The Experts below are selected from a list of 369 Experts worldwide ranked by ideXlab platform
Mineji Hayakawa - One of the best experts on this subject based on the ideXlab platform.
-
hyperfibrinolysis in severe isolated traumatic brain injury may occur without tissue hypoperfusion a retrospective observational multicentre study
Critical Care, 2017Co-Authors: Mineji Hayakawa, Kunihiko Maekawa, Shigeki Kushimoto, Hiroshi Kato, Junichi Sasaki, Hiroshi Ogura, Tetsuya Matsuoka, Toshifumi Uejima, Naoto Morimura, Hiroyasu IshikuraAbstract:Hyperfibrinolysis is a critical complication in severe trauma. Hyperfibrinolysis is traditionally diagnosed via elevated D-dimer or fibrin/Fibrinogen Degradation Product levels, and recently, using thromboelastometry. Although hyperfibrinolysis is observed in patients with severe isolated traumatic brain injury (TBI) on arrival at the emergency department (ED), it is unclear which factors induce hyperfibrinolysis. The present study aimed to investigate the factors associated with hyperfibrinolysis in patients with isolated severe TBI. We conducted a multicentre retrospective review of data for adult trauma patients with an injury severity score ≥ 16, and selected patients with isolated TBI (TBI group) and extra-cranial trauma (non-TBI group). The TBI group included patients with an abbreviated injury score (AIS) for the head ≥ 4 and an extra-cranial AIS < 2. The non-TBI group included patients with an extra-cranial AIS ≥ 3 and head AIS < 2. Hyperfibrinolysis was defined as a D-dimer level ≥ 38 mg/L on arrival at the ED. We evaluated the relationships between hyperfibrinolysis and injury severity/tissue injury/tissue perfusion in TBI patients by comparing them with non-TBI patients. We enrolled 111 patients in the TBI group and 126 in the non-TBI group. In both groups, patients with hyperfibrinolysis had more severe injuries and received transfusion more frequently than patients without hyperfibrinolysis. Tissue injury, evaluated on the basis of lactate dehydrogenase and creatine kinase levels, was associated with hyperfibrinolysis in both groups. Among patients with TBI, the mortality rate was higher in those with hyperfibrinolysis than in those without hyperfibrinolysis. Tissue hypoperfusion, evaluated on the basis of lactate level, was associated with hyperfibrinolysis in only the non-TBI group. Although the increase in lactate level was correlated with the deterioration of coagulofibrinolytic variables (prolonged prothrombin time and activated partial thromboplastin time, decreased Fibrinogen levels, and increased D-dimer levels) in the non-TBI group, no such correlation was observed in the TBI group. Hyperfibrinolysis is associated with tissue injury and trauma severity in TBI and non-TBI patients. However, tissue hypoperfusion is associated with hyperfibrinolysis in non-TBI patients, but not in TBI patients. Tissue hypoperfusion may not be a prerequisite for the occurrence of hyperfibrinolysis in patients with isolated TBI.
-
disseminated intravascular coagulation at an early phase of trauma is associated with consumption coagulopathy and excessive fibrinolysis both by plasmin and neutrophil elastase
Surgery, 2011Co-Authors: Mineji Hayakawa, Atsushi Sawamura, Satoshi Gando, Nobuhiko Kubota, Shinji Uegaki, Hidekazu Shimojima, Masahiro Sugano, Masahiro IekoAbstract:Background The aims of the present study were to confirm the consumption coagulopathy of disseminated intravascular coagulation with the fibrinolytic phenotype at an early phase of trauma and to test the hypothesis that thrombin-activatable fibrinolysis inhibitor, neutrophil elastase, and plasmin contribute to the increased fibrinolysis of this type of disseminated intravascular coagulation. Furthermore, we hypothesized that disseminated intravascular coagulation at an early phase of trauma progresses dependently to disseminated intravascular coagulation with a thorombotic phenotype from 3 to 5 days after injury. Methods Fifty-seven trauma patients, including 30 patients with disseminated intravascular coagulation and 27 patients without disseminated intravascular coagulation, were studied prospectively. Levels of thrombin-activatable fibrinolysis inhibitor, tissue-type plasminogen activator plasminogen activator inhibitor-1 complex, plasmin alpha2 plasmin inhibitor complex, D-dimer, neutrophil elastase, and fibrin Degradation Product by neutrophil elastase were measured on days 1, 3, and 5 after trauma. The prothrombin time, Fibrinogen, fibrin/Fibrinogen Degradation Product, antithrombin, and lactate also were measured. Results Independent of the lactate levels, disseminated intravascular coagulation patients showed a prolonged prothrombin time, lesser Fibrinogen and antithrombin levels, and increased levels of fibrin/Fibrinogen Degradation Product on day 1. Disseminated intravascular coagulation diagnosed on day 1 continued to late-phase disseminated intravascular coagulation on days 3 and 5 after trauma. Increased levels of tissue-type plasminogen activator plasminogen activator inhibitor-1 complex, plasmin alpha2 plasmin inhibitor complex, D-dimer, neutrophil elastase, and fibrin Degradation Product by neutrophil elastase but not thrombin-activatable fibrinolysis inhibitor were observed in the disseminated intravascular coagulation patients. No correlation was observed between plasmin alpha2 plasmin inhibitor complex and fibrin Degradation Product by neutrophil elastase in disseminated intravascular coagulation patients. Multiple regression analysis showed the disseminated intravascular coagulation score and the tissue-type plasminogen activator plasminogen activator inhibitor-1 complex levels on day 1 to correlate with the total volume of transfused blood. Patient prognosis deteriorated in accordance with the increasing disseminated intravascular coagulation severity. Conclusion Disseminated intravascular coagulation at an early phase of trauma is associated with consumption coagulopathy and excessive fibrinolysis both by plasmin and neutrophil elastase independent of hypoperfusion and continues to disseminated intravascular coagulation at a late phase of trauma. Increased fibrinolysis requires more blood transfusions, contributing to a poor patient outcome.
Jawahar L Mehta - One of the best experts on this subject based on the ideXlab platform.
-
combined thrombolytic effects of tissue plasminogen activator and a Fibrinogen Degradation Product peptide 6a or iloprost
Journal of Cardiovascular Pharmacology, 1991Co-Authors: Wilmer W Nichols, F A Nicolini, T G P Saldeen, Jawahar L MehtaAbstract:Thrombolytic effects of tissue-type plasminogen activator (t-PA) are limited by in vivo platelet activation and dynamic coronary vasoconstriction. To examine if the concurrent administration of a fibrin(ogen)-Degradation Product, pentapeptide 6A (Ala-Arg-Pro-Ala-Lys) with t-PA would improve the thrombolytic effects of t-PA, dogs with electrically induced coronary thrombus were given t-PA alone or with peptide 6A. In dogs given t-PA alone (0.75 mg/kg over 20 min), coronary blood flow was restored in 69% of animals (9 of 13 dogs), with a mean time to reflow of 21 +/- 10 min and duration of reflow of 35 +/- 18 min. Reocclusion occurred in 77% of dogs (7 of 9 dogs). With concurrent administration of peptide 6A (200 mumol), coronary venous 6-keto-PGF1 alpha concentrations increased from 221 +/- 71 to 422 +/- 161 pg/ml (p less than 0.05), but not with t-PA given alone. Coronary blood flow was restored in 7 of 11 dogs (reperfusion rate 64%), with mean time to reflow of 17 +/- 7 min and duration of reflow of 35 +/- 15 min. The coronary reocclusion rate was 86%. All these indices of thrombolysis were similar to those in dogs given t-PA alone. In ex vivo experiments, we also demonstrated release of endothelium-derived relaxing factor from canine coronary artery rings in response to peptide 6A. To further examine the role of prostacyclin (PGI2) in thrombolytic response to t-PA, eight other dogs were given t-PA with a PGI2 analog iloprost (100 ng/kg/min for 40 min).(ABSTRACT TRUNCATED AT 250 WORDS)
-
fibrin ogen Degradation Product peptide 6a increases femoral artery blood flow in dogs
Acta Physiologica Scandinavica, 1991Co-Authors: K Saldeen, Wilmer W Nichols, D L Lawson, R Andersson, Tom Saldeen, Jawahar L MehtaAbstract:To determine the effects of peptide 6A (a Fibrinogen-Degradation Product) on femoral blood flow, anaesthetized dogs were given saline or peptide 6A intravenously in random order. Bolus injection of peptide 6A (10, 20 or 50 mumoles) caused a short-lasting dose-dependent decrease in femoral bed resistance and an increase in femoral blood flow. Continuous infusion of peptide 6A (50 mumoles min-1) resulted in a sustained decrease in resistance and an increase in femoral artery blood flow (54 +/- 33%), with a small, insignificant decrease in femoral artery mean pressure. Indomethacin pretreatment caused only slight attenuation of the peptide 6A-induced increase in femoral blood flow. In in vitro experiments, peptide 6A relaxed rings of femoral artery, and this effect was associated with an increase in 6-keto-PGF1 alpha in the vascular ring supernatants and in the tissue cyclic GMP concentrations. Peptide 6A-induced relaxation was abolished by de-endothelialization, but not by treatment with indomethacin. These observations suggest that peptide 6A induces vasorelaxation largely by stimulating release of endothelium-derived relaxing factor. PGI2 release appears to play only a minor role in the vasodilator effects of peptide 6A in the femoral bed.
Shigeki Kushimoto - One of the best experts on this subject based on the ideXlab platform.
-
hyperfibrinolysis in severe isolated traumatic brain injury may occur without tissue hypoperfusion a retrospective observational multicentre study
Critical Care, 2017Co-Authors: Mineji Hayakawa, Kunihiko Maekawa, Shigeki Kushimoto, Hiroshi Kato, Junichi Sasaki, Hiroshi Ogura, Tetsuya Matsuoka, Toshifumi Uejima, Naoto Morimura, Hiroyasu IshikuraAbstract:Hyperfibrinolysis is a critical complication in severe trauma. Hyperfibrinolysis is traditionally diagnosed via elevated D-dimer or fibrin/Fibrinogen Degradation Product levels, and recently, using thromboelastometry. Although hyperfibrinolysis is observed in patients with severe isolated traumatic brain injury (TBI) on arrival at the emergency department (ED), it is unclear which factors induce hyperfibrinolysis. The present study aimed to investigate the factors associated with hyperfibrinolysis in patients with isolated severe TBI. We conducted a multicentre retrospective review of data for adult trauma patients with an injury severity score ≥ 16, and selected patients with isolated TBI (TBI group) and extra-cranial trauma (non-TBI group). The TBI group included patients with an abbreviated injury score (AIS) for the head ≥ 4 and an extra-cranial AIS < 2. The non-TBI group included patients with an extra-cranial AIS ≥ 3 and head AIS < 2. Hyperfibrinolysis was defined as a D-dimer level ≥ 38 mg/L on arrival at the ED. We evaluated the relationships between hyperfibrinolysis and injury severity/tissue injury/tissue perfusion in TBI patients by comparing them with non-TBI patients. We enrolled 111 patients in the TBI group and 126 in the non-TBI group. In both groups, patients with hyperfibrinolysis had more severe injuries and received transfusion more frequently than patients without hyperfibrinolysis. Tissue injury, evaluated on the basis of lactate dehydrogenase and creatine kinase levels, was associated with hyperfibrinolysis in both groups. Among patients with TBI, the mortality rate was higher in those with hyperfibrinolysis than in those without hyperfibrinolysis. Tissue hypoperfusion, evaluated on the basis of lactate level, was associated with hyperfibrinolysis in only the non-TBI group. Although the increase in lactate level was correlated with the deterioration of coagulofibrinolytic variables (prolonged prothrombin time and activated partial thromboplastin time, decreased Fibrinogen levels, and increased D-dimer levels) in the non-TBI group, no such correlation was observed in the TBI group. Hyperfibrinolysis is associated with tissue injury and trauma severity in TBI and non-TBI patients. However, tissue hypoperfusion is associated with hyperfibrinolysis in non-TBI patients, but not in TBI patients. Tissue hypoperfusion may not be a prerequisite for the occurrence of hyperfibrinolysis in patients with isolated TBI.
-
Implications of excessive fibrinolysis and alpha(2)-plasmin inhibitor deficiency in patients with severe head injury.
Neurosurgery, 2001Co-Authors: Shigeki Kushimoto, Yasuhiro Yamamoto, Yasushi Shibata, Hidetaka Sato, Yuichi KoidoAbstract:OBJECTIVE To evaluate the involvement of the fibrinolytic system, especially focused on alpha(2)-plasmin inhibitor, in patients with head injury. METHODS This study consisted of 47 patients with isolated blunt head trauma in whom blood sampling could be initiated within 3 hours after injury. Patients were divided into two groups according to Glasgow Outcome Scale score status at 3 months after injury. In Group 1 patients (n = 26), the outcome was characterized as good recovery or moderate disability; in Group 2 patients (n = 21), the outcome was characterized as severe disability, vegetative state, or death. RESULTS Concentrations of thrombin-antithrombin III complex were greater than 100 microg/L in 39 of 47 patients, and concentrations in Group 2 patients were elevated significantly beyond the concentrations in Group 1 patients. Activities of alpha(2)-plasmin inhibitor in Group 2 were significantly lower than in Group 1 (P < 0.0001). In Group 1 patients, alpha(2)-plasmin inhibitor activity was greater than 60%, while in all but four Group 2 patients, the inhibitor was reduced to less than 60% of normal activity within 3 hours of injury. All patients with alpha(2)-plasmin inhibitor activity less than 60% showed a marked bleeding tendency and/or severe brain edema. Using sandwich enzyme-linked immunosorbent assay, Fibrinogen Degradation Product and fibrin Degradation Product were measured separately. A significant correlation was apparent between thrombin-antithrombin III complex and Fibrinogen Degradation Product, as well as between the complex and fibrin Degradation Product. Marked decreases in alpha(2)-plasmin inhibitor were noted only in patients with thrombin-antithrombin III complex concentrations exceeding 500 microg/L. CONCLUSION Fibrinolysis and Fibrinogenolysis may be involved according to the degree of coagulation activation in the pathophysiology of severe head injury. Decreased activity of alpha(2)-plasmin inhibitor indicated poor prognosis and may be an exacerbating factor in the acute phase of head trauma.
Asrar B Malik - One of the best experts on this subject based on the ideXlab platform.
-
Fibrinogen Degradation Product fragment d induces endothelial cell detachment by activation of cell mediated fibrinolysis
Journal of Clinical Investigation, 1992Co-Authors: Gexin Tang, Thomas J Ryan, Asrar B MalikAbstract:We studied the effects of Fibrinogen Degradation Product (FDP) fragment D on endothelial monolayer integrity and the mechanisms of fragment D-induced endothelial cell detachment from the substratum. Incubation of bovine pulmonary artery endothelial cells (BPAEC) with fragment D caused concentration- and time-dependent cell detachment from the substratum. The optimal response occurred at fragment D concentrations of 2 microM and required an incubation time of 24 h. BPAEC challenged with fragment D increased the concentration and activity of urokinase-type plasminogen activator (uPA) in the conditioned medium within 2 to 4 h of incubation. Fragment D also induced the release of tissue-type plasminogen activator, but to a lesser extent than uPA. Fragment D concurrently increased plasminogen activator (PA) activity in a concentration-dependent manner. Increased PA activity was followed by augmentation of cell-associated plasmin activity and subsequent increase in the Degradation of 125I-Fibrinogen and 125I-vitronectin precoated in the subendothelial matrix. Pretreatment of BPAEC with anti-uPA antibody, and inhibitors of uPA (dansyl-GGACK) and plasmin (aprotinin) prevented approximately 60% of the fragment D-induced endothelial cell detachment. We conclude that FDP fragment D increases secretion of endothelial PAs and enhances the generation of plasmin, thereby contributing to proteolysis of extracellular matrix and endothelial cell detachment. Fragment D may be a critical mediator linking activation of fibrinolysis to vascular endothelial injury in inflammatory disorders.
-
Fibrinogen Degradation Product fragment d increases endothelial monolayer permeability
American Journal of Physiology-lung Cellular and Molecular Physiology, 1991Co-Authors: T J Ryan, Hazel Lum, Asrar B MalikAbstract:We assessed the effects of the two primary high-molecular-weight Fibrinogen Degradation Products (FDP), fragments D and E, on the pulmonary vascular endothelial barrier function. Fragments D and E were purified to homogeneity by QAE Sephadex chromatography followed by gel filtration. Incubation of bovine pulmonary artery endothelial monolayers with 0.5-2.0 microM fragment D for 2 h caused a doubling of transendothelial 125I-albumin clearance rate (a measure of 125I-albumin permeability). Fragment E only produced a 0.6-fold increase in 125I-albumin clearance rate at concentration of 4.0 microM. Both FDP remained active in incubating media with serum. The permeability-increasing effect of fragment D was reversible and was not due to cell detachment or lysis. The fragment-D effect was time dependent and was associated with redistribution of endothelial F-actin microfilaments. The effect was independent of the carboxy-terminal sequence on gamma-chain of fragment D. Fragments D and E binding to pulmonary artery endothelial cells was specific and reversible, but fragment D binding was three-fold greater than fragment E, which may account for the greater permeability increase mediated by fragment D. The results indicate that FDP, especially fragment D, increase endothelial permeability to albumin. The response involves specific binding of fragment D to endothelial cells and redistribution of intracellular actin.
Hiroyasu Ishikura - One of the best experts on this subject based on the ideXlab platform.
-
hyperfibrinolysis in severe isolated traumatic brain injury may occur without tissue hypoperfusion a retrospective observational multicentre study
Critical Care, 2017Co-Authors: Mineji Hayakawa, Kunihiko Maekawa, Shigeki Kushimoto, Hiroshi Kato, Junichi Sasaki, Hiroshi Ogura, Tetsuya Matsuoka, Toshifumi Uejima, Naoto Morimura, Hiroyasu IshikuraAbstract:Hyperfibrinolysis is a critical complication in severe trauma. Hyperfibrinolysis is traditionally diagnosed via elevated D-dimer or fibrin/Fibrinogen Degradation Product levels, and recently, using thromboelastometry. Although hyperfibrinolysis is observed in patients with severe isolated traumatic brain injury (TBI) on arrival at the emergency department (ED), it is unclear which factors induce hyperfibrinolysis. The present study aimed to investigate the factors associated with hyperfibrinolysis in patients with isolated severe TBI. We conducted a multicentre retrospective review of data for adult trauma patients with an injury severity score ≥ 16, and selected patients with isolated TBI (TBI group) and extra-cranial trauma (non-TBI group). The TBI group included patients with an abbreviated injury score (AIS) for the head ≥ 4 and an extra-cranial AIS < 2. The non-TBI group included patients with an extra-cranial AIS ≥ 3 and head AIS < 2. Hyperfibrinolysis was defined as a D-dimer level ≥ 38 mg/L on arrival at the ED. We evaluated the relationships between hyperfibrinolysis and injury severity/tissue injury/tissue perfusion in TBI patients by comparing them with non-TBI patients. We enrolled 111 patients in the TBI group and 126 in the non-TBI group. In both groups, patients with hyperfibrinolysis had more severe injuries and received transfusion more frequently than patients without hyperfibrinolysis. Tissue injury, evaluated on the basis of lactate dehydrogenase and creatine kinase levels, was associated with hyperfibrinolysis in both groups. Among patients with TBI, the mortality rate was higher in those with hyperfibrinolysis than in those without hyperfibrinolysis. Tissue hypoperfusion, evaluated on the basis of lactate level, was associated with hyperfibrinolysis in only the non-TBI group. Although the increase in lactate level was correlated with the deterioration of coagulofibrinolytic variables (prolonged prothrombin time and activated partial thromboplastin time, decreased Fibrinogen levels, and increased D-dimer levels) in the non-TBI group, no such correlation was observed in the TBI group. Hyperfibrinolysis is associated with tissue injury and trauma severity in TBI and non-TBI patients. However, tissue hypoperfusion is associated with hyperfibrinolysis in non-TBI patients, but not in TBI patients. Tissue hypoperfusion may not be a prerequisite for the occurrence of hyperfibrinolysis in patients with isolated TBI.