Early goal-directed hemostatic therapy for severe acute bleeding management in the Intensive Care Unit: A narrative review

This is a narrative review of the published evidence for bleeding management in critically ill patients in different clinical settings in the intensive care unit (ICU). We aimed to describe “The Ten Steps” approach to early goal-directed hemostatic therapy (EGDHT) using point-of-care testing (POCT), coagulation factor concentrates, and hemostatic drugs, according to the individual needs of each patient. We searched National Library of Medicine, MEDLINE for publications relevant to management of critical ill bleeding patients in different settings in the ICU. Bibliographies of included articles were also searched to identify additional relevant studies. English-language systematic reviews, meta-analyses, randomized trials, observational studies, and case reports were reviewed. Data related to study methodology, patient population, bleeding management strategy, and clinical outcomes were qualitatively evaluated. According to systematic reviews and meta-analyses, EGDHT guided by viscoelastic testing (VET) has been associated with a reduction in transfusion utilization, improved morbidity and outcome in patients with active bleeding. Furthermore, literature data showed an increased risk of severe adverse events and poor clinical outcomes with inappropriate prophylactic uses of blood components to correct altered conventional coagulation tests (CCTs). Finally, prospective, randomized, controlled trials point to the role of goal-directed fibrinogen substitution to reduce bleeding and the amount of red blood cell (RBC) transfusion with the potential to decrease mortality. In conclusion, severe acute bleeding management in the ICU is still a major challenge for intensive care physicians. The organized and sequential approach to the bleeding patient, guided by POCT allows for rapid and effective bleeding control, through the rational use of blood components and hemostatic drugs, since VET can identify specific coagulation disorders in real time, guiding hemostatic therapy with coagulation factor concentrates and hemostatic drugs with individual goals. Hemorrhage and thrombosis are frequent complications in the intensive care unit (ICU), compromising the clinical outcome of patients.1 Among them, the main cause of death in the world is thrombosis. However, there is concern about the risk of bleeding in patients who have pathological results from conventional coagulation tests (CCTs).2 For this reason, prophylactic transfusion of allogeneic blood components is still very frequent, even in the absence of bleeding. However, transfusion is associated with life-threatening adverse events.3 In this literature review, we aimed to describe critical aspects of the approach to patients with severe acute bleeding in the ICU, focusing on the importance of point-of-care testing (POCT) for early identification of coagulopathy to guide early goal-directed hemostatic therapy (EGDHT) using coagulation factor concentrates and hemostatic drugs

Goal-directed therapy in trauma induced coagulopathy and focus on traumatic brain injury

In recent years there have been major advances in the management of trauma-induced coagulopathy (TIC) and many experiences have demonstrated how we can achieve significant improvements with multidisciplinary approach and implementation of standardized protocols and algorithms. Central nervous system injuries and exanguination remain the primary causes of early trauma-related mortality. Traumatic brain injuries (TBI) make hemostasis in TIC even more complex and it is known that the onset of coagulopathy in a patient with severe brain injury has a negative impact on the patient’s outcome in terms of mortality. Standard coagulation tests provide limited information on coagulation disorder. The advantages of whole-blood viscoelastic tests, such as rotational thromboelastometry or thrombelastography, are shorter turn-around time and better diagnostic performance compared to routine plasmatic coagulation tests. In contrast to a fixed ratio of FFP:PC:RBC, the aim of the goal-directed coagulation therapy is to set treatment to the actual needs of the individual patient, based on viscoelastic test results. This article describes the improvements achieved through the implementation of ROTEM-guided treatment algorithms for visceral surgery and liver trasplantation, severe trauma and post-partum hemorrhage and cardiovascular surgery

Early goal-directed hemostatic therapy for severe acute bleeding management in the intensive care unit: a narrative review.

This is a narrative review of the published evidence for bleeding management in critically ill patients in different clinical settings in the intensive care unit (ICU). We aimed to describe “The Ten Steps” approach to early goal-directed hemostatic therapy (EGDHT) using point-of-care testing (POCT), coagulation factor concentrates, and hemostatic drugs, according to the individual needs of each patient. We searched National Library of Medicine, MEDLINE for publications relevant to management of critical ill bleeding patients in different settings in the ICU. Bibliographies of included articles were also searched to identify additional relevant studies. English-language systematic reviews, meta-analyses, randomized trials, observational studies, and case reports were reviewed. Data related to study methodology, patient population, bleeding management strategy, and clinical outcomes were qualitatively evaluated. According to systematic reviews and meta-analyses, EGDHT guided by viscoelastic testing (VET) has been associated with a reduction in transfusion utilization, improved morbidity and outcome in patients with active bleeding. Furthermore, literature data showed an increased risk of severe adverse events and poor clinical outcomes with inappropriate prophylactic uses of blood components to correct altered conventional coagulation tests (CCTs). Finally, prospective, randomized, controlled trials point to the role of goal-directed fibrinogen substitution to reduce bleeding and the amount of red blood cell (RBC) transfusion with the potential to decrease mortality. In conclusion, severe acute bleeding management in the ICU is still a major challenge for intensive care physicians. The organized and sequential approach to the bleeding patient, guided by POCT allows for rapid and effective bleeding control, through the rational use of blood components and hemostatic drugs, since VET can identify specific coagulation disorders in real time, guiding hemostatic therapy with coagulation factor concentrates and hemostatic drugs with individual goals

Early and individualized goal-directed therapy for trauma-induced coagulopathy

Severe trauma-related bleeding is associated with high mortality. Standard coagulation tests provide limited information on the underlying coagulation disorder. Whole-blood viscoelastic tests such as rotational thromboelastometry or thrombelastography offer a more comprehensive insight into the coagulation process in trauma. The results are available within minutes and they provide information about the initiation of coagulation, the speed of clot formation, and the quality and stability of the clot. Viscoelastic tests have the potential to guide coagulation therapy according to the actual needs of each patient, reducing the risks of over- or under-transfusion. The concept of early, individualized and goal-directed therapy is explored in this review and the AUVA Trauma Hospital algorithm for managing trauma-induced coagulopathy is presented

Point-of-care detection and differentiation of anticoagulant therapy - development of thromboelastometry-guided decision-making support algorithms

BACKGROUND DOAC detection is challenging in emergency situations. Here, we demonstrated recently, that modified thromboelastometric tests can reliably detect and differentiate dabigatran and rivaroxaban. However, whether all DOACs can be detected and differentiated to other coagulopathies is unclear. Therefore, we now tested the hypothesis that a decision tree-based thromboelastometry algorithm enables detection and differentiation of all direct Xa-inhibitors (DXaIs), the direct thrombin inhibitor (DTI) dabigatran, as well as vitamin K antagonists (VKA) and dilutional coagulopathy (DIL) with high accuracy. METHODS Following ethics committee approval (No 17-525-4), and registration by the German clinical trials database we conducted a prospective observational trial including 50 anticoagulated patients (n = 10 of either DOAC/VKA) and 20 healthy volunteers. Blood was drawn independent of last intake of coagulation inhibitor. Healthy volunteers served as controls and their blood was diluted to simulate a 50% dilution in vitro. Standard (extrinsic coagulation assay, fibrinogen assay, etc.) and modified thromboelastometric tests (ecarin assay and extrinsic coagulation assay with low tissue factor) were performed. Statistical analyzes included a decision tree analyzes, with depiction of accuracy, sensitivity and specificity, as well as receiver-operating-characteristics (ROC) curve analysis including optimal cut-off values (Youden-Index). RESULTS First, standard thromboelastometric tests allow a good differentiation between DOACs and VKA, DIL and controls, however they fail to differentiate DXaIs, DTIs and VKAs reliably resulting in an overall accuracy of 78%. Second, adding modified thromboelastometric tests, 9/10 DTI and 28/30 DXaI patients were detected, resulting in an overall accuracy of 94%. Complex decision trees even increased overall accuracy to 98%. ROC curve analyses confirm the decision-tree-based results showing high sensitivity and specificity for detection and differentiation of DTI, DXaIs, VKA, DIL, and controls. CONCLUSIONS Decision tree-based machine-learning algorithms using standard and modified thromboelastometric tests allow reliable detection of DTI and DXaIs, and differentiation to VKA, DIL and controls. TRIAL REGISTRATION Clinical trial number: German clinical trials database ID: DRKS00015704

Defining trauma-induced coagulopathy with respect to future implications for patient management : Communication from the SSC of the ISTH

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