A prothrombotic coagulopathy is commonly found in critically ill COVID‐19 patients with acute respiratory distress syndrome (ARDS). A unique feature of COVID‐19 respiratory failure is a relatively ...preserved lung compliance and high Alveolar‐arterial oxygen gradient, with pathology reports consistently demonstrating diffuse pulmonary microthrombi on autopsy, all consistent with a vascular occlusive etiology of respiratory failure rather than the more classic findings of low‐compliance in ARDS. The COVID‐19 pandemic is overwhelming the world’s medical care capacity with unprecedented needs for mechanical ventilators and high rates of mortality once patients progress to needing mechanical ventilation, and in many environments including in parts of the United States the medical capacity is being exhausted. Fibrinolytic therapy has previously been used in a Phase 1 clinical trial that led to reduced mortality and marked improvements in oxygenation. Here we report a series of three patients with severe COVID‐19 respiratory failure who were treated with tissue plasminogen activator. All three patients had a temporally related improvement in their respiratory status, with one of them being a durable response.
Abstract Background Fibrinolysis is a physiologic process to maintain microvascular patency by breaking down excessive fibrin clot. Hyperfibrinolysis (HF) is associated with a doubling of mortality. ...Fibrinolysis shutdown (SD), an acute impairment of fibrinolysis, has been recognized as a risk factor for increased mortality. The purpose of this study was to assess the incidence and outcomes of fibrinolysis phenotypes in two urban trauma centers. Study Design Injured patients admitted 2010-2013, who were ≥18 years of age, had an injury severity score (ISS) >15 were included in the analysis. Admission fibrinolysis phenotypes were determined by the clot lysis at 30 minutes (LY30): SD ≤0.8%, physiologic 0.9-2.9%, HF ≥3%. Logistic regression was used to adjust for age, arrival blood pressure, ISS, mechanism, and facility. Results 2540 patients met inclusion. Median age was 39(IQR 26-55) and median ISS was 25(IQR 20-33) with a mortality rate of 21%. Fibrinolysis shutdown was the most common phenotype (46%) followed by physiologic (36%) and hyperfibrinolysis(18%). HF was associated with the highest death rate (34%), followed by SD(22%), and physiologic (14%, p<0.001). The risk of mortality remained increased for HF(OR=3.3, 95%C: 2.4-4.6, p<0.0001) and SD(OR 1.6 95%CI 1.3-2.1, p=0.0003) compared to physiologic when adjusting for age, ISS, mechanism, head injury, and blood pressure (AUROC=0.82, 95% CI 0.80-0.84). Conclusions Fibrinolysis SD is the most common phenotype upon admission and is associated with increased mortality. Moreover, these data provide additional evidence of distinct phenotypes of coagulation impairment and that individualized hemostatic therapy may be required.
The COVID-19 pandemic has introduced a global public health threat unparalleled in our history. The most severe cases are marked by ARDS attributed to microvascular thrombosis. Hypercoagulability, ...resulting in a profoundly prothrombotic state, is a distinct feature of COVID-19 and is accentuated by a high incidence of fibrinolysis shutdown. The aims of this review were to describe the manifestations of fibrinolysis shutdown in COVID-19 and its associated outcomes, review the molecular mechanisms of dysregulated fibrinolysis associated with COVID-19, and discuss potential implications and therapeutic targets for patients with severe COVID-19.
The management of patients with exsanguinating torso hemorrhage is challenging. Emergency surgery, with the occasional use of resuscitative thoracotomy for patient in extremis, is the current ...standard. Recent reports of REBOA (resuscitative endovascular balloon occlusion of the aorta) have led to discussions about changing paradigms in the management of patients in both civilian and military are nas. We submit that broad and liberal application of this technique is premature given the current data and in light of historical experience. We propose an algorithm for the management of patients with exsanguinating torso hemorrhage, as well as a set of research questions that we feel can help clarify the role of REBOA in modern trauma care in a variety of trauma settings.
COVID-19 predisposes patients to a prothrombotic state with demonstrated microvascular involvement. The degree of hypercoagulability appears to correlate with outcomes; however, optimal criteria to ...assess for the highest-risk patients for thrombotic events remain unclear; we hypothesized that deranged thromboelastography measurements of coagulation would correlate with thromboembolic events.
Patients admitted to an ICU with COVID-19 diagnoses who had thromboelastography analyses performed were studied. Conventional coagulation assays, d-dimer levels, and viscoelastic measurements were analyzed using a receiver operating characteristic curve to predict thromboembolic outcomes and new-onset renal failure.
Forty-four patients with COVID-19 were included in the analysis. Derangements in coagulation laboratory values, including elevated d-dimer, fibrinogen, prothrombin time, and partial thromboplastin time, were confirmed; viscoelastic measurements showed an elevated maximum amplitude and low lysis of clot at 30 minutes. A complete lack of lysis of clot at 30 minutes was seen in 57% of patients and predicted venous thromboembolic events with an area under the receiver operating characteristic curve of 0.742 (p = 0.021). A d-dimer cutoff of 2,600 ng/mL predicted need for dialysis with an area under the receiver operating characteristic curve of 0.779 (p = 0.005). Overall, patients with no lysis of clot at 30 minutes and a d-dimer > 2,600 ng/mL had a venous thromboembolic event rate of 50% compared with 0% for patients with neither risk factor (p = 0.008), and had a hemodialysis rate of 80% compared with 14% (p = 0.004).
Fibrinolysis shutdown, as evidenced by elevated d-dimer and complete failure of clot lysis at 30 minutes on thromboelastography predicts thromboembolic events and need for hemodialysis in critically ill patients with COVID-19. Additional clinical trials are required to ascertain the need for early therapeutic anticoagulation or fibrinolytic therapy to address this state of fibrinolysis shutdown.
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Despite technological advancements, REBOA is associated with significant risks due to complications of vascular access and ischemia-reperfusion. The inherent morbidity and mortality of REBOA is often ...compounded by coexisting injury and hemorrhagic shock. Additionally, the potential for REBOA-related injuries is exaggerated due to the growing number of interventions being performed by providers who have limited experience in endovascular techniques, inadequate resources, minimal training in the technique, and who are performing this maneuver in emergency situations. In an effort to ultimately improve outcomes with REBOA, we sought to compile a list of complications that may be encountered during REBOA usage. To address the current knowledge gap, we assembled a list of anecdotal complications from high-volume REBOA users internationally. More importantly, through a consensus model, we identify contributory factors that may lead to complications and deliberate on how to recognize, mitigate, and manage such events. An understanding of the pitfalls of REBOA and strategies to mitigate their occurrence is of vital importance to optimize patient outcomes.
Viscoelastic assays, such as thrombelastography (TEG) and rotational thrombelastometry (ROTEM), have emerged as point-of-care tools that can guide the hemostatic resuscitation of bleeding injured ...patients. This article describes the role of TEG in contemporary trauma care by explaining this assay's methodology, clinical applications, and result interpretation through description of supporting studies to provide the reader with an evidence-based user's guide. Although TEG and ROTEM are assays based on the same viscoelastic principle, this article is focused on data supporting the use of TEG in trauma, because it is available in trauma centers in North America; ROTEM is mostly available in Europe.
Summary Postinjury abdominal compartment syndrome (ACS) is an example of a deadly clinical occurrence that was eliminated by strategic research and focused preventions. In the 1990s, the syndrome ...emerged with the widespread use of damage control surgery and aggressive crystalloid-based resuscitation. Patients who previously exsanguinated on the operating table made it to intensive care units, but then developed highly lethal hyperacute respiratory, renal, and cardiac failure due to increased abdominal pressure. Among many factors, delayed haemorrhage control and preload driven excessive use of crystalloid resuscitation were identified as modifiable predictors. The surrogate effect of preventive strategies, including the challenge of the 40-year-old standard of large volume crystalloid resuscitation for traumatic shock, greatly reduced cases of ACS. The discoveries were rapidly translated to civilian and military trauma surgical practices and fundamentally changed the way trauma patients are resuscitated today with substantially improved outcomes.
Fibrinolysis was initially defined using rapid thrombelastography (rTEG). The cutoffs for the pathologic extremes of the fibrinolytic system, hyperfibrinolysis and shutdown, were both defined based ...on association with mortality. We propose to redefine these phenotypes for both TEG and for rotational thrombelastometry, the other commonly used viscoelastic assay.
Rotational thrombelastometry, rTEG, and clinical data were prospectively collected on trauma patients admitted to an urban Level I trauma center from 2010 to 2016. Hyperfibrinolysis was defined as the Youden index from EXTEM-clot lysis index 60 minutes after clotting time (CLI60) and rTEG-fibrinolysis 30 minutes after achieving MA (LY30) for predicting massive transfusion (>10 red blood cell units, or death per 6 hours after injury) as a surrogate for severe bleeding. Patients identified as having hyperfibrinolysis were then removed from the data set, and the cutoff for fibrinolysis shutdown was derived as the optimal cutoff for predicting mortality in the remaining patients.
Overall, 216 patients (median age, 36 years (interquartile range, 27-49 years), 82% men, 58% blunt injury) were included. Of these, 16% required massive transfusion, and 12.5% died. Rapid thrombelastography phenotypes were redefined as hyperfibrinolysis: rTEG-LY30 greater than7.7%, physiologic rTEG-LY30 0.6% to7.6%, and shutdown rTEG-LY30 less than 0.6%. EXTEM-CLI60 fibrinolysis phenotypes were hyperfibrinolysis CLI60 less than 82%, physiologic (CLI60, 82-97.9%), and shutdown (CLI60 > 98%). Weighted kappa statistics revealed moderate agreement between rotational thrombelastometry- and rTEG-defined fibrinolysis (k = 0.51; 95% confidence interval, 0.39-0.63), with disagreement mostly in the shutdown and physiologic categories.
We confirmed the U-shaped distribution of death related to fibrinolysis system abnormalities. Both rTEG LY30 and EXTEM CLI60 can identify the spectrum of fibrinolytic phenotypes, have moderate agreement, and can be used to guide hemostatic resuscitation.
Diagnostic study, level III.
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