RESUMO
Compared with conventional coagulation tests and factor-specific assays, viscoelastic hemostatic assays (VHAs) can provide a more thorough evaluation of clot formation and lysis but have several limitations including clot deformation. In this proof-of-concept study, we test a noncontact technique, termed resonant acoustic rheometry (RAR), for measuring the kinetics of human plasma coagulation. Specifically, RAR utilizes a dual-mode ultrasound technique to induce and detect surface oscillation of blood samples without direct physical contact and measures the resonant frequency of the surface oscillation over time, which is reflective of the viscoelasticity of the sample. Analysis of RAR results of normal plasma allowed defining a set of parameters for quantifying coagulation. RAR detected a flat-line tracing of resonant frequency in hemophilia A plasma that was corrected with the addition of tissue factor. Our RAR results captured the kinetics of plasma coagulation and the newly defined RAR parameters correlated with increasing tissue factor concentration in both healthy and hemophilia A plasma. These findings demonstrate the feasibility of RAR as a novel approach for VHA, providing the foundation for future studies to compare RAR parameters to conventional coagulation tests, factor-specific assays, and VHA parameters.
Assuntos
Hemofilia A , Humanos , Tromboplastina , Cinética , Coagulação Sanguínea , Testes de Coagulação Sanguínea/métodos , AcústicaRESUMO
There has been a significant interest in the last decade in the use of viscoelastic tests (VETs) to determine the hemostatic competence of bleeding patients. Previously, common coagulation tests (CCTs) such as the prothrombin time (PT) and partial thromboplastin time (PTT) were used to assist in the guidance of blood component and hemostatic adjunctive therapy for these patients. However, the experience of decades of VET use in liver failure with transplantation, cardiac surgery, and trauma has now spread to obstetrical hemorrhage and congenital and acquired coagulopathies. Since CCTs measure only 5 to 10% of the lifespan of a clot, these assays have been found to be of limited use for acute surgical and medical conditions, whereby rapid results are required. However, there are medical indications for the PT/PTT that cannot be supplanted by VETs. Therefore, the choice of whether to use a CCT or a VET to guide blood component therapy or hemostatic adjunctive therapy may often require consideration of both methodologies. In this review, we provide examples of the relative indications for CCTs and VETs in monitoring hemostatic competence of bleeding patients.
Assuntos
Transtornos da Coagulação Sanguínea , Hemostáticos , Humanos , Tromboelastografia/métodos , Testes de Coagulação Sanguínea , Hemostasia , Transtornos da Coagulação Sanguínea/terapia , Hemorragia/terapiaRESUMO
Earlier variants of SARS-CoV-2 have been associated with hypercoagulability and an extensive formation of fibrin amyloid microclots, which are considered to contribute to the pathology of the coronavirus 2019 disease (COVID-19). The newer omicron variants appear to be far more transmissible, but less virulent, even when taking immunity acquired from previous infections or vaccination into account. We here show that while the clotting parameters associated with omicron variants are significantly raised over those of healthy, matched controls, they are raised to levels significantly lower than those seen with more severe variants such as beta and delta. We also observed that individuals infected with omicron variants manifested less extensive microclot formation in platelet-poor plasma compared with those harboring the more virulent variants. The measurement of clotting effects between the different variants acts as a kind of "internal control" that demonstrates the relationship between the extent of coagulopathies and the virulence of the variant of interest. This adds to the evidence that microclots may play an important role in reflecting the severity of symptoms observed in COVID-19.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , FibrinaAssuntos
Anticoagulantes/efeitos adversos , COVID-19/sangue , Monitoramento de Medicamentos/métodos , Enoxaparina/efeitos adversos , Hemorragia/prevenção & controle , Heparina/efeitos adversos , SARS-CoV-2 , Tromboelastografia , Trombofilia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Testes de Coagulação Sanguínea , Proteínas Sanguíneas/análise , COVID-19/complicações , COVID-19/terapia , Protocolos Clínicos , Cuidados Críticos , Enoxaparina/administração & dosagem , Enoxaparina/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Heparina/administração & dosagem , Heparina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Testes Imediatos , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Respiração Artificial , Fatores de Risco , Trombofilia/etiologiaRESUMO
An 18-year-old female presented to the emergency department after a motor vehicle collision. Initial imaging revealed a liver laceration. Subsequent labs showed significantly elevated prothrombin time, international normalized ratio, and activated partial thromboplastin time. Thromboelastography demonstrated a flatline tracing. The patient denied use of anticoagulation but admitted to synthetic cannabinoid use. It was believed the patient had taken synthetic cannabinoid contaminated by brodifacoum. She was therefore given prothrombin complex concentrate and vitamin K with blood products. The patient underwent sequential embolization, laparotomy, thoracotomy, and repair of the vena cava with a shunt. Thirty minutes postoperatively, her coagulation tests and thromboelastography were much improved. Two and a half hours postoperatively, it was determined she had sustained non-survivable injuries. The patient experienced brain death due to prolonged hypotension as a result of hemorrhagic shock with bleeding exacerbated by brodifacoum. To our knowledge, this is the first case reported of a trauma-induced coagulopathy exacerbated by brodifacoum-contaminated synthetic cannabinoid. Her coagulopathy was clearly not due to trauma alone and contributed greatly to the difficulty in controlling hemorrhage. The synthetic cannabinoid-associated coagulopathy rendered her otherwise potentially survivable injuries fatal. Given the frequency of multiple trauma and the recent increase in the prevalence of synthetic cannabinoid, it can be expected that the incidence of trauma complicated by synthetic cannabinoid-associated coagulopathy will increase in the near future. For patients that present with prolonged prothrombin time and/or activated partial thromboplastin time, it is important to inquire about recent synthetic cannabinoid use.
RESUMO
This review explores the concept of futility timeouts and the use of traumatic brain injury (TBI) as an independent predictor of the futility of resuscitation efforts in severely bleeding trauma patients. The national blood supply shortage has been exacerbated by the lingering influence of the COVID-19 pandemic on the number of blood donors available, as well as by the adoption of balanced hemostatic resuscitation protocols (such as the increasing use of 1:1:1 packed red blood cells, plasma, and platelets) with and without early whole blood resuscitation. This has underscored the urgent need for reliable predictors of futile resuscitation (FR). As a result, clinical, radiologic, and laboratory bedside markers have emerged which can accurately predict FR in patients with severe trauma-induced hemorrhage, such as the Suspension of Transfusion and Other Procedures (STOP) criteria. However, the STOP criteria do not include markers for TBI severity or transfusion cut points despite these patients requiring large quantities of blood components in the STOP criteria validation cohort. Yet, guidelines for neuroprognosticating patients with TBI can require up to 72 h, which makes them less useful in the minutes and hours following initial presentation. We examine the impact of TBI on bleeding trauma patients, with a focus on those with coagulopathies associated with TBI. This review categorizes TBI into isolated TBI (iTBI), hemorrhagic isolated TBI (hiTBI), and polytraumatic TBI (ptTBI). Through an analysis of bedside parameters (such as the proposed STOP criteria), coagulation assays, markers for TBI severity, and transfusion cut points as markers of futilty, we suggest amendments to current guidelines and the development of more precise algorithms that incorporate prognostic indicators of severe TBI as an independent parameter for the early prediction of FR so as to optimize blood product allocation.
RESUMO
[This corrects the article DOI: 10.3389/fimmu.2023.1230049.].
RESUMO
We are pleased to see that Bareille et al. have written a Commentary: "Are viscoelastometric assays of old generation ready for disposal?" [...].
RESUMO
Type B lactic acidosis is an uncommon medical emergency in which acid production overwhelms hepatic clearance. This specific etiology of lactic acidosis occurs without organ hypoperfusion and has been most commonly described in patients with hematologic malignancies but also in patients with solid tumors. The mechanism by which cancer cells switch their glucose metabolism toward increasingly anaerobic glycolytic phenotypes has been described as the "Warburg effect." Without treating the underlying malignancy, the prognosis for patients diagnosed with malignancy-related type B lactic acidosis is extremely poor. Here, we present a case of a 66-year-old male who was diagnosed with type B lactic acidosis secondary to mantle cell lymphoma. Bicarbonate drip was started to correct the lactic acidosis. The patient was also immediately treated with rituximab chemotherapy combined with rasburicase to avoid the hyperuricemia associated with tumor lysis syndrome. He responded to the early treatment and was discharged with normal renal function. Type B lactic acidosis secondary to hematologic malignancy is important to recognize. In order to successfully treat this syndrome, early diagnosis and simultaneous treatment of the imbalance of lactic acid levels and the underlying malignancy are necessary.
RESUMO
Irrespective of the reason for hypoperfusion, hypocoagulable and/or hyperfibrinolytic hemostatic aberrancies afflict up to one-quarter of critically ill patients in shock. Intensivists and traumatologists have embraced the concept of SHock-INduced Endotheliopathy (SHINE) as a foundational derangement in progressive shock wherein sympatho-adrenal activation may cause systemic endothelial injury. The pro-thrombotic endothelium lends to micro-thrombosis, enacting a cycle of worsening perfusion and increasing catecholamines, endothelial injury, de-endothelialization, and multiple organ failure. The hypocoagulable/hyperfibrinolytic hemostatic phenotype is thought to be driven by endothelial release of anti-thrombogenic mediators to the bloodstream and perivascular sympathetic nerve release of tissue plasminogen activator directly into the microvasculature. In the shock state, this hemostatic phenotype may be a counterbalancing, yet maladaptive, attempt to restore blood flow against a systemically pro-thrombotic endothelium and increased blood viscosity. We therefore review endothelial physiology with emphasis on glycocalyx function, unique biomarkers, and coagulofibrinolytic mediators, setting the stage for understanding the pathophysiology and hemostatic phenotypes of SHINE in various etiologies of shock. We propose that the hyperfibrinolytic phenotype is exemplified in progressive shock whether related to trauma-induced coagulopathy, sepsis-induced coagulopathy, or post-cardiac arrest syndrome-associated coagulopathy. Regardless of the initial insult, SHINE appears to be a catecholamine-driven entity which early in the disease course may manifest as hyper- or hypocoagulopathic and hyper- or hypofibrinolytic hemostatic imbalance. Moreover, these hemostatic derangements may rapidly evolve along the thrombohemorrhagic spectrum depending on the etiology, timing, and methods of resuscitation. Given the intricate hemochemical makeup and changes during these shock states, macroscopic whole blood tests of coagulative kinetics and clot strength serve as clinically useful and simple means for hemostasis phenotyping. We suggest that viscoelastic hemostatic assays such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are currently the most applicable clinical tools for assaying global hemostatic function-including fibrinolysis-to enable dynamic resuscitation with blood products and hemostatic adjuncts for those patients with thrombotic and/or hemorrhagic complications in shock states.
RESUMO
Iatrogenic vascular air embolism is a relatively infrequent event but is associated with significant morbidity and mortality. These emboli can arise in many clinical settings such as neurosurgery, cardiac surgery, and liver transplantation, but more recently, endoscopy, hemodialysis, thoracentesis, tissue biopsy, angiography, and central and peripheral venous access and removal have overtaken surgery and trauma as significant causes of vascular air embolism. The true incidence may be greater since many of these air emboli are asymptomatic and frequently go undiagnosed or unreported. Due to the rarity of vascular air embolism and because of the many manifestations, diagnoses can be difficult and require immediate therapeutic intervention. An iatrogenic air embolism can result in both venous and arterial emboli whose anatomic locations dictate the clinical course. Most clinically significant iatrogenic air emboli are caused by arterial obstruction of small vessels because the pulmonary gas exchange filters the more frequent, smaller volume bubbles that gain access to the venous circulation. However, there is a subset of patients with venous air emboli caused by larger volumes of air who present with more protean manifestations. There have been significant gains in the understanding of the interactions of fluid dynamics, hemostasis, and inflammation caused by air emboli due to in vitro and in vivo studies on flow dynamics of bubbles in small vessels. Intensive research regarding the thromboinflammatory changes at the level of the endothelium has been described recently. The obstruction of vessels by air emboli causes immediate pathoanatomic and immunologic and thromboinflammatory responses at the level of the endothelium. In this review, we describe those immunologic and thromboinflammatory responses at the level of the endothelium as well as evaluate traditional and novel forms of therapy for this rare and often unrecognized clinical condition.
Assuntos
Embolia Aérea , Trombose , Humanos , Embolia Aérea/diagnóstico , Embolia Aérea/etiologia , Embolia Aérea/terapia , Tromboinflamação , Inflamação/terapia , Inflamação/complicações , Trombose/complicações , Doença IatrogênicaRESUMO
BACKGROUND: Improvements in health care innovations have resulted in an enhanced ability to extend patient viability. As a consequence, resources are being increasingly utilized at an unsustainable level. As we implement novel treatments, identifying futility should be a focus. The "death diamond" (DD) is a unique thrombelastography (TEG) tracing that is indicative of failure of the coagulation system, with a mortality rate exceeding 90%. The purpose of this study was to determine if the DD was a consistent marker of poor survival in a multicenter study population. We hypothesize that the DD, while an infrequent occurrence, predicts poor survival and can be used to stratify patients in whom resuscitation efforts are futile. METHODS: A retrospective multi-institutional study of trauma patients presenting with TEG DDs between 8/2008 and 12/2018 at four American College of Surgeons trauma centers was completed. Demographics, injury mechanisms, TEG results, management, and survival were examined. RESULTS: A total of 50 trauma patients presented with DD tracings, with a 94% (n = 47) mortality rate. Twenty-six (52%) patients received a repeat TEG with 10 patients re-demonstrating the DD tracing. There was 100% mortality in patients with serial DD tracings. The median use of total blood products was 18 units (interquartile range 6, 34.25) per patient. DISCUSSION: The DD is highly predictive of trauma-associated mortality. This multicenter study highlights that serial DDs may represent a possible biomarker of futility.
Assuntos
Transtornos da Coagulação Sanguínea , Ferimentos e Lesões , Biomarcadores , Humanos , Estudos Retrospectivos , Tromboelastografia/métodos , Centros de Traumatologia , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/terapiaRESUMO
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.
RESUMO
Viscoelastic hemostatic assay (VHAs) are whole blood point-of-care tests that have become an essential method for assaying hemostatic competence in liver transplantation, cardiac surgery, and most recently, trauma surgery involving hemorrhagic shock. It has taken more than three-quarters of a century of research and clinical application for this technology to become mainstream in these three clinical areas. Within the last decade, the cup and pin legacy devices, such as thromboelastography (TEG® 5000) and rotational thromboelastometry (ROTEM® delta), have been supplanted not only by cartridge systems (TEG® 6S and ROTEM® sigma), but also by more portable point-of-care bedside testing iterations of these legacy devices (e.g., Sonoclot®, Quantra®, and ClotPro®). Here, the legacy and new generation VHAs are compared on the basis of their unique hemostatic parameters that define contributions of coagulation factors, fibrinogen/fibrin, platelets, and clot lysis as related to the lifespan of a clot. In conclusion, we offer a brief discussion on the meteoric adoption of VHAs across the medical and surgical specialties to address COVID-19-associated coagulopathy.
RESUMO
SARS-CoV-2 infection can manifest many rashes. However, thrombotic retiform purpura rarely occurs during COVID-19 illness. Aggressive anti-COVID-19 therapy with a high-dose steroid regimen led to rapid recovery. This immunothrombotic phenomenon likely represents a poor type 1 interferon response and complement activation on the endothelial surface in response to acute infection.
RESUMO
Early in the coronavirus disease 2019 (COVID-19) pandemic, global governing bodies prioritized transmissibility-based precautions and hospital capacity as the foundation for delay of elective procedures. As elective surgical volumes increased, convalescent COVID-19 patients faced increased postoperative morbidity and mortality and clinicians had limited evidence for stratifying individual risk in this population. Clear evidence now demonstrates that those recovering from COVID-19 have increased postoperative morbidity and mortality. These data-in conjunction with the recent American Society of Anesthesiologists guidelines-offer the evidence necessary to expand the early pandemic guidelines and guide the surgeon's preoperative risk assessment. Here, we argue elective surgeries should still be delayed on a personalized basis to maximize postoperative outcomes. We outline a framework for stratifying the individual COVID-19 patient's fitness for surgery based on the symptoms and severity of acute or convalescent COVID-19 illness, coagulopathy assessment, and acuity of the surgical procedure. Although the most common manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is COVID-19 pneumonitis, every system in the body is potentially afflicted by an endotheliitis. This endothelial derangement most often manifests as a hypercoagulable state on admission with associated occult and symptomatic venous and arterial thromboembolisms. The delicate balance between hyper and hypocoagulable states is defined by the local immune-thrombotic crosstalk that results commonly in a hemostatic derangement known as fibrinolytic shutdown. In tandem, the hemostatic derangements that occur during acute COVID-19 infection affect not only the timing of surgical procedures, but also the incidence of postoperative hemostatic complications related to COVID-19-associated coagulopathy (CAC). Traditional methods of thromboprophylaxis and treatment of thromboses after surgery require a tailored approach guided by an understanding of the pathophysiologic underpinnings of the COVID-19 patient. Likewise, a prolonged period of risk for developing hemostatic complications following hospitalization due to COVID-19 has resulted in guidelines from differing societies that recommend varying periods of delay following SARS-CoV-2 infection. In conclusion, we propose the perioperative, personalized assessment of COVID-19 patients' CAC using viscoelastic hemostatic assays and fluorescent microclot analysis.
RESUMO
BACKGROUND The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), often manifests a coagulopathy in severely ill patients, which may cause hemorrhage and/or thrombosis of varying severity. This report comprises the cases of 3 patients with COVID-19-associated coagulopathy who were evaluated with thromboelastography (TEG) and activated partial thromboplastin time (aPTT) to enable personalized anticoagulant therapy. CASE REPORT Three patients presented with COVID-19 pneumonia, confirmed by reverse transcription-polymerase chain reaction, who developed thrombohemorrhagic coagulopathy.Case 1: A 72-year-old woman on long-term warfarin therapy for a history of venous thromboembolism developed a right upper lobe pulmonary embolus, despite an international normalized ratio of 6.4 and aPTT of 120.7 s. TEG enabled successful anticoagulation with heparin, and her pulmonary infarct was no longer present 2 weeks later.Case 2: A 55-year-old woman developed a rectus sheath hematoma while on heparin, and TEG demonstrated increased fibrinolysis despite COVID-19 patients more commonly undergoing fibrinolytic shutdown.Case 3: A 43-year-old woman had significant thrombus burden while severely hypocoagulable according to laboratory testing. As the venous thrombi enlarged in a disseminated intravascular coagulopathic-like state, the heparin dose was escalated to achieve a target aPTT of 70 to 80 s, resulting in a flat line TEG tracing. CONCLUSIONS These 3 cases of COVID-19 pneumonia with complex and varied clinical histories demonstrated the clinical value of TEG combined with the measurement of aPTT to facilitate personalized anticoagulation, resulting in good clinical outcomes.
Assuntos
Anticoagulantes/uso terapêutico , COVID-19/complicações , Hemorragia/tratamento farmacológico , Tromboelastografia , Terapia Trombolítica , Trombose/tratamento farmacológico , Adulto , Idoso , Feminino , Hemorragia/virologia , Heparina/uso terapêutico , Humanos , Pessoa de Meia-Idade , Trombose/virologiaRESUMO
INTRODUCTION: Pathologic fracture of the femur due to Streptococcus anginosus osteomyelitis has rarely been described. With limited evidence for treating S. anginosus osteomyelitis, the orthopaedic surgeon is presented with a difficult treatment decision at index presentation. Presented here is a case of failed conservative management, diagnostic dilemma, failed hardware stabilization, and definitive surgical treatment resulting in good clinical outcome. CASE PRESENTATION: A 69-year-old male experienced acute right thigh pain, edema, and erythema after dental treatment 17 days prior. He was diagnosed with right femoral diaphyseal osteomyelitis and Brodie's abscess. Blood cultures grew S. anginosus, but all site-specific tissue cultures resulted negative. Initial management consisted of intravenous antibiotic therapy and percutaneous abscess drainage. Months later, the patient sustained a displaced pathologic fracture of the diaphyseal femur and there was concern for neoplasm, but biopsies were negative. Stabilization was attempted with a lateral plate and screws. This hardware catastrophically failed in the setting of an oligotrophic femoral nonunion. Ultimately, the patient was successfully treated with an intramedullary nail coated with antibiotic-impregnated cement. Twelve months later, the patient achieved clinical and radiographic healing with no evidence of relapse of his osteomyelitis. CLINICAL DISCUSSION: Conservative management of S. anginosus femoral osteomyelitis was inadequate and corroborates the existing literature. S. anginosus osteomyelitis and pyomyositis may be most optimally treated aggressively with early surgical intervention. CONCLUSION: Early surgical debridement and stabilization of the compromised bone with an antibiotic coated intramedullary nail following medullary reaming may prevent pathologic fracture, eradicate infection, and achieve predictable outcomes.
RESUMO
Tension pneumomediastinum is a rare complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that has increased in incidence with the novel coronavirus disease 2019 pandemic. Although traditionally managed with conservative measures, we present the indications and methods for the first operative management of tension pneumomediastinum with concomitant SARS-CoV-2 infection.