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Fatal dysfunction and disintegration of thrombin-stimulated platelets. Platelets play a key role in formation of hemostatic clots and obstructive thrombi as well as in other biological processes. In response to physiological stimulants, including thrombin, platelets change their morphology, express adhesive molecules, undergo aggregation, and secrete bioactive substances, but their subsequent fate is largely unknown. Here we examine late-stage structural, metabolic, and functional consequences (...) of thrombin-induced platelet activation. Using a combination of confocal microscopy, scanning and transmission electron microscopy, flow cytometry, biochemical and biomechanical measurements, we show that thrombin-induced activation is followed by time-dependent platelet dysfunction and disintegration. After ~30 minutes of incubation with thrombin, unlike with collagen or ADP, human platelets underwent disintegration into cellular fragments containing organelles, such as mitochondria, glycogen granules
Effects of platelet-sparing leukocyte reduction and agitation methods on in vitro measures of hemostatic function in cold-stored whole blood. Agitation of platelet units stored at room temperature is performed routinely to maintain platelet function, and leukoreduction of blood products is the standard of care in many countries to reduce immune consequences of transfusion. The effect of agitation and leukoreduction on whole blood stored at 4°C requires investigation, as reductions in hemostatic (...) capacity of whole blood may reduce its efficacy in treating trauma-induced coagulopathy and platelet dysfunction. We hypothesize that agitation of whole blood will not affect hemostatic function and that leukoreduction will reduce hemostatic function of whole blood.In this in vitro randomized controlled study, 21 units of leukoreduced and 20 nonleukoreduced whole blood units were each randomly assigned into four agitation groups. Hemostatic parameters were measured using viscoelastic assays (rotational
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 in neurosurgical, ophthalmic, and urological procedures. Active Comparator: FLOSEAL (Hemostatic Device) Bleeding sites will be treated with FLOSEAL per its approved Indications for Use Device: FLOSEAL The FLOSEAL Matrix consists of a bovine-derived Gelatin Matrix (...) component, a human-derived Thrombin component, applicator tips, and several mixing accessories. FLOSEAL is indicated in surgical procedures (other than ophthalmic) as an adjunct to hemostasis when control of bleeding by ligature or conventional procedures is ineffective or impractical. Outcome Measures Go to Primary Outcome Measures : 3 minute hemostasis - hemostatic success (yes/no) at 3 minutes [ Time Frame: Intraoperative ] The primary endpoint of this study is the superiority of HEMOBLAST™ relative
without in terms of type and number of hemostatic abnormalities. Results Fifty-nine of 141 patients with EDS (41.7%) had an abnormal BSS. Prothrombin time and activated partial thromboplastin time were slightly prolonged in 10 patients (7.1%) because of mild coagulation factor deficiencies, which were not responsible for the bleeding diathesis. von Willebrand factor antigen, ristocetin cofactor, endogenous thrombin potential and platelet count were normal in all patients. At least one platelet (...) Hemostatic abnormalities in patients with ehlers-danlos syndrome. Essentials Ehlers-Danlos Syndrome (EDS) is a rare heterogeneous group of inherited collagen disorders. A cohort of EDS patients was investigated for bleeding tendency and hemostatic abnormalities. EDS is associated with an increased risk of bleeding. EDS patients have platelet function abnormalities, whose severity correlates with bleeding risk. SUMMARY: Background Ehlers-Danlos syndrome (EDS) includes a heterogeneous group
Effects of Repeated Bouts of Exercise on the Hemostatic System. Physical activity is beneficial for health, for example, by lowering the risk of cardiovascular events. However, vigorous exercise is associated with the occurrence of thromboembolic events and sudden cardiac death, in particular in untrained individuals. Whereas acute exercise is known to cause a hypercoagulable state, repeated exposure to (strenuous) exercise by means of training may actually condition the hemostatic response (...) ) and von Willebrand factor (VWF) increase after exercise, but we found that this increase in FVIII and VWF (antigen, propeptide, and VWF in active conformation) was smaller on each of three subsequent days, suggesting either adaptation of endothelial activation or exhaustion of endothelial VWF supplies. With respect to thrombin generation, elevated FVIII significantly increased the thrombin generation peak but not the endogenous thrombin potential. In contrast, platelet activation in terms of P
Hemostatic Abnormalities in Multiple Myeloma Patients Background: Multiple myeloma (MM) is a neoplastic plasma cell disorder characterized by clonal proliferation of
plasma cells in the bone marrow. Diverse hemostatic abnormalities have been reported in patients with myeloma which
predispose to bleeding and also thrombosis. Methods: Complete blood count, biochemical parameters and parameters
of hemostasis i.e. platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT (...) ), thrombin time
(TT), factor VIII assay results, plasma fibrinogen, D-dimer and lupus anticoagulant, were assessed in 29 MM patients
and 30 age matched controls. Results: The most frequent abnormal screening parameter was APTT. Of the six indicative
of a bleeding tendency i.e. thrombocytopenia, prolonged PT, APTT, TT, reduced plasma fibrinogen and factor VIII, at
least one was abnormal in 8 (27.6%) patients. Of the four prothrombotic markers, lupus anticoagulant, D-dimer, elevated
factor VIII and plasma
with hemophilia B, with residual factor activity of 3 IU/dL or less and without inhibitors. Patients with hemophilia A and B received injected CFCs according to reimbursement guidelines. Fifteen minutes after injection, we assessed hemostatic response with global hemostatic assays: thrombin generation assay (TGA), thromboelastography (TEG), and clot waveform analysis (CWA).Normal healthy men and patients with hemophilia A and B were 36.7, 37.2, and 35.1 years old, respectively. FVIII and recombinant FIX (...) are insufficient to achieve hemostatic responses comparable to those after reimbursed doses for FVIII concentrates in terms of peak thrombin concentration, ETP, and TEG index.
The role of CORM-2 as a modulator of oxidative stress and hemostatic parameters of human plasma in vitro. The main aim of the experiment is to examine the effect of CORM-2, a donor of carbon monoxide (CO), on oxidative stress in human plasma in vitro. In addition, it examines the effects of CORM-2 on the hemostatic parameters of plasma: the activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT).Human plasma was incubated for 5-60 min with different (...) concentrations of CORM-2: 0.1-100 μM. Following this, various hemostatic factors and biomarkers of oxidative stress were studied. Lipid peroxidation was measured as thiobarbituric acid reactive substance (TBARS) concentration, and the oxidation of amino acid residues in proteins was measured by determining the amounts of carbonyl and thiol groups.Two oxidative stress inducers: hydrogen peroxide (H2O2) and the donor of hydroxyl radical (H2O2/Fe) were used. Decrease in protein carbonylation, thiol group
Pleiotropic effects of the hemostatic system. Atherothrombosis is characterized by the inflammatory process of atherosclerosis combined with a hypercoagulable state leading to superimposed thrombus formation. In atherosclerotic plaques, cell signaling can occur via protease-activated receptors (PARs), four of which have been identified so far (PAR1-PAR4). Proteases that are able to activate PARs can be produced systemically, but also at the sites of lesions, and they include thrombin
Hemostatic state augmented with platelet indices among Sudanese diabetic septic foot. Diabetes mellitus is a very rampant metabolic disorder, particularly type II. It has many complications such as the septic foot. Diabetic septic foot (DSF) patients are at high risk for coagulation abnormalities as well as surgical hazards. Owing to the potential sequelae of coagulation and vascular abnormalities, this work aimed at studying the hemostatic state and platelet indices in diabetes type II (...) ) value was significant in diabetic septic foot (32.64 ± 5.2 vs 28.49 ± 4.13, P < 0.000), and thrombin time (TT) did not changed in DSF. Mean platelet volume (MPV), platelet distribution width (PDW), and platelet large cell ratio (P-LCR) values were significantly decreased in DSF compared to control (P < 0.013, 0.034, and 0.020, respectively). PDW values were positively correlated with PT, APTT, and D-Dimer (DD) (r = 0.28/p < 0.003, r = 0.29/p < 0.029, and r = 0.32/p < 0.016, respectively). FVIII
, prothrombin complex concentrate (PCC), and combinations thereof on the hemostatic profile of rivaroxaban-anticoagulated whole blood and plasma. We used rivaroxaban-spiked whole blood and plasma from healthy donors, as well as plasma from patients on rivaroxaban, and mimicked a resuscitation approach in a 50% plasma dilution setting. Thromboelastography, thrombin generation, and fibrin generation clot lysis test were assessed using tissue factor to initiate coagulation and tissue plasminogen activator (...) Hemostatic profile under fluid resuscitation during rivaroxaban anticoagulation: an in vitro survey. Uncontrollable bleeding is the leading cause of death in traumatically injured patients. The extent to which direct factor Xa inhibitors interfere with the applied resuscitation measures is presently unknown.In this study, we investigated the effect of the resuscitation fluids saline, albumin, fresh frozen plasma (FFP) and solvent/detergent (S/D)-treated plasma, fibrinogen concentrate
Platelet packing density is an independent regulator of the hemostatic response to injury. Essentials Platelet packing density in a hemostatic plug limits molecular movement to diffusion. A diffusion-dependent steep thrombin gradient forms radiating outwards from the injury site. Clot retraction affects the steepness of the gradient by increasing platelet packing density. Together, these effects promote hemostatic plug core formation and inhibit unnecessary growth.Background Hemostasis studies (...) performed in vivo have shown that hemostatic plugs formed after penetrating injuries are characterized by a core of highly activated, densely packed platelets near the injury site, covered by a shell of less activated and loosely packed platelets. Thrombin production occurs near the injury site, further activating platelets and starting the process of platelet mass retraction. Tightening of interplatelet gaps may then prevent the escape and exchange of solutes. Objectives To reconstruct the hemostatic
In vitro analysis of growth patterns of invasive fungal species on commonly used endonasal hemostatic agents. Previous studies have not examined the potential role of endonasal hemostatic agents in facilitating growth of fungal species. We aim to determine the possibility of these to serve as a nutrient source for fungal growth.Cultures of Aspergillus, Fusarium, and Mucor were harvested and placed in solution in sterile saline at standardized high and low concentrations. Thrombin gelatin matrix (...) Fusarium growth was noted on all packing material by day three. Carboxyl methylcellulose also supported growth of high-concentration Mucor appreciated on day five. The potato starch derivative supported fulminant growth of all fungal species.Endonasal hemostatic agents may be nutrient sources that facilitate growth of fungal species. This may be a consideration in a surgeon's decision to use a hemostatic agent. Prompt initial post-operative debridement may be warranted in select patients. Our findings
A systematic review on the use of topical hemostats in trauma and emergency surgery. A wide variety of hemostats are available as adjunctive measures to improve hemostasis during surgical procedures if residual bleeding persists despite correct application of conventional methods for hemorrhage control. Some are considered active agents, since they contain fibrinogen and thrombin and actively participate at the end of the coagulation cascade to form a fibrin clot, whereas others to be effective (...) require an intact coagulation system. The aim of this study is to provide an evidence-based approach to correctly select the available agents to help physicians to use the most appropriate hemostat according to the clinical setting, surgical problem and patient's coagulation status.The literature from 2000 to 2016 was systematically screened according to PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses] protocol. Sixty-six articles were reviewed by a panel of experts
Evarrest - human fibrinogen / human thrombin 7 Westferry Circus ? Canary Wharf ? London E14 4HB ? United Kingdom An agency of the European Union Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7523 7455 E-mail email@example.com Website www.ema.europa.eu 27 June 2013 EMA/464286/2013 Committee for Medicinal Products for Human Use (CHMP) Assessment report EVARREST Common name: Human Fibrinogen / Human Thrombin Procedure No. EMEA/H/C/002515 Note Assessment report as adopted by the CHMP with all (...) Haemostasis is an essential and often challenging part of surgical procedures. As first line, surgeons need to apply conventional haemostatic methods i.e. meticulous surgical techniques such as sutures, ligatures, or cautery. Topical haemostatic agents (gelatine, collagen, or oxidized regenerated cellulose) are widely used as an adjunct to these methods. Fibrin sealants consisting of the biological components human fibrinogen and human thrombin directly apply a fibrin layer on the tissue, either
Efficacy of intra-articular injection of thrombin-based hemostatic agent in the control of bleeding after primary total knee arthroplasty. To evaluate the hemostatic effect of intraarticular injection of a thrombin-based hemostatic agent in total knee arthroplasty (TKA).We performed a prospective randomized controlled trial on the use of a thrombin-based hemostatic agent in patients undergoing unilateral TKA. A total of 100 TKA patients were enrolled, with 50 patients randomized into the study (...) and total red blood cell loss (p>0.05).The thrombin-based hemostatic agent demonstrated efficacy in reducing drain output and blood transfusion rates. Thus, we believe the use of a thrombin-based hemostatic agent should be considered as an option in orthopedic surgery that involves massive bleeding.
Prospective, Randomized Trial to Evaluate Efficacy of a Thrombin-Based Hemostatic Agent in Total Knee Arthroplasty. Total knee arthroplasty (TKA) can be associated with substantial blood loss, leading to increased morbidity and transfusion rates. The study objective was to evaluate routine use of a thrombin-based topical hemostatic matrix in reducing blood loss and transfusion requirements in primary TKA. 108 patients were enrolled in a prospective, randomized, single-center trial. Patients (...) receiving the hemostatic agent demonstrated a lower mean calculated blood loss (1325.2±464.8mL vs. control, 1509.3±432.8mL; P=0.02), drain output (415.6±202.0mL vs. control, 579.9±306.7mL; P=0.008), and length of stay (3.3±0.8days vs. control, 3.7±1.1days; P=0.03), without a statistically significant difference in mean hemoglobin loss or transfusion requirements. The clinical utility of this hemostatic agent to reduce transfusions after uncomplicated, primary TKA continues to remain unclear.Published
The efficacy of a thrombin-based hemostatic agent in primary total knee arthroplasty: a meta-analysis. Total knee arthroplasty (TKA) is a popular procedure in severe osteoarthritis. But perioperative bleeding remains a problem. Floseal® is a mixture of thrombin and bovine gelatin which can benefit a lot on reducing intraoperative and postoperative bleeding. However, there is no enough evidence judging its safety and efficiency. So a meta-analysis is conducted by us to evaluate the efficacy (...) and safety of a thrombin-based hemostatic agent compared with conventional methods in TKA.Two independent reviewers selected literatures published before August 2014 from MEDLINE, Embase, and The Cochrane Central Register of Controlled Trials. Other internet databases were also performed to identify trials according to the Cochrane Collaboration guidelines. High-quality randomized controlled trials (RCTs), prospective control trials (PCTs), and case controlled trials (CCTs) were selected. The meta
Effectiveness of Thrombin-Collagen and Autologous Platelet-Rich Plasma in Total Hip Arthroplasty Hemostasis: A Prospective, Randomized, Controlled Trial. Bovine derived thrombin-collagen combined with autologous platelet-rich plasma (PRP) has shown promise as a topical, surgical hemostatic agent. The purpose of this study was to determine the effect of thrombin-collagen-PRP on perioperative blood loss in total hip arthroplasty (THA). A prospective, single-blinded, randomized, controlled study (...) evidence to support the routine use of a topical thrombin-collagen-autologous PRP hemostatic agent in primary total hip arthroplasty. (Journal of Surgical Orthopaedic Advances 27(2):136-141, 2018).