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Thrombin Hemostatic

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321. Registry Study for the Use of HEMOBLASTâ„¢ Bellows in Abdominoplasty

to control minimal, mild, or moderate bleeding for which conventional means of hemostasis are ineffective or impractical Device: HEMOBLAST Bellows The HEMOBLAST™ Bellows hemostatic agent consists of a bellows pre-loaded with 1.65g of powder composed of collagen, chondroitin sulfate, and thrombin (1500 IU). HEMOBLAST™ Bellows is indicated in surgical procedures as an adjunct to hemostasis when control of minimal, mild, and moderate bleeding by conventional procedures is ineffective or impractical, except (...) .: No Keywords provided by Biom'Up SA: Hemostatics Coagulants

2018 Clinical Trials

322. The multifaceted role of fibrinogen in tissue injury and inflammation. Full Text available with Trip Pro

The multifaceted role of fibrinogen in tissue injury and inflammation. The canonical role of the hemostatic and fibrinolytic systems is to maintain vascular integrity. Perturbations in either system can prompt primary pathological end points of hemorrhage or thrombosis with vessel occlusion. However, fibrin(ogen) and proteases controlling its deposition and clearance, including (pro)thrombin and plasmin(ogen), have powerful roles in driving acute and reparative inflammatory pathways that affect (...) to the identification of novel hemostatic factor-targeted therapies for a range of tissue injuries and disease.© 2019 by The American Society of Hematology.

2018 Blood

323. Coagulation markers and echocardiography predict atrial fibrillation, malignancy or recurrent stroke after cryptogenic stroke. Full Text available with Trip Pro

Coagulation markers and echocardiography predict atrial fibrillation, malignancy or recurrent stroke after cryptogenic stroke. We evaluated the utility of left atrial volume index (LAVI) and markers of coagulation and hemostatic activation (MOCHA) in cryptogenic stroke (CS) patients to identify those more likely to have subsequent diagnosis of atrial fibrillation (AF), malignancy or recurrent stroke during follow-up.Consecutive CS patients who met embolic stroke of undetermined source (ESUS (...) ) who underwent transthoracic echocardiography and outpatient cardiac monitoring following stroke were identified from the Emory cardiac registry. In a subset of consecutive patients, d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex and fibrin monomer (MOCHA panel) were obtained ≥2 weeks post-stroke and repeated ≥4 weeks later if abnormal; abnormal MOCHA panel was defined as ≥2 elevated markers which did not normalize when repeated. We assessed the predictive abilities of LAVI

2018 Medicine

324. The Tissue Factor Pathway and Wound Healing. (Abstract)

The Tissue Factor Pathway and Wound Healing. The role of tissue factor (TF) as the major initiator of hemostatic blood coagulation is well recognized. The ability to form an adequate hemostatic clot is essential to the normal healing of an injury by staunching bleeding, stabilizing the injured tissue, and serving as a scaffold for repair processes. Also, some molecules produced during hemostasis, particularly thrombin, have cytokine and growth factor-like activities that contribute (...) to inflammation and repair. However, TF itself has activities as a regulator of cellular processes via direct signaling, as well as by facilitating activation of proteolytically activated receptors by activated factors VII and X. The importance of hemostasis in the host response to injury makes it very difficult to separate the hemostatic from nonhemostatic effects of TF on wound healing. The literature in this area remains sparse but suggests that TF influences the course and tempo of healing by cell

2018 Seminars In Thrombosis And Hemostasis

325. The expression and localization of RNase and RNase inhibitor in blood cells and vascular endothelial cells in homeostasis of the vascular system. Full Text available with Trip Pro

in the human umbilical vein endothelial cell line, EAhy926. Additionally, we further investigated the effect of thrombin on the expression of RNase 1 and RI in platelets. We used an RNase activity assay, reverse transcription-polymerase chain reaction, western blot, immunocytochemistry, transmission electron microscopy, and immunoelectron microscopy (pre- and post-embedding methods). RNase activity in the supernatant from EAhy926 cells was 50 times than in blood cells (after 60 min). RNase 1 mRNA (...) injury show very low RNase activity, which may support hemostatic thrombus formation. However, activated platelets and leukocytes may accelerate pathologic thrombus formation.

2017 PLoS ONE

326. Evaluation of hemostasis parameters and the role of the oxidative damage to plasma proteins in the modulation of hemostasis in patients with nephrolithiasis before and after extracorporeal shock wave lithotripsy. Full Text available with Trip Pro

of the present study was to determine whether oxidative stress may modulate the hemostatic activity of plasma in patients with nephrolithiasis before ESWL and the day after treatment ESWL. This will be performed by measuring selected parameters of hemostasis in these patients, both before ESWL and the following day, and assessing the level of oxidative damage to plasma proteins in these patients by measuring two biomarkers.Twelve patients with nephrolithiasis and 10 healthy participants were included (...) . The following parameters of hemostasis were measured: the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) of plasma, the level of fibrinogen, the level of D-dimer and blood platelet count. In addition, two selected biomarkers of oxidative stress were measured: protein carbonylation level and the number of protein thiol groups.No difference was observed between patients with nephrolithiasis before and after ESWL and healthy controls with regard to PT, TT or APTT

2017 PLoS ONE

327. Human platelet interaction with E. coli O111 promotes tissue-factor-dependent procoagulant activity, involving Toll like receptor 4. Full Text available with Trip Pro

is that E. coli O111-TLR4 interaction activates platelets and elicits their procoagulant activity. We demonstrated that the strain, but not ultrapure LPS, increased surface P-selectin expression, platelet dependent TF procoagulant activity (TF-PCA) and prompted a faster thrombin generation (TG). Blockade of TLR4 resulted in decreased platelet activation, TF-PCA and TG, revealing the participation of this immune receptor on the procoagulant response of platelets. Our results provide a novel mechanism (...) by which individuals with bacterial infections would have an increased incidence of blood clots. Furthermore, the identification of platelet TF and TLR4 as regulators of the effect of E. coli O111 might represent a novel therapeutic target to reduce the devastating consequences of the hemostatic disorder during sepsis.

2017 PLoS ONE

328. Tissue Factor: An Essential Mediator of Hemostasis and Trigger of Thrombosis. Full Text available with Trip Pro

Tissue Factor: An Essential Mediator of Hemostasis and Trigger of Thrombosis. Tissue factor (TF) is the high-affinity receptor and cofactor for factor (F)VII/VIIa. The TF-FVIIa complex is the primary initiator of blood coagulation and plays an essential role in hemostasis. TF is expressed on perivascular cells and epithelial cells at organ and body surfaces where it forms a hemostatic barrier. TF also provides additional hemostatic protection to vital organs, such as the brain, lung, and heart (...) . For instance, TF-dependent activation of the coagulation cascade generates coagulation proteases, such as FVIIa, FXa, and thrombin, which induce signaling in a variety of cells by cleavage of protease-activated receptors. This review will focus on the roles of TF in protective hemostasis and pathological thrombosis.© 2018 American Heart Association, Inc.

2018 Thrombosis and Vascular Biology

329. Measuring fibrinolysis: from research to routine diagnostic assays. Full Text available with Trip Pro

Measuring fibrinolysis: from research to routine diagnostic assays. Development and standardization of fibrinolysis methods have progressed more slowly than coagulation testing and routine high-throughput screening tests for fibrinolysis are still lacking. In laboratory research, a variety of approaches are available and are applied to understand the regulation of fibrinolysis and its contribution to the hemostatic balance. Fibrinolysis in normal blood is slow to develop. For practical purposes (...) plasminogen activators can be added to clotting plasma, or euglobulin prepared to reduce endogenous inhibitors, but results are complicated by these manipulations. Observational studies to identify a 'fibrinolysis deficit' have concluded that excess fibrinolysis inhibitors, plasminogen activator inhibitor 1 (PAI-1) or thrombin-activatable fibrinolysis inhibitor (TAFI), zymogen or active enzyme, may be associated with an increased risk of thrombosis. However, results are not always consistent and problems

2018 Journal of Thrombosis and Haemostasis

330. Transcriptomic landscape of acute promyelocytic leukemia reveals aberrant surface expression of the platelet aggregation agonist Podoplanin. (Abstract)

Transcriptomic landscape of acute promyelocytic leukemia reveals aberrant surface expression of the platelet aggregation agonist Podoplanin. Acute promyelocytic leukemia (APL) is a medical emergency because of associated lethal early bleeding, a condition preventable by prompt diagnosis and therapeutic intervention. The mechanisms underlying the hemostatic anomalies of APL are not completely elucidated. RNA-sequencing-based characterization of APL (n = 30) was performed and compared (...) to that of other acute myeloid leukemia (n = 400) samples and normal promyelocytes. Perturbations in the transcriptome of coagulation and fibrinolysis-related genes in APL extend beyond known culprits and now include Thrombin, Factor X and Urokinase Receptor. Most intriguingly, the Podoplanin (PDPN) gene, involved in platelet aggregation, is aberrantly expressed in APL promyelocytes and is the most distinctive transcript for this disease. Using an antibody panel optimized for AML diagnosis by flow cytometry

2018 Leukemia

331. Safety and efficacy of cryopreserved platelets in bleeding patients with thrombocytopenia. Full Text available with Trip Pro

) was performed in bleeding patients with thrombocytopenia. Within each of four cohorts, six patients received escalating doses of CPP (0.5 unit, 1 unit, and sequential transfusions of 2 and 3 units) and one received a LSP transfusion. Patients were monitored for adverse events (AEs), coagulation markers, PLT responses, and hemostatic efficacy.Patients with a World Health Organization bleeding score of 2 or more received from 0.5 to 3 units of CPP (n = 24) or 1 unit of LSP (n = 4). There were no related (...) . After transfusion, the CPP recipients had improvements in some variables of thrombin generation tests and thromboelastography.Cryopreserved PLT transfusions appear to be safe and effective when given to bleeding patients with thrombocytopenia.© 2018 AABB.

2018 Transfusion Controlled trial quality: uncertain

332. Elevated plasma levels of cell-free DNA during orthotopic liver transplantation are associated with activation of coagulation. Full Text available with Trip Pro

fragment 1+2 and thrombin-antithrombin complex levels, which are established markers for activation of coagulation. Neutrophils undergoing NETosis were observed by immunostainings in postreperfusion biopsies. In conclusion, although NETosis occurs during liver transplantation, the majority of circulating DNA appears to be derived from cell death within the graft. The perioperative increases in cfDNA and nucleosomes might contribute to the complex hemostatic rebalance during liver (...) Elevated plasma levels of cell-free DNA during orthotopic liver transplantation are associated with activation of coagulation. Patients undergoing liver transplantation have complex changes in their hemostatic system, and the net effect of these changes appears to be a "rebalanced" hemostatic profile. Recently, a process called NETosis in which a neutrophil expels DNA and proteins that form a weblike structure, has been described as a mechanism of pathogen entrapment. Increasing evidence

2018 Liver Transplantation

333. Characterization of biologic response modifiers in the supernatant of conventional, refrigerated, and cryopreserved platelets. (Abstract)

cryopreserved PLTs had reduced Factor (F)V and FVIII activity. Cold-stored PLTs retained α-granule proteins better than room temperature or cryopreserved PLTs. Cryopreservation resulted in 10-fold higher microparticle generation than cold-stored PLTs, but both groups contained significantly more microparticles than those stored at room temperature. The supernatant from both cold and cryopreserved PLTs initiated faster clot formation and thrombin generation than room temperature PLTs.Cold storage (...) and cryopreservation alter the composition of the soluble fraction of stored PLTs. These differences in coagulation proteins, cytokines, and microparticles likely influence both the hemostatic capacity of the components and the auxiliary functions.© 2017 AABB.

2018 Transfusion

334. Modified clot waveform analysis to measure plasma coagulation potential in the presence of the anti-factor IXa/factor X bispecific antibody, emicizumab. Full Text available with Trip Pro

in Emi-treated hemophilia A.Background Emicizumab is an anti-activated factor IX/FX bispecific antibody that mimics activated FVIII cofactor function. Emicizumab does not require activation by thrombin, and its effect on shortening the activated partial thromboplastin time (APTT) is much greater than that of FVIII. Therefore, the APTT has limited utility in hemophilia A (HA) patients treated with emicizumab. Aim To evaluate the global coagulation potential of emicizumab. Methods Clot waveform (...) analysis (CWA) with prothrombin time (PT)/APTT mixed reagents was used to define hemostatic monitoring protocols in HA patients. A modified parameter, adjusted-|min1| (Ad|min1|), was developed. Maximum and minimum percentage transmittance were defined as 100% and 0% in the precoagulation and postcoagulation phases, respectively. Ad|min1| was calculated as an index of the maximum velocity of the coagulation process. Results Ad|min1| obtained with mixed-trigger reagent (PT/APTT/buffer, 1 : 15 : 135

2018 Journal of Thrombosis and Haemostasis

335. Registry for the Use of HEMOBLAST Bellows in Total Knee Arthroplasty

Total Knee Arthroplasty Patients Patients undergoing primary or revision total knee arthroplasty procedures in which the surgeon elects to use HEMOBLAST Bellows to control minimal, mild, or moderate bleeding for which conventional means of hemostasis are ineffective or impractical Device: HEMOBLAST Bellows The HEMOBLAST™ Bellows hemostatic agent consists of a bellows pre-loaded with 1.65g of powder composed of collagen, chondroitin sulfate, and thrombin (1500 IU). HEMOBLAST™ Bellows is indicated (...) . FDA-regulated Device Product: Yes Device Product Not Approved or Cleared by U.S. FDA: No Pediatric Postmarket Surveillance of a Device Product: No Product Manufactured in and Exported from the U.S.: No Keywords provided by Biom'Up SA: Hemostatics Coagulants

2018 Clinical Trials

336. An investigational RNAi therapeutic targeting antithrombin for the treatment of hemophilia A and B Full Text available with Trip Pro

, but in one subject with severe hemophilia A, the concomitant use of daily high-dose factor VIII, inconsistent with trial guidance to avoid high, repeat doses of clotting factor, was associated with fatal thrombosis, suggesting the need for caution when using hemostatic agents in conjunction with fitusiran. Preclinical in vitro and in silico studies indicate improvement in thrombin generation in rare bleeding disorder plasmas, including in plasmas from patients with severe factors V, VII, and X deficiency (...) trials, fitusiran dose escalation has resulted in improved thrombin generation and clinical hemostasis as measured by reduction in annualized bleed rate. Unlike currently licensed drugs, this improvement was not only in patients with hemophilia A but in also those with hemophilia B, with or without inhibitors. In dental and surgical procedures, fitusiran also provided perioperative hemostasis in association with AT lowering. Fitusiran is well tolerated, with minor local injection site reactions

2018 Journal of blood medicine

337. Human platelets express Endothelial Protein C Receptor which can be utilized to enhance localization of Factor VIIa activity. Full Text available with Trip Pro

therapeutics.Background High-dose factor VIIa (FVIIa) is routinely used as an effective bypassing agent to treat hemophilia patients with inhibitory antibodies that compromise factor replacement. However, the mechanism by which FVIIa binds activated platelets to promote hemostasis is not fully understood. FVIIa-DVQ is an analog of FVIIa with enhanced tissue factor (TF)-independent activity and hemostatic efficacy relative to FVIIa. Our previous studies have shown that FVIIa-DVQ exhibits greater platelet binding (...) protein C or an anti-EPCR antibody. This decreased binding results in a corresponding decrease in the activity of both molecules in FXa and thrombin generation assays. Enhanced binding to EPCR was sufficient to account for the increased platelet binding of FVIIa-DVQ compared with wild-type FVIIa. As EPCR protein expression has not previously been shown in platelets, we confirmed the presence of EPCR in platelets using immunofluorescence, flow cytometry, immunoprecipitation, and mass spectrometry

2018 Journal of Thrombosis and Haemostasis

338. Plasma from Patients Undergoing Liver Transplantation Is Resistant to Anticoagulant Activity of Soluble Thrombomodulin (ART-123). Full Text available with Trip Pro

alterations in the hemostatic system may complicate its use in this setting. Here, we studied the in vitro effect of ART-123 on coagulation of patients with end-stage liver disease undergoing liver transplantation. Ten patients with end-stage liver disease undergoing liver transplantation were included in this study. Plasma samples of 10 healthy individuals were included to establish reference values. Different concentrations of ART-123 were added to plasma samples, and peak thrombin generation and clot (...) lysis times (CLTs) were determined. In patient samples, plasma was profoundly resistant to the anticoagulant action of ART-123, as reflected by significantly higher median inhibitory concentration (IC50 ) values of peak thrombin generation compared with controls. This might be partially explained by low levels of protein C, protein S, and elevated levels of factor VIII during transplantation. Intraoperative levels of thrombin activatable fibrinolysis inhibitor were significantly lower when compared

2018 Liver Transplantation

339. Carboxypeptidase U (CPU, CPB2, TAFIa) inhibition stimulates the fibrinolytic rate in different in vitro models. Full Text available with Trip Pro

, carboxypeptidase B2, activated thrombin-activatable fibrinolysis inhibitor) is a basic carboxypeptidase that attenuates fibrinolysis. This characteristic has raised interest in the scientific community and pharmaceutical industry for the development of inhibitors as profibrinolytic agents. Objectives Little is known about the contribution of CPU to clot resistance in more advanced hemostatic models, which include blood cells and shear stress. The aim of this study was to evaluate the effects of the CPU system (...) Carboxypeptidase U (CPU, CPB2, TAFIa) inhibition stimulates the fibrinolytic rate in different in vitro models. Essentials AZD9684 is a potent inhibitor of carboxypeptidase U (CPU, TAFIa, CPB2). The effect of AZD9684 on fibrinolysis was investigated in four in vitro systems. The CPU system also attenuates fibrinolysis in more advanced hemostatic systems. The size of the observed effect on fibrinolysis is dependent on the exact experimental conditions.Background Carboxypeptidase U (CPU

2018 Journal of Thrombosis and Haemostasis

340. Clinical effect of enoxaparin on international normalized ratio following hepato-pancreatico-biliary and gastroesophageal resection. (Abstract)

Clinical effect of enoxaparin on international normalized ratio following hepato-pancreatico-biliary and gastroesophageal resection. Enoxaparin inactivates factor Xa via a complex formed after binding to circulating anti-thrombin III. This mechanism is reported not to alter hemostatic measures such as clotting time, PT, or PTT. To date, no clinical trials have shown a causal relationship between the clinical/pharmacological effects of enoxaparin on international normalized ratio (INR). The aim

2018 Journal of Surgical Oncology

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