Changes in Coagulation following Brain Injury.

Traumatic brain injury (TBI) is a worldwide public health concern due to increasing mortality, affecting around 10 million patients per year. A wide variety of clinical presentations are a function of the magnitude of injury and the anatomical perturbation of the brain parenchyma, supporting structures, and cerebral vasculature, with subsequent alteration of the blood-brain barrier. These disturbances correspond with the evolution of intracerebral hemorrhage and clinical outcomes. The associated hemostatic alterations associated with TBI are caused by the disruption of the delicate balance between bleeding and thrombosis formation, which can exacerbate initial injury. TBI-associated coagulopathy is a function of a cross-talk between coagulation and inflammation, with varying influences on the immunomodulation and regulation of coagulation that occur on platelets and the endothelium of injured TBI patients. In addition to the severity of initial injury, the following factors modulate the hemocoagulative response to TBI: time from the onset of injury to treatment, age, gender, catecholamine secretion, platelet dysfunction, endotheliopathy, premorbid anticoagulation, fibrinolysis, tissue factor, and activated protein C contribution. All these entities are intertwined and influence the pathologic evolution of TBI. These factors have implications for therapeutic options such as the choice of blood components for transfusion and hemostatic agents such as tranexamic acid. Monitoring hemostatic changes of TBI patients requires an understanding of these interactions between immunology and coagulation, which can be discerned by point-of-care viscoelastic testing with specific limitations. This review considers the implications of these interrelated influences on the evaluation of coagulopathy in TBI.

Whole Blood for Civilian Urban Trauma Resuscitation: Historical, Present, and Future Considerations.

Whole blood (WB) has been used for more than a century for far-forward combat resuscitation. Following the Iraq/Afghanistan combat, maritime, and austere environment use of WB for the resuscitation of severely hemorrhaging patients, there has been an increasing use of WB for the civilian urban resuscitation environment population. The impetus for this was not just improved outcomes in far-forward hospitals, which had different populations and different needs than the civilian urban population, but also an application of the lessons suggested by recent 1:1:1 plasma:platelets:packed red cells fixed-ratio studies for patients with massive transfusion needs. Mechanistic, logistic, and standardization concerns have been addressed and are evolving as the WB project advances. A small number of studies have been published on WB in the civilian urban trauma population. In addition, European experience with viscoelastic testing and resuscitation with fibrinogen and prothrombin complex concentrate has provided another viewpoint regarding the choice of resuscitation strategies for severely bleeding trauma patients in urban civilian environments. There are randomized controlled trials in process, which are testing the hypothesis that WB may be beneficial for the civilian urban population. Whether WB will improve mortality significantly is now a matter of intense study, and this commentary reviews the history, mechanistic foundations, and logistical aspects for the use of WB in the civilian trauma population.

Viscoelastic testing in benign hematologic disorders: Clinical perspectives and future implications of point-of-care testing to assess hemostatic competence.

Viscoelastic tests (VETs) have been used routinely for liver transplantation, cardiac surgery, and trauma, but only recently have found clinical utility in benign hematologic disorders. Therefore, guidelines for diagnosis and treatment of these disorders based on viscoelastic variables have been adapted from the existing transplant, cardiothoracic surgery, and trauma resuscitation literature. As a result, diagnostic and therapeutic strategies for benign hematologic disorders utilizing VETs are not uniform. Accordingly, even though there has been a recent increase in the utilization of VET for the diagnosis and treatment of such disorders, the literature is still in its early stages. Analysis of point-of-care viscoelastic tracings from benign hematologic disorders has the potential to allow prompt recognition of disease and to guide patient-specific intervention. Here we present a review describing the application of VETs to benign hematologic disorders.

Viscoelastic testing in oncology patients (including for the diagnosis of fibrinolysis): Review of existing evidence, technology comparison, and clinical utility.

The quantification of the coagulopathic state associated with oncologic and hematologic diseases is imperfectly assessed by common coagulation tests such as prothrombin time, activated partial thromboplastin time, fibrinogen levels, and platelet count. These tests provide a static representation of a component of hemostatic integrity, presenting an incomplete picture of coagulation in these patients. Viscoelastic tests (VETs), such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), as whole blood analyses, provide data related to the cumulative effects of blood components and all stages of the coagulation and fibrinolytic processes. The utility of VETs has been demonstrated since the late 1960s in guiding blood component therapy for patients undergoing liver transplantation. Since then, the scope of viscoelastic testing has expanded to become routinely used for cardiac surgery, obstetrics, and trauma. In the past decade, VETs' expanded usage has been most significant in trauma resuscitation. However, use of VETs for patients with malignancy-associated coagulopathy (MAC) and hematologic malignancies is increasing. For the purposes of this narrative review, we discuss the similarities between trauma-induced coagulopathy (TIC) and MAC. These similarities center on the thrombomodulin-thrombin complex as it switches between the thrombin-activatable fibrinolysis inhibitor coagulation pathway and activating the protein C anticoagulation pathway. This produces a spectrum of coagulopathy and fibrinolytic alterations ranging from shutdown to hyperfibrinolysis that are common to TIC, MAC, and hematologic malignancies. There is expanding literature regarding the utility of TEG and ROTEM to describe the hemostatic integrity of patients with oncologic and hematologic conditions, which we review here.

Use of Thromboelastography and Rotational Thromboelastometry in Otolaryngology: A Narrative Review.

In the field of otolaryngology-head and neck surgery (ENT), coagulopathies present unique diagnostic and therapeutic challenges. In both hyper- and hypocoagulable patients, management of coagulopathies requires intricate attention to the nature of hemostatic competence. Common coagulation tests (CCTs) offer only a snapshot of hemostatic competence and do not provide a clear insight into the patient's real-time hemostatic condition. Viscoelastic tests (VETs) offer a holistic and concurrent picture of the coagulation process. Although VETs have found prominent utilization in hepatic transplants, obstetrics, and emergent surgical settings, they have not been fully adopted in the realm of otolaryngology. The objective of this manuscript is to provide an overview of the literature evaluating the current utilization and possible future uses of VETs in the field of otolaryngology. The authors performed a comprehensive literature search of the utilization of VETs in otolaryngology and identified applicable studies that included descriptions of viscoelastic testing. Twenty-five studies were identified in this search, spanning topics from head and neck oncology, microvascular free flap reconstruction, obstructive sleep apnea, adenotonsillectomy, facial trauma, and epistaxis. The applicability of VETs has been demonstrated in head and neck oncology and microvascular free flap management, although their pervasiveness in practice is limited. Underutilization of VETs in the field of otolaryngology may be due to a lack of familiarity of the tests amongst practitioners. Instead, most otolaryngologists continue to rely on CCTs, including PT, PTT, INR, CBC, fibrinogen levels, and thrombin time. Learning to perform, interpret, and skillfully employ VETs in clinical and operative practice can greatly improve the management of coagulopathic patients who are at increased risk of bleeding or thrombosis.

Hemorrhagic Resuscitation Guided by Viscoelastography in Far-Forward Combat and Austere Civilian Environments: Goal-Directed Whole-Blood and Blood-Component Therapy Far from the Trauma Center.

Modern approaches to resuscitation seek to bring patient interventions as close as possible to the initial trauma. In recent decades, fresh or cold-stored whole blood has gained widespread support in multiple settings as the best first agent in resuscitation after massive blood loss. However, whole blood is not a panacea, and while current guidelines promote continued resuscitation with fixed ratios of blood products, the debate about the optimal resuscitation strategy-especially in austere or challenging environments-is by no means settled. In this narrative review, we give a brief history of military resuscitation and how whole blood became the mainstay of initial resuscitation. We then outline the principles of viscoelastic hemostatic assays as well as their adoption for providing goal-directed blood-component therapy in trauma centers. After summarizing the nascent research on the strengths and limitations of viscoelastic platforms in challenging environmental conditions, we conclude with our vision of how these platforms can be deployed in far-forward combat and austere civilian environments to maximize survival.

Whole Blood, Fixed Ratio, or Goal-Directed Blood Component Therapy for the Initial Resuscitation of Severely Hemorrhaging Trauma Patients: A Narrative Review.

This narrative review explores the pathophysiology, geographic variation, and historical developments underlying the selection of fixed ratio versus whole blood resuscitation for hemorrhaging trauma patients. We also detail a physiologically driven and goal-directed alternative to fixed ratio and whole blood, whereby viscoelastic testing guides the administration of blood components and factor concentrates to the severely bleeding trauma patient. The major studies of each resuscitation method are highlighted, and upcoming comparative trials are detailed.

Viscoelastic Testing and Coagulopathy of Traumatic Brain Injury.

A unique coagulopathy often manifests following traumatic brain injury, leading the clinician down a difficult decision path on appropriate prophylaxis and therapy. Conventional coagulation assays-such as prothrombin time, partial thromboplastin time, and international normalized ratio-have historically been utilized to assess hemostasis and guide treatment following traumatic brain injury. However, these plasma-based assays alone often lack the sensitivity to diagnose and adequately treat coagulopathy associated with traumatic brain injury. Here, we review the whole blood coagulation assays termed viscoelastic tests and their use in traumatic brain injury. Modified viscoelastic tests with platelet function assays have helped elucidate the underlying pathophysiology and guide clinical decisions in a goal-directed fashion. Platelet dysfunction appears to underlie most coagulopathies in this patient population, particularly at the adenosine diphosphate and/or arachidonic acid receptors. Future research will focus not only on the utility of viscoelastic tests in diagnosing coagulopathy in traumatic brain injury, but also on better defining the use of these tests as evidence-based and/or precision-based tools to improve patient outcomes.