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Fibrinolysis Shutdown

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
J B Walker, L Bajzar
BACKGROUND: The antifibrinolytic effect of activated thrombin-activatable fibrinolysis inhibitor (TAFIa) and carboxypeptidase B (CPB) displays threshold behavior. When CPB was used to simulate conditions mimicking continuous TAFIa activity, it affected the lysis of plasma clots differently to clots formed from a minimal fibrinolytic system comprising fibrinogen, plasminogen and alpha(2)-antiplasmin. Whereas CPB saturably prolonged clot lysis in the purified system, the effect of CPB did not appear saturable in plasma clots...
June 2007: Journal of Thrombosis and Haemostasis: JTH
E Olsson, N Svartling, S Asko-Seljavaara
We report on a rare case of major intra-abdominal bleeding that occurred in a patient undergoing late breast reconstruction with a transversus rectus abdominis musculocutaneous (TRAM) flap. During the flap-raising procedure, a small rupture was found at the base of the superior mesenteric artery, probably caused by electric current. The ruptured vessel required immediate laparotomy and suturing, and the final outcome of the patient was good. The massive bleeding, almost 8-fold as compared with three normal cases, caused clear activation of coagulation seen with elevated TAT values at the end of the operation, and remarkably enhanced fibrin turnover with elevated D-dimer, up to 25-fold from baseline, on the first postoperative day...
2005: Microsurgery
Peter N Walsh, Syed S Ahmad
The serine proteases, cofactors and cell-receptor molecules that comprise the haemostatic mechanism are highly conserved modular proteins that have evolved to participate in biochemical reactions in blood coagulation, anticoagulation and fibrinolysis. Blood coagulation is initiated by exposure of tissue factor, which forms a complex with factor VIIa and factor X, which results in the generation of small quantities of thrombin and is rapidly shutdown by the tissue factor pathway inhibitor. The generation of these small quantities of thrombin then activates factor XI, resulting in a sequence of events that lead to the activation of factor IX, factor X and prothrombin...
2002: Essays in Biochemistry
J Neudecker, T Junghans, S Ziemer, W Raue, W Schwenk
BACKGROUND: Although the pneumoperitoneum decreases venous reflux from the lower extremities, the rate of thromboembolic complcations seems to be lower after laparoscopic than after conventional procedures. Therefore, it has been assumed that laparoscopic surgery better preserves the intravasal fibrinolytic capacity. The aim of this study was to determine the influence of the operative technique on intravasal fibrinolytic capacity in colorectal resection. METHODS: Randomized controlled trial conducted in parallel with the multicenter trial LAPKON II comparing the long-term effects of elective laparoscopic (group I) and conventional (group II) resections for colorectal cancer...
January 2003: Surgical Endoscopy
Petros V Anagnostopoulos, Alexander D Shepard, Iraklis I Pipinos, Sundara B K Raman, Pervaiz A Chaudhry, Takayuki Mishima, Hideaki Morita, George Suzuki
PURPOSE: The causative role of consumptive coagulopathy in the development of bleeding complications after supraceliac (SC) aortic cross-clamping (AXC) has been challenged by recent reports that ascribe this coagulopathy to primary fibrinolysis. This theory is made on the basis of evidence that tissue plasminogen activator (t-PA) antigen (Ag) levels increase after SC AXC. However, t-PA Ag levels reflect both active and inactive (bound to serum t-PA inhibitors) forms of serum t-PA, and elevations confirm the presence of fibrinolysis only in conjunction with an increase in t-PA activity...
January 2002: Journal of Vascular Surgery
M A Cahan, D J Hanna, L A Wiley, D K Cox, L A Killewich
INTRODUCTION: External pneumatic compression (EPC) devices prevent lower extremity deep venous thrombosis by increasing venous flow and thereby reducing stasis. Early studies suggested that they also enhance systemic fibrinolytic activity and thus prevent thrombus formation; more recent studies have been conflicting. The hypothesis of this study was that EPC devices enhance systemic fibrinolysis or reduce postoperative fibrinolytic impairment in patients undergoing abdominal surgical procedures...
September 2000: Journal of Vascular Surgery
F V Mortensen, B Jørgensen, H M Christiansen, J Sloth-Nielsen, B Wolff, I Hessov
Colonic ischaemia may complicate aortic graft surgery with high mortality from associated colonic necrosis. Loss of the mucosal barrier function due to ischaemia may promote translocation of endotoxins with secondary systemic disseminated coagulation leading to multiple organ failure. Short-chain fatty acids (SCFAs) stimulate the microcirculation in the human rectum. The aim of this study was to investigate whether SCFA enemas influence systemic endotoxinaemia and fibrinolytic activity during and after elective aortic graft surgery for arteriosclerosis...
June 1, 2000: Thrombosis Research
M Szczepański, J Kubiak, L Lembas
Twenty-nine patients undergoing cholecystectomy because of chronic calculous cholecystitis were randomised to receive phenylbutazone 10 mg/kg intramuscularly or a control injection (vehicle-containing local anaesthetic) immediately after completion of surgery. Fibrinogen and plasminogen concentrations in plasma, plasminogen activator inhibitor activity in plasma and fibrinolytic activity in concentrated euglobulins were determined before surgery and on the first, third and seventh postoperative days. Phenylbutazone delayed the postoperative rise of fibrinogen concentration and reduced the plasminogen level on the first day after surgery...
1998: Current Medical Research and Opinion
E de Jonge, M Levi, C P Stoutenbeek, S J van Deventer
Disseminated intravascular coagulation (DIC) can be caused by a variety of diseases. Experimental models of DIC have provided substantial insight into the pathogenesis of this disorder, which may ultimately result in improved treatment. Disseminated coagulation is the result of a complex imbalance of coagulation and fibrinolysis. Simultaneously occurring tissue factor-dependent activation of coagulation, depression of natural anticoagulant pathways and shutdown of endogenous fibrinolysis all contribute to the clinical picture of widespread thrombotic deposition in the microvasculature and subsequent multiple organ failure...
June 1998: Drugs
L A Killewich, R F Macko, A W Gardner, K Cox, M P Lilly, W R Flinn
PURPOSE: Early thrombosis of infrainguinal bypass grafts may occur as a result of hypercoagulable states. Major surgical procedures are known to induce a procoagulant state that is manifested in part by reduced endogenous fibrinolytic activity or fibrinolytic shutdown. This study was performed to assess the timing and biologic mechanism of fibrinolytic shutdown after infrainguinal bypass procedures by direct assay of the serologic markers of in vivo fibrinolytic activity. METHODS: Twenty patients underwent infrainguinal bypass procedures under epidural anesthesia...
May 1997: Journal of Vascular Surgery
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