithrombotic aFXa range. After 12 and 24 h, 6% achieved antithrombotic aFXa levels. Because of a severe pulmonary embolism in one study patient, an interim analysis was performed, and the dosage of certoparin was increased to 3,000 IU twice daily. This regime attained recommended antithrombotic aFXa levels in 47%, 27%, 40% and 30% of patients at 4, 12, 16 and 24 h, respectively, after twice daily certoparin injection (n = 30). Antithrombin and fibrinogen concentrations slightly increased during the observation period. Low antithrombin concentrations before certoparin were independently correlated with underdosing of certoparin. Patients with aFXa levels <0.1 IU/ml 4 h after certoparin injection required vasopressors more often and had lower serum concentrations of creatinine and urea than patients with antithrombotic aFXa levels. CONCLUSION: Standard dosages of certoparin of 3,000 IU given once or twice daily are ineffective for attaining the recommended aFXa levels of 0.1 to 0.3 IU/ml in critically ill patients. Low antithrombin levels before certoparin administration were independently associated with low aFXa levels. Renal function and vasopressor therapy may further influence the effectiveness of certoparin in ensuring adequate antithrombotic prophylaxis

Coherence Potentials: Loss-Less, All-or-None Network Events in the Cortex

Transient associations among neurons are thought to underlie memory and behavior. However, little is known about how such associations occur or how they can be identified. Here we recorded ongoing local field potential (LFP) activity at multiple sites within the cortex of awake monkeys and organotypic cultures of cortex. We show that when the composite activity of a local neuronal group exceeds a threshold, its activity pattern, as reflected in the LFP, occurs without distortion at other cortex sites via fast synaptic transmission. These large-amplitude LFPs, which we call coherence potentials, extend up to hundreds of milliseconds and mark periods of loss-less spread of temporal and amplitude information much like action potentials at the single-cell level. However, coherence potentials have an additional degree of freedom in the diversity of their waveforms, which provides a high-dimensional parameter for encoding information and allows identification of particular associations. Such nonlinear behavior is analogous to the spread of ideas and behaviors in social networks

Emergency Blood Transfusion for Trauma and Perioperative Resuscitation: Standard of Care

Uncontrolled and massive bleeding with derangement of coagulation is a major challenge in the management of both surgical and seriously injured patients. The underlying mechanism of trauma-induced or -associated coagulopathy is tissue injury in the presence of shock and acidosis provoking endothelial damage, activation of inflammation, and coagulation disbalancing. Furthermore, the combination of ongoing blood loss and consumption of blood components that are essential for effective coagulation worsens uncontrolled hemorrhage. Additionally, therapeutic actions, such as resuscitation with replacement fluids or allogeneic blood products, can further aggravate coagulopathy. Of the coagulation factors essential to the clotting process, fibrinogen is the first to be consumed to critical levels during acute bleeding and current evidence suggests that normalizing fibrinogen levels in bleeding patients improves clot formation and clot strength, thereby controlling hemorrhage. Three different therapeutic approaches are discussed controversially. Whole blood transfusion is used especially in the military scenario and is also becoming more and more popular in the civilian world, although it is accompanied by a strong lack of evidence and severe safety issues. Transfusion of allogeneic blood concentrates in fixed ratios without any targets has been investigated extensively with disappointing results. Individualized and target-controlled coagulation management based on point-of-care diagnostics with respect to the huge heterogeneity of massive bleeding situations is an alternative and advanced approach to managing coagulopathy associated with massive bleeding in the trauma as well as the perioperative setting

Emergency Blood Transfusion for Trauma and Perioperative Resuscitation: Standard of Care

Uncontrolled and massive bleeding with derangement of coagulation is a major challenge in the management of both surgical and seriously injured patients. The underlying mechanism of trauma-induced or -associated coagulopathy is tissue injury in the presence of shock and acidosis provoking endothelial damage, activation of inflammation, and coagulation disbalancing. Furthermore, the combination of ongoing blood loss and consumption of blood components that are essential for effective coagulation worsens uncontrolled hemorrhage. Additionally, therapeutic actions, such as resuscitation with replacement fluids or allogeneic blood products, can further aggravate coagulopathy. Of the coagulation factors essential to the clotting process, fibrinogen is the first to be consumed to critical levels during acute bleeding and current evidence suggests that normalizing fibrinogen levels in bleeding patients improves clot formation and clot strength, thereby controlling hemorrhage. Three different therapeutic approaches are discussed controversially. Whole blood transfusion is used especially in the military scenario and is also becoming more and more popular in the civilian world, although it is accompanied by a strong lack of evidence and severe safety issues. Transfusion of allogeneic blood concentrates in fixed ratios without any targets has been investigated extensively with disappointing results. Individualized and target-controlled coagulation management based on point-of-care diagnostics with respect to the huge heterogeneity of massive bleeding situations is an alternative and advanced approach to managing coagulopathy associated with massive bleeding in the trauma as well as the perioperative setting

Transfusion approaches and mortality in trauma patients: a narrative review

Trauma is one of the leading causes of mortality in the world, accounting for millions of deaths per year. One of the most frequent causes of death in trauma patients is hemorrhage. The presence of a coagulopathy in trauma patients more than doubles the expected mortality. Coagulation management is a key aspect of care for bleeding trauma patients and has been investigated in many studies. However, it is unclear whether a particular approach to coagulation management is associated with a reduction in mortality. Treatment may be guided (e.g., viscoelastic test-guided administration of coagulation factor concentrates) or nonguided (e.g., treatment with a fixed ratio of plasma:red blood cells). This review aimed to assess the published literature regarding coagulation management technique and mortality rate. From the 41 articles obtained in the literature search, there appeared to be a trend toward lower mortality in studies utilizing a guided approach, despite a higher injury severity score in these patients. There were many methodological variations across studies including coagulation management approaches, inclusion criteria, time and type of measurements, use of early fast coagulation monitoring and damage control surgery principles, additional products to those under study, and potential regional differences. It is essential that controlled trials are performed to ascertain optimal transfusion approaches in trauma patients

The endothelial glycocalyx and its disruption, protection and regeneration : A narrative review

The glycocalyx is a carbohydrate-rich layer that lines the luminal side of the vascular endothelium. Its soluble components exist in a dynamic equilibrium with the bloodstream and play an important role in maintaining endothelial layer integrity. However, the glycocalyx can be easily damaged and is extremely vulnerable to insults from a variety of sources, including inflammation, trauma, haemorrhagic shock, hypovolemia and ischaemia-reperfusion. Damage to the glycocalyx commonly precedes further damage to the vascular endothelium. Preclinical research has identified a number of different factors capable of protecting or regenerating the glycocalyx. Initial investigations suggest that plasma may convey protective and regenerative effects. However, it remains unclear which exact components or properties of plasma are responsible for this protective effect. Studies have reported protective effects for several plasma proteins individually, including antithrombin, orosomucoid and albumin; the latter of which may be of particular interest, due to the high levels of albumin present in plasma. A further possibility is that plasma is simply a better intravascular volume expander than other resuscitation fluids. It has also been proposed that the protective effects are mediated indirectly via plasma resuscitation-induced changes in gene expression. Further work is needed to determine the importance of specific plasma proteins or other factors for glycocalyx protection, particularly in a clinical setting