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Fibrinolysis Shutdown

Takeshi Wada
Whole-body ischemia and reperfusion due to cardiac arrest and subsequent return of spontaneous circulation constitute post-cardiac arrest syndrome (PCAS), which consists of four syndromes including systemic ischemia/reperfusion responses and post-cardiac arrest brain injury. The major pathophysiologies underlying systemic ischemia/reperfusion responses are systemic inflammatory response syndrome and increased coagulation, leading to disseminated intravascular coagulation (DIC), which clinically manifests as obstruction of microcirculation and multiple organ dysfunction...
2017: Frontiers in Medicine
M J Madurska, K A Sachse, J O Jansen, T E Rasmussen, J J Morrison
Fibrinolytic dysregulation is an important mechanism in traumatic coagulopathy. It is an incompletely understood process that consists of a spectrum ranging from excessive breakdown (hyperfibrinolysis) and the shutdown of fibrinolysis. Both hyperfibrinolysis and shutdown are associated with excess mortality and post-traumatic organ failure. The pathophysiology appears to relate to endothelial injury and hypoperfusion, with several molecular markers identified in playing a role. Although there are no universally accepted diagnostic tests, viscoelastic studies appear to offer the greatest potential for timely identification of patients presenting with fibrinolytic dysregulation...
September 16, 2017: European Journal of Trauma and Emergency Surgery: Official Publication of the European Trauma Society
John R Taylor, Erin E Fox, John B Holcomb, Sandro Rizoli, Kenji Inaba, Martin A Schreiber, Karen Brasel, Thomas M Scalea, Charles E Wade, Eileen Bulger, Bryan A Cotton
BACKGROUND: Among bleeding patients, we hypothesized that the hyperfibrinolytic (HF) phenotype would be associated with the highest mortality, while shutdown (SD) patients would have the greatest complication burden. METHODS: Severely injured patients predicted to receive a massive transfusion at 12 level-1 trauma centers were randomized to one of two transfusion ratios as described in the PROPPR trial. Fibrinolysis phenotypes were determined based on admission clot lysis at 30 minutes (LY30): SD ≤0...
September 13, 2017: Journal of Trauma and Acute Care Surgery
Christopher D Barrett, Hunter B Moore, Anirban Banerjee, Christopher C Silliman, Ernest E Moore, Michael B Yaffe
BACKGROUND: A subset of trauma patients undergo fibrinolysis shutdown rather than pathologic hyperfibrinolysis, contributing to organ failure. The molecular basis for fibrinolysis shutdown in trauma is incompletely understood. Elastase released from primed/activated human neutrophils (HNE) has historically been described as fibrin(ogen)olytic. However, HNE can also degrade plasminogen (PLG) to angiostatin (ANG), retaining the Kringle domains but not the proteolytic function, and could thereby compete for generation of active plasmin by tPA...
August 23, 2017: Journal of Trauma and Acute Care Surgery
Hunter B Moore, Ernest E Moore, Benjamin R Huebner, Gregory R Stettler, Geoffrey R Nunns, Peter M Einersen, Christopher C Silliman, Angela Sauaia
BACKGROUND: Tranexamic acid (TXA) administration after trauma has not been proven to improve survival in the United States. Trauma patients were presented to the hospital with a spectrum of fibrinolytic activity, in which physiological levels of fibrinolysis are associated with the lowest mortality. We hypothesize that trauma patients who present to the hospital with physiological levels of fibrinolysis will have increased mortality if they receive TXA. MATERIALS AND METHODS: Severely injured trauma patients, followed prospectively from 2014 to 2016, were included in the analysis...
May 8, 2017: Journal of Surgical Research
Christine M Leeper, Matthew D Neal, Christine J McKenna, Barbara A Gaines
OBJECTIVE: To trend fibrinolysis after injury and determine the influence of traumatic brain injury (TBI) and massive transfusion on fibrinolysis status. BACKGROUND: Admission fibrinolytic derangement is common in injured children and adults, and is associated with poor outcome. No studies examine fibrinolysis days after injury. METHODS: Prospective study of severely injured children at a level 1 pediatric trauma center. Rapid thromboelastography was obtained on admission and daily for up to 7 days...
September 2017: Annals of Surgery
Antoni R Macko, Hunter B Moore, Andrew P Cap, M Adam Meledeo, Ernest E Moore, Forest R Sheppard
BACKGROUND: Hypoperfusion is associated with hyperfibrinolysis and early death from exsanguination, whereas tissue trauma is associated with hypofibrinolysis and delayed death from organ failure. We sought to elucidate the effects of injury patterns on fibrinolysis phenotypes using a nonhuman primate (NHP) model. METHODS: NHPs were randomized to three injury groups (n = 8/group): 60 minutes severe pressure-targeted controlled hemorrhagic shock (HS); HS + soft tissue injury (HS+); or HS + soft tissue injury + femur fracture (HS++)...
April 2017: Journal of Trauma and Acute Care Surgery
Jonathan P Meizoso, Charles A Karcutskie, Juliet J Ray, Nicholas Namias, Carl I Schulman, Kenneth G Proctor
BACKGROUND: Acute fibrinolysis shutdown is associated with early mortality after trauma; however, no previous studies have investigated the incidence of persistent fibrinolysis or its association with mortality. We tested the hypothesis that persistent fibrinolysis shutdown is associated with mortality in critically ill trauma patients. STUDY DESIGN: Thromboelastography was performed on ICU admission in 181 adult trauma patients and at 1 week in a subset of 78 patients...
April 2017: Journal of the American College of Surgeons
Ricardo J Ramirez, Philip C Spinella, Grant V Bochicchio
Following results from the CRASH-2 trial, tranexamic acid (TXA) gained considerable interest for the treatment of hemorrhage in trauma patients. Although TXA is effective at reducing mortality in patients presenting within 3 hours of injury, optimal dosing, timing of administration, mechanism, and pharmacokinetics require further elucidation. The concept of fibrinolysis shutdown in hemorrhagic trauma patients has prompted discussion of real-time viscoelastic testing and its potential role for appropriate patient selection...
January 2017: Critical Care Clinics
Christine M Leeper, Matthew D Neal, Christine McKenna, Jason L Sperry, Barbara A Gaines
BACKGROUND: Abnormalities in fibrinolysis are common and associated with increased mortality in injured adults. While hyperfibrinolysis (HF) and fibrinolysis shutdown (SD) are potential prognostic indicators and treatment targets in adults, these derangements are not well described in a pediatric trauma cohort. METHODS: This was a prospective analysis of highest level trauma activations in subjects aged 0 to 18 years presenting to our academic center between June 1, 2015, and July 31, 2016, with admission rapid thrombelastograph...
January 2017: Journal of Trauma and Acute Care Surgery
Ernest E Moore, Hunter B Moore, Eduardo Gonzalez, Angela Sauaia, Anirban Banerjee, Christopher C Silliman
Postinjury fibrinolysis can manifest as three distinguishable phenotypes: 1) hyperfibrinolysis, 2) physiologic, and 3) hypofibrinolysis (shutdown). Hyperfibrinolysis is associated with uncontrolled bleeding due to clot dissolution; whereas, fibrinolysis shutdown is associated with organ dysfunction due to microvascular occlusion. The incidence of fibrinolysis phenotypes at hospital arrival in severely injured patients is: 1) hyperfibrinolysis 18%, physiologic 18%, and shutdown 64%. The mechanisms responsible for dysregulated fibrinolysis following injury remain uncertain...
April 2016: Transfusion
Hunter B Moore, Ernest E Moore, Ioannis N Liras, Eduardo Gonzalez, John A Harvin, John B Holcomb, Angela Sauaia, Bryan A Cotton
BACKGROUND: Fibrinolysis is a physiologic process that maintains microvascular patency by breaking down excessive fibrin clot. Hyperfibrinolysis is associated with a doubling of mortality. Fibrinolysis shutdown, 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 2 urban trauma centers. STUDY DESIGN: Injured patients included in the analysis were admitted between 2010 and 2013, were 18 years of age or older, and had an Injury Severity Score (ISS) > 15...
April 2016: Journal of the American College of Surgeons
Ernest E Moore, Hunter B Moore, Eduardo Gonzalez, Michael P Chapman, Kirk C Hansen, Angela Sauaia, Christopher C Silliman, Anirban Banerjee
No abstract text is available yet for this article.
June 2015: Journal of Trauma and Acute Care Surgery
Hunter B Moore, Ernest E Moore, Peter J Lawson, Eduardo Gonzalez, Miguel Fragoso, Alex P Morton, Fabia Gamboni, Michael P Chapman, Angela Sauaia, Anirban Banerjee, Christopher C Silliman
INTRODUCTION: Systemic hyperfibrinolysis (accelerated clot degradation) and fibrinolysis shutdown (impaired clot degradation) are associated with increased mortality compared with physiologic fibrinolysis after trauma. Animal models have not reproduced these changes. We hypothesize rodents have a shutdown phenotype that require an exogenous profibrinolytic to differentiate mechanisms that promote or inhibit fibrinolysis. METHODS: Fibrinolysis resistance was assessed by thrombelastography (TEG) using exogenous tissue plasminogen activator (tPA) titrations in whole blood...
August 2015: Surgery
Hunter B Moore, Ernest E Moore, Eduardo Gonzalez, Kirk C Hansen, Monika Dzieciatkowska, Michael P Chapman, Angela Sauaia, Bernadette West, Anirban Banerjee, Christopher C Silliman
INTRODUCTION: We have recently identified a spectrum of fibrinolysis in response to injury, in which there is increased mortality in patients who have either excessive fibrinolysis (hyperfibrinolysis [HF]) or impaired fibrinolysis (shutdown). The regulation of the fibrinolytic system after trauma remains poorly understood. Our group's previous proteomic and metabolomic work identified elevated red blood cell (RBC) degradation products in trauma patients manifesting HF. We therefore hypothesized that hemolysis was contributory to the pathogenesis of HF...
January 2015: Shock
Hunter B Moore, Ernest E Moore, Eduardo Gonzalez, Michael P Chapman, Theresa L Chin, Christopher C Silliman, Anirban Banerjee, Angela Sauaia
BACKGROUND: Fibrinolysis is a physiologic process maintaining patency of the microvasculature. Maladaptive overactivation of this essential function (hyperfibrinolysis) is proposed as a pathologic mechanism of trauma-induced coagulopathy. Conversely, the shutdown of fibrinolysis has also been observed as a pathologic phenomenon. We hypothesize that there is a level of fibrinolysis between these two extremes that have a survival benefit for the severely injured patients. METHODS: Thrombelastography and clinical data were prospectively collected on trauma patients admitted to our Level I trauma center from 2010 to 2013...
December 2014: Journal of Trauma and Acute Care Surgery
Takeshi Wada, Satoshi Gando, Asumi Mizugaki, Yuichiro Yanagida, Subrina Jesmin, Hiroyuki Yokota, Masahiro Ieko
INTRODUCTION: Post-cardiac arrest syndrome (PCAS) is often associated with disseminated intravascular coagulation (DIC), thus leading to the development of multiple organ dysfunction syndrome (MODS). The aim of this study was to examine the pathophysiological relationships between coagulation, fibrinolysis and fibrinolytic shutdown by evaluating the levels of coagulofibrinolytic markers, including soluble fibrin, thrombin-activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator-plasminogen activator inhibitor-1 complex (tPAIC), plasmin-alpha2 plasmin inhibitor complex (PPIC), neutrophil elastase and fibrin degradation product by neutrophil elastase (EXDP)...
July 2013: Thrombosis Research
Sisse R Ostrowski, Ronan M G Berg, Nis A Windeløv, Martin A S Meyer, Ronni R Plovsing, Kirsten Møller, Pär I Johansson
BACKGROUND: Sepsis induces early activation of coagulation and fibrinolysis followed by late fibrinolytic shutdown and progressive endothelial damage. The aim of the present study was to investigate and compare the functional hemostatic response in whole blood and plasma during experimental human endotoxemia by the platelet function analyzer, Multiplate and by standard and modified thrombelastography (TEG). METHODS: Prospective physiologic study of nine healthy male volunteers undergoing endotoxemia by means of a 4-hour infusion of E...
2013: PloS One
Mineji Hayakawa, Atsushi Sawamura, Satoshi Gando, Subrina Jesmin, Sumiyoshi Naito, Masahiro Ieko
INTRODUCTION: We hypothesized that thrombin activatable fibrinolysis inhibitor (TAFI) and the activation of fibrinolysis by both plasmin and neutrophil elastase is insufficient to overcome fibrinolytic shutdown, contributing to multiple organ dysfunction syndrome (MODS) in sepsis-induced disseminated intravascular coagulation (DIC). MATERIALS AND METHODS: Fifty patients with sepsis were prospectively enrolled. The DIC was diagnosed based on the Japanese Association for Acute Medicine (JAAM) DIC and the International Society on Thrombosis and Haemostasis (ISTH) overt DIC criteria...
December 2012: Thrombosis Research
Satoshi Gando, Mineji Hayakawa, Atsushi Sawamura, Hirokatsu Hoshino, Akiko Oshiro, Nobuhiko Kubota, Subrina Jesmin
INTRODUCTION: We conducted a prospective study to test the hypothesis that the activation of neutrophil elastase-mediated fibrinolysis is insufficient to overcome the fibrinolytic shutdown of disseminated intravascular coagulation (DIC) in patients associated with systemic inflammation. MATERIALS AND METHODS: We investigated 45 consecutive patients with systemic inflammatory response syndrome (SIRS) and sepsis, classified as 11 DIC and 34 non-DIC. Fibrin degradation products by neutrophil elastase (Elastase-XDP) and by plasmin (FDP), cross-linked fibrin degradation products (D-dimer), soluble fibrin, antithrombin, protein C, plasminogen activator inhibitor-1 (PAI-1), and urinary trypsin inhibitor (UTI) were measured within 24 h after the patients met either the SIRS or sepsis criteria (day 0), as well as on days 2 and 4...
2007: Thrombosis Research
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