Tissue Factor Coagulant Activity is Regulated by the Plasma Membrane Microenvironment.

PubMed

Yu, Yuanjie; Böing, Anita N; Hau, Chi M; Hajji, Najat; Ruf, Wolfram; Sturk, Auguste; Nieuwland, Rienk

2018-06-01

 Tissue factor (TF) can be present in a non-coagulant and coagulant form. Whether the coagulant activity is affected by the plasma membrane microenvironment is unexplored.  This article studies the presence and coagulant activity of human TF in plasma membrane micro-domains.  Plasma membranes were isolated from human MIA PaCa2 cells, MDA-MB-231 cells and human vascular smooth muscle cells by Percoll gradient ultracentrifugation after cell disruption. Plasma membranes were fractionated by OptiPrep gradient ultracentrifugation, and the presence of TF, flotillin, caveolin, clathrin, protein disulphide isomerase (PDI), TF pathway inhibitor (TFPI) and phosphatidylserine (PS) were determined.  Plasma membranes contain two detergent-resistant membrane (DRM) compartments differing in density and biochemical composition. High-density DRMs (DRM-H) have a density ( ρ ) of 1.15 to 1.20 g/mL and contain clathrin, whereas low-density DRMs (DRM-L) have a density between 1.09 and 1.13 g/mL and do not contain clathrin. Both DRMs contain TF, flotillin and caveolin. PDI is detectable in DRM-H, TFPI is not detectable in either DMR-H or DRM-L and PS is detectable in DRM-L. The DRM-H-associated TF (> 95% of the TF antigen) lacks detectable coagulant activity, whereas the DRM-L-associated TF triggers coagulation. This coagulant activity is inhibited by lactadherin and thus PS-dependent, but seemed insensitive to 16F16, an inhibitor of PDI.  Non-coagulant and coagulant TF are present within different types of DRMs in the plasma membrane, and the composition of these DRMs may affect the TF coagulant activity. Schattauer GmbH Stuttgart.

Purification and Autoactivation Method for Recombinant Coagulation Factor VII.

PubMed

Granovski, Vladimir; Freitas, Marcela C C; Abreu-Neto, Mario Soares; Covas, Dimas T

2018-01-01

Recombinant coagulation factor VII is a very important and complex protein employed for treatment of hemophiliac patients (hemophilia A/B) who develop inhibitors antibodies to conventional treatments (FVIII and FIX). The rFVII is a glycosylated molecule and circulates in plasma as zymogen of 50 kDa. When activated the molecule is cleaved to 20-30 kDa and has a half-life of about 3 h, needing to be processed fast and efficiently until freeze-drying. Here, we describe a very simple and fast purification sequence for rFVII using affinity FVII Select resin and a dialysis system that can be easily scaled up.

Effects on coagulation factor production following primary hepatomitogen-induced direct hyperplasia.

PubMed

Tatsumi, Kohei; Ohashi, Kazuo; Taminishi, Sanae; Takagi, Soichi; Utoh, Rie; Yoshioka, Akira; Shima, Midori; Okano, Teruo

2009-11-14

To investigate the molecular mechanisms involved in coagulation factor expression and/or function during direct hyperplasia (DH)-mediated liver regeneration. Direct hyperplasia-mediated liver regeneration was induced in female C57BL/6 mice by administering 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), a representative hepatomitogen. Mice were weighed and sacrificed at various time points [Day 0 (D0: prior to injection), 3 h, D1, D2, D3, and D10] after TCPOBOP administration to obtain liver and blood samples. Using the RNA samples extracted from the liver, a comprehensive analysis was performed on the hepatic gene expression profiling of coagulation-related factors by real-time RT-PCR (fibrinogen, prothrombin, factors V, VII, VIII, IX, X, XI, XII, XIIIbeta, plasminogen, antithrombin, protein C, protein S, ADAMTS13, and VWF). The corresponding plasma levels of coagulation factors (fibrinogen, prothrombin, factors V, VII, VIII, IX, X, XI, XII, XIII, and VWF) were also analyzed and compared with their mRNA levels. Gavage administration of TCPOBOP (3 mg/kg body weight) resulted in a marked and gradual increase in the weight of the mouse livers relative to the total body weight to 220% by D10 relative to the D0 (control) ratios. At the peak of liver regeneration (D1 and D2), the gene expression levels for most of the coagulation-related factors (fibrinogen, prothrombin, factors V, VII, VIII, IX, XI, XII, XIIIbeta, plasminogen, antithrombin, protein C, ADAMTS13, VWF) were found to be down-regulated in a time-dependent manner, and gradually recovered by D10 to the basal levels. Only mRNA levels of factor X and protein S failed to show any decrease during the regenerative phase. As for the plasma levels, 5 clotting factors (prothrombin, factors VIII, IX, XI, and XII) demonstrated a significant decrease (P<0.05) during the regeneration phase compared with D0. Among these 5 factors, factor IX and factor XI showed the most dramatic decline in their activities by about

Biological and analytical variations of 16 parameters related to coagulation screening tests and the activity of coagulation factors.

PubMed

Chen, Qian; Shou, Weiling; Wu, Wei; Guo, Ye; Zhang, Yujuan; Huang, Chunmei; Cui, Wei

2015-04-01

To accurately estimate longitudinal changes in individuals, it is important to take into consideration the biological variability of the measurement. The few studies available on the biological variations of coagulation parameters are mostly outdated. We confirmed the published results using modern, fully automated methods. Furthermore, we added data for additional coagulation parameters. At 8:00 am, 12:00 pm, and 4:00 pm on days 1, 3, and 5, venous blood was collected from 31 healthy volunteers. A total of 16 parameters related to coagulation screening tests as well as the activity of coagulation factors were analyzed; these included prothrombin time, fibrinogen (Fbg), activated partial thromboplastin time, thrombin time, international normalized ratio, prothrombin time activity, activated partial thromboplastin time ratio, fibrin(-ogen) degradation products, as well as the activity of factor II, factor V, factor VII, factor VIII, factor IX, and factor X. All intraindividual coefficients of variation (CVI) values for the parameters of the screening tests (except Fbg) were less than 5%. Conversely, the CVI values for the activity of coagulation factors were all greater than 5%. In addition, we calculated the reference change value to determine whether a significant difference exists between two test results from the same individual. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Coagulation management in trauma-associated coagulopathy: allogenic blood products versus coagulation factor concentrates in trauma care.

PubMed

Klages, Matthias; Zacharowski, Kai; Weber, Christian Friedrich

2016-04-01

Coagulation management by transfusion of allogenic blood products and coagulation factors are competing concepts in current trauma care. Rapid and adequate therapy of trauma-associated coagulopathy is crucial to survival of severely injured patients. Standard coagulation tests such as prothrombin time and activated partial thromboplastin time are commonly used, but these tests are inappropriate for monitoring and guiding therapy in trauma patients. Coagulation factor-based treatment showed promising results, but randomized trials have not yet been performed. In addition, viscoelastic tests are needed to guide therapy, although there is in fact limited evidence for these in tests in trauma care. Regarding transfusion therapy with allogenic blood products, plasma transfusion has been associated with improved survival in trauma patients following massive transfusion. In contrast, patients not requiring massive transfusion seem to be at risk for suffering complications with increasing volumes of plasma transfused. The collective of trauma patients is heterogeneous. Despite the lack of evidence, there are strong arguments for individualized patient treatment with coagulation factors for some indications and to abstain from the use of fresh frozen plasma. In patients with severe trauma and major bleeding, plasma, platelets, and red blood cells should be considered to be administered at a ratio of 1 : 1 : 1.

Genetic Factors Influencing Coagulation Factor XIII B-Subunit Contribute to Risk of Ischemic Stroke.

PubMed

Hanscombe, Ken B; Traylor, Matthew; Hysi, Pirro G; Bevan, Stephen; Dichgans, Martin; Rothwell, Peter M; Worrall, Bradford B; Seshadri, Sudha; Sudlow, Cathie; Williams, Frances M K; Markus, Hugh S; Lewis, Cathryn M

2015-08-01

Abnormal coagulation has been implicated in the pathogenesis of ischemic stroke, but how this association is mediated and whether it differs between ischemic stroke subtypes is unknown. We determined the shared genetic risk between 14 coagulation factors and ischemic stroke and its subtypes. Using genome-wide association study results for 14 coagulation factors from the population-based TwinsUK sample (N≈2000 for each factor), meta-analysis results from the METASTROKE consortium ischemic stroke genome-wide association study (12 389 cases, 62 004 controls), and genotype data for 9520 individuals from the WTCCC2 ischemic stroke study (3548 cases, 5972 controls-the largest METASTROKE subsample), we explored shared genetic risk for coagulation and stroke. We performed three analyses: (1) a test for excess concordance (or discordance) in single nucleotide polymorphism effect direction across coagulation and stroke, (2) an estimation of the joint effect of multiple coagulation-associated single nucleotide polymorphisms in stroke, and (3) an evaluation of common genetic risk between coagulation and stroke. One coagulation factor, factor XIII subunit B (FXIIIB), showed consistent effects in the concordance analysis, the estimation of polygenic risk, and the validation with genotype data, with associations specific to the cardioembolic stroke subtype. Effect directions for FXIIIB-associated single nucleotide polymorphisms were significantly discordant with cardioembolic disease (smallest P=5.7×10(-04)); the joint effect of FXIIIB-associated single nucleotide polymorphisms was significantly predictive of ischemic stroke (smallest P=1.8×10(-04)) and the cardioembolic subtype (smallest P=1.7×10(-04)). We found substantial negative genetic covariation between FXIIIB and ischemic stroke (rG=-0.71, P=0.01) and the cardioembolic subtype (rG=-0.80, P=0.03). Genetic markers associated with low FXIIIB levels increase risk of ischemic stroke cardioembolic subtype. © 2015 The

Neuro-Coagulopathy: Blood Coagulation Factors in Central Nervous System Diseases.

PubMed

De Luca, Ciro; Virtuoso, Assunta; Maggio, Nicola; Papa, Michele

2017-10-12

Blood coagulation factors and other proteins, with modulatory effects or modulated by the coagulation cascade have been reported to affect the pathophysiology of the central nervous system (CNS). The protease-activated receptors (PARs) pathway can be considered the central hub of this regulatory network, mainly through thrombin or activated protein C (aPC). These proteins, in fact, showed peculiar properties, being able to interfere with synaptic homeostasis other than coagulation itself. These specific functions modulate neuronal networks, acting both on resident (neurons, astrocytes, and microglia) as well as circulating immune system cells and the extracellular matrix. The pleiotropy of these effects is produced through different receptors, expressed in various cell types, in a dose- and time-dependent pattern. We reviewed how these pathways may be involved in neurodegenerative diseases (amyotrophic lateral sclerosis, Alzheimer's and Parkinson's diseases), multiple sclerosis, ischemic stroke and post-ischemic epilepsy, CNS cancer, addiction, and mental health. These data open up a new path for the potential therapeutic use of the agonist/antagonist of these proteins in the management of several central nervous system diseases.

Imaging analyses of coagulation-dependent initiation of fibrinolysis on activated platelets and its modification by thrombin-activatable fibrinolysis inhibitor.

PubMed

Brzoska, Tomasz; Suzuki, Yuko; Sano, Hideto; Suzuki, Seiichirou; Tomczyk, Martyna; Tanaka, Hiroki; Urano, Tetsumei

2017-04-03

Using intravital confocal microscopy, we observed previously that the process of platelet phosphatidylserine (PS) exposure, fibrin formation and lysine binding site-dependent plasminogen (plg) accumulation took place only in the centre of thrombi, not at their periphery. These findings prompted us to analyse the spatiotemporal regulatory mechanisms underlying coagulation and fibrinolysis. We analysed the fibrin network formation and the subsequent lysis in an in vitro experiment using diluted platelet-rich plasma supplemented with fluorescently labelled coagulation and fibrinolytic factors, using confocal laser scanning microscopy. The structure of the fibrin network formed by supplemented tissue factor was uneven and denser at the sites of coagulation initiation regions (CIRs) on PS-exposed platelets. When tissue-type plasminogen activator (tPA; 7.5 nM) was supplemented, labelled plg (50 nM) as well as tPA accumulated at CIRs, from where fibrinolysis started and gradually expanded to the peripheries. The lysis time at CIRs and their peripheries (50 µm from the CIR) were 27.9 ± 6.6 and 44.4 ± 9.7 minutes (mean ± SD, n=50 from five independent experiments) after the addition of tissue factor, respectively. Recombinant human soluble thrombomodulin (TMα; 2.0 nM) attenuated the CIR-dependent plg accumulation and strongly delayed fibrinolysis at CIRs. A carboxypeptidase inhibitor dose-dependently enhanced the CIR-dependent fibrinolysis initiation, and at 20 µM it completely abrogated the TMα-induced delay of fibrinolysis. Our findings are the first to directly present crosstalk between coagulation and fibrinolysis, which takes place on activated platelets' surface and is further controlled by thrombin-activatable fibrinolysis inhibitor (TAFI).

Differential roles of tissue factor and phosphatidylserine in activation of coagulation.

PubMed

Spronk, Henri M H; ten Cate, Hugo; van der Meijden, Paola E J

2014-05-01

It has been suggested that the main physiological trigger of coagulation, tissue factor, possesses limited procoagulant activity and occurs in an inactive or so-called encrypted state. For the conversion of encrypted into decrypted tissue factor with sufficient procoagulant activity, four distinct models have been proposed: 1; dimer formation, 2; lipid rafts, 3; disulfide bonds, and 4; phosphatidylserine exposure. Pro and cons can be given for each of these mechanisms of tissue factor encryption/decryption, however, it seems most likely that two or more mechanisms act together in activating the procoagulant activity. The exposure of phosphatidylserine in the outer layer of cell membranes supports coagulation through enhanced formation of the tenase (factors IXa, VIIIa and X) and prothrombinase (factors Xa, Va and prothrombin) complexes. The proposed role for phosphatidylserine in decryption of tissue factor could contribute to the correct orientation of the tissue factor - factor VII complex. Overall, the contribution of both tissue factor and phosphatidylserine to coagulation seems distinct with tissue factor being the physiological activator and phosphatidylserine the driving force of propagation of coagulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Comparison of thromboelastography and routine coagulation tests for evaluation of blood coagulation function in patients].

PubMed

Chen, Guan-Yi; Ou Yang, Xi-Lin; Wu, Jing-Hui; Wang, Li-Hua; Yang, Jin-Hua; Gu, Li-Nan; Lu, Zhu-Jie; Zhao, Xiao-Zi

2015-04-01

To investigate the correlation and consistency between thromboelastography(TEG) and routine coagulation tests, and to evaluate the value of the two methods in determining the blood coagulation of patients. The TEG, routine coagulation tests and platelet counts of 182 patients from the Intensive Care Unit(ICU) and Department of Gastroenterology in our hospital from January to September 2014 were performed and analyzed retrospectively for their correlation, Kappa identity test analysis and chi-square test, and the diagnostic sensitivity and specificity of both methods in the patients with bleeding were evaluated. The TEG R time and PT, R time and APTT showed a linear dependence (P<0.01). The relationship between the TEG K value, α-Angle, MA and Fibrinogen showed a linear dependence (P<0.001). And the relationship between the TEG K value, α-Angle, MA and the platelet count were in a linear dependent way (P<0.001). The Kappa values of the TEG R time with PT and APTT were 0.038 (P>0.05) and 0.061 (P>0.05), respectively. The chi-square test values of the TEG R time with PT and APTT were 35.309 (P<0.001) and 15.848 (P<0.001), respectively. The Fibrinogen and the TEG K value, α-Angle, MA value had statistical significance (P<0.001), with a Kappa value of 0.323, 0.288 and 0.427, respectively. The chi-square test values between Fibrinogen and the TEG K value, α-Angle, MA value were not statistically significant, with X2=1.091 (P=0.296), X2=1.361 (P=0.243), X2=0.108 (P=0.742). The Kappa values of the platelet count and the TEG K value, α-Angle, MA value were 0.379, 0.208 and 0.352, respectively, which were also statistically significant difference (P<0.001). The chi-square test values between the platelet count and the TEG K value, α-Angle, MA value showed a statistically significant difference (P<0.001), with X2=37.5, X2=37.23, X2=26.630. The diagnostic sensitivity of the two methods for the patients with bleeding was less than 50%. There was a significant correlation

Different Recovery Profiles of Coagulation Factors, Thrombin Generation, and Coagulation Function After Hemorrhagic Shock in Pigs

DTIC Science & Technology

2012-06-06

Different recovery profiles of coagulation factors, thrombin generation, and coagulation function after hemorrhagic shock in pigs Wenjun Z. Martini ...Defense. Address for reprints: Wenjun Z. Martini , PhD, The US Army Institute of Surgical Research, 3698 Chambers Pass, Ft. Sam Houston, San Antonio, TX...control number 1. REPORT DATE 01 SEP 2015 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Different recovery profiles of

Sepsis-Induced Coagulation in the Baboon Lung Is Associated with Decreased Tissue Factor Pathway Inhibitor

PubMed Central

Tang, Haiwang; Ivanciu, Lacramioara; Popescu, Narcis; Peer, Glenn; Hack, Erik; Lupu, Cristina; Taylor, Fletcher B.; Lupu, Florea

2007-01-01

Increased tissue factor (TF)-dependent procoagulant activity in sepsis may be partly due to decreased expression or function of tissue factor pathway inhibitor (TFPI). To test this hypothesis, baboons were infused with live Escherichia coli and sacrificed after 2, 8, or 24 hours. Confocal and electron microscopy revealed increased leukocyte infiltration and fibrin deposition in the intravascular and interstitial compartments. Large amounts of TF were detected by immunostaining in leukocytes and platelet-rich microthrombi. TF induction was documented by quantitative reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and coagulation assays. Lung-associated TFPI antigen and mRNA decreased during sepsis, and TFPI activity diminished abruptly at 2 hours. Blocking antibodies against TFPI increased fibrin deposition in septic baboon lungs, suggesting that TF-dependent coagulation might be aggravated by reduced endothelial TFPI. Decreased TFPI activity coincided with the release of tissue plasminogen activator and the peak of plasmin generation, suggesting that TFPI could undergo proteolytic inactivation by plasmin. Enhanced plasmin produced in septic baboons by infusion of blocking antibodies against plasminogen activator inhibitor-1 led to decreased lung-associated TFPI and unforeseen massive fibrin deposition. We conclude that activation of TF-driven coagulation not adequately countered by TFPI may underlie the widespread thrombotic complications of sepsis. PMID:17640967

Reduced plasma levels of coagulation factors in relation to prostate cancer.

PubMed

Beecken, Wolf-Dietrich; Bentas, Wassilios; Engels, Knut; Glienke, Wolfgang; Urbschat, Anja; Jonas, Dietger; Binder, Jochen; Scharrer, Inge

2002-10-01

Prostate cancer has historically been associated with coagulation abnormalities. This study was undertaken to investigate the prevalence of abnormalities of coagulation factors in patients with prostate cancer before and after radical prostatectomy (RP). Because coagulation factors have been shown to be involved in tumor angiogenesis, the vascular density of the prostate tumors was assessed. Plasma of 40 consecutive patients with histologically proven prostate cancer was investigated pre-RP and post-RP. The antigen level for antithrombin, plasminogen activator inhibitor-1, and heparin cofactor-II, and the plasma activity of antithrombin and plasminogen were determined by using immunologic and chromogenic assays. The values of these assays were compared with a group of 28 male, age-matched patients without any evidence of cancer and 18 patients with orthopedic interventions preoperatively and postoperatively. The vascular density of the prostate tumors was assessed by staining paraffin sections with an antibody to CD34. The median plasma antigen levels and/or activities of the investigated factors were below normal in the prostate cancer patients before RP. Furthermore, coagulation factors were significantly lower than in the age-matched control group and patients before and after orthopedic surgery. In prostate cancer patients, the median values of all investigated factors went up to normal levels within 2 weeks after RP, whereas postsurgical levels in orthopedic patients remained stable. No correlations to tumor parameters have been observed. We assume that the reduction of these coagulation factors is a principle concept in prostate cancer that needs further investigation. Copyright 2002 Wiley-Liss, Inc.

Congenital combined deficiency of coagulation factors: a study of seven patients.

PubMed

Naderi, Majid; Tabibian, Shadi; Hosseini, Maryam Sadat; Alizadeh, Shaban; Hosseini, Soudabeh; Shamsizadeh, Morteza; Dorgalaleh, Akbar

2015-01-01

Combined deficiency of coagulation factors is considered as an extremely rare bleeding disorder (RBD) inherited in an autosomal recessive pattern. This disorder is more likely to occur in regions with a high rate of consanguineous marriages or in restricted communities. Sistan and Baluchistan, a province in southeast of Iran with a high rate of consanguinity, is a clear model of such regions with a very high prevalence of recessively inherited disorders. The aim of this study was to report the frequency of combined factor deficiency in this province. This descriptive study was conducted on 358 patients with RBD. Demographic information and medical history of each patient were recorded, and the patients were examined by a physician. Routine screening tests were carried out for all patients, and further coagulation tests including coagulation factor activity and antigen assays were subsequently performed for all suspected patients. Among 358 patients, four were found to be affected with combined factor (F)V and FVIII deficiency (F5F8D). In addition, one patient with combined deficiency of FVII-FXIII, one with combined FVII-FX and one with combined FVIII-FIX deficiency were identified. In Sistan and Baluchistan Province, coinheritance of recessively inherited disorders like combined coagulation factor deficiencies was surprisingly higher than expected.

Positive Feedback Loops for Factor V and Factor VII Activation Supply Sensitivity to Local Surface Tissue Factor Density During Blood Coagulation

PubMed Central

Balandina, A.N.; Shibeko, A.M.; Kireev, D.A.; Novikova, A.A.; Shmirev, I.I.; Panteleev, M.A.; Ataullakhanov, F.I.

2011-01-01

Blood coagulation is triggered not only by surface tissue factor (TF) density but also by surface TF distribution. We investigated recognition of surface TF distribution patterns during blood coagulation and identified the underlying molecular mechanisms. For these investigations, we employed 1), an in vitro reaction-diffusion experimental model of coagulation; and 2), numerical simulations using a mathematical model of coagulation in a three-dimensional space. When TF was uniformly immobilized over the activating surface, the clotting initiation time in normal plasma increased from 4 min to >120 min, with a decrease in TF density from 100 to 0.7 pmol/m2. In contrast, surface-immobilized fibroblasts initiated clotting within 3–7 min, independently of fibroblast quantity and despite a change in average surface TF density from 0.5 to 130 pmol/m2. Experiments using factor V-, VII-, and VIII-deficient plasma and computer simulations demonstrated that different responses to these two TF distributions are caused by two positive feedback loops in the blood coagulation network: activation of the TF–VII complex by factor Xa, and activation of factor V by thrombin. This finding suggests a new role for these reactions: to supply sensitivity to local TF density during blood coagulation. PMID:22004734

Increased production of functional recombinant human clotting factor IX by baby hamster kidney cells engineered to overexpress VKORC1, the vitamin K 2,3-epoxide-reducing enzyme of the vitamin K cycle.

PubMed

Wajih, Nadeem; Hutson, Susan M; Owen, John; Wallin, Reidar

2005-09-09

Some recombinant vitamin K-dependent blood coagulation factors (factors VII, IX, and protein C) have become valuable pharmaceuticals in the treatment of bleeding complications and sepsis. Because of their vitamin K-dependent post-translational modification, their synthesis by eukaryotic cells is essential. The eukaryotic cell harbors a vitamin K-dependent gamma-carboxylation system that converts the proteins to gamma-carboxyglutamic acid-containing proteins. However, the system in eukaryotic cells has limited capacity, and cell lines overexpressing vitamin K-dependent clotting factors produce only a fraction of the recombinant proteins as fully gamma-carboxylated, physiologically competent proteins. In this work we have used recombinant human factor IX (r-hFIX)-producing baby hamster kidney (BHK) cells, engineered to stably overexpress various components of the gamma-carboxylation system of the cell, to determine whether increased production of functional r-hFIX can be accomplished. All BHK cell lines secreted r-hFIX into serum-free medium. Overexpression of gamma-carboxylase is shown to inhibit production of functional r-hFIX. On the other hand, cells overexpressing VKORC1, the reduced vitamin K cofactor-producing enzyme of the vitamin K-dependent gamma-carboxylation system, produced 2.9-fold more functional r-hFIX than control BHK cells. The data are consistent with the notion that VKORC1 is the rate-limiting step in the system and is a key regulatory protein in synthesis of active vitamin K-dependent proteins. The data suggest that overexpression of VKORC1 can be utilized for increased cellular production of recombinant vitamin K-dependent proteins.

Influence of blood lipids on global coagulation test results.

PubMed

Kim, Jung-Ah; Kim, Ji-Eun; Song, Sang Hoon; Kim, Hyun Kyung

2015-01-01

High levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). PT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absence-II (PIVKA-II). The procoagulant factors II, VII, IX, X, and XI and anticoagulant factors protein C and protein S showed significant correlations with triglyceride, and the procoagulant factors II, V, VII, IX, X, XI, and XII and anticoagulant factors antithrombin and protein C correlated with total cholesterol. There were no correlations of blood lipid levels with PIVKA-II levels. Subjects with high triglyceride levels (≥200 mg/dL) showed shorter PT values than those with lower triglyceride levels. However, aPTT value was not changed in terms of blood lipid levels. In both 1 and 5 pM tissue factor-induced TGAs, subjects in the high-triglyceride or high-cholesterol groups (≥240 mg/dL) had high levels of lag time, time-to-peak, and endogenous thrombin potential. Total cholesterol was a significant determinant of PT and TGA values. High blood lipids were related with increased coagulation activity in a normal population. Our findings are expected to help interpret the global coagulation test results in individuals with high lipid levels.

Platelet Surface-Associated Activation and Secretion-Mediated Inhibition of Coagulation Factor XII

PubMed Central

Zakharova, Natalia V.; Artemenko, Elena O.; Podoplelova, Nadezhda A.; Sveshnikova, Anastasia N.; Demina, Irina A.; Ataullakhanov, Fazly I.; Panteleev, Mikhail A.

2015-01-01

Coagulation factor XII (fXII) is important for arterial thrombosis, but its physiological activation mechanisms are unclear. In this study, we elucidated the role of platelets and platelet-derived material in fXII activation. FXII activation was only observed upon potent platelet stimulation (with thrombin, collagen-related peptide, or calcium ionophore, but not ADP) accompanied by phosphatidylserine exposure and was localised to the platelet surface. Platelets from three patients with grey platelet syndrome did not activate fXII, which suggests that platelet-associated fXII-activating material might be released from α-granules. FXII was preferentially bound by phosphotidylserine-positive platelets and annexin V abrogated platelet-dependent fXII activation; however, artificial phosphotidylserine/phosphatidylcholine microvesicles did not support fXII activation under the conditions herein. Confocal microscopy using DAPI as a poly-phosphate marker did not reveal poly-phosphates associated with an activated platelet surface. Experimental data for fXII activation indicates an auto-inhibition mechanism (k i/k a = 180 molecules/platelet). Unlike surface-associated fXII activation, platelet secretion inhibited activated fXII (fXIIa), particularly due to a released C1-inhibitor. Platelet surface-associated fXIIa formation triggered contact pathway-dependent clotting in recalcified plasma. Computer modelling suggests that fXIIa inactivation was greatly decreased in thrombi under high blood flow due to inhibitor washout. Combined, the surface-associated fXII activation and its inhibition in solution herein may be regarded as a flow-sensitive regulator that can shift the balance between surface-associated clotting and plasma-dependent inhibition, which may explain the role of fXII at high shear and why fXII is important for thrombosis but negligible in haemostasis. PMID:25688860

Effect of platelet-derived β-thromboglobulins on coagulation.

PubMed

Egan, Karl; van Geffen, Johanna P; Ma, Hui; Kevane, Barry; Lennon, Aine; Allen, Seamus; Neary, Elaine; Parsons, Martin; Maguire, Patricia; Wynne, Kieran; O' Kennedy, Richard; Heemskerk, Johan W M; Áinle, Fionnuala Ní

2017-06-01

β-thromboglobulins are derived from the cleavage of the CXC chemokine platelet basic protein and are released in high concentrations by activated platelets. Platelet-derived β-thromboglobulins (βTG) share 70% homology with platelet factor 4 (PF4), another CXC chemokine released by activated platelets. PF4 modulates coagulation by inhibiting heparin-antithrombin interactions, promoting protein C activation, and attenuating the activity of activated protein C. In contrast, the effect of βTG on coagulation is unknown. Clotting times, thrombin generation, chromogenic clotting factor assays, and surface plasmon resonance (SPR) were used to assess the effect of purified βTG on coagulation. In normal pooled plasma, βTG shortened the lagtime and time to peak thrombin generation of tissue factor (TF)-dependent and TF-independent thrombin generation. In factor VIII and factor IX-deficient plasmas, βTG induced thrombin generation in the absence of a TF stimulus and in the presence of anti-TF and factor VIIa inhibitory antibodies. The procoagulant effect was not observed when thrombin generation was independent of factor X activation (supplementation of factor X-deficient plasma with factor Xa). Cleavage of a factor Xa-specific chromogenic substrate was observed when βTG was incubated with factor X, suggesting a direct interaction between βTG and factor X. Using SPR, βTG were found to bind to immobilised factor X in a dose dependent manner. βTG modulate coagulation in vitro via an interaction with factor X. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of Hemodilution on Coagulation and Recombinant Factor VIIa Efficacy in Human Blood In Vitro

DTIC Science & Technology

2011-11-01

thrombasthenia.12 In trauma, when a blood vessel is injured, tissue factor on subendothelial pericytes is exposed and binds to endogenous FVII ...a more complex effect on coagulation than simply dilution of any single coagulation factor like FVII or fibrinogen (Fig. 1). It is interesting to note...ORIGINAL ARTICLE Effect of Hemodilution on Coagulation and Recombinant Factor VIIa Efficacy in Human Blood In Vitro Daniel N. Darlington, PhD, Angel

Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells

PubMed Central

Göbel, Kerstin; Pankratz, Susann; Asaridou, Chloi-Magdalini; Herrmann, Alexander M.; Bittner, Stefan; Merker, Monika; Ruck, Tobias; Glumm, Sarah; Langhauser, Friederike; Kraft, Peter; Krug, Thorsten F.; Breuer, Johanna; Herold, Martin; Gross, Catharina C.; Beckmann, Denise; Korb-Pap, Adelheid; Schuhmann, Michael K.; Kuerten, Stefanie; Mitroulis, Ioannis; Ruppert, Clemens; Nolte, Marc W.; Panousis, Con; Klotz, Luisa; Kehrel, Beate; Korn, Thomas; Langer, Harald F.; Pap, Thomas; Nieswandt, Bernhard; Wiendl, Heinz; Chavakis, Triantafyllos; Kleinschnitz, Christoph; Meuth, Sven G.

2016-01-01

Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein–kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells. Immune activation by FXII is mediated by dendritic cells in a CD87-dependent manner and involves alterations in intracellular cyclic AMP formation. Our study demonstrates that a member of the plasmatic coagulation cascade is a key mediator of autoimmunity. FXII inhibition may provide a strategy to combat MS and other immune-related disorders. PMID:27188843

Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells.

PubMed

Yokota, N; Koizume, S; Miyagi, E; Hirahara, F; Nakamura, Y; Kikuchi, K; Ruf, W; Sakuma, Y; Tsuchiya, E; Miyagi, Y

2009-12-15

Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian cancer cells express fVII transcripts under normoxia and that this transcription is inducible under hypoxia. These findings led us to hypothesise that ovarian cancer cells are intrinsically associated with TF-fVIIa coagulation activity, which could result in thrombosis. In this study, we examined whether ectopically expressed fVII could cause thrombosis by means of immunohistochemistry, RT-PCR, western blotting and flow cytometry. Ectopic fVII expression occurs frequently in ovarian cancers, particularly in clear cell carcinoma. We further showed that ovarian cancer cells express TF-fVIIa on the cell surface under normoxia and that this procoagulant activity is enhanced by hypoxic stimuli. Moreover, we showed that ovarian cancer cells secrete microparticles (MPs) with TF-fVIIa activity. Production of this procoagulant secretion is enhanced under hypoxia. These results raise the possibility that cancer cell-derived TF-fVIIa could cause thrombotic events in ovarian cancer patients.

Influence of Blood Lipids on Global Coagulation Test Results

PubMed Central

Kim, Jung-Ah; Kim, Ji-Eun; Song, Sang Hoon

2015-01-01

Background High levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). Methods PT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absence-II (PIVKA-II). Results The procoagulant factors II, VII, IX, X, and XI and anticoagulant factors protein C and protein S showed significant correlations with triglyceride, and the procoagulant factors II, V, VII, IX, X, XI, and XII and anticoagulant factors antithrombin and protein C correlated with total cholesterol. There were no correlations of blood lipid levels with PIVKA-II levels. Subjects with high triglyceride levels (≥200 mg/dL) showed shorter PT values than those with lower triglyceride levels. However, aPTT value was not changed in terms of blood lipid levels. In both 1 and 5 pM tissue factor-induced TGAs, subjects in the high-triglyceride or high-cholesterol groups (≥240 mg/dL) had high levels of lag time, time-to-peak, and endogenous thrombin potential. Total cholesterol was a significant determinant of PT and TGA values. Conclusion High blood lipids were related with increased coagulation activity in a normal population. Our findings are expected to help interpret the global coagulation test results in individuals with high lipid levels. PMID:25553275

Upregulation of the coagulation factor VII gene during glucose deprivation is mediated by activating transcription factor 4.

PubMed

Cronin, Katherine R; Mangan, Thomas P; Carew, Josephine A

2012-01-01

Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/- SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/-15% to 188+/-27% and 100+/-8.8% to 176.3+/-17.3% respectively, p<0.001) at 24 hr of treatment. The integrated stress response was induced, as indicated by upregulation of transcription factor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress.

Simultaneous expression of tissue factor and tissue factor pathway inhibitor by human monocytes. A potential mechanism for localized control of blood coagulation

PubMed Central

1994-01-01

Cells of monocytic lineage can initiate extravascular fibrin deposition via expression of blood coagulation mediators. This report is about experiments on three mechanisms with the potential to modulate monocyte- initiated coagulation. Monocyte procoagulant activity was examined as a function of lipid cofactor, protein cofactor, and specific inhibitor expression during short-term culture in vitro. Lipid cofactor activity was measured as the initial rate of factor X activation by intrinsic- pathway components, the assembly of which depends on this cofactor. Lipid cofactor activity levels changed by < 30% during 48-h culture. Protein cofactor, i.e., tissue factor (TF) antigen was measured by enzyme immunoassay. It increased from 461 pg/ml to a maximum value of 3,550 pg/ml at 24 h and remained at 70% of this value. Specific TF activity, measured as factor VII-dependent factor X activation rate, decreased from 54 to 18 nM FXa/min between 24 and 48 h. TF activity did not correlate well with either lipid cofactor or TF protein levels. In contrast, the decrease in TF activity coincided in time with maximal expression of tissue factor pathway inhibitor (TFPI) mRNA, which was determined using reverse transcriptase polymerase chain reaction (RT- PCR), and with maximal TFPI protein levels measured by immunoassay. The number of mRNA copies coding for TFPI and TF in freshly isolated blood monocytes were 46 and 20 copies/cells, respectively. These values increased to 220 and 63 copies/cell during short-term cell culture in the presence of endotoxin. Results demonstrate concomitant expression by monocytes of genes coding for both the essential protein cofactor and the specific inhibitor of the extrinsic coagulation pathway. Together with functional and antigenic analyses, they also imply that the initiation of blood clotting by extravascular monocyte/macrophages can be modulated locally by TFPI independently of plasma sources of the inhibitor. PMID:8195712

Autotransfusion from experimental hemothorax: levels of coagulation factors.

PubMed

Napoli, V M; Symbas, P J; Vroon, D H; Symbas, P N

1987-03-01

The coagulation system was investigated in five dogs undergoing autotransfusion from experimental hemothorax. One fourth of the blood volume was bled into the pleural space, drained, and autotransfused. The hemothorax blood showed: very prolonged PT and PTT; very low platelets and fibrinogen; midly elevated FDP; very low coagulation factors VIII, and V; reduced XII, prothrombin, X, XI, and VII. Partial clotting, mild fibrinolysis, and fibrin deposition over the pulmonary pleura seemed to cause incoagulability of hemothorax blood. Post autotransfusion arterial blood showed: normal PT and PTT; 25% decrease in platelets, and 31% decrease in fibrinogen from baseline values. There was also an overall 20% reduction of fibrinogen from baseline values. There was also an overall 20% reduction of all clotting factors, but their levels remained above 50% activity. It was concluded that autotransfusion from a hemothorax of 25% the blood volume in dogs causes a mild loss of hemostatic components, but does not significantly compromise the clotting mechanism.

Coagulation Testing in Acute Ischemic Stroke Patients Taking Non-Vitamin K Antagonist Oral Anticoagulants.

PubMed

Purrucker, Jan C; Haas, Kirsten; Rizos, Timolaos; Khan, Shujah; Poli, Sven; Kraft, Peter; Kleinschnitz, Christoph; Dziewas, Rainer; Binder, Andreas; Palm, Frederick; Jander, Sebastian; Soda, Hassan; Heuschmann, Peter U; Veltkamp, Roland

2017-01-01

In patients who present with acute ischemic stroke while on treatment with non-vitamin K antagonist oral anticoagulants (NOACs), coagulation testing is necessary to confirm the eligibility for thrombolytic therapy. We evaluated the current use of coagulation testing in routine clinical practice in patients who were on NOAC treatment at the time of acute ischemic stroke. Prospective multicenter observational RASUNOA registry (Registry of Acute Stroke Under New Oral Anticoagulants; February 2012-2015). Results of locally performed nonspecific (international normalized ratio, activated partial thromboplastin time, and thrombin time) and specific (antifactor Xa tests, hemoclot assay) coagulation tests were documented. The implications of test results for thrombolysis decision-making were explored. In the 290 patients enrolled, nonspecific coagulation tests were performed in ≥95% and specific coagulation tests in 26.9% of patients. Normal values of activated partial thromboplastin time and international normalized ratio did not reliably rule out peak drug levels at the time of the diagnostic tests (false-negative rates 11%-44% [95% confidence interval 1%-69%]). Twelve percent of patients apparently failed to take the prescribed NOAC prior to the acute event. Only 5.7% (9/159) of patients in the 4.5-hour time window received thrombolysis, and NOAC treatment was documented as main reason for not administering thrombolysis in 52.7% (79/150) of patients. NOAC treatment currently poses a significant barrier to thrombolysis in ischemic stroke. Because nonspecific coagulation test results within normal range have a high false-negative rate for detection of relevant drug concentrations, rapid drug-specific tests for thrombolysis decision-making should be established. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01850797. © 2016 American Heart Association, Inc.

Upregulation of the Coagulation Factor VII Gene during Glucose Deprivation Is Mediated by Activating Transcription Factor 4

PubMed Central

Cronin, Katherine R.; Mangan, Thomas P.; Carew, Josephine A.

2012-01-01

Background Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. Methodology/Principal Findings Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/− SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/−15% to 188+/−27% and 100+/−8.8% to 176.3+/−17.3% respectively, p<0.001) at 24 hr of treatment. The integrated stress response was induced, as indicated by upregulation of transcription factor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. Conclusions/Significance Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress. PMID:22848420

Chronic sleep deprivation markedly reduces coagulation factor VII expression

PubMed Central

Pinotti, Mirko; Bertolucci, Cristiano; Frigato, Elena; Branchini, Alessio; Cavallari, Nicola; Baba, Kenkichi; Contreras-Alcantara, Susana; Ehlen, J. Christopher; Bernardi, Francesco; Paul, Ketema N.; Tosini, Gianluca

2010-01-01

Chronic sleep loss, a common feature of human life in industrialized countries, is associated to cardiovascular disorders. Variations in functional parameters of coagulation might contribute to explain this relationship. By exploiting the mouse model and a specifically designed protocol, we demonstrated that seven days of partial sleep deprivation significantly decreases (−30.5%) the thrombin generation potential in plasma evaluated upon extrinsic (TF/FVIIa pathway) but not intrinsic activation of coagulation. This variation was consistent with a decrease (−49.8%) in the plasma activity levels of factor VII (FVII), the crucial physiologicalal trigger of coagulation, which was even more pronounced at the liver mRNA level (−85.7%). The recovery in normal sleep conditions for three days completely restored thrombin generation and FVII activity in plasma. For the first time, we demonstrate that chronic sleep deprivation on its own reduces, in a reversible manner, the FVII expression levels, thus influencing the TF/FVIIa activation pathway efficiency. PMID:20418241

Coagulation factor VIIa-mediated protease-activated receptor 2 activation leads to β-catenin accumulation via the AKT/GSK3β pathway and contributes to breast cancer progression.

PubMed

Roy, Abhishek; Ansari, Shabbir A; Das, Kaushik; Prasad, Ramesh; Bhattacharya, Anindita; Mallik, Suman; Mukherjee, Ashis; Sen, Prosenjit

2017-08-18

Cell migration and invasion are very characteristic features of cancer cells that promote metastasis, which is one of the most common causes of mortality among cancer patients. Emerging evidence has shown that coagulation factors can directly mediate cancer-associated complications either by enhancing thrombus formation or by initiating various signaling events leading to metastatic cancer progression. It is well established that, apart from its distinct role in blood coagulation, coagulation factor FVIIa enhances aggressive behaviors of breast cancer cells, but the underlying signaling mechanisms still remain elusive. To this end, we investigated FVIIa's role in the migration and invasiveness of the breast cancer cell line MDA-MB-231. Consistent with previous observations, we observed that FVIIa increased the migratory and invasive potential of these cells. We also provide molecular evidence that protease-activated receptor 2 activation followed by PI3K-AKT activation and GSK3β inactivation is involved in these processes and that β-catenin, a well known tumor-regulatory protein, contributes to this signaling pathway. The pivotal role of β-catenin was further indicated by the up-regulation of its downstream targets cyclin D1, c-Myc, COX-2, MMP-7, MMP-14, and Claudin-1. β-Catenin knockdown almost completely attenuated the FVIIa-induced enhancement of breast cancer migration and invasion. These findings provide a new perspective to counteract the invasive behavior of breast cancer, indicating that blocking PI3K-AKT pathway-dependent β-catenin accumulation may represent a potential therapeutic approach to control breast cancer. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Multiple roles of the coagulation protease cascade during virus infection.

PubMed

Antoniak, Silvio; Mackman, Nigel

2014-04-24

The coagulation cascade is activated during viral infections. This response may be part of the host defense system to limit spread of the pathogen. However, excessive activation of the coagulation cascade can be deleterious. In fact, inhibition of the tissue factor/factor VIIa complex reduced mortality in a monkey model of Ebola hemorrhagic fever. Other studies showed that incorporation of tissue factor into the envelope of herpes simplex virus increases infection of endothelial cells and mice. Furthermore, binding of factor X to adenovirus serotype 5 enhances infection of hepatocytes but also increases the activation of the innate immune response to the virus. Coagulation proteases activate protease-activated receptors (PARs). Interestingly, we and others found that PAR1 and PAR2 modulate the immune response to viral infection. For instance, PAR1 positively regulates TLR3-dependent expression of the antiviral protein interferon β, whereas PAR2 negatively regulates expression during coxsackievirus group B infection. These studies indicate that the coagulation cascade plays multiple roles during viral infections.

Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases.

PubMed

Massberg, Steffen; Grahl, Lenka; von Bruehl, Marie-Luise; Manukyan, Davit; Pfeiler, Susanne; Goosmann, Christian; Brinkmann, Volker; Lorenz, Michael; Bidzhekov, Kiril; Khandagale, Avinash B; Konrad, Ildiko; Kennerknecht, Elisabeth; Reges, Katja; Holdenrieder, Stefan; Braun, Siegmund; Reinhardt, Christoph; Spannagl, Michael; Preissner, Klaus T; Engelmann, Bernd

2010-08-01

Blood neutrophils provide the first line of defense against pathogens but have also been implicated in thrombotic processes. This dual function of neutrophils could reflect an evolutionarily conserved association between blood coagulation and antimicrobial defense, although the molecular determinants and in vivo significance of this association remain unclear. Here we show that major microbicidal effectors of neutrophils, the serine proteases neutrophil elastase and cathepsin G, together with externalized nucleosomes, promote coagulation and intravascular thrombus growth in vivo. The serine proteases and extracellular nucleosomes enhance tissue factor- and factor XII-dependent coagulation in a process involving local proteolysis of the coagulation suppressor tissue factor pathway inhibitor. During systemic infection, activation of coagulation fosters compartmentalization of bacteria in liver microvessels and reduces bacterial invasion into tissue. In the absence of a pathogen challenge, neutrophil-derived serine proteases and nucleosomes can contribute to large-vessel thrombosis, the main trigger of myocardial infarction and stroke. The ability of coagulation to suppress pathogen dissemination indicates that microvessel thrombosis represents a physiological tool of host defense.

[Influencing factors and mechanism of arsenic removal during the aluminum coagulation process].

PubMed

Chen, Gui-Xia; Hu, Cheng-Zhi; Zhu, Ling-Feng; Tong, Hua-Qing

2013-04-01

Aluminum coagulants are widely used in arsenic (As) removal during the drinking water treatment process. Aluminium chloride (AlCl3) and polyaluminium chloride (PACl) which contains high content of Al13 were used as coagulants. The effects of aluminum species, pH, humic acid (HA) and coexisting anions on arsenic removal were investigated. Results showed that AlCl3 and PACl were almost ineffective in As(II) removal while the As(V) removal efficiency reached almost 100%. pH was an important influencing factor on the arsenic removal efficiency, because pH influenced the distribution of aluminum species during the coagulation process. The efficiency of arsenic removal by aluminum coagulants was positively correlated with the content of Al13 species. HA and some coexisting anions showed negative impact on arsenic removal because of the competitive adsorption. The negative influence of HA was more pronounced at low coagulant dosages. PO4(3-) and F(-) showed marked influence during arsenic removal, but there was no obvious influence when SiO3(2-), CO3(2-) and SO4(2-) coexisted. The present study would be helpful to direct arsenic removal by enhanced coagulation during the drinking water treatment.

[Serum vitamin K concentration and nutrition].

PubMed

Tsugawa, Naoko; Okano, Toshio

2007-11-01

Vitamin K (VK) is well known for its role in the synthesis of a number of blood coagulation factors. VK is also an important factor for bone metabolism via gamma-carboxylation of VK-dependent proteins such as osteocalcin, matrix Gla protein, and protein S. Recently, it is rare that severe VK deficiency is observed. However, low dietary VK intake or low VK status has been shown to be associated with low bone mineral density and increased hip fracture risk. These studies suggest that there is potential VK insufficiency in bone, even in sufficient VK status for blood coagulation. In the present review, the studies concerning relationship between serum VK concentration and bone health, including pharmacokinetics of VK analogues (such as phylloquinone and menaquinone) and factors which affect on blood circulation of VK, are reviewed.

Vitamin K

USDA-ARS?s Scientific Manuscript database

Vitamin K, a fat-soluble vitamin, is an enzyme cofactor for post-translation modification of specific glutamate residues that are converted into '-carboxyglutamic acid (Gla) residues by a vitamin K-dependent (VKD) carboxylase. Seven VKD coagulation proteins are synthesized in the liver. The extra-he...

Risk factors for disseminated intravascular coagulation in patients with lung cancer.

PubMed

Nakano, Kentaro; Sugiyama, Kumiya; Satoh, Hideyuki; Shiromori, Sadaaki; Sugitate, Kei; Arifuku, Hajime; Yoshida, Naruo; Watanabe, Hiroyoshi; Tokita, Shingo; Wakayama, Tomoshige; Tatewaki, Masamitsu; Souma, Ryosuke; Koyama, Kenya; Hirata, Hirokuni; Fukushima, Yasutsugu

2018-05-31

The mortality rate from disseminated intravascular coagulation (DIC) is higher in patients with lung cancer than in non-lung cancer patients. Moreover, the prevalence of DIC varies among the pathologic types of lung cancer. This study analyzed the relationship between coagulation factors and the pathologic types of lung cancer. Twenty-six patients with progressive, inoperable stage IIB or higher lung cancer (20 men, 6 women; mean age 71 years; 11 Adeno, 10 squamous cell carcinoma, and 5 small cell carcinoma) and five healthy volunteers without respiratory disease (3 men, 2 women; mean age 72 years) were enrolled in the study. Blood samples were collected at lung cancer diagnosis, before treatment. White blood cell count, platelet count, serum C-reactive protein, fibrin/fibrinogen degradation products, fibrinogen, thrombin-antithrombin complex, and D-dimer levels differed significantly between lung cancer patients and the control group, but not among the pathologic types of lung cancer. Thrombomodulin levels were significantly higher in patients with Adeno and squamous cell carcinoma than in those with small cell carcinoma (P < 0.05 and P < 0.01, respectively). Antithrombin levels were significantly lower in patients with squamous cell carcinoma than in those with Adeno (P < 0.05). Coagulation disorders may develop secondary to chronic inflammation in patients with progressive lung cancer. DIC in lung cancer may be attributed to changes in anticoagulation factors, such as thrombomodulin and antithrombin, but not in other coagulation factors. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Quality control in the development of coagulation factor concentrates.

PubMed

Snape, T J

1987-01-01

Limitation of process change is a major factor contributing to assurance of quality in pharmaceutical manufacturing. This is particularly true in the manufacture of coagulation factor concentrates, for which presumptive testing for poorly defined product characteristics is an integral feature of finished product quality control. The development of new or modified preparations requires that this comfortable position be abandoned, and that the effect on finished product characteristics of changes to individual process steps (and components) be assessed. The degree of confidence in the safety and efficacy of the new product will be determined by, amongst other things, the complexity of the process alteration and the extent to which the results of finished product tests can be considered predictive. The introduction of a heat-treatment step for inactivation of potential viral contaminants in coagulation factor concentrates presents a significant challenge in both respects, quite independent of any consideration of assessment of the effectiveness of the viral inactivation step. These interactions are illustrated by some of the problems encountered with terminal dry heat-treatment (72 h. at 80 degrees C) of factor VIII and prothrombin complex concentrates manufactured by the Blood Products Laboratory.

Abnormal factor VIII coagulant antigen in patients with renal dysfunction and in those with disseminated intravascular coagulation.

PubMed Central

Weinstein, M J; Chute, L E; Schmitt, G W; Hamburger, R H; Bauer, K A; Troll, J H; Janson, P; Deykin, D

1985-01-01

Factor VIII antigen (VIII:CAg) exhibits molecular weight heterogeneity in normal plasma. We have compared the relative quantities of VIII:CAg forms present in normal individuals (n = 22) with VIII:CAg forms in renal dysfunction patients (n = 19) and in patients with disseminated intravascular coagulation (DIC; n = 7). In normal plasma, the predominant VIII: CAg form, detectable by sodium dodecyl sulfate polyacrylamide gel electrophoresis, was of molecular weight 2.4 X 10(5), with minor forms ranging from 8 X 10(4) to 2.6 X 10(5) D. A high proportion of VIII:CAg in renal dysfunction patients, in contrast, was of 1 X 10(5) mol wt. The patients' high 1 X 10(5) mol wt VIII: CAg level correlated with increased concentrations of serum creatinine, F1+2 (a polypeptide released upon prothrombin activation), and with von Willebrand factor. Despite the high proportion of the 1 X 10(5) mol wt VIII:CAg form, which suggests VIII:CAg proteolysis, the ratio of Factor VIII coagulant activity to total VIII:CAg concentration was normal in renal dysfunction patients. These results could be simulated in vitro by thrombin treatment of normal plasma, which yielded similar VIII:CAg gel patterns and Factor VIII coagulant activity to antigen ratios. DIC patients with high F1+2 levels but no evidence of renal dysfunction had an VIII:CAg gel pattern distinct from renal dysfunction patients. DIC patients had elevated concentrations of both the 1 X 10(5) and 8 X 10(4) mol wt VIII:CAg forms. We conclude that an increase in a particular VIII:CAg form correlates with the severity of renal dysfunction. The antigen abnormality may be the result of VIII:CAg proteolysis by a thrombinlike enzyme and/or prolonged retention of proteolyzed VIII:CAg fragments. Images PMID:3932466

Normal Hemostatic Profiles and Coagulation Factors in Healthy Free-Living Florida Manatees ( Trichechus manatus latirostris).

PubMed

Barratclough, Ashley; Floyd, Ruth Francis; Conner, Bobbi; Reep, Roger; Ball, Ray; Stacy, Nicole

2016-10-01

Hemostatic disorders presumptively play an important role in the pathophysiology of several important disease conditions in the Florida manatee ( Trichechus manatus latirostris). Prior to pursuing such clinical implications, it is essential to establish normal hemostatic profiles in clinically healthy animals. During annual health assessments of free-living manatees organized by the US Geological Survey, blood samples were collected from 12 healthy animals from the Atlantic coast and 28 from the Gulf of Mexico coast of Florida, with body lengths of 210-324 cm. The following analyses were performed on citrated plasma: prothrombin (PT), partial thromboplastin time (PTT), and concentrations of fibrinogen, D-dimers, and coagulation factors VII, VIII, IX, X, XI, and XII. Compared to other mammalian species, manatees had short PT (9.2±1.5 s) and PTT (10.7±0.5 s), fibrinogen was 369±78.7 mg/dL, antithrombin III was 132±11%, and D-dimer was 142±122 ng/mL. Baseline concentrations for the listed coagulation factors were established. When comparing coagulation factors between locations, Atlantic coast manatees had significantly higher factors VIII, IX, and X than did Gulf Coast manatees. This finding may reflect differences in water salinity, diet, or genetics. There were no differences in coagulation factors when among sexes and sizes. These baselines for hemostatic profiles and coagulation factors in healthy free-living manatees lay the foundation for diagnosis and future research of hemostatic disorders and contribute to understanding their role in the pathophysiology of manatees affected by various diseases.

The first EGF domain of coagulation factor IX attenuates cell adhesion and induces apoptosis.

PubMed

Ishikawa, Tomomi; Kitano, Hisataka; Mamiya, Atsushi; Kokubun, Shinichiro; Hidai, Chiaki

2016-07-01

Coagulation factor IX (FIX) is an essential plasma protein for blood coagulation. The first epidermal growth factor (EGF) motif of FIX (EGF-F9) has been reported to attenuate cell adhesion to the extracellular matrix (ECM). The purpose of the present study was to determine the effects of this motif on cell adhesion and apoptosis. Treatment with a recombinant EGF-F9 attenuated cell adhesion to the ECM within 10 min. De-adhesion assays with native FIX recombinant FIX deletion mutant proteins suggested that the de-adhesion activity of EGF-F9 requires the same process of FIX activation as that which occurs for coagulation activity. The recombinant EGF-F9 increased lactate dehydrogenase (LDH) activity release into the medium and increased the number of cells stained with annexin V and activated caspase-3, by 8.8- and 2.7-fold respectively, indicating that EGF-F9 induced apoptosis. Activated caspase-3 increased very rapidly after only 5 min of administration of recombinant EGF-F9. Treatment with EGF-F9 increased the level of phosphorylated p38 mitogen-activated protein kinase (MAPK), but not that of phosphorylated MAPK 44/42 or c-Jun N-terminal kinase (JNK). Inhibitors of caspase-3 suppressed the release of LDH. Caspase-3 inhibitors also suppressed the attenuation of cell adhesion and phosphorylation of p38 MAPK by EGF-F9. Our data indicated that EGF-F9 activated signals for apoptosis and induced de-adhesion in a caspase-3 dependent manner. © 2016 The Author(s).

[Role and clinical significance of coagulation and inflammatory factors in moderate and severe ovarian endometriosis].

PubMed

Lin, Q; Ding, S J; Zhu, T H; Li, T T; Huang, X F; Zhang, X M

2018-03-25

.05). The levels of FIB and PLR in patients with stage Ⅳ endometriosis were significantly higher than those in patients with stage Ⅲ endometriosis ( P <0.01) . (2) The cut-off value of CA(125) was 27.2 kU/L with a sensitivity of 83.6%, the cut-off value of FIB was 3.1 g/L with a sensitivity of 53.2%, while the sensitivity of combination index (FIB×CA(125)) was 84.9%. Conclusion: The abnormality of coagulation and inflammatory factors may be involved in the pathogenesis of moderate and severe ovarian endometriosis, and the detection of coagulation and inflammatory factors may be have important clinical significance for the diagnosis and treatment of moderate and severe ovarian endometriosis.

Age dependency for coagulation parameters in paediatric populations. Results of a multicentre study aimed at defining the age-specific reference ranges.

PubMed

Toulon, Pierre; Berruyer, Micheline; Brionne-François, Marie; Grand, François; Lasne, Dominique; Telion, Caroline; Arcizet, Julien; Giacomello, Roberta; De Pooter, Neila

2016-07-04

Understanding of developmental haemostasis is critical to ensure optimal prevention, diagnosis, and treatment of haemorrhagic and thrombotic diseases in children. As coagulation test results are known to be dependent on the reagents/analysers used, it is recommended for each laboratory to define the age-dependent reference ranges by using its own technical condition. That study was carried out in seven centers to establish age-specific reference ranges using the same reagents and analyser. Plasma samples were obtained from 1437 paediatric patients from the following age groups: 15 days-4 weeks (n=36), 1-5 months (n=320), 6-12 months (n=176), 1-5 years (n=507), 6-10 years (n=132) and 11-17 years (n=262). Indication of coagulation testing was pre-operative screening for non-acute diseases in most cases. PT values were similar in the different age groups to those in adults, whereas longer aPTTs were demonstrated in the younger children. Plasma levels of all clotting factors, except for FV, were significantly decreased (p<0.0001) in the youngest children, adult values being usually reached before the end of the first year. The same applied to antithrombin, protein C/S, and plasminogen. In contrast, FVIII and VWF levels were elevated in the youngest children and returned to adult values within six months. The same applied to D-dimer levels, which were found elevated, particularly until six months of life, until puberty. These data suggest that most coagulation test results are highly dependent on age, mainly during the first year of life, and that age-specific reference ranges must be used to ensure proper evaluation of coagulation in children.

Functional assembly of intrinsic coagulation proteases on monocytes and platelets. Comparison between cofactor activities induced by thrombin and factor Xa

PubMed Central

1992-01-01

Generation of coagulation factor Xa by the intrinsic pathway protease complex is essential for normal activation of the coagulation cascade in vivo. Monocytes and platelets provide membrane sites for assembly of components of this protease complex, factors IXa and VIII. Under biologically relevant conditions, expression of functional activity by this complex is associated with activation of factor VIII to VIIIa. In the present studies, autocatalytic regulatory pathways operating on monocyte and platelet membranes were investigated by comparing the cofactor function of thrombin-activated factor VIII to that of factor Xa-activated factor VIII. Reciprocal functional titrations with purified human factor VIII and factor IXa were performed at fixed concentrations of human monocytes, CaCl2, factor X, and either factor IXa or factor VIII. Factor VIII was preactivated with either thrombin or factor Xa, and reactions were initiated by addition of factor X. Rates of factor X activation were measured using chromogenic substrate specific for factor Xa. The K1/2 values, i.e., concentration of factor VIIIa at which rates were half maximal, were 0.96 nM with thrombin- activated factor VIII and 1.1 nM with factor Xa-activated factor VIII. These values are close to factor VIII concentration in plasma. The Vsat, i.e., rates at saturating concentrations of factor VIII, were 33.3 and 13.6 nM factor Xa/min, respectively. The K1/2 and Vsat values obtained in titrations with factor IXa were not significantly different from those obtained with factor VIII. In titrations with factor X, the values of Michaelis-Menten coefficients (Km) were 31.7 nM with thrombin- activated factor VIII, and 14.2 nM with factor Xa-activated factor VIII. Maximal rates were 23.4 and 4.9 nM factor Xa/min, respectively. The apparent catalytic efficiency was similar with either form of factor VIIIa. Kinetic profiles obtained with platelets as a source of membrane were comparable to those obtained with monocytes

Opposite effects of Agrimonia pilosa Ledeb aqueous extracts on blood coagulation function

PubMed Central

Yuan, Wufeng; Jiang, Lei; Wang, Huan

2017-01-01

Background Agrimonia pilosa Ledeb (APL) has showed anticoagulant and antithrombotic activities in some studies, whereas its actual effects on blood coagulation are still unclear. This study was designed to observe the in vitro effects of APL aqueous extracts on blood coagulation, as well as to investigate the underlying mechanisms. Methods Studies were divided into four groups: 0, 4, 20, and 80 g/L of APL aqueous extracts mixed with plasma or whole blood samples. Clotting time of whole blood, plasma coagulation tests, activities of plasma coagulation factors, plasma calcium ion, platelet aggregation test, and platelet fibrinogen receptor as well as the blood viscosity were measured. Results It was observed that the APL aqueous extracts in 4 g/L significantly prolonged the whole blood clotting time and activated partial thromboplastin time, shortened prothrombin time, decreased activities of coagulation factor VIII, IX and XI, and levels of platelet aggregation and fibrinogen receptor expression. However, coagulation factor VII activity, and blood viscosity were increased after the extracts treatment. And the effects of APL extracts were in a concentration-dependent manner (0–80 g/L). Conclusions The results suggest that APL aqueous extracts have a total anticoagulant activity, whereas they exhibit opposite effects of greater anticoagulant activity than pro-coagulant activity. PMID:28480193

Treatment tailoring for factor V deficient patients and perioperative management using global hemostatic coagulation assays.

PubMed

Levy-Mendelovich, Sarina; Barg, Assaf Arie; Rosenberg, Nurit; Avishai, Einat; Luboshitz, Jacob; Misgav, Mudi; Kenet, Gili; Livnat, Tami

2018-07-01

Congenital factor V deficiency (FVD) is a rare bleeding disorder with an estimated incidence of 1 in 1000,000 in the general population. Since the common coagulation tests do not correlate with the bleeding tendency there is an unmet need to predict FVD patients' bleeding hazard prior to surgical interventions. To optimize treatment prior to surgical interventions, using global coagulation assays, thrombin generation (TG) and rotating thromboelastogram (ROTEM). Our cohort included 5 patients with FVD, 4 severe and one mild. Two of them underwent TG and ROTEM prior to surgical interventions, including ex vivo spiking assays using bypass agents and platelets spiking. All five patients exhibited prolonged PT and PTT, non-dependent on their bleeding tendency. Patient 1, who demonstrated severe bleeding phenotype, underwent surgery treated by combination of APCC (FEIBA) and platelet transfusion. Therapy was guided by global tests (TG as well as ROTEM) results. During the pre and post-operative period neither excessive bleeding nor any thrombosis was noted. In contrast, TG and ROTEM analysis of patient 4 has lead us to perform the surgery without any blood products' support. Indeed, the patient did not encounter any bleeding. Global coagulation assays may be useful ancillary tools guiding treatment decisions in FVD patients undergoing surgical procedures. Copyright © 2018 Elsevier Inc. All rights reserved.

Vitamin K: an old vitamin in a new perspective.

PubMed

Gröber, U; Reichrath, J; Holick, M F; Kisters, K

2014-01-01

The topic of "Vitamin K" is currently booming on the health products market. Vitamin K is known to be important for blood coagulation. Current research increasingly indicates that the antihaemorrhagic vitamin has a considerable benefit in the prevention and treatment of bone and vascular disease. Vitamin K1 (phylloquinone) is more abundant in foods but less bioactive than the vitamin K2 menaquinones (especially MK-7, menaquinone-7). Vitamin K compounds undergo oxidation-reduction cycling within the endoplasmic reticulum membrane, donating electrons to activate specific proteins via enzymatic gamma-carboxylation of glutamate groups before being enzymatically reduced. Along with coagulation factors (II, VII, IX, X, and prothrombin), protein C and protein S, osteocalcin (OC), matrix Gla protein (MGP), periostin, Gas6, and other vitamin K-dependent (VKD) proteins support calcium homeostasis, inhibit vessel wall calcification, support endothelial integrity, facilitate bone mineralization, are involved in tissue renewal and cell growth control, and have numerous other effects. The following review describes the history of vitamin K, the physiological significance of the K vitamers, updates skeletal and cardiovascular benefits and important interactions with drugs.

Development of a microplate coagulation assay for Factor V in human plasma.

PubMed

Tilley, Derek; Levit, Irina; Samis, John A

2011-06-28

Factor V (FV) in its activated form, FVa, is a critical regulator of thrombin generation during fibrin clot formation. There is a need of a simple, fast, and inexpensive microplate-based coagulation assay to measure the functional activity of FV in human plasma. The objective of this study was to develop a microplate-based assay that measures FV coagulation activity during clot formation in human plasma, which is currently not available. The FV assay requires a kinetic microplate reader to measure the change in absorbance at 405nm during fibrin formation in human plasma. The FV assay accurately measures the time, initial rate, and extent of fibrin clot formation in human plasma. The FV microplate assay is simple, fast, economical, sensitive to approx 24-80pM, and multiple samples may be analyzed simultaneously. All the required materials are commercially available. Standard curves of time or initial rate of fibrin clot formation vs FV activity in the 1-stage assay (Without activation by thrombin) may be used to measure FV activity in samples of human plasma. The assay was used to demonstrate that in nine patients with disseminated intravascular coagulation (DIC), the FV 1-stage, 2-stage (With activation by thrombin), and total (2-stage activity - 1-stage activity) activities were decreased, on average, by approximately 54%, 44%, and 42%, respectively, from prolonged clot times when compared to normal pooled human reference plasma (NHP). The results indicate that the FV in the DIC patient plasmas supported both a delayed and slower rate of fibrin clot formation compared with NHP; however, the extent of fibrin clot formation in the DIC patients remained largely unchanged from that observed with NHP. The FV microplate assay may be easily adapted to measure the activity of any coagulation factor using the appropriate factor-deficient plasma and clot initiating reagent. The microplate assay will find use in both research and clinical laboratories to provide measurement

Development of a microplate coagulation assay for Factor V in human plasma

PubMed Central

2011-01-01

Background Factor V (FV) in its activated form, FVa, is a critical regulator of thrombin generation during fibrin clot formation. There is a need of a simple, fast, and inexpensive microplate-based coagulation assay to measure the functional activity of FV in human plasma. The objective of this study was to develop a microplate-based assay that measures FV coagulation activity during clot formation in human plasma, which is currently not available. Methods The FV assay requires a kinetic microplate reader to measure the change in absorbance at 405nm during fibrin formation in human plasma. The FV assay accurately measures the time, initial rate, and extent of fibrin clot formation in human plasma. Results The FV microplate assay is simple, fast, economical, sensitive to approx 24-80pM, and multiple samples may be analyzed simultaneously. All the required materials are commercially available. Standard curves of time or initial rate of fibrin clot formation vs FV activity in the 1-stage assay (Without activation by thrombin) may be used to measure FV activity in samples of human plasma. The assay was used to demonstrate that in nine patients with disseminated intravascular coagulation (DIC), the FV 1-stage, 2-stage (With activation by thrombin), and total (2-stage activity - 1-stage activity) activities were decreased, on average, by approximately 54%, 44%, and 42%, respectively, from prolonged clot times when compared to normal pooled human reference plasma (NHP). The results indicate that the FV in the DIC patient plasmas supported both a delayed and slower rate of fibrin clot formation compared with NHP; however, the extent of fibrin clot formation in the DIC patients remained largely unchanged from that observed with NHP. Conclusions The FV microplate assay may be easily adapted to measure the activity of any coagulation factor using the appropriate factor-deficient plasma and clot initiating reagent. The microplate assay will find use in both research and

Monitoring of coagulation factor therapy in patients with von Willebrand disease type 3 using a microchip flow chamber system.

PubMed

Ågren, Anna; Holmström, Margareta; Schmidt, David E; Hosokawa, Kazuya; Blombäck, Margareta; Hjemdahl, Paul

2017-01-05

Patients with type 3 von Willebrand disease (VWD-3) have no measurable levels of VW factor (VWF) and usually require treatment with VWF-FVIII concentrate to prevent and/or stop bleeding. Even though the patients are treated prophylactically, they may experience bleeding symptoms. The aim of this study was to evaluate the effect of VWF-FVIII concentrate treatment in VWD-3 patients with the Total Thrombus Analysis System (T-TAS ® ), which measures thrombus formation under flow conditions. Coagulation profiles of 10 VWD-3 patients were analysed using T-TAS before and 30 minutes after VWF-FVIII concentrate (Haemate ® ) injection. Results were compared to VWF- and FVIII activity in plasma, and results with thromboelastometry and ristocetin-activated platelet impedance aggregometry (Multiplate ® ) in whole blood. For comparison, 10 healthy controls were also analysed with T-TAS. A median dose of 27 (range 15-35) IU/kg of VWF-FVIII concentrate increased VWF- and FVIII activity as expected. T-TAS thrombus formation was enhanced when a tissue factor/collagen-coated flow chamber was used at low shear, but treatment effects at high shear using a collagen-coated flow chamber were minimal. Whole blood coagulation assessed by thromboelastometry was normal and did not change (p > 0.05) but ristocetin-induced platelet aggregation improved (p < 0.001). In conclusion, T-TAS detects effects of VWF-FVIII concentrate treatment on coagulation-dependent thrombus formation at low shear, but minor effects are observed on platelet-dependent thrombus formation at high shear. The poor prediction of bleeding by conventional laboratory monitoring in VWD-3 patients might be related to insufficient restoration of platelet-dependent thrombus formation.

Bloodcurdling movies and measures of coagulation: Fear Factor crossover trial.

PubMed

Nemeth, Banne; Scheres, Luuk J J; Lijfering, Willem M; Rosendaal, Frits R

2015-12-16

To assess whether, as has been hypothesised since medieval times, acute fear can curdle blood. Crossover trial. Main meeting room of Leiden University's Department of Clinical Epidemiology, the Netherlands, converted to a makeshift cinema. 24 healthy volunteers aged ≤30 years recruited among students, alumni, and employees of the Leiden University Medical Center: 14 were assigned to watch a frightening (horror) movie followed by a non-threatening (educational) movie and 10 to watch the movies in reverse order. The movies were viewed more than a week apart at the same time of day and both lasted approximately 90 minutes. The primary outcome measures were markers, or "fear factors" of coagulation activity: blood coagulant factor VIII, D-dimer, thrombin-antithrombin complexes, and prothrombin fragments 1+2. The secondary outcome was participant reported fear experienced during each movie using a visual analogue fear scale. All participants completed the study. The horror movie was perceived to be more frightening than the educational movie on a visual analogue fear scale (mean difference 5.4, 95% confidence interval 4.7 to 6.1). The difference in factor VIII levels before and after watching the movies was higher for the horror movie than for the educational movie (mean difference of differences 11.1 IU/dL (111 IU/L), 95% confidence interval 1.2 to 21.0 IU/dL). The effect of either movie on levels of thrombin-antithrombin complexes, D-dimer, and prothrombin fragments 1+2 did not differ. Frightening (in this case, horror) movies are associated with an increase of blood coagulant factor VIII without actual thrombin formation in young and healthy adults. Trial registration ClinicalTrials.gov NCT02601053. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A new approach using coagulation rate constant for evaluation of turbidity removal

NASA Astrophysics Data System (ADS)

Al-Sameraiy, Mukheled

2017-06-01

Coagulation-flocculation-sedimentation processes for treating three levels of bentonite synthetic turbid water using date seeds (DS) and alum (A) coagulants were investigated in the previous research work. In the current research, the same experimental results were used to adopt a new approach on a basis of using coagulation rate constant as an investigating parameter to identify optimum doses of these coagulants. Moreover, the performance of these coagulants to meet (WHO) turbidity standard was assessed by introducing a new evaluating criterion in terms of critical coagulation rate constant (kc). Coagulation rate constants (k2) were mathematically calculated in second order form of coagulation process for each coagulant. The maximum (k2) values corresponded to doses, which were obviously to be considered as optimum doses. The proposed criterion to assess the performance of coagulation process of these coagulants was based on the mathematical representation of (WHO) turbidity guidelines in second order form of coagulation process stated that (k2) for each coagulant should be ≥ (kc) for each level of synthetic turbid water. For all tested turbid water, DS coagulant could not satisfy it. While, A coagulant could satisfy it. The results obtained in the present research are exactly in agreement with the previous published results in terms of finding optimum doses for each coagulant and assessing their performances. On the whole, it is recommended considering coagulation rate constant to be a new approach as an indicator for investigating optimum doses and critical coagulation rate constant to be a new evaluating criterion to assess coagulants' performance.

Targeted inactivation of the mouse locus encoding coagulation factor XIII-A: hemostatic abnormalities in mutant mice and characterization of the coagulation deficit.

PubMed

Lauer, Peter; Metzner, Hubert J; Zettlmeissl, Gerd; Li, Meng; Smith, Austin G; Lathe, Richard; Dickneite, Gerhard

2002-12-01

Blood coagulation factor XIII (FXIII) promotes cross-linking of fibrin during blood coagulation; impaired clot stabilization in human genetic deficiency is associated with marked pathologies of major clinical impact, including bleeding symptoms and deficient wound healing. To investigate the role of FXIII we employed homologous recombination to generate a targeted deletion of the inferred exon 7 of the FXIII-A gene. FXIII transglutaminase activity in plasma was reduced to about 50% in mice heterozygous for the mutant allele, and was abolished in homozygous null mice. Plasma fibrin gamma-dimerization was also indetectable in the homozygous deficient animals, confirming the absence of activatable FXIII. Homozygous mutant mice were fertile, although reproduction was impaired. Bleeding episodes, hematothorax, hematoperitoneum and subcutaneous hemorrhage in mutant mice were associated with reduced survival. Arrest of tail-tip bleeding in FXIII-A deficient mice was markedly and significantly delayed; replacement of mutant mice with human plasma FXIII (Fibrogammin P) restored bleeding time to within the normal range. Thrombelastography (TEG) experiments demonstrated impaired clot stabilization in FXIII-A mutant mice, replacement with human FXIII led to dose-dependent TEG normalization. The mutant mice thus reiterate some key features of the human genetic disorder: they will be valuable in assessing the role of FXIII in other associated pathologies and the development of new therapies.

Finding the optimal dose of vitamin K1 to treat vitamin K deficiency and to avoid anaphylactoid reactions.

PubMed

Mi, Yan-Ni; Ping, Na-Na; Li, Bo; Xiao, Xue; Zhu, Yan-Bing; Cao, Lei; Ren, Jian-Kang; Cao, Yong-Xiao

2017-10-01

Vitamin K1 injection induces severe dose-related anaphylactoid reactions and overdose for the treatment of vitamin K deficiency. We aimed to find an optimal and small dose of vitamin K1 injection to treat vitamin K deficiency and avoid anaphylactoid reactions in animal. Rats were administered a vitamin K-deficient diet and gentamicin to establish vitamin K deficiency model. Behaviour tests were performed in beagle dogs to observe anaphylactoid reactions. The results showed an increased protein induced by vitamin K absence or antagonist II (PIVKA-II) levels, a prolonging of prothrombin time (PT) and activated partial thromboplastin time (APTT) and a decrease in vitamin K-dependent coagulation factor (F) II, VII, IX and X activities in the model group. In vitamin K1 0.01 mg/kg group, the liver vitamin K1 levels increased fivefold and the liver vitamin K2 levels increased to the normal amount. Coagulation markers PT, APTT, FVII and FIX activities returned to normal. Both in the 0.1 and 1.0 mg/kg vitamin K1 groups, coagulation functions completely returned to normal. Moreover, the amount of liver vitamin K1 was 40 (0.1 mg/kg) or 100 (1.0 mg/kg) times as in normal. Vitamin K2 was about 4 (0.1 mg/kg) or 5 (1.0 mg/kg) times as the normal amount. There was no obvious anaphylactoid symptom in dogs with the dose of 0.03 mg/kg, which is equivalent to the dose of 0.01 mg/kg in rats. These results demonstrated that a small dose of vitamin K1 is effective to improve vitamin K deficiency and to prevent anaphylactoid reactions, simultaneously. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Multiplexed targeted proteomic assay to assess coagulation factor concentrations and thrombosis-associated cancer

PubMed Central

van Vlijmen, Bart J.; Yang, Juncong; Percy, Andrew J.

2017-01-01

The plasma levels of pro- and anticoagulant proteins are important markers for venous thrombosis (VT) risk and can be affected by both genetic and acquired factors, including cancer. Generally, these markers are measured using activity- or antibody-based assays. Targeted proteomics with stable-isotope–labeled internal standards has proven adept at the rapid, multiplex, and precise quantification of proteins in complex biological samples such as plasma. We used liquid chromatography coupled to multiple reaction monitoring (MRM) mass spectrometry to evaluate the concentrations of 31 coagulation- and fibrinolysis-related proteins in plasma from 25 healthy controls, 25 patients with VT, and 25 patients with VT who were also diagnosed with cancer. The concentration level of 1 to 3 proteotypic peptides per protein was determined, and all samples were previously characterized using traditional antibody- or activity-based methods. When comparing the conventional and the MRM strategies, the mean Pearson correlation for the 13 proteins (covered by 36 target peptides) shared between the 2 approaches was 0.77, indicating a good correlation. Additionally, MRM offers higher sensitivity (mean regression slope, 0.81), higher multiplicity in a single run, and good ability to leverage all measurements to discriminate groups using unsupervised clustering, which identified vitamin K antagonist users as well as patients with VT and cancer. The data collected using MRM show that the combination of coagulation factor levels yields signature information on VT and cancer, which was not obvious from a single measurement. These results encourage the further validation and investigation of MRM in profiling protein signature of disease. PMID:29296750

Coagulation factor Xa drives tumor cells into apoptosis through BH3-only protein Bim up-regulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borensztajn, Keren S.; Bijlsma, Maarten F.; Groot, Angelique P.

2007-07-15

Coagulation Factor (F)Xa is a serine protease that plays a crucial role during blood coagulation by converting prothrombin into active thrombin. Recently, however, it emerged that besides this role in coagulation, FXa induces intracellular signaling leading to different cellular effects. Here, we show that coagulation factor (F)Xa drives tumor cells of epithelial origin, but not endothelial cells or monocytes, into apoptosis, whereas it even enhances fibroblast survival. FXa signals through the protease activated receptor (PAR)-1 to activate extracellular-signal regulated kinase (ERK) 1/2 and p38. This activation is associated with phosphorylation of the transcription factor CREB, and in tumor cells withmore » up-regulation of the BH3-only pro-apoptotic protein Bim, leading to caspase-3 cleavage, the main hallmark of apoptosis. Transfection of tumor cells with dominant negative forms of CREB or siRNA for either PAR-1, Bim, ERK1 and/or p38 inhibited the pro-apoptotic effect of FXa. In fibroblasts, FXa-induced PAR-1 activation leads to down-regulation of Bim and pre-treatment with PAR-1 or Bim siRNA abolishes proliferation. We thus provide evidence that beyond its role in blood coagulation, FXa plays a key role in cellular processes in which Bim is the central player in determining cell survival.« less

Effects of MASP-1 of the Complement System on Activation of Coagulation Factors and Plasma Clot Formation

PubMed Central

Hess, Katharina; Ajjan, Ramzi; Phoenix, Fladia; Dobó, József; Gál, Péter; Schroeder, Verena

2012-01-01

Background Numerous interactions between the coagulation and complement systems have been shown. Recently, links between coagulation and mannan-binding lectin-associated serine protease-1 (MASP-1) of the complement lectin pathway have been proposed. Our aim was to investigate MASP-1 activation of factor XIII (FXIII), fibrinogen, prothrombin, and thrombin-activatable fibrinolysis inhibitor (TAFI) in plasma-based systems, and to analyse effects of MASP-1 on plasma clot formation, structure and lysis. Methodology/Principal Findings We used a FXIII incorporation assay and specific assays to measure the activation products prothrombin fragment F1+2, fibrinopeptide A (FPA), and activated TAFI (TAFIa). Clot formation and lysis were assessed by turbidimetric assay. Clot structure was studied by scanning electron microscopy. MASP-1 activated FXIII and, contrary to thrombin, induced FXIII activity faster in the Val34 than the Leu34 variant. MASP-1-dependent generation of F1+2, FPA and TAFIa showed a dose-dependent response in normal citrated plasma (NCP), albeit MASP-1 was much less efficient than FXa or thrombin. MASP-1 activation of prothrombin and TAFI cleavage were confirmed in purified systems. No FPA generation was observed in prothrombin-depleted plasma. MASP-1 induced clot formation in NCP, affected clot structure, and prolonged clot lysis. Conclusions/Significance We show that MASP-1 interacts with plasma clot formation on different levels and influences fibrin structure. Although MASP-1-induced fibrin formation is thrombin-dependent, MASP-1 directly activates prothrombin, FXIII and TAFI. We suggest that MASP-1, in concerted action with other complement and coagulation proteins, may play a role in fibrin clot formation. PMID:22536427

Bloodcurdling movies and measures of coagulation: Fear Factor crossover trial

PubMed Central

Nemeth, Banne; Scheres, Luuk J J; Lijfering, Willem M

2015-01-01

Objective To assess whether, as has been hypothesised since medieval times, acute fear can curdle blood. Design Crossover trial. Setting Main meeting room of Leiden University’s Department of Clinical Epidemiology, the Netherlands, converted to a makeshift cinema. Participants 24 healthy volunteers aged ≤30 years recruited among students, alumni, and employees of the Leiden University Medical Center: 14 were assigned to watch a frightening (horror) movie followed by a non-threatening (educational) movie and 10 to watch the movies in reverse order. The movies were viewed more than a week apart at the same time of day and both lasted approximately 90 minutes. Main outcome measures The primary outcome measures were markers, or “fear factors” of coagulation activity: blood coagulant factor VIII, D-dimer, thrombin-antithrombin complexes, and prothrombin fragments 1+2. The secondary outcome was participant reported fear experienced during each movie using a visual analogue fear scale. Results All participants completed the study. The horror movie was perceived to be more frightening than the educational movie on a visual analogue fear scale (mean difference 5.4, 95% confidence interval 4.7 to 6.1). The difference in factor VIII levels before and after watching the movies was higher for the horror movie than for the educational movie (mean difference of differences 11.1 IU/dL (111 IU/L), 95% confidence interval 1.2 to 21.0 IU/dL). The effect of either movie on levels of thrombin-antithrombin complexes, D-dimer, and prothrombin fragments 1+2 did not differ. Conclusion Frightening (in this case, horror) movies are associated with an increase of blood coagulant factor VIII without actual thrombin formation in young and healthy adults. Trial registration ClinicalTrials.gov NCT02601053. PMID:26673787

Nanoparticles and the blood coagulation system. Part II: safety concerns

PubMed Central

Ilinskaya, Anna N; Dobrovolskaia, Marina A

2014-01-01

Nanoparticle interactions with the blood coagulation system can be beneficial or adverse depending on the intended use of a nanomaterial. Nanoparticles can be engineered to be procoagulant or to carry coagulation-initiating factors to treat certain disorders. Likewise, they can be designed to be anticoagulant or to carry anticoagulant drugs to intervene in other pathological conditions in which coagulation is a concern. An overview of the coagulation system was given and a discussion of a desirable interface between this system and engineered nanomaterials was assessed in part I, which was published in the May 2013 issue of Nanomedicine. Unwanted pro- and anti-coagulant properties of nanoparticles represent significant concerns in the field of nanomedicine, and often hamper the development and transition into the clinic of many promising engineered nanocarriers. This part will focus on the undesirable effects of engineered nanomaterials on the blood coagulation system. We will discuss the relationship between the physicochemical properties of nanoparticles (e.g., size, charge and hydrophobicity) that determine their negative effects on the blood coagulation system in order to understand how manipulation of these properties can help to overcome unwanted side effects. PMID:23730696

Cross-talk between the Tissue Factor/coagulation factor VIIa complex and the tyrosine kinase receptor EphA2 in cancer.

PubMed

Eriksson, Oskar; Thulin, Åsa; Asplund, Anna; Hegde, Geeta; Navani, Sanjay; Siegbahn, Agneta

2016-05-31

Tissue Factor (TF) forms a proteolytically active complex together with coagulation factor VIIa (FVIIa) and functions as the trigger of blood coagulation or alternatively activates cell signaling. We recently described that EphA2 of the Eph tyrosine kinase receptor family is cleaved directly by the TF/FVIIa complex. The aim of the present study was to further characterize the cross-talk between TF/FVIIa and EphA2 using in vitro model systems and human cancer specimens. Cleavage and phosphorylation of EphA2 was studied by Western blot. Subcellular localization of TF and EphA2 was investigated by a proximity ligation assay and confocal microscopy. Phalloidin staining of the actin cytoskeleton was used to study cell rounding and retraction fiber formation. Expression of TF and EphA2 in human colorectal cancer specimens was examined by immunohistochemistry. TF and EphA2 co-localized constitutively in MDA-MB-231 cells, and addition of FVIIa resulted in cleavage of EphA2 by a PAR2-independent mechanism. Overexpression of TF in U251 glioblastoma cells lead to co-localization with EphA2 at the leading edge and FVIIa-dependent cleavage of EphA2. FVIIa potentiated ephrin-A1-induced cell rounding and retraction fiber formation in MDA-MB-231 cells through a RhoA/ROCK-dependent pathway that did not require PAR2-activation. TF and EphA2 were expressed in colorectal cancer specimens, and were significantly correlated. These results suggest that TF/FVIIa-EphA2 cross-talk might potentiate ligand-dependent EphA2 signaling in human cancers, and provide initial evidence that it is possible for this interaction to occur in vivo.

Anomalous coagulation factors in non-arteritic anterior ischemic optic neuropathy with central retinal vein occlusion: A case report.

PubMed

Kim, Ji Hong; Kang, Min Ho; Seong, Mincheol; Cho, Heeyoon; Shin, Yong Un

2018-04-01

Non-arteritic anterior ischemic optic neuropathy (NAION) is characterized by sudden, painless visual loss and optic disc edema. NAION occurs mainly in the presence of cardiovascular disease and hypercoagulability, mainly in patients over 50 years of age. We experienced a case of NAION associated with central retinal vein occlusion (CRVO) in a young man with no underlying disease. A 46-year-old man was referred to our clinic following a sudden loss of vision in his right eye. The patient exhibited no underlying disease and reported no ongoing medication. Significant visual loss and visual disturbance of the right eye were observed. The pupil of the right eye was enlarged and an afferent pupillary defect was observed. On fundus examination, retinal hemorrhage was observed in the peripheral retina; macular edema was observed in optical coherence tomography analysis. However, optic disc edema was not evident. No abnormal findings were found in routine blood tests for hypercoagulability. After 3 days of steroid intravenous injection, macular edema disappeared and visual acuity was improved, but optic disc edema began to appear. One week later, optic disc edema was evident and visual acuity was significantly reduced; thus, the patient was diagnosed with NAION. In fluorescein angiography, peripheral retinal ischemia was observed, suggesting that CRVO was complicated. Blood tests, including analysis of coagulation factors, were performed again, showing that coagulation factors IX and XI were increased. Anomalous coagulation factors in non-arteritic anterior ischemic optic neuropathy with central retinal vein occlusion. Systemic steroids were administered. One month later, optic disc edema and retinal hemorrhage gradually diminished and eventually disappeared; however, visual acuity did not recover. In young patients without underlying disease, cases of NAION require careful screening for coagulation disorders. Even if there is no abnormality in the test for routine

Development and Implementation of a Coagulation Factor Testing Method Utilizing Autoverification in a High-volume Clinical Reference Laboratory Environment

PubMed Central

Riley, Paul W.; Gallea, Benoit; Valcour, Andre

2017-01-01

Background: Testing coagulation factor activities requires that multiple dilutions be assayed and analyzed to produce a single result. The slope of the line created by plotting measured factor concentration against sample dilution is evaluated to discern the presence of inhibitors giving rise to nonparallelism. Moreover, samples producing results on initial dilution falling outside the analytic measurement range of the assay must be tested at additional dilutions to produce reportable results. Methods: The complexity of this process has motivated a large clinical reference laboratory to develop advanced computer algorithms with automated reflex testing rules to complete coagulation factor analysis. A method was developed for autoverification of coagulation factor activity using expert rules developed with on an off the shelf commercially available data manager system integrated into an automated coagulation platform. Results: Here, we present an approach allowing for the autoverification and reporting of factor activity results with greatly diminished technologist effort. Conclusions: To the best of our knowledge, this is the first report of its kind providing a detailed procedure for implementation of autoverification expert rules as applied to coagulation factor activity testing. Advantages of this system include ease of training for new operators, minimization of technologist time spent, reduction of staff fatigue, minimization of unnecessary reflex tests, optimization of turnaround time, and assurance of the consistency of the testing and reporting process. PMID:28706751

Development and Implementation of a Coagulation Factor Testing Method Utilizing Autoverification in a High-volume Clinical Reference Laboratory Environment.

PubMed

Riley, Paul W; Gallea, Benoit; Valcour, Andre

2017-01-01

Testing coagulation factor activities requires that multiple dilutions be assayed and analyzed to produce a single result. The slope of the line created by plotting measured factor concentration against sample dilution is evaluated to discern the presence of inhibitors giving rise to nonparallelism. Moreover, samples producing results on initial dilution falling outside the analytic measurement range of the assay must be tested at additional dilutions to produce reportable results. The complexity of this process has motivated a large clinical reference laboratory to develop advanced computer algorithms with automated reflex testing rules to complete coagulation factor analysis. A method was developed for autoverification of coagulation factor activity using expert rules developed with on an off the shelf commercially available data manager system integrated into an automated coagulation platform. Here, we present an approach allowing for the autoverification and reporting of factor activity results with greatly diminished technologist effort. To the best of our knowledge, this is the first report of its kind providing a detailed procedure for implementation of autoverification expert rules as applied to coagulation factor activity testing. Advantages of this system include ease of training for new operators, minimization of technologist time spent, reduction of staff fatigue, minimization of unnecessary reflex tests, optimization of turnaround time, and assurance of the consistency of the testing and reporting process.

Overview of the coagulation system.

PubMed

Palta, Sanjeev; Saroa, Richa; Palta, Anshu

2014-09-01

Coagulation is a dynamic process and the understanding of the blood coagulation system has evolved over the recent years in anaesthetic practice. Although the traditional classification of the coagulation system into extrinsic and intrinsic pathway is still valid, the newer insights into coagulation provide more authentic description of the same. Normal coagulation pathway represents a balance between the pro coagulant pathway that is responsible for clot formation and the mechanisms that inhibit the same beyond the injury site. Imbalance of the coagulation system may occur in the perioperative period or during critical illness, which may be secondary to numerous factors leading to a tendency of either thrombosis or bleeding. A systematic search of literature on PubMed with MeSH terms 'coagulation system, haemostasis and anaesthesia revealed twenty eight related clinical trials and review articles in last 10 years. Since the balance of the coagulation system may tilt towards bleeding and thrombosis in many situations, it is mandatory for the clinicians to understand physiologic basis of haemostasis in order to diagnose and manage the abnormalities of the coagulation process and to interpret the diagnostic tests done for the same.

Overview of the coagulation system

PubMed Central

Palta, Sanjeev; Saroa, Richa; Palta, Anshu

2014-01-01

Coagulation is a dynamic process and the understanding of the blood coagulation system has evolved over the recent years in anaesthetic practice. Although the traditional classification of the coagulation system into extrinsic and intrinsic pathway is still valid, the newer insights into coagulation provide more authentic description of the same. Normal coagulation pathway represents a balance between the pro coagulant pathway that is responsible for clot formation and the mechanisms that inhibit the same beyond the injury site. Imbalance of the coagulation system may occur in the perioperative period or during critical illness, which may be secondary to numerous factors leading to a tendency of either thrombosis or bleeding. A systematic search of literature on PubMed with MeSH terms ‘coagulation system, haemostasis and anaesthesia revealed twenty eight related clinical trials and review articles in last 10 years. Since the balance of the coagulation system may tilt towards bleeding and thrombosis in many situations, it is mandatory for the clinicians to understand physiologic basis of haemostasis in order to diagnose and manage the abnormalities of the coagulation process and to interpret the diagnostic tests done for the same. PMID:25535411

Mannose-binding lectin and its associated proteases (MASPs) mediate coagulation and its deficiency is a risk factor in developing complications from infection, including disseminated intravascular coagulation

PubMed Central

Takahashi, Kazue; Chang, Wei-Chuan; Takahashi, Minoru; Pavlov, Vasile; Ishida, Yumi; La Bonte, Laura; Shi, Lei; Fujita, Teizo; Stahl, Gregory L.; Van Cott, Elizabeth M.

2010-01-01

The first line of host defense is the innate immune system that includes coagulation factors and pattern recognition molecules, one of which is mannose-binding lectin (MBL). Previous studies have demonstrated that MBL deficiency increases susceptibility to infection. Several mechanisms are associated with increased susceptibility to infection, including reduced opsonophagocytic killing and reduced lectin complement pathway activation. In this study, we demonstrate that MBL and MBL-associated serine protease (MASP)-1/3 together mediate coagulation factor-like activities, including thrombin-like activity. MBL and/or MASP-1/3 deficient hosts demonstrate in vivo evidence that MBL and MASP-1/3 are involved with hemostasis following injury. Staphylococcus aureus infected MBL null mice developed disseminated intravascular coagulation (DIC), which was associated with elevated blood IL-6 levels (but not TNF-α and multi-organ inflammatory responses). Infected MBL null mice also develop liver injury. These findings suggest that MBL deficiency may manifest into DIC and organ failure during infectious diseases. PMID:20399528

Effect of chitosan and coagulation factors on the wound repair phenotype of bioengineered blood clots.

PubMed

Hoemann, Caroline D; Marchand, Catherine; Rivard, Georges-Etienne; El-Gabalawy, Hani; Poubelle, Patrice E

2017-11-01

Controlling the blood clot phenotype in a surgically prepared wound is an evolving concept in scaffold-guided tissue engineering. Here, we investigated the effect of added chitosan (80% or 95% Degree of Deacetylation, DDA) or coagulation factors (recombinant human Factor VIIa, Tissue Factor, thrombin) on inflammatory factors released by blood clots. We tested the hypothesis that 80% DDA chitosan specifically enhances leukotriene B 4 (LTB 4 ) production. Human or rabbit whole blood was combined with isotonic chitosan solutions, coagulation factors, or lipopolysaccharide, cultured in vitro at 37°C, and after 4hours the serum was assayed for LTB 4 or inflammatory factors. Only 80% DDA chitosan clots produced around 15-fold more LTB 4 over other clots including 95% DDA chitosan clots. All serum contained high levels of PDGF-BB and CXCL8. Normal clots produced very low type I cytokines compared to lipopolysaccharide clots, with even lower IL-6 and IL-12 and more CCL3/CCL4 produced by chitosan clots. Coagulation factors had no detectable effect on clot phenotype. Conclusion In blood clots from healthy individuals, 80% DDA chitosan has a unique influence of inducing more LTB 4 , a potent neutrophil chemoattractant, with similar production of PDGF-BB and CXCL8, and lower type I cytokines, compared to whole blood clots. Copyright © 2017 Elsevier B.V. All rights reserved.

Contact activation of blood-plasma coagulation

NASA Astrophysics Data System (ADS)

Golas, Avantika

Surface engineering of biomaterials with improved hemocompatibility is an imperative, given the widespread global need for cardiovascular devices. Research summarized in this dissertation focuses on contact activation of FXII in buffer and blood plasma frequently referred to as autoactivation. The extant theory of contact activation imparts FXII autoactivation ability to negatively charged, hydrophilic surfaces. According to this theory, contact activation of plasma involves assembly of proteins comprising an "activation complex" on activating surfaces mediated by specific chemical interactions between complex proteins and the surface. This work has made key discoveries that significantly improve our core understanding of contact activation and unravel the existing paradigm of plasma coagulation. It is shown herein that contact activation of blood factor XII (FXII, Hageman factor) in neat-buffer solution exhibits a parabolic profile when scaled as a function of silanized-glass-particle activator surface energy (measured as advancing water adhesion tension t°a=g° Iv costheta in dyne/cm, where g°Iv is water interfacial tension in dyne/cm and theta is the advancing contact angle). Nearly equal activation is observed at the extremes of activator water-wetting properties --36 < t°a < 72 dyne/cm (O° ≤ theta < 120°), falling sharply through a broad minimum within the 20 < t°a < 40 dyne/cm (55° < theta < 75°). Furthermore, contact activation of FXII in buffer solution produces an ensemble of protein fragments exhibiting either procoagulant properties in plasma (proteolysis of blood factor XI or prekallikrein), amidolytic properties (cleavage of s-2302 chromogen), or the ability to suppress autoactivation through currently unknown biochemistry. The relative proportions of these fragments depend on activator surface chemistry/energy. We have also discovered that contact activation is moderated by adsorption of plasma proteins unrelated to coagulation through an

Does whole blood coagulation analysis reflect developmental haemostasis?

PubMed

Ravn, Hanne Berg; Andreasen, Jo Bønding; Hvas, Anne-Mette

2017-04-01

: Developmental haemostasis has been well documented over the last 3 decades and age-dependent reference ranges have been reported for a number of plasmatic coagulation parameters. With the increasing use of whole blood point-of-care tests like rotational thromboelastometry (ROTEM) and platelet function tests, an evaluation of age-dependent changes is warranted for these tests as well. We obtained blood samples from 149 children, aged 1 day to 5.9 years, and analysed conventional plasmatic coagulation tests, including activated partial prothrombin time, prothrombin time, and fibrinogen (functional). Whole blood samples were analysed using ROTEM to assess overall coagulation capacity and Multiplate analyzer to evaluate platelet aggregation. Age-dependent changes were analysed for all variables. We found age-dependent differences in all conventional coagulation tests (all P values < 0.05), but there was no sign of developmental changes in whole blood coagulation assessment when applying ROTEM, apart from clotting time in the EXTEM assay (P < 0.03). Despite marked differences in mean platelet aggregation between age groups, data did not reach statistical significance. Citrate-anticoagulated blood showed significantly reduced platelet aggregation compared with blood anticoagulated with heparin or hirudin (all P values < 0.003). We confirmed previous developmental changes in conventional plasmatic coagulation test. However, these age-dependent changes were not displayed in whole blood monitoring using ROTEM or Multiplate analyzer. Type of anticoagulant had a significant influence on platelet aggregation across all age groups.

Coagulation factor VII variants resistant to inhibitory antibodies.

PubMed

Branchini, Alessio; Baroni, Marcello; Pfeiffer, Caroline; Batorova, Angelika; Giansily-Blaizot, Muriel; Schved, Jean F; Mariani, Guglielmo; Bernardi, Francesco; Pinotti, Mirko

2014-11-01

Replacement therapy is currently used to prevent and treat bleeding episodes in coagulation factor deficiencies. However, structural differences between the endogenous and therapeutic proteins might increase the risk for immune complications. This study was aimed at identifying factor (F)VII variants resistant to inhibitory antibodies developed after treatment with recombinant activated factor VII (rFVIIa) in a FVII-deficient patient homozygous for the p.A354V-p.P464Hfs mutation, which predicts trace levels of an elongated FVII variant in plasma. We performed fluorescent bead-based binding, ELISA-based competition as well as fluorogenic functional (activated FX and thrombin generation) assays in plasma and with recombinant proteins. We found that antibodies displayed higher affinity for the active than for the zymogen FVII (half-maximal binding at 0.54 ± 0.04 and 0.78 ± 0.07 BU/ml, respectively), and inhibited the coagulation initiation phase with a second-order kinetics. Isotypic analysis showed a polyclonal response with a large predominance of IgG1. We hypothesised that structural differences in the carboxyl-terminus between the inherited FVII and the therapeutic molecules contributed to the immune response. Intriguingly, a naturally-occurring, poorly secreted and 5-residue truncated FVII (FVII-462X) escaped inhibition. Among a series of truncated rFVII molecules, we identified a well-secreted and catalytically competent variant (rFVII-464X) with reduced binding to antibodies (half-maximal binding at 0.198 ± 0.003 BU/ml) as compared to the rFVII-wt (0.032 ± 0.002 BU/ml), which led to a 40-time reduced inhibition in activated FX generation assays. Taken together our results provide a paradigmatic example of mutation-related inhibitory antibodies, strongly support the FVII carboxyl-terminus as their main target and identify inhibitor-resistant FVII variants.

Prediction of settled water turbidity and optimal coagulant dosage in drinking water treatment plant using a hybrid model of k-means clustering and adaptive neuro-fuzzy inference system

NASA Astrophysics Data System (ADS)

Kim, Chan Moon; Parnichkun, Manukid

2017-11-01

Coagulation is an important process in drinking water treatment to attain acceptable treated water quality. However, the determination of coagulant dosage is still a challenging task for operators, because coagulation is nonlinear and complicated process. Feedback control to achieve the desired treated water quality is difficult due to lengthy process time. In this research, a hybrid of k-means clustering and adaptive neuro-fuzzy inference system ( k-means-ANFIS) is proposed for the settled water turbidity prediction and the optimal coagulant dosage determination using full-scale historical data. To build a well-adaptive model to different process states from influent water, raw water quality data are classified into four clusters according to its properties by a k-means clustering technique. The sub-models are developed individually on the basis of each clustered data set. Results reveal that the sub-models constructed by a hybrid k-means-ANFIS perform better than not only a single ANFIS model, but also seasonal models by artificial neural network (ANN). The finally completed model consisting of sub-models shows more accurate and consistent prediction ability than a single model of ANFIS and a single model of ANN based on all five evaluation indices. Therefore, the hybrid model of k-means-ANFIS can be employed as a robust tool for managing both treated water quality and production costs simultaneously.

Evaluation of Consequences of Dust Positioned in Southwest of Iran on Coagulant Factors

PubMed Central

Saeb, Keivan; Sarizade, Gholamreza; Khodadi, Mohammad; Biazar, Esmaeil

2013-01-01

Background: Various regions in Iran, especially the Khuzestan Province, have been covered by dust and dirt during the past two years due to environmental changes in the Middle East. We sought to evaluate the effect of these pollutants on the coagulant factors of people residing in Abadan and Khoramshahr, two major cities of Khuzestan Province. Methods: One hundred twenty-nine healthy individuals were enrolled into this study, and their prothrombin time as well as fibrinogen, platelet, and Factor VIII levels were measured before and after climate changes. Results: After climate changes, the mean prothrombin time decreased, while the fibrinogen, platelet, and Factor VIII levels rose. Conclusion: The results of this study suggest that the pollutants deployed in the Middle East can affect prothrombin time as well as fibrinogen, platelet, and Factor VII levels considerably and increase coagulant state. The pollutants can, consequently, increase the risk of cardiovascular diseases. It seems that cooperation at government levels between Iran and its neighboring countries is required to reverse desertification and avoid inaccurate usage of subterranean water resources so as to lessen air pollution. PMID:23825886

Vitamin K: dietary intake and requirements in different clinical conditions

USDA-ARS?s Scientific Manuscript database

Purpose of review: Vitamin K is an enzyme cofactor for the carboxylation of vitamin K dependent proteins (VKDP). Functions include coagulation and regulation of calcification. Different clinical conditions may alter vitamin K requirements by affecting vitamin K status and VKDP carboxylation, which a...

Coagulation disorders in dogs with hepatic disease.

PubMed

Prins, M; Schellens, C J M M; van Leeuwen, M W; Rothuizen, J; Teske, E

2010-08-01

Liver disease has been associated with abnormalities in haemostasis. In this study, coagulation times, platelet counts, platelet activity parameters, activities of individual coagulation factors, D-dimers, antithrombin (AT) and protein C activity were measured in 42 dogs with histologically confirmed liver disease. Outcome was correlated with histological diagnosis. One or more coagulation abnormalities were present in 57% of dogs with hepatic disease. Activated partial thromboplastin time was significantly prolonged in dogs with chronic hepatitis (CH), with or without cirrhosis. Mean platelet numbers, AT and factor IX activity were significantly lower in dogs with CH plus cirrhosis, compared to dogs with other hepatopathies. D-dimers were not significantly increased in any group. Only three dogs, all with different histological diagnoses, satisfied the criteria for disseminated intravascular coagulation (DIC). Haemostatic abnormalities were primarily seen in dogs with cirrhosis and this may be due to reduced synthesis rather than increased consumption of coagulation factors. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Emergent self-similarity of cluster coagulation

NASA Astrophysics Data System (ADS)

Pushkin, Dmtiri O.

A wide variety of nonequilibrium processes, such as coagulation of colloidal particles, aggregation of bacteria into colonies, coalescence of rain drops, bond formation between polymerization sites, and formation of planetesimals, fall under the rubric of cluster coagulation. We predict emergence of self-similar behavior in such systems when they are 'forced' by an external source of the smallest particles. The corresponding self-similar coagulation spectra prove to be power laws. Starting from the classical Smoluchowski coagulation equation, we identify the conditions required for emergence of self-similarity and show that the power-law exponent value for a particular coagulation mechanism depends on the homogeneity index of the corresponding coagulation kernel only. Next, we consider the current wave of mergers of large American banks as an 'unorthodox' application of coagulation theory. We predict that the bank size distribution has propensity to become a power law, and verify our prediction in a statistical study of the available economical data. We conclude this chapter by discussing economically significant phenomenon of capital condensation and predicting emergence of power-law distributions in other economical and social data. Finally, we turn to apparent semblance between cluster coagulation and turbulence and conclude that it is not accidental: both of these processes are instances of nonlinear cascades. This class of processes also includes river network formation models, certain force-chain models in granular mechanics, fragmentation due to collisional cascades, percolation, and growing random networks. We characterize a particular cascade by three indicies and show that the resulting power-law spectrum exponent depends on the indicies values only. The ensuing algebraic formula is remarkable for its simplicity.

ZnO Film Bulk Acoustic Resonator for the Kinetics Study of Human Blood Coagulation

PubMed Central

Chen, Da; Zhang, Zhen; Ma, Jilong; Wang, Wei

2017-01-01

Miniaturized and rapid blood coagulation assay technologies are critical in many clinical settings. In this paper, we present a ZnO film bulk acoustic resonator for the kinetic analysis of human blood coagulation. The resonator operated in thickness shear resonance mode at 1.4 GHz. When the resonator contacted the liquid environment, the viscous loading effect was considered as the additional resistance and inductance in the equivalent circuits, resulting in a linear relationship with a slope of approximately −217 kHz/cP between the liquid viscosity and the frequency of the resonator. The downshift of the resonant frequency and the viscosity change during the blood coagulation were correlated to monitor the coagulation process. The sigmoidal trend was observed in the frequency response for the blood samples activated by thromboplastin and calcium ions. The coagulation kinetics involving sequential phases of steady reaction, growth and saturation were revealed through the time-dependent frequency profiles. The enzymatic cascade time, the coagulation rate, the coagulation time and the clot degree were provided by fitting the time-frequency curves. The prothrombin times were compared with the results measured by a standard coagulometer and show a good correlation. Thanks to the excellent potential of integration, miniaturization and the availability of direct digital signals, the film bulk acoustic resonator has promising application for both clinical and personal use coagulation testing technologies. PMID:28467374

Should vitamin K be supplemented instead of antagonised in patients with idiopathic pulmonary fibrosis?

PubMed

De Brouwer, Bart; Piscaer, Ianthe; Von Der Thusen, Jan H; Grutters, Jan C; Schutgens, Roger Eg; Wouters, Emiel Fm; Janssen, Rob

2018-03-01

There is an ongoing need for additional interventions in idiopathic pulmonary fibrosis (IPF) as antifibrotic drugs currently available only inhibit and do not stall disease progression. Vitamin K is a co-factor for the activation of coagulation factors. However, it is also required to activate proteins with functions outside of the coagulation cascade, such as matrix Gla protein (MGP), a defender against soft tissue calcification. Vitamin K antagonists are anticoagulants that are, for unknown reasons, associated with increased mortality in IPF. Areas covered: We advance the hypothesis that modulation of vitamin K-dependent MGP activation in IPF patients by either vitamin K antagonism or administration may result in acceleration and deceleration of fibrosis progression, respectively. Furthermore, shortfall in vitamin K could be suspected in IPF based on the high prevalence of certain co-morbidities, such as vascular calcification and lung cancer. Expert commentary: We hypothesize that vitamin K status is reduced in IPF patients. This, in combination with studies suggesting that vitamin K may play a role in lung fibrosis pathogenesis, would provide a rationale for conducting a clinical trial assessing the potential mitigating effects of vitamin K administration on progression of lung fibrosis, prevention of co-morbidities and mortality in IPF.

An updated concept of coagulation with clinical implications.

PubMed

Romney, Gregory; Glick, Michael

2009-05-01

Over the past century, a series of models have been put forth to explain the coagulation mechanism. The coagulation cascade/waterfall model has gained the most widespread acceptance. This model, however, has problems when it is used in different clinical scenarios. A more recently proposed cell-based model better describes the coagulation process in vivo and provides oral health care professionals (OHCPs) with a better understanding of the clinical implications of providing dental care to patients with potentially increased bleeding tendencies. The authors conducted a literature search using the PubMed database. They searched for key words including "coagulation," "hemostasis," "bleeding," "coagulation factors," "models," "prothrombin time," "activated partial thromboplastin time," "international normalized ratio," "anticoagulation therapy" and "hemophilia" separately and in combination. The coagulation cascade/waterfall model is insufficient to explain coagulation in vivo, predict a patient's bleeding tendency, or correlate clinical outcomes with specific laboratory screening tests such as prothrombin time, activated partial thromboplastin time and international normalized ratio. However, the cell-based model of coagulation that reflects the in vivo process of coagulation provides insight into the clinical ramifications of treating dental patients with specific coagulation factor deficiencies. Understanding the in vivo coagulation process will help OHCPs better predict a patient's bleeding tendency. In addition, applying the theoretical concept of the cell-based model of coagulation to commonly used laboratory screening tests for coagulation and bleeding will result in safer and more appropriate dental care.

Rational and timely haemostatic interventions following cardiac surgery - coagulation factor concentrates or blood bank products.

PubMed

Tang, Mariann; Fenger-Eriksen, Christian; Wierup, Per; Greisen, Jacob; Ingerslev, Jørgen; Hjortdal, Vibeke; Sørensen, Benny

2017-06-01

Cardiac surgery may cause a serious coagulopathy leading to increased risk of bleeding and transfusion demands. Blood bank products are commonly first line haemostatic intervention, but has been associated with hazardous side effect. Coagulation factor concentrates may be a more efficient, predictable, and potentially a safer treatment, although prospective clinical trials are needed to further explore these hypotheses. This study investigated the haemostatic potential of ex vivo supplementation of coagulation factor concentrates versus blood bank products on blood samples drawn from patients undergoing cardiac surgery. 30 adults were prospectively enrolled (mean age=63.9, females=27%). Ex vivo haemostatic interventions (monotherapy or combinations) were performed in whole blood taken immediately after surgery and two hours postoperatively. Fresh-frozen plasma, platelets, cryoprecipitate, fibrinogen concentrate, prothrombin complex concentrate (PCC), and recombinant FVIIa (rFVIIa) were investigated. The haemostatic effect was evaluated using whole blood thromboelastometry parameters, as well as by thrombin generation. Immediately after surgery the compromised maximum clot firmness was corrected by monotherapy with fibrinogen or platelets or combination therapy with fibrinogen. At two hours postoperatively the coagulation profile was further deranged as illustrated by a prolonged clotting time, a reduced maximum velocity and further diminished maximum clot firmness. The thrombin lagtime was progressively prolonged and both peak thrombin and endogenous thrombin potential were compromised. No monotherapy effectively corrected all haemostatic abnormalities. The most effective combinations were: fibrinogen+rFVIIa or fibrinogen+PCC. Blood bank products were not as effective in the correction of the coagulopathy. Coagulation factor concentrates appear to provide a more optimal haemostasis profile following cardiac surgery compared to blood bank products. Copyright © 2017

Intraoperative Changes in Blood Coagulation and Thrombelastographic Monitoring in Liver Transplantation

PubMed Central

Kang, Yoo Goo; Martin, Douglas J.; Marquez, Jose; Lewis, Jessica H.; Bontempo, Franklin A.; Shaw, Byers W.; Starzl, Thomas E.; Winter, Peter M.

2010-01-01

The blood coagulation system of 66 consecutive patients undergoing consecutive liver transplantations was monitored by thrombelastograph and analytic coagulation profile. A poor preoperative coagulation state, decrease in levels of coagulation factors, progressive fibrinolysis, and whole blood clot lysis were observed during the preanhepatic and anhepatic stages of surgery. A further general decrease in coagulation factors and platelets, activation of fibrinolysis, and abrupt decrease in levels of factors V and VIII occurred before and with reperfusion of the homograft. Recovery of blood coagulability began 30–60 min after reperfusion of the graft liver, and coagulability had returned toward baseline values 2 hr after reperfusion. A positive correlation was shown between the variables of thrombelastography and those of the coagulation profile. Thrombelastography was shown to be a reliable and rapid monitoring system. Its use was associated with a 33% reduction of blood and fluid infusion volume, whereas blood coagulability was maintained without an increase in the number of blood product donors. PMID:3896028

Physiotherapy, rehabilitation and sports in countries with limited replacement coagulation factor supply.

PubMed

Buzzard, B M

2007-09-01

It is well documented that physiotherapy and rehabilitation benefit people with haemophilia by strengthening the key muscle groups and protecting joints from the adverse effects of repeated haemorrhages. Rehabilitation, in conjunction with the availability of replacement coagulation factor products, has revolutionized approaches to the management of patients with haemophilia in developed countries and has led to a substantial decrease in both the morbidity and mortality rates among the haemophilic population. Modern treatment approaches have also enabled persons with haemophilia to participate in sporting activities along with their peers; however, these improvements in care have not been achieved in developing nations, where health-care resources and facilities are scarce and the supply of coagulation factor products is limited. This article attempts to address the following questions about the management of haemophilic patients in developing countries: Can physiotherapy, rehabilitation and sports prevent disabilities and preserve independence? Is participation in sports activities possible in developing countries? Do countries differ with regard to guidelines for participation in sports? Should we be encouraging participation in sports or allowing patients with haemophilia to do as they choose?

Thymoquinone Modulates Blood Coagulation in Vitro via Its Effects on Inflammatory and Coagulation Pathways

PubMed Central

Muralidharan-Chari, Vandhana; Kim, Jaehan; Abuawad, Ahlam; Naeem, Mubeena; Cui, Huadong; Mousa, Shaker A.

2016-01-01

Thymoquinone (THQ) is a major component of black seeds. Given that both THQ and black seeds exhibit anti-cancer and anti-inflammatory activities, we hypothesized that THQ will affect cancer-associated thrombosis (CAT), which is primarily triggered by tissue factor (TF) and inflammation. The effect of both black seed-extracted and purchased (“pure”) THQ on normal blood coagulation was tested with in vitro thromboelastography (TEG) and activated partial thromboplastin time (aPTT) coagulation assays. The effect of pure THQ on CAT was tested with aPTT assay using pancreatic cancer cell lines that are either positive or negative for TF, and with TEG assay using lipopolysaccharide as an inflammatory trigger. Additionally, the direct effect of THQ on the inactivation of factors IIa and Xa was assessed. Since TNF-α facilitates crosstalk between inflammation and thrombosis by triggering the NF-κB pathway, we tested THQ’s ability to interfere with this communication with a luciferase assay. Both extracted and pure THQ had minimal effects on normal blood coagulation. Pure THQ reversed CAT initiated by both TF and inflammation to basal levels (p < 0.001). Mechanistically, while THQ had minimal to no effect on factor IIa and Xa inactivation, it strongly reduced the effects of TNF-α on NF-κB elements (p < 0.001). THQ has a minimal effect on basal coagulation and can reverse CAT in vitro, possibly by interfering with the crosstalk between inflammation and coagulation. This study suggests the utility of THQ as a preventative anticoagulant and/or as a supplement to existing chemotherapies and anticoagulant therapies. PMID:27043539

Establishment of the 2nd Korean national biological reference standard for blood coagulation factor VIII:C concentrate.

PubMed

Lee, Naery; Seo, Ji Suk; Kim, Jae Ok; Ban, Sang Ja

2017-05-01

Since the 1st Korean national biological reference standard for factor (F)VIII concentrate, established in 2001, has shown declining potency, we conducted this study to replace this standard with a 2nd Korean national biological reference standard for blood coagulation FVIII concentrate. The candidate materials for the 2nd standard were prepared in 8000 vials with 10 IU/ml of target potency, according to the approved manufacturing process of blood coagulation Factor VIII:C Monoclonal Antibody-purified, Freeze-dried Human Blood Coagulation Factor VIII:C. Potency was evaluated by one-stage clotting and chromogenic methods and the stability was confirmed to meet the specifications during a period of 73 months. Since the potencies obtained by the two methods differed significantly (P < 0.015), the values were determined separately according to the geometric means (8.9 and 7.4 IU/vial, respectively). The geometric coefficients of interlaboratory variability were 3.4% and 7.6% by the one-stage clotting and chromogenic assays, respectively. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Tissue Factor-Factor VIIa Complex Triggers Protease Activated Receptor 2-Dependent Growth Factor Release and Migration in Ovarian Cancer

PubMed Central

Chanakira, Alice; Westmark, Pamela R.; Ong, Irene M.; Sheehan, John P.

2017-01-01

Objective Enhanced tissue factor (TF) expression in epithelial ovarian cancer (EOC) is associated with aggressive disease. Our objective was to evaluate the role of the TF-factor VIIa-protease-activated receptor-2 (PAR-2) pathway in human EOC. Methods TCGA RNAseq data from EOC databases were analyzed for PAR expression. Cell and microparticle (MP) associated TF protein expression (Western blot) and MP-associated coagulant activity were determined in human EOC (SKOV-3, OVCAR-3 and CaOV-3) and control cell lines. PAR-1 and PAR-2 protein expression were similarly examined. The PAR dependence of VEGF-A release (ELISA) and chemotactic migration in response to FVIIa and cellular proliferation in response to thrombin was evaluated with small molecule antagonists. Results Relative mRNA expression consistently demonstrated PAR-2>PAR-1≫PAR-3/4 in multiple EOC datasets. Human EOC cell line lysates confirmed expression of TF, PAR-1 and PAR-2 proteins. MPs isolated from EOC cell lines demonstrated markedly enhanced (4–10 fold) TF coagulant activity relative to control cell lines. FVIIa induced a dose-dependent increase in VEGF-A release (2.5-3 fold) from EOC cell lines that was abrogated by the PAR-2 antagonist ENMD-1068. FVIIa treatment of CaOV-3 and OVCAR-3 cells resulted in increased chemotactic migration that was abolished by ENMD-1068. Thrombin induced dose-dependent EOC cell line proliferation was completely reversed by the PAR-1 antagonist vorapaxar. Small molecule antagonists had no effect on these phenotypes without protease present. Conclusions Enhanced activity of the TF-FVIIa-PAR-2 axis may contribute to the EOC progression via PAR-2 dependent signaling that supports an angiogenic and invasive phenotype and local thrombin generation supporting PAR-1 dependent proliferation. PMID:28148395

Betrixaban: Impact on Routine and Specific Coagulation Assays-A Practical Laboratory Guide.

PubMed

Siriez, Romain; Evrard, Jonathan; Dogné, Jean-Michel; Pochet, Lionel; Gheldof, Damien; Chatelain, Bernard; Mullier, François; Douxfils, Jonathan

2018-06-11

 Betrixaban is a novel direct oral factor Xa inhibitor approved by the Food and Drug Administration for prophylaxis of venous thromboembolism in adult patients hospitalized for an acute illness at risk for thromboembolic complications. Assessment of the anti-coagulant effect of betrixaban may be useful in some situations. Also, clinicians need to know how routine coagulation assays are influenced.  The aim of this study is to determine which coagulation assay(s) should be used to assess the impact of betrixaban on haemostasis and provide laboratory guidance for their interpretation.  Betrixaban was spiked at final concentrations ranging from 0 to 250 ng/mL in platelet-poor plasma. Different reagents from several manufacturers were tested and the impact of betrixaban on pro-thrombin time (PT), activated partial thromboplastin time (aPTT), dilute Russel viper venom time (dRVV-T), chromogenic anti-Xa assays, thrombin generation assay (TGA), and a large panel of haemostasis diagnostic tests has been assessed.  A concentration-dependent prolongation of aPTT, PT and dRVV-T is observed. The sensitivity mainly depends on the reagent. Chromogenic anti-Xa assays show high sensitivity depending on the reagent and/or the methodology. These assays applicable for other direct factor Xa inhibitors have to be adapted to obtain a relevant range of measurement. TGA may also be attractive to assess the anti-coagulant activity of betrixaban.  Adapted chromogenic anti-Xa assays are the most appropriate assays to estimate the concentration of betrixaban. Betrixaban significantly affects several haemostasis diagnostic tests and this needs to be taken into consideration when requesting and interpreting such tests. Schattauer GmbH Stuttgart.

Measurement of Factor V Activity in Human Plasma Using a Microplate Coagulation Assay

PubMed Central

Tilley, Derek; Levit, Irina; Samis, John A.

2012-01-01

In response to injury, blood coagulation is activated and results in generation of the clotting protease, thrombin. Thrombin cleaves fibrinogen to fibrin which forms an insoluble clot that stops hemorrhage. Factor V (FV) in its activated form, FVa, is a critical cofactor for the protease FXa and accelerator of thrombin generation during fibrin clot formation as part of prothrombinase 1, 2. Manual FV assays have been described 3, 4, but they are time consuming and subjective. Automated FV assays have been reported 5-7, but the analyzer and reagents are expensive and generally provide only the clot time, not the rate and extent of fibrin formation. The microplate platform is preferred for measuring enzyme-catalyzed events because of convenience, time, cost, small volume, continuous monitoring, and high-throughput 8, 9. Microplate assays have been reported for clot lysis 10, platelet aggregation 11, and coagulation Factors 12, but not for FV activity in human plasma. The goal of the method was to develop a microplate assay that measures FV activity during fibrin formation in human plasma. This novel microplate method outlines a simple, inexpensive, and rapid assay of FV activity in human plasma. The assay utilizes a kinetic microplate reader to monitor the absorbance change at 405nm during fibrin formation in human plasma (Figure 1) 13. The assay accurately measures the time, initial rate, and extent of fibrin clot formation. It requires only μl quantities of plasma, is complete in 6 min, has high-throughput, is sensitive to 24-80pM FV, and measures the amount of unintentionally activated (1-stage activity) and thrombin-activated FV (2-stage activity) to obtain a complete assessment of its total functional activity (2-stage activity - 1-stage activity). Disseminated intravascular coagulation (DIC) is an acquired coagulopathy that most often develops from pre-existing infections 14. DIC is associated with a poor prognosis and increases mortality above the pre

Measurement of factor v activity in human plasma using a microplate coagulation assay.

PubMed

Tilley, Derek; Levit, Irina; Samis, John A

2012-09-09

In response to injury, blood coagulation is activated and results in generation of the clotting protease, thrombin. Thrombin cleaves fibrinogen to fibrin which forms an insoluble clot that stops hemorrhage. Factor V (FV) in its activated form, FVa, is a critical cofactor for the protease FXa and accelerator of thrombin generation during fibrin clot formation as part of prothrombinase (1, 2). Manual FV assays have been described (3, 4), but they are time consuming and subjective. Automated FV assays have been reported (5-7), but the analyzer and reagents are expensive and generally provide only the clot time, not the rate and extent of fibrin formation. The microplate platform is preferred for measuring enzyme-catalyzed events because of convenience, time, cost, small volume, continuous monitoring, and high-throughput (8, 9). Microplate assays have been reported for clot lysis (10), platelet aggregation (11), and coagulation Factors (12), but not for FV activity in human plasma. The goal of the method was to develop a microplate assay that measures FV activity during fibrin formation in human plasma. This novel microplate method outlines a simple, inexpensive, and rapid assay of FV activity in human plasma. The assay utilizes a kinetic microplate reader to monitor the absorbance change at 405 nm during fibrin formation in human plasma (Figure 1) (13). The assay accurately measures the time, initial rate, and extent of fibrin clot formation. It requires only μl quantities of plasma, is complete in 6 min, has high-throughput, is sensitive to 24-80 pM FV, and measures the amount of unintentionally activated (1-stage activity) and thrombin-activated FV (2-stage activity) to obtain a complete assessment of its total functional activity (2-stage activity - 1-stage activity). Disseminated intravascular coagulation (DIC) is an acquired coagulopathy that most often develops from pre-existing infections (14). DIC is associated with a poor prognosis and increases mortality

Principles of dielectric blood coagulometry as a comprehensive coagulation test.

PubMed

Hayashi, Yoshihito; Brun, Marc-Aurèle; Machida, Kenzo; Nagasawa, Masayuki

2015-10-06

Dielectric blood coagulometry (DBCM) is intended to support hemostasis management by providing comprehensive information on blood coagulation from automated, time-dependent measurements of whole blood dielectric spectra. We discuss the relationship between the series of blood coagulation reactions, especially the aggregation and deformation of erythrocytes, and the dielectric response with the help of clot structure electron microscope observations. Dielectric response to the spontaneous coagulation after recalcification presented three distinct phases that correspond to (P1) rouleau formation before the onset of clotting, (P2) erythrocyte aggregation and reconstitution of aggregates accompanying early fibrin formation, and (P3) erythrocyte shape transformation and/or structure changes within aggregates after the stable fibrin network is formed and platelet contraction occurs. Disappearance of the second phase was observed upon addition of tissue factor and ellagic acid for activation of extrinsic and intrinsic pathways, respectively, which is attributable to accelerated thrombin generation. A series of control experiments revealed that the amplitude and/or quickness of dielectric response reflect platelet function, fibrin polymerization, fibrinolysis activity, and heparin activity. Therefore, DBCM sensitively measures blood coagulation via erythrocytes aggregation and shape changes and their impact on the dielectric permittivity, making possible the development of the battery of assays needed for comprehensive coagulation testing.

Vitamin K: novel molecular mechanisms of action and its roles in osteoporosis.

PubMed

Azuma, Kotaro; Ouchi, Yasuyoshi; Inoue, Satoshi

2014-01-01

Vitamin K is a fat-soluble vitamin, which is involved in blood coagulation mediated by maintaining the activity of coagulation factors in the liver. Vitamin K also has extrahepatic actions and has been shown to prevent bone fractures in clinical studies. In addition, epidemiological studies suggest that a lack of vitamin K is associated with several geriatric diseases, including osteoporosis, osteoarthritis, dementia and arteriosclerosis. It has also been shown that vitamin K contributes to the prevention and treatment of some kinds of malignancies. Recently, we discovered a novel role for vitamin K as a ligand of the nuclear receptor, steroid and xenobiotic receptor (SXR), and its murine ortholog, pregnane X receptor (PXR). In addition to its established roles as a cofactor of γ-glutamyl carboxylase (GGCX) in mediating post-transcriptional modifications, vitamin K has a different mode of action mediated by transcriptional regulation of SXR/PXR target genes. Analysis of bone tissue from PXR-deficient mice showed that the bone protective effects of vitamin K are partially mediated by SXR/PXR-dependent signaling. The discoveries of a novel mode of vitamin K action have opened up new possibilities that vitamin K might be useful for prevention or treatment of a variety of diseases that affect the geriatric population. © 2013 Japan Geriatrics Society.

Influential factors of formation kinetics of flocs produced by water treatment coagulants.

PubMed

Wu, Chunde; Wang, Lin; Hu, Bing; Ye, Jian

2013-05-01

The growth rate and size of floc formation is of great importance in water treatment especially in coagulation process. The floc formation kinetics and the coagulation efficiency of synthetic water were investigated by using an on-line continuous optical photometric dispersion analyze and the analysis of water quality. Experimental conditions such as alum dosage, pH value for coagulation, stirring intensity and initial turbidity were extensively examined. The photometric dispersion analyze results showed that coagulation of kaolin suspensions with two coagulants (alum and polyaluminium chloride) could be taken as a two-phase process: slow and rapid growth periods. Operating conditions with higher coagulant doses, appropriate pH and average shear rate might be particularly advantageous. The rate of overall floc growth was mainly determined by a combination of hydraulic and water quality conditions such as pH and turbidity. The measurement of zeta potential indicates that polyaluminium chloride exhibited higher charge-neutralizing ability than alum and achieved lower turbidities than alum for equivalent Al dosages. Under the same operating conditions, the alum showed a higher grow rate, but with smaller floc size.

Principal component analysis to assess the efficiency and mechanism for enhanced coagulation of natural algae-laden water using a novel dual coagulant system.

PubMed

Ou, Hua-Se; Wei, Chao-Hai; Deng, Yang; Gao, Nai-Yun; Ren, Yuan; Hu, Yun

2014-02-01

A novel dual coagulant system of polyaluminum chloride sulfate (PACS) and polydiallyldimethylammonium chloride (PDADMAC) was used to treat natural algae-laden water from Meiliang Gulf, Lake Taihu. PACS (Aln(OH)mCl3n-m-2k(SO4)k) has a mass ratio of 10 %, a SO4 (2-)/Al3 (+) mole ratio of 0.0664, and an OH/Al mole ratio of 2. The PDADMAC ([C8H16NCl]m) has a MW which ranges from 5 × 10(5) to 20 × 10(5) Da. The variations of contaminants in water samples during treatments were estimated in the form of principal component analysis (PCA) factor scores and conventional variables (turbidity, DOC, etc.). Parallel factor analysis determined four chromophoric dissolved organic matters (CDOM) components, and PCA identified four integrated principle factors. PCA factor 1 had significant correlations with chlorophyll-a (r=0.718), protein-like CDOM C1 (0.689), and C2 (0.756). Factor 2 correlated with UV254 (0.672), humic-like CDOM component C3 (0.716), and C4 (0.758). Factors 3 and 4 had correlations with NH3-N (0.748) and T-P (0.769), respectively. The variations of PCA factors scores revealed that PACS contributed less aluminum dissolution than PAC to obtain equivalent removal efficiency of contaminants. This might be due to the high cationic charge and pre-hydrolyzation of PACS. Compared with PACS coagulation (20 mg L(-1)), the removal of PCA factors 1, 2, and 4 increased 45, 33, and 12 %, respectively, in combined PACS-PDADMAC treatment (0.8 mg L(-1) +20 mg L(-1)). Since PAC contained more Al (0.053 g/1 g) than PACS (0.028 g/1 g), the results indicated that PACS contributed less Al dissolution into the water to obtain equivalent removal efficiency.

Discovery of glycyrrhetinic acid as an orally active, direct inhibitor of blood coagulation factor xa.

PubMed

Jiang, Lilong; Wang, Qiong; Shen, Shu; Xiao, Tongshu; Li, Youbin

2014-03-01

Factor Xa (FXa) plays an important role in blood coagulation. This study investigated glycyrrhetinic acid, a small molecule derived from Chinese herbs, and whether it has a direct inhibitory effect on FXa to display its anticoagulant activity. Enzyme activities of FXa, plasmin, trypsin and thrombin, inhibition of FXa enzyme kinetics and plasma clotting time by glycyrrhentinic acid were performed in vitro. A rat tail-bleeding model and a rat venous stasis model were also used to evaluate in vivo tail-bleeding time and thrombus formation, respectively. Glycyrrhetinic acid in vitro directly inhibited FXa uncompetitivly with IC50 of 32.6 ± 1.24 μmol/L, and displayed 2-, 14- and 20-fold selectivity for FXa when compared to plasmin, thrombin and trypsin, respectively. The plasma clotting time was increased in a dose-dependent manner. The prothrombin time doubled (PT2), when the concentration of glycyrrhetinic acid reached 2.02 mmol/L. During in vivo experiments intragastric administration of glycyrrhetinic acid caused a dose-dependent reduction in thrombus weight on the rat venous stasis model (all P<0.05). 50 mg/kg glycyrrhetinic acid resulted in 34.8% of venous thrombus weight lost, compared to the control. In addition, 200, 300 and 400 mg/kg doses of glycyrrhetinic acid caused a moderate hemorrhagic effect in the rat tail-bleeding model by prolonging bleeding time 1.1-, 1.5- and 1.9-fold compared to the control, respectively. Glycyrrhetinic acid is a direct inhibitor of FXa that is effective by oral administration, and with further research could be used to treat blood coagulation disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Molecular genetic analysis for a pedigree with severe hereditary coagulation factor VII deficiency].

PubMed

Ding, Qiu-lan; Wang, Hong-li; Wang, Xue-feng; Wang, Ming-shan; Fu, Qi-hua; Wu, Wen-man; Hu, Yi-qun; Wang, Zhen-yi

2003-10-01

To identify the genetic mutations of a severe inherited coagulation factor VII (FVII) deficiency pedigree. The diagnosis was validated by coagulant and haemostatic parameters. FVII gene mutations were screened in the propositus and his family members by DNA direct sequencing and confirmed by digestions of the restriction enzymes of the PCR production. Two heterozygous missense mutations were found in the propositus of the pedigree: a G to T transversion at position 9482 in exon 6 and a C to T mutation at position 11348 in exon 8 resulting in the amino acid substitution of Arg152 with Leu and Arg304 with Trp, respectively. A heterozygous single nucleotide deletion (C) at position 11487-11489(CCC) within exon 8 was identified, which predicted the frameshift mutation at position His351 followed by the changes of six corresponding amino acids and appearance of a premature protein caused by stop codon. The heterozygous mutations identified in the proband were derived from his father (Arg152 to Leu) and his mother (Arg304 to Trp mutation) and a heterozygous deletion (C) at position 11487-9(CCC). By tracing the other pedigree members, it was found that his grandmother had a heterozygous mutation of Arg304Trp and a heterozygous polymorphism of Arg353Gln and his grandfather had a heterozygous Arg152Leu mutation. Three heterozygous mutations were found in a pedigree with hereditary coagulation factor VII deficiency. Arg152Leu and deletion C at position 11487-9(CCC) were novel mutations.

Transforming growth factor-β1 induces expression of human coagulation factor XII via Smad3 and JNK signaling pathways in human lung fibroblasts.

PubMed

Jablonska, Ewa; Markart, Philipp; Zakrzewicz, Dariusz; Preissner, Klaus T; Wygrecka, Malgorzata

2010-04-09

Coagulation factor XII (FXII) is a liver-derived serine protease involved in fibrinolysis, coagulation, and inflammation. The regulation of FXII expression is largely unknown. Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that has been linked to several pathological processes, including tissue fibrosis by modulating procoagulant and fibrinolytic activities. This study investigated whether TGF-beta1 may regulate FXII expression in human lung fibroblasts. Treatment of human lung fibroblasts with TGF-beta1 resulted in a time-dependent increase in FXII production, activation of p44/42, p38, JNK, and Akt, and phosphorylation and translocation into the nucleus of Smad3. However, TGF-beta1-induced FXII expression was repressed only by the JNK inhibitor and JNK and Smad3 antisense oligonucleotides but not by MEK, p38, or phosphoinositide 3-kinase blockers. JNK inhibition had no effect on TGF-beta1-induced Smad3 phosphorylation, association with Smad4, and its translocation into the nucleus but strongly suppressed Smad3-DNA complex formation. FXII promoter analysis revealed that the -299/+1 region was sufficient for TGF-beta1 to induce FXII expression. Sequence analysis of this region detected a potential Smad-binding element at position -272/-269 (SBE-(-272/-269)). Chromatin immunoprecipitation and streptavidin pulldown assays demonstrated TGF-beta1-dependent Smad3 binding to SBE-(-272/-269). Mutation or deletion of SBE-(-272/-269) substantially reduced TGF-beta1-mediated activation of the FXII promoter. Clinical relevance was demonstrated by elevated FXII levels and its co-localization with fibroblasts in the lungs of patients with acute respiratory distress syndrome. Our results show that JNK/Smad3 pathway plays a critical role in TGF-beta1-induced FXII expression in human lung fibroblasts and implicate its possible involvement in pathological conditions characterized by elevated TGF-beta1 levels.

Effects of Rivaroxaban on Platelet Activation and Platelet–Coagulation Pathway Interaction

PubMed Central

Heitmeier, Stefan; Laux, Volker

2015-01-01

Introduction: Activation of coagulation and platelets is closely linked, and arterial thrombosis involves coagulation activation as well as platelet activation and aggregation. In these studies, we investigated the possible synergistic effects of rivaroxaban in combination with antiplatelet agents on thrombin generation and platelet aggregation in vitro and on arterial thrombosis and hemostasis in rat models. Materials and Methods: Thrombin generation was measured by the Calibrated Automated Thrombogram method (0.5 pmol/L tissue factor) using human platelet-rich plasma (PRP) spiked with rivaroxaban (15, 30, or 60 ng/mL), ticagrelor (1.0 µg/mL), and acetylsalicylic acid (ASA; 100 µg/mL). Tissue factor-induced platelet aggregation was measured in PRP spiked with rivaroxaban (15 or 30 ng/mL), ticagrelor (1 or 3 µg/mL), or a combination of these. An arteriovenous (AV) shunt model in rats was used to determine the effects of rivaroxaban (0.01, 0.03, or 0.1 mg/kg), clopidogrel (1 mg/kg), ASA (3 mg/kg), and combinations on arterial thrombosis. Results: Rivaroxaban inhibited thrombin generation in a concentration-dependent manner and the effect was enhanced with ticagrelor and ticagrelor plus ASA. Rivaroxaban and ticagrelor also concentration-dependently inhibited tissue factor-induced platelet aggregation, and their combination increased the inhibition synergistically. In the AV shunt model, rivaroxaban dose-dependently reduced thrombus formation. Combining subefficacious or weakly efficacious doses of rivaroxaban with ASA or ASA plus clopidogrel increased the antithrombotic effect. Conclusion: These data indicate that the combination of rivaroxaban with single or dual antiplatelet agents works synergistically to reduce platelet activation, which may in turn lead to the delayed/reduced formation of coagulation complexes and vice versa, thereby enhancing antithrombotic potency. PMID:25848131

In Vitro Assessment of Nanoparticle Effects on Blood Coagulation.

PubMed

Potter, Timothy M; Rodriguez, Jamie C; Neun, Barry W; Ilinskaya, Anna N; Cedrone, Edward; Dobrovolskaia, Marina A

2018-01-01

Blood clotting is a complex process which involves both cellular and biochemical components. The key cellular players in the blood clotting process are thrombocytes or platelets. Other cells, including leukocytes and endothelial cells, contribute to clotting by expressing the so-called pro-coagulant activity (PCA) complex on their surface. The biochemical component of blood clotting is represented by the plasma coagulation cascade, which includes plasma proteins also known as coagulation factors. The coordinated interaction between platelets, leukocytes, endothelial cells, and plasma coagulation factors is necessary for maintaining hemostasis and for preventing excessive bleeding. Undesirable activation of all or some of these components may lead to pathological blood coagulation and life-threatening conditions such as consumptive coagulopathy or disseminated intravascular coagulation (DIC). In contrast, unintended inhibition of the coagulation pathways may lead to hemorrhage. Thrombogenicity is the property of a test material to induce blood coagulation by affecting one or more elements of the clotting process. Anticoagulant activity refers to the property of a test material to inhibit coagulation. The tendency to cause platelet aggregation, perturb plasma coagulation, and induce leukocyte PCA can serve as an in vitro measure of a nanomaterial's likelihood to be pro- or anticoagulant in vivo. This chapter describes three procedures for in vitro analyses of platelet aggregation, plasma coagulation time, and activation of leukocyte PCA. Platelet aggregation and plasma coagulation procedures have been described earlier. The revision here includes updated details about nanoparticle sample preparation, selection of nanoparticle concentration for the in vitro study, and updated details about assay controls. The chapter is expanded to describe a method for the leukocyte PCA analysis and case studies demonstrating the performance of these in vitro assays.

An exploratory factor analysis of inflammatory and coagulation markers associated with femoral artery atherosclerosis in the San Diego Population Study.

PubMed

Egnot, Natalie Suder; Barinas-Mitchell, Emma; Criqui, Michael H; Allison, Matthew A; Ix, Joachim H; Jenny, Nancy S; Wassel, Christina L

2018-04-01

Several biomarkers of inflammation and coagulation have been implicated in lower extremity atherosclerosis. We utilized an exploratory factor analysis (EFA) to identify distinct factors derived from circulating inflammatory and coagulation biomarkers then examined the associations of these factors with measures of lower extremity subclinical atherosclerosis, including the ankle-brachial index (ABI), common and superficial femoral intima-media thickness (IMT), and atherosclerotic plaque presence, burden, and characteristics. The San Diego Population Study (SDPS) is a prospective, community-living, multi-ethnic cohort of 1103 men and women averaged age 70. Regression analysis was used to assess cross-sectional associations between the identified groupings of biomarkers (factors) and the ABI and femoral artery atherosclerosis measurements. Two biomarker factors emerged from the factor analysis. Factor 1 consisting of C-reactive protein (CRP), interleukin (IL)-6, and fibrinogen was significantly associated with higher odds (OR = 1.99, p < 0.01) of a borderline ABI value (0.91-0.99), while Factor 2 containing D-dimer and pentraxin (PTX)-3 was significantly associated with higher common femoral artery (CFA) IMT (β = 0.23, p < 0.01) and lower ABI (β = -0.03, p < 0.01). Two groupings of biomarkers were identified via EFA of seven circulating biomarkers of inflammation and coagulation. These distinct groups are differentially associated with markers of lower extremity subclinical atherosclerosis. Our findings suggest that high inflammatory and coagulation burden were better markers of more severe lower-extremity disease as indicated by low ABI rather than early atherosclerotic lesion development in the femoral artery. Copyright © 2018 Elsevier Ltd. All rights reserved.

Coagulation Profile as a Risk Factor for 30-Day Morbidity and Mortality Following Posterior Lumbar Fusion.

PubMed

Bronheim, Rachel S; Oermann, Eric K; Cho, Samuel K; Caridi, John M

2017-06-15

A retrospective cohort study. The aim of this study was to identify associations between abnormal coagulation profile and postoperative morbidity and mortality in patients undergoing posterior lumbar fusion (PLF). The literature suggests that abnormal coagulation profile is associated with postoperative complications, notably the need for blood transfusion. However, there is little research that directly addresses the influence of coagulation profile on postoperative complications following PLF. The American College of Surgeons National Surgical Quality Improvement Program database (ACS-NSQIP) was utilized to identify patients undergoing PLF between 2006 and 2013. Nine thousand two hundred ninety-five patients met inclusion criteria. Multivariate analysis was utilized to identify associations between abnormal coagulation profile and postoperative complications. Low platelet count was an independent risk factor for organ space surgical site infections (SSIs) [odds ratio (OR) = 6.0, P < 0.001], ventilation >48 hours (OR = 4.5, P = 0.002), Acute renal failure (OR = 5.8, P = 0.007), transfusion (OR = 1.6, P < 0.001), sepsis (OR = 2.2, P = 0.037), reoperation (OR = 2.5, P = 0.001), and death (OR = 3.7, P = 0.049). High partial thromboplastin time (PTT) was an independent risk factor for ventilation >48 hours (OR = 5.6, P = 0.002), cerebrovascular accident (CVA)/stroke with neurological deficit (OR = 5.1, P = 0.011), cardiac arrest (OR = 5.4, P = 0.030), transfusion (OR = 1.5, P = 0.020), and death (OR = 4.5, P = 0.050). High International Normalized Ration (INR) was an independent risk factor for pneumonia (OR = 8.7, P = 0.001), pulmonary embolism (OR = 5.6, P = 0.021), deep venous thrombosis/Thrombophlebitis (OR = 4.8, P = 0.011), septic shock (OR = 8.4, P = 0.048), and death (OR = 9.8, P = 0.034). Bleeding disorder was an

The feed gas composition determines the degree of physical plasma-induced platelet activation for blood coagulation

NASA Astrophysics Data System (ADS)

Bekeschus, Sander; Brüggemeier, Janik; Hackbarth, Christine; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Partecke, Lars-Ivo; van der Linde, Julia

2018-03-01

Cold atmospheric (physical) plasma has long been suggested to be a useful tool for blood coagulation. However, the clinical applicability of this approach has not been addressed sufficiently. We have previously demonstrated the ability of a clinically accepted atmospheric pressure argon plasma jet (kINPen® MED) to coagulate liver incisions in mice with similar performance compared to the gold standard electrocauterization. We could show that plasma-mediated blood coagulation was dependent on platelet activation. In the present work, we extended on this by investigating kINPen®-mediated platelet activation in anticoagulated human donor blood ex vivo. With focus on establishing high-throughput, multi-parametric platelet activation assays and performing argon feed gas parameter studies we achieved the following results: (i) plasma activated platelets in heparinized but not in EDTA-anticoagulated blood; (ii) plasma decreased total platelet counts but increased numbers of microparticles; (iii) plasma elevated the expression of several surface activation markers on platelets (CD62P, CD63, CD69, and CD41/61); (iv) in platelet activation, wet and dry argon plasma outperformed feed gas admixtures with oxygen and/or nitrogen; (v) plasma-mediated platelet activation was accompanied by platelet aggregation. Platelet aggregation is a necessary requirement for blood clot formation. These findings are important to further elucidate molecular details and clinical feasibility of cold physical plasma-mediated blood coagulation.

Adhesion of Blood Clots Can Be Enhanced When Copolymerized with a Macromer That Is Crosslinked by Coagulation Factor XIIIa.

PubMed

Chan, Karen Y T; Zhao, Chunyi; Siren, Erika M J; Chan, Jeanne C Y; Boschman, Jeffrey; Kastrup, Christian J

2016-06-13

The adhesion of blood clots to blood vessels, such as through the adhesion of fibrin, is essential in hemostasis. While numerous strategies for initiating clot formation and preventing clot lysis are being developed to create improved hemostatic agents, strategies for enhancing clot adhesion have not been widely explored. Here, we show that adhesion of blood clots can be increased by adding a previously characterized synthetic polymer that is crosslinked by coagulation factor XIIIa during clotting. Addition of the polymer to normal plasma increased the adhesive strength of clots by 2-fold. It also recovered the adhesive strength of nonadhesive fibrinogen-deficient whole blood clots from <0.06 kPa to 1.9 ± 0.14 kPa, which is similar to the adhesive strength of a fibrinogen-rich clot (1.8 ± 0.64 kPa). The polymer also enabled plasma clots to remain adhered under fibrinolytic conditions. By demonstrating that the adhesive strength of clots can be increased with a synthetic material, this provides a potential strategy for creating advanced hemostatic materials, such as treatments for fibrinogen deficiency in trauma-induced coagulopathy.

Fish as bioreactors: transgene expression of human coagulation factor VII in fish embryos.

PubMed

Hwang, Gyulin; Müller, Ferenc; Rahman, M Aziz; Williams, Darren W; Murdock, Paul J; Pasi, K John; Goldspink, Geoffrey; Farahmand, Hamid; Maclean, Norman

2004-01-01

A plasmid containing human coagulation factor VII (hFVII) complementary DNA regulated by a cytomegalovirus promoter was microinjected into fertilized eggs of zebrafish, African catfish, and tilapia. The active form of hFVll was detected in the fish embryos by various assays. This positive expression of human therapeutic protein in fish embryos demonstrates the possibility of exploitation of transgenic fish as bioreactors.

Model of a ternary complex between activated factor VII, tissue factor and factor IX.

PubMed

Chen, Shu-wen W; Pellequer, Jean-Luc; Schved, Jean-François; Giansily-Blaizot, Muriel

2002-07-01

Upon binding to tissue factor, FVIIa triggers coagulation by activating vitamin K-dependent zymogens, factor IX (FIX) and factor X (FX). To understand recognition mechanisms in the initiation step of the coagulation cascade, we present a three-dimensional model of the ternary complex between FVIIa:TF:FIX. This model was built using a full-space search algorithm in combination with computational graphics. With the known crystallographic complex FVIIa:TF kept fixed, the FIX docking was performed first with FIX Gla-EGF1 domains, followed by the FIX protease/EGF2 domains. Because the FIXa crystal structure lacks electron density for the Gla domain, we constructed a chimeric FIX molecule that contains the Gla-EGF1 domains of FVIIa and the EGF2-protease domains of FIXa. The FVIIa:TF:FIX complex has been extensively challenged against experimental data including site-directed mutagenesis, inhibitory peptide data, haemophilia B database mutations, inhibitor antibodies and a novel exosite binding inhibitor peptide. This FVIIa:TF:FIX complex provides a powerful tool to study the regulation of FVIIa production and presents new avenues for developing therapeutic inhibitory compounds of FVIIa:TF:substrate complex.

Coagulation Testing in the Core Laboratory.

PubMed

Winter, William E; Flax, Sherri D; Harris, Neil S

2017-11-08

Primary hemostasis begins with endothelial injury. VWF, produced by endothelial cells, binds to platelets and links them to subendothelial collagen. Platelet-derived ADP and thromboxane activate non-adhered platelets via their GPIIb/IIIa receptors, allowing these platelets to participate in platelet aggregation. Secondary hemostasis is initiated with the binding of factor VII to extravascular tissue factor (TF). Factors II, VII, IX and X are vitamin K-dependent factors. The role of vitamin K is to assist in the addition of gamma carboxylate groups to glutamic acids in the "GLA" domains of these factors.In vitro the intrinsic pathway is initiated when fresh whole blood is placed in a glass tube. The negative charge of the glass initiates the "contact pathway" where FXII is activated and then FXIa cleaves FIX to FIXa. The extrinsic pathway is triggered when tissue factor, phospholipid and calcium are added to plasma anticoagulated with citrate. In vitro, FVII is activated to FVIIa, and TF-FVIIa preferentially converts FX to FXa activating the common pathway.The prothrombin time is commonly used to monitor warfarin anticoagulant therapy. To correct for differences in reagent and instrument, the international normalized ratio was developed to improve standardization of PT reporting globally. The activated partial thromboplastin time (aPTT) is used to evaluate the intrinsic and common pathways of coagulation. The aPTT is useful clinically as a screening test for inherited and acquired factor deficiencies as well as to monitor unfractionated heparin therapy although the anti-Xa assay is now the preferred measure of the effects of unfractionated heparin. The Clauss assay is the most commonly performed fibrinogen assay and uses diluted plasma where clotting is initiated with a high concentration of reagent thrombin.The mixing study assists in the assessment of an abnormally prolonged PT or aPTT. An equal volume of citrated patient plasma is mixed with normal pooled plasma

Uniqueness of Mass-Conserving Self-similar Solutions to Smoluchowski's Coagulation Equation with Inverse Power Law Kernels

NASA Astrophysics Data System (ADS)

Laurençot, Philippe

2018-03-01

Uniqueness of mass-conserving self-similar solutions to Smoluchowski's coagulation equation is shown when the coagulation kernel K is given by K(x,x_*)=2(x x_*)^{-α } , (x,x_*)\\in (0,∞)^2 , for some α >0.

Coagulation Profile as a Risk Factor for 30-day Morbidity Following Cervical Laminectomy and Fusion.

PubMed

Bronheim, Rachel S; Oermann, Eric K; Cho, Samuel K; Caridi, John M

2018-02-15

Retrospective analysis of prospectively collected data. The aim of this study was to determine the ability of abnormal coagulation profile to predict adverse events following posterior cervical laminectomy and fusion (PCLF). PCLF is an increasingly common procedure used to treat a variety of traumatic and degenerative spinal conditions. Abnormal coagulation profile is associated with postoperative adverse events, including blood transfusion. There is a paucity of literature that specifically addresses the relationship between coagulation profile and complications following PCLF. ACS-NSQIP was utilized to identify patients undergoing PCLF between 2006 and 2013. A total of 3546 patients met inclusion criteria. Multivariate analysis was utilized to identify associations between abnormal coagulation profile and postoperative complications. Membership in the low-platelet cohort was an independent risk factor for myocardial infarction (Odds Ratio (OR) = 5.4 [1.0, 29.1], P = 0.049) and bleeding transfusion (OR = 2.0 [1.2, 3.4], P = 0.011). Membership in the high international normalized ratio group was an independent risk factor for pneumonia (OR = 6.3 [2.5, 16.1], P < 0.001), ventilation >48 hours (OR = 6.5 [2.3, 18.4], P < 0.001), organ space surgical site infection (OR = 11.1 [2.1, 57.3], P = 0.004), urinary tract infection (OR = 3.0 [1.2, 8.0], P = 0.024), bleeding transfusion (OR = 6.0 [3.4, 10.7], P < 0.001), sepsis (OR = 5.1 [1.6, 16.4], P = 0.006), and septic shock (OR = 6.8 [1.7, 27.4], P = 0.007). Membership in the bleeding disorders cohort was an independent predictor of unplanned intubation (OR = 3.2 [1.1, 9.5], P = 0.041), pneumonia (OR = 2.9 [1.2, 7.2], P = 0.023), ventilation >48 hours (OR = 4.8 [1.9, 12.4], P = 0.001), cerebrovascular accident/stroke with neurological deficit (OR = 24.8 [2.9, 210.6], P = 0.003), bleeding transfusion (OR = 2.1 [1

Diagnostic Error of a Patient with Combined Inherited Factor VII and Factor X Deficiency due to Accidental Ingestion of a Diphacinone Rodenticide.

PubMed

Li, Min; Jin, Yanhui; Wang, Mingshan; Xie, Yaosheng; Ding, Hongxiang

2016-11-01

To explore the characteristics of laboratory examination and confirm the diagnosis of a patient with combined inherited FVII and FX deficiency after he ingested diphacinone rodenticide accidentally. The coagulant parameter screening tests and coagulation factor activities were tested many times in the patient due to accidental ingestion of a diphacinone rodenticide. After the patient was treated for more than one year, gene analysis of correlated coagulation factors was analyzed in the patient and other family members by DNA direct sequencing. 106 persons were selected as controls from routine health examinations. After the patient was admitted to hospital, routine coagulation screening tests revealed the prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT) and low levels of vitamin K-dependent coagulation factors (FII, FVII, FIX, FX) activity, which was 102.4 seconds, 88.5 seconds, 7%, 3%, 8%, and 2%, respectively. During more than one year of treatment, the value of PT and APTT still showed significantly prolonged activity and FVII and FX activity levels were about 5%. While FII and FIX activity levels were in the normal range after 12 weeks of treatment. Two homozygous mutations, g.11267C>T of F7 gene resulting in the substitution Arg277Cys and g.28139G>T of F10 gene leading to the substitution Val384Phe, were identified in the patient. The patient's parents and sister was heterozygous for Arg277Cys and Val384Phe mutations. FVII and FX antigen levels in the patient were 7% and 30%, respectively. There were many similarities in the characteristics of laboratory examination between combined inherited FVII and FX deficiency and acquired vitamin K deficiency. The best way to identify them was gene analysis.

Effects of Oritavancin on Coagulation Tests in the Clinical Laboratory.

PubMed

Belley, Adam; Robson, Richard; Francis, John L; Adcock, Dorothy M; Tiefenbacher, Stefan; Rubino, Christopher M; Moeck, Greg; Sylvester, David; Dudley, Michael N; Loutit, Jeffery

2017-02-01

Previous studies have shown that some lipoglycopeptide and lipopeptide antimicrobial agents may cause falsely elevated values for some phospholipid-dependent coagulation tests. The effect of oritavancin, a lipoglycopeptide antibiotic, on coagulation test results was explored using pooled human plasma samples spiked with drug and in a clinical study after an infusion of a single 1,200-mg intravenous dose of oritavancin in normal healthy volunteers. Pooled plasma with oritavancin added ex vivo showed concentration-dependent prolongation of prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), and dilute Russell viper venom time (DRVVT) test results. In contrast, oritavancin had no effect on the activated protein C resistance assay, chromogenic anti-factor Xa assay (anti-FXa), thrombin time, and an immunoassay for the laboratory diagnosis of heparin-induced thrombocytopenia. In participants that received a single dose of oritavancin, elevations in PT/INR result, aPTT, DRVVT, activated clotting time, and silica clotting time occurred, with the maximum times to resolution of test interference determined to be 12, 120, 72, 24, and 18 h, respectively. The anti-FXa assay was unaffected, whereas transient elevations in D dimer levels were observed in 30% of participants, with a maximum time to resolution of 72 h. Although oritavancin has no impact on the coagulation system in vivo, a single dose of oritavancin can produce falsely elevated values of some coagulation tests used to monitor hemostasis. The interference of oritavancin on affected tests is transient, and the test results revert to normal ranges within specified times after dosing. Copyright © 2017 American Society for Microbiology.

Effects of Oritavancin on Coagulation Tests in the Clinical Laboratory

PubMed Central

Robson, Richard; Francis, John L.; Adcock, Dorothy M.; Tiefenbacher, Stefan; Rubino, Christopher M.; Moeck, Greg; Sylvester, David; Dudley, Michael N.; Loutit, Jeffery

2016-01-01

ABSTRACT Previous studies have shown that some lipoglycopeptide and lipopeptide antimicrobial agents may cause falsely elevated values for some phospholipid-dependent coagulation tests. The effect of oritavancin, a lipoglycopeptide antibiotic, on coagulation test results was explored using pooled human plasma samples spiked with drug and in a clinical study after an infusion of a single 1,200-mg intravenous dose of oritavancin in normal healthy volunteers. Pooled plasma with oritavancin added ex vivo showed concentration-dependent prolongation of prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), and dilute Russell viper venom time (DRVVT) test results. In contrast, oritavancin had no effect on the activated protein C resistance assay, chromogenic anti-factor Xa assay (anti-FXa), thrombin time, and an immunoassay for the laboratory diagnosis of heparin-induced thrombocytopenia. In participants that received a single dose of oritavancin, elevations in PT/INR result, aPTT, DRVVT, activated clotting time, and silica clotting time occurred, with the maximum times to resolution of test interference determined to be 12, 120, 72, 24, and 18 h, respectively. The anti-FXa assay was unaffected, whereas transient elevations in D dimer levels were observed in 30% of participants, with a maximum time to resolution of 72 h. Although oritavancin has no impact on the coagulation system in vivo, a single dose of oritavancin can produce falsely elevated values of some coagulation tests used to monitor hemostasis. The interference of oritavancin on affected tests is transient, and the test results revert to normal ranges within specified times after dosing. PMID:27956417

Plasmodium falciparum-infected erythrocytes induce Tissue Factor expression in endothelial cells and support the assembly of multimolecular coagulation complexes

PubMed Central

Francischetti, Ivo MB; Seydel, Karl B; Monteiro, Robson Q; Whitten, Richard O; Erexson, Cindy R; Noronha, Almério LL; Ostera, Graciela R.; Kamiza, Steve B; Molyneux, Malcolm E; Ward, Jerrold M; Taylor, Terrie E

2010-01-01

Summary Background Plasmodium falciparum malaria infects 300–500 million people every year causing 1–2 million deaths annually. Evidence of a coagulation disorder, activation of endothelial cells (EC) and increase in inflammatory cytokines are often present in malaria. Objectives We have asked whether parasitized red blood cells (pRBC) interaction with EC induces Tissue Factor expression in vitro and in vivo. The potential of phosphatidylserine-containing pRBC to support the assembly of blood coagulation complexes was also investigated. Results We demonstrate that mature forms of pRBC induce functional expression of tissue factor (TF) by endothelial cells (EC) in vitro with productive assembly of the extrinsic Xnase complex and initiation of the coagulation cascade. Late stage pRBC also support the prothrombinase and intrinsic Xnase complex formation in vitro, and may function as activated platelets in the amplification phase of the blood coagulation. Notably, postmortem brain sections obtained from P. falciparum-infected children who died from Cerebral Malaria and other causes display a consistent staining for TF in the EC. Conclusions These findings place TF expression by endothelium and the amplification of the coagulation cascade by pRBC and/or activated platelets as potentially critical steps in the pathogenesis of malaria. Furthermore, it may allow investigators to test other therapeutic alternatives targeting TF or modulators of EC function in the treatment of malaria and/or its complications. PMID:17002660

Effects of dairy factory, milk casein content and titratable acidity on coagulation properties in Trentingrana dairy industry.

PubMed

Penasa, Mauro; Toffanin, Valentina; Cologna, Nicola; Cassandro, Martino; De Marchi, Massimo

2016-05-01

The objective of the present study was to investigate the effect of environmental factors, milk casein content and titratable acidity on milk coagulation properties (MCP) of samples routinely collected in the Trento province (northeast Italy) under field conditions. Rennet coagulation time (RCT, min), curd-firming time (k20, min) and curd firmness (a30, mm) were determined by Formagraph on 14 971 samples from 635 herds associated to 17 dairy factories. Besides MCP, fat, protein, and casein percentages, titratable acidity (TA), and somatic cell and bacterial counts were available. A standardised index of milk aptitude to coagulate (IAC) was derived using information of RCT and a30. An analysis of variance was conducted on MCP and IAC using a fixed effects linear model. Approximately 3% of milk samples did not form a curd within the testing time (30 min) and k20 was missing for 26% of milks. The percentage of samples without information on k20 largely differed among dairy factories (1·7-20·9%). Significant differences were estimated between the best and the worst dairy factory for RCT (-2 min), k20 (-1·2 min), a30 (+3·4 mm) and IAC (+2·6 points). Milk casein content and TA were important factors in explaining the variation of MCP and IAC, supporting the central role of these two traits on technological properties. The Trento province is heterogeneous in terms of dairy systems and this could explain the differences among dairy factories.

Dietary vitamin K variability affects International Normalized Ratio (INR) coagulation indices.

PubMed

Couris, Rebecca; Tataronis, Gary; McCloskey, William; Oertel, Lynn; Dallal, Gerard; Dwyer, Johanna; Blumberg, Jeffrey B

2006-03-01

Changes in daily vitamin K intake may contribute to marked variations in the International Normalized Ratio (INR) coagulation index in patients receiving oral warfarin anticoagulant therapy, with potentially serious adverse outcomes. Thus, patients receiving warfarin therapy are routinely counseled regarding this drug-nutrient interaction and are instructed to maintain consistent vitamin K intakes, though little quantitative information about this relationship is available. To determine the quantitative impact of variability in dietary vitamin K(1) (phylloquinone) intake, assessed by a validated patient self-monitoring instrument, on weekly INR in patients receiving warfarin anticoagulant therapy. A prospective dietary assessment study was conducted at the Massachusetts General Hospital in Boston. Sixty outpatients (37 males and 23 females) were selected with a mean age 60.3 +/- 16.8 years, who began oral warfarin anticoagulant therapy within 14 days prior to their first clinic visit to an outpatient anticoagulation therapy unit. Exclusion criteria included more than 2 drinks of alcohol per day, inability to speak English, and concurrent disease states affecting warfarin therapy such as liver disease and terminal illness. Over the five-week study period, participants recorded daily intakes in specified amounts of all food items appearing on a validated dietary self-assessment tool. Concomitant use of prescription and/or non-prescription medications was also obtained. Concurrent daily warfarin dose and adherence to the drug regimen, concomitant use of prescription and/or non-prescription medications known to interact with warfarin, and weekly INR were obtained. Week-to-week changes in vitamin K intake, warfarin dose, and INR were determined and cross-correlated. Forty-three patients (28 males and 15 females) completed the study and 17 dropped out. Pearson's correlation coefficient revealed the variability in INR and changes in vitamin K intake were inversely

Histology assessment of bipolar coagulation and argon plasma coagulation on digestive tract

PubMed Central

Garrido, Teresa; Baba, Elisa R; Wodak, Stephanie; Sakai, Paulo; Cecconello, Ivan; Maluf-Filho, Fauze

2014-01-01

AIM: To analyze the effect of bipolar electrocoagulation and argon plasma coagulation on fresh specimens of gastrointestinal tract. METHODS: An experimental evaluation was performed at Hospital das Clinicas of the University of São Paulo, on 31 fresh surgical specimens using argon plasma coagulation and bipolar electrocoagulation at different time intervals. The depth of tissue damage was histopathologically analyzed by single senior pathologist unaware of the coagulation method and power setting applied. To analyze the results, the mucosa was divided in superficial mucosa (epithelial layer of the esophagus and superficial portion of the glandular layer of the stomach and colon) intermediate mucosa (until the lamina propria of the esophagus and until the bottom of the glandular layer of the stomach and colon) and muscularis mucosa. Necrosis involvement of the layers was compared in several combinations of power and time interval. RESULTS: Involvement of the intermediate mucosa of the stomach and of the muscularis mucosa of the three organs was more frequent when higher amounts of energy were used with argon plasma. In the esophagus and in the colon, injury of the intermediate mucosa was frequent, even when small amounts of energy were used. The use of bipolar electrocoagulation resulted in more frequent involvement of the intermediate mucosa and of the muscularis mucosa of the esophagus and of the colon when higher amounts of energy were used. In the stomach, these involvements were rare. The risk of injury of the muscularis propria was significant only in the colon when argon plasma coagulation was employed. CONCLUSION: Tissue damage after argon plasma coagulation is deeper than bipolar electrocoagulation. Both of them depend on the amount of energy used. PMID:25031789

Quarantine versus pathogen-reduced plasma-coagulation factor content and rotational thromboelastometry coagulation.

PubMed

Theusinger, Oliver M; Goslings, David; Studt, Jan-Dirk; Brand-Staufer, Brigitte; Seifert, Burkhardt; Spahn, Donat R; Frey, Beat M

2017-03-01

Different types of fresh-frozen plasma (FFP) exist, and the concentrations of plasma proteins vary between individuals and blood groups. Furthermore, processing may also influence the content. Quarantine-stored plasma (qFFP) and plasma that was pathogen-reduced using blood-safety (Intercept) technology (piFFP) were analyzed regarding procoagulant and anticoagulant hemostasis proteins, including endogenous thrombin (thrombin-generation) potential (ETP). Thirty-five samples of each type of FFP were analyzed using only male Blood Group O donors. FFP units were stored frozen for comparable periods of time before plasma protein content was assessed. Once the units were thawed, all tests were completed within 4 hours. The results are presented as means ± standard deviations or as median (minimum; maximum) and were compared using independent-sample t tests (significance, p < 0.01). Significantly higher concentrations of adintegrin-like and metalloprotease with thrombospondin type-13 motifs (ADAMTS13), fibrinogen, Factor (F)V, FVIII, FXIII, protein S, protein S activity, antithrombin, microvesicle (<900 nm), and α2 antiplasmin were observed in qFFP. The variability of factors was significantly lower in piFFP. Tissue factor (TF) at 1 picomolar (pM) exhibited significantly longer lag time, a lower peak, lower ETP, and a lower velocity index in qFFP compared with piFFP. In TF at 5 pM, significant differences in lag time (longer in qFFP), velocity index (lower in qFFP), and peak (lower in qFFP) were observed. Rotational thromboelastometry revealed a significantly longer (p = 0.002) clot-formation time with intrinsic thromboelastometry for piFFP and a significantly shorter clotting time (p = 0.004) with thromboelastometry fibrinogen testing for piFFP. Pathogen reduction reduces procoagulant and anticoagulant coagulation factors as well as variability. A thrombin-generation assay showed no reduced ETP and no supraphysiological thrombin generation. None of the

The evolution of biomass-burning aerosol size distributions due to coagulation: dependence on fire and meteorological details and parameterization

NASA Astrophysics Data System (ADS)

Sakamoto, Kimiko M.; Laing, James R.; Stevens, Robin G.; Jaffe, Daniel A.; Pierce, Jeffrey R.

2016-06-01

Biomass-burning aerosols have a significant effect on global and regional aerosol climate forcings. To model the magnitude of these effects accurately requires knowledge of the size distribution of the emitted and evolving aerosol particles. Current biomass-burning inventories do not include size distributions, and global and regional models generally assume a fixed size distribution from all biomass-burning emissions. However, biomass-burning size distributions evolve in the plume due to coagulation and net organic aerosol (OA) evaporation or formation, and the plume processes occur on spacial scales smaller than global/regional-model grid boxes. The extent of this size-distribution evolution is dependent on a variety of factors relating to the emission source and atmospheric conditions. Therefore, accurately accounting for biomass-burning aerosol size in global models requires an effective aerosol size distribution that accounts for this sub-grid evolution and can be derived from available emission-inventory and meteorological parameters. In this paper, we perform a detailed investigation of the effects of coagulation on the aerosol size distribution in biomass-burning plumes. We compare the effect of coagulation to that of OA evaporation and formation. We develop coagulation-only parameterizations for effective biomass-burning size distributions using the SAM-TOMAS large-eddy simulation plume model. For the most-sophisticated parameterization, we use the Gaussian Emulation Machine for Sensitivity Analysis (GEM-SA) to build a parameterization of the aged size distribution based on the SAM-TOMAS output and seven inputs: emission median dry diameter, emission distribution modal width, mass emissions flux, fire area, mean boundary-layer wind speed, plume mixing depth, and time/distance since emission. This parameterization was tested against an independent set of SAM-TOMAS simulations and yields R2 values of 0.83 and 0.89 for Dpm and modal width, respectively. The

Dust Coagulation in Protoplanetary Accretion Disks

NASA Technical Reports Server (NTRS)

Schmitt, W.; Henning, Th.; Mucha, R.

1996-01-01

The time evolution of dust particles in circumstellar disk-like structures around protostars and young stellar objects is discussed. In particular, we consider the coagulation of grains due to collisional aggregation. The coagulation of the particles is calculated by solving numerically the non-linear Smoluchowski equation. The different physical processes leading to relative velocities between the grains are investigated. The relative velocities may be induced by Brownian motion, turbulence and drift motion. Starting from different regimes which can be identified during the grain growth we also discuss the evolution of dust opacities. These opacities are important for both the derivation of the circumstellar dust mass from submillimeter/millimeter continuum observations and the dynamical behavior of the disks. We present results of our numerical studies of the coagulation of dust grains in a turbulent protoplanetary accretion disk described by a time-dependent one-dimensional (radial) alpha-model. For several periods and disk radii, mass distributions of coagulated grains have been calculated. From these mass spectra, we determined the corresponding Rosseland mean dust opacities. The influence of grain opacity changes due to dust coagulation on the dynamical evolution of a protostellar disk is considered. Significant changes in the thermal structure of the protoplanetary nebula are observed. A 'gap' in the accretion disk forms at the very frontier of the coagulation, i.e., behind the sublimation boundary in the region between 1 and 5 AU.

Effects of an acidic environment on coagulation dynamics.

PubMed

Gissel, M; Brummel-Ziedins, K E; Butenas, S; Pusateri, A E; Mann, K G; Orfeo, T

2016-10-01

Essentials Acidosis, an outcome of traumatic injury, has been linked to impaired procoagulant efficiency. In vitro model systems were used to assess coagulation dynamics at pH 7.4 and 7.0. Clot formation dynamics are slightly enhanced at pH 7.0 in blood ex vivo. Acidosis induced decreases in antithrombin efficacy offset impairments in procoagulant activity. Background Disruption of hydrogen ion homeostasis is a consequence of traumatic injury often associated with clinical coagulopathy. Mechanisms by which acidification of the blood leads to aberrant coagulation require further elucidation. Objective To examine the effects of acidified conditions on coagulation dynamics using in vitro models of increasing complexity. Methods Coagulation dynamics were assessed at pH 7.4 and 7.0 as follows: (i) tissue factor (TF)-initiated coagulation proteome mixtures (±factor [F]XI, ±fibrinogen/FXIII), with reaction progress monitored as thrombin generation or fibrin formation; (ii) enzyme/inhibitor reactions; and (iii) TF-dependent or independent clot dynamics in contact pathway-inhibited blood via viscoelastometry. Results Rate constants for antithrombin inhibition of FXa and thrombin were reduced by ~ 25-30% at pH 7.0. At pH 7.0 (+FXI), TF-initiated thrombin generation showed a 20% increase in maximum thrombin levels and diminished thrombin clearance rates. Viscoelastic analyses showed a 25% increase in clot time and a 25% reduction in maximum clot firmness (MCF). A similar MCF reduction was observed at pH 7.0 when fibrinogen/FXIII were reacted with thrombin. In contrast, in contact pathway-inhibited blood (n = 6) at pH 7.0, MCF values were elevated 6% (95% confidence interval [CI]: 1%-11%) in TF-initiated blood and 15% (95% CI: 1%- 29%) in the absence of TF. Clot times at pH 7.0 decreased 32% (95% CI: 15%-49%) in TF-initiated blood and 51% (95% CI: 35%-68%) in the absence of TF. Conclusions Despite reported decreased procoagulant catalysis at pH 7.0, clot formation dynamics

[Influence of cytostatic combination therapy with vincristine sulphate and iphosphamide on blood coagulation].

PubMed

Neidhardt, B; Hartwich, G

1975-02-28

Disorders of blood coagulation were investigated before and during a cytostatic combination therapy with vincristine sulphate and iphosphamide (Asta Z 4942) in 12 patients with malignant tumours or haemoblastoses. Thromboplastin time, partial thromboplastin time, thrombin time, heat-dependent fibrin, clot retraction, and clotting factors II, V, VIII, IX, X, and the platelet count were determined. A change in the plasmatic coagulation system attributable to the combination therapy could not be demonstrated in any patient. The influence of the cytostatic combination on the platelet-dependent haemostasis was small; a decrease in platelet count could be observed in only one patient, in whom an additional causative damage to thrombopoiesis due to the underlying disease could be assumed. Regardless of the cytostatic therapy there were indications of a hypercoagulability in 10 patients. This explains the increased susceptibility of such patients for thromboses or consumption coagulopathy.

A small amount can make a difference: a prospective human study of the paradoxical coagulation characteristics of hemothorax.

PubMed

Smith, W Zachary; Harrison, Hannah B; Salhanick, Marc A; Higgins, Russell A; Ortiz, Alfonso; Olson, John D; Schwacha, Martin G; Harrison, Chantal R; Aydelotte, Jayson D; Stewart, Ronald M; Dent, Daniel L

2013-12-01

The evacuated hemothorax has been poorly described because it varies with time, it has been found to be incoagulable, and its potential effect on the coagulation cascade during autotransfusion is largely unknown. This is a prospective descriptive study of adult patients with traumatic chest injury necessitating tube thoracostomy. Pleural and venous samples were analyzed for coagulation, hematology, and electrolytes at 1 to 4 hours after drainage. Pleural samples were also analyzed for their effect on the coagulation cascade via mixing studies. Thirty-four subjects were enrolled with a traumatic hemothorax. The following measured coagulation factors were significantly depleted compared with venous blood: international normalized ratio (>9 vs 1.1) (P < .001) and activated partial thromboplastin time (aPTT) (>180 vs 24.5 seconds) (P < .001). Mixing studies showed a dose-dependent increase in coagulation dilutions through 1:8 (P < .05). An evacuated hemothorax does not vary in composition significantly with time and is incoagulable alone. Mixing studies with hemothorax plasma increased coagulation, raising safety concerns. Copyright © 2013 Elsevier Inc. All rights reserved.

Insulin-like growth factor binding protein-3 induces angiogenesis through IGF-I- and SphK1-dependent mechanisms.

PubMed

Granata, R; Trovato, L; Lupia, E; Sala, G; Settanni, F; Camussi, G; Ghidoni, R; Ghigo, E

2007-04-01

Angiogenesis is critical for development and repair, and is a prominent feature of many pathological conditions. Based on evidence that insulin-like growth factor binding protein (IGFBP)-3 enhances cell motility and activates sphingosine kinase (SphK) in human endothelial cells, we have investigated whether IGFBP-3 plays a role in promoting angiogenesis. IGFBP-3 potently induced network formation by human endothelial cells on Matrigel. Moreover, it up-regulated proangiogenic genes, such as vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP)-2 and -9. IGFBP-3 even induced membrane-type 1 MMP (MT1-MMP), which regulates MMP-2 activation. Decreasing SphK1 expression by small interfering RNA (siRNA), blocked IGFBP-3-induced network formation and inhibited VEGF, MT1-MMP but not IGF-I up-regulation. IGF-I activated SphK, leading to sphingosine-1-phosphate (S1P) formation. The IGF-I effect on SphK activity was blocked by specific inhibitors of IGF-IR, PI3K/Akt and ERK1/2 phosphorylation. The disruption of IGF-I signaling prevented the IGFBP-3 effect on tube formation, SphK activity and VEGF release. Blocking ERK1/2 signaling caused the loss of SphK activation and VEGF and IGF-I up-regulation. Finally, IGFBP-3 dose-dependently stimulated neovessel formation into subcutaneous implants of Matrigel in vivo. Thus, IGFBP-3 positively regulates angiogenesis through involvement of IGF-IR signaling and subsequent SphK/S1P activation.

Integration of coagulation and adsorption for removal of N-nitrosodimethylamine (NDMA) precursors from biologically treated municipal wastewater.

PubMed

Wang, Miaomiao; Meng, Yingjie; Ma, Defang; Wang, Yan; Li, Fengli; Xu, Xing; Xia, Chufan; Gao, Baoyu

2017-05-01

This study investigated the N-nitrosodimethylamine (NDMA) formation potential of various dissolved organic matter (DOM) fractions in biologically treated municipal wastewater by UF fractionation, XAD-8 resin adsorption isolation, and excitation and emission matrix (EEM) fluorescence spectroscopy. Removal of various NDMA precursor fractions was also analyzed to evaluate the efficiency of traditional water treatment processes (coagulation, adsorption, and coagulation-adsorption). Results showed that NDMA were mainly formed by low molecular weight (MW) fractions (<30 kDa) and hydrophilic fractions (HiS) in biologically treated municipal wastewater. Integrated coagulation-adsorption treatments showed the highest reduction capacity for NDMA formation potential (57%), followed by isolated adsorption treatment (50%) and isolated coagulation treatment (28%). The powdered activated carbon (PAC) adsorption process could reduce the high MW precursors (>30 kDa) by 48%, which was higher than other treatments. In contrast, the highest uptake (66%) of low MW precursors (<30 kDa) was achieved by the coagulation-adsorption process. All treatments preferentially removed the hydrophobic acids (HoA) fraction compared to other fractions. Coagulation could remove more fulvic acid-like substances and adsorption could remove more microbial by-products and aromatic proteins.

Synergistic effect of a factor Xa inhibitor, TAK-442, and antiplatelet agents on whole blood coagulation and arterial thrombosis in rats.

PubMed

Konishi, Noriko; Hiroe, Katsuhiko; Kawamura, Masaki

2010-08-01

Activated platelets facilitate blood coagulation by providing factor V and a procoagulant surface for prothrombinase. Here, we investigated the potential synergy of a potent factor Xa/prothrombinase inhibitor, TAK-442, plus aspirin or clopidogrel in preventing arterial thrombosis and whole blood coagulation. Thrombus formation was initiated by FeCl(3)-induced rat carotid injury. Bleeding time was evaluated with the rat tail transection model. Whole blood coagulation was assessed by thromboelastographic examination (TEG) for which blood obtained from control, aspirin-, or clopidogrel-treated rats was transferred to a TEG analyzer containing, collagen or adenosine diphosphate (ADP), and TAK-442 or vehicle. TAK-442 (3mg/kg, po), aspirin (100mg/kg, po) or clopidogrel (3mg/kg, po) alone had no significant effect on thrombus formation, whereas the combination of TAK-442 with aspirin and clopidogrel remarkably prolonged the time to thrombus formation without additional significant prolongation of bleeding time. TEG demonstrated that the onset of collagen-induced blood coagulation were slightly longer in aspirin-treated rats than control; however, when the blood from aspirin-treated rats was subsequently treated in vitro with 100 nM TAK-442, the onset of clotting was significantly prolonged. In contrast, only marginal prolongation was observed with TAK-442 treatment of blood from control animals. The onset time of ADP-induced blood coagulation was slightly longer in clopidogrel-treated rats compared with control, and it was further extended by TAK-442 treatment. These results demonstrate that blood coagulation can be markedly delayed by the addition of TAK-442 to antiplatelets treatment which could contribute to synergistic antithrombotic efficacy in these settings. (c) 2010 Elsevier Ltd. All rights reserved.

Absence of in vitro Procoagulant Activity in Immunoglobulin Preparations due to Activated Coagulation Factors

PubMed Central

Oviedo, Adriana E.; Bernardi, María E.; Guglielmone, Hugo A.; Vitali, María S.

2015-01-01

Summary Background Immunoglobulin (IG) products, including intravenous (IVIG) or subcutaneous (SCIG) immunoglobulins are considered safe and effective for medical therapy; however, a sudden and unexpected increase in thromboembolic events (TE) after administration of certain batches of IVIG products has been attributed to the presence of activated coagulation factors, mainly factor XIa. Our aims were to examine the presence of enduring procoagulant activity during the manufacturing process of IGs, with special focus on monitoring factor XIa, and to evaluate the presence of in vitro procoagulant activity attributed to coagulation factors in different lots of IVIG and SCIG. Methods Samples of different steps of IG purification, 19 lots of IVIG and 9 of SCIG were analyzed and compared with 1 commercial preparation of IVIG and 2 of SCIG, respectively. Factors II, VII, IX, XI and XIa and non-activated partial thromboplastin time (NAPTT) were assayed. Results The levels of factors II, VII, IX, X and XI were non-quantifiable once fraction II had been re-dissolved and in all analyzed lots of IVIG and SCIG. The level of factor XIa at that point was under the detection limits of the assay, and NAPTT yielded values greater than the control during the purification process. In SCIG, we detected higher concentrations of factor XIa in the commercial products, which reached values up to 5 times higher than the average amounts found in the 9 batches produced by UNC-Hemoderivados. Factor XIa in commercial IVIG reached levels slightly higher than those of the 19 batches produced by UNC-Hemoderivados. Conclusion IVIG and SCIG manufactured by UNC-Hemoderivados showed a lack of thrombogenic potential, as demonstrated not only by the laboratory data obtained in this study but also by the absence of any reports of TE registered by the post marketing pharmacovigilance department. PMID:26733772

Measurement of the coagulation dynamics of bovine liver using the modified microscopic Beer-Lambert law.

PubMed

Terenji, Albert; Willmann, Stefan; Osterholz, Jens; Hering, Peter; Schwarzmaier, Hans-Joachim

2005-06-01

During heating, the optical properties of biological tissues change with the coagulation state. In this study, we propose a technique, which uses these changes to monitor the coagulation process during laser-induced interstitial thermotherapy (LITT). Untreated and coagulated (water bath, temperatures between 35 degrees C and 90 degrees C for 20 minutes.) samples of bovine liver tissue were examined using a Nd:YAG (lambda = 1064 nm) frequency-domain reflectance spectrometer. We determined the time integrated intensities (I(DC)) and the phase shifts (Phi) of the photon density waves after migration through the tissue. From these measured quantities, the time of flight (TOF) of the photons and the absorption coefficients of the samples were derived using the modified microscopic Beer-Lambert law. The absorption coefficients of the liver samples decreased significantly with the temperature in the range between 50 degrees C and 70 degrees C. At the same time, the TOF of the investigated photos was found increased indicating an increased scattering. The coagulation dynamics could be well described using the Arrhenius formalism with the activation energy of 106 kJ/mol and the frequency factor of 1.59 x 10(13)/second. Frequency-domain reflectance spectroscopy in combination with the modified microscopic Beer-Lambert (MBL) is suitable to measure heat induced changes in the absorption and scattering properties of bovine liver in vitro. The technique may be used to monitor the coagulation dynamics during local thermo-coagulation in vivo. Copyright 2005 Wiley-Liss, Inc.

Blocking of platelets or intrinsic coagulation pathway-driven thrombosis does not prevent cerebral infarctions induced by photothrombosis.

PubMed

Kleinschnitz, Christoph; Braeuninger, Stefan; Pham, Mirko; Austinat, Madeleine; Nölte, Ingo; Renné, Thomas; Nieswandt, Bernhard; Bendszus, Martin; Stoll, Guido

2008-04-01

Models of photochemically-induced thrombosis are widely used in cerebrovascular research. Photothrombotic brain infarctions can be induced by systemic application of photosensitizing dyes followed by focal illumination of the cerebral cortex. Although the ensuing activation of platelets is well established, their contribution for thrombosis and tissue damage has not formally been proved. Infarction to the cerebral cortex was induced in mice by Rose Bengal and a cold light source. To assess the functional role of platelets, animals were platelet-depleted by anti-GPIbalpha antibodies or treated with GPIIb/IIIa-blocking F(ab)(2) fragments. The significance of the plasmatic coagulation cascade was determined by using blood coagulation factor XII (FXII)-deficient mice or heparin. Infarct development and infarct volumes were determined by serial MRI and conventional and electron microscopy. There was no difference in development and final size of photothrombotic infarctions in mice with impaired platelet function. Moreover, deficiency of FXII, which initiates the intrinsic pathway of coagulation and is essential for thrombus formation, or blockade of FXa, the key protease during the waterfall cascade of plasmatic coagulation, by heparin likewise did not affect lesion development. Our data demonstrate that platelet activation, factor XII-driven thrombus formation, and plasmatic coagulation pathways downstream of FX are not a prerequisite for ensuing tissue damage in models of photothrombotic vessel injury indicating that other pathomechanisms are involved. We suggest that this widely used model does not depend on platelet- or plasmatic coagulation-derived thrombosis.

Blood coagulation profiling in patients using optical thromboelastography (OTEG) (Conference Presentation)

NASA Astrophysics Data System (ADS)

Tripathi, Markandey M.; Tshikudi, Diane M.; Hajjarian, Zeinab; Van Cott, Elizabeth M.; Nadkarni, Seemantini K.

2016-02-01

Impaired blood coagulation is often associated with increased postoperative mortality and morbidity in cardiovascular patients. The capability for blood coagulation profiling rapidly at the bedside will enable the timely detection of coagulation defects and open the opportunity for tailoring therapy to correct specific coagulation deficits Optical Thromboelastography (OTEG), is an optical approach to quantify blood coagulation status within minutes using a few drops of whole blood. The goal of the current study is to evaluate the diagnostic accuracy of OTEG for rapid coagulation profiling in patients. In OTEG, temporal laser speckle intensity fluctuations from a drop of clotting blood are measured using a CMOS camera. To quantify coagulation status, the speckle intensity autocorrelation function is measured, the mean square displacement of scattering particles is extracted, and viscoelastic modulus (G), during coagulation is measured via the generalized Stokes-Einstein relation. By quantifying time-resolved changes in G, the coagulation parameters, reaction time (R), clot progression time (K), clot progression rate (Angle), and maximum clot strength (MA) are derived. In this study, the above coagulation parameters were measured using OTEG in 269 patients and compared with standard mechanical Thromboelastography (TEG). Our results showed a strong correlation between OTEG and TEG measurements for all parameters: R-time (R=0.80, p<0.001), clotting time (R=0.78, p<0.001), Angle (R=0.58, p<0.001), and MA (R=0.60, p<0.001). These results demonstrate the unique capability of OTEG for rapid quantification of blood coagulation status to potentially improve clinical capability for identifying impaired coagulation in cardiovascular patients at the point of care.

Clay-catalyzed reactions of coagulant polymers during water chlorination

USGS Publications Warehouse

Lee, J.-F.; Liao, P.-M.; Lee, C.-K.; Chao, H.-P.; Peng, C.-L.; Chiou, C.T.

2004-01-01

The influence of suspended clay/solid particles on organic-coagulant reactions during water chlorination was investigated by analyses of total product formation potential (TPFP) and disinfection by-product (DBP) distribution as a function of exchanged clay cation, coagulant organic polymer, and reaction time. Montmorillonite clays appeared to act as a catalytic center where the reaction between adsorbed polymer and disinfectant (chlorine) was mediated closely by the exchanged clay cation. The transition-metal cations in clays catalyzed more effectively than other cations the reactions between a coagulant polymer and chlorine, forming a large number of volatile DBPs. The relative catalytic effects of clays/solids followed the order Ti-Mont > Fe-Mont > Cu-Mont > Mn-Mont > Ca-Mont > Na-Mont > quartz > talc. The effects of coagulant polymers on TPFP follow the order nonionic polymer > anionic polymer > cationic polymer. The catalytic role of the clay cation was further confirmed by the observed inhibition in DBP formation when strong chelating agents (o-phenanthroline and ethylenediamine) were added to the clay suspension. Moreover, in the presence of clays, total DBPs increased appreciably when either the reaction time or the amount of the added clay or coagulant polymer increased. For volatile DBPs, the formation of halogenated methanes was usually time-dependent, with chloroform and dichloromethane showing the greatest dependence. ?? 2003 Elsevier Inc. All rights reserved.

Effect of flomoxef on blood coagulation and alcohol metabolism.

PubMed

Uchida, K; Matsubara, T

1991-01-01

The effect of flomoxef, a newly developed oxacephem antibiotic with an N-hydroxyethyltetrazolethiol (HTT) side chain, on blood coagulation and alcohol metabolism was compared with that of a series of cephalosporin antibiotics with N-methyltetrazolethiol (NMTT), thiadiazolethiol (TDT) or methylthiadiazolethiol (MTDT) side chains in position 3' of the cephalosporin nucleus known to cause hypoprothrombinemia and bleeding in patients who are malnourished, debilitated and/or of high age. A disulfiram-like effect caused by inhibition of aldehyde dehydrogenase was observed for NMTT-containing antibiotics. Studies were carried out on healthy volunteers and on rats. Eight-day treatment with 2 g flomoxef i.v. once or twice daily in five and six healthy male volunteers, respectively, did not cause any significant changes in prothrombin time (PT), coagulation factors II, VII, IX or X, in hepaplastin values or fibrinogen levels, activated partial thromboplastin time (APTT), platelet counts, bleeding time, or collagen- and ADP-induced platelet aggregation. Inhibition of vitamin K epoxide reductase was observed in rats treated with flomoxef, yet to a much lesser extent than observed for cephalosporins with NMTT, TDT or MTDT side chains. This defect was quickly normalized by vitamin K injection. There were no differences between oxacephem (1-O) and cephem (1-S) compounds with respect to effects on blood clotting and platelet aggregation. Flomoxef and its side chain HTT showed no influence on alcohol metbolism.

Simultaneous assessment of blood coagulation and hematocrit levels in dielectric blood coagulometry.

PubMed

Hayashi, Yoshihito; Brun, Marc-Aurèle; Machida, Kenzo; Lee, Seungmin; Murata, Aya; Omori, Shinji; Uchiyama, Hidetoshi; Inoue, Yoshinori; Kudo, Toshifumi; Toyofuku, Takahiro; Nagasawa, Masayuki; Uchimura, Isao; Nakamura, Tomomasa; Muneta, Takeshi

2017-01-01

In a whole blood coagulation test, the concentration of any in vitro diagnostic agent in plasma is dependent on the hematocrit level but its impact on the test result is unknown. The aim of this work was to clarify the effects of reagent concentration, particularly Ca2+, and to find a method for hematocrit estimation compatible with the coagulation test. Whole blood coagulation tests by dielectric blood coagulometry (DBCM) and rotational thromboelastometry were performed with various concentrations of Ca2+ or on samples with different hematocrit levels. DBCM data from a previous clinical study of patients who underwent total knee arthroplasty were re-analyzed. Clear Ca2+ concentration and hematocrit level dependences of the characteristic times of blood coagulation were observed. Rouleau formation made hematocrit estimation difficult in DBCM, but use of permittivity at around 3 MHz made it possible. The re-analyzed clinical data showed a good correlation between permittivity at 3 MHz and hematocrit level (R2=0.83). Changes in the hematocrit level may affect whole blood coagulation tests. DBCM has the potential to overcome this effect with some automated correction using results from simultaneous evaluations of the hematocrit level and blood coagulability.

A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa.

PubMed

Lu, Genmin; DeGuzman, Francis R; Hollenbach, Stanley J; Karbarz, Mark J; Abe, Keith; Lee, Gail; Luan, Peng; Hutchaleelaha, Athiwat; Inagaki, Mayuko; Conley, Pamela B; Phillips, David R; Sinha, Uma

2013-04-01

Inhibitors of coagulation factor Xa (fXa) have emerged as a new class of antithrombotics but lack effective antidotes for patients experiencing serious bleeding. We designed and expressed a modified form of fXa as an antidote for fXa inhibitors. This recombinant protein (r-Antidote, PRT064445) is catalytically inactive and lacks the membrane-binding γ-carboxyglutamic acid domain of native fXa but retains the ability of native fXa to bind direct fXa inhibitors as well as low molecular weight heparin-activated antithrombin III (ATIII). r-Antidote dose-dependently reversed the inhibition of fXa by direct fXa inhibitors and corrected the prolongation of ex vivo clotting times by such inhibitors. In rabbits treated with the direct fXa inhibitor rivaroxaban, r-Antidote restored hemostasis in a liver laceration model. The effect of r-Antidote was mediated by reducing plasma anti-fXa activity and the non-protein bound fraction of the fXa inhibitor in plasma. In rats, r-Antidote administration dose-dependently and completely corrected increases in blood loss resulting from ATIII-dependent anticoagulation by enoxaparin or fondaparinux. r-Antidote has the potential to be used as a universal antidote for a broad range of fXa inhibitors.

Platelet-Derived Short-Chain Polyphosphates Enhance the Inactivation of Tissue Factor Pathway Inhibitor by Activated Coagulation Factor XI.

PubMed

Puy, Cristina; Tucker, Erik I; Ivanov, Ivan S; Gailani, David; Smith, Stephanie A; Morrissey, James H; Gruber, András; McCarty, Owen J T

2016-01-01

Factor (F) XI supports both normal human hemostasis and pathological thrombosis. Activated FXI (FXIa) promotes thrombin generation by enzymatic activation of FXI, FIX, FX, and FV, and inactivation of alpha tissue factor pathway inhibitor (TFPIα), in vitro. Some of these reactions are now known to be enhanced by short-chain polyphosphates (SCP) derived from activated platelets. These SCPs act as a cofactor for the activation of FXI and FV by thrombin and FXIa, respectively. Since SCPs have been shown to inhibit the anticoagulant function of TFPIα, we herein investigated whether SCPs could serve as cofactors for the proteolytic inactivation of TFPIα by FXIa, further promoting the efficiency of the extrinsic pathway of coagulation to generate thrombin. Purified soluble SCP was prepared by size-fractionation of sodium polyphosphate. TFPIα proteolysis was analyzed by western blot. TFPIα activity was measured as inhibition of FX activation and activity in coagulation and chromogenic assays. SCPs significantly accelerated the rate of inactivation of TFPIα by FXIa in both purified systems and in recalcified plasma. Moreover, platelet-derived SCP accelerated the rate of inactivation of platelet-derived TFPIα by FXIa. TFPIα activity was not affected by SCP in recalcified FXI-depleted plasma. Our data suggest that SCP is a cofactor for TFPIα inactivation by FXIa, thus, expanding the range of hemostatic FXIa substrates that may be affected by the cofactor functions of platelet-derived SCP.

Imaging of blood plasma coagulation at supported lipid membranes.

PubMed

Faxälv, Lars; Hume, Jasmin; Kasemo, Bengt; Svedhem, Sofia

2011-12-15

The blood coagulation system relies on lipid membrane constituents to act as regulators of the coagulation process upon vascular trauma, and in particular the 2D configuration of the lipid membranes is known to efficiently catalyze enzymatic activity of blood coagulation factors. This work demonstrates a new application of a recently developed methodology to study blood coagulation at lipid membrane interfaces with the use of imaging technology. Lipid membranes with varied net charges were formed on silica supports by systematically using different combinations of lipids where neutral phosphocholine (PC) lipids were mixed with phospholipids having either positively charged ethylphosphocholine (EPC), or negatively charged phosphatidylserine (PS) headgroups. Coagulation imaging demonstrated that negatively charged SiO(2) and membrane surfaces exposing PS (obtained from liposomes containing 30% of PS) had coagulation times which were significantly shorter than those for plain PC membranes and EPC exposing membrane surfaces (obtained from liposomes containing 30% of EPC). Coagulation times decreased non-linearly with increasing negative surface charge for lipid membranes. A threshold value for shorter coagulation times was observed below a PS content of ∼6%. We conclude that the lipid membranes on solid support studied with the imaging setup as presented in this study offers a flexible and non-expensive solution for coagulation studies at biological membranes. It will be interesting to extend the present study towards examining coagulation on more complex lipid-based model systems. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of dairy farming system, herd, season, parity, and days in milk on modeling of the coagulation, curd firming, and syneresis of bovine milk.

PubMed

Bittante, G; Cipolat-Gotet, C; Malchiodi, F; Sturaro, E; Tagliapietra, F; Schiavon, S; Cecchinato, A

2015-04-01

The objectives of this study were to characterize the variation in curd firmness model parameters obtained from coagulating bovine milk samples, and to investigate the effects of the dairy system, season, individual farm, and factors related to individual cows (days in milk and parity). Individual milk samples (n = 1,264) were collected during the evening milking of 85 farms representing different environments and farming systems in the northeastern Italian Alps. The dairy herds were classified into 4 farming system categories: traditional system with tied animals (29 herds), modern dairy systems with traditional feeding based on hay and compound feed (30 herds), modern dairy system with total mixed ration (TMR) that included silage as a large proportion of the diet (9 herds), and modern dairy system with silage-free TMR (17 herds). Milk samples were analyzed for milk composition and coagulation properties, and parameters were modeled using curd firmness measures (CFt) collected every 15 s from a lacto-dynamographic analysis of 90 min. When compared with traditional milk coagulation properties (MCP), the curd firming measures showed greater variability and yielded a more accurate description of the milk coagulation process: the model converged for 93.1% of the milk samples, allowing estimation of 4 CFt parameters and 2 derived traits [maximum CF (CF(max)) and time from rennet addition to CF(max) (t(max))] for each sample. The milk samples whose CFt equations did not converge showed longer rennet coagulation times obtained from the model (RCT(eq)) and higher somatic cell score, and came from less-productive cows. Among the sources of variation tested for the CFt parameters, dairy herd system yielded the greatest differences for the contrast between the traditional farm and the 3 modern farms, with the latter showing earlier coagulation and greater instant syneresis rate constant (k(SR)). The use of TMR yielded a greater tmax because of a higher instant curd

Quinine-induced disseminated intravascular coagulation.

PubMed

Spearing, R L; Hickton, C M; Sizeland, P; Hannah, A; Bailey, R R

Recurrent disseminated intravascular coagulation occurred in 3 women after ingestion of quinine tablets for cramp. All had circulating quinine-dependent antibodies to platelets and in 2 there was initial evidence of antibody consumption, with low titres that rose steeply over the next few days and remained high for many months.

Molecular cloning, characterization and expression analysis of coagulation factor VII gene in grass carp (Ctenopharyngodon idella).

PubMed

Liu, Qiaolin; Xu, Baohong; Xiao, Tiaoyi; Su, Jianming; Zhong, Lei

2013-08-01

Coagulation factor VII has been studied in several species but, to date, not in grass carp (Ctenopharyngodon idella), a commercially important freshwater fish found in China. In this study, the full-length cDNA of grass carp coagulation factor VII (GcCFVII) was cloned using a RACE-Ready cDNA Kit, grass carp were challenged with a hemorrhagic virus, and temporal expression profiles of GcCFVII in the thymus, gills, liver, spleen, and head kidney were examined at 0 h, 24 h, 48 h, 72 h, 96 h, and 138 h using fluorescence quantitative PCR. The results showed the 1480 bp GcCFVII to contain three conservative motifs: Gla, EGF-CA, and Tryp-SPc, similar to other species. Phylogenetic analysis showed the evolution of GcCFVII gene to be consistent with the evolution of the species. After viral challenge, GcCFVII expression in five tissues of grass carp showed different patterns of fluctuation. These results provide a solid basis for further investigation of GcCFVII and its relationship with grass carp hemorrhage. Copyright © 2013 Elsevier Ltd. All rights reserved.

Simultaneous assessment of blood coagulation and hematocrit levels in dielectric blood coagulometry

PubMed Central

Hayashi, Yoshihito; Brun, Marc-Aurèle; Machida, Kenzo; Lee, Seungmin; Murata, Aya; Omori, Shinji; Uchiyama, Hidetoshi; Inoue, Yoshinori; Kudo, Toshifumi; Toyofuku, Takahiro; Nagasawa, Masayuki; Uchimura, Isao; Nakamura, Tomomasa; Muneta, Takeshi

2017-01-01

Background: In a whole blood coagulation test, the concentration of any in vitro diagnostic agent in plasma is dependent on the hematocrit level but its impact on the test result is unknown. Objective: The aim of this work was to clarify the effects of reagent concentration, particularly Ca2+, and to find a method for hematocrit estimation compatible with the coagulation test. Methods: Whole blood coagulation tests by dielectric blood coagulometry (DBCM) and rotational thromboelastometry were performed with various concentrations of Ca2+ or on samples with different hematocrit levels. DBCM data from a previous clinical study of patients who underwent total knee arthroplasty were re-analyzed. Results: Clear Ca2+ concentration and hematocrit level dependences of the characteristic times of blood coagulation were observed. Rouleau formation made hematocrit estimation difficult in DBCM, but use of permittivity at around 3 MHz made it possible. The re-analyzed clinical data showed a good correlation between permittivity at 3 MHz and hematocrit level (R2=0.83). Conclusions: Changes in the hematocrit level may affect whole blood coagulation tests. DBCM has the potential to overcome this effect with some automated correction using results from simultaneous evaluations of the hematocrit level and blood coagulability. PMID:28800301

Coagulation Management in Jersey Calves: An ex vivo Study.

PubMed

Gröning, Sabine; Maas, Judith; van Geul, Svenja; Rossaint, Rolf; Steinseifer, Ulrich; Grottke, Oliver

2017-01-01

Jersey calves are frequently used as an experimental animal model for in vivo testing of cardiac assist devices or orthopedic implants. In this ex vivo study, we analyzed the coagulation system of the Jersey calves and the potential of human-based coagulation management to circumvent perioperative bleeding complications during surgery. Experimental Procedure: Blood from 7 Jersey calves was subjected to standard laboratory tests and thromboelastometry analysis. An ex vivo model of dilutional coagulopathy was used to study the effects of fibrinogen or prothrombin complex concentrate supplementation. Fibrinolysis was induced with tissue plasminogen activator to identify potential therapeutic strategies involving tranexamic acid or aprotinin. Furthermore, anticoagulation strategies were evaluated by incubating the blood samples with dabigatran or rivaroxaban. Baseline values for thromboelastometry and standard laboratory parameters, including prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, and D-dimers, were established. Fifty percent diluted blood showed a statistically significant impairment of hemostasis. The parameters significantly improved after the administration of fibrinogen or prothrombin complex concentrate. Tranexamic acid and aprotinin ameliorated tissue plasminogen activator-induced fibrinolysis. Both dabigatran and rivaroxaban significantly prolonged the coagulation parameters. In this ex vivo study, coagulation factors, factor concentrate, antifibrinolytic reagents, and anticoagulants regularly used in the clinic positively impacted coagulation parameters in Jersey calf blood. © 2017 S. Karger AG, Basel.

Elastic scattering spectroscopy of coagulated brain tissues

NASA Astrophysics Data System (ADS)

Ateş, Filiz; Tabakoğlu, Haşim Özgür; Bozkulak, Özgüncem; Canpolat, Murat; Gülsoy, Murat

2006-02-01

The goal of this study was to differentiate the parts of lamb brain according to elastic scattering spectroscopy and detect the optical alterations due to coagulation. Cells and tissues are not uniform and have complex structures and shapes. They can be referred to as scattering particles. The process of scattering depends on the light wavelength and on the scattering medium properties; especially on the size and the density of the medium. When elastic scattering spectroscopy (ESS) is employed, the morphological alterations of tissues can be detected using spectral measurements of the elastic scattered light over a wide range of wavelengths. In this study firstly, the slopes of ESS spectra were used to differentiate the parts of lamb brains (brainstem, cerebellum, gray matter, white matter) in vitro in the range of 450 - 750 nm. Secondly, tissues were coagulated at different temperatures (45, 60, and 80 °C) and ESS spectra were taken from native and coagulated tissues. It was observed that as the coagulation temperature increased, the slope of the elastic scattering spectra decreased. Thus, optical properties of tissues were changed with respect to the change in nuclear to cytoplasmic ratio due to the water loss. Results showed that the slopes of ESS spectra in the visible range revealed valuable information about the morphological changes caused by coagulation.

A high affinity monoclonal antibody recognizing the light chain of human coagulating factor VII.

PubMed

Sarial, Sheila; Asadi, Farzad; Jeddi-Tehrani, Mahmood; Hadavi, Reza; Bayat, Ali Ahmad; Mahmoudian, Jafar; Taghizadeh-Jahed, Masoud; Shokri, Fazel; Rabbani, Hodjattallah

2012-12-01

Factor VII (FVII) is a serine protease-coagulating element responsible for the initiation of an extrinsic pathway of clot formation. Here we generated and characterized a high affinity monoclonal antibody that specifically recognizes human FVII. Recombinant human FVII (rh-FVII) was used for the production of a monoclonal antibody using BALB/c mice. The specificity of the antibody was determined by Western blot using plasma samples from human, mouse, sheep, goat, bovine, rabbit, and rat. Furthermore, the antibody was used to detect transiently expressed rh-FVII in BHK21 cell line using Western blot and sandwich ELISA. A mouse IgG1 (kappa chain) monoclonal antibody clone 1F1-B11 was produced against rh-FVII. The affinity constant (K(aff)) of the antibody was calculated to be 6.4×10(10) M(-1). The antibody could specifically recognize an epitope on the light chain of hFVII, with no reactivity with factor VII from several other animals. In addition, transiently expressed rh-FVII in BHK21 cells was recognized by 1F1-B11. The high affinity as well as the specificity of 1F1-B11 for hFVII will facilitate the affinity purification of hFVII and also production of FVII deficient plasma and minimizes the risk of bovine FVII contamination when fetal bovine serum-supplemented media are used for production and subsequent purification of rh-FVII.

Prevalence of nucleic acid sequences specific for human parvoviruses, hepatitis A and hepatitis E viruses in coagulation factor concentrates.

PubMed

Modrow, S; Wenzel, J J; Schimanski, S; Schwarzbeck, J; Rothe, U; Oldenburg, J; Jilg, W; Eis-Hübinger, A M

2011-05-01

Due to their high resistance to inactivation procedures, nonenveloped viruses such as parvovirus B19, human bocavirus (HBoV), human parvovirus 4 (PARV4), hepatitis A (HAV) and hepatitis E virus (HEV) pose a particular threat to blood products. Virus transmission to patients treated with blood products presents an additional burden to disease. We determined the frequency and the amount of nucleic acid specific for nonenveloped viruses in recently manufactured preparations of commercial coagulation factor concentrates. At least three different batches of each of 13 different plasma-derived and recombinant coagulation factor products were tested for the presence and the amount of nucleic acid for parvovirus B19, HBoV, human parvovirus 4, hepatitis A virus and HEV by using quantitative polymerase chain reaction. Whereas none of the recombinant products tested positive for any of these viruses, parvovirus B19 DNA with amounts ranging between 2×10(1) and 1.3×10(3) genome equivalents/ml was detected in five plasma-derived products. In addition to parvovirus B19 genotype 1, genotypes 2 and 3 were observed in two batches of a factor VIII/von-Willebrand factor product. In two products (one factor VIII concentrate and one activated prothrombin complex concentrate), a combination of both genotypes 1 and 2 of parvovirus B19 was detected. The data show that nucleic acids from several relevant nonenveloped viruses are not found at detectable levels in coagulation factor concentrates. In some cases, parvovirus B19 DNA was detectable at low levels. Testing of the plasma pools for the full range of parvovirus genotypes is advocated for ensuring product safety. © 2010 The Author(s). Vox Sanguinis © 2010 International Society of Blood Transfusion.

Size-Resolved Ultrafine Particle Deposition and Brownian Coagulation from Gasoline Vehicle Exhaust in an Environmental Test Chamber.

PubMed

Zhao, Yu; Wang, Fang; Zhao, Jianing

2015-10-20

Size-resolved deposition rates and Brownian coagulation of particles between 20 and 900 nm (mobility diameter) were estimated in a well-mixed environmental chamber from a gasoline vehicle exhaust with a total peak particle concentration of 10(5)-10(6) particles/cm(3) at 12.24-25.22 °C. A deposition theory with modified friction velocity and coagulation model was also employed to predict particle concentration decay. Initially during particle decay, approximately 85% or more of the particles had diameters of <100 nm. Particle deposition rates with standard deviations were highly dependent on particle size ranges, and varied from 0.012 ± 0.003 to 0.48 ± 0.02 h(-1). In the experiment, the friction velocity obtained was in the range 1.5-2.5 cm/s. The most explainable fractal dimension and Hamaker constant in coagulation model were 2.5-3 and 20 kT, respectively, and the contribution from coagulation dominated the total particle decay during the first 1 h of decay. It is considered that the modified friction velocity and best fitted fractal dimension and Hamaker constants could be further used to analyze gasoline vehicle exhaust particle dynamics and assess human exposure to vehicle particle pollutants in urban areas, tunnels, and underground parking lots.

The effect of corn trypsin inhibitor and inhibiting antibodies for FXIa and FXIIa on coagulation of plasma and whole blood.

PubMed

Hansson, K M; Nielsen, S; Elg, M; Deinum, J

2014-10-01

Corn trypsin inhibitor (CTI), an inhibitor of FXIIa, is used to prevent plasma coagulation by contact activation, to specifically investigate tissue factor (TF)-initiated coagulation. In the present work the specificity of CTI for factor (F) XIIa is questioned. In the commercial available plasma coagulation assays CTI was found to double activated partial thromboplastin time (APTT) at a plasma concentration of 7.3 ± 1.5 μm CTI (assay concentration 2.4 μm). No effect was found on the prothrombin time (PT) when high TF concentrations were used. Also, with specific antibodies for FXIIa and for FXIa only APTT was found to be extended but not PT. With specific enzyme assays using chromogenic substrates CTI was shown to be a strong inhibitor of FXIIa and a competitive inhibitor of FXIa with Ki  = 8.1 ± 0.3 μm, without effect on the coagulation factors FVIIa, FIXa, FXa and thrombin. In thrombin generation and coagulation (free oscillation rheometry, FOR) assays, initiated with low TF concentrations, no effect of CTI (plasma concentrations of 4.4 and 13.6 μm CTI, 25 resp. 100 mg L(-1) in blood) was found with ≥ 1 pm TF. At ≤ 0.1 pm TF in the FOR whole blood assay the coagulation time (CT) concentration dependently increased while the plasma CT became longer than the observation time. To avoid inhibition of FXIa and the thrombin feedback loop we recommend that for coagulation assays the concentration of CTI in blood should be below 20 mg L(-1) (1.6 μm) and in plasma below 3 μm. © 2014 International Society on Thrombosis and Haemostasis.

The effects of three factor VII polymorphisms on factor VII coagulant levels in healthy Singaporean Chinese, Malay and Indian newborns.

PubMed

Quek, S C; Low, P S; Saha, N; Heng, C K

2006-11-01

Factor VII (FVII) is an independent risk factor for coronary artery disease. Three polymorphisms of the factor VII gene (F7) were studied in a group of healthy newborns comprising 561 Chinese, 398 Malays and 226 Asian Indians from Singapore. The allele frequencies of 3 polymorphisms (R353Q, Promoter 0/10bp Del/Ins and Intron 7) in the FVII gene were ascertained through genotyping by polymerase chain reaction and restriction digestion of amplified fragments. In Chinese the minor allele frequencies are Q: 0.04, Ins: 0.03, R7: 0.44; Malays, Q: 0.06, Ins: 0.10, R7: 0.41; and Indians, Q: 0.25, Ins: 0.23, R7: 0.43. Strong linkage disequilibrium (Delta > 0.7) is observed between the 0/10 bp and the R353Q sites in all ethnic groups. We conclude that: (i) the prevalence of the minor Q and Ins alleles of the R353Q and 0/10 bp polymorphisms are significantly higher in the Indian newborns than the Chinese and Malays; (ii) the Q allele is significantly associated (p = 0.01) with a lower plasma FVII coagulant level in the Indian and Malay neonates; and this polymorphism explains up to 3.8% of the variance in FVII coagulant levels; (iii) there is no significant difference in allele frequencies of the three polymorphisms between neonates with and without family histories of CAD.

Poplar potassium transporters capable of controlling K+ homeostasis and K+-dependent xylogenesis.

PubMed

Langer, Katharina; Ache, Peter; Geiger, Dietmar; Stinzing, Andrea; Arend, Matthias; Wind, Christa; Regan, Sharon; Fromm, Jörg; Hedrich, Rainer

2002-12-01

The cambial K+ content of poplar increases during the growth period in a K+ supply dependent manner. Upon K+ starvation or application of tetraethylammoniumchloride (TEA+), a K+ channel blocker, the average vessel lumen and expansion zone area were significantly reduced. In search for the molecular basis of potassium-dependent xylogenesis in poplar, K+ transporters homologous to those of known function in Arabidopis phloem- and xylem-physiology were isolated from a poplar wood EST library. The expression profile of three distinct K+ channel types and one K+ transporter, Populus tremula K+ uptake transporter 1 (PtKUP1), was analysed by quantitative RT-PCR. Thereby, we found P. tremula outward rectifying K+ channel (PTORK) and P. tremula K+ channel 2 (PTK2) correlated with the seasonal wood production. K+ transporter P. tremula 1 (KPT1) was predominantly found in guard cells. Following the heterologous expression in Xenopus oocytes the biophysical properties of the different channels were determined. PTORK, upon membrane de-polarization mediates potassium release. PTK2 is almost voltage independent, carrying inward K+ flux at hyperpolarized potential and K+ release upon de-polarization. PtKUP1 was expressed in a K+ uptake-deficient Escherichia coli strain, where this K+ transporter rescued K+-dependent growth. In order to link the different K+ transporters to the cambial activity and wood production, we compared the expression profiles to seasonal changes in the K+ content of the bark as well as xylem vessel diameter. Thereby, we found PTORK and PTK2 transcripts to follow the annual K+ variations in poplar branches. PtKUP1 was expressed at a low level throughout the year, suggesting a housekeeping function. From these data, we conclude that K+ channels are involved in the regulation of K+-dependent wood production.

[Haplotype Analysis of Coagulation Factor VII Gene in a Patient with Congenital Coagulation Factor VII Deficiency with Heterozygous p.Arg337Cys Mutation and o.Aro413Gin Polymorphism..

PubMed

Suzuki, Keijiro; Yoshioka, Tomoko; Obara, Takehiro; Suwabe, Akira

2016-05-01

Congenital coagulation factor VII (FVII) deficiency is a rare hemorrhagic disease with an autosomal reces- sive inheritance pattern. We analyzed coagulation factor VII gene (F7) of a patient with FVII deficiency and used expression studies to investigate the effect of a missense mutation on FVII secretion. The proband, a 69-year-old Japanese woman, had a history of postpartum bleeding and excessive bleeding after dental extrac- tion. She was found to have mildly increased PT-INR (1.17) before an ophthalmic operation. FVII activity and antigen were reduced (29.0% and 32.8%). Suspecting that the proband was FVII deficient, we analyzed F7 of the patient. Sequence analysis revealed that the patient was heterozygous for a point mutation (p.Arg337Cys) in the catalytic domain and polymorphisms: the decanucleotide insertion at the promoter re- gion, dimorphism (c.525C >T) in exon 5, and p.Arg413Gln in exon 8. Haplotype analysis clarified that p.Arg337Cys was located on the p.Arg413 allele (Ml allele). The other allele had the p.Arg413Gln polymor- phism(M2 allele) which is known to produce less FVII. Expression studies revealed that p.Arg337Cys causes impairment of FVII secretion. Insufficient secretion of FVII arising from both the p.Arg337Cys/M1 allele and the p.Arg337/M2 allele might lower the FVII level of this patient(<50%). The FVII level in a heterozygous FVII deficient patient might be influenced by F7 polymorphisms on the normal allele. There- fore, genetic analyses are important for the diagnosis of heterozygous FVII deficiency.

Expression of the human blood coagulation protein factor XIIIa in Saccharomyces cerevisiae: dependence of the expression levels from host-vector systems and medium conditions.

PubMed

Bröker, M; Bäuml, O; Göttig, A; Ochs, J; Bodenbenner, M; Amann, E

1991-03-01

The human blood coagulation protein Factor XIIIa (FXIIIa) was expressed in Saccharomyces cerevisiae employing Escherichia coli-yeast shuttle vectors based on a 2-mu plasmid. Several factors affecting high production yield of recombinant FXIIIa were analysed. The use of the regulatable GAL-CYC1 hybrid promoter resulted in higher FXIIIa expression when compared with the constitutive ADCI promoter. Screening for suitable yeast strains for expression of FXIIIa under the transcriptional control of the GAL-CYC1 hybrid promoter revealed a broad spectrum of productivity. No obvious correlation between the expression rate and the genetic markers of the strains could be identified. The medium composition markedly influenced the FXIIIa expression rates. The expression of FXIIIa was strictly regulated by the carbon source. Glucose as the only sugar and energy source repressed the synthesis of FXIIIa, whereas addition of galactose induced FXIIIa expression. Special feeding schemes resulted in a productivity of up to 100 mg FXIIIa/l in shake flasks.

A quantitative systems pharmacology model of blood coagulation network describes in vivo biomarker changes in non-bleeding subjects.

PubMed

Lee, D; Nayak, S; Martin, S W; Heatherington, A C; Vicini, P; Hua, F

2016-12-01

Essentials Baseline coagulation activity can be detected in non-bleeding state by in vivo biomarker levels. A detailed mathematical model of coagulation was developed to describe the non-bleeding state. Optimized model described in vivo biomarkers with recombinant activated factor VII treatment. Sensitivity analysis predicted prothrombin fragment 1 + 2 and D-dimer are regulated differently. Background Prothrombin fragment 1 + 2 (F 1 + 2 ), thrombin-antithrombin III complex (TAT) and D-dimer can be detected in plasma from non-bleeding hemostatically normal subjects or hemophilic patients. They are often used as safety or pharmacodynamic biomarkers for hemostatis-modulating therapies in the clinic, and provide insights into in vivo coagulation activity. Objectives To develop a quantitative systems pharmacology (QSP) model of the blood coagulation network to describe in vivo biomarkers, including F 1 + 2 , TAT, and D-dimer, under non-bleeding conditions. Methods The QSP model included intrinsic and extrinsic coagulation pathways, platelet activation state-dependent kinetics, and a two-compartment pharmacokinetics model for recombinant activated factor VII (rFVIIa). Literature data on F 1 + 2 and D-dimer at baseline and changes with rFVIIa treatment were used for parameter optimization. Multiparametric sensitivity analysis (MPSA) was used to understand key proteins that regulate F 1 + 2 , TAT and D-dimer levels. Results The model was able to describe tissue factor (TF)-dependent baseline levels of F 1 + 2 , TAT and D-dimer in a non-bleeding state, and their increases in hemostatically normal subjects and hemophilic patients treated with different doses of rFVIIa. The amount of TF required is predicted to be very low in a non-bleeding state. The model also predicts that these biomarker levels will be similar in hemostatically normal subjects and hemophilic patients. MPSA revealed that F 1 + 2 and TAT levels are highly correlated, and that D-dimer is

[Use of thrombelastography to guide posttraumatic hemostatic therapy: More coagulation factor concentrates and less allogenic blood transfusion?

PubMed

David, J S; Imhoff, E; Parat, S; Augey, L; Geay-Baillat, M-O; Incagnoli, P; Tazarourte, K

2016-11-01

Viscoelastic technics are used for 10 years and include the ROTEM ® and the TEG ® . These devices that exploit the viscoelastic properties of the clotting blood, allow a rapid and global analysis of the haemostatic process taking into account all the process interfering with haemostasis such as inflammation. It has been shown that the use of these technics in clinical situations such as trauma, postpartum haemorrhage, gastrointestinal bleeding or cardiac surgery may reduce the need for blood product, the cost and perhaps may improve the outcome of the patients. Thanks to a rapid identification of the underlying coagulation deficit, these technics facilitate decision-making during acute care and help to guide the treatment, particularly with coagulation factor's concentrate. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Competition of coagulation sink and source rate: New particle formation in the Pearl River Delta of China

NASA Astrophysics Data System (ADS)

Gong, Youguo; Hu, Min; Cheng, Yafang; Su, Hang; Yue, Dingli; Liu, Feng; Wiedensohler, A.; Wang, Zhibin; Kalesse, H.; Liu, Shang; Wu, Zhijun; Xiao, Kaitao; Mi, Puchun; Zhang, Yuanhang

The coagulation sink and its role in new particle formation are investigated based on data obtained during the PRIDE-PRD2004 campaign at Xinken of Pearl River Delta, China. Analysis of size distributions and mode contributions of the coagulation sink show that the observed higher load of accumulation mode particles impose a significant effect on the coagulation sink and result in higher coagulation sinks at Xinken despite of the lower total particle number compared with other areas. Hence it is concluded that the higher coagulation sink may depress the occurrence frequency of new particle formation events. The strategies targeting at controlling accumulation mode particles may have influences on the frequency of new particle formation events at this area. The factors affecting the coagulation sink are evaluated. The relatively lower ambient relative humidities may weaken the coagulation sink and facilitate the occurrence of new particle formation events during noontime, while the surmise of nucleation and growth involving organic matter may imply an actually higher coagulation sink than expected. These factors have a significant influence on the ultimate fate of the newly formed nuclei and new particle formation. A comparison of event and non-event days indicates that the coagulation sink is not the only decisive factor affecting new particle formation, other factors including the precursor vapors and photochemical activity are none the less important either. Competition of coagulation sink and high source rate leads to the occurrence of new particle formation events at Xinken.

Relation of thromboelastography parameters to conventional coagulation tests used to evaluate the hypercoagulable state of aged fracture patients

PubMed Central

Liu, Chen; Guan, Zhao; Xu, Qinzhu; Zhao, Lei; Song, Ying; Wang, Hui

2016-01-01

Abstract Fractures are common among aged people, and rapid assessment of the coagulation status is important. The thromboelastography (TEG) test can give a series of coagulation parameters and has been widely used in clinics. In this research, we looked at fracture patients over 60 and compared their TEG results with those of healthy controls. Since there is a paucity of studies comparing TEG assessments with conventional coagulation tests, we aim to clarify the relationship between TEG values and the values given by conventional coagulation tests. Forty fracture patients (27 femur and 13 humerus) over 60 years old were included in the study. The change in their coagulation status was evaluated by TEG before surgery within 4 hours after the fracture. Changes in TEG parameters were analyzed compared with controls. Conventional coagulation test results for the patients, including activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen, and platelets, were also acquired, and correlation analysis was done with TEG parameters, measuring similar aspects of the coagulation cascade. In addition, the sensitivity and specificity of TEG parameters for detecting raised fibrinogen levels were also analyzed. The K (time to 20 mm clot amplitude) and R (reaction time) values of aged fracture patients were lower than controls. The values for angle, maximal amplitude (MA), and coagulation index (CI) were raised compared with controls, indicating a hypercoagulable state. Correlation analysis showed that there were significant positive correlations between fibrinogen and MA/angle, between platelets and MA, and between APTT and R as well. There was significant negative correlation between fibrinogen and K. In addition, K values have better sensitivity and specificity for detecting elevated fibrinogen concentration than angle and MA values. Aged fracture patients tend to be in a hypercoagulable state, and this could be effectively reflected by

Relation of thromboelastography parameters to conventional coagulation tests used to evaluate the hypercoagulable state of aged fracture patients.

PubMed

Liu, Chen; Guan, Zhao; Xu, Qinzhu; Zhao, Lei; Song, Ying; Wang, Hui

2016-06-01

Fractures are common among aged people, and rapid assessment of the coagulation status is important. The thromboelastography (TEG) test can give a series of coagulation parameters and has been widely used in clinics. In this research, we looked at fracture patients over 60 and compared their TEG results with those of healthy controls. Since there is a paucity of studies comparing TEG assessments with conventional coagulation tests, we aim to clarify the relationship between TEG values and the values given by conventional coagulation tests.Forty fracture patients (27 femur and 13 humerus) over 60 years old were included in the study. The change in their coagulation status was evaluated by TEG before surgery within 4 hours after the fracture. Changes in TEG parameters were analyzed compared with controls. Conventional coagulation test results for the patients, including activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen, and platelets, were also acquired, and correlation analysis was done with TEG parameters, measuring similar aspects of the coagulation cascade. In addition, the sensitivity and specificity of TEG parameters for detecting raised fibrinogen levels were also analyzed.The K (time to 20 mm clot amplitude) and R (reaction time) values of aged fracture patients were lower than controls. The values for angle, maximal amplitude (MA), and coagulation index (CI) were raised compared with controls, indicating a hypercoagulable state. Correlation analysis showed that there were significant positive correlations between fibrinogen and MA/angle, between platelets and MA, and between APTT and R as well. There was significant negative correlation between fibrinogen and K. In addition, K values have better sensitivity and specificity for detecting elevated fibrinogen concentration than angle and MA values.Aged fracture patients tend to be in a hypercoagulable state, and this could be effectively reflected by a TEG test

Effects of oversulfated and fucosylated chondroitin sulfates on coagulation. Challenges for the study of anticoagulant polysaccharides.

PubMed

Fonseca, Roberto J C; Oliveira, Stephan-Nicollas M C G; Pomin, Vitor H; Mecawi, André S; Araujo, Iracema G; Mourão, Paulo A S

2010-05-01

We report the effects of a chemically oversulfated chondroitin sulfate and a naturally fucosylated chondroitin sulfate on the coagulation system. The former has been recently identified as a contaminant of heparin preparations and the latter has been proposed as an alternative anticoagulant. The mechanism of action of these polymers on coagulation is complex and target different components of the coagulation system. They have serpin-independent anticoagulant activity, which preponderates in plasma. They also have serpin-dependent anticoagulant activity but differ significantly in the target coagulation protease and preferential serpin. Their anticoagulant effects differ even more markedly when tested as inhibitors of coagulation proteases using plasma as a source of serpins. It is possible that the difference is due to the high availability of fucosylated chondroitin sulfate whereas oversulfated chondroitin sulfate has strong unspecific binding to plasma protein and low availability for the binding to serpins. When tested using a venous thrombosis experimental model, oversulfated chondroitin sulfate is less potent as an antithrombotic agent than fucosylated chondroitin sulfate. These highly sulfated chondroitin sulfates activate factor XII in in vitro assays, based on kallikrein release. However, only fucosylated chondroitin sulfate induces hypotension when intravenously injected into rats. In conclusion, the complexity of the regulatory mechanisms involved in the action of highly sulfated polysaccharides in coagulation requires their analysis by a combination of in vitro and in vivo assays. Our results are relevant due to the urgent need for new anticoagulant drugs or alternative sources of heparin.

Economic aspects of intraoperative coagulation management targeting higher fibrinogen concentrations during major craniosynostosis surgery.

PubMed

Haas, Thorsten; Spielmann, Nelly; Restin, Tanja; Schmidt, Alexander R; Schmugge, Markus; Cushing, Melissa M

2016-01-01

Results of a previously published study demonstrated a significant decrease in transfusion requirements and calculated blood loss for pediatric major craniosynostosis surgery, if a ROTEM(®) FIBTEM trigger of <13 mm (early substitution group) was applied as compared to a trigger of <8 mm (conventional group). The aim of this study was a posthoc analysis of the costs for this coagulation management. The total volume as well as the number of units or bags for all transfused blood products and coagulation factors were recorded for each case. The number of laboratory and point-of-care coagulation tests was also analyzed. Total blood product costs were calculated according to the local prices per unit. The total cost for all transfused/administered blood products/coagulation factors per patient was a median of 1023EUR (IQR 850EUR-1058EUR) in the early substitution group as compared to a median of 910EUR (IQR 719EUR-1351EUR) in the conventional group (P = 0.81). No difference in the number of coagulation tests performed was observed. In this study, the use of a higher fibrinogen trigger was not linked to a significant increase in total costs for transfused blood products and coagulation factors, and may offer an economically equivalent approach to coagulation management. © 2015 John Wiley & Sons Ltd.

Factor XI and XII as antithrombotic targets.

PubMed

Müller, Felicitas; Gailani, David; Renné, Thomas

2011-09-01

Arterial and venous thrombosis are major causes of morbidity and mortality, and the incidence of thromboembolic diseases increases as a population ages. Thrombi are formed by activated platelets and fibrin. The latter is a product of the plasma coagulation system. Currently available anticoagulants such as heparins, vitamin K antagonists and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation. However, fibrin is also necessary for terminating blood loss at sites of vascular injury. As a result, anticoagulants currently in clinical use increase the risk of bleeding, partially offsetting the benefits of reduced thrombosis. This review focuses on new targets for anticoagulation that are associated with minimal or no therapy-associated increased bleeding. Data from experimental models using mice and clinical studies of patients with hereditary deficiencies of coagulation factors XI or XII have shown that both of these clotting factors are important for thrombosis, while having minor or no apparent roles in processes that terminate blood loss (hemostasis). Hereditary deficiency of factor XII (Hageman factor) or factor XI, plasma proteases that initiate the intrinsic pathway of coagulation, impairs thrombus formation and provides protection from vascular occlusive events, while having a minimal impact on hemostasis. As the factor XII-factor XI pathway contributes to thrombus formation to a greater extent than to normal hemostasis, pharmacological inhibition of these coagulation factors may offer the exciting possibility of anticoagulation therapies with minimal or no bleeding risk.

Structure of a bacterial homologue of vitamin K epoxide reductase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Weikai; Schulman, Sol; Dutton, Rachel J.

Vitamin K epoxide reductase (VKOR) generates vitamin K hydroquinone to sustain {gamma}-carboxylation of many blood coagulation factors. Here, we report the 3.6 {angstrom} crystal structure of a bacterial homologue of VKOR from Synechococcus sp. The structure shows VKOR in complex with its naturally fused redox partner, a thioredoxin-like domain, and corresponds to an arrested state of electron transfer. The catalytic core of VKOR is a four transmembrane helix bundle that surrounds a quinone, connected through an additional transmembrane segment with the periplasmic thioredoxin-like domain. We propose a pathway for how VKOR uses electrons from cysteines of newly synthesized proteins tomore » reduce a quinone, a mechanism confirmed by in vitro reconstitution of vitamin K-dependent disulphide bridge formation. Our results have implications for the mechanism of the mammalian VKOR and explain how mutations can cause resistance to the VKOR inhibitor warfarin, the most commonly used oral anticoagulant.« less

Retinal venous thrombosis in a young patient with coagulation factor XII deficiency.

PubMed

Borrego-Sanz, L; Santos-Bueso, E; Sáenz-Francés, F; Martínez-de-la-Casa, J M; García-Feijoo, J; Gegúndez-Fernández, J A; García-Sánchez, J

2014-08-01

A 35-year-old woman, with no relevant medical history, was referred for sudden vision loss in the left eye. Ophthalmological examination showed best corrected visual acuity of 1.0 in the right eye and 0.3 in left eye, with normal anterior pole and intraocular pressure. Fundus examination of the left eye revealed a venous thrombosis in the superior temporal branch, with dilated and tortuous retinal veins. The patient was referred to the hematology unit for thrombophilia study, and was diagnosed with a coagulation XII or Hageman factor deficiency. The development of retinal vessel occlusions, in patients under 50 years of age, is frequently associated with thrombophilia or hypercoagulability disorders. Factor XII deficiency is a rare condition, and its presence could contribute to a higher risk of thromboembolic events. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

A Pilot Study of Tissue Factor-Tissue Factor Pathway Inhibitor Axis and Other Selected Coagulation Parameters in Broiler Chickens Administered in Ovo with Selected Prebiotics*.

PubMed

Buzala, Mateusz; Ponczek, Michal Blazej; Slomka, Artur; Roslewska, Aleksandra; Janicki, Bogdan; Zekanowska, Ewa; Bednarczyk, Marek

The tissue factor (TF) - tissue factor pathway inhibitor (TFPI) axis plays a major role in hemostasis. Disorders of the coagulation system are commonly diagnosed with the help of screening tests such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and plasma fibrinogen concentration (PFC). However, the effect of prebiotics on the hemostasis system has not been characterized in poultry yet. This study was designed to determine the effect of in ovo administration ofprebiotics on blood coagulation parameters of broiler chickens depending on their age. The study was conducted with 180 broiler chick embryos, the air cells of which were injected on day 12 of incubation with prebiotics (experimental groups: Bi2tos, DiNovoo and RFO) or physiological saline solution (control group). At 1, 21 and 42 days of rearing, blood was sampled from 15 broiler chickens from each group. An enzyme immunoassay was performed to determine plasma TF and TFPI levels, and PT, aPTT and PFC were determined in the chicken blood. We demonstrated that: 1) total TF levels increased with age in the experimental groups, 2) prebiotics had no significant effect on TF levels between the groups at a particular age, 3) total TFPI levels differed between both the type of in ovo injected substance and the broiler chicken age, 4) in the control group, PT and aPTT were found to increase with age whilst fibrinogen concentration decreased. The main conclusion from this pilot study is that total TF and TFPI levels change with age, however no clear patterns regarding TFPI were detected yet. The levels of PT, aPTT and PFC varied with the prebiotics administered in ovo as well as with the age of broiler chickens.

Coagulation activation in autoimmune bullous diseases

PubMed Central

Marzano, A V; Tedeschi, A; Spinelli, D; Fanoni, D; Crosti, C; Cugno, M

2009-01-01

The main autoimmune blistering skin disorders are pemphigus vulgaris (PV) and bullous pemphigoid (BP). They differ in the inflammatory infiltrate, which is more intense in BP. Inflammation is known to activate coagulation in several disorders. Local and systemic activation of coagulation was evaluated in BP and PV. We studied 20 BP patients (10 active and 10 remittent), 23 PV patients (13 active and 10 remittent) and 10 healthy subjects. The coagulation markers prothrombin fragment F1+2 and D-dimer were measured by enzyme-immunoassays in plasma. The presence of tissue factor (TF), the main initiator of blood coagulation, was evaluated immunohistochemically in skin specimens from 10 patients with active PV, 10 patients with active BP and 10 controls. Plasma F1+2 and D-dimer levels were significantly high in active BP (P = 0·001), whereas in active PV the levels were normal. During remission, F1+2 and D-dimer plasma levels were normal in both BP and PV. TF immunoreactivity was found in active BP but neither in active PV nor in normal skin. TF reactivity scores were higher in active BP than in controls or active PV (P = 0·0001). No difference in TF scores was found between active PV and controls. BP is associated with coagulation activation, which is lacking in PV. This suggests that BP but not PV patients have an increased thrombotic risk. The observation that thrombotic complications occur more frequently in BP than in PV further supports this view. PMID:19737228

Coagulation under flow: the influence of flow-mediated transport on the initiation and inhibition of coagulation.

PubMed

Fogelson, Aaron L; Tania, Nessy

2005-01-01

A mathematical model of intravascular coagulation is presented; it encompasses the biochemistry of the tissue factor pathway, platelet activation and deposition on the subendothelium, and flow- and diffusion-mediated transport of coagulation proteins and platelets. Simulation experiments carried out with the model indicate the predominant role played by the physical processes of platelet deposition and flow-mediated removal of enzymes in inhibiting coagulation in the vicinity of vascular injury. Sufficiently rapid production of factors IXa and Xa by the TF:VIIa complex can overcome this inhibition and lead to formation of significant amounts of the tenase complex on the surface of activated platelets and, as a consequence, to substantial thrombin production. Chemical inhibitors are seen to play almost no (TFPI) or little (AT-III and APC) role in determining whether substantial thrombin production will occur. The role of APC is limited by the necessity for diffusion of thrombin from the site of injury to nearby endothelial cells to form the thrombomodulin-thrombin complex and for diffusion in the reverse direction of the APC made by this complex. TFPI plays an insignificant part in inhibiting the TF:VIIa complex under the conditions studied whether its action involves sequential binding of TFPI to Xa and then TFPI:Xa to TF:VIIa, or direct binding of TFPI to Xa already bound to the TF:VIIa complex. Copyright 2005 S. Karger AG, Basel.

Coagulation/flocculation process with polyaluminum chloride for the remediation of oil sands process-affected water: Performance and mechanism study.

PubMed

Wang, Chengjin; Alpatova, Alla; McPhedran, Kerry N; Gamal El-Din, Mohamed

2015-09-01

This study investigated the application of polyaluminum chloride (PACl) for the treatment of the oil sands process-affected water (OSPW). These coagulants are commonly used in water treatment with the most effective species reported to be Al13. PACl with 83.6% Al13 was synthesized using the slow base titration method and compared with a commercially available PACl in terms of aluminum species distribution, coagulation/flocculation (CF) performance, floc morphology, and contaminant removal. Both coagulants were effective in removing suspended solids, achieving over 96% turbidity removal at all applied coagulant doses (0.5-3.0 mM Al). The removal efficiencies of metals varied among different metals depending on their pKa values with metal cations having pKa values (Fe, Al, Ga, and Ti) below OSPW pH of 6.9-8.1 (dose dependent) being removed by more than 90%, while cations with higher pKa values (K, Na, Ca, Mg and Ni) had removals of less than 40%. Naphthenic acids were not removed due to their low molecular weights, negative charges, and hydrophilic characteristics at the OSPW pH. At the highest applied coagulant dose of 3.0 mM Al, the synthetic PACl reduced Vibrio fischeri inhibition effect to 43.3 ± 3.0% from 49.5 ± 0.4% in raw OSPW. In contrast, no reduction of toxicity was found for OSPW treated with the commercial PACl. Based on water quality and floc analyses, the dominant CF mechanism for particle removal during OSPW treatment was considered to be enmeshment in the precipitates (i.e., sweep flocculation). Overall, the CF using synthesized PACl can be a valuable pretreatment process for OSPW to create wastewater that is more easily treated by downstream processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Intrinsic Pathway of Coagulation as a Target for Antithrombotic Therapy

PubMed Central

Wheeler, Allison P.; Gailani, David

2016-01-01

Plasma coagulation in the activated partial thromboplastin time assay is initiated by sequential activation of coagulation factors XII, XI and IX – the classical intrinsic pathway of coagulation. It is well recognized that this series of proteolytic reactions is not an accurate model for hemostasis in vivo, as factor XII deficiency does not cause abnormal bleeding, and fXI deficiency causes a relatively mild propensity to bleed excessively with injury. Despite their limited roles in hemostasis, there is mounting evidence that fXI and fXII contribute to thrombosis, and that inhibiting them can produce an antithrombotic effect with a relatively small effect on hemostasis. In this chapter the contributions of components of the intrinsic pathway to thrombosis in animal models and humans are discussed, and results of early clinical trials of drugs targeting factors IX, XI and XII are presented. PMID:27637310

A natural coagulant protein from Moringa oleifera: isolation, characterization, and potential use for water treatment

NASA Astrophysics Data System (ADS)

Choudhary, Manisha; Neogi, Sudarsan

2017-10-01

In developing countries pond water is still widely used for drinking and household purposes, which develops higher turbidity during rainy seasons and requires a large amount of chemical coagulants, and this leads to high cost of treatment. To mitigate this, it is important to find an economical and natural coagulant to treat turbid water. The present study is focused on using a plant based component as a natural coagulant that is sustainable and environment-friendly. This work focuses on the extraction, isolation and purification of a natural coagulant from seed kernels of Moringa oleifera to enhance its turbidity removal efficiency. The determination of themolecular weight of the purified proteins was done using sodium dodecyl sulfate polyacrylamide gel electrophoresis. The active coagulant proteins were isolated using 30-60% and 60-80% saturation of ammonium sulfate. It was observed that proteins with molecular weight less than 36 kDa have superior coagulation activity. Turbidity removal efficiency of these active coagulant proteins was compared with alum. The possibility of using Moringa oleifera seeds as a natural antimicrobial agent was also investigated.

Accumulation of functional recombinant human coagulation factor IX in transgenic soybean seeds.

PubMed

Cunha, Nicolau B; Murad, André M; Ramos, Gustavo L; Maranhão, Andréia Q; Brígido, Marcelo M; Araújo, Ana Cláudia G; Lacorte, Cristiano; Aragão, Francisco J L; Covas, Dimas T; Fontes, Aparecida M; Souza, Gustavo H M F; Vianna, Giovanni R; Rech, Elíbio L

2011-08-01

The seed-based production of recombinant proteins is an efficient strategy to achieve the accumulation, correct folding, and increased stability of these recombinant proteins. Among potential plant molecular farming systems, soybean [Glycine max (L.) Merrill] is a viable option for the production of recombinant proteins due to its high protein content, known regulatory sequences, efficient gene transfer protocols, and a scalable production system under greenhouse conditions. We report here the expression and stable accumulation of human coagulation factor IX (hFIX) in transgenic soybean seeds. A biolistic process was utilised to co-introduce a plasmid carrying the hFIX gene under the transcriptional control of the α' subunit of a β-conglycinin seed-specific promoter and an α-Coixin signal peptide in soybean embryonic axes from mature seeds. The 56-kDa hFIX protein was expressed in the transgenic seeds at levels of up to 0.23% (0.8 g kg(-1) seed) of the total soluble seed protein as determined by an enzyme-linked immunosorbent assay (ELISA) and western blot. Ultrastructural immunocytochemistry assays indicated that the recombinant hFIX in seed cotyledonary cells was efficiently directed to protein storage vacuoles. Mass spectrometry characterisation confirmed the presence of the hFIX recombinant protein sequence. Protein extracts from transgenic seeds showed a blood-clotting activity of up to 1.4% of normal plasma. Our results demonstrate the correct processing and stable accumulation of functional hFIX in soybean seeds stored for 6 years under room temperature conditions (22 ± 2°C).

Circulating erythrocyte-derived microparticles are associated with coagulation activation in sickle cell disease

PubMed Central

van Beers, Eduard J.; Schaap, Marianne C.L.; Berckmans, René J.; Nieuwland, Rienk; Sturk, Augueste; van Doormaal, Frederiek F.; Meijers, Joost C.M.; Biemond, Bart J.

2009-01-01

Background Sickle cell disease is characterized by a hypercoagulable state as a result of multiple factors, including chronic hemolysis and circulating cell-derived microparticles. There is still no consensus on the cellular origin of such microparticles and the exact mechanism by which they may enhance coagulation activation in sickle cell disease. Design and Methods In the present study, we analyzed the origin of circulating microparticles and their procoagulant phenotype during painful crises and steady state in 25 consecutive patients with sickle cell disease. Results The majority of microparticles originated from platelets (GPIIIa,CD61) and erythrocytes (glycophorin A,CD235), and their numbers did not differ significantly between crisis and steady state. Erythrocyte-derived microparticles strongly correlated with plasma levels of markers of hemolysis, i.e. hemoglobin (r=−0.58, p<0.001) and lactate dehydrogenase (r=0.59, p<0.001), von Willebrand factor as a marker of platelet/endothelial activation (r=0.44, p<0.001), and D-dimer and prothrombin fragment F1+2 (r=0.52, p<0.001 and r=0.59, p<0.001, respectively) as markers of fibrinolysis and coagulation activation. Thrombin generation depended on the total number of microparticles (r=0.63, p<0.001). Anti-human factor XI inhibited thrombin generation by about 50% (p<0.001), whereas anti-human factor VII was ineffective (p>0.05). The extent of factor XI inhibition was associated with erythrocyte-derived microparticles (r=0.50, p=0.023). Conclusions We conclude that the procoagulant state in sickle cell disease is partially explained by the factor XI-dependent procoagulant properties of circulating erythrocyte-derived microparticles. PMID:19815831

A simple purification and activity assay of the coagulant protein from Moringa oleifera seed.

PubMed

Ghebremichael, Kebreab A; Gunaratna, K R; Henriksson, Hongbin; Brumer, Harry; Dalhammar, Gunnel

2005-06-01

Use of extracts from Moringa oleifera (MO) is of great interest for low-cost water treatment. This paper discusses water and salt extraction of a coagulant protein from the seed, purification using ion exchange, its chemical characteristics, coagulation and antimicrobial properties. The coagulant from both extracts is a cationic protein with pI greater than 9.6 and molecular mass less than 6.5 kDa. Mass spectrometric analysis of the purified water extract indicated that it contained at least four homologous proteins, based on MS/MS peptide sequence data. The protein is thermoresistant and remained active after 5h heat treatment at 95 degrees C. The coagulant protein showed both flocculating and antibacterial effects of 1.1--4 log reduction. With samples of high turbidity, the MO extract showed similar coagulation activity as alum. Cecropin A and MO extract were found to have similar flocculation effects for clay and microorganisms. Simple methods for both the purification and assay of MO coagulating proteins are presented, which are necessary for large-scale water treatment applications.

Structure and dynamics of zymogen human blood coagulation factor X.

PubMed

Venkateswarlu, Divi; Perera, Lalith; Darden, Tom; Pedersen, Lee G

2002-03-01

The solution structure and dynamics of the human coagulation factor X (FX) have been investigated to understand the key structural elements in the zymogenic form that participates in the activation process. The model was constructed based on the 2.3-A-resolution x-ray crystallographic structure of active-site inhibited human FXa (PDB:1XKA). The missing gamma-carboxyglutamic acid (GLA) and part of epidermal growth factor 1 (EGF1) domains of the light chain were modeled based on the template of GLA-EGF1 domains of the tissue factor (TF)-bound FVIIa structure (PDB:1DAN). The activation peptide and other missing segments of FX were introduced using homology modeling. The full calcium-bound model of FX was subjected to 6.2 ns of molecular dynamics simulation in aqueous medium using the AMBER6.0 package. We observed significant reorientation of the serine-protease (SP) domain upon activation leading to a compact multi-domain structure. The solution structure of zymogen appears to be in a well-extended conformation with the distance between the calcium ions in the GLA domain and the catalytic residues estimated to be approximately 95 A in contrast to approximately 83 A in the activated form. The latter is in close agreement with fluorescence studies on FXa. The S1-specificity residues near the catalytic triad show significant differences between the zymogen and activated structures.

Activation of blood coagulation in cancer: implications for tumour progression

PubMed Central

Lima, Luize G.; Monteiro, Robson Q.

2013-01-01

Several studies have suggested a role for blood coagulation proteins in tumour progression. Herein, we discuss (1) the activation of the blood clotting cascade in the tumour microenvironment and its impact on primary tumour growth; (2) the intravascular activation of blood coagulation and its impact on tumour metastasis and cancer-associated thrombosis; and (3) antitumour therapies that target blood-coagulation-associated proteins. Expression levels of the clotting initiator protein TF (tissue factor) have been correlated with tumour cell aggressiveness. Simultaneous TF expression and PS (phosphatidylserine) exposure by tumour cells promote the extravascular activation of blood coagulation. The generation of blood coagulation enzymes in the tumour microenvironment may trigger the activation of PARs (protease-activated receptors). In particular, PAR1 and PAR2 have been associated with many aspects of tumour biology. The procoagulant activity of circulating tumour cells favours metastasis, whereas the release of TF-bearing MVs (microvesicles) into the circulation has been correlated with cancer-associated thrombosis. Given the role of coagulation proteins in tumour progression, it has been proposed that they could be targets for the development of new antitumour therapies. PMID:23889169

Positive Selection during the Evolution of the Blood Coagulation Factors in the Context of Their Disease-Causing Mutations

PubMed Central

Rallapalli, Pavithra M.; Orengo, Christine A.; Studer, Romain A.; Perkins, Stephen J.

2014-01-01

Blood coagulation occurs through a cascade of enzymes and cofactors that produces a fibrin clot, while otherwise maintaining hemostasis. The 11 human coagulation factors (FG, FII–FXIII) have been identified across all vertebrates, suggesting that they emerged with the first vertebrates around 500 Ma. Human FVIII, FIX, and FXI are associated with thousands of disease-causing mutations. Here, we evaluated the strength of selective pressures on the 14 genes coding for the 11 factors during vertebrate evolution, and compared these with human mutations in FVIII, FIX, and FXI. Positive selection was identified for fibrinogen (FG), FIII, FVIII, FIX, and FX in the mammalian Primates and Laurasiatheria and the Sauropsida (reptiles and birds). This showed that the coagulation system in vertebrates was under strong selective pressures, perhaps to adapt against blood-invading pathogens. The comparison of these results with disease-causing mutations reported in FVIII, FIX, and FXI showed that the number of disease-causing mutations, and the probability of positive selection were inversely related to each other. It was concluded that when a site was under positive selection, it was less likely to be associated with disease-causing mutations. In contrast, sites under negative selection were more likely to be associated with disease-causing mutations and be destabilizing. A residue-by-residue comparison of the FVIII, FIX, and FXI sequence alignments confirmed this. This improved understanding of evolutionary changes in FVIII, FIX, and FXI provided greater insight into disease-causing mutations, and better assessments of the codon sites that may be mutated in applications of gene therapy. PMID:25158795

Plasma-based proteomics reveals immune response, complement and coagulation cascades pathway shifts in heat-stressed lactating dairy cows.

PubMed

Min, Li; Cheng, Jianbo; Zhao, Shengguo; Tian, He; Zhang, Yangdong; Li, Songli; Yang, Hongjian; Zheng, Nan; Wang, Jiaqi

2016-09-02

Heat stress (HS) has an enormous economic impact on the dairy industry. In recent years, many researchers have investigated changes in the gene expression and metabolomics profiles in dairy cows caused by HS. However, the proteomics profiles of heat-stressed dairy cows have not yet been completely elucidated. We compared plasma proteomics from HS-free and heat-stressed dairy cows using an iTRAQ labeling approach. After the depletion of high abundant proteins in the plasma, 1472 proteins were identified. Of these, 85 proteins were differentially abundant in cows exposed to HS relative to HS-free. Database searches combined with GO and KEGG pathway enrichment analyses revealed that many components of the complement and coagulation cascades were altered in heat-stressed cows compared with HS-free cows. Of these, many factors in the complement system (including complement components C1, C3, C5, C6, C7, C8, and C9, complement factor B, and factor H) were down-regulated by HS, while components of the coagulation system (including coagulation factors, vitamin K-dependent proteins, and fibrinogens) were up-regulated by HS. In conclusion, our results indicate that HS decreases plasma levels of complement system proteins, suggesting that immune function is impaired in dairy cows exposed to HS. Though many aspects of heat stress (HS) have been extensively researched, relatively little is known about the proteomics profile changes that occur during heat exposure. In this work, we employed a proteomics approach to investigate differential abundance of plasma proteins in HS-free and heat-stressed dairy cows. Database searches combined with GO and KEGG pathway enrichment analyses revealed that HS resulted in a decrease in complement components, suggesting that heat-stressed dairy cows have impaired immune function. In addition, through integrative analyses of proteomics and previous metabolomics, we showed enhanced glycolysis, lipid metabolic pathway shifts, and nitrogen

Charging and coagulation of radioactive and nonradioactive particles in the atmosphere

DOE PAGES

Kim, Yong-ha; Yiacoumi, Sotira; Nenes, Athanasios; ...

2016-01-01

Charging and coagulation influence one another and impact the particle charge and size distributions in the atmosphere. However, few investigations to date have focused on the coagulation kinetics of atmospheric particles accumulating charge. This study presents three approaches to include mutual effects of charging and coagulation on the microphysical evolution of atmospheric particles such as radioactive particles. The first approach employs ion balance, charge balance, and a bivariate population balance model (PBM) to comprehensively calculate both charge accumulation and coagulation rates of particles. The second approach involves a much simpler description of charging, and uses a monovariate PBM and subsequentmore » effects of charge on particle coagulation. The third approach is further simplified assuming that particles instantaneously reach their steady-state charge distributions. It is found that compared to the other two approaches, the first approach can accurately predict time-dependent changes in the size and charge distributions of particles over a wide size range covering from the free molecule to continuum regimes. The other two approaches can reliably predict both charge accumulation and coagulation rates for particles larger than about 0.04 micrometers and atmospherically relevant conditions. These approaches are applied to investigate coagulation kinetics of particles accumulating charge in a radioactive neutralizer, the urban atmosphere, and an atmospheric system containing radioactive particles. Limitations of the approaches are discussed.« less

Hi-tech of the prostate: interstitial laser coagulation of benign prostatic hypertrophy

NASA Astrophysics Data System (ADS)

Muschter, Rolf; Hofstetter, Alfons G.; Hessel, Stefan F. F.; Keiditsch, Ernst; Rothenberger, Karl-Heinz; Schneede, Peter; Frank, Klaus H.

1992-06-01

We report on the new technique of interstitial laser coagulation of the prostate (ILCP) in the treatment of benign prostatic hyperplasia (BPH). Basic experiments by use of a Nd:YAG laser in combination with a newly designed fiber tip homogeneously distributing the laser irradiation have been performed in potato, muscle, liver, and surgically removed human BPH-tissue to determine the volume of coagulation. The coagulation zone surrounding the probe was well defined and homogeneous. The size was dependent on laser power and irradiation time. Carbonization was never present except in darker tissues irradiated with high energy. Volume and time resolved measurements correlated well with the size of coagulation. 10 W and 5 minutes, for example, resulted in a coagulation zone of 17 X 15 mm. Comparable results have been seen in in-vivo experiments in surgically exposed canine prostates. Specimen for macroscopic and microscopic examination were taken immediately after treatment and after 5 and 35 days. The well demarked coagulation necrosis of the early stage resulted in cystic degeneration and fibrosis in the later stages. This was combined with shrinkage and reduction in volume. The urothelium of the urethra, the external sphincter and the rectum showed no damage. Until now, 15 patients suffering from obstructive symptoms due to BPH have been treated with interstitial laser coagulation. The probes were inserted from the perineum into the center of each lateral lobe of the prostate by transrectal ultrasound guidance, while the median lobe was treated by urethroscopic guidance, while the median lobe was treated by urethroscopic control. Dependent on the size of the prostate irradiation, time was 5 to 10 minutes per lobe at a power setting of 5 to 10 W.

Exact combinatorial approach to finite coagulating systems

NASA Astrophysics Data System (ADS)

Fronczak, Agata; Chmiel, Anna; Fronczak, Piotr

2018-02-01

This paper outlines an exact combinatorial approach to finite coagulating systems. In this approach, cluster sizes and time are discrete and the binary aggregation alone governs the time evolution of the systems. By considering the growth histories of all possible clusters, an exact expression is derived for the probability of a coagulating system with an arbitrary kernel being found in a given cluster configuration when monodisperse initial conditions are applied. Then this probability is used to calculate the time-dependent distribution for the number of clusters of a given size, the average number of such clusters, and that average's standard deviation. The correctness of our general expressions is proved based on the (analytical and numerical) results obtained for systems with the constant kernel. In addition, the results obtained are compared with the results arising from the solutions to the mean-field Smoluchowski coagulation equation, indicating its weak points. The paper closes with a brief discussion on the extensibility to other systems of the approach presented herein, emphasizing the issue of arbitrary initial conditions.

Application of Cox model in coagulation function in patients with primary liver cancer.

PubMed

Guo, Xuan; Chen, Mingwei; Ding, Li; Zhao, Shan; Wang, Yuefei; Kang, Qinjiong; Liu, Yi

2011-01-01

To analyze the distribution of coagulation parameters in patients with primary liver cancer; explore the relationship between clinical staging, survival, and coagulation parameters by using Coxproportional hazard model; and provide a parameter for clinical management and prognosis. Coagulation parameters were evaluated in 228 patients with primary liver cancer, 52 patients with common liver disease, and 52 normal healthy controls. The relationship between primary livercancer staging and coagulation parameters wasanalyzed. Follow-up examinations were performed. The Cox proportional hazard model was used to analyze the relationship between coagulationparameters and survival. The changes in the coagulation parameters in patients with primary liver cancer were significantly different from those in normal controls. The effect of the disease on coagulation function became more obvious as the severity of liver cancer increased (p<0.05). The levels of D-dimer, fibrinogen degradation products (FDP), fibrinogen (FIB), and platelets (PLT) were negatively correlated with the long-term survival of patients with advanced liver cancer. The stages of primary liver cancer are associated with coagulation parameters. Coagulation parameters are related to survival and risk factors. Monitoring of coagulation parameters may help ensure better surveillance and treatment for liver cancer patients.

Statin use decreases coagulation in users of vitamin K antagonists.

PubMed

van Rein, Nienke; Biedermann, J S; Bonafacio, S M; Kruip, M J H A; van der Meer, F J M; Lijfering, W M

2016-12-01

The purpose of the study is to determine the immediate and long-term effect of statins on coagulation in patients treated with vitamin K antagonists (VKAs). We selected patients on VKAs of two Dutch anticoagulation clinics who initiated treatment with a statin between 2009 and 2013. Patients who initiated or stopped concomitant drugs that interact with VKAs or were hospitalised during follow-up were excluded. The VKA dosage (mg/day) after statin initiation was compared with the last VKA dosage before the statin was started. Immediate and long-term differences in VKA dosage (at 6 and 12 weeks) were calculated with a paired student t test. Four hundred thirty-five phenprocoumon users (mean age 70 years, 60 % men) and 303 acenocoumarol users (mean age 69 years, 58 % men) were included. After start of statin use, the immediate phenprocoumon dosage was 0.02 mg/day (95 % CI, 0.00 to 0.03) lower. At 6 and 12 weeks, these phenprocoumon dosages were 0.03 (95 % CI, 0.01 to 0.05) and 0.07 mg/day (95 % CI, 0.04 to 0.09) lower as compared with the dosage before first statin use. In acenocoumarol users, VKA dosage was 0.04 mg/day (95%CI, 0.01 to 0.07) (immediate effect), 0.10 (95 % CI, 0.03 to 0.16) (at 6 weeks), and 0.11 mg/day (95 % CI, 0.04 to 0.18) (after 12 weeks) lower. Initiation of statin treatment was associated with an immediate and long-term minor although statistically significant decrease in VKA dosage in both phenprocoumon and acenocoumarol users, which suggests that statins may have anticoagulant properties.

Adenovirus Type 5 Early Region 1B 55K Oncoprotein-Dependent Degradation of Cellular Factor Daxx Is Required for Efficient Transformation of Primary Rodent Cells▿

PubMed Central

Schreiner, Sabrina; Wimmer, Peter; Groitl, Peter; Chen, Shuen-Yuan; Blanchette, Paola; Branton, Philip E.; Dobner, Thomas

2011-01-01

Early region 1B 55K (E1B-55K) from adenovirus type 5 (Ad5) is a multifunctional regulator of lytic infection and contributes in vitro to complete cell transformation of primary rodent cells in combination with Ad5 E1A. Inhibition of p53 activated transcription plays a key role in processes by which E1B-55K executes its oncogenic potential. Nevertheless, additional functions of E1B-55K or further protein interactions with cellular factors of DNA repair, transcription, and apoptosis, including Mre11, PML, and Daxx, may also contribute to the transformation process. In line with previous results, we performed mutational analysis to define a Daxx interaction motif within the E1B-55K polypeptide. The results from these studies showed that E1B-55K/Daxx binding is not required for inhibition of p53-mediated transactivation or binding and degradation of cellular factors (p53/Mre11). Surprisingly, these mutants lost the ability to degrade Daxx and showed reduced transforming potential in primary rodent cells. In addition, we observed that E1B-55K lacking the SUMO-1 conjugation site (SCS/K104R) was sufficient for Daxx interaction but no longer capable of E1B-55K-dependent proteasomal degradation of the cellular factor Daxx. These results, together with the observation that E1B-55K SUMOylation is required for efficient transformation, provides evidence for the idea that SUMO-1-conjugated E1B-55K-mediated degradation of Daxx plays a key role in adenoviral oncogenic transformation. We assume that the viral protein contributes to cell transformation through the modulation of Daxx-dependent pathways. This further substantiates the assumption that further mechanisms for efficient transformation of primary cells can be separated from functions required for the inhibition of p53-stimulated transcription. PMID:21697482

Coagulation factor VII is regulated by androgen receptor in breast cancer.

PubMed

Naderi, Ali

2015-02-01

Androgen receptor (AR) is widely expressed in breast cancer; however, there is limited information on the key molecular functions and gene targets of AR in this disease. In this study, gene expression data from a cohort of 52 breast cancer cell lines was analyzed to identify a network of AR co-expressed genes. A total of 300 genes, which were significantly enriched for cell cycle and metabolic functions, showed absolute correlation coefficients (|CC|) of more than 0.5 with AR expression across the dataset. In this network, a subset of 35 "AR-signature" genes were highly co-expressed with AR (|CC|>0.6) that included transcriptional regulators PATZ1, NFATC4, and SPDEF. Furthermore, gene encoding coagulation factor VII (F7) demonstrated the closest expression pattern with AR (CC=0.716) in the dataset and factor VII protein expression was significantly associated to that of AR in a cohort of 209 breast tumors. Moreover, functional studies demonstrated that AR activation results in the induction of factor VII expression at both transcript and protein levels and AR directly binds to a proximal region of F7 promoter in breast cancer cells. Importantly, AR activation in breast cancer cells induced endogenous factor VII activity to convert factor X to Xa in conjunction with tissue factor. In summary, F7 is a novel AR target gene and AR activation regulates the ectopic expression and activity of factor VII in breast cancer cells. These findings have functional implications in the pathobiology of thromboembolic events and regulation of factor VII/tissue factor signaling in breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

The effect of different methods of leucoreduction on plasma coagulation factors.

PubMed

Aboul Enein, Azza A; Abdel Rahman, Hala A; Abdel Maged, Mohamed M M; El Sissy, Maha H

2017-03-01

Removal of leucocytes from blood products, namely leucoreduction, improves the safety of blood transfusion by reducing adverse events associated with the incidental transfusion of leucocytes. Coagulation factors might be compromised during leucoreduction because of exposure of plasma to a variety of filter materials. The aim of the current study was to assess the effect of different methods of prestorage leucofiltration (apheresis and whole blood filters) on prothrombin time, international normalized ratio, partial thromboplastin time and factors V and VIII. There was a significant prolongation of prothrombin time as well as elevation of international normalized ratio in plasma after leucoreduction (14.5 ± 0.7 s vs. 13.9 ± 0.7 s, P = 0.008 and 1.14 ± 0.07 vs. 1.09 ± 0.07, P = 0.005, respectively). Also, there was a statistically significant prolongation of activated partial thromboplastin time in nonleucoreduced plasma (55.6 ± 9.9 s vs. 43.2 ± 12.8 s, P = 0.001). There was no significant filtration effect on factors V and VIII levels. Furthermore, there was no significant difference in factors V and VIII levels between plasma filtered by inline whole blood filters and apheresis machine. Leucodepleted plasma originating from both inline whole blood filter and apheresis machine maintained satisfactory levels of factors V and VIII.

Monitoring and treatment of coagulation abnormalities in burn patients. an international survey on current practices

PubMed Central

Lavrentieva, A.; Depetris, N.; Kaimakamis, E.; Berardino, M.; Stella, M.

2016-01-01

Summary The magnitude of coagulation abnormalities, and the definition and treatment of coagulopathy in burn patients are inadequately understood and continue to be discussed in the literature. We aimed to analyse physicians’ views on monitoring and treating coagulation abnormalities in burn patients. A total of 350 questionnaires were distributed electronically to burn ICU physicians. Participation was voluntary and anonymous. Responses were analysed electronically and comparisons were made according to the region of the ICU or the specialty of the physician. Of the 350 questionnaires distributed, 55 (15.7%) were returned. The majority of burn specialists consider sepsis-induced coagulopathy to be the most frequent coagulopathy in burn patients, and 74.5% declare that they do not use any specific definition/scoring system in their department to detect coagulopathy. The majority of specialists (70.8%) use standard coagulation tests. The most frequent indications for plasma transfusion are massive bleeding (32.8%) and Disseminated Intravascular Coagulation syndrome treatment (20%). The main specific factors reported in our study are cryoprecipitate (23.2%) and fibrinogen concentrate (18.9%). 21.1% of respondents state that they do not use any specific coagulation factor substitution in burn patients. Specific coagulation factor substitution is not a routine practice. The low response rate precludes the generalization of our results. PMID:28149244

Vitamin K supplementation increases vitamin K tissue levels but fails to counteract ectopic calcification in a mouse model for pseudoxanthoma elasticum.

PubMed

Gorgels, Theo G M F; Waarsing, Jan H; Herfs, Marjolein; Versteeg, Daniëlle; Schoensiegel, Frank; Sato, Toshiro; Schlingemann, Reinier O; Ivandic, Boris; Vermeer, Cees; Schurgers, Leon J; Bergen, Arthur A B

2011-11-01

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder in which calcification of connective tissue leads to pathology in skin, eye and blood vessels. PXE is caused by mutations in ABCC6. High expression of this transporter in the basolateral hepatocyte membrane suggests that it secretes an as-yet elusive factor into the circulation which prevents ectopic calcification. Utilizing our Abcc6 (-/-) mouse model for PXE, we tested the hypothesis that this factor is vitamin K (precursor) (Borst et al. 2008, Cell Cycle). For 3 months, Abcc6 (-/-) and wild-type mice were put on diets containing either the minimum dose of vitamin K required for normal blood coagulation or a dose that was 100 times higher. Vitamin K was supplied as menaquinone-7 (MK-7). Ectopic calcification was monitored in vivo by monthly micro-CT scans of the snout, as the PXE mouse model develops a characteristic connective tissue mineralization at the base of the whiskers. In addition, calcification of kidney arteries was measured by histology. Results show that supplemental MK-7 had no effect on ectopic calcification in Abcc6 ( -/- ) mice. MK-7 supplementation increased vitamin K levels (in skin, heart and brain) in wild-type and in Abcc6 (-/-) mice. Vitamin K tissue levels did not depend on Abcc6 genotype. In conclusion, dietary MK-7 supplementation increased vitamin K tissue levels in the PXE mouse model but failed to counteract ectopic calcification. Hence, we obtained no support for the hypothesis that Abcc6 transports vitamin K and that PXE can be cured by increasing tissue levels of vitamin K.

Two-incision laparoscopic appendectomy for a severe hemophilia A child patient with coagulation factor VII deficiency

PubMed Central

He, Jin Peng; Feng, Jie Xiong

2017-01-01

Abstract Rationale: The main complication of patients with severe hemophilia is recurrent bleeding events that usually affected musculoskeletal contractures. And replacement therapy methods were continuously improved to minimize adverse impacts brought by those complications. However, only several cases reported about the appendectomy for hemophilia A. We report a case of acute appendicitis treated by two-incision laparoscopy in a boy with hemophilia A and coagulation factor VII deficiency for the first time. Patient concerns: An 8y7m-old Chinese boy presented with half a day of right sided abdominal pain, fever, nausea, and vomiting. Diagnoses: He received a computed tomography (CT) scan which revealed an enlarged appendix, thickened wall and appendiceal fecalith, and had received a conservative anti-bacterial treatment for his acute appendicitis but failed. He was diagnosed with hemophilia A and coagulation factor VII deficiency. Interventions: Two-incision laparoscopic appendectomy was made in success with a careful management of perioperative period. We monitored the clotting factor FVIII level and gave him a replacement therapy. Outcomes: The patient had an uneventful recovery. Lessons: It is important to exclude intraabdominal or retroperitoneal hemorrhage in patients suffering from hemophilia and acute abdominal pain. Pre-operative evaluation of validity of the FVIII replacement therapy is another effective strategy to assess the safety and feasibility of applying an operation procedure. The two-incision laparoscopic appendectomy is an effective treatment for this kind of patients for its minimal trauma and fast recovery characteristics. Our report shows that laparoscopic appendectomy is feasible in a child suffering from hemophilia after adequate blood clotting factor replacement treatment. PMID:29019885

Voltage-dependent K+ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane.

PubMed

Schmidt, Daniel; MacKinnon, Roderick

2008-12-09

Voltage-dependent K(+) (Kv) channels underlie action potentials through gating conformational changes that are driven by membrane voltage. In this study of the paddle chimera Kv channel, we demonstrate that the rate of channel opening, the voltage dependence of the open probability, and the maximum achievable open probability depend on the lipid membrane environment. The activity of the voltage sensor toxin VsTx1, which interferes with voltage-dependent gating by partitioning into the membrane and binding to the channel, also depends on the membrane. Membrane environmental factors that influence channel function are divisible into two general categories: lipid compositional and mechanical state. The mechanical state can have a surprisingly large effect on the function of a voltage-dependent K(+) channel, including its pharmacological interaction with voltage sensor toxins. The dependence of VSTx1 activity on the mechanical state of the membrane leads us to hypothesize that voltage sensor toxins exert their effect by perturbing the interaction forces that exist between the channel and the membrane.

Coagulation management in patients undergoing neurosurgical procedures.

PubMed

Robba, Chiara; Bertuetti, Rita; Rasulo, Frank; Bertuccio, Alessando; Matta, Basil

2017-10-01

Management of coagulation in neurosurgical procedures is challenging. In this contest, it is imperative to avoid further intracranial bleeding. Perioperative bleeding can be associated with a number of factors, including anticoagulant drugs and coagulation status but is also linked to the characteristic and the site of the intracranial disorder. The aim of this review will be to focus primarily on the new evidence regarding the management of coagulation in patients undergoing craniotomy for neurosurgical procedures. Antihemostatic and anticoagulant drugs have shown to be associated with perioperative bleeding. On the other hand, an increased risk of venous thromboembolism and hypercoagulative state after elective and emergency neurosurgery, in particular after brain tumor surgery, has been described in several patients. To balance the risk between thrombosis and bleeding, it is important to be familiar with the perioperative changes in coagulation and with the recent management guidelines for anticoagulated patients undergoing neurosurgical procedures, in particular for those taking new direct anticoagulants. We have considered the current clinical trials and literature regarding both safety and efficacy of deep venous thrombosis prophylaxis in the neurosurgical population. These were mainly trials concerning both elective surgical and intensive care patients with a poor grade intracranial bleed or multiple traumas with an associated severe traumatic brain injury (TBI). Coagulation management remains a major issue in patients undergoing neurosurgical procedures. However, in this field of research, literature quality is poor and further studies are necessary to identify the best strategies to minimize risks in this group of patients.

Purification and characterization of a heteromultimeric glycoprotein from Artocarpus heterophyllus latex with an inhibitory effect on human blood coagulation.

PubMed

Siritapetawee, Jaruwan; Thammasirirak, Sompong

2011-01-01

Plant latex has many health benefits and has been used in folk medicine. In this study, the biological effect of Artocarpus heterophyllus (jackfruit) latex on human blood coagulation was investigated. By a combination of heat precipitation and ion-exchange chromatography, a heat stable heteromultimeric glycoprotein (HSGPL1) was purified from jackfruit milky latex. The apparent molecular masses of the monomeric proteins on SDS/PAGE were 33, 31 and 29 kDa. The isoelectric points (pIs) of the monomers were 6.63, 6.63 and 6.93, respectively. Glycosylation and deglycosylation tests confirmed that each subunit of HSGPL1 formed the native multimer by sugar-based interaction. Moreover, the multimer of HSGPL1 also resisted 2-mercaptoethanol action. Peptide mass fingerprint analysis indicated that HSGPL1 was a complex protein related to Hsps/chaperones. HSGPL1 has an effect on intrinsic pathways of the human blood coagulation system by significantly prolonging the activated partial thrombin time (APTT). In contrast, it has no effect on the human extrinsic blood coagulation system using the prothrombin time (PT) test. The prolonged APTT resulted from the serine protease inhibitor property of HSGPL1, since it reduced activity of human blood coagulation factors XI(a) and α-XII(a).

[The blood coagulation system and microcirculatory disorders in ixodid tick-borne borreliosis caused by Borrelia miyamotoi].

PubMed

Platonov, A E; Sarksyan, D S; Karan, L S; Shipulin, G A; Gordygina, E V; Malinin, O V; Maleev, V V

2015-01-01

To study blood coagulation and microcirculatory disorders as a possible cause of transient dysfunctions of organs (the kidney, liver, heart, lung, etc.) in patients with ixodid tick-borne borreliosis caused by Borrelia miyamotoi (Bmt). SUBJECTS AND METHODS; Twenty-four patients with Lyme disease (LD) and 28 Bmt patients treated at Izhevsk City Hospital (Udmurtia) were examined in the study. Platelet counts and the presence of D-dimers were determined; activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen and antithrombin III levels, and Factor XIIa-dependent fibrin clot lysis time were measured. Slit lamp microscopy of the conjunctiva was. also carried out. Results. Platelet counts'were less than 150,000 per pL of blood in 43% of the Bmt patients. All the Bmt patients had at least one abnormal coagulation parameter of the eight ones that were tested; 64% of them had marked coagulation disorders with three or more abnormal laboratory findings. In contrast, all the eight parameters were normal in 71% of the LD patients. The other seven LD patients had only one or two abnormal coagulation parameters (p < 0.001 in comparison with Bmt patients). Microscopic examination of eye capillary blood flow revealed pathological findings that included aggregates of erythrocytes and obstructed and/or sinuous capillaries in 22 (79%) of the Bmt patients, but none of the LD patients. A total of 14 Bmt patients had both coagulation and microcirculatory abnormalities. Eleven of them also had transient signs of organ dysfunction. As far as Borrelia secrete no known toxins, we hypothesized that uncovered disorders of blood coagulation and microcirculation in Bmt patients may contribute to organ dysfunction.

Comparison of functional aspects of the coagulation cascade in human and sea turtle plasmas.

PubMed

Soslau, Gerald; Wallace, Bryan; Vicente, Catherine; Goldenberg, Seth J; Tupis, Todd; Spotila, James; George, Robert; Paladino, Frank; Whitaker, Brent; Violetta, Gary; Piedra, Rotney

2004-08-01

Functional hemostatic pathways are critical for the survival of all vertebrates and have been evolving for more than 400 million years. The overwhelming majority of studies of hemostasis in vertebrates have focused on mammals with very sparse attention paid to reptiles. There have been virtually no studies of the coagulation pathway in sea turtles whose ancestors date back to the Jurassic period. Sea turtles are often exposed to rapidly altered environmental conditions during diving periods. This may reduce their blood pH during prolonged hypoxic dives. This report demonstrates that five species of turtles possess only one branch of the mammalian coagulation pathway, the extrinsic pathway. Mixing studies of turtle plasmas with human factor-deficient plasmas indicate that the intrinsic pathway factors VIII and IX are present in turtle plasma. These two factors may play a significant role in supporting the extrinsic pathway by feedback loops. The intrinsic factors, XI and XII are not detected which would account for the inability of reagents to induce coagulation via the intrinsic pathway in vitro. The analysis of two turtle factors, factor II (prothrombin) and factor X, demonstrates that they are antigenically/functionally similar to the corresponding human factors. The turtle coagulation pathway responds differentially to both pH and temperature relative to each turtle species and relative to human samples. The coagulation time (prothrombin time) increases as the temperature decreases between 37 and 15 degrees C. The increased time follows a linear relationship, with similar slopes for loggerhead, Kemps ridley and hawksbill turtles as well as for human samples. Leatherback turtle samples show a dramatic nonlinear increased time below 23 degrees C, and green turtle sample responses were similar but less dramatic. All samples also showed increased prothrombin times as the pH decreased from 7.8 to 6.4, except for three turtle species. The prothrombin times decreased

Studies of Factors V and VIII:C in an animal model of disseminated intravascular coagulation.

PubMed Central

Giles, A R; Nesheim, M E; Mann, K G

1984-01-01

An experimental animal model of disseminated intravascular coagulation (DIC) induced by the co-infusion of coagulant-active phospholipid and activated Factor X (Factor Xa) is described. The infusion of Factor Xa at a dose of 6.6 X 10(-12) mol/kg with phosphatidylcholine/phosphatidylserine (PCPS) lipid vesicles at a dose of 4.0 X 10(-8) mol/kg was associated with significant falls in the levels of fibrinogen and Factors V and VIII, and a bleeding diathesis developed. Assays of Factors V and VIII were performed by a one-stage prothrombin time and activated partial thrombin time system, respectively. In additional experiments, the effect of the same dose combination of Factor Xa/PCPS on Factor V kinetics was studied by preinfusing 125I-labeled Factor V. After Factor Xa/PCPS infusion, Factors VIII and V were reduced at 2 min by 90 and 50% of the preinfusion levels, respectively, and at 1 h by 80 and 75%, respectively. During the same period, there was little change in the total circulating radioactivity. Autoradiography indicated small but detectable levels of circulating proteolytic products of Factor V that comigrated with peptides obtained by the incubation of Factor V with Factor Xa and activated protein C. The majority of radioactivity remained associated with the intact single-chain precursor Factor V. These observations suggested maintenance of the precursor pool after the onset of DIC. This was confirmed by performing two-stage assays of Factors V and VIII, whereby each was completely converted to the active cofactor, i.e., Va and VIII:Ca, by preincubation of the test sample with thrombin before assaying in a one-stage system as before. The Factor V levels assayed by the two-stage procedure did not change appreciably over 1 h. The Factor VIII levels fell but corrected within 1 h at a time when the level measured by a one-stage assay remained depressed. These results indicate that in the dog, infusion of Factor Xa/PCPS induces changes characteristic of DIC, and

Na and K Dependence of the Na/K Pump in Cystic Fibrosis Fibroblasts

NASA Astrophysics Data System (ADS)

Reznik, Vivian M.; Schneider, Jerry A.; Mendoza, Stanley A.

1981-11-01

The Na and K dependence of the Na/K pump was measured in skin fibroblasts from patients with cystic fibrosis and age/sex-matched controls. Under basal conditions, there was no difference between control and cystic fibrosis cells in protein per cell, intracellular Na and K content, or Na/K pump activity (measured as ouabain-sensitive 86Rb uptake). There was no difference in the Na dependence of the Na/K pump between cystic fibrosis cells and control cells. In cells from patients with cystic fibrosis, the Na/K pump had a significantly lower affinity for K (Km = 1.6 mM) when compared to normals (Km = 0.9 mM). This difference was demonstrated by using two independent experimental designs.

Recombinant epidermal growth factor-like domain-1 from coagulation factor VII functionalized iron oxide nanoparticles for targeted glioma magnetic resonance imaging.

PubMed

Liu, Heng; Chen, Xiao; Xue, Wei; Chu, Chengchao; Liu, Yu; Tong, Haipeng; Du, Xuesong; Xie, Tian; Liu, Gang; Zhang, Weiguo

The highly infiltrative and invasive nature of glioma cells often leads to blurred tumor margins, resulting in incomplete tumor resection and tumor recurrence. Accurate detection and precise delineation of glioma help in preoperative delineation, surgical planning and survival prediction. In this study, recombinant epidermal growth factor-like domain-1, derived from human coagulation factor VII, was conjugated to iron oxide nanoparticles (IONPs) for targeted glioma magnetic resonance (MR) imaging. The synthesized EGF1-EGFP-IONPs exhibited excellent targeting ability toward tissue factor (TF)-positive U87MG cells and human umbilical vein endothelial cells in vitro, and demonstrated persistent and efficient MR contrast enhancement up to 12 h for preclinical glioma models with high targeting specificity in vivo. They hold great potential for clinical translation and developing targeted theranostics against brain glioma.

Optimum coagulant forecasting by modeling jar test experiments using ANNs

NASA Astrophysics Data System (ADS)

Haghiri, Sadaf; Daghighi, Amin; Moharramzadeh, Sina

2018-01-01

Currently, the proper utilization of water treatment plants and optimizing their use is of particular importance. Coagulation and flocculation in water treatment are the common ways through which the use of coagulants leads to instability of particles and the formation of larger and heavier particles, resulting in improvement of sedimentation and filtration processes. Determination of the optimum dose of such a coagulant is of particular significance. A high dose, in addition to adding costs, can cause the sediment to remain in the filtrate, a dangerous condition according to the standards, while a sub-adequate dose of coagulants can result in the reducing the required quality and acceptable performance of the coagulation process. Although jar tests are used for testing coagulants, such experiments face many constraints with respect to evaluating the results produced by sudden changes in input water because of their significant costs, long time requirements, and complex relationships among the many factors (turbidity, temperature, pH, alkalinity, etc.) that can influence the efficiency of coagulant and test results. Modeling can be used to overcome these limitations; in this research study, an artificial neural network (ANN) multi-layer perceptron (MLP) with one hidden layer has been used for modeling the jar test to determine the dosage level of used coagulant in water treatment processes. The data contained in this research have been obtained from the drinking water treatment plant located in Ardabil province in Iran. To evaluate the performance of the model, the mean squared error (MSE) and correlation coefficient (R2) parameters have been used. The obtained values are within an acceptable range that demonstrates the high accuracy of the models with respect to the estimation of water-quality characteristics and the optimal dosages of coagulants; so using these models will allow operators to not only reduce costs and time taken to perform experimental jar tests

Dose control for noncontact laser coagulation of tissue

NASA Astrophysics Data System (ADS)

Roggan, Andre; Albrecht, Hansjoerg; Bocher, Thomas; Rygiel, Reiner; Winter, Harald; Mueller, Gerhard J.

1995-01-01

Nd:YAG lasers emitting at 1064 nm are often used for coagulation of tissue in a non-contact mode, i.e. the treatment of verrucae, endometriosis, tumor coagulation and hemostasis. During this process an uncontrolled temperature rise of the irradiated area leads to vaporization and, finally, to a carbonization of the tissue surface. To prevent this, a dose controlled system was developed using an on-line regulation of the output laser power. The change of the backscattered intensity (remission) of the primary beam was used as a dose dependent feedback parameter. Its dependence on the temperature was determined with a double integrating sphere system and Monte-Carlo simulations. The remission of the tissue was calculated in slab geometry from diffusion theory and Monte-Carlo simulations. The laser control was realized with a PD-circuit and an A/D-converter, enabling the direct connection to the internal bus of the laser system. Preliminary studies with various tissues revealed the practicability of the system.

Enhanced coagulation for improving coagulation performance and reducing residual aluminum combining polyaluminum chloride with diatomite.

PubMed

Hu, Wenchao; Wu, Chunde

2016-01-01

The feasibility of using enhanced coagulation, which combined polyaluminum chloride (PAC) with diatomite for improving coagulation performance and reducing the residual aluminum (Al), was discussed. The effects of PAC and diatomite dosage on the coagulation performance and residual Al were mainly investigated. Results demonstrated that the removal efficiencies of turbidity, dissolved organic carbon (DOC), and UV254 were significantly improved by the enhanced coagulation, compared with PAC coagulation alone. Meaningfully, the five forms of residual Al (total Al (TAl), total dissolved Al (TDAl), dissolved organic Al (DOAl), dissolved monomeric Al (DMAl), and dissolved organic monomeric Al (DOMAl)) all had different degrees of reduction in the presence of diatomite and achieved the lowest concentrations (0.185, 0.06, 0.053, 0.014, and 0 mg L(-1), respectively) at a PAC dose of 15 mg L(-1) and diatomite dose of 40 mg L(-1). In addition, when PAC was used as coagulant, the majority of residual Al existed in dissolved form (about 31.14-70.16%), and the content of DOMAl was small in the DMAl.

Coagulation indices in very preterm infants from cord blood and postnatal samples.

PubMed

Neary, E; McCallion, N; Kevane, B; Cotter, M; Egan, K; Regan, I; Kirkham, C; Mooney, C; Coulter-Smith, S; Ní Áinle, F

2015-11-01

Very premature infants are at high risk of bleeding complications; however, few data exist on ranges for standard coagulation tests. The primary objective of this study was to measure standard plasma coagulation tests and thrombin generation in very premature infants compared with term infants. The secondary objective was to evaluate whether an association existed between coagulation indices and intraventricular hemorrhage (IVH). Cord and peripheral blood of neonates < 30 weeks gestational age (GA) was drawn at birth, on days 1 and 3 and fortnightly until 30 weeks corrected gestational age. Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen and coagulation factor levels were measured and tissue factor-stimulated thrombin generation was characterized. Control plasma was obtained from cord blood of term neonates. One hundred and sixteen infants were recruited. Median (range) GA was 27.7 (23.7-29.9) weeks and mean (SD) birth weight was 1020 (255) g. Median (5th-95th percentile) day 1 PT, APTT and fibrinogen were 17.5 (12.7-26.6) s, 78.7 (48.7-134.3) s and 1.4 (0.72-3.8) g L(-1) , respectively. No difference in endogenous thrombin potential between preterm and term plasma was observed, where samples were available. Levels of coagulation factors II, VII, IX and X, protein C, protein S and antithrombin were reduced in preterm compared with term plasma. Day 1 APTT and PT were not associated with IVH. In the largest cross-sectional study to date of very preterm infants, typical ranges for standard coagulation tests were determined. Despite long clotting times, thrombin generation was observed to be similar in very preterm and term infants. © 2015 International Society on Thrombosis and Haemostasis.

Use of combined coagulation-adsorption process as pretreatment of landfill leachate

PubMed Central

2013-01-01

Landfill leachate is an important pollution factor resulting from municipal landfill sites. Physical and chemical processes are the better option for pretreatment or full treatment of landfill leachate. This article presents a combination of pre-treatment method (coagulation and adsorption) for leachate collected from municipal solid waste open dumping site. Physico chemical characteristics of stabilized and fresh leachate were examined. Coagulation process was examined by using alum and ferric chloride. A low cost adsorbent, fly ash was used for adsorption studies. Coagulation studies were carried out for fresh and stabilized leachate. Adsorption studies have been conducted for alum pre-treated stabilized leachate. Effect of coagulant dose, adsorbent dose, pH and contact time were carried out. The effective optimum coagulant dosages were 0.6 g/L and 0.7 g/L for alum and ferric chloride respectively for stabilized leachate and incase of fresh leachate 0.8 g/L and 0.6 g/L for alum and ferric chloride respectively. For the alum pretreated stabilized leachate, the maximum COD removal is 28% using fly ash adsorbent with equilibrium time of 210 min and optimum dose of 6 g/L. Overall COD removal efficiency of 82% was obtained by coagulation using alum and adsorption using fly ash for stabilized leachate. The results obtained showed that combined coagulation and adsorption process can be used effectively for stabilized leachate treatment. PMID:23517661

The effect of exercise on coagulation and fibrinolysis factors in patients with peripheral arterial disease.

PubMed

Patelis, Nikolaos; Karaolanis, Georgios; Kouvelos, Georgios N; Hart, Collin; Metheiken, Sean

2016-09-01

Peripheral arterial disease is a widely prevalent atherosclerotic occlusive disorder. Symptoms commence with exercise-induced pain in the lower extremities, known as claudication. Despite the fact that exercise has been shown to improve fibrinolytic profile some patients, the effect of exercise on coagulation and fibrinolysis cascades in claudicants has not been comprehensively defined. Literature search in English language yielded 13 studies of exercise on claudicants, including 420 patients. Claudicants tend to have a higher coagulation activity at rest compared to healthy individuals, a trend that persists even after exercise. Post-exercise coagulation activity of claudicants is increased when compared to their respective baseline levels, but it is so in a non-consistent manner. From the available data, it has been suggested that claudicants have a functional and effective fibrinolytic mechanism in place, operating continuously at a relatively higher activity level compared to healthy individuals. Fibrinolysis seems to be activated by exercise; a positive outcome with a prolonged effect as shown by a few of the studies. A final conclusion whether coagulation or fibrinolysis activity is affected mostly by exercise type and intensity in claudicants could not be answered. All conclusions regarding the effect of exercise on the coagulation and fibrinolysis mechanisms should be taken under cautious consideration, due to the limited number of studies, the small number of patients and the different exercise strategies employed in each study. Further randomized studies with similar exercise protocols could provide safer conclusions in the future. © 2016 by the Society for Experimental Biology and Medicine.

The production of coagulation factor VII by adipocytes is enhanced by tumor necrosis factor-α or isoproterenol.

PubMed

Takahashi, N; Yoshizaki, T; Hiranaka, N; Kumano, O; Suzuki, T; Akanuma, M; Yui, T; Kanazawa, K; Yoshida, M; Naito, S; Fujiya, M; Kohgo, Y; Ieko, M

2015-05-01

A relationship has been reported between blood concentrations of coagulation factor VII (FVII) and obesity. In addition to its role in coagulation, FVII has been shown to inhibit insulin signals in adipocytes. However, the production of FVII by adipocytes remains unclear. We herein investigated the production and secretion of FVII by adipocytes, especially in relation to obesity-related conditions including adipose inflammation and sympathetic nerve activation. C57Bl/6J mice were fed a low- or high-fat diet and the expression of FVII messenger RNA (mRNA) was then examined in adipose tissue. 3T3-L1 cells were used as an adipocyte model for in vitro experiments in which these cells were treated with tumor necrosis factor-α (TNF-α) or isoproterenol. The expression and secretion of FVII were assessed by quantitative real-time PCR, Western blotting and enzyme-linked immunosorbent assays. The expression of FVII mRNA in the adipose tissue of mice fed with high-fat diet was significantly higher than that in mice fed with low-fat diet. Expression of the FVII gene and protein was induced during adipogenesis and maintained in mature adipocytes. The expression and secretion of FVII mRNA were increased in the culture medium of 3T3-L1 adipocytes treated with TNF-α, and these effects were blocked when these cells were exposed to inhibitors of mitogen-activated kinases or NF-κB activation. The β-adrenoceptor agonist isoproterenol stimulated the secretion of FVII from mature adipocytes via the cyclic AMP/protein kinase A pathway. Blockade of secreted FVII with the anti-FVII antibody did not affect the phosphorylation of Akt in the isoproterenol-stimulated adipocytes. Obese adipose tissue produced FVII. The production and secretion of FVII by adipocytes was enhanced by TNF-α or isoproterenol via different mechanisms. These results indicate that FVII is an adipokine that plays an important role in the pathogenesis of obesity.

Theories of blood coagulation.

PubMed

Riddel, James P; Aouizerat, Bradley E; Miaskowski, Christine; Lillicrap, David P

2007-01-01

Although the concept of the coagulation cascade represented a significant advance in the understanding of coagulation and served for many years as a useful model, more recent clinical and experimental observations demonstrate that the cascade/waterfall hypothesis does not fully and completely reflect the events of hemostasis in vivo. The goal of this article is to review the evolution of the theories of coagulation and their proposed models to serve as a tool when reviewing the research and practice literature that was published in the context of these different theories over time.

Tissue factor-dependent vascular endothelial growth factor production by human fibroblasts in response to activated factor VII.

PubMed

Ollivier, V; Bentolila, S; Chabbat, J; Hakim, J; de Prost, D

1998-04-15

The transmembrane protein tissue factor (TF) is the cell surface receptor for coagulation factor VII (FVII) and activated factor VII (FVIIa). Recently, TF has been identified as a regulator of angiogenesis, tumor growth, and metastasis. This study was designed to link the binding of FVII(a) to its receptor, TF, with the subsequent triggering of angiogenesis through vascular endothelial growth factor (VEGF) production by human lung fibroblasts. We report that incubation of fibroblasts, which express constitutive surface TF, with FVII(a) induces VEGF synthesis. FVII(a)-induced VEGF secretion, assessed by a specific enzyme-linked immunosorbent assay, was time- and concentration-dependent. VEGF secretion was maximal after 24 hours of incubation of the cells with 100 nmol/L FVII(a) and represented a threefold induction of the basal VEGF level. Reverse transcriptase-polymerase chain reaction analysis of VEGF detected three mRNA species of 180, 312, and 384 bp corresponding, respectively, to VEGF121, VEGF165, and VEGF189. A 2.5- to 3.5-fold increase was observed for the 180- and 312-bp transcripts at 12 and 24 hours, respectively. FVII(a)-dependent VEGF production was inhibited by a pool of antibodies against TF, pointing to the involvement of this receptor. On specific active-site inhibition with dansyl-glutamyl-glycinyl-arginyl chloromethyl ketone, FVIIa lost 70% of its capacity to elicit VEGF production. Consistent with this, the native form (zymogen) of FVII only had a 1.8-fold stimulating effect. Protein tyrosine kinase and protein kinase C are involved in signal transduction leading to VEGF production, as shown by the inhibitory effects of genistein and GF 109203X. The results of this study indicate that TF is essential for VIIa-induced VEGF production by human fibroblasts and that its role is mainly linked to the proteolytic activity of the TF-VIIa complex.

Mathematical Modeling of Intravascular Blood Coagulation under Wall Shear Stress

PubMed Central

Rukhlenko, Oleksii S.; Dudchenko, Olga A.; Zlobina, Ksenia E.; Guria, Georgy Th.

2015-01-01

Increased shear stress such as observed at local stenosis may cause drastic changes in the permeability of the vessel wall to procoagulants and thus initiate intravascular blood coagulation. In this paper we suggest a mathematical model to investigate how shear stress-induced permeability influences the thrombogenic potential of atherosclerotic plaques. Numerical analysis of the model reveals the existence of two hydrodynamic thresholds for activation of blood coagulation in the system and unveils typical scenarios of thrombus formation. The dependence of blood coagulation development on the intensity of blood flow, as well as on geometrical parameters of atherosclerotic plaque is described. Relevant parametric diagrams are drawn. The results suggest a previously unrecognized role of relatively small plaques (resulting in less than 50% of the lumen area reduction) in atherothrombosis and have important implications for the existing stenting guidelines. PMID:26222505

Blood coagulation, fibrinolytic activity and lipid profile in subclinical thyroid disease: subclinical hyperthyroidism increases plasma factor X activity.

PubMed

Erem, Cihangir

2006-03-01

Various abnormalities of coagulation and fibrinolysis occur in patients with thyroid diseases, and may range from subclinical laboratory abnormalities to clinically significant disorders of coagulation and, rarely, major haemorrhage or thromboembolism. The influence of subclinical hypothyroidism (SHypo) on haemostasis is controversial, both hypercoagulable and hypocoagulable states have been reported. A hypercoagulable state might be a risk factor for thromboembolic disease in SHypo. On the other hand, subclinical hyperthyroidism (SCHyper) is associated with enhanced cardiovascular risk. In the English literature, there are no studies on changes in coagulation and fibriolytic status in subjects with SCHyper. Therefore, the aim of the present study was to investigate the markers of endogenous coagulation and fibrinolysis, and to evaluate the relationships between serum lipid profile and thyroid hormones and these haemostatic parameters in subclinical thyroid patients. Various haemostatic parameters were investigated in 30 patients with SHypo and 20 patients with SCHyper and compared to 20 euthyroid controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, factors V, VII, VIII, IX and X activities, vWF, antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor-1 (PAI-1), as well as common lipid variables, were measured. The relationships between serum thyroid hormones and these haemostatic parameters were examined. Compared with the control subjects, only FX activity was significantly increased in patients with SCHyper (P < 0.01). Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in patients with SHypo compared with the control group (P < 0.001 and P < 0.01, respectively). TC levels were significantly higher in patients with SCHyper than in controls (P < 0.05). No differences could be found in coagulation

Effects of storage conditions of Moringa oleifera seeds on its performance in coagulation.

PubMed

Katayon, S; Noor, M J Megat Mohd; Asma, M; Ghani, L A Abdul; Thamer, A M; Azni, I; Ahmad, J; Khor, B C; Suleyman, A M

2006-09-01

Moringa oleifera is a plant whose seeds have coagulation properties for treating water and wastewater. In this study the coagulation efficiency of Moringa oleifera kept in different storage conditions were studied. The Moringa oleifera seeds were stored at different conditions and durations; open container and closed container at room temperature (28 degrees C) and refrigerator (3 degrees C) for durations of 1, 3 and 5 months. Comparison between turbidity removal efficiency of Moringa oleifera kept in refrigerator and room temperature revealed that there was no significant difference between them. The Moringa oleifera kept in refrigerator and room temperature for one month showed higher turbidity removal efficiency, compared to those kept for 3 and 5 months, at both containers. The coagulation efficiency of Moringa oleifera was found to be dependent on initial turbidity of water samples. Highest turbidity removals were obtained for water with very high initial turbidity. In summary coagulation efficiency of Moringa oleifera was found independent of storage temperature and container, however coagulation efficiency of Moringa oleifera decreased as storage duration increased. In addition, Moringa oleifera can be used as a potential coagulant especially for very high turbidity water.

Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector.

PubMed

Herzog, R W; Yang, E Y; Couto, L B; Hagstrom, J N; Elwell, D; Fields, P A; Burton, M; Bellinger, D A; Read, M S; Brinkhous, K M; Podsakoff, G M; Nichols, T C; Kurtzman, G J; High, K A

1999-01-01

Hemophilia B is a severe X-linked bleeding diathesis caused by the absence of functional blood coagulation factor IX, and is an excellent candidate for treatment of a genetic disease by gene therapy. Using an adeno-associated viral vector, we demonstrate sustained expression (>17 months) of factor IX in a large-animal model at levels that would have a therapeutic effect in humans (up to 70 ng/ml, adequate to achieve phenotypic correction, in an animal injected with 8.5x10(12) vector particles/kg). The five hemophilia B dogs treated showed stable, vector dose-dependent partial correction of the whole blood clotting time and, at higher doses, of the activated partial thromboplastin time. In contrast to other viral gene delivery systems, this minimally invasive procedure, consisting of a series of percutaneous intramuscular injections at a single timepoint, was not associated with local or systemic toxicity. Efficient gene transfer to muscle was shown by immunofluorescence staining and DNA analysis of biopsied tissue. Immune responses against factor IX were either absent or transient. These data provide strong support for the feasibility of the approach for therapy of human subjects.

Voltage-dependent K+ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane

PubMed Central

Schmidt, Daniel; MacKinnon, Roderick

2008-01-01

Voltage-dependent K+ (Kv) channels underlie action potentials through gating conformational changes that are driven by membrane voltage. In this study of the paddle chimera Kv channel, we demonstrate that the rate of channel opening, the voltage dependence of the open probability, and the maximum achievable open probability depend on the lipid membrane environment. The activity of the voltage sensor toxin VsTx1, which interferes with voltage-dependent gating by partitioning into the membrane and binding to the channel, also depends on the membrane. Membrane environmental factors that influence channel function are divisible into two general categories: lipid compositional and mechanical state. The mechanical state can have a surprisingly large effect on the function of a voltage-dependent K+ channel, including its pharmacological interaction with voltage sensor toxins. The dependence of VSTx1 activity on the mechanical state of the membrane leads us to hypothesize that voltage sensor toxins exert their effect by perturbing the interaction forces that exist between the channel and the membrane. PMID:19050073

Enhanced algae removal by Ti-based coagulant: comparison with conventional Al- and Fe-based coagulants.

PubMed

Xu, Jie; Zhao, Yanxia; Gao, Baoyu; Zhao, Qian

2018-05-01

The water eutrophication caused by cyanobacteria seasonally proliferates, which is a hot potato to be resolved for water treatment plants. This study firstly investigated coagulation performance of titanium tetrachloride (TiCl 4 ) for Microcystis aeruginosa synthetic water treatment. Results show complete algal cell removal by TiCl 4 coagulation without damage to cell membrane integrity even under harsh conditions; 60 mg/L TiCl 4 was effective in removing the microcystins up to 85%. Furthermore, besides having stronger UV 254 removal capability and the higher removal of fluorescent substances over Al- and Fe-based coagulants, TiCl 4 coagulant required more compact coagulation and sedimentation tanks due to its significantly improved floc growth and sedimentation speed. Meanwhile, its' short hydraulic retention time avoided algal cell breakage and subsequent algal organic matter release. Microcystin concentrations were kept at a low level during sludge storage period, indicating that the TiCl 4 flocs could prevent algal cells from natural lysis. To facilitate water recycling without secondary contamination, the algae-containing sludge after TiCl 4 coagulation ought to be disposed within 12 days at 20 °C and 8 days at 35 °C.

Removal of Arsenic from Drinking Water by Adsorption and Coagulation

NASA Astrophysics Data System (ADS)

Zhang, M.; Sugita, H.; Hara, J.; Takahashi, S.

2013-12-01

Removal of arsenic from drinking water has been an important issue worldwide, which has attracted greater attentions in recent years especially for supplying safe drinking water in developing countries. Although many kinds of treatment approaches that are available or applicable both in principle and practice, such as adsorption, coagulation, membrane filtration, ion exchange, biological process, electrocoagulation and so on, the first 2 approaches (i.e., adsorption and coagulation) are most promising due to the low-cost, high-efficiency, simplicity of treating systems, and thus can be practically used in developing countries. In this study, a literature survey on water quality in Bangladesh was performed to understand the ranges of arsenic concentration and pH of groundwater in Bangladesh. A series of tests were then organized and performed to investigate the effects of arsenic concentration, arsenic forms, pH, chemical compositions of the materials used for adsorption and coagulation, particle size distribution and treatment time on quality of treated water. The experimental results obtained in the study illustrated that both adsorption and coagulation can be used to effectively reduce the concentrations of either arsenic (V) or arsenic (III) from the contaminated water. Coagulation of arsenic with a magnesium-based material developed in this study can be very effective to remove arsenic, especially arsenic (V), from contaminated water with a concentration of 10 ppm to an undetectable level of 0.002 ppm by ICP analyses. Compared to arsenic (III), arsenic (V) is easier to be removed. The materials used for adsorption and coagulation in this study can remove arsenic (V) up to 9 mg/g and 6 mg/g, and arsenic (III) up to 4 mg/g and 3 mg/g, respectively, depending on test conditions and compositions of the materials being used. The control of pH during treatment can be a challenging technical issue for developing both adsorbent and coagulant. Keywords: Water Treatment

Synthesis of Phosphatidylserine and Its Stereoisomers: Their Role in Activation of Blood Coagulation.

PubMed

Mallik, Suman; Prasad, Ramesh; Bhattacharya, Anindita; Sen, Prosenjit

2018-05-10

Natural phosphatidylserine (PS), which contains two chiral centers, enhances blood coagulation. However, the process by which PS enhanced blood coagulation is not completely understood. An efficient and flexible synthetic route has been developed to synthesize all of the possible stereoisomers of PS. In this study, we examined the role of PS chiral centers in modulating the activity of the tissue factor (TF)-factor VIIa coagulation initiation complex. Full length TF was relipidated with phosphatidylcholine, and the synthesized PS isomers were individually used to estimate the procoagulant activity of the TF-FVIIa complex via a FXa generation assay. The results revealed that the initiation complex activity was stereoselective and had increased sensitivity to the configuration of the PS glycerol backbone due to optimal protein-lipid interactions.

Dust coagulation in ISM

NASA Technical Reports Server (NTRS)

Chokshi, Arati; Tielens, Alexander G. G. M.; Hollenbach, David

1989-01-01

Coagulation is an important mechanism in the growth of interstellar and interplanetary dust particles. The microphysics of the coagulation process was theoretically analyzed as a function of the physical properties of the coagulating grains, i.e., their size, relative velocities, temperature, elastic properties, and the van der Waal interaction. Numerical calculations of collisions between linear chains provide the wave energy in individual particles and the spectrum of the mechanical vibrations set up in colliding particles. Sticking probabilities are then calculated using simple estimates for elastic deformation energies and for the attenuation of the wave energy due to absorption and scattering processes.

Treatment of Arctic wastewater by chemical coagulation, UV and peracetic acid disinfection.

PubMed

Chhetri, Ravi Kumar; Klupsch, Ewa; Andersen, Henrik Rasmus; Jensen, Pernille Erland

2017-02-16

Conventional wastewater treatment is challenging in the Arctic region due to the cold climate and scattered population. Thus, no wastewater treatment plant exists in Greenland, and raw wastewater is discharged directly to nearby waterbodies without treatment. We investigated the efficiency of physicochemical wastewater treatment, in Kangerlussuaq, Greenland. Raw wastewater from Kangerlussuaq was treated by chemical coagulation and UV disinfection. By applying 7.5 mg Al/L polyaluminium chloride (PAX XL100), 73% of turbidity and 28% phosphate was removed from raw wastewater. E. coli and Enterococcus were removed by 4 and 2.5 log, respectively, when UV irradiation of 0.70 kWh/m 3 was applied to coagulated wastewater. Furthermore, coagulated raw wastewater in Denmark, which has a chemical quality similar to Greenlandic wastewater, was disinfected by peracetic acid or UV irradiation. Removal of heterotrophic bacteria by applying 6 and 12 mg/L peracetic acid was 2.8 and 3.1 log, respectively. Similarly, removal of heterotrophic bacteria by applying 0.21 and 2.10 kWh/m 3 for UV irradiation was 2.1 and greater than 4 log, respectively. Physicochemical treatment of raw wastewater followed by UV irradiation and/or peracetic acid disinfection showed the potential for treatment of arctic wastewater.

Effect of rivaroxaban on blood coagulation using the viscoelastic coagulation test ROTEM™.

PubMed

Casutt, M; Konrad, C; Schuepfer, G

2012-11-01

This study investigated the influence of the oral direct inhibitor of factor Xa rivaroxaban on blood coagulation measured by rotation thrombelastometry ROTEM™. Blood was obtained from 11 healthy male volunteers before and 2.5 h after oral administration of 10 mg rivaroxaban. In addition to standard coagulation tests clot formation was measured by ROTEM™ analyzing extrinsic (Extem) and intrinsic thrombelastometry (Intem). Significant differences to the baseline values were found in the Extem clotting time (Extem-CT, 58 ± 9 s and 87 ± 17 s, p < 0.01), Intem-CT (194 ± 26 s and 239 ± 43 s; p = 0.02), prothrombin time (PT, 86 ± 9% and 67 ± 7%; p < 0.01) and activated partial thromboplastin time (aPTT, 28 ± 1 s and 35 ± 2 s; p < 0.01). There was a low correlation between Extem-CT and PT as well as between Intem-CT and aPTT before and after rivaroxaban intake. The receiver operating characteristic curve (ROC) analysis determined aPTT to be the most appropriate parameter for the prediction of rivaroxaban-induced anticoagulation, Intem-CT and Extem-CT proved to be moderate tests and PT had no significance in the prediction of rivaroxaban-induced anticoagulation. Of utmost clinical importance was the fact that rivaroxaban treated patients could still show normal ROTEM™ values. Thus, ROTEM™ cannot be a suitable test method to exclude inhibition of blood coagulation by rivaroxaban.

Effect of fibrinogen on blood coagulation detected by optical coherence tomography.

PubMed

Xu, Xiangqun; Teng, Xiangshuai

2015-05-21

Our previous work demonstrated that an optical coherence tomography (OCT) technique and the parameter 1/e light penetration depth (d1/e) were able to characterize the whole blood coagulation process in contrast to existing optical tests that are performed on plasma samples. To evaluate the feasibility of the technique for quantifying the effect of fibrinogen (Fbg) on blood coagulation, a dynamic study of d1/e of blood in various Fbg concentrations was performed in static state. Two groups of blood samples of hematocrit (HCT) in 35, 45, and 55% were reconstituted of red blood cells with: 1) treated plasma with its intrinsic Fbg removed and commercial Fbg added (0-8 g L(-1)); and 2) native plasma with commercial Fbg added (0-8 g L(-1)). The results revealed a typical behavior due to coagulation induced by calcium ions and the clotting time is Fbg concentration-dependent. The clotting time was decreased by the increasing amount of Fbg in both groups. Besides, the blood of lower HCT with various levels of Fbg took shorter time to coagulate than that of higher HCT. Consequently, the OCT method is a useful and promising tool for the detection of blood-coagulation processes induced with different Fbg levels.

The first report on coagulation and phospholipase A2 activities of Persian Gulf lionfish, Pterois russelli, an Iranian venomous fish.

PubMed

Memar, Bahareh; Jamili, Shahla; Shahbazzadeh, Delavar; Bagheri, Kamran Pooshang

2016-04-01

Pterois russelli is a venomous fish belonging to scorpionidae family. Regarding to high significance value for tracing potential therapeutic molecules and special agents from venomous marine creatures, the present study was aimed to characterization of the Persian Gulf lionfish venom. Proteolytic, phospholipase, hemolytic, coagulation, edematogenic and dermonecrotic activities were determined for extracted venom. The LD50 of P. russelli venom was determined by intravenous injection in white Balb/c mice. Phospholipase A2 activity was recorded at 20 μg of total venom. Coagulation activity on human plasma was shown by Prothrombin Time (PT) and activated Partial Thromboplastin Time (APTT) assays and coagulation visualized after 7 and 14 s respectively for 60 μg of crude venom. LD50 was calculated as 10.5 mg/kg. SDS-PAGE revealed the presence of major and minor protein bands between 6 and 205 kDa. Different amounts of crude venom ranged from 1.87 to 30 μg showed proteolytic activity on casein. The highest edematic activity was detected at 20 μg. Our findings showed that the edematic activity was dose dependent and persisted for 48 h after injection. The crude venom did not induce dermonecrotic activity on rabbit skin and showed no hemolytic activity on human, mouse and rabbit erythrocytes. This is the first report for phospholipase A2 and coagulation activity in venomous fish and venomous marine animals respectively. Proteolytic activity of P. russelli venom is in accordance with the other genara of scorpionidae family. According to venom activity on intrinsic and extrinsic coagulation pathways, lionfish venom would be contained an interesting pharmaceutical agent. This study is pending to further characterization of phospholipase A2, coagulation, and protease activities and also in vivo activity on animal model of surface and internal bleeding. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pilot testing of dissolved air flotation (DAF) in a highly effective coagulation-flocculation integrated (FRD) system.

PubMed

Wang, Yili; Guo, Jinlong; Tang, Hongxiao

2002-01-01

Factors of pretreatment coagulation/flocculation units were studied using raw water of low temperature and low turbidity. Aluminum sulfate (AS) and selected polyaluminium chlorides (PACls) were all effective in the DAF process when used under favorable conditions of coagulant addition, coagulation, flocculation and flotation units. Compared with the AS coagulant, PACls, at lower dosage, could give the same effective performance even with shorter coagulation/flocculation time or lower recycle ratio during the treatment of cold water. This is attributed to the higher-charged polymeric Al species, and the lower hydrophilic and more compact flocculated flocs of PACl coagulant. Based on results of pilot experiments, the goal of FRD system can be achieved by combining a DAF heterocoagulation reactor with PACl coagulant (F), an efficient flocculation reactor (R), as well as an economical auto-dosing system (D).

Breeding of transgenic cattle for human coagulation factor IX by a combination of lentiviral system and cloning.

PubMed

Monzani, P S; Sangalli, J R; De Bem, T H C; Bressan, F F; Fantinato-Neto, P; Pimentel, J R V; Birgel-Junior, E H; Fontes, A M; Covas, D T; Meirelles, F V

2013-02-28

Recombinant coagulation factor IX must be produced in mammalian cells because FIX synthesis involves translational modifications. Human cell culture-based expression of human coagulation factor IX (hFIX) is expensive, and large-scale production capacity is limited. Transgenic animals may greatly increase the yield of therapeutic proteins and reduce costs. In this study, we used a lentiviral system to obtain transgenic cells and somatic cell nuclear transfer (SCNT) to produce transgenic animals. Lentiviral vectors carrying hFIX driven by 3 bovine β-casein promoters were constructed. Bovine epithelial mammary cells were transduced by lentivirus, selected with blasticidin, plated on extracellular matrix, and induced by lactogenic hormones; promoter activity was evaluated by quantitative PCR. Transcriptional activity of the 5.335-kb promoter was 6-fold higher than the 3.392- and 4.279-kb promoters, which did not significantly differ. Transgenic bovine fibroblasts were transduced with lentivirus carrying the 5.335-kb promoter and used as donor cells for SCNT. Cloned transgenic embryo production yielded development rates of 28.4%, similar to previous reports on cloned non-transgenic embryos. The embryos were transferred to recipient cows (N = 21) and 2 births of cloned transgenic cattle were obtained. These results suggest combination of the lentiviral system and cloning may be a good strategy for production of transgenic cattle.

An Easy Method to Eliminate the Effect of Lupus Anticoagulants in the Coagulation Factor Assay.

PubMed

Tang, Ning; Yin, Shiyu

2016-07-01

To build and evaluate intrinsic coagulation factor assays which can eliminate the effect of lupus anticoagulants (LAC). Commercial silica clotting time confirmatory (SCT-C) reagent containing sufficient synthetic phospholipid and routine activated partial thromboplastin time (APTT) reagent were each used for one-stage detection of FVIII, FIX, and FXI activities, in samples with or without LAC, and the results were compared. For samples without LAC, consistent results of FVIII, FIX, and FXI using both SCT-C reagent and APTT reagent were obtained. For samples with LAC, the assays with SCT-C reagent not only could eliminate the effect of strong lupus anticoagulants but also needed fewer dilutions than that with routine APTT reagent. The intrinsic factor detections by SCT-C reagent are credible and convenient to be used for samples with LAC.

Factor X/Xa elicits protective signaling responses in endothelial cells directly via PAR-2 and indirectly via endothelial protein C receptor-dependent recruitment of PAR-1.

PubMed

Bae, Jong-Sup; Yang, Likui; Rezaie, Alireza R

2010-11-05

We recently demonstrated that the Gla domain-dependent interaction of protein C with endothelial protein C receptor (EPCR) leads to dissociation of the receptor from caveolin-1 and recruitment of PAR-1 to a protective signaling pathway. Thus, the activation of PAR-1 by either thrombin or PAR-1 agonist peptide elicited a barrier-protective response if endothelial cells were preincubated with protein C. In this study, we examined whether other vitamin K-dependent coagulation protease zymogens can modulate PAR-dependent signaling responses in endothelial cells. We discovered that the activation of both PAR-1 and PAR-2 in endothelial cells pretreated with factor FX (FX)-S195A, but not other procoagulant protease zymogens, also results in initiation of protective intracellular responses. Interestingly, similar to protein C, FX interaction with endothelial cells leads to dissociation of EPCR from caveolin-1 and recruitment of PAR-1 to a protective pathway. Further studies revealed that, FX activated by factor VIIa on tissue factor bearing endothelial cells also initiates protective signaling responses through the activation of PAR-2 independent of EPCR mobilization. All results could be recapitulated by the receptor agonist peptides to both PAR-1 and PAR-2. These results suggest that a cross-talk between EPCR and an unknown FX/FXa receptor, which does not require interaction with the Gla domain of FX, recruits PAR-1 to protective signaling pathways in endothelial cells.

Coagulation Imbalance and Neurocognitive Functioning in Older HIV+ Adults on Suppressive Antiretroviral Therapy

PubMed Central

Montoya, Jessica l.; Iudicello, Jennifer; Oppenheim, Hannah A.; Fazeli, Pariya l.; Potter, Michael; MA, Qing; Mills, Paul J.; Ellis, Ronald J.; Grant, Igor; Letendre, Scott l.; Moore, David J.

2017-01-01

Objectives To compare plasma biomarkers of coagulation between HIV-infected individuals and HIV-uninfected controls and to assess the impact of disturbances in coagulation on neurocognitive functioning in HIV. Design Cross-sectional study of 66 antiretroviral therapy-treated virally suppressed HIV-infected and 34 HIV-uninfected older (≥50 years of age) adults. Methods Participants completed standardized neurobehavioral and neuromedical assessments. Neurocognitive functioning was evaluated using a well-validated comprehensive neuropsychological battery. Plasma biomarkers associated with procoagulation (fibrinogen, p-selectin, tissue factor, and von Willebrand factor), anticoagulation (antithrombin, protein C, and thrombomodulin), fibrinolysis (d-dimer, plasminogen activator inhibitor-1, and plasminogen) were collected. Multivariable linear regression was used to test the interaction of HIV and coagulation on neurocognitive functioning. Results Most participants were male (78.0%) and non-Hispanic white (73.0%) with a mean age of 57.8 years. Among HIV-infected participants, mean estimated duration of HIV infection was 19.4 years and median current CD4+ cell count was 654 cells/mm3. Levels of soluble biomarkers of procoagulation, anticoagulation, and fibrinolysis were comparable between the HIV serostatus groups. Coagulation and HIV had an interacting effect on neurocognitive functioning, such that greater coagulation imbalance was associated with poorer neurocognitive functioning among the HIV-infected participants. The moderating effect of coagulation on neurocognition was driven by procoagulant but not anticoagulant or fibrinolytic biomarkers. Conclusions Elevated levels of procoagulants may exert a particularly detrimental effect on neurocognitive functioning among older HIV-infected persons. A better understanding of the specific role of coagulation in the etiology of HIV-associated neurocognitive disorders may lead to treatments aimed at reducing coagulopathy

Effects of alum coagulation on speciation and distribution of trihalomethanes (THMs) and haloacetic acids (HAAs).

PubMed

Gang, Dianchen; Clevenger, Thomas E; Banerji, Shankha K

2005-01-01

The impacts of alum coagulation on the distribution of disinfection by-products (DBPs), trihalomethanes (THMs), and haloacetic acids (HAAs) were evaluated under controlled chlorination conditions using four surface waters. Among the nine HAAs found in waters, dihaloacetic acids (X2AAs) have been found to be the dominant species in all of the raw and alum treated waters. Alum coagulation tends to remove more monohaloacetic acids (XAAs) and trihaloacetic acids (X3AAs) precursors than that of dihaloacetic acids (X2AAs). Alum coagulation treated water had a lower HAA9/TTHM ratio compared with that of the raw water. The increase of THM bromine incorporation factors (BIFalpha) value of alum treated water was statistically significant in comparison with the raw water. On average, BIFalpha increased by 54% after the alum coagulation process in these four different waters. This indicated that THM speciations shifted in favor of the more brominated compounds. However, alum coagulation treatment process had less effect on HAA bromi ne incorporation factors (BIFbeta)than it did on BIFalpha. Bromine incorporation factor (BIF) values decreased with time in the THM and HAA formation processes, especially within the first 10 h of the reaction time. This suggested that brominated THMs or HAAs formed faster than the chlorinated species in the initial period.

Coagulation tests show significant differences in patients with breast cancer.

PubMed

Tas, Faruk; Kilic, Leyla; Duranyildiz, Derya

2014-06-01

Activated coagulation and fibrinolytic system in cancer patients is associated with tumor stroma formation and metastasis in different cancer types. The aim of this study is to explore the correlation of blood coagulation assays for various clinicopathologic factors in breast cancer patients. A total of 123 female breast cancer patients were enrolled into the study. All the patients were treatment naïve. Pretreatment blood coagulation tests including PT, APTT, PTA, INR, D-dimer, fibrinogen levels, and platelet counts were evaluated. Median age of diagnosis was 51 years old (range 26-82). Twenty-two percent of the group consisted of metastatic breast cancer patients. The plasma level of all coagulation tests revealed statistically significant difference between patient and control group except for PT (p<0.001 for all variables except for PT; p=0.08). Elderly age (>50 years) was associated with higher D-dimer levels (p=0.003). Metastatic patients exhibited significantly higher D-dimer values when compared with early breast cancer patients (p=0.049). Advanced tumor stage (T3 and T4) was associated with higher INR (p=0.05) and lower PTA (p=0.025). In conclusion, coagulation tests show significant differences in patients with breast cancer.

Coagulation Factor XIIIA (F13A1): Novel Perspectives in Treatment and Pharmacogenetics.

PubMed

Gemmati, Donato; Vigliano, Marco; Burini, Francesco; Mari, Rosella; El Mohsein, Hodeib Hossam Abd; Parmeggiani, Francesco; Serino, Maria L

2016-01-01

Factor XIII (FXIII) is a key molecule in the field of blood coagulation and in the last decades it has weakened attention within the field of angiogenesis and tissue repair. FXIII positively influences wound healing in several tissues by exerting multiple plasma and cellular functions. In the field of haemostasis, FXIII cross-links the neo formed fibrin fibers and supports platelet adhesion to the damaged sub-endothelium warranting a solid architecture. In addition, the pro-angiogenic functions of FXIII are directed by the interaction of vascular endothelial growth factor receptor 2 (VEGFR2) and the integrin αVβ3, on the cell membrane, favouring an important step in the formation of granulation tissue at the wound site for optimal tissue healing. Conversely, the same mechanisms could lead to undesired increased neovascularisation, for example in inflammatory bowel disease or in the retinal degenerative pathologies. The classical symptoms of FXIII deficiency span from intracranial haemorrhage to delay bleeding or the staying of chronic wounds in the skin including impaired mucosal healing. In this view, FXIII bridges primary haemostasis, coagulation and definite tissue healing. Another important recently discovered function ascribed to FXIII is its ability to limit bacterial spreading from the lesion by incorporating specific macromolecules addressed to cellular infiltration, favouring in turn cell migration and survival, as observed also in fibrin-heart cultures for stem cell recruitment. In the field of the novel prognostic biomarkers, the monitoring of the residual circulating FXIII level during acute myocardial infarction has been considered predictive of the post-myocardial infarction healing. Accordingly, adequate FXIII levels can drive and predict the prognosis of complex diseases and the outcome of the associated therapies or interventions. In addition, peculiar pharmacogenetics aspects of the FXIII gene are of extraordinary interest. The present review

Bio-refractory dissolved organic matter and colorants in cassava distillery wastewater: Characterization, coagulation treatment and mechanisms.

PubMed

Zhang, Ming; Wang, Zhou; Li, Penghui; Zhang, Hua; Xie, Li

2017-07-01

An important portion of organic matter and colorants still remain in the biologically treated distillery wastewater, leaving the dark brown and odorous downstream with the heavy loading of chemical oxygen demand and the potential of forming disinfection byproducts. However, those bio-recalcitrant colorants have not been clearly recognized. The current study investigated the features of the bio-refractory organic matter and colorants in a typical distillery effluent, cassava distillery wastewater; special attention was paid to their change and behaviors in the coagulation treatment following the bio-processes. The wastewater analyses denoted that the fraction of high molecular weight (1-50 kDa and >50 kDa) became predominant after the anaerobic-aerobic processes. Importantly, the lignin breakdown products, melanoidins and lignin phenols were confirmed to be the leading colored components, according to the parallel factor analysis of fluorescence excitation-emission matrixes results. Compared with lignin phenols, the former two types of colorants exhibited stronger bio-refractory activity and resulted in smaller color reduction after the aerobic treatment. Neither advanced oxidation nor adsorption could perform efficiently as post-treatment for decolorization in this study. Nevertheless, high removal of color and dissolved organic matter (∼94.0% and ∼78.3%, respectively) could be achieved by the FeCl 3 -involved coagulation under the optimal conditions. The ferric coagulant was found to preferably interact with the aromatic compounds (such as lignin derivatives) and melanoidins via either surface complexation or electric charge neutralization, or both. The findings presented herein might provide an insight into the evaluation of bio-refractory organic colorants and the Fe(III)-involved decolorization mechanisms of ethanol production wastewaters. Copyright © 2017 Elsevier Ltd. All rights reserved.

Associations of activated coagulation factor VII and factor VIIa-antithrombin levels with genome-wide polymorphisms and cardiovascular disease risk.

PubMed

Olson, N C; Raffield, L M; Lange, L A; Lange, E M; Longstreth, W T; Chauhan, G; Debette, S; Seshadri, S; Reiner, A P; Tracy, R P

2018-01-01

Essentials A fraction of coagulation factor VII circulates in blood as an activated protease (FVIIa). We evaluated FVIIa and FVIIa-antithrombin (FVIIa-AT) levels in the Cardiovascular Health Study. Polymorphisms in the F7 and PROCR loci were associated with FVIIa and FVIIa-AT levels. FVIIa may be an ischemic stroke risk factor in older adults and FVIIa-AT may assess mortality risk. Background A fraction of coagulation factor (F) VII circulates as an active protease (FVIIa). FVIIa also circulates as an inactivated complex with antithrombin (FVIIa-AT). Objective Evaluate associations of FVIIa and FVIIa-AT with genome-wide single nucleotide polymorphisms (SNPs) and incident coronary heart disease, ischemic stroke and mortality. Patients/Methods We measured FVIIa and FVIIa-AT in 3486 Cardiovascular Health Study (CHS) participants. We performed a genome-wide association scan for FVIIa and FVIIa-AT in European-Americans (n = 2410) and examined associations of FVII phenotypes with incident cardiovascular disease. Results In European-Americans, the most significant SNP for FVIIa and FVIIa-AT was rs1755685 in the F7 promoter region on chromosome 13 (FVIIa, β = -25.9 mU mL -1 per minor allele; FVIIa-AT, β = -26.6 pm per minor allele). Phenotypes were also associated with rs867186 located in PROCR on chromosome 20 (FVIIa, β = 7.8 mU mL -1 per minor allele; FVIIa-AT, β = 9.9 per minor allele). Adjusted for risk factors, a one standard deviation higher FVIIa was associated with increased risk of ischemic stroke (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.01, 1.23). Higher FVIIa-AT was associated with mortality from all causes (HR, 1.08; 95% CI, 1.03, 1.12). Among European-American CHS participants the rs1755685 minor allele was associated with lower ischemic stroke (HR, 0.69; 95% CI, 0.54, 0.88), but this association was not replicated in a larger multi-cohort analysis. Conclusions The results support the importance of the F7 and PROCR loci in

Coagulation of grains in static and collapsing protostellar clouds

NASA Technical Reports Server (NTRS)

Weidenschilling, S. J.; Ruzmaikina, T. V.

1993-01-01

The wavelength dependence of extinction in the diffuse interstellar medium implies that it is produced by particles of dominant size of approximately 10(exp -5) cm. There is some indication that in the cores of dense molecular clouds, sub-micron grains can coagulate to form larger particles; this process is probably driven by turbulence. The most primitive meteorites (carbonaceous chondrites) are composed of particles with a bimodal size distribution with peaks near 1 micron (matrix) and 1 mm (chondrules). Models for chondrule formation that involve processing of presolar material by chemical reactions or through an accretion shock during infall assume that aggregates of the requisite mass could form before or during collapse. The effectiveness of coagulation during collapse has been disputed; it appears to depend on specific assumptions. The first results of detailed numerical modeling of spatial and temporal variations of particle sizes in presolar clouds, both static and collapsing, is reported in this article.

A Common Suite of Coagulation Proteins Function in Drosophila Muscle Attachment.

PubMed

Green, Nicole; Odell, Nadia; Zych, Molly; Clark, Cheryl; Wang, Zong-Heng; Biersmith, Bridget; Bajzek, Clara; Cook, Kevin R; Dushay, Mitchell S; Geisbrecht, Erika R

2016-11-01

The organization and stability of higher order structures that form in the extracellular matrix (ECM) to mediate the attachment of muscles are poorly understood. We have made the surprising discovery that a subset of clotting factor proteins are also essential for muscle attachment in the model organism Drosophila melanogaster One such coagulation protein, Fondue (Fon), was identified as a novel muscle mutant in a pupal lethal genetic screen. Fon accumulates at muscle attachment sites and removal of this protein results in decreased locomotor behavior and detached larval muscles. A sensitized genetic background assay reveals that fon functions with the known muscle attachment genes Thrombospondin (Tsp) and Tiggrin (Tig). Interestingly, Tig is also a component of the hemolymph clot. We further demonstrate that an additional clotting protein, Larval serum protein 1γ (Lsp1γ), is also required for muscle attachment stability and accumulates where muscles attach to tendons. While the local biomechanical and organizational properties of the ECM vary greatly depending on the tissue microenvironment, we propose that shared extracellular protein-protein interactions influence the strength and elasticity of ECM proteins in both coagulation and muscle attachment. Copyright © 2016 by the Genetics Society of America.

A Common Suite of Coagulation Proteins Function in Drosophila Muscle Attachment

PubMed Central

Green, Nicole; Odell, Nadia; Zych, Molly; Clark, Cheryl; Wang, Zong-Heng; Biersmith, Bridget; Bajzek, Clara; Cook, Kevin R.; Dushay, Mitchell S.; Geisbrecht, Erika R.

2016-01-01

The organization and stability of higher order structures that form in the extracellular matrix (ECM) to mediate the attachment of muscles are poorly understood. We have made the surprising discovery that a subset of clotting factor proteins are also essential for muscle attachment in the model organism Drosophila melanogaster. One such coagulation protein, Fondue (Fon), was identified as a novel muscle mutant in a pupal lethal genetic screen. Fon accumulates at muscle attachment sites and removal of this protein results in decreased locomotor behavior and detached larval muscles. A sensitized genetic background assay reveals that fon functions with the known muscle attachment genes Thrombospondin (Tsp) and Tiggrin (Tig). Interestingly, Tig is also a component of the hemolymph clot. We further demonstrate that an additional clotting protein, Larval serum protein 1γ (Lsp1γ), is also required for muscle attachment stability and accumulates where muscles attach to tendons. While the local biomechanical and organizational properties of the ECM vary greatly depending on the tissue microenvironment, we propose that shared extracellular protein–protein interactions influence the strength and elasticity of ECM proteins in both coagulation and muscle attachment. PMID:27585844

[Evaluation of coagulation disorders with thrombelastography in patients with sepsis].

PubMed

Zhong, Shengjian; Zhang, Chunbao; Hu, Juntao; Tang, Zhanhong

2016-02-01

To compare the results of thrombelastography (TEG) and the conventional coagulability test in patients with sepsis, and to discuss the value of TEG in monitoring blood coagulation dysfunction in patients with sepsis. The clinical data of 92 adult patients with sepsis admitted to Department of Critical Care Medicine of the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. The patients were divided into sequential organ failure assessment (SOFA) score ≥ 12 group (n = 47) and SOFA < 12 group (n = 45). Thirty-five non-sepsis adult patients with normal coagulation function served as control group. The venous blood was collected for conventional blood coagulation test and routine examination of blood, D-dimer, procalcitonin (PCT), and TEG, and the differences were compared among three groups. Correlations between SOFA and various indexes of patients with sepsis were analyzed by Spearman rank correlation method. As shown in the results of the conventional blood coagulation test, D-dimer was gradually increased with the aggravation of the disease, the values in non-sepsis, SOFA < 12, and SOFA ≥ 12 groups were 0.523 (0.273, 0.928), 0.863 (0.673, 4.221), and 4.118 (2.420, 5.653) mg/L respectively (Z = 25.163, P = 0.000). Platelet count (PLT) in SOFA ≥ 12 group was significantly lower than that of the SOFA < 12 group and non-sepsis group [×10(9)/L: 28.6 (12.8, 48.9) vs. 257.3 (152.6, 339.8), 182.0 (118.0, 229.0), both P < 0.01]. There was no significant difference in prothrombin time (PT) and international normalized ratio (INR) among three groups, and it indicated that the conventional blood coagulation test might not respond quickly to the change in coagulation status of sepsis patients. As shown in the results of TEG, the values of reaction time (R value) and kinetics time (K value) in SOFA < 12 group were lower than those of the non-sepsis group [R value (minutes): 4.4 (3.6, 6.1) vs. 6.3 (6.0, 6.7), P < 0.01; K value (minutes

Investigational drugs for coagulation disorders.

PubMed

Mannucci, Pier Mannuccio; Mancuso, Maria Elisa

2013-08-01

The current standard treatment in persons with hemophilia (PWH) is prophylaxis, given intravenously twice or thrice weekly, which is associated with a non negligible burden on patients' quality of life. Therefore the main attempts aiming to improve the management of PWH are targeted towards the development of a new generation of coagulation factors endowed with properties facilitating prophylaxis and/or a better control of bleeding. This article summarizes the main results obtained so far in the development of new antihemophilic products, and emphasizes the formidable requirements imposed upon by regulatory agencies to get marketing authorization for new drugs, which make progress in this field difficult. Published literature on new molecules for replacement treatment in hemophilia A and B has been retrieved by using PubMed search and all ongoing clinical trials have been looked for online. New molecules are usually engineered to have a longer plasma half-life but also in some instances a higher potency. The prolongation of half-life may be obtained by using sustained release delivery vehicles, by chemical modification or by creating fusion proteins. Factors VIII, IX and VII have been variably modified in order to obtain improved coagulation products and results from Phase I/II studies are encouraging, particularly for factor IX. However, Phase III studies that should provide evidence on efficacy and effectiveness more cogent for clinical use are still ongoing and results are not yet available.

Treatment of a long-acting anticoagulant rodenticide poisoning cohort with vitamin K1 during the maintenance period

PubMed Central

Long, Jianhai; Peng, Xiaobo; Luo, Yuan; Sun, Yawei; Lin, Guodong; Wang, Yongan; Qiu, Zewu

2016-01-01

Abstract Currently, there are few guidelines for the use of vitamin K1 in the maintenance treatment of long-acting anticoagulant rodenticide (LAAR) poisonings. We explored factors in the treatment of LAAR poisoning during the maintenance period in order to suggest feasible treatment models. Data from 24 cases of anticoagulant rodenticide poisoning in our hospital were collected from January 2013 to May 2016. The patients’ sex, age, coagulation function, total time from poisoning to treatment with vitamin K1 (prehospital time), vitamin K1 sustained treatment time (VKSTT), anticoagulant rodenticide category, and specific poison dosage were collected. Multivariate analysis was used to evaluate the correlation between vitamin K1 dosage and other factors during the maintenance period. Only VKSTT (partial regression coefficient −1.133, 0.59, P = 0.035) had an obvious influence on the therapeutic dose of vitamin K1 required during the maintenance period. After an initial pulse therapy, the bleeding and coagulation functions were stabilized, and the patients were subsequently treated with vitamin K1 during the maintenance period. Over time, the maintenance dose of vitamin K1 (10–120 mg/d, intravenous drip) was gradually decreased and was not related to toxicant concentration. PMID:28002326

Hepatic dysfunction contributes to coagulation disturbances in patients undergoing whole body hyperthermia by use of extracorporeal circulation.

PubMed

Worel, Nina; Knöbl, Paul; Karanikas, Georgios; Fuchs, Eva-Maria; Bojic, Andja; Brodowicz, Thomas; Jilma, Petra; Zielinski, Christoph C; Köstler, Wolfgang J; Locker, Gottfried J

2014-09-01

This phase I study was performed to evaluate coagulation alterations during extracorporeal circulation (ECC) induced whole body hyperthermia (WBHT) in 12 patients with advanced soft tissue sarcomas. To distinguish between effects of normothermic ECC and ECC-WBHT, blood samples were drawn at different time points: at baseline, after 30 min on normothermic ECC, at the end of the heating period, and 24 h and 7 days thereafter. Standard coagulation tests, coagulation factors, thrombelastography,platelets and reticulated platelets, liver enzymes, and scintigraphic platelet imaging were performed. Normothermic ECC resulted in coagulation alterations most likely due to systemic anticoagulation. Induction of hyperthermia caused thrombocytopenia, increased fibrin degradation products,prolonged clotting times, alteration in coagulation factors, and increased liver enzymes. The majority of these effects was most pronounced 24 h after ECC-WBHT. In addition, late liver sequestration of platelets was demonstrated in scintigraphic imaging at that time point. Temporal correlation between hemostatic alterations and elevation in liver enzymes leads to the assumption that liver impairment might play a crucial role in coagulation disturbances observed during ECC-WBHT and thereafter, thus strongly supported by liver sequestration of platelets.Therefore a close monitoring of hepatic derived coagulation alterations in patients undergoing extracorporeal whole body hypothermia is warranted.

Protein corona changes mediated by surface modification of amorphous silica nanoparticles suppress acute toxicity and activation of intrinsic coagulation cascade in mice

NASA Astrophysics Data System (ADS)

Yoshida, Tokuyuki; Yoshioka, Yasuo; Morishita, Yuki; Aoyama, Michihiko; Tochigi, Saeko; Hirai, Toshiro; Tanaka, Kota; Nagano, Kazuya; Kamada, Haruhiko; Tsunoda, Shin-ichi; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Higashisaka, Kazuma; Tsutsumi, Yasuo

2015-06-01

Recently, nanomaterial-mediated biological effects have been shown to be governed by the interaction of nanomaterials with some kinds of proteins in biological fluids, and the physical characteristics of the nanomaterials determine the extent and type of their interactions with proteins. Here, we examined the relationships between the surface properties of amorphous silica nanoparticles with diameters of 70 nm (nSP70), their interactions with some proteins in biological fluids, and their toxicity in mice after intravenous administration. The surface modification of nSP70 with amino groups (nSP70-N) prevented acute lethality and abnormal activation of the coagulation cascade found in the nSP70-treated group of mice. Since our previous study showed that coagulation factor XII played a role in the nSP70-mediated abnormal activation of the coagulation cascade, we examined the interaction of nSP70 and nSP70-N with coagulation factor XII. Coagulation factor XII bonded to the surface of nSP70 to a greater extent than that observed for nSP70-N, and consequently more activation of coagulation factor XII was observed for nSP70 than for nSP70-N. Collectively, our results suggest that controlling the interaction of nSP70 with blood coagulation factor XII by modifying the surface properties would help to inhibit the nSP70-mediated abnormal activation of the blood coagulation cascade.

Coagulation of micro-polluted Pearl River water with IPF-PACls.

PubMed

Xu, Yi; Sun, Wei; Wang, Dong-sheng; Tang, Hong-xiao

2004-01-01

Water samples collected from early March 2001 to the end of April 2002 at the branch of Pearl River around the Guangzhou City were analyzed for its micro-polluted characteristics. The coagulation behavior of polyaluminum chlorides (PACls) was then examined focusing on the effect of primary water quality and speciation distribution. The results showed that PACls exhibit better coagulation efficiency than alum in accordance with the different speciation. The turbidity removal property of PACls is evidently better than alum at low dosage. While in neutral zone (about 6.5-7.5), the turbidity removal of PACls decreases owing to the restabilization of particles at higher dosage. The organic matters in raw water exhibit marked influence on coagulation. In acidic zone, organic matters complex with polymer species and promote the formation of flocs. With an increase in pH, the complexation of organics with polymer species gradually decreases, and the removal of organics mainly depends on adsorption. The effect is evidently improved with the raise of B value.

Impact of organic polyelectrolytes on coagulation of source-separated black water.

PubMed

Kozminykh, Pavlo; Heistad, Arve; Ratnaweera, Harsha C; Todt, Daniel

2016-01-01

Household wastewater is originated from common people's activities and has a potential harmful impact on the environment if discharged directly without proper treatment. Toilet wastewater or black water (BW) contains urine, faeces, toilet paper and flushing water and it contains the majority of pollutants obtained from a single household. In this study, the focus was on BW treatment using chemical methods. The main goal of current research was to define the possibility and applicability of conventional coagulants and flocculants in direct chemical treatment of vacuum-collected BW to remove particles, organic matter and phosphorous. After the definition of dosing ranges, based on the equivalent doses in conventional municipal and industrial wastewater treatment data, aluminium and iron coagulants, organic polyelectrolytes (polymers with anionic, neutral and cationic charge with different molecular weights) and their various combinations were tested using the well-known jar-test laboratory method to study aggregation and solid-liquid separation processes in raw BW. The most important process parameter during the coagulation was pH level, dependent on the type and doses of metal salts. Some side processes were found to occur while using iron-based coagulants. Dosing of either single coagulants or single polymers did not give satisfactory results, while a combination of aluminium salts and cationic polymers showed high removal rates in total suspended solids, total chemical oxygen demand and ortho-phosphates, reaching 97.8%, 92% and 98.6%, respectively, with the optimal doses of chemicals. Cationic polymers with the lowest molecular weight and highest charge density were the most efficient in combination with aluminium coagulants.

The Organophosphate Paraoxon and Its Antidote Obidoxime Inhibit Thrombin Activity and Affect Coagulation In Vitro

PubMed Central

Golderman, Valery; Shavit-Stein, Efrat; Tamarin, Ilia; Rosman, Yossi; Shrot, Shai; Rosenberg, Nurit

2016-01-01

Organophosphates (OPs) are potentially able to affect serine proteases by reacting with their active site. The potential effects of OPs on coagulation factors such as thrombin and on coagulation tests have been only partially characterized and potential interactions with OPs antidotes such as oximes and muscarinic blockers have not been addressed. In the current study, we investigated the in vitro interactions between coagulation, thrombin, the OP paraoxon, and its antidotes obidoxime and atropine. The effects of these substances on thrombin activity were measured in a fluorescent substrate and on coagulation by standard tests. Both paraoxon and obidoxime but not atropine significantly inhibited thrombin activity, and prolonged prothrombin time, thrombin time, and partial thromboplastin time. When paraoxon and obidoxime were combined, a significant synergistic effect was found on both thrombin activity and coagulation tests. In conclusion, paraoxon and obidoxime affect thrombin activity and consequently alter the function of the coagulation system. Similar interactions may be clinically relevant for coagulation pathways in the blood and possibly in the brain. PMID:27689805

Proteins, Platelets, and Blood Coagulation at Biomaterial Interfaces

PubMed Central

Xu, Li-Chong; Bauer, James; Siedlecki, Christopher A.

2015-01-01

Blood coagulation and platelet adhesion remain major impediments to the use of biomaterials in implantable medical devices. There is still significant controversy and question in the field regarding the role that surfaces play in this process. This manuscript addresses this topic area and reports on state of the art in the field. Particular emphasis is placed on the subject of surface engineering and surface measurements that allow for control and observation of surface-mediated biological responses in blood and test solutions. Appropriate use of surface texturing and chemical patterning methodologies allow for reduction of both blood coagulation and platelet adhesion, and new methods of surface interrogation at high resolution allow for measurement of the relevant biological factors. PMID:25448722

Coagulation imbalance and neurocognitive functioning in older HIV-positive adults on suppressive antiretroviral therapy.

PubMed

Montoya, Jessica L; Iudicello, Jennifer; Oppenheim, Hannah A; Fazeli, Pariya L; Potter, Michael; Ma, Qing; Mills, Paul J; Ellis, Ronald J; Grant, Igor; Letendre, Scott L; Moore, David J

2017-03-27

The aim of this study was to compare plasma biomarkers of coagulation between HIV-infected individuals and HIV-uninfected controls and to assess the impact of disturbances in coagulation on neurocognitive functioning in HIV. A cross-sectional study of 66 antiretroviral therapy treated, virally suppressed, HIV-infected and 34 HIV-uninfected older (≥50 years of age) adults. Participants completed standardized neurobehavioral and neuromedical assessments. Neurocognitive functioning was evaluated using a well validated comprehensive neuropsychological battery. Plasma biomarkers associated with procoagulation (fibrinogen, p-selectin, tissue factor and von Willebrand factor), anticoagulation (antithrombin, protein C and thrombomodulin), fibrinolysis (d-dimer, plasminogen activator inhibitor-1 and plasminogen) were collected. Multivariable linear regression was used to test the interaction of HIV and coagulation on neurocognitive functioning. Most participants were male (78.0%) and non-Hispanic white (73.0%) with a mean age of 57.8 years. Among HIV-infected participants, mean estimated duration of HIV infection was 19.4 years and median current CD4 cell count was 654 cells/μl. Levels of soluble biomarkers of procoagulation, anticoagulation and fibrinolysis were comparable between the HIV serostatus groups. Coagulation and HIV had an interacting effect on neurocognitive functioning, such that greater coagulation imbalance was associated with poorer neurocognitive functioning among the HIV-infected participants. The moderating effect of coagulation on neurocognition was driven by procoagulant but not anticoagulant or fibrinolytic biomarkers. Elevated levels of procoagulants may exert a particularly detrimental effect on neurocognitive functioning among older HIV-infected persons. A better understanding of the specific role of coagulation in the cause of HIV-associated neurocognitive disorders may lead to treatments aimed at reducing coagulopathy, thereby improving

Simple and rapid methods for purification and characterization of active coagulants from the seeds of Vigna unguiculata and Parkinsonia aculeata.

PubMed

Marobhe, N J; Dalhammar, G; Gunaratna, K R

2007-06-01

The coagulating properties of aqueous crude extracts and purified proteins of Vigna unguiculata and Parkinsonia aculeata seeds, which are traditional water coagulants in rural areas of Tanzania, were studied. The coagulation activity assays were done using one millilitre (ml) of kaolin water samples. Coagulating proteins were purified in two-step ion exchange chromatography. The properties of coagulant protein were compared with Moringa oleifera. Coagulating components eluted by 0.6 M NaCl in both coagulants are cationic proteins that have the molecular mass of about 6 kDa, which is very similar to that of M. oleifera. The proteins of V. unguiculata and P. aculeata eluted by 0.3 M NaCl also harbour coagulation activity but proteins eluted with 0.6 M NaCl have higher activity. The dosage for coagulation using purified proteins of both coagulants is about 5 to 10 times lower than that of crude seed extracts. The optimum floc settling time of water treated by crude seed extracts and purified proteins ranged between two and two and half hours. Coagulating proteins of both coagulants eluted by 0.6 M NaCl are thermoresistant and retained coagulation activity of 87% to 92% after boiling for two hours at 80 degrees C and one hour at 95 degrees C. Thermotolerant proteins of V. unguiculata eluted by 0.6 M NaCl and P. aculeata have wider pH range of 5.5 to 8.5 for coagulation activity than those of M. oleifera proteins. The present investigation reveals the possibility of using purified natural coagulants for water treatment to produce safe drinking water.

Assessing blood coagulation status with laser speckle rheology

PubMed Central

Tripathi, Markandey M.; Hajjarian, Zeinab; Van Cott, Elizabeth M.; Nadkarni, Seemantini K.

2014-01-01

We have developed and investigated a novel optical approach, Laser Speckle Rheology (LSR), to evaluate a patient’s coagulation status by measuring the viscoelastic properties of blood during coagulation. In LSR, a blood sample is illuminated with laser light and temporal speckle intensity fluctuations are measured using a high-speed CMOS camera. During blood coagulation, changes in the viscoelastic properties of the clot restrict Brownian displacements of light scattering centers within the sample, altering the rate of speckle intensity fluctuations. As a result, blood coagulation status can be measured by relating the time scale of speckle intensity fluctuations with clinically relevant coagulation metrics including clotting time and fibrinogen content. Our results report a close correlation between coagulation metrics measured using LSR and conventional coagulation results of activated partial thromboplastin time, prothrombin time and functional fibrinogen levels, creating the unique opportunity to evaluate a patient’s coagulation status in real-time at the point of care. PMID:24688816

New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events.

PubMed

Mekaj, Ymer H; Mekaj, Agon Y; Duci, Shkelzen B; Miftari, Ermira I

2015-01-01

Despite the discovery and application of many parenteral (unfractionated and low-molecular-weight heparins) and oral anticoagulant vitamin K antagonist (VKA) drugs, the prevention and treatment of venous and arterial thrombotic phenomena remain major medical challenges. Furthermore, VKAs are the only oral anticoagulants used during the past 60 years. The main objective of this study is to present recent data on non-vitamin K antagonist oral anticoagulants (NOACs) and to analyze their advantages and disadvantages compared with those of VKAs based on a large number of recent studies. NOACs are novel direct-acting medications that are selective for one specific coagulation factor, either thrombin (IIa) or activated factor X (Xa). Several NOACs, such as dabigatran (a direct inhibitor of FIIa) and rivaroxaban, apixaban and edoxaban (direct inhibitors of factor Xa), have been used for at least 5 years but possibly 10 years. Unlike traditional VKAs, which prevent the coagulation process by suppressing the synthesis of vitamin K-dependent factors, NOACs directly inhibit key proteases (factors IIa and Xa). The important indications of these drugs are the prevention and treatment of deep vein thrombosis and pulmonary embolisms, and the prevention of atherothrombotic events in the heart and brain of patients with acute coronary syndrome and atrial fibrillation. They are not fixed, and dose-various strengths are available. Most studies have reported that more advantages than disadvantages for NOACs when compared with VKAs, with the most important advantages of NOACs including safety issues (ie, a lower incidence of major bleeding), convenience of use, minor drug and food interactions, a wide therapeutic window, and no need for laboratory monitoring. Nonetheless, there are some conditions for which VKAs remain the drug of choice. Based on the available data, we can conclude that NOACs have greater advantages and fewer disadvantages compared with VKAs. New studies are required

New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events

PubMed Central

Mekaj, Ymer H; Mekaj, Agon Y; Duci, Shkelzen B; Miftari, Ermira I

2015-01-01

Despite the discovery and application of many parenteral (unfractionated and low-molecular-weight heparins) and oral anticoagulant vitamin K antagonist (VKA) drugs, the prevention and treatment of venous and arterial thrombotic phenomena remain major medical challenges. Furthermore, VKAs are the only oral anticoagulants used during the past 60 years. The main objective of this study is to present recent data on non-vitamin K antagonist oral anticoagulants (NOACs) and to analyze their advantages and disadvantages compared with those of VKAs based on a large number of recent studies. NOACs are novel direct-acting medications that are selective for one specific coagulation factor, either thrombin (IIa) or activated factor X (Xa). Several NOACs, such as dabigatran (a direct inhibitor of FIIa) and rivaroxaban, apixaban and edoxaban (direct inhibitors of factor Xa), have been used for at least 5 years but possibly 10 years. Unlike traditional VKAs, which prevent the coagulation process by suppressing the synthesis of vitamin K-dependent factors, NOACs directly inhibit key proteases (factors IIa and Xa). The important indications of these drugs are the prevention and treatment of deep vein thrombosis and pulmonary embolisms, and the prevention of atherothrombotic events in the heart and brain of patients with acute coronary syndrome and atrial fibrillation. They are not fixed, and dose-various strengths are available. Most studies have reported that more advantages than disadvantages for NOACs when compared with VKAs, with the most important advantages of NOACs including safety issues (ie, a lower incidence of major bleeding), convenience of use, minor drug and food interactions, a wide therapeutic window, and no need for laboratory monitoring. Nonetheless, there are some conditions for which VKAs remain the drug of choice. Based on the available data, we can conclude that NOACs have greater advantages and fewer disadvantages compared with VKAs. New studies are required

No effect of isolated long-term supine immobilization or profound prolonged hypoxia on blood coagulation.

PubMed

Venemans-Jellema, A; Schreijer, A J M; Le Cessie, S; Emmerich, J; Rosendaal, F R; Cannegieter, S C

2014-06-01

Long-distance air travel is associated with an increased risk of venous thrombosis. The most obvious factor that can explain air travel-related thrombosis is prolonged seated immobilization. In addition, hypobaric hypoxia has been shown to affect coagulation, and the lowered atmospheric pressures present in the cabin during the flight may therefore play an etiologic role. Because immobilization and hypoxic conditions are usually present simultaneously in airplanes or hypobaric chambers, their separate effects on the coagulation system or on thrombosis risk have not been studied extensively. To investigate the separate effects of long-term immobilization and profound prolonged hypoxia on blood coagulation. We performed two studies in collaboration with European Space Agency/European Space Research and Technology Centre. In the first study, 24 healthy, non-smoking, adult women underwent 60 days of -6° head-down bed rest. In the second study, we took blood samples from 25 healthy men who participated during their stay in the Concordia station in Antarctica, where, due to the atmospheric conditions, continuous severe hypobaric hypoxia is present. In both studies, we measured markers of blood coagulation at baseline and at several time points during the exposures. We observed no increase in coagulation markers during immobilization or in the hypobaric environment, compared with baseline measurements. Our results indicate that neither immobilization nor hypoxia per se affects blood coagulation. These results implicate that a combination of risk factors is necessary to induce the coagulation system during air travel. © 2014 International Society on Thrombosis and Haemostasis.

Solutions of Smoluchowski's coagulation equation at large cluster sizes

NASA Astrophysics Data System (ADS)

Van Dongen, P. G. J.

1987-09-01

In this paper we determine the behavior of solutions ck( t) of Smoluchowski's coagulation equation for cluster sizes much larger than the mean cluster size s( t). We consider in general the homogeneous rate constants K( i, j), behaving as K( i, j) ∼ iμjv as j → ∞, where special attention is paid to models with an exponent v = 1. The behavior of ck( t) is studied in three different limits: (i) the short-time limit ( t ↓ 0), with k ≫ 1, (ii) the limit k → ∞, with t > 0 fixed, and (iii) the scaling limit, with k ≫ s( t). The two most important conclusions of this paper are, first, that the detailed behavior of ck( t) at large cluster sizes ( k ≫ s( t)) may be drastically different for different rate constants K( i, j) and, secondly, that the results for ck( t), obtained in the limits (i), (ii) and (iii), are closely related.

The M358R variant of α{sub 1}-proteinase inhibitor inhibits coagulation factor VIIa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheffield, William P., E-mail: sheffiel@mcmaster.ca; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario; Bhakta, Varsha

The naturally occurring M358R mutation of the plasma serpin α{sub 1}-proteinase inhibitor (API) changes both its cleavable reactive centre bond to Arg–Ser and the efficacy with which it inhibits different proteases, reducing the rate of inhibition of neutrophil elastase, and enhancing that of thrombin, factor XIa, and kallikrein, by several orders of magnitude. Although another plasma serpin with an Arg–Ser reactive centre, antithrombin (AT), has been shown to inhibit factor VIIa (FVIIa), no published data are available with respect to FVIIa inhibition by API M358R. Recombinant bacterially-expressed API M358R and plasma-derived AT were therefore compared using gel-based and kinetic assaysmore » of FVIIa integrity and activity. Under pseudo-first order conditions of excess serpin over protease, both AT and API M358R formed denaturation-resistant inhibitory complexes with FVIIa in reactions accelerated by TF; AT, but not API M358R, also required heparin for maximal activity. The second order rate constant for heparin-independent API M358R-mediated FVIIa inhibition was determined to be 7.8 ± 0.8 × 10{sup 2} M{sup −1}sec{sup −1}. We conclude that API M358R inhibits FVIIa by forming inhibitory complexes of the serpin type more rapidly than AT in the absence of heparin. The likely 20-fold excess of API M358R over AT in patient plasma during inflammation raises the possibility that it could contribute to the hemorrhagic tendencies manifested by rare individuals expressing this mutant serpin. - Highlights: • The inhibitory specificity of the serpin alpha-1-proteinase inhibitor (API) is sharply altered in the M358R variant. • API M358R forms denaturation-resistant complexes with coagulation factor VIIa at a rate accelerated by tissue factor but unaffected by heparin. • Complex formation was shown by gel-based assays and quantified kinetically by inhibition of FVIIa-dependent amidolysis.« less

Platelet-derived growth factor regulates K-Cl cotransport in vascular smooth muscle cells.

PubMed

Zhang, Jing; Lauf, Peter K; Adragna, Norma C

2003-03-01

Platelet-derived growth factor (PDGF), a potent serum mitogen for vascular smooth muscle cells (VSMCs), plays an important role in membrane transport regulation and in atherosclerosis. K-Cl cotransport (K-Cl COT/KCC), the coupled-movement of K and Cl, is involved in ion homeostasis. VSMCs possess K-Cl COT activity and the KCC1 and KCC3 isoforms. Here, we report on the effect of PDGF on K-Cl COT activity and mRNA expression in primary cultures of rat VSMCs. K-Cl COT was determined as the Cl-dependent Rb influx and mRNA expression by semiquantitative RT-PCR. Twenty four-hour serum deprivation inhibited basal K-Cl COT activity. Addition of PDGF increased total protein content and K-Cl COT activity in a time-dependent manner. PDGF activated K-Cl COT in a dose-dependent manner, both acutely (10 min) and chronically (12 h). AG-1296, a selective inhibitor of the PDGF receptor tyrosine kinase, abolished these effects. Actinomycin D and cycloheximide had no effect on the acute PDGF activation of K-Cl COT, suggesting posttranslational regulation by the drug. Furthermore, PDGF increased KCC1 and decreased KCC3 mRNA expression in a time-dependent manner. These results indicate that chronic activation of K-Cl COT activity by PDGF may involve regulation of the two KCC mRNA isoforms, with KCC1 playing a dominant role in the mechanism of PDGF-mediated activation.

Evaluation of the treatment of reverse osmosis concentrates from municipal wastewater reclamation by coagulation and granular activated carbon adsorption.

PubMed

Sun, Ying-Xue; Yang, Zhe; Ye, Tao; Shi, Na; Tian, Yuan

2016-07-01

Reverse osmosis concentrate (ROC) from municipal wastewater reclamation reverse osmosis (mWRRO) contains elevated concentrations of contaminants which pose potential risks to aquatic environment. The treatment of ROC from an mWRRO using granular activated carbon (GAC) combined pretreatment of coagulation was optimized and evaluated. Among the three coagulants tested, ferric chloride (FeCl3) presented relatively higher DOC removal efficiency than polyaluminium chloride and lime at the same dosage and coagulation conditions. The removal efficiency of DOC, genotoxicity, and antiestrogenic activity concentration of the ROC could achieve 16.9, 18.9, and 39.7 %, respectively, by FeCl3 coagulation (with FeCl3 dosage of 180.22 mg/L), which can hardly reduce UV254 and genotoxicity normalized by DOC of the DOM with MW <5 kDa. However, the post-GAC adsorption column (with filtration velocity of 5.7 m/h, breakthrough point adsorption capacity of 0.22 mg DOC/g GAC) exhibited excellent removal efficiency on the dominant DOM fraction of MW <5 kDa in the ROC. The removal efficiency of DOC, UV254, and TDS in the ROC was up to 91.8, 96, and 76.5 %, respectively, by the FeCl3 coagulation and post-GAC adsorption. Also, the DOM with both genotoxicity and antiestrogenic activity were completely eliminated by the GAC adsorption. The results suggest that GAC adsorption combined pretreatment of FeCl3 coagulation as an efficient method to control organics, genotoxicity, and antiestrogenic activity in the ROC from mWRRO system.

Direct observation on the Brownian coagulation of PSL particles through optical microscope in the regime near critical coagulation concentration (CCC).

PubMed

Fukasawa, Tomonori; Adachi, Yasuhisa

2010-04-15

Microscopic monitoring of floc structure, floc size distribution and the rate of coagulation was carried out for Brownian coagulation of PSL particles. Experiments were designed for the condition of salt concentration that is slightly below critical coagulation concentration (CCC). The density of the solvent was controlled by using deuterium oxide (D(2)O) to avoid sedimentation. Results are summarized as follows: (i) Near CCC, floc restructuring from the beginning stage of coagulation was evidenced, i.e., the ratio of linear triplet is found to be remarkably reduced as compared with the result obtained for the case of rapid coagulation which was implemented under sufficiently high salt concentration. (ii) The increase of fractal dimension from 1.8 in the case of rapid coagulation to 2.2 was confirmed by the analysis of mass balance using size distribution of flocs. This increment resulted in the decrease of effective excluded volume of flocs. (iii) The rate of coagulation was constant until later stage. This result contrasts to the result of rapid coagulation [T. Fukasawa, Y. Adachi, J. Colloid Interface Sci. 304 (2006) 115]. 2010 Elsevier Inc. All rights reserved.

Anticoagulation beyond direct thrombin and factor Xa inhibitors: indications for targeting the intrinsic pathway?

PubMed

van Montfoort, Maurits L; Meijers, Joost C M

2013-08-01

Antithrombotic drugs like vitamin K antagonists and heparin have been the gold standard for the treatment and prevention of thromboembolic disease for many years. Unfortunately, there are several disadvantages of these antithrombotic drugs: they are accompanied by serious bleeding problems, it is necessary to monitor the therapeutic window, and there are various interactions with food and other drugs. This has led to the development of new oral anticoagulants, specifically inhibiting either thrombin or factor Xa. In terms of effectiveness, these drugs are comparable to the currently available anticoagulants; however, they are still associated with issues such as bleeding, reversal of the drug and complicated laboratory monitoring. Vitamin K antagonists, heparin, direct thrombin and factor Xa inhibitors have in common that they target key proteins of the haemostatic system. In an attempt to overcome these difficulties we investigated whether the intrinsic coagulation factors (VIII, IX, XI, XII, prekallikrein and high-molecular-weight kininogen) are superior targets for anticoagulation. We analysed epidemiological data concerning thrombosis and bleeding in patients deficient in one of the intrinsic pathway proteins. Furthermore, we discuss several thrombotic models in intrinsic coagulation factor-deficient animals. The combined results suggest that intrinsic coagulation factors could be suitable targets for anticoagulant drugs.

Thermodynamic analysis of the interaction of factor VIII with von Willebrand factor.

PubMed

Dimitrov, Jordan D; Christophe, Olivier D; Kang, Jonghoon; Repessé, Yohann; Delignat, Sandrine; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien

2012-05-22

Factor VIII (FVIII) is a glycoprotein that plays an important role in the intrinsic pathway of coagulation. In circulation, FVIII is protected upon binding to von Willebrand factor (VWF), a chaperone molecule that regulates its half-life, distribution, and activity. Despite the biological significance of this interaction, its molecular mechanisms are not fully characterized. We determined the equilibrium and activation thermodynamics of the interaction between FVIII and VWF. The equilibrium affinity determined by surface plasmon resonance was temperature-dependent with a value of 0.8 nM at 35 °C. The FVIII-VWF interaction was characterized by very fast association (8.56 × 10(6) M(-1) s(-1)) and fast dissociation (6.89 × 10(-3) s(-1)) rates. Both the equilibrium association and association rate constants, but not the dissociation rate constant, were dependent on temperature. Binding of FVIII to VWF was characterized by favorable changes in the equilibrium and activation entropy (TΔS° = 89.4 kJ/mol, and -TΔS(++) = -8.9 kJ/mol) and unfavorable changes in the equilibrium and activation enthalpy (ΔH° = 39.1 kJ/mol, and ΔH(++) = 44.1 kJ/mol), yielding a negative change in the equilibrium Gibbs energy. Binding of FVIII to VWF in solid-phase assays demonstrated a high sensitivity to acidic pH and a sensitivity to ionic strength. Our data indicate that the interaction between FVIII and VWF is mediated mainly by electrostatic forces, and that it is not accompanied by entropic constraints, suggesting the absence of conformational adaptation but the presence of rigid "pre-optimized" binding surfaces.

Effects of anti-aggregant, anti-inflammatory and anti-coagulant drug consumption on the preparation and therapeutic potential of plasma rich in growth factors (PRGF).

PubMed

Anitua, Eduardo; Troya, María; Zalduendo, Mar; Orive, Gorka

2015-02-01

The prevalence and incidence of trauma-related injuries, coronary heart disease and other chronic diseases increase dramatically with age. This population sector is therefore a regular consumer of different types of drugs that may affect platelet aggregation and the coagulation cascade. We have evaluated whether the consumption of acetylsalicylic acid, acenocoumarol, glucosamine sulfate and chondroitin sulfate, and therefore their presence in blood, could interfere with the preparation and biological outcomes of plasma rich in growth factors (PRGF). Clotting time, clot retraction and platelet activation of PRGF was evaluated. PRGF growth factor content and the release of different biomolecules by tendon fibroblasts were also quantified, as well as cell proliferation and cell migration. The preparation and biological potential of PRGF is not affected by the intake of the evaluated drugs, and solely its angiogenic potential and its capacity to induce HA and fibronectin synthesis, is reduced in patients taking anti-coagulants.

Fate of nanoparticles during alum and ferric coagulation monitored using single particle ICP-MS.

PubMed

Donovan, Ariel R; Adams, Craig D; Ma, Yinfa; Stephan, Chady; Eichholz, Todd; Shi, Honglan

2018-03-01

In this study, aluminum sulfate, ferric sulfate, ferric chloride, and poly(diallyldimethylammonium chloride) (pDADMAC) coagulation removal of citrate-stabilized silver and gold nanoparticles (NPs) and uncoated titanium dioxide, cerium dioxide, and zinc oxide NPs was investigated using a single particle (SP) ICP-MS direct monitoring technique. Zone 2 (charge neutralization) coagulation was performed in river water and more commonly used Zone 4 (sweep floc) coagulation was performed in both river and lake water with environmentally relevant concentrations of selected NPs added. SP-ICP-MS was used to detect NP and dissolved species, characterize the size distribution, and quantify particle concentration as well as dissolved species before and after treatments. Other parameters including pH, dissolved organic carbon, turbidity, and UV 254 absorbance were monitored to characterize treatment efficiency. Charge neutralization (Zone 2) coagulation resulted in 48-85% removal of citrate-stabilized NPs and 90-99% removal of uncoated NPs from river water. Sweep floc (Zone 4) coagulation in river water resulted in 36-94% removal of citrate-stabilized NPs and 91-99% removal of uncoated NPs both with and without polymer addition. Zone 4 coagulation conditions in lake water resulted in 77-98% removal of citrate-stabilized NPs and 59-96% removal of uncoated NPs without polymer. These results indicate that NP removal depends on NP surface and stability, the nature of the source water, and the coagulant type and approach. Copyright © 2017 Elsevier Ltd. All rights reserved.

Industrial production of clotting factors: Challenges of expression, and choice of host cells.

PubMed

Kumar, Sampath R

2015-07-01

The development of recombinant forms of blood coagulation factors as safer alternatives to plasma derived factors marked a major advance in the treatment of common coagulation disorders. These are complex proteins, mostly enzymes or co-enzymes, involving multiple post-translational modifications, and therefore are difficult to express. This article reviews the nature of the expression challenges for the industrial production of these factors, vis-à-vis the translational and post-translational bottlenecks, as well as the choice of host cell lines for high-fidelity production. For achieving high productivities of vitamin K dependent proteins, which include factors II (prothrombin), VII, IX and X, and protein C, host cell limitation of γ-glutamyl carboxylation is a major bottleneck. Despite progress in addressing this, involvement of yet unidentified protein(s) impedes a complete cell engineering solution. Human factor VIII expresses at very low levels due to limitations at several steps in the protein secretion pathway. Protein and cell engineering, vector improvement and alternate host cells promise improvement in the productivity. Production of Von Willebrand factor is constrained by its large size, complex structure, and the need for extensive glycosylation and disulfide-bonded oligomerization. All the licensed therapeutic factors are produced in CHO, BHK or HEK293 cells. While HEK293 is a recent adoption, BHK cells appear to be disfavored. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Relative effects of plasma, fibrinogen concentrate, and factor XIII on ROTEM coagulation profiles in an in vitro model of massive transfusion in trauma.

PubMed

Schmidt, David E; Halmin, Märit; Wikman, Agneta; Östlund, Anders; Ågren, Anna

2017-10-01

Massive traumatic haemorrhage is aggravated through the development of trauma-induced coagulopathy, which is managed by plasma transfusion and/or fibrinogen concentrate administration. It is yet unclear whether these treatments are equally potent in ensuring adequate haemostasis, and whether additional factor XIII (FXIII) administration provides further benefits. In this study, we compared ROTEM whole blood coagulation profiles after experimental massive transfusion with different transfusion regimens in an in vitro model of dilution- and transfusion-related coagulopathy. Healthy donor blood was mixed 1 + 1 with six different transfusion regimens. Each regimen contained RBC, platelet concentrate, and either fresh frozen plasma (FFP) or Ringer's acetate (RA). The regimens were further augmented through addition of a low- or medium-dose fibrinogen concentrate and FXIII. Transfusion with FFP alone was insufficient to maintain tissue-factor activated clot strength, coincidental with a deficiency in fibrin-based clot strength. Fibrinogen concentrate conserved, but did not improve coagulation kinetics and overall clot strength. Only combination therapy with FFP and low-dose fibrinogen concentrate improved both coagulation kinetics and fibrin-based clot strength. Administration of FXIII did not result in an improvement of clot strength. In conclusion, combination therapy with both FFP and low-dose fibrinogen concentrate improved clotting time and produced firm clots, representing a possible preferred first-line regimen to manage trauma-induced coagulopathy when RBC and platelets are also transfused. Further research is required to identify optimal first-line transfusion fluids for massive traumatic haemorrhage.

On coagulation mechanisms of charged nanoparticles produced by combustion of hydrocarbon and metallized fuels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Savel'ev, A. M.; Starik, A. M.

2009-02-15

The contributions of van der Waals, Coulomb, and polarization interactions between nanometersized particles to the particle coagulation rate in both free-molecular and continuum regimes are analyzed for particle charges of various magnitudes and signs. Analytical expressions are obtained for the coagulation rate constant between particles whose interaction in the free-molecular regime is described by a singular potential. It is shown that van der Waals and polarization forces significantly increase the coagulation rate between a neutral and a charged particle (by a factor of up to 10) and can even suppress the Coulomb repulsion between like-charged particles of widely different sizes.

Anxiety and depression in patients three months after myocardial infarction: Association with markers of coagulation and the relevance of age.

PubMed

Geiser, Franziska; Urbach, Anne Sarah; Harbrecht, Ursula; Conrad, Rupert; Pötzsch, Bernd; Amann, Nele; Kiesewetter, Katharina; Sieke, Alexandra; Wolffs, Kyra; Skowasch, Dirk

2017-08-01

Anxiety and depression are associated with an activation of coagulation and an impairment of fibrinolysis, which may contribute to the increased cardiovascular risk associated with the two disorders. However, very few studies have examined the impact of psychological distress on coagulation factors in coronary artery disease patients. The aim of this study was to assess the correlation between anxiety/depression and factors of coagulation and fibrinolysis in patients who had suffered an acute MI three months prior. In 148 patients, anxiety and depression were assessed by the Hospital Anxiety and Depression Scale (HADS) shortly after MI and three months later. At the second time of assessment, plasma levels of fibrinogen, factor VII, factor VIII, von Willebrand factor, prothrombin-fragment 1 and 2, tissue-plasminogen-activator, plasminogen activator inhibitor-1, D-dimer, and homocysteine were measured. In 32% of the patients, elevated levels of anxiety and depression were found three months after a MI. Multiple regression analyses showed that coagulation and fibrinolysis markers were not significantly associated with HADS anxiety and depression scores. We found that age, gender, BMI, and smoking status were significant predictors for haemostasis factors. A higher age was associated with a higher coagulability but lower anxiety levels. We measured parameters of coagulation and fibrinolysis in patients three months after MI and found no predictive value of HADS anxiety and depression scores shortly after MI or at the time of blood sampling. The effects of age on the relationship between anxiety and haemostasis should be further investigated. Copyright © 2017 Elsevier Inc. All rights reserved.

Minimizing residual aluminum concentration in treated water by tailoring properties of polyaluminum coagulants.

PubMed

Kimura, Masaoki; Matsui, Yoshihiko; Kondo, Kenta; Ishikawa, Tairyo B; Matsushita, Taku; Shirasaki, Nobutaka

2013-04-15

Aluminum coagulants are widely used in water treatment plants to remove turbidity and dissolved substances. However, because high aluminum concentrations in treated water are associated with increased turbidity and because aluminum exerts undeniable human health effects, its concentration should be controlled in water treatment plants, especially in plants that use aluminum coagulants. In this study, the effect of polyaluminum chloride (PACl) coagulant characteristics on dissolved residual aluminum concentrations after coagulation and filtration was investigated. The dissolved residual aluminum concentrations at a given coagulation pH differed among the PACls tested. Very-high-basicity PACl yielded low dissolved residual aluminum concentrations and higher natural organic matter (NOM) removal. The low residual aluminum concentrations were related to the low content of monomeric aluminum (Ala) in the PACl. Polymeric (Alb)/colloidal (Alc) ratio in PACl did not greatly influence residual aluminum concentration. The presence of sulfate in PACl contributed to lower residual aluminum concentration only when coagulation was performed at around pH 6.5 or lower. At a wide pH range (6.5-8.5), residual aluminum concentrations <0.02 mg/L were attained by tailoring PACl properties (Ala percentage ≤0.5%, basicity ≥85%). The dissolved residual aluminum concentrations did not increase with increasing the dosage of high-basicity PACl, but did increase with increasing the dosage of normal-basicity PACl. We inferred that increasing the basicity of PACl afforded lower dissolved residual aluminum concentrations partly because the high-basicity PACls could have a small percentage of Ala, which tends to form soluble aluminum-NOM complexes with molecular weights of 100 kDa-0.45 μm. Copyright © 2013 Elsevier Ltd. All rights reserved.

Analysis and optimization of coagulation and flocculation process

NASA Astrophysics Data System (ADS)

Saritha, V.; Srinivas, N.; Srikanth Vuppala, N. V.

2017-03-01

Natural coagulants have been the focus of research of many investigators through the last decade owing to the problems caused by the chemical coagulants. Optimization of process parameters is vital for the effectiveness of coagulation process. In the present study optimization of parameters like pH, dose of coagulant and mixing speed were studied using natural coagulants sago and chitin in comparison with alum. Jar test apparatus was used to perform the coagulation. The results showed that the removal of turbidity was up to 99 % by both alum and chitin at lower doses of coagulant, i.e., 0.1-0.3 g/L, whereas sago has shown a reduction of 70-100 % at doses of 0.1 and 0.2 g/L. The optimum conditions observed for sago were 6 and 7 whereas chitin was stable at all pH ranges, lower coagulant doses, i.e., 0.1-0.3 g/L and mixing speed—rapid mixing at 100 rpm for 10 min and slow mixing 20 rpm for 20 min. Hence, it can be concluded that sago and chitin can be used for treating water even with large seasonal variation in turbidity.

Coagulant recovery and reuse for drinking water treatment.

PubMed

Keeley, James; Jarvis, Peter; Smith, Andrea D; Judd, Simon J

2016-01-01

Coagulant recovery and reuse from waterworks sludge has the potential to significantly reduce waste disposal and chemicals usage for water treatment. Drinking water regulations demand purification of recovered coagulant before they can be safely reused, due to the risk of disinfection by-product precursors being recovered from waterworks sludge alongside coagulant metals. While several full-scale separation technologies have proven effective for coagulant purification, none have matched virgin coagulant treatment performance. This study examines the individual and successive separation performance of several novel and existing ferric coagulant recovery purification technologies to attain virgin coagulant purity levels. The new suggested approach of alkali extraction of dissolved organic compounds (DOC) from waterworks sludge prior to acidic solubilisation of ferric coagulants provided the same 14:1 selectivity ratio (874 mg/L Fe vs. 61 mg/L DOC) to the more established size separation using ultrafiltration (1285 mg/L Fe vs. 91 mg/L DOC). Cation exchange Donnan membranes were also examined: while highly selective (2555 mg/L Fe vs. 29 mg/L DOC, 88:1 selectivity), the low pH of the recovered ferric solution impaired subsequent treatment performance. The application of powdered activated carbon (PAC) to ultrafiltration or alkali pre-treated sludge, dosed at 80 mg/mg DOC, reduced recovered ferric DOC contamination to <1 mg/L but in practice, this option would incur significant costs. The treatment performance of the purified recovered coagulants was compared to that of virgin reagent with reference to key water quality parameters. Several PAC-polished recovered coagulants provided the same or improved DOC and turbidity removal as virgin coagulant, as well as demonstrating the potential to reduce disinfection byproducts and regulated metals to levels comparable to that attained from virgin material. Copyright © 2015 Elsevier Ltd. All rights reserved.

Probing Coagulation Behavior of Individual Aluminum Species for Removing Corresponding Disinfection Byproduct Precursors: The Role of Specific Ultraviolet Absorbance

PubMed Central

Zhao, He; Hu, Chengzhi; Zhang, Di; Liu, Huijuan; Qu, Jiuhui

2016-01-01

Coagulation behavior of aluminum chloride and polyaluminum chloride (PACl) for removing corresponding disinfection byproduct (DBP) precursors was discussed in this paper. CHCl3, bromine trihalomethanes (THM-Br), dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) formation potential yields were correlated with specific ultraviolet absorbance (SUVA) values in different molecular weight (MW) fractions of humic substances (HS), respectively. Correlation analyses and principal component analysis were performed to examine the relationships between SUVA and different DBP precursors. To acquire more structural characters of DBP precursors and aluminum speciation, freeze-dried precipitates were analyzed by fourier transform infrared (FTIR) and C 1s, Al 2p X-ray photoelectron spectroscopy (XPS). The results indicated that TCAA precursors (no MW limits), DCAA and CHCl3 precursors in low MW fractions (MW<30 kDa) had a relatively good relations with SUVA values. These DBP precursors were coagulated more easily by in situ Al13 of AlCl3 at pH 5.0. Due to relatively low aromatic content and more aliphatic structures, THM-Br precursors (no MW limits) and CHCl3 precursors in high MW fractions (MW>30 kDa) were preferentially removed by PACl coagulation with preformed Al13 species at pH 5.0. Additionally, for DCAA precursors in high MW fractions (MW>30 kDa) with relatively low aromatic content and more carboxylic structures, the greatest removal occurred at pH 6.0 through PACl coagulation with aggregated Al13 species. PMID:26824243

Factor Xa Activation of Factor V is of Paramount Importance in Initiating the Coagulation System: Lessons from a Tick Salivary Protein

PubMed Central

Schuijt, Tim J.; Bakhtiari, Kamran; Daffre, Sirlei; DePonte, Kathleen; Wielders, Simone J.H.; Marquart, J. Arnoud; Hovius, Joppe W.; van der Poll, Tom; Fikrig, Erol; Bunce, Matthew W.; Camire, Rodney M.; Nicolaes, Gerry A.F.; Meijers, Joost C.M.; van 't Veer, Cornelis

2013-01-01

Background Generation of active procoagulant cofactor FVa and its subsequent association with the enzyme FXa to form the prothrombinase complex is a pivotal initial event in blood coagulation and has been the subject of investigative effort, speculation and controversy. The current paradigm assumes that FV activation is initiated by limited proteolysis by traces of (meizo) thrombin. Methods and Results Recombinant tick salivary protein TIX-5 was produced and anticoagulant properties were studied using plasma, whole blood and purified systems. Here we report that TIX-5 specifically inhibits FXa-mediated FV activation involving the B-domain of FV and show that FXa activation of FV is pivotal for plasma and blood clotting. In line, tick feeding is impaired on TIX-5 immune rabbits displaying the in vivo importance of TIX-5. Conclusions Our data elucidate a unique molecular mechanism by which ticks inhibit the host's coagulation system. Based on our data we propose a revised blood coagulation scheme wherein direct FXa-mediated FV activation occurs in the initiation phase during which thrombin-mediated FV activation is restrained by fibrinogen and inhibitors. PMID:23817575

Enhancement of sedimentation and coagulation with static magnetic field

NASA Astrophysics Data System (ADS)

Zieliński, Marcin; Dębowski, Marcin; Hajduk, Anna; Rusanowska, Paulina

2017-11-01

The static magnetic field can be an alternative method for wastewater treatment. It has been proved that this physical factor, accelerates the biochemical processes, catalyzes advanced oxidation, intensifies anaerobic and aerobic processes or reduces swelling of activated sludge. There are also reports proving the positive impact of the static magnetic field on the coagulation and sedimentation, as well as the conditioning and dewatering of sludge. In order to be applied in larger scale the published results should be verified and confirmed. In the studies, the enhancement of sedimentation by the static magnetic field was observed. The best sedimentation was noted in the experiment, where magnetizers were placed on activated sludge bioreactor and secondary settling tank. No effect of the static magnetic field on coagulation with the utilization of PIX 113 was observed. However, the static magnetic field enhanced coagulation with the utilization of PAX-XL9. The results suggest that increased sedimentation of colloids and activated sludge, can in practice mean a reduction in the size of the necessary equipment for sedimentation with an unchanged efficiency of the process.

Comparison of coagulation pretreatment of produced water from natural gas well by polyaluminium chloride and polyferric sulphate coagulants.

PubMed

Zhai, Jun; Huang, Zejin; Rahaman, Md Hasibur; Li, Yue; Mei, Longyue; Ma, Hongpu; Hu, Xuebin; Xiao, Haiwen; Luo, Zhiyong; Wang, Kunping

2017-05-01

This study aimed to optimise coagulation pretreatment of the produced water (PW) collected from a natural gas field. Two coagulants, polyferric sulphate (PFS) and polyaluminium chloride (PACl), were applied separately for the organics, suspended solids (SS), and colour removal. Treatment performance at different coagulant dosages, initial pH values, stirring patterns, and the addition of cationic polyacrylamide (PAM) was investigated in jar tests. The optimal coagulation conditions were dosage of PACl 25 g/L or PFS 20 g/L with that of PAM 30 mg/L, initial pH of 11, and fast mixing of 1.5 min (for PACl) or 2 min (for PFS) at 250 rpm followed by slow mixing of 15 min at 50 rpm for both coagulants. PACl performed better than PFS to remove chemical oxygen demand (COD), total organic carbon (TOC), SS, and colour, and achieved a removal efficiency of 90.1%, 89.4%, 99.0%, and 99.9%, respectively, under the optimal condition; while PFS efficiency was 86.1%, 86.1%, 99.0%, and 98.2%, respectively. However, oil removal was higher in PFS coagulation compared to PACl and showed 98.9% and 95.3%, respectively. Biodegradability, ratio of the biological oxygen demand (five-day) (BOD 5 )/COD, of the PW after pretreatment increased from 0.08 to 0.32 for PFS and 0.43 for PACl. Zeta potential (Z-potential) analysis at the optimum coagulant dosage of PACl and PFS suggests that charge neutralisation was the predominant mechanism during coagulation. Better efficiency was observed at higher pH. The addition of PAM and starring pattern had a minor influence on the removal performance of both coagulants. The results suggest that PACl or PFS can be applied for the pretreatment of PW, which can provide substantial removal of carbon, oil, and colour, a necessary first step for subsequent main treatment units such as chemical oxidation or biological treatment.

Plasmapheresis in severe septic shock with disseminated intravascular coagulation.

PubMed

Zilow, E P; Selle, B; Zilow, G

1994-01-01

An 18-year-old female with CNS relapse of acute lymphoblastic leukemia after previous complete remission of the disease underwent chemotherapy. Due to the therapy she suffered from profound suppression of bone marrow with consecutive thrombocytopenia and leukopenia. Despite prophylactic treatment, severe septicemia occurred with septic shock, hemolysis and disseminated intravascular coagulation (DIC). As the clinical course became uncontrollable by means of conventional therapy, including broad-spectrum antibiotics, substitution of fresh frozen plasma, antithrombin III and heparin therapy, plasma exchange was used as a rescue therapy. This method succeeded in effective replacement of clotting factors and normalization of coagulation, in removal of fibrinogen degradation products and probably of toxins and shock mediators. The patient recovered from shock.

The impact of pre-oxidation with potassium permanganate on cyanobacterial organic matter removal by coagulation.

PubMed

Naceradska, Jana; Pivokonsky, Martin; Pivokonska, Lenka; Baresova, Magdalena; Henderson, Rita K; Zamyadi, Arash; Janda, Vaclav

2017-05-01

The study investigates the effect of permanganate pre-oxidation on the coagulation of peptides/proteins of Microcystis aeruginosa which comprise a major proportion of the organic matter during cyanobacterial bloom decay. Four different permanganate dosages (0.1, 0.2, 0.4 and 0.6 mg KMnO 4 mg -1 DOC) were applied prior to coagulation by ferric sulphate. Moreover, changes in sample characteristics, such as UV 254 , DOC content and molecular weight distribution, after pre-oxidation were monitored. The results showed that permanganate pre-oxidation led to a reduction in coagulant dose, increased organic matter removals by coagulation (by 5-12% depending on permanganate dose), microcystin removal (with reductions of 91-96%) and a shift of the optimum pH range from 4.3 to 6 without to 5.5-7.3 with pre-oxidation. Degradation of organic matter into inorganic carbon and adsorption of organic matter onto hydrous MnO 2 are suggested as the main processes responsible for coagulation improvement. Moreover, permanganate prevented the formation of Fe-peptide/protein complexes that inhibit coagulation at pH about 6.2 without pre-oxidation. The study showed that carefully optimized dosing of permanganate improves cyanobacterial peptide/protein removal, with the benefit of microcystin elimination. Copyright © 2017 Elsevier Ltd. All rights reserved.

Local activation of coagulation factor XIII reduces systemic complications and improves the survival of mice after Streptococcus pyogenes M1 skin infection.

PubMed

Deicke, Christin; Chakrakodi, Bhavya; Pils, Marina C; Dickneite, Gerhard; Johansson, Linda; Medina, Eva; Loof, Torsten G

2016-11-01

Coagulation is a mechanism for wound healing after injury. Several recent studies delineate an additional role of the intrinsic pathway of coagulation, also known as the contact system, in the early innate immune response against bacterial infections. In this study, we investigated the role of factor XIII (FXIII), which is activated upon coagulation induction, during Streptococcus pyogenes-mediated skin and soft tissue infections. FXIII has previously been shown to be responsible for the immobilization of bacteria within a fibrin network which may prevent systemic bacterial dissemination. In order to investigate if the FXIII-mediated entrapment of S. pyogenes also influences the disease outcome we used a murine S. pyogenes M1 skin and soft tissue infection model. Here, we demonstrate that a lack of FXIII leads to prolonged clotting times, increased signs of inflammation, and elevated bacterial dissemination. Moreover, FXIII-deficient mice show an impaired survival when compared with wildtype animals. Additionally, local reconstitution of FXIII-deficient mice with a human FXIII-concentrate (Fibrogammin ® P) could reduce the systemic complications, suggesting a protective role for FXIII during early S. pyogenes skin infection. FXIII therefore might be a possible therapeutically application to support the early innate immune response during skin infections caused by S. pyogenes. Copyright © 2016 Elsevier GmbH. All rights reserved.

Causal relationships between milk quality and coagulation properties in Italian Holstein-Friesian dairy cattle.

PubMed

Tiezzi, Francesco; Valente, Bruno D; Cassandro, Martino; Maltecca, Christian

2015-05-13

Recently, selection for milk technological traits was initiated in the Italian dairy cattle industry based on direct measures of milk coagulation properties (MCP) such as rennet coagulation time (RCT) and curd firmness 30 min after rennet addition (a30) and on some traditional milk quality traits that are used as predictors, such as somatic cell score (SCS) and casein percentage (CAS). The aim of this study was to shed light on the causal relationships between traditional milk quality traits and MCP. Different structural equation models that included causal effects of SCS and CAS on RCT and a30 and of RCT on a30 were implemented in a Bayesian framework. Our results indicate a non-zero magnitude of the causal relationships between the traits studied. Causal effects of SCS and CAS on RCT and a30 were observed, which suggests that the relationship between milk coagulation ability and traditional milk quality traits depends more on phenotypic causal pathways than directly on common genetic influence. While RCT does not seem to be largely controlled by SCS and CAS, some of the variation in a30 depends on the phenotypes of these traits. However, a30 depends heavily on coagulation time. Our results also indicate that, when direct effects of SCS, CAS and RCT are considered simultaneously, most of the overall genetic variability of a30 is mediated by other traits. This study suggests that selection for RCT and a30 should not be performed on correlated traits such as SCS or CAS but on direct measures because the ability of milk to coagulate is improved through the causal effect that the former play on the latter, rather than from a common source of genetic variation. Breaking the causal link (e.g. standardizing SCS or CAS before the milk is processed into cheese) would reduce the impact of the improvement due to selective breeding. Since a30 depends heavily on RCT, the relative emphasis that is put on this trait should be reconsidered and weighted for the fact that the pure

Magnetic Resonance Mediated Radio Frequency Coagulation for Vascular Repair

NASA Astrophysics Data System (ADS)

Zhao, Ming

Purpose. Magnetic Resonance Mediated Radiofrequency Coagulation employs the RF heating effect of MRI scanning to coagulate biomaterials for repair of vascular defects. Coagulation of a protein biomaterial by MR-induced RF heating is a novel means to effect repair of defects such as aneurysms or arteriovenous malformations. Our novel method is to coagulate a thermosetting material (such as egg white, which can be used for investigating heat coagulation behavior and MR relaxation properties) delivered endovascularly by catheter and coagulated by RF-induced heating of an intracatheter resonant wire antenna in the scanner. Methods. Experiments were performed on a Siemens 1.5 T MRI scanner and a Bruker 14T NMR spectrometer. Egg white was brought to equilibrium at seven temperatures (20, 30, 40, 50, 60, 70 and 37 °C) in sequence. Measurement of the water spin-lattice relaxation time Ti, spin-spin relaxation time T2, spin-lattice relaxation time in the rotating frame T1p, or full width at half maximum of the MT spectrum were performed at each temperature. Relaxation parameters of raw egg white and egg white after coagulation at 70 °C were measured in the scanner at 20 °C to determine optimum inversion time, echo time and offset frequency for good image contrast between coagulated and uncoagulated protein. Finally, coagulation of egg white within a glass aneurysm phantom by RF heating in the scanner was performed to demonstrate the MR coagulation methodology and the ability to achieve image contrast between coagulated and uncoagulated biomaterial. Results. Water T2, T1p and MT gave the most definitive indication of the change from uncoagulated at low temperature to fully coagulated at 60 °C, while water T1 showed only the expected gradual increase with temperature, and no response to coagulation. MT weighted imaging is expected to be the optimum method to establish the coagulation condition of the biomaterial.

Technical note: Improving modeling of coagulation, curd firming, and syneresis of sheep milk.

PubMed

Cipolat-Gotet, Claudio; Pazzola, Michele; Ferragina, Alessandro; Cecchinato, Alessio; Dettori, Maria L; Vacca, Giuseppe M

2018-04-18

The importance of milk coagulation properties for milk processing, cheese yield, and quality is widely recognized. The use of traditional coagulation traits presents several limitations for testing bovine milk and even more for sheep milk, due to its rapid coagulation and curd firming, and early syneresis of coagulum. The aim of this technical note is to test and improve model fitting for assessing coagulation, curd firming, and syneresis of sheep milk. Using milk samples from 87 Sarda ewes, we performed in duplicate lactodynamographic testing. On each of the 174 analyzed milk aliquots, using 180 observations from each aliquot (one every 15 s for 45 min after rennet addition), we compared 4 different curd firming models as a function of time (CF t , mm) using a nonlinear procedure. The most accurate and informative results were observed using a modified 4-parameter model, structured as follows: [Formula: see text] , where t is time, RCT eq (min) is the gelation time, CF P (mm) is the potential asymptotical CF at an infinite time, k CF (%/min) is the curd firming rate constant, and k SR (%/min) is the curd syneresis rate constant. To avoid nonconvergence and computational problems due to interrelations among the equation parameters, CF P was preliminarily defined as a function of maximum observed curd firmness (CF max , mm) recorded during the analysis. For this model, all the modeling equations of individual sheep milk aliquots were converging, with a negligible standard error of the estimates (coefficient of determination >0.99 for all individual sample equations). Repeatability of the modeled parameters was acceptable, also in the presence of curd syneresis during the lactodynamographic analysis. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Radio-frequency lesioning in brain tissue with coagulation-dependent thermal conductivity: modelling, simulation and analysis of parameter influence and interaction.

PubMed

Johansson, Johannes D; Eriksson, Ola; Wren, Joakim; Loyd, Dan; Wårdell, Karin

2006-09-01

Radio-frequency brain lesioning is a method for reducing e.g. symptoms of movement disorders. A small electrode is used to thermally coagulate malfunctioning tissue. Influence on lesion size from thermal and electric conductivity of the tissue, microvascular perfusion and preset electrode temperature was investigated using a finite-element model. Perfusion was modelled as an increased thermal conductivity in non-coagulated tissue. The parameters were analysed using a 2(4)-factorial design (n=16) and quadratic regression analysis (n=47). Increased thermal conductivity of the tissue increased lesion volume, while increased perfusion decreased it since coagulation creates a thermally insulating layer due to the cessation of blood perfusion. These effects were strengthened with increased preset temperature. The electric conductivity had negligible effect. Simulations were found realistic compared to in vivo experimental lesions.

Measured and Monte Carlo calculated k{sub Q} factors: Accuracy and comparison

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muir, B. R.; McEwen, M. R.; Rogers, D. W. O.

2011-08-15

sleeve effect and the effect of cavity length on k{sub Q}. The mean percent differences between experimental and Monte Carlo calculated k{sub Q} factors are -0.08, -0.07, and -0.23% for the Elekta 6, 10, and 25 MV nominal beam energies, respectively. An upper limit on the variation of W/e in photon beams from cobalt-60 to 25 MV is determined as 0.4% with 95% confidence. The combined uncertainty on Monte Carlo calculated k{sub Q} factors is reassessed and amounts to between 0.40 and 0.49% depending on the wall material of the chamber. Conclusions: Excellent agreement (mean percent difference of only 0.13% for the entire data set) between experimental and calculated k{sub Q} factors is observed. For some chambers, k{sub Q} is measured for only one chamber of each type--the level of agreement observed in this study would suggest that for those chambers the measured k{sub Q} values are generally representative of the chamber type.« less

Thrombin-dependent Incorporation of von Willebrand Factor into a Fibrin Network*

PubMed Central

Miszta, Adam; Pelkmans, Leonie; Lindhout, Theo; Krishnamoorthy, Ganeshram; de Groot, Philip G.; Hemker, Coenraad H.; Heemskerk, Johan W. M.; Kelchtermans, Hilde; de Laat, Bas

2014-01-01

Attachment of platelets from the circulation onto a growing thrombus is a process involving multiple platelet receptors, endothelial matrix components, and coagulation factors. It has been indicated previously that during a transglutaminase reaction activated factor XIII (FXIIIa) covalently cross-links von Willebrand factor (VWF) to polymerizing fibrin. Bound VWF further recruits and activates platelets via interactions with the platelet receptor complex glycoprotein Ib (GPIb). In the present study we found proof for binding of VWF to a fibrin monomer layer during the process of fibrinogen-to-fibrin conversion in the presence of thrombin, arvin, or a snake venom from Crotalus atrox. Using a domain deletion mutant we demonstrated the involvement of the C domains of VWF in this binding. Substantial binding of VWF to fibrin monomers persisted in the presence of the FXIIIa inhibitor K9-DON, illustrating that cross-linking via factor XIII is not essential for this phenomenon and suggesting the identification of a second mechanism through which VWF multimers incorporate into a fibrin network. Under high shear conditions, platelets were shown to adhere to fibrin only if VWF had been incorporated. In conclusion, our experiments show that the C domains of VWF and the E domain of fibrin monomers are involved in the incorporation of VWF during the polymerization of fibrin and that this incorporation fosters binding and activation of platelets. Fibrin thus is not an inert end product but partakes in further thrombus growth. Our findings help to elucidate the mechanism of thrombus growth and platelet adhesion under conditions of arterial shear rate. PMID:25381443

A Novel Role for Pro-Coagulant Microvesicles in the Early Host Defense against Streptococcus pyogenes

PubMed Central

Oehmcke, Sonja; Westman, Johannes; Malmström, Johan; Mörgelin, Matthias; Olin, Anders I.; Kreikemeyer, Bernd; Herwald, Heiko

2013-01-01

Previous studies have shown that stimulation of whole blood or peripheral blood mononuclear cells with bacterial virulence factors results in the sequestration of pro-coagulant microvesicles (MVs). These particles explore their clotting activity via the extrinsic and intrinsic pathway of coagulation; however, their pathophysiological role in infectious diseases remains enigmatic. Here we describe that the interaction of pro-coagulant MVs with bacteria of the species Streptococcus pyogenes is part of the early immune response to the invading pathogen. As shown by negative staining electron microscopy and clotting assays, pro-coagulant MVs bind in the presence of plasma to the bacterial surface. Fibrinogen was identified as a linker that, through binding to the M1 protein of S. pyogenes, allows the opsonization of the bacteria by MVs. Surface plasmon resonance analysis revealed a strong interaction between pro-coagulant MVs and fibrinogen with a KD value in the nanomolar range. When performing a mass-spectrometry-based strategy to determine the protein quantity, a significant up-regulation of the fibrinogen-binding integrins CD18 and CD11b on pro-coagulant MVs was recorded. Finally we show that plasma clots induced by pro-coagulant MVs are able to prevent bacterial dissemination and possess antimicrobial activity. These findings were confirmed by in vivo experiments, as local treatment with pro-coagulant MVs dampens bacterial spreading to other organs and improved survival in an invasive streptococcal mouse model of infection. Taken together, our data implicate that pro-coagulant MVs play an important role in the early response of the innate immune system in infectious diseases. PMID:23935504

A Comparison of Blood Factor XII Autoactivation in Buffer, Protein Cocktail, Serum, and Plasma Solutions

PubMed Central

Golas, Avantika; Yeh, Chyi-Huey Josh; Pitakjakpipop, Harit; Siedlecki, Christopher A.; Vogler, Erwin A.

2012-01-01

Activation of blood plasma coagulation in vitro by contact with material surfaces is demonstrably dependent on plasma-volume-to-activator-surface-area ratio. The only plausible explanation consistent with current understanding of coagulation-cascade biochemistry is that procoagulant stimulus arising from the activation complex of the intrinsic pathway is dependent on activator surface area. And yet, it is herein shown that activation of the blood zymogen factor XII (Hageman factor, FXII) dissolved in buffer, protein cocktail, heat-denatured serum, and FXI deficient plasma does not exhibit activator surface-area dependence. Instead, a highly-variable burst of procoagulant-enzyme yield is measured that exhibits no measurable kinetics, sensitivity to mixing, or solution-temperature dependence. Thus, FXII activation in both buffer and protein-containing solutions does not exhibit characteristics of a biochemical reaction but rather appears to be a “mechanochemical” reaction induced by FXII molecule interactions with hydrophilic activator particles that do not formally adsorb blood proteins from solution. Results of this study strongly suggest that activator surface-area dependence observed in contact activation of plasma coagulation does not solely arise at the FXII activation step of the intrinsic pathway. PMID:23117212

A PMMA microfluidic dielectric sensor for blood coagulation monitoring at the point-of-care.

PubMed

Maji, Debnath; Suster, Michael A; Kucukal, Erdem; Gurkan, Umut A; Stavrou, Evi X; Mohseni, Pedram

2016-08-01

This paper describes the design and construct of a fully biocompatible, microfluidic, dielectric sensor targeted at monitoring human whole blood coagulation at the point-of-care (POC). The sensor assembly procedure involves using sputtered electrodes in a microfluidic channel with a physiologically relevant height of 50μm to create a three-dimensional (3D), parallel-plate, capacitive sensing area. The sensor is constructed with biocompatible materials of polymethyl methacrylate (PMMA) for the substrate and titanium nitride (TiN) for the sensing and floating electrodes. The real part of the complex relative dielectric permittivity of human whole blood is measured from 10kHz to 100MHz using an impedance analyzer and under static conditions. The temporal variation in dielectric permittivity at 1MHz for human whole blood undergoing coagulation shows a peak in permittivity at 5 minutes, which closely matches our previously established results. This sensor can pave the way for monitoring blood coagulation under physiologically relevant shear flow rates in the future.

Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease

PubMed Central

Uderhardt, Stefan; Ackermann, Jochen A.; Fillep, Tobias; Hammond, Victoria J.; Willeit, Johann; Stark, Konstantin; Rossaint, Jan; Schubert, Irene; Mielenz, Dirk; Dietel, Barbara; Raaz-Schrauder, Dorette; Ay, Cihan; Thaler, Johannes; Heim, Christian; Collins, Peter W.; Schabbauer, Gernot; Mackman, Nigel; Voehringer, David; Nadler, Jerry L.; Lee, James J.; Massberg, Steffen; Rauh, Manfred; O’Donnell, Valerie B.

2017-01-01

Blood coagulation is essential for physiological hemostasis but simultaneously contributes to thrombotic disease. However, molecular and cellular events controlling initiation and propagation of coagulation are still incompletely understood. In this study, we demonstrate an unexpected role of eosinophils during plasmatic coagulation, hemostasis, and thrombosis. Using a large-scale epidemiological approach, we identified eosinophil cationic protein as an independent and predictive risk factor for thrombotic events in humans. Concurrent experiments showed that eosinophils contributed to intravascular thrombosis by exhibiting a strong endogenous thrombin-generation capacity that relied on the enzymatic generation and active provision of a procoagulant phospholipid surface enriched in 12/15-lipoxygenase–derived hydroxyeicosatetraenoic acid–phosphatidylethanolamines. Our findings reveal a previously unrecognized role of eosinophils and enzymatic lipid oxidation as regulatory elements that facilitate both hemostasis and thrombosis in response to vascular injury, thus identifying promising new targets for the treatment of thrombotic disease. PMID:28566277

Evaluation of Optical Coherence Tomography for the Measurement of the Effects of Activators and Anticoagulants on the Blood Coagulation In Vitro

PubMed Central

Geng, Jinhai; Liu, Gangjun; Chen, Zhongping

2013-01-01

Optical properties of human blood during coagulation were studied using optical coherence tomography (OCT) and the parameter of clotting time derived from the 1/e light penetration depth (d1/e) versus time was developed in our previous work. In this study, in order to know if a new OCT test can characterize the blood-coagulation process under different treatments in vitro, the effects of two different activators (calcium ions and thrombin) and anticoagulants, i.e., acetylsalicylic acid (ASA, a well-known drug aspirin) and melagatran (a direct thrombin inhibitor), at various concentrations are evaluated. A swept-source OCT system with a 1300 nm center wavelength is used for detecting the blood-coagulation process in vitro under a static condition. A dynamic study of d1/e reveals a typical behavior due to coagulation induced by both calcium ions and thrombin, and the clotting time is concentration-dependent. Dose-dependent ASA and melagatran prolong the clotting times. ASA and melagatran have different effects on blood coagulation. As expected, melagatran is much more effective than ASA in anticoagulation by the OCT measurements. The OCT assay appears to be a simple method for the measurement of blood coagulation to assess the effects of activators and anticoagulants, which can be used for activator and anticoagulant screening. PMID:23392340

Evaluation of optical coherence tomography for the measurement of the effects of activators and anticoagulants on the blood coagulation in vitro.

PubMed

Xu, Xiangqun; Geng, Jinhai; Liu, Gangjun; Chen, Zhongping

2013-08-01

Optical properties of human blood during coagulation were studied using optical coherence tomography (OCT) and the parameter of clotting time derived from the 1/e light penetration depth (d(1/e)) versus time was developed in our previous work. In this study, in order to know if a new OCT test can characterize the blood-coagulation process under different treatments in vitro, the effects of two different activators (calcium ions and thrombin) and anticoagulants, i.e., acetylsalicylic acid (ASA, a well-known drug aspirin) and melagatran (a direct thrombin inhibitor), at various concentrations are evaluated. A swept-source OCT system with a 1300 nm center wavelength is used for detecting the blood-coagulation process in vitro under a static condition. A dynamic study of d1/e reveals a typical behavior due to coagulation induced by both calcium ions and thrombin, and the clotting time is concentration-dependent. Dose-dependent ASA and melagatran prolong the clotting times. ASA and melagatran have different effects on blood coagulation. As expected, melagatran is much more effective than ASA in anticoagulation by the OCT measurements. The OCT assay appears to be a simple method for the measurement of blood coagulation to assess the effects of activators and anticoagulants, which can be used for activator and anticoagulant screening.

Evaluation of risk factors in patients with vitamin K-dependent coagulopathy presumed to be caused by exposure to brodifacoum.

PubMed

Lee, Hee-Jeong; You, Mi-Ra; Moon, Woo-Ram; Sul, Hyoung; Chung, Choon-Hae; Park, Chi-Young; Park, Sang-Gon

2014-07-01

Recently, many cases of vitamin K-dependent coagulopathy of unknown origin have been reported. Such patients lack any relevant family history and have no systemic disease, raising suspicion of superwarfarin intoxication. We evaluated individual risk factors causing coagulopathy and hemorrhagic symptoms in patients with suspected superwarfarin intoxication. In addition, we determined how to effectively treat vitamin K-dependent coagulopathy caused by suspected superwarfarin intoxication. Seven patients with suspected superwarfarin intoxication who lacked any definitive history of rodenticide ingestion were included. Thirty-one patients initially diagnosed with rodenticide poisoning were also included. We performed a retrospective chart review of all subjects and examined clinical data including patient demographics and medical histories. Patients initially diagnosed with rodenticide poisoning were divided into two groups, one of which had a laboratory abnormality (prothrombin time [PT] > 13 seconds) and another group with PTs in the normal range. There was no significant difference between the two groups in any of age, gender, the extent of chronic alcohol consumption, the causative rodenticide, psychiatric problems, ingestion of drugs interacting with warfarin, the extent of intoxication, or the type of ingestion attempt. The albumin level of the former group was significantly lower than that of the latter group (p = 0.014). Furthermore, a significant difference between the two groups was evident in terms of simultaneous ingestion of rodenticide and alcohol (p = 0.023). Most patients with superwarfarin poisoning did not exhibit any complication. When such complications were evident, they were associated with serum albumin level and coingestion of rodenticide and alcohol.

Coagulation activation by MC28 fibrosarcoma cells facilitates lung tumor formation.

PubMed

Amirkhosravi, M; Francis, J L

1995-01-01

Tumor cells interact with the hemostatic system in various ways and may thus influence malignant growth and spread. MC28 fibrosarcoma cells possess a potent procoagulant activity (PCA) and form lung tumors following intravenous injection. The aim of this work was to study the relationship between PCA, intravascular coagulation and lung seeding in the MC28 model. MC28 cells were injected into control, warfarinized and heparinized hooded Lister rats. Coagulation changes were monitored by thromboelastography (TEG) and Sonoclot analysis (SA), lung fibrin formation by light and electron microscopy, tumor seeding by macroscopic counting and tumor cell and platelet deposition in the lungs by radiolabelling. PCA was measured by chromogenic assay. MC28 PCA was characterized as a tissue factor-factor VIIa complex that probably arose during cell culture or disaggregation of solid tumors. Injection of tumor cells caused marked coagulopathy and was rapidly (within 30 min) followed by fibrin deposition in the lungs and accumulation of radiolabelled platelets. Heparin and warfarin significantly reduced lung seeding (p < 0.001) and reduced retention of radiolabelled tumor cells in the pulmonary circulation (p < 0.01). Inhibition of cellular PCA by prior treatment with concanavalin A markedly reduced intravascular coagulation and lung seeding. We conclude that MC28 cells cause intravascular coagulation as a direct result of their procoagulant activity. The data suggest that tumor cells form complexes with platelets and fibrin which are retained in the lungs long enough for extravasation and seeding to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Trihalomethanes (THMs) precursor fractions removal by coagulation and adsorption for bio-treated municipal wastewater: Molecular weight, hydrophobicity/hydrophily and fluorescence.

PubMed

Han, Qi; Yan, Han; Zhang, Feng; Xue, Nan; Wang, Yan; Chu, Yongbao; Gao, Baoyu

2015-10-30

Due to concerns over health risk of disinfection byproducts (DBPs), removal of trihalomethanes (THMs) precursor from bio-treated wastewater by coagulation and adsorption was investigated in this study. Ultrafiltration (UF) membranes and nonionic resins were applied to fractionate THMs precursor into various molecular weight (MW) fractions and hydrophobic/hydrophilic fractions. Characteristics of coagulated water and adsorbed water were evaluated by the three-dimensional excitation and emission matrix (3DEEM) fluorescence spectroscopy. Results showed that coagulation and adsorption were suitable for removing different hydrophobic/hydrophilic and fluorescent fractions. Coagulation decreased THMs concentration in hydrophobic acids (HoA) fraction from 59 μg/L to 39 μg/L, while the lowest THMs concentration (9 μg/L) in hydrophilic substances (HiS) fraction was obtained in adsorbed water. However, both coagulation and adsorption were ineffective for removing fractions with MW<5 kDa. Although coagulation and adsorption processes could reduce THMs formation, some specific THMs formation potential (STHMFP) in residual dissolved organic matter (DOM) fractions increased in this study. Hydrophobic acid and hydrophilic fractions increased after coagulation treatment, and low MW and hydrophobic fractions increased after adsorption treatment. In addition, active carbon adsorbed more organic matter than coagulant, but brominated disinfection byproducts (Br-DBPs) in adsorbed water turned to the major THMs species after chlorination. Copyright © 2015 Elsevier B.V. All rights reserved.

Vitamin K

USDA-ARS?s Scientific Manuscript database

Vitamin K was identified in the early 1930’s when it was shown to be essential for normal blood coagulation. Phylloquinone (2-methyl-3-phytyl-1,4-naphthoquinone) found in green plants is the major source of the vitamin. Large amounts of menaquinones with lengthy side chains are also synthesized in...

In situ coagulation versus pre-coagulation for gravity-driven membrane bioreactor during decentralized sewage treatment: Permeability stabilization, fouling layer formation and biological activity.

PubMed

Ding, An; Wang, Jinlong; Lin, Dachao; Tang, Xiaobin; Cheng, Xiaoxiang; Li, Guibai; Ren, Nanqi; Liang, Heng

2017-12-01

Gravity-driven membrane filtration systems are promising for decentralized sewage treatment due to their low energy consumption and low maintenance. However, the low stable permeability/flux is currently limiting their wider application. With the ultimate goal of increasing permeability, the aim of this study was to evaluate the effect of coagulation (in situ coagulation and pre-coagulation) on the performance of a gravity-driven membrane bioreactor (GDMBR) during treatment of synthetic sewage. Results show that in situ coagulation significantly increased permeability (more than two-fold); however, no stabilization of permeability occurred over the whole operation, when non-coagulated and pre-coagulated reactors were compared. The high permeability observed was attributed to the accumulated aluminium floc in the reactor, which prevented formation of fluorescent microbial metabolites (aromatic and tryptophan proteins, as well as fulvic acids), and further avoided membrane pore blocking. In addition, the surface porosity of the fouling layer was improved (from 11.2% to 32.4% for non-coagulated and in situ coagulated reactors). The unstable permeability was possibly associated with lower biological processes within the fouling layer. These might include lower adenosine triphosphate (ATP) content and lower fluorescent metabolites from the extracellular polymeric substances (EPS) caused by the accumulated Al (compared with the control). On the other hand, pre-coagulation improved the level of stable permeability compared with the control (80 versus 40 L/m 2 h bar), mainly because pre-coagulation decreased the EPS content and also maintained high ATP content of the fouling layer. In addition, both coagulation processes reduced the total filtration resistance, mainly the hydraulically reversible resistance and cake layer resistance, which could lower the cleaning frequency. Overall, coagulation could greatly increase the removal efficiency and improve the GDMBR

The fibrinogen/CRP ratio as a new parameter for the diagnosis of disseminated intravascular coagulation in patients with HELLP syndrome and as a predictive factor for neonatal outcome.

PubMed

Windsperger, Karin; Lehner, Rainer

2013-02-01

The aim of this study was to determine if the fibrinogen/C-reactive protein (CRP) ratio could be used in obstetrics as a predictor for a disseminated intravascular coagulation. One hundred eleven patients with hemolysis, elevated liver enzymes, and low platelet count syndrome at the Department of Obstetrics and Fetomaternal Medicine (General Hospital, Vienna, Austria) were selected and divided into 2 groups (overt disseminated intravascular coagulation, no overt disseminated intravascular coagulation). The classical parameters and the fibrinogen/CRP ratio were compared. The analysis was carried out using IBM SPSS statistical package (SPSS, Inc, Cary, NC). The fibrinogen/CRP ratio showed significant differences. The receiver-operating characteristic analysis showed for the ratio (area under the curve, 0.74) significantly better discriminative power than for fibrinogen (area under curve, 0.59). The odds ratio for the fibrinogen/CRP ratio was 7.04. Finally, significant correlations between the ratio and the neonatal outcome were found. We suggest the implementation of the fibrinogen/CRP ratio within patients with hemolysis, elevated liver enzymes, and low platelet count syndrome as a diagnostic and prognostic factor for the occurrence of disseminated intravascular coagulation. Copyright © 2013 Mosby, Inc. All rights reserved.

EXTRINSIC COAGULATION BLOCKADE ATTENUATES LUNG INJURY AND PROINFLAMMATORY CYTOKINE RELEASE AFTER INTRATRACHEAL LIPOPOLYSACCHARIDE

EPA Science Inventory

Initiation of coagulation by tissue factor (TF) is a potentially powerful regulator of local inflammatory responses. We hypothesized that blockade of TF-factor VIIa (FVIIa) complex would decrease lung inflammation and proinflammatory cytokine release after tracheal instillation o...

Sonoclot evaluation of whole blood coagulation in healthy adult dogs.

PubMed

Babski, Danielle M; Brainard, Benjamin M; Krimer, Paula M; Ralph, Alan G; Pittman, Jennifer R; Koenig, Amie

2012-12-01

To establish a standard protocol for analysis of canine whole blood and generate reference intervals for healthy dogs using the Sonoclot analyzer, and to compare Sonoclot values to standard and viscoelastic coagulation tests. Prospective study. Veterinary University research facility and teaching hospital. Twelve healthy random source dogs and 52 healthy dogs from the general veterinary school population. Blood sampling for viscoelastic coagulation testing. Blood was collected from 12 healthy adult dogs by jugular venipuncture. After a rest period at room temperature of 30, 60, or 120 minutes, 340 μL of citrated blood was added to 20 μL of 0.2 M CaCl(2) in 1 of 2 cuvette types warmed to 37° C. Cuvettes contained a magnetic stir-bar with glass beads (gbACT+) or only a magnetic stir-bar (nonACT). Reference interval samples were collected from 52 healthy adult dogs and analyzed in duplicate. The ACT, CR, and PF were not affected by duration of rest period for either cuvette type. ACT variability was decreased when using gbACT+ cuvettes (P < 0.05). In normal dogs reference intervals (mean ± 2 SD) using gbACT+ cuvettes were: ACT 56.0-154.0 seconds, CR 14.85-46.0, and PF 2.1-4.05. ACT correlated to TEG R-time, K-time, and angle, while CR correlated with all TEG parameters. Fibrinogen correlated with ACT, CR, and PF. Sonoclot did not correlate with other common coagulation tests. Sonoclot provides viscoelastic evaluation of canine whole blood coagulation and correlated to several TEG parameters and fibrinogen. A standard protocol and reference intervals were established. © Veterinary Emergency and Critical Care Society 2012.

Associations of coagulation factors IX and XI levels with incident coronary heart disease and ischemic stroke: the REGARDS study.

PubMed

Olson, N C; Cushman, M; Judd, S E; Kissela, B M; Safford, M M; Howard, G; Zakai, N A

2017-06-01

Essentials Coagulation factors (F) IX and XI have been implicated in cardiovascular disease (CVD) risk. We studied associations of FIX and FXI with incident coronary heart disease (CHD) and stroke. Higher FIX antigen was associated with incident CHD risk in blacks but not whites. Higher levels of FIX antigen may be a CHD risk factor among blacks. Background Recent studies have suggested the importance of coagulation factor IX and FXI in cardiovascular disease (CVD) risk. Objectives To determine whether basal levels of FIX or FXI antigen were associated with the risk of incident coronary heart disease (CHD) or ischemic stroke. Patients/Methods The REasons for Geographic And Racial Differences in Stroke (REGARDS) study recruited 30 239 participants across the contiguous USA between 2003 and 2007. In a case-cohort study within REGARDS, FIX and FXI antigen were measured in participants with incident CHD (n = 609), in participants with incident ischemic stroke (n = 538), and in a cohort random sample (n = 1038). Hazard ratios (HRs) for CHD and ischemic stroke risk were estimated with Cox models per standard deviation higher FIX or FXI level, adjusted for CVD risk factors. Results In models adjusting for CHD risk factors, higher FIX levels were associated with incident CHD risk (HR 1.19; 95% confidence interval [CI] 1.01-1.40) and the relationship of higher FXI levels was slightly weaker (HR 1.15; 95% CI 0.97-1.36). When stratified by race, the HR of FIX was higher in blacks (HR 1.39; 95% CI 1.10-1.75) than in whites (HR 1.06; 95% CI 0.86-1.31). After adjustment for stroke risk factors, there was no longer an association of FIX levels with ischemic stroke, whereas the association of FXI levels with ischemic stroke was slightly attenuated. Conclusions Higher FIX antigen levels were associated with incident CHD in blacks but not in whites. FIX levels may increase CHD risk among blacks. © 2017 International Society on Thrombosis and Haemostasis.

PI3K-dependent antagonism in mammalian olfactory receptor neurons

PubMed Central

Ukhanov, Kirill; Brunert, Daniela; Corey, Elizabeth; Ache, Barry W.

2011-01-01

Phosphoinositide (PI) signaling, in particular PI3Kinase (PI3K) signaling, has been implicated in mediating inhibitory odorant input to mammalian olfactory receptor neurons (ORNs). To better understand this phenomenon we investigated PI3K-dependent inhibition between single odorant pairs. The concentration-dependent inhibition of the response of native rat ORNs to octanol by citral is PI3K-dependent; blocking PI3K activity with the β and γ isoform-specific inhibitors AS252424 and TGX221 eliminated or strongly reduced the inhibition. Interestingly, blocking PI3K also changed the apparent agonist strength of the otherwise non-competitive antagonist citral. The excitation evoked by citral after blocking PI3K, could be suppressed by the adenylate cyclase III (ACIII) blockers MDL12330A and SQ22536, indicating that citral could also activate ACIII, presumably through the canonical OR. The G protein Gβγ subunit blockers suramin, gallein and M119 suppressed citral’s inhibition of the response to octanol, indicating that the activation of PI3K by citral was G protein dependent, consistent with the idea that inhibition acts through the canonical OR. Lilial similarly antagonized the response to isoamyl acetate in other ORNs, indicating the effect generalizes to at least one other odorant pair. The ability of methyl-isoeugenol, limonene, α-pinene, isovaleric acid and isosafrole to inhibit the response of other ORNs to IBMX/forskolin in a PI3K-dependent manner argues the effect generalizes to yet other structurally dissimilar odorants. Our findings collectively raise the interesting possibility that the OR serves as a molecular logic gate when mammalian ORNs are activated by natural, complex mixtures containing both excitatory and inhibitory odorants. PMID:21209212

Evaluation of the efficacy and safety of rivaroxaban using a computer model for blood coagulation.

PubMed

Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Kuepfer, Lars; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Lippert, Joerg

2011-04-22

Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery and is in advanced clinical development for the treatment of thromboembolic disorders. Its mechanism of action is antithrombin independent and differs from that of other anticoagulants, such as warfarin (a vitamin K antagonist), enoxaparin (an indirect thrombin/Factor Xa inhibitor) and dabigatran (a direct thrombin inhibitor). A blood coagulation computer model has been developed, based on several published models and preclinical and clinical data. Unlike previous models, the current model takes into account both the intrinsic and extrinsic pathways of the coagulation cascade, and possesses some unique features, including a blood flow component and a portfolio of drug action mechanisms. This study aimed to use the model to compare the mechanism of action of rivaroxaban with that of warfarin, and to evaluate the efficacy and safety of different rivaroxaban doses with other anticoagulants included in the model. Rather than reproducing known standard clinical measurements, such as the prothrombin time and activated partial thromboplastin time clotting tests, the anticoagulant benchmarking was based on a simulation of physiologically plausible clotting scenarios. Compared with warfarin, rivaroxaban showed a favourable sensitivity for tissue factor concentration inducing clotting, and a steep concentration-effect relationship, rapidly flattening towards higher inhibitor concentrations, both suggesting a broad therapeutic window. The predicted dosing window is highly accordant with the final dose recommendation based upon extensive clinical studies.

Evaluation of the Efficacy and Safety of Rivaroxaban Using a Computer Model for Blood Coagulation

PubMed Central

Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Kuepfer, Lars; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Lippert, Joerg

2011-01-01

Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery and is in advanced clinical development for the treatment of thromboembolic disorders. Its mechanism of action is antithrombin independent and differs from that of other anticoagulants, such as warfarin (a vitamin K antagonist), enoxaparin (an indirect thrombin/Factor Xa inhibitor) and dabigatran (a direct thrombin inhibitor). A blood coagulation computer model has been developed, based on several published models and preclinical and clinical data. Unlike previous models, the current model takes into account both the intrinsic and extrinsic pathways of the coagulation cascade, and possesses some unique features, including a blood flow component and a portfolio of drug action mechanisms. This study aimed to use the model to compare the mechanism of action of rivaroxaban with that of warfarin, and to evaluate the efficacy and safety of different rivaroxaban doses with other anticoagulants included in the model. Rather than reproducing known standard clinical measurements, such as the prothrombin time and activated partial thromboplastin time clotting tests, the anticoagulant benchmarking was based on a simulation of physiologically plausible clotting scenarios. Compared with warfarin, rivaroxaban showed a favourable sensitivity for tissue factor concentration inducing clotting, and a steep concentration–effect relationship, rapidly flattening towards higher inhibitor concentrations, both suggesting a broad therapeutic window. The predicted dosing window is highly accordant with the final dose recommendation based upon extensive clinical studies. PMID:21526168

PI3K/Akt-dependent functions of TFII-I transcription factors in mouse embryonic stem cells.

PubMed

Chimge, Nyam-Osor; Makeyev, Aleksandr V; Waigel, Sabine J; Enkhmandakh, Badam; Bayarsaihan, Dashzeveg

2012-04-01

Activation of PI3K/Akt signaling is sufficient to maintain the pluripotency of mouse embryonic stem cells (mESC) and results in down-regulation of Gtf2i and Gtf2ird1 encoding TFII-I family transcription factors. To investigate how these genes might be involved in the process of embryonic stem cell differentiation, we performed expression microarray profiling of mESC upon inhibition of PI3K by LY294002. This analysis revealed significant alterations in expression of genes for specific subsets of chromatin-modifying enzymes. Surprisingly, genome-wide promoter ChIP-chip mapping indicated that the majority of differently expressed genes could be direct targets of TFII-I regulation. The data support the hypothesis that upregulation of TFII-I factors leads to activation of a specific group of developmental genes during mESC differentiation. © 2011 Wiley Periodicals, Inc.

Moderate-intensity exercise improves the thromboelastography coagulation index in children with severe hemophilia A.

PubMed

Li, Kui-Xing; Xiao, Juan; Zhao, Yong-Qiang; Shou, Wei-Ling; Chen, Meng; Li, Zhuo; Poon, Man-Chiu; Han, Hui-Jun

2016-10-01

This pilot study explored the effect of moderate-intensity exercise on factor VIII (FVIII) activity and global hemostatic status of the children with severe hemophilia A. Eleven children aged 6 to 15 years with severe hemophilia A participated in a moderate-intensity exercise test by using Recumbent Cross Trainer (NuStep, T5XR) for at least 10 min after reaching the target heart rate or until volitional exhaustion within a safety framework. Blood samples were collected pre and postexercise for plasma FVIII: C and thromboelastography (TEG) parameters and coagulation index. The average duration of exercise was 11.8 min (10-13 min). There was no report on bleeding events or adverse symptoms requiring termination of the exercise test. The average FVIII activity of the 11 children was 0.66 (0.5-0.8) IU/dl before and 0.93 (0.5-2.3) IU/dl after exercise. The increase of FVIII in the 11 children as a group was not statistically significant (P = 0.052). There were significant changes of TEG measurements, with shortening of R (P < 0.05), and increase in K decrease (P < 0.05), alpha angle (P < 0.05), maximum amplitude (P < 0.05), and coagulation index (P < 0.01). Among the 11 children, the relative coagulation index increase after exercise was greater than 50% in seven (63.6%), less than 20% in three (27.3%), and less than 10% in one (9.1%). TEG analysis showed that the global hemostatic function for the children with severe hemophilia A can be enhanced after moderate-intensity exercise.

Aqueous extract from Brownea grandiceps flowers with effect on coagulation and fibrinolytic system.

PubMed

Pereira, Betzabeth; Brazón, Josmary

2015-02-03

concentrations and was due to FXa inhibitor found in BGE and this effect could be strengthened by degradation of fibrinogen and fibronectin, which were also produced by BGE. Moreover, BGE did not clot fibrinogen or human plasma, and neither did it cleave the chromogenic substrates specific to FXa nor thrombin. These results suggest the pro-coagulant components could be acting on some factor of the extrinsic pathway, since only PT was shortened. Furthermore, BGE did not hydrolyze the chromogenic substrate specific to plasmin, t-PA and u-PA nor did it produce fibrin degradation. However, all BGE concentrations tested inhibited the plasmin activity in a dose-dependent manner. The outcomes of this study reveal the presence of fibrinogenolytic, fibronectinase and anti-FXa components in BGE, plus anti-plasmin compounds that could be acting as antifibrinolytic, thus delaying the fibrin degradation in pathophysiological processes, as it has been observed in women presenting with menorrhagia due to a high plasmin concentration. Where this anti-plasmin compound, along with pro-coagulant components also present in BGE, could be made responsible for reducing heavy menstrual bleeding in women, since a deficiency in one or more blood coagulation factors such as factor VII, V or X, is a potential cause of menorrhagia. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

[Significance of vitamin K (VK) administration in patients under chemotherapy during postoperative fasting period].

PubMed

Ojiro, M; Takenoshita, M; Toshinaga, T; Shimazu, H

1992-01-01

Recently coagulopathy caused by vitamin K (VK) deficiency following antibiotic therapy in malnourished patients has been reported. We studied on the same problem particularly in patients under chemotherapy during postoperative fasting period. For this purpose, prothrombin time (PT), vitamin K-dependent coagulation factors (Factor II (F-II), VII (F-VII) and protein C), PIVKA-II (PK-II) and plasma level of VK in two groups of patients with or without VK administration were measured in esophageal cancer patients. In the group with VK, VK2 were given intravenously everyday. In the group without VK, PT prolonged and F-II decreased from the seventh postoperative day, especially on the 14th day significantly. Although F-VII and protein C decreased on the first day and returned subsequently on the seventh day, no significance was observed between two groups. PK-II increased clearly in the group without VK from the seventh day, whereas no significant changes were observed in the group with VK. The plasma level of VK1 decreased in both groups, but VK2, especially MK-4, was high in the group with VK.

Multiple response optimization of the coagulation process for upgrading the quality of effluent from municipal wastewater treatment plant

NASA Astrophysics Data System (ADS)

Li, Na; Hu, Yi; Lu, Yong-Ze; Zeng, Raymond J.; Sheng, Guo-Ping

2016-05-01

To meet the high quality standard of receiving water, the coagulation process using polyferric chloride (PFC) was used to further improve the water quality of effluent from wastewater treatment plants. Uniform design (UD) coupled with response surface methodology (RSM) was adopted to assess the effects of the main influence factors: coagulant dosage, pH and basicity, on the removal of total organic carbon (TOC), NH4+-N and PO43--P. A desirability function approach was used to effectively optimize the coagulation process for the comprehensive removal of TOC, NH4+-N and PO43--P to upgrade the effluent quality in practical application. The optimized operating conditions were: dosage 28 mg/L, pH 8.5 and basicity 0.001. The corresponding removal efficiencies for TOC, NH4+-N and PO43--P were 77.2%, 94.6% and 20.8%, respectively. More importantly, the effluent quality could upgrade to surface water Class V of China through coagulation under optimal region. In addition, grey relational analysis (GRA) prioritized these three factors as: pH > basicity > dosage (for TOC), basicity > dosage > pH (for NH4+-N), pH > dosage > basicity (for PO43--P), which would help identify the most important factor to control the treatment efficiency of various effluent quality indexes by PFC coagulation.

Virus elimination during the recycling of chromatographic columns used during the manufacture of coagulation factors.

PubMed

Roberts, Peter L

2014-07-01

Various chromatographic procedures are used during the purification and manufacture of plasma products such as coagulation factors. These steps contribute to the overall safety of such products by removing potential virus contamination. Virus removal by two affinity chromatography procedures, i.e. monoclonal antibody chromatography and metal chelate chromatography (immobilised metal ion affinity chromatography), used during the manufacture of the high purity factor VIII (Replenate®) and factor IX (Replenine®-VF), respectively, has been investigated. In addition, as these columns are recycled after use, the effectiveness of the sanitisation procedures for preventing possible cross-contamination, has also been investigated. Both chromatographic steps proved effective for eliminating a range of model enveloped and non-enveloped viruses by 4 to >6 and 5 to >8 log for the monoclonal and metal chelate columns, respectively. The effectiveness of the relatively mild column sanitisation conditions used, i.e. ethanol for factor IX and acetic acid for factor VIII, was confirmed using non-spiked column runs. The chemicals used contributed to virus elimination by inactivation and/or by physical removal of the virus. In summary, these studies demonstrate that potential virus contamination between chromatographic runs can be prevented when an effective column recycling and sanitisation procedure is included. Copyright © 2014 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Blood coagulation status of small-for-dates and postmature infants.

PubMed Central

Perlman, M; Dvilansky, A

1975-01-01

In a prospective study of blood coagulation status in small-for-dates and postmature infants there was often evidence of intravascular coagulation. Abnormal coagulation findings correlated with the degree of growth retardation and with the degree of postmaturity. Macroscopical placental infarction and neonatal polycythaemia were associated with coagulation abnormalities; asphyxia, however, was not. Intravascular coagulation may be an additional hazard to small-for-dates and postmature infants. PMID:1170815

Groundwater arsenic removal by coagulation using ferric(III) sulfate and polyferric sulfate: A comparative and mechanistic study.

PubMed

Cui, Jinli; Jing, Chuanyong; Che, Dongsheng; Zhang, Jianfeng; Duan, Shuxuan

2015-06-01

Elevated arsenic (As) in groundwater poses a great threat to human health. Coagulation using mono- and poly-Fe salts is becoming one of the most cost-effective processes for groundwater As removal. However, a limitation comes from insufficient understanding of the As removal mechanism from groundwater matrices in the coagulation process, which is critical for groundwater treatment and residual solid disposal. Here, we overcame this hurdle by utilizing microscopic techniques to explore molecular As surface complexes on the freshly formed Fe flocs and compared ferric(III) sulfate (FS) and polyferric sulfate (PFS) performance, and finally provided a practical solution in As-geogenic areas. FS and PFS exhibited a similar As removal efficiency in coagulation and coagulation/filtration in a two-bucket system using 5mg/L Ca(ClO)2. By using the two-bucket system combining coagulation and sand filtration, 500 L of As-safe water (<10 μg/L) was achieved during five treatment cycles by washing the sand layer after each cycle. Fe k-edge X-ray absorption near-edge structure (XANES) and As k-edge extended X-ray absorption fine structure (EXAFS) analysis of the solid residue indicated that As formed a bidentate binuclear complex on ferrihydrite, with no observation of scorodite or poorly-crystalline ferric arsenate. Such a stable surface complex is beneficial for As immobilization in the solid residue, as confirmed by the achievement of much lower leachate As (0.9 μg/L-0.487 mg/L) than the US EPA regulatory limit (5 mg/L). Finally, PFS is superior to FS because of its lower dose, much lower solid residue, and lower cost for As-safe drinking water. Copyright © 2015. Published by Elsevier B.V.

Comparison of Moringa stenopetala seed extract as a clean coagulant with Alum and Moringa stenopetala-Alum hybrid coagulant to remove direct dye from Textile Wastewater.

PubMed

Dalvand, Arash; Gholibegloo, Elham; Ganjali, Mohammad Reza; Golchinpoor, Najmeh; Khazaei, Mohammad; Kamani, Hossein; Hosseini, Sara Sadat; Mahvi, Amir Hossein

2016-08-01

In this study, the efficiency of Moringa stenopetala seed extract was compared with alum and M. stenopetala-alum hybrid coagulant to remove Direct Red 23 azo dye from textile wastewater. The effects of parameters such as pH, coagulant dose, type of salt used for the extraction of coagulant and initial dye concentration on dye removal efficiency were investigated. Moreover, the existing functional groups on the structure of M. stenopetala coagulant (MSC) were determined by Fourier transform infrared spectroscopy, and the morphology of sludge produced by MSC, alum, and hybrid coagulant was characterized by scanning electron microscopy. Ninhydrin test was also used to determine the quantity of primary amines in the MSC and Moringa oleifera coagulant (MOC). According to the results, with increasing the coagulant dose and decreasing the initial dye concentration, dye removal efficiency has increased. The maximum dye removal of 98.5, 98.2, and 98.3 % were obtained by using 240, 120, and 80 mg/L MSC, alum and hybrid coagulant at pH 7, respectively. The results also showed MSC was much more effective than MOC for dye removal. The volume of sludge produced by MSC was one fourth and half of those produced by alum and hybrid coagulant, respectively. Based on the results, hybrid coagulant was the most efficient coagulant for direct dye removal from colored wastewater.

Milk yield, quality, and coagulation properties of 6 breeds of goats: Environmental and individual variability.

PubMed

Vacca, Giuseppe M; Stocco, Giorgia; Dettori, Maria L; Pira, Emanuela; Bittante, Giovanni; Pazzola, Michele

2018-05-09

Goat milk and cheese production is continuously increasing and milk composition and coagulation properties (MCP) are useful tools to predict cheesemaking aptitude. The present study was planned to investigate the extension of lactodynamographic analysis up to 60 min in goat milk, to measure the farm and individual factors, and to investigate differences among 6 goat breeds. Daily milk yield (dMY) was recorded and milk samples collected from 1,272 goats reared in 35 farms. Goats were of 6 different breeds: Saanen and Camosciata delle Alpi for the Alpine type, and Murciano-Granadina, Maltese, Sarda, and Sarda Primitiva for the Mediterranean type. Milk composition (fat, protein, lactose, pH; somatic cell score; logarithmic bacterial count) and MCP [rennet coagulation time (RCT, min), curd-firming time (k 20 , min), curd firmness at 30, 45, and 60 min after rennet addition (a 30 , a 45 , and a 60 , mm)] were recorded, and daily fat and protein yield (dFPY g/d) was calculated as the sum of fat and protein concentration multiplied by the dMY. Data were analyzed using different statistical models to measure the effects of farm, parity, stage of lactation and breed; lastly, the direct and the indirect effect of breed were quantified by comparing the variance of breed from models with or without the inclusion of linear regression of fat, protein, lactose, pH, bacterial, somatic cell counts, and dMY. Orthogonal contrasts were performed to compare least squares means. Almost all traits exhibited high variability, with coefficients of variation between 32 (for RCT) and 63% (for a 30 ). The proportion of variance regarding dMY, dFPY, and milk composition due to the farm was moderate, whereas for MCP it was low, except for a 60 , at 69%. Parity affected both yield and quality traits of milk, with least squares means of dMY and dFPY showing an increase and RCT and curd firmness traits a decrease from the first to the last parity class. All milk quality traits, excluding fat, were

In silico designing of hyper-glycosylated analogs for the human coagulation factor IX.

PubMed

Ghasemi, Fahimeh; Zomorodipour, Alireza; Karkhane, Ali Asghar; Khorramizadeh, M Reza

2016-07-01

N-glycosylation is a process during which a glycan moiety attaches to the asparagine residue in the N-glycosylation consensus sequence (Asn-Xxx-Ser/Thr), where Xxx can be any amino acid except proline. Introduction of a new N-glycosylation site into a protein backbone leads to its hyper-glycosylation, and may improve the protein properties such as solubility, folding, stability, and secretion. Glyco-engineering is an approach to facilitate the hyper-glycosylation of recombinant proteins by application of the site-directed mutagenesis methods. In this regard, selection of a suitable location on the surface of a protein for introduction of a new N-glycosylation site is a main concern. In this work, a computational approach was conducted to select suitable location(s) for introducing new N-glycosylation sites into the human coagulation factor IX (hFIX). With this aim, the first 45 residues of mature hFIX were explored to find out suitable positions for introducing either Asn or Ser/Thr residues, to create new N-glycosylation site(s). Our exploration lead to detection of five potential positions, for hyper-glycosylation. For each suggested position, an analog was defined and subjected for N-glycosylation efficiency prediction. After generation of three-dimensional structures, by homology-based modeling, the five designed analogs were examined by molecular dynamic (MD) simulations, to predict their stability levels and probable structural distortions caused by amino acid substitutions, relative to the native counterpart. Three out of five suggested analogs, namely; E15T, K22N, and R37N, reached equilibration state with relatively constant Root Mean Square Deviation values. Additional analysis on the data obtained during MD simulations, lead us to conclude that, R37N is the only qualified analog with the most similar structure and dynamic behavior to that of the native counterpart, to be considered for further experimental investigations. Copyright © 2016 Elsevier Inc

Human extrahepatic portal vein obstruction correlates with decreased factor VII and protein C transcription but increased hepatocyte proliferation.

PubMed

Chiu, Bill; Melin-Aldana, Hector; Superina, Riccardo A

2007-10-01

A 3-year-old girl developed extrahepatic portal vein obstruction (EHPVO) after a liver transplant. She had sequelae of portal hypertension that required another transplantation. The circumstances allowed for comparison of liver-dependent coagulation factor production between the second donor liver and the explanted liver with EHPVO. Liver samples from the explanted first graft and the second transplant were obtained. Fresh tissue was used to perform reverse transcription-polymerase chain reaction with primers against factors V, VII, as well as VIII, protein C, and paraffin-embedded sections for hepatocyte proliferation using Ki-67 antibody as well as for apoptosis using TUNEL assay. The transcription of factor VII and that of protein C were decreased in the explant as compared with the newly transplanted liver (factor VII, 77% of the donor; protein C, 88% of the donor). The transcription of factor V and that of factor VIII were unchanged. The explant had a greater percentage of proliferating hepatocytes than the new organ (0.85% +/- 0.75% vs 0.11% +/- 0.21%). The percentage of apoptotic cells was similar between the 2 livers (0.09% +/- 0.13% vs 0.09% +/- 0.13%). Idiopathic EHPVO is associated with a reduction in liver-dependent coagulation factor transcription and an increase in hepatocyte proliferation. Portal blood flow deprivation alters hepatic homeostasis and initiates mechanisms that attempt to restore liver-dependent coagulation factors.

Differences in coagulation among Asians and Caucasians and the implication for reconstructive microsurgery.

PubMed

Singhal, Dhruv; Smorodinsky, Emmanuil; Guo, Lifei

2011-01-01

Microvascular reconstructive surgery has seen a revival with the introduction of muscle-sparing perforator flaps. Recognition of potential ethnic differences in coagulation profiles would be important to a microvascular surgeon. Based on clinical observations, we hypothesize that Asian patients have a less thrombogenic coagulation profile than Caucasians. An extensive retrospective review was performed. The annual incidence of venous thromboembolism in the United States is generally accepted to range from 70 to 120 events per 100,000 people versus 16 to 17 events per 100,000 persons in Asia. Autopsy analysis of pulmonary embolism incidence was noted to be 15% in North Americans and less than 1% in Asian populations. Thromboelastography analysis of Asian and Caucasian patients undergoing cholecystectomy revealed different hemostatic mechanisms. Comparison of Asians and Caucasians undergoing the Fontan procedure revealed significantly lower postoperative factor levels in Asians than Caucasians. Baseline comparison of factor and serum levels revealed Asians with the least thrombogenic profiles compared with other ethnic groups. Asians and Caucasians demonstrate different baseline rates of deep vein thrombosis and pulmonary embolism, different hemostatic responses to surgery, and different baseline levels of clotting factors. Further study may lead to better pre-, intra-, and postoperative care of the free flap patient based on their ethnic coagulation profile. © Thieme Medical Publishers.

Inhibition of Protease-Activated Receptor (PAR1) Reduces Activation of the Endothelium, Coagulation, Fibrinolysis and Inflammation during Human Endotoxemia.

PubMed

Schoergenhofer, Christian; Schwameis, Michael; Gelbenegger, Georg; Buchtele, Nina; Thaler, Barbara; Mussbacher, Marion; Schabbauer, Gernot; Wojta, Johann; Jilma-Stohlawetz, Petra; Jilma, Bernd

2018-06-04

The protease-activated receptor-1 (PAR-1) is critically involved in the co-activation of coagulation and inflammatory responses. Vorapaxar is a reversible, orally active, low molecular weight, competitive antagonist of PAR-1.We investigated the effects of PAR-1 inhibition by vorapaxar on the inflammatory response, the activation of coagulation, fibrinolysis and endothelium during experimental endotoxemia. In this randomized, double blind, crossover trial, 16 healthy volunteers received a bolus infusion of 2 ng/kg lipopolysaccharide (LPS) ± placebo/vorapaxar with a washout period of 8 weeks. Vorapaxar dosing was guided by thrombin receptor-activating peptide-6-induced whole blood aggregometry. Participants received 10 mg vorapaxar or placebo as an initial dose and, depending on the aggregometry, potentially an additional 10 mg. Goal was > 80% inhibition of aggregation compared with baseline. Vorapaxar significantly reduced the LPS-induced increase in pro-thrombin fragments F1 + 2 by a median of 27% (quartiles: 11-49%), thrombin-anti-thrombin concentrations by 22% (-3 to 46%) and plasmin-anti-plasmin levels by 38% (23-53%). PAR-1 inhibition dampened peak concentrations of tumour necrosis factor -α, interleukin-6 and consequently C-reactive protein by 66% (-11-71%), 50% (15-79%) and 23% (16-38%), respectively. Vorapaxar decreased maximum von Willebrand factor levels by 29% (26-51%) and soluble E-selectin concentrations by 30% (25-38%) after LPS infusion. PAR-1 inhibition did not affect thrombomodulin, soluble P-selectin and platelet factor-4 concentrations.PAR-1 inhibition significantly reduced the activation of coagulation, fibrinolysis, the inflammatory response and endothelial activation during experimental human endotoxemia. Schattauer GmbH Stuttgart.

Vitamin K deficiency: a case report and review of current guidelines.

PubMed

Marchili, Maria Rosaria; Santoro, Elisa; Marchesi, Alessandra; Bianchi, Simona; Rotondi Aufiero, Lelia; Villani, Alberto

2018-03-14

Vitamin K, a fat soluble vitamin, is a necessary cofactor for the activation of coagulation factors II, VII, IX, X, and protein C and S. In neonatal period, vitamin K deficiency may lead to Vitamin K Deficiency Bleeding (VKDB). We present the case of a 2 months and 20 days Caucasian male, presented for bleeding from the injections sites of vaccines. At birth oral vitamin K prophylaxis was administered. Neonatal period was normal. He was exclusively breastfed and received a daily oral supplementation with 25 μg of vitamin K. A late onset vitamin K deficiency bleeding was suspected. Intravenous Vitamin K was administered with complete recovery. Nevertheless the oral prophylaxis, our case developed a VKDB: it is necessary to revise the current guidelines in order to standardize timing and dosage in different clinical conditions.

Polyferric sulphate: preparation, characterisation and application in coagulation experiments.

PubMed

Zouboulis, A I; Moussas, P A; Vasilakou, F

2008-07-15

The process of coagulation is a core environmental protection technology, which is mainly used in the water or wastewater treatment facilities. Research is now focused on the development of inorganic pre-polymerised coagulants. A characteristic example is PFS (polyferric sulphate), a relatively new pre-polymerised inorganic coagulant with high cationic charge. In this paper, the role of major parameters, including temperature, types of chemical reagents, ratio r=[OH]/[Fe], rate of base addition in the preparation stages of PFS were investigated. Furthermore, the prepared PFS was characterised based on typical properties, such as the percentage of the polymerised iron present in the compound, z-potential, pH, etc. Moreover, dynamics of coagulation process were examined by means of the Photometric Dispersion Analyzer (PDA). Finally, the coagulation efficiency of PFS in treating kaolin suspension and biologically pre-treated wastewater was evaluated in comparison with the respective conventional coagulant agent. The results indicate that certain parameters, such as the r value, the rate of base addition and the duration and temperature of the polymerisation stage, significantly affected the properties of the PFS. Additionally, the prepared PFS polymerised coagulants exhibit a significantly better coagulation performance than the respective non-polymerised one, i.e. ferric sulphate.

Chemical coagulation-based processes for trace organic contaminant removal: current state and future potential.

PubMed

Alexander, Jonathan T; Hai, Faisal I; Al-Aboud, Turki M

2012-11-30

Trace organic contaminants have become an increasing cause of concern for governments and water authorities as they attempt to respond to the potential challenges posed by climate change by implementing sustainable water cycle management practices. The augmentation of potable water supplies through indirect potable water reuse is one such method currently being employed. Given the uncertainty surrounding the potential human health impacts of prolonged ingestion of trace organic contaminants, it is vital that effective and sustainable treatment methods are utilized. The purpose of this article is to provide a comprehensive literature review of the performance of the chemical coagulation process in removing trace organic contaminants from water. This study evaluated the removal data collated from recent research relating to various trace organic contaminants during the coagulation process. It was observed that there is limited research data relating to the removal of trace organic contaminants using coagulation. The findings of this study suggest that there is a gap in the current research investigating the potential of new types of coagulants and exploring coagulation-based hybrid processes to remove trace organic contaminants from water. The data analysed in this study regarding removal efficiency suggests that, even for the significantly hydrophobic compounds, hydrophobicity is not the sole factor governing removal of trace organic contaminants by coagulation. This has important implications in that the usual practice of screening coagulants based on turbidity (suspended solid) removal proves inadequate in the case of trace organic contaminant removal. Copyright © 2012 Elsevier Ltd. All rights reserved.

Coagulation behavior and floc characteristics of a novel composite poly-ferric aluminum chloride-polydimethyl diallylammonium chloride coagulant with different OH/(Fe3+ + Al3+) molar ratios.

PubMed

Sun, Cuizhen; Qiu, Jinwei; Zhang, Zhibin; Marhaba, Taha F; Zhang, Yanhao

2016-10-01

In this paper, flocculating performance and mechanisms of a new composite coagulant, poly-ferric aluminum chloride-polydimethyl diallylammonium chloride (PFAC-PD) with different OH - /(Fe 3+ + Al 3+ ) molar ratios, were investigated for humic acid (HA)-kaolin synthetic wastewater treatment. The impact of OH - /(Fe 3+ + Al 3+ ) molar ratios on the removal efficiencies of turbidity and dissolved organic carbon, specific UV absorbance, coagulation mechanisms and dynamics was explored during the coagulation process using composite coagulants. The coagulation experimental results revealed that the composite coagulants with lower OH - /(Fe 3+ + Al 3+ ) molar ratio exhibited better coagulation efficiency. When OH - /(Fe 3+ + Al 3+ ) molar ratio of the composite coagulant was 1.5, adsorption-bridging played a dominant role in coagulating HA-kaolin synthetic wastewater. The floc growth rate and floc size, increased with increasing OH - /(Fe 3+ + Al 3+ ) molar ratio and the highest peak height of the size distribution was obtained by PFAC-PD with OH - /(Fe 3+ + Al 3+ ) = 1.5. Also, the composite coagulants with higher OH - /(Fe 3+ + Al 3+ ) molar ratio formed more compact flocs, as reflected by the higher fractal dimension value. The flocs coagulated by PFAC-PD with basicity value of 1.0 gave strong strength and good recoverability.

The role of coagulation/fibrinolysis during Streptococcus pyogenes infection.

PubMed

Loof, Torsten G; Deicke, Christin; Medina, Eva

2014-01-01

The hemostatic system comprises platelet aggregation, coagulation and fibrinolysis and is a host defense mechanism that protects the integrity of the vascular system after tissue injury. During bacterial infections, the coagulation system cooperates with the inflammatory system to eliminate the invading pathogens. However, pathogenic bacteria have frequently evolved mechanisms to exploit the hemostatic system components for their own benefit. Streptococcus pyogenes, also known as Group A Streptococcus, provides a remarkable example of the extraordinary capacity of pathogens to exploit the host hemostatic system to support microbial survival and dissemination. The coagulation cascade comprises the contact system (also known as the intrinsic pathway) and the tissue factor pathway (also known as the extrinsic pathway), both leading to fibrin formation. During the early phase of S. pyogenes infection, the activation of the contact system eventually leads to bacterial entrapment within a fibrin clot, where S. pyogenes is immobilized and killed. However, entrapped S. pyogenes can circumvent the antimicrobial effect of the clot by sequestering host plasminogen on the bacterial cell surface that, after conversion into its active proteolytic form, plasmin, degrades the fibrin network and facilitates the liberation of S. pyogenes from the clot. Furthermore, the surface-localized fibrinolytic activity also cleaves a variety of extracellular matrix proteins, thereby enabling S. pyogenes to migrate across barriers and disseminate within the host. This review summarizes the knowledge gained during the last two decades on the role of coagulation/fibrinolysis in host defense against S. pyogenes as well as the strategies developed by this pathogen to evade and exploit these host mechanisms for its own benefit.

Mature landfill leachate treatment by coagulation/flocculation combined with Fenton and solar photo-Fenton processes.

PubMed

Amor, Carlos; De Torres-Socías, Estefanía; Peres, José A; Maldonado, Manuel I; Oller, Isabel; Malato, Sixto; Lucas, Marco S

2015-04-09

This work reports the treatment of a mature landfill leachate through the application of chemical-based treatment processes in order to achieve the discharge legal limits into natural water courses. Firstly, the effect of coagulation/flocculation with different chemicals was studied, evaluating the role of different initial pH and chemicals concentration. Afterwards, the efficiency of two different advanced oxidation processes for leachate remediation was assessed. Fenton and solar photo-Fenton processes were applied alone and in combination with a coagulation/flocculation pre-treatment. This physicochemical conditioning step, with 2 g L(-1) of FeCl3 · 6H2O at pH 5, allowed removing 63% of COD, 80% of turbidity and 74% of total polyphenols. Combining the coagulation/flocculation pre-treatment with Fenton reagent, it was possible to reach 89% of COD removal in 96 h. Moreover, coagulation/flocculation combined with solar photo-Fenton revealed higher DOC (75%) reductions than single solar photo-Fenton (54%). In the combined treatment (coagulation/flocculation and solar photo-Fenton), it was reached a DOC reduction of 50% after the chemical oxidation, with 110 kJ L(-1) of accumulated UV energy and a H2O2 consumption of 116 mM. Toxicity and biodegradability assays were performed to evaluate possible variations along the oxidation processes. After the combined treatment, the leachate under study presented non-toxicity but biodegradability increased. Copyright © 2014 Elsevier B.V. All rights reserved.

Amino acid-dependent signaling via S6K1 and MYC is essential for regulation of rDNA transcription

PubMed Central

Kang, Jian; Kusnadi, Eric P.; Ogden, Allison J.; Hicks, Rodney J.; Bammert, Lukas; Kutay, Ulrike; Hung, Sandy; Sanij, Elaine; Hannan, Ross D.; Hannan, Katherine M.; Pearson, Richard B.

2016-01-01

Dysregulation of RNA polymerase I (Pol I)-dependent ribosomal DNA (rDNA) transcription is a consistent feature of malignant transformation that can be targeted to treat cancer. Understanding how rDNA transcription is coupled to the availability of growth factors and nutrients will provide insight into how ribosome biogenesis is maintained in a tumour environment characterised by limiting nutrients. We demonstrate that modulation of rDNA transcription initiation, elongation and rRNA processing is an immediate, co-regulated response to altered amino acid abundance, dependent on both mTORC1 activation of S6K1 and MYC activity. Growth factors regulate rDNA transcription initiation while amino acids modulate growth factor-dependent rDNA transcription by primarily regulating S6K1-dependent rDNA transcription elongation and processing. Thus, we show for the first time amino acids regulate rRNA synthesis by a distinct, post-initiation mechanism, providing a novel model for integrated control of ribosome biogenesis that has implications for understanding how this process is dysregulated in cancer. PMID:27385002

Anticoagulation by factor Xa inhibitors.

PubMed

Orfeo, T; Butenas, S; Brummel-Ziedins, K E; Gissel, M; Mann, K G

2010-08-01

Therapeutic agents that regulate blood coagulation are critical to the management of thrombotic disorders, with the selective targeting of factor (F) Xa emerging as a promising approach. To assess anticoagulant strategies targeting FXa. A deterministic computational model of tissue factor (Tf)-initiated thrombin generation and two empirical experimental systems (a synthetic coagulation proteome reconstruction using purified proteins and a whole blood model) were used to evaluate clinically relevant examples of the two available types of FXa-directed anticoagulants [an antithrombin (AT)-dependent agent, fondaparinux, and an AT-independent inhibitor, Rivaroxaban] in experimental regimens relevant to long-term (suppression of new Tf-initiated events) and acute (suppression of ongoing coagulation processes) clinical applications. Computational representations of each anticoagulant's efficacy in suppressing thrombin generation over a range of anticoagulant concentrations in both anticoagulation regimens were validated by results from corresponding empirical reconstructions and were consistent with those recommended for long-term and acute clinical applications, respectively. All three model systems suggested that Rivaroxaban would prove more effective in the suppression of an ongoing coagulation process than fondaparinux, reflecting its much higher reactivity toward the prothrombinase complex. The success of fondaparinux in acute settings in vivo is not explained solely by its properties as an FXa inhibitor. We have reported that FIXa contributes to the long-term capacity of clot-associated catalysts to restart a coagulation process, suggesting that the enhanced anti-FIXa activity of fondaparinux-AT may be critical to its success in acute settings in vivo. © 2010 International Society on Thrombosis and Haemostasis.

[Pilot study on pentavalent arsenic removal by coagulation and the strengthening effect of flocs recycling].

PubMed

Yao, Juan-Juan; Gao, Nai-Yun; Xia, Sheng-Ji; Chen, Bei-Bei

2009-06-15

The pilot and bench scale studies on pentavalent arsenic removal by coagulation and the strengthening effect of flocs recycling were performed. The results show that above 95% As (V) in the raw water exists in the form of dissolved As (V). Furthermore, the removal efficiencies of dissolved arsenic and total arsenic by mixing, first flocculation, second flocculation, sedimentation, filtration units were 87.92%, 6.18%, 2.38%, 1.55%, 1.23% and 1.10%, 1.83%, 2.20%, 86.42%, 7.38% respectively. Therefore, conversion rate of dissolved As(V) into particulate As(V) and the settlement performance of flocs were strongly dependent on the coagulation effect, which determined the As(V) removal efficiency in the whole system. Flocs have a strong adsorption capacity for As(V) and the adsorption obeys a second order reaction kinetics and well fits the modified Freundlich model. Flocs recycling can obviously promoted the As(V) removal by enhanced coagulation and reduce the dosage of coagulant with recycling point set at rapid mixed site and recycling ratio at 50%.

Application of low-mixing energy input for the coagulation process.

PubMed

Vadasarukkai, Yamuna S; Gagnon, Graham A

2015-11-01

Rapid-mixing tanks with mechanical mixers are a common design used in treatment plants. Yet, the role of such rapid-mixing systems on the effectiveness of the coagulation performance is unclear. This study looked at optimizing the direct energy used in the coagulation process for removal of natural dissolved organic matter (DOM). The role of coagulation mixing intensity (G-value) on total organic carbon (TOC) and turbidity removal was examined for the water types with high organic content, with a specific ultraviolet absorbance (SUVA) of at least 2-2.5 units of m(-1) of absorbance per mg/L. A standard jar test using ferric sulfate coagulant was performed to optimize the chemical condition in coagulation for removal of dissolved organics as well as particles. The jar test analysis at an acidic pH (4.5 ± 0.3) required an iron dose <0.3 mM to arrive at an optimal coagulant concentration and resulted in above 75% of TOC removal. The influence of coagulation mixing on TOC and turbidity removal was evaluated at G varying from 0 to 1500 s(-1) at the optimized coagulant dose and pH conditions for enhanced coagulation. In this study, a combined effective removal of TOC and turbidity was achieved at a low-mixing intensity range of 110 s(-1) < G < 450 s(-1). Coagulation operated at G greater than 450 s(-1) showed negligible improvement in TOC removal. Minimizing energy consumption in enhanced coagulation is feasible at the proposed mixing intensity range (i.e., 110 s(-1) < G < 450 s(-1)), without sacrificing the effectiveness of DOM removal by coagulation. These findings represent an opportunity for energy savings for the water industry without sacrificing quality. Copyright © 2015 Elsevier Ltd. All rights reserved.

Interaction Between Dietary Vitamin K Intake and Anticoagulation by Vitamin K Antagonists: Is It Really True?: A Systematic Review.

PubMed

Violi, Francesco; Lip, Gregory Yh; Pignatelli, Pasquale; Pastori, Daniele

2016-03-01

Educational advice is often given to patients starting treatment with vitamin K Antagonists (VKAs). A great emphasis is made on nutritional information. Common belief is that dietary vitamin K intake could counteract the anticoagulant effect by VKAs and for many years, patients have been discouraged to consume vitamin-K-rich foods, such as green leafy vegetables.The objective of this study is to summarize the current evidence supporting the putative interaction between dietary vitamin K intake and changes in INR with the VKAs.Data sources are MEDLINE via PubMed and Cochrane database.All clinical studies investigating the relationship between dietary vitamin K and measures of anticoagulation were included. We excluded all studies of supplementation of vitamin K alone.We performed a systematic review of the literature up to October 2015, searching for a combination of "food," "diet," "vitamin K," "phylloquinone," "warfarin," "INR," "coagulation," and "anticoagulant."Two dietary interventional trials and 9 observational studies were included. We found conflicting evidence on the effect of dietary intake of vitamin K on coagulation response. Some studies found a negative correlation between vitamin K intake and INR changes, while others suggested that a minimum amount of vitamin K is required to maintain an adequate anticoagulation. Median dietary intake of vitamin K1 ranged from 76 to 217 μg/day among studies, and an effect on coagulation may be detected only for high amount of vitamin intake (>150 μg/day).Most studies included patients with various indications for VKAs therapy, such as atrial fibrillation, prosthetic heart valves, and venous thromboembolism. Thus, INR target was dishomogeneous and no subanalyses for specific populations or different anticoagulants were conducted. Measures used to evaluate anticoagulation stability were variable.The available evidence does not support current advice to modify dietary habits when starting therapy with VKAs

Zeolite-based hemostat QuikClot releases calcium into blood and promotes blood coagulation in vitro

PubMed Central

Li, Jing; Cao, Wei; Lv, Xiao-xing; Jiang, Li; Li, Yue-jun; Li, Wang-zhou; Chen, Shao-zong; Li, Xue-yong

2013-01-01

Aim: To examine the changes in electrolyte concentrations after addition of zeolite-based hemostat QuikClot in blood and the effects of zeolite on blood coagulation in vitro. Methods: Fresh blood was taken from healthy adult volunteers and sheep, and the electrolyte concentrations in blood were measured using a blood electrolyte analyzer. Zeolite Saline Solution (ZSS) was prepared by addition of 2 g zeolite to 0.9% NaCl solution (4, 8, or 16 mL). The electrolytes in ZSS were measured using inductively coupled plasma atomic emission spectroscopy. The prothrombin time (PT) and activated partial thromboplastin time (APTT) of blood were measured using the test tube method. The activated clotting time (ACT) and clotting rate (CR) of blood were measured with Sonoclot Coagulation and Platelet Function Analyzer. Results: Addition of zeolite (50 and 100 mg) in 2 mL human blood significantly increased Ca2+ concentration, while Na+ and K+ concentrations were significantly decreased. Addition of zeolite (50 and 100 mg) in 0.9% NaCl solution (2 mL) caused similar changes in Ca2+ and Na+ concentrations. Si4+ (0.2434 g/L) and Al3+ (0.2575 g/L) were detected in ZSS (2 g/8 mL). Addition of ZSS in sheep blood shortened APTT in a concentration dependent manner, without changing PT. ZSS or aqueous solution of CaCl2 that contained Ca2+ concentration identical to that of ZSS significantly shortened ACT in human blood without significantly changing CR, and the effect of ZSS on ACT was not significantly different from that of CaCl2. Conclusion: Zeolite releases Ca2+ into blood, thus accelerating the intrinsic pathway of blood coagulation and shortening the clot formation time. PMID:23334236

Zeolite-based hemostat QuikClot releases calcium into blood and promotes blood coagulation in vitro.

PubMed

Li, Jing; Cao, Wei; Lv, Xiao-xing; Jiang, Li; Li, Yue-jun; Li, Wang-zhou; Chen, Shao-zong; Li, Xue-yong

2013-03-01

To examine the changes in electrolyte concentrations after addition of zeolite-based hemostat QuikClot in blood and the effects of zeolite on blood coagulation in vitro. Fresh blood was taken from healthy adult volunteers and sheep, and the electrolyte concentrations in blood were measured using a blood electrolyte analyzer. Zeolite Saline Solution (ZSS) was prepared by addition of 2 g zeolite to 0.9% NaCl solution (4, 8, or 16 mL). The electrolytes in ZSS were measured using inductively coupled plasma atomic emission spectroscopy. The prothrombin time (PT) and activated partial thromboplastin time (APTT) of blood were measured using the test tube method. The activated clotting time (ACT) and clotting rate (CR) of blood were measured with Sonoclot Coagulation and Platelet Function Analyzer. Addition of zeolite (50 and 100 mg) in 2 mL human blood significantly increased Ca(2+) concentration, while Na(+) and K(+) concentrations were significantly decreased. Addition of zeolite (50 and 100 mg) in 0.9% NaCl solution (2 mL) caused similar changes in Ca(2+) and Na(+) concentrations. Si(4+) (0.2434 g/L) and Al(3+) (0.2575 g/L) were detected in ZSS (2 g/8 mL). Addition of ZSS in sheep blood shortened APTT in a concentration dependent manner, without changing PT. ZSS or aqueous solution of CaCl2 that contained Ca(2+) concentration identical to that of ZSS significantly shortened ACT in human blood without significantly changing CR, and the effect of ZSS on ACT was not significantly different from that of CaCl2. Zeolite releases Ca(2+) into blood, thus accelerating the intrinsic pathway of blood coagulation and shortening the clot formation time.

Two-incision laparoscopic appendectomy for a severe hemophilia A child patient with coagulation factor VII deficiency: Case report and review of literature.

PubMed

He, Jin Peng; Feng, Jie Xiong

2017-10-01

The main complication of patients with severe hemophilia is recurrent bleeding events that usually affected musculoskeletal contractures. And replacement therapy methods were continuously improved to minimize adverse impacts brought by those complications. However, only several cases reported about the appendectomy for hemophilia A. We report a case of acute appendicitis treated by two-incision laparoscopy in a boy with hemophilia A and coagulation factor VII deficiency for the first time. An 8y7m-old Chinese boy presented with half a day of right sided abdominal pain, fever, nausea, and vomiting. He received a computed tomography (CT) scan which revealed an enlarged appendix, thickened wall and appendiceal fecalith, and had received a conservative anti-bacterial treatment for his acute appendicitis but failed. He was diagnosed with hemophilia A and coagulation factor VII deficiency. Two-incision laparoscopic appendectomy was made in success with a careful management of perioperative period. We monitored the clotting factor FVIII level and gave him a replacement therapy. The patient had an uneventful recovery. It is important to exclude intraabdominal or retroperitoneal hemorrhage in patients suffering from hemophilia and acute abdominal pain. Pre-operative evaluation of validity of the FVIII replacement therapy is another effective strategy to assess the safety and feasibility of applying an operation procedure. The two-incision laparoscopic appendectomy is an effective treatment for this kind of patients for its minimal trauma and fast recovery characteristics. Our report shows that laparoscopic appendectomy is feasible in a child suffering from hemophilia after adequate blood clotting factor replacement treatment.

[The implantation of bipolar coagulation to remove endometriosis foci].

PubMed

Sobkiewicz, S; Palatyński, A; Salata, I

2001-05-01

The paper compares the results of bipolar coagulation bey means of ERBE ICC 300 diatermy coagulator and WISAP endocoagulator. The results of both types of coagulation were assessed with reference to the changes occurring on peritoneum ligamenti sacro-uterini, Douglas pouch and ovary. The best results of endometriosis foci coagulation were obtained with bipolar ball at 20-30 W; no side effects or feelings of malaise were observed in patients just after the operation or over a longer period of convalescence.

Dependence of renal (Na+ + k+)-adenosine triphosphatase activity on thyroid status.

PubMed

Lo, S C; August, T R; Liberman, U A; Edelman, I S

1976-12-25

In thyroidectomized rats, a single injection of L-2,,5,2'-triiodothyronine (T3) (50mug/100 g body weight) elicited at 45% increase in (Na+ + k+)-dependent adenosine triphosphatase (NaK-ATPase) activity of the membrane-rich fraction of renal cortex at the optimal time of response, 48 h after injection. Three successive doses of T3 (50 mug/100 g body weight), given on alternate days, increased NaK-ATPase by 67% in the renal cortex but had no significant effect on the outer medulla or the papilla. Moreover, T3 had no effect on Mg2+-dependent adenosine trisphatase (MgATPase) in cortex, cedulla, or papilla. Three doses of T3 (50 mug/100 g body weight) given on alternate days to thyroidectomized rats elecited a 134, 79, and 46% increase in Vmax for ATP, Na4, and K+, respectively. There were no changes in the Km for ATP or the K1/2 values for Na+ and K+. Two methods were used to estimate the effect of T3 on the number of NaK-ATPase units (assumed to represent the number of Na+ pump sites); rat renal plasma membrane fractions were incubated with [gamma-32P]ATP, Mg2+, and Na+; the 32P-labeled membrane protein yeild was quantitatively dependent on Na+ and was hydrolyzed on addition of K+. There was a linear correlation between the specific activity of NaK-ATPase (Vmax) and the amount of phosphorylated intermediate formed, in renal cortical membrane fractions from thyroidectomized rats given T3 or the diluent. There was also a linear correlation between the specific activity of NaK-ATPase (Vmax) and the amount of [3H]ouabain specifically bound (Na+-, Mg2+-, APT-dependent) to the NaK-ATPase preparation. Injection of T3 resulted in a 70% increase in NaK-ATPase activity, a 79% increase in formation of the phosphorylated intermediate, and a 65% increase in the [H]ouabain specifically bound to the NaK-ATPase system. The T3-dependent increases in Vmax for ATP, Na+, and K+ and the proportionate increases in the phosphorylated intermediate and in the amount of [3H]ouabain bound

The Mast Cell, Contact, and Coagulation System Connection in Anaphylaxis

PubMed Central

Guilarte, Mar; Sala-Cunill, Anna; Luengo, Olga; Labrador-Horrillo, Moisés; Cardona, Victoria

2017-01-01

Anaphylaxis is the most severe form of allergic reaction, resulting from the effect of mediators and chemotactic substances released by activated cells. Mast cells and basophils are considered key players in IgE-mediated human anaphylaxis. Beyond IgE-mediated activation of mast cells/basophils, further mechanisms are involved in the occurrence of anaphylaxis. New insights into the potential relevance of pathways other than mast cell and basophil degranulation have been unraveled, such as the activation of the contact and the coagulation systems. Mast cell heparin released upon activation provides negatively charged surfaces for factor XII (FXII) binding and auto-activation. Activated FXII, the initiating serine protease in both the contact and the intrinsic coagulation system, activates factor XI and prekallikrein, respectively. FXII-mediated bradykinin (BK) formation has been proven in the human plasma of anaphylactic patients as well as in experimental models of anaphylaxis. Moreover, the severity of anaphylaxis is correlated with the increase in plasma heparin, BK formation and the intensity of contact system activation. FXII also activates plasminogen in the fibrinolysis system. Mast cell tryptase has been shown to participate in fibrinolysis through plasmin activation and by facilitating the degradation of fibrinogen. Some usual clinical manifestations in anaphylaxis, such as angioedema or hypotension, or other less common, such as metrorrhagia, may be explained by the direct effect of the activation of the coagulation and contact system driven by mast cell mediators. PMID:28798744

Population pharmacokinetics of recombinant coagulation factor VIII-SingleChain in patients with severe hemophilia A.

PubMed

Zhang, Y; Roberts, J; Tortorici, M; Veldman, A; St Ledger, K; Feussner, A; Sidhu, J

2017-06-01

Essentials rVIII-SingleChain is a unique recombinant factor VIII (FVIII) molecule. A population pharmacokinetic model was based on FVIII activity of severe hemophilia A patients. The model was used to simulate factor VIII activity-time profiles for various dosing scenarios. The model supports prolonged dosing of rVIII-SingleChain with intervals of up to twice per week. Background Single-chain recombinant coagulation factor VIII (rVIII-SingleChain) is a unique recombinant coagulation factor VIII molecule. Objectives To: (i) characterize the population pharmacokinetics (PK) of rVIII-SingleChain in patients with severe hemophilia A; (ii) identify correlates of variability in rVIII-SingleChain PK; and (iii) simulate various dosing scenarios of rVIII-SingleChain. Patients/Methods A population PK model was developed, based on FVIII activity levels of 130 patients with severe hemophilia A (n = 91 for ≥ 12-65 years; n = 39 for < 12 years) who had participated in a single-dose PK investigation with rVIII-SingleChain 50 IU kg -1 . PK sampling was performed for up to 96 h. Results A two-compartment population PK model with first-order elimination adequately described FVIII activity. Body weight and predose level of von Willebrand factor were significant covariates on clearance, and body weight was a significant covariate on the central distribution volume. Simulations using the model with various dosing scenarios estimated that > 85% and > 93% of patients were predicted to maintain FVIII activity level above 1 IU dL -1 , at all times with three-times-weekly dosing (given on days 0, 2, and 4.5) at the lowest (20 IU kg -1 ) and highest (50 IU kg -1 ) doses, respectively. For twice weekly dosing (days 0 and 3.5) of 50 IU kg -1 rVIII-SingleChain, 62-80% of patients across all ages were predicted to maintain a FVIII activity level above 1 IU dL -1 at day 7. Conclusions The population PK model adequately characterized rVIII-SingleChain PK, and the model

Coagulation of Dust Particles in Argon Plasma of RF Discharge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mankelevich, Yu. A.; Olevanov, M. A.; Pal, A. F.

2008-09-07

The experiments on coagulation of poly-disperse particles with various size distributions injected into the argon plasma of the magnetron radio-frequency discharge are discussed. The experiments were carried out under the conditions similar to those using dusty plasma for technology applications. Within the created theory the threshold behavior of the coagulation process was explained for the first time, the estimation of the critical particle size for onset of a fast coagulation was made, and the analytical calculation of the coagulation rate of dust particles was performed. The proposed coagulation mechanism makes it possible to describe the typical features of coagulation processesmore » observed in experiments and to explain the effects of attraction and coalescence of highly negatively charged microns size particles.« less

Coagulation profile of Sudanese children with homozygous sickle cell disease and the effect of treatment with omega-3 fatty acid on the coagulation parameters.

PubMed

Awoda, Shiekh; Daak, Ahmed A; Husain, Nazik Elmalaika; Ghebremeskel, Kebreab; Elbashir, Mustafa I

2017-01-01

It has been reported that patients with SCD do have an abnormal coagulation profile. Coagulopathy is thought to be one of the key factors that contribute to the vaso-occlusive crisis that characterises sickle cell disease (SCD). In this study, we investigated whether Sudanese sickle cell patients have an abnormal coagulation profile. In addition, the effect of treatment with either omega-3 fatty acids or hydroxyurea on coagulation profile was assessed. Homozygous SCD patients untreated ( n  = 52), omega-3 treated ( n  = 44), hydroxyurea (HU) treated ( n  = 8) and healthy (HbAA) controls ( n  = 52) matched for age (4-20 years), gender and socioeconomic status were enrolled. Patients on omega-3 fatty acids, according to age, received one to four capsules containing 277.8 mg DHA and 39.0 mg eicosapentnoic. Patients on Hydroxyurea were in on dosage more than 20 mg/kg/day. The steady state levels of the coagulation parameters and the effect of the treatments with either HU or omega-3 fatty acids on markers of coagulation were investigated. Compared to the healthy controls, treated and untreated HbSS patients had lower hemoglobin, plasma Protein C, proteins S and higher white blood cell count (WBC), platelets count (PLTs) and plasma D-dimer levels,( p  < 0.05). In comparison to untreated HbSS, treatment with neither omega-3 nor HU had effect on the WBC, plasma proteins C and S, ( p  > 0.05). HU treated group had a lower PLTs count compared to HbSS untreated group ( p  < 0.5). The prothrombin and activated partial thromboplastin times and international normalized ratio (INR) of untreated patients are significantly higher than n-3 treated, HU-treated patients and health controls, ( p  < 0.05). Patients treated with omega-3 had lowered D-dimer levels in comparison to HU-treated and untreated HbSS patients, ( p  < 0.001). This study provides evidence that Sudanes patients have abnormal coagulation profile and treatment with either HU or omega-3 fatty

Optical factors determined by the T-matrix method in turbidity measurement of absolute coagulation rate constants.

PubMed

Xu, Shenghua; Liu, Jie; Sun, Zhiwei

2006-12-01

Turbidity measurement for the absolute coagulation rate constants of suspensions has been extensively adopted because of its simplicity and easy implementation. A key factor in deriving the rate constant from experimental data is how to theoretically evaluate the so-called optical factor involved in calculating the extinction cross section of doublets formed during aggregation. In a previous paper, we have shown that compared with other theoretical approaches, the T-matrix method provides a robust solution to this problem and is effective in extending the applicability range of the turbidity methodology, as well as increasing measurement accuracy. This paper will provide a more comprehensive discussion of the physical insight for using the T-matrix method in turbidity measurement and associated technical details. In particular, the importance of ensuring the correct value for the refractive indices for colloidal particles and the surrounding medium used in the calculation is addressed, because the indices generally vary with the wavelength of the incident light. The comparison of calculated results with experiments shows that the T-matrix method can correctly calculate optical factors even for large particles, whereas other existing theories cannot. In addition, the data of the optical factor calculated by the T-matrix method for a range of particle radii and incident light wavelengths are listed.

Electromagnetic induction sensor for dynamic testing of coagulation process.

PubMed

Wang, Zhe; Yu, Yuanhua; Yu, Zhanjiang; Chen, Qimeng

2018-03-01

With the increasing demand for coagulation POCT for patients in the surgery department or the ICU, rapid coagulation testing techniques and methods have drawn widespread attention from scholars and businessmen. This paper proposes the use of electromagnetic induction sensor probe for detection of dynamic process causing changes in the blood viscosity and density before and after coagulation based on the damped vibration principle, in order to evaluate the coagulation status. Utilizing the dynamic principle, the differential equation of vibration system comprising elastic support and electromagnetic induction device is established through sensor dynamic modeling. The structural parameters of elastic support are optimized, and the circular sheet spring is designed. Furthermore, harmonic response analysis and vibration fatigue coupling analysis are performed on the elastic support of the sensor by considering the natural frequency of the system, and the electromagnetic induction sensor testing device is set up. Using the device and coagulation reagent, the standard curve for coagulation POCT is plotted, and the blood sample application in clinical patients is established, which are methodologically compared with the imported POCT coagulation analyzer. The results show that the sensor designed in this paper has a first-order natural frequency of 11.368 Hz, which can withstand 5.295 × 10 2 million times of compressions and rebounds. Its correlation with the results of SONOCLOT analyzer reaches 0.996, and the reproducibility 0.002. The electromagnetic induction coagulation testing sensor designed has good elasticity and anti-fatigue, which can meet the accuracy requirement of clinical detection. This study provides the core technology for developing the electromagnetic induction POCT instrument for dynamic testing of coagulation process.

TREATMENT OF LANDFILL LEACHATE BY COUPLING COAGULATION-FLOCCULATION OR OZONATION TO GRANULAR ACTIVATED CARBON ADSORPTION.

PubMed

Oloibiri, Violet; Ufomba, Innocent; Chys, Michael; Audenaert, Wim; Demeestere, Kristof; Van Hulle, Stijn W H

2015-01-01

A major concern for landfilling facilities is the treatment of their leachate. To optimize organic matter removal from this leachate, the combination of two or more techniques is preferred in order to meet stringent effluent standards. In our study, coagulation-flocculation and ozonation are compared as pre- treatment steps for stabilized landfill leachate prior to granular activated carbon (GAC) adsorption. The efficiency of the pre treatment techniques is evaluated using COD and UVA254 measurements. For coagulation- flocculation, different chemicals are compared and optimal dosages are determined. After this, iron (III) chloride is selected for subsequent adsorption studies due to its high percentage of COD and UVA254 removal and good sludge settle-ability. Our finding show that ozonation as a single treatment is effective in reducing COD in landfill leachate by 66% compared to coagulation flocculation (33%). Meanwhile, coagulation performs better in UVA254 reduction than ozonation. Subsequent GAC adsorption of ozonated effluent, coagulated effluent and untreated leachate resulted in 77%, 53% and 8% total COD removal respectively (after 6 bed volumes). The effect of the pre-treatment techniques on GAC adsorption properties is evaluated experimentally and mathematically using Thomas and Yoon-Nelson models. Mathematical modelling of the experimental GAC adsorption data shows that ozonation increases the adsorption capacity and break through time with a factor of 2.5 compared to coagulation-flocculation.

[Investigation on the impact of hot temperature methods of the tissue dissection and coagulation on parenchymatous organs in experiment].

PubMed

Sukhin, I A; Khudets'kyĭ, I Iu; Kachan, S H; Bilylovets', O M

2013-01-01

There are adduced the results of experimental operations on mongrel rabbits with dissection and coagulation of the liver and the spleen, using highly temperature coagulation apparatuses of various kinds. There was established, that while application of various highly temperature technologies a typical process occurs, consisting of the heat spreading inside the organ. The temperature raising grade depends on the method and duration of the impact.

[Effect of ferrate preoxidation on coagulation of Songhua River].

PubMed

Li, Chun-juan; Ma, Jun; Liang, Tao

2008-06-01

The preoxidation of polluted surface water with ferrate was conducted with respect to its impact on the following coagulation. It can be seen that UV254-absorbance, turbidity and TOC substantially decreased by 36.7%, 80.2%, 31.1%, respectively, after coagulation, without ferrate preoxidation, and by 63.3%, 89.6%, 37.0%, respectively, after coagulation, with ferrate preoxidation. It is noted that NH4+-N concentration is increased by 17% after coagulation with ferrate. This phenomenon can be explained by the fact that organics containing nitrogen in raw water were partly oxidized to inorganic nitrogen by ferrate preoxidation. After coagulation, AOC and AOC/TOC are increased from 998 microg x L(-1) to 1241 microg x L(-1), from 28.4% to 38.7%, respectively, by ferrate preoxidation. AOC-P17/AOC after coagulation is up to 83% with ferrate preoxidation. These suggest that preoxidation with ferrate promoted the biodegradation of organics with substantial increases of AOC, AOC/TOC. The results indicate that the concentration of organics with relative molecular mass (Mr) of 10000-100000 and less than 500 were substantially increased after the raw water was coagulated with ferrate preoxidation, which suggested that some high molecular weight organic substances were broken into smaller ones during ferrate preoxidation. After coagulation, organics of less than Mr = 500 in TOC are increased up to 65.0% with preoxidation from 38.9% without ferrate preoxidation. These oxidation products are biodegradable.

EFFECT OF THE TREATMENT WITH P-32 ON BLOOD COAGULATION FACTORS IN POLYCYTHEMIA VERA (in Italian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Austoni, M.; Masetto, I.; Butto, M.

1961-01-01

Blood coagulation factors were investigated in 14 patients with polycythemia vera, before and after P/sup 32/ treatment. In connection with the improvement of clinical signs of thrombosis or hemorrhage and with the red cell count decrease, significant changes were observed, especially in the platelet sector. A general normalization of the platelet function occurred with a decrease from 420000 before to 186200/cmm after the therapy. This was evident with the Heparin tolerance test in vitro: the mean values, which were 6'39"/3 heparin Units/ml, 8'57"/7 heparin U/ml, and 12'31"/10 heparin U/ml before treatment, passed to 7'36", 11'10", and 16'08", in connection withmore » the improvement of the plasmatic thrombogenic diathesis. (P.C.H.)« less

Point-of-Care Coagulation Monitoring in Trauma Patients.

PubMed

Stein, Philipp; Kaserer, Alexander; Spahn, Gabriela H; Spahn, Donat R

2017-06-01

Trauma remains one of the major causes of death and disability all over the world. Uncontrolled blood loss and trauma-induced coagulopathy represent preventable causes of trauma-related morbidity and mortality. Treatment may consist of allogeneic blood product transfusion at a fixed ratio or in an individualized goal-directed way based on point-of-care (POC) and routine laboratory measurements. Viscoelastic POC measurement of the developing clot in whole blood and POC platelet function testing allow rapid and tailored coagulation and transfusion treatment based on goal-directed, factor concentrate-based algorithms. The first studies have been published showing that this concept reduces the need for allogeneic blood transfusion and improves outcome. This review highlights the concept of goal-directed POC coagulation management in trauma patients, introduces a selection of POC devices, and presents algorithms which allow a reduction in allogeneic blood product transfusion and an improvement of trauma patient outcome. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Coagulation is more affected by quick than slow bleeding in patients with massive blood loss.

PubMed

Zhao, Juan; Yang, Dejuan; Zheng, Dongyou

2017-03-01

Profuse blood loss affects blood coagulation to various degrees. However, whether bleeding speed affects coagulation remains uncertain. This study aimed to evaluate the effect of bleeding speed on coagulation function. A total of 141 patients in the Department of Thoracic Surgery of our hospital were evaluated between January 2007 and February 2014. There are two groups of patients, those who received decortication for chronic encapsulated empyema were called the slow-bleeding group, and those who received thoracoscopic upper lobectomy were called the fast bleeding group; each group was further subdivided into three: group A, 1000 ml ≤ bleeding amount < 1500 ml; group B, 1500 ml ≤ bleeding amount < 1700 ml; group C, 1700 ml ≤ bleeding amount < 2000 ml. Then, coagulation function was assessed in all patients before and during surgery and at 1, 2, and 24 h after surgery, measuring prothrombin time, activated partial thromboplastin time (APTT), fibrinogen, blood pressure, hematocrit, hemoglobin, and platelets. Bleeding duration was overtly longer in the slow-bleeding group than that in quick bleeding individuals (2.3 ± 0.25 h vs. 0.41 ± 0.13 h, P < 0.001). Fibrinogen, hematocrit, hemoglobin, and platelets strikingly decreased, whereas prothrombin time and APTT values significantly increased with bleeding amounts in both quick and slow-bleeding groups. Interestingly, compared with slow-bleeding patients, coagulation indices at each time point and bleeding amounts had significant differences in the quick bleeding group.Increased consumption of coagulation factors in quick bleeding may have greater impact on coagulation function.

Surface-mediated molecular events in material-induced blood-plasma coagulation

NASA Astrophysics Data System (ADS)

Chatterjee, Kaushik

Coagulation and thrombosis persist as major impediments associated with the use of blood-contacting medical devices. We are investigating the molecular mechanism underlying material-induced blood-plasma coagulation focusing on the role of the surface as a step towards prospective development of improved hemocompatible biomaterials. A classic observation in hematology is that blood/blood-plasma in contact with clean glass surface clots faster than when in contact with many plastic surfaces. The traditional biochemical theory explaining the underlying molecular mechanism suggests that hydrophilic surfaces, like that of glass, are specific activators of the coagulation cascade because of the negatively-charged groups on the surface. Hydrophobic surfaces are poor procoagulants or essentially "benign" because they lack anionic groups. Further, these negatively-charged surfaces are believed to not only activate blood factor XII (FXII), the key protein in contact activation, but also play a cofactor role in the amplification and propagation reactions that ultimately lead to clot formation. In sharp contrast to the traditional theory, our investigations indicate a need for a paradigm shift in the proposed sequence of contact activation events to incorporate the role of protein adsorption at the material surfaces. These studies have lead to the central hypothesis for this work proposing that protein adsorption to hydrophobic surfaces attenuates the contact activation reactions so that poorly-adsorbent hydrophilic surfaces appear to be stronger procoagulants relative to hydrophobic surfaces. Our preliminary studies measuring the plasma coagulation response of activated FXII (FXIIa) on different model surfaces suggested that the material did not play a cofactor role in the processing of this enzyme dose through the coagulation pathway. Therefore, we focused our efforts on studying the mechanism of initial production of enzyme at the procoagulant surface. Calculations for the

The role of coagulation/fibrinolysis during Streptococcus pyogenes infection

PubMed Central

Loof, Torsten G.; Deicke, Christin; Medina, Eva

2014-01-01

The hemostatic system comprises platelet aggregation, coagulation and fibrinolysis and is a host defense mechanism that protects the integrity of the vascular system after tissue injury. During bacterial infections, the coagulation system cooperates with the inflammatory system to eliminate the invading pathogens. However, pathogenic bacteria have frequently evolved mechanisms to exploit the hemostatic system components for their own benefit. Streptococcus pyogenes, also known as Group A Streptococcus, provides a remarkable example of the extraordinary capacity of pathogens to exploit the host hemostatic system to support microbial survival and dissemination. The coagulation cascade comprises the contact system (also known as the intrinsic pathway) and the tissue factor pathway (also known as the extrinsic pathway), both leading to fibrin formation. During the early phase of S. pyogenes infection, the activation of the contact system eventually leads to bacterial entrapment within a fibrin clot, where S. pyogenes is immobilized and killed. However, entrapped S. pyogenes can circumvent the antimicrobial effect of the clot by sequestering host plasminogen on the bacterial cell surface that, after conversion into its active proteolytic form, plasmin, degrades the fibrin network and facilitates the liberation of S. pyogenes from the clot. Furthermore, the surface-localized fibrinolytic activity also cleaves a variety of extracellular matrix proteins, thereby enabling S. pyogenes to migrate across barriers and disseminate within the host. This review summarizes the knowledge gained during the last two decades on the role of coagulation/fibrinolysis in host defense against S. pyogenes as well as the strategies developed by this pathogen to evade and exploit these host mechanisms for its own benefit. PMID:25309880

Temperature and composition dependence of Mg-based amorphous-alloy structure factors

NASA Astrophysics Data System (ADS)

From, M.; Muir, W. B.

1992-01-01

Measurements of the x-ray total structure factors for amorphous Mg70Zn30, Ca70Mg30, and Mg85.5Cu14.5 at 9, 150, and 300 K have been made. The composition dependence of the room-temperature structure factors of MgxZn1-x have also been measured for values of x=0.65, 0.70, and 0.75. These compositional changes can be accounted for by the increase in average atomic size as the fraction of the larger Mg atoms increases with x. Also the Perkus-Yevick hard-sphere model is sufficient to calculate the change in structure factor with composition if an experimental structure factor is available from which the sphere diameters and packing fraction can be extracted. The temperature dependence of the structure factors is consistent with the observed thermal expansion and a Debye phonon model with Meisel and Cote's approximation for the multiphonon contribution to the structure factor.

External K+ dependence of strong inward rectifier K+ channel conductance is caused not by K+ but by competitive pore blockade by external Na.

PubMed

Ishihara, Keiko

2018-06-15

Strong inward rectifier K + (sKir) channels determine the membrane potentials of many types of excitable and nonexcitable cells, most notably the resting potentials of cardiac myocytes. They show little outward current during membrane depolarization (i.e., strong inward rectification) because of the channel blockade by cytoplasmic polyamines, which depends on the deviation of the membrane potential from the K + equilibrium potential ( V - E K ) when the extracellular K + concentration ([K + ] out ) is changed. Because their open - channel conductance is apparently proportional to the "square root" of [K + ] out , increases/decreases in [K + ] out enhance/diminish outward currents through sKir channels at membrane potentials near their reversal potential, which also affects, for example, the repolarization and action-potential duration of cardiac myocytes. Despite its importance, however, the mechanism underlying the [K + ] out dependence of the open sKir channel conductance has remained elusive. By studying Kir2.1, the canonical member of the sKir channel family, we first show that the outward currents of Kir2.1 are observed under the external K + -free condition when its inward rectification is reduced and that the complete inhibition of the currents at 0 [K + ] out results solely from pore blockade caused by the polyamines. Moreover, the noted square-root proportionality of the open sKir channel conductance to [K + ] out is mediated by the pore blockade by the external Na + , which is competitive with the external K + Our results show that external K + itself does not activate or facilitate K + permeation through the open sKir channel to mediate the apparent external K + dependence of its open channel conductance. The paradoxical increase/decrease in outward sKir channel currents during alternations in [K + ] out , which is physiologically relevant, is caused by competition from impermeant extracellular Na . © 2018 Ishihara.

Treatment of waste water by coagulation and flocculation using biomaterials

NASA Astrophysics Data System (ADS)

Muruganandam, L.; Saravana Kumar, M. P.; Jena, Amarjit; Gulla, Sudiv; Godhwani, Bhagesh

2017-11-01

The present study deals with the determination of physical and chemical parameters in the treatment process of waste water by flocculation and coagulation processes using natural coagulants and assessing their feasibility for water treatment by comparing the performance with each other and with a synthetic coagulant. Initial studies were done on the synthetic waste water to determine the optimal pH and dosage, the activity of natural coagulant, followed by the real effluent from tannery waste. The raw tannery effluent was bluish-black in colour, mildly basic in nature, with high COD 4000mg/l and turbidity in the range 700NTU, was diluted and dosed with organic coagulants, AloeVera, MoringaOleifera and Cactus (O.ficus-indica). The study observed that coagulant Moringa Oleifera of 15 mg/L dose at 6 pH gave the best reduction efficiencies for major physicochemical parameters followed by Aloe Vera and Cactus under identical conditions. The study reveals that the untreated tannery effluents can be treated with environmental confirmative naturally occurring coagulants.

Coagulation chemistries for silica removal from cooling tower water.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nyman, May Devan; Altman, Susan Jeanne; Stewart, Tom

2010-02-01

The formation of silica scale is a problem for thermoelectric power generating facilities, and this study investigated the potential for removal of silica by means of chemical coagulation from source water before it is subjected to mineral concentration in cooling towers. In Phase I, a screening of many typical as well as novel coagulants was carried out using concentrated cooling tower water, with and without flocculation aids, at concentrations typical for water purification with limited results. In Phase II, it was decided that treatment of source or make up water was more appropriate, and that higher dosing with coagulants deliveredmore » promising results. In fact, the less exotic coagulants proved to be more efficacious for reasons not yet fully determined. Some analysis was made of the molecular nature of the precipitated floc, which may aid in process improvements. In Phase III, more detailed study of process conditions for aluminum chloride coagulation was undertaken. Lime-soda water softening and the precipitation of magnesium hydroxide were shown to be too limited in terms of effectiveness, speed, and energy consumption to be considered further for the present application. In Phase IV, sodium aluminate emerged as an effective coagulant for silica, and the most attractive of those tested to date because of its availability, ease of use, and low requirement for additional chemicals. Some process optimization was performed for coagulant concentration and operational pH. It is concluded that silica coagulation with simple aluminum-based agents is effective, simple, and compatible with other industrial processes.« less

Coagulation monitoring based on blood elastic measurement using optical coherence tomography

NASA Astrophysics Data System (ADS)

Xu, Xiangqun; Zhu, Jiang; Chen, Zhongping

2017-02-01

Blood coagulation monitoring is important to diagnose hematological diseases and cardiovascular diseases and to predict the risk of bleeding and excessive clotting. In this study, we developed a system to dynamically monitor blood coagulation and quantitatively determine the coagulation function by blood elastic measurement. When blood forms a clot from a liquid, ultrasonic force induces a shear wave, which is detected by optical coherence tomography (OCT). The coagulation of porcine whole blood recalcified by calcium chloride is assessed using the metrics of reaction time, clot formation kinetics and maximum shear modulus. The OCE system can noninvasively monitor the blood coagulation and quantitatively determine the coagulation function.

Study of coagulation processes of selected humic acids under copper ions influence*

NASA Astrophysics Data System (ADS)

Boguta, Patrycja; Sokolowska, Zofia

2013-04-01

(carbon analyzer: Multi NC2000, Analityk Jena) and measurements of copper content in solution (atomic absorption spectrometer: Contraa300, Analityk Jena). On the base of obtained results initial and end point of coagulation was determined for each of humic acids. Results showed that coagulation points differed for different humic acids and it was probably depended on sorption possibilities. Coagulation points determined from UV-VIS measurements overlapped with points from carbon measurement. Loss of carbon during coagulation was almost total but loss of copper in solution during humic acid coagulation was much smaller and did not cover exactly points of carbon precipitation. So that, coagulation of humic acids under copper influence could resulted from both bonding of metal by functional groups and creating complexes and also from increasing ionic strength. Important is that organic carbon went to insoluble form and copper stayed in movable compounds. Such studies and conclusions coming from them, can be very important from ecological side. *This work was partly supported by the National Science Centre in Poland, grant No. UMO-2011/03/N/NZ9/04239.

Coagulant from Leucaena leucocephala for Chromium Removal

NASA Astrophysics Data System (ADS)

Razak, N. H. Abd; Khairuddin, N.; Ismail, K. N.; Musa, M.

2018-05-01

This research investigated the effectiveness of leucaena leucocephala as a natural coagulant for chromium removal. Leucaena leucocephala is a permanent non-climbing shrub tree which is wild and abundant in Malaysia and commonly known as petai belalang. Coagulation experiment using jar test were performed where the effect of coagulant dosage and pH were examined. The parameters investigated were suspended solid (SS), chemical oxygen demand (COD), biological oxygen demand (BOD), turbidity and chromium content. The optimum of leucaena leucocephala coagulant dosage for removal of suspended solid, turbidity, COD, BOD and Chromium is at range 400-600 mg/L which yielded 45, 31.4, 38.5, 27.5 and 4.05% removal respectively. While the optimum pH is at pH 2-4 (acidic) which give 33.3, 26.8, 33.75, 31.4 and 14.06% removal of suspended solid, COD, BOD, turbidity and chromium content respectively. It is concluded that the leucaena leucocephala showed tremendous potential for chromium removal.

The asymptotic behavior in a reversible random coagulation-fragmentation polymerization process with sub-exponential decay

NASA Astrophysics Data System (ADS)

Dong, Siqun; Zhao, Dianli

2018-01-01

This paper studies the subcritical, near-critical and supercritical asymptotic behavior of a reversible random coagulation-fragmentation polymerization process as N → ∞, with the number of distinct ways to form a k-clusters from k units satisfying f(k) =(1 + o (1)) cr-ke-kαk-β, where 0 < α < 1 and β > 0. When the cluster size is small, its distribution is proved to converge to the Gaussian distribution. For the medium clusters, its distribution will converge to Poisson distribution in supercritical stage, and no large clusters exist in this stage. Furthermore, the largest length of polymers of size N is of order ln N in the subcritical stage under α ⩽ 1 / 2.

Honey Bee Venom (Apis mellifera) Contains Anticoagulation Factors and Increases the Blood-clotting Time

PubMed Central

Zolfagharian, Hossein; Mohajeri, Mohammad; Babaie, Mahdi

2015-01-01

Objectives: Bee venom (BV) is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera) on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Methods: Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50), and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Blood samples were obtained from 10 rabbits, and the prothrombin time (PT) and the partial thromboplastin time (PTT) tests were conducted. The approximate lethal dose (LD) values of BV were determined. Results: Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations (SDs) = ± 0.71; however, clotting was observed in the control group 13.8 s, SDs = ± 0.52. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa), respectively. The LD50 of the crude BV was found to be 177.8 μg/mouse. Conclusion: BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase A2 (PLA2) and melittin, and that can increase the blood clotting times in vitro. PMID:26998384

Honey Bee Venom (Apis mellifera) Contains Anticoagulation Factors and Increases the Blood-clotting Time.

PubMed

Zolfagharian, Hossein; Mohajeri, Mohammad; Babaie, Mahdi

2015-12-01

Bee venom (BV) is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera) on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50), and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Blood samples were obtained from 10 rabbits, and the prothrombin time (PT) and the partial thromboplastin time (PTT) tests were conducted. The approximate lethal dose (LD) values of BV were determined. Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations (SDs) = ± 0.71; however, clotting was observed in the control group 13.8 s, SDs = ± 0.52. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa), respectively. The LD50 of the crude BV was found to be 177.8 μg/mouse. BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase A2 (PLA2) and melittin, and that can increase the blood clotting times in vitro.

Coagulation dynamics of a blood sample by multiple scattering analysis

NASA Astrophysics Data System (ADS)

Faivre, Magalie; Peltié, Philippe; Planat-Chrétien, Anne; Cosnier, Marie-Line; Cubizolles, Myriam; Nougier, Christophe; Négrier, Claude; Pouteau, Patrick

2011-05-01

We report a new technique to measure coagulation dynamics on whole-blood samples. The method relies on the analysis of the speckle figure resulting from a whole-blood sample mixed with coagulation reagent and introduced in a thin chamber illuminated with a coherent light. A dynamic study of the speckle reveals a typical behavior due to coagulation. We compare our measured coagulation times to a reference method obtained in a medical laboratory.

Nanoparticle coagulation in fractionally charged and charge fluctuating dusty plasmas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nunomura, Shota; Kondo, Michio; Shiratani, Masaharu

2008-08-15

The kinetics of nanoparticle coagulation has been studied in fractionally charged and charge fluctuating dusty plasmas. The coagulation occurs when the mutual collision frequency among nanoparticles exceeds their charging and decharging/neutralization frequency. Interestingly, the coagulation is suppressed while a fraction (several percent) of nanoparticles are negatively charged in a plasma, in which stochastic charging plays an important role. A model is developed to predict a phase diagram of the coagulation and its suppression.

Coagulation and oxidative stress plasmatic levels in a type 2 diabetes population.

PubMed

Barillari, Giovanni; Fabbro, Elisabetta; Pasca, Samantha; Bigotto, Enrico

2009-06-01

Type 2 diabetes mellitus (DM2) is a metabolic disorder characterized by relative insulin deficiency, insulin resistance and hyperglycemia. DM2 improperly managed can cause severe complications such as renal failure, blindness or arterial disease. In addition to serious complications due to DM2, in the past 20 years, several studies have demonstrated the association between DM2, insulin resistance and prothrombotic risk. In our study, we wanted to evaluate the correlation between coagulation factor levels, oxidative plasmatic levels and DM2. We considered 20 DM2 patients (65% women and 35% men), 40-65 years of age, who had a BMI between 25 and 40 kg/m2 and followed a diet with or without oral antidiabetic treatment and 20 controls, blood donors, 15 men (75%) and five women (25%), who had a BMI between 25 and 40 kg/m2 and their age was between 40 and 65 years. Plasmatic levels of oxidative stress markers (tumor necrosis factor-alpha, nitrotyrosine, oxidized low-density lipoprotein) and coagulation markers (factors VII, VIII, IX, XI, XII, antithrombin III and fibrinogen) of both populations were analyzed following statistic criteria. The analyzed data of this study related to oxidative stress and coagulation factors proved that the differences observed between diabetic patients and controls were not statistically significant (P < 0.05) for tumor necrosis factor-alpha, nitrotyrosine, oxidized low-density lipoprotein, factor VII and factor XI; conversely for factor VIII, factor IX, factor XII, antithrombin III and fibrinogen, the results gave a difference statistically significant (P < 0.01). In patients with DM2, factor VIII increased from 79 to 103%, factor IX from 88 to 103%, factor XII from 87 to 105% and finally, antithrombin III from 81 to 103%. Different results between literature and our study could be due to fact that the patients considered were in the early stage of diabetes when endothelial damage is absent and vascular complications are not clinically

What Is Combined Deficiency of Vitamin K-Dependent Clotting Factors?

MedlinePlus

... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

Performance and characterization of a new tannin-based coagulant

NASA Astrophysics Data System (ADS)

Beltrán-Heredia, J.; Sánchez-Martín, J.; Gómez-Muñoz, C.

2012-09-01

Diethanolamine and formaldehyde were employed to cationize tannins from black wattle. This novel coagulant called CDF was functionally characterized in removing sodium dodecylbenzene sulfonate (anionic surfactant) and Palatine Fast Black WAN (azoic dye). Refined tannin-derived commercial coagulants exhibited similar efficiency, while CDF presented higher coagulant ability than alum, a usual coagulant agent. Low doses of CDF (ca. 100 mg L-1) were able to remove more than 70 % of surfactant and more than 85 % of dye (initial pollutant concentration of ca. 100 mg L-1) and it presented no temperature affection and worked at a relatively wide pH range. Surfactant and dye removal responded to the classical coagulant-and-adsorption models, such as Frumkin-Fowler-Guggenheim or Gu and Zhu in the case of surfactant, and Langmuir and Freundlich in the case of dye.

The relevance of coagulation factor X protection of adenoviruses in human sera

PubMed Central

Duffy, M R; Doszpoly, A; Turner, G; Nicklin, S A; Baker, A H

2016-01-01

Intravenous delivery of adenoviruses is the optimal route for many gene therapy applications. Once in the blood, coagulation factor X (FX) binds to the adenovirus capsid and protects the virion from natural antibody and classical complement-mediated neutralisation in mice. However, to date, no studies have examined the relevance of this FX/viral immune protective mechanism in human samples. In this study, we assessed the effects of blocking FX on adenovirus type 5 (Ad5) activity in the presence of human serum. FX prevented human IgM binding directly to the virus. In individual human sera samples (n=25), approximately half of those screened inhibited adenovirus transduction only when the Ad5–FX interaction was blocked, demonstrating that FX protected the virus from neutralising components in a large proportion of human sera. In contrast, the remainder of sera tested had no inhibitory effects on Ad5 transduction and FX armament was not required for effective gene transfer. In human sera in which FX had a protective role, Ad5 induced lower levels of complement activation in the presence of FX. We therefore demonstrate for the first time the importance of Ad–FX protection in human samples and highlight subject variability and species-specific differences as key considerations for adenoviral gene therapy. PMID:27014840

Influence of vegetable coagulant and ripening time on the lipolytic and sensory profile of cheeses made with raw goat milk from Canary breeds.

PubMed

Rincón, Arturo A; Pino, Verónica; Fresno, María R; Jiménez-Abizanda, Ana I; Álvarez, Sergio; Ayala, Juan H; Afonso, Ana M

2017-04-01

Free fatty acids and sensory profiles were obtained for cheeses made with raw goat milk and vegetable coagulant, derived from the cardoon flower ( Cynara cardunculus), at different ripening times (7 and 20 days). A solid-liquid phase extraction method followed by solid-phase extraction and gas chromatography was used. Profiles were also obtained with cheeses made with commercial coagulant, traditional kid rennet paste, and mixture coagulant (vegetable coagulant-kid rennet). The use of vegetable coagulant and vegetable coagulant-kid rennet is common in traditional Protected Designation of Origin cheeses such as " Queso Flor de Guía" and " Queso Media Flor de Guía" (Spain). Contents of short-chain free fatty acids (7.5-22.5 mmol·kg -1 ), medium-chain free fatty acids (0.4-3.7 mmol·kg -1 ), and long-chain free fatty acids (0.2-2.1 mmol·kg -1 ) varied depending on the coagulant type and the ripening time. Vegetable coagulant cheeses present odour intensity and flavour intensity much higher than commercial coagulant cheeses in the sensory analysis for cheeses obtained with seven days of ripening, but the values decrease when increasing the ripening time. Multivariate analysis allowed us to differentiate cheese samples according to the ripening time when using lipolytic profile and according to the coagulant type using the sensory profile.

The Role of Na,k-Atpase α Subunit Serine 775 and Glutamate 779 in Determining the Extracellular K+And Membrane Potential–Dependent Properties of the Na,k -Pump

PubMed Central

Peluffo, R. Daniel; Argüello, José M.; Berlin, Joshua R.

2000-01-01

The roles of Ser775 and Glu779, two amino acids in the putative fifth transmembrane segment of the Na,K -ATPase α subunit, in determining the voltage and extracellular K + (K + o) dependence of enzyme-mediated ion transport, were examined in this study. HeLa cells expressing the α1 subunit of sheep Na,K -ATPase were voltage clamped via patch electrodes containing solutions with 115 mM Na+ (37°C). Na,K -pump current produced by the ouabain-resistant control enzyme (RD), containing amino acid substitutions Gln111Arg and Asn122Asp, displayed a membrane potential and K + o dependence similar to wild-type Na,K -ATPase during superfusion with 0 and 148 mM Na+-containing salt solutions. Additional substitution of alanine at Ser775 or Glu779 produced 155- and 15-fold increases, respectively, in the K + o concentration that half-maximally activated Na,K -pump current at 0 mV in extracellular Na+-free solutions. However, the voltage dependence of Na,K -pump current was unchanged in RD and alanine-substituted enzymes. Thus, large changes in apparent K + o affinity could be produced by mutations in the fifth transmembrane segment of the Na,K -ATPase with little effect on voltage-dependent properties of K + transport. One interpretation of these results is that protein structures responsible for the kinetics of K + o binding and/or occlusion may be distinct, at least in part, from those that are responsible for the voltage dependence of K + o binding to the Na,K -ATPase. PMID:10871639

Coagulation monitoring during extracorporeal membrane oxygenation: the role of thrombelastography.

PubMed

Stammers, A H; Willett, L; Fristoe, L; Merrill, J; Stover, T; Hunt, A; Morrow, J; Newberry, J

1995-09-01

Patients undergoing extracorporeal membrane oxygenation (ECMO) are at an increased risk for developing coagulopathies due to the adverse effects of extracorporeal circulation on the hemostatic mechanism. Methods of determining causative factors of bleeding diathesis are often inconsistent and non-specific. ECMO patients require aggressive transfusion therapy with autogenic blood products to stabilize and maintain hemostasis. The present study evaluated the coagulation status of newborn patients undergoing ECMO therapy, using a viscoelastic monitor (Thrombelastograph -TEG) that measures functional aspects of clot development and stabilization. Seventeen neonatal patients undergoing ECMO for severe respiratory dysfunction were entered into this study. Serial blood samples were obtained and routine coagulation assessment including fibrinogen concentration, platelet count and ionized calcium was performed. In addition, fibrin(ogen) degradation products (FDP), d-Dimers, antithrombin III and plasma free hemoglobin were measured. Transfusion indicators were established and total transfusion requirements recorded. TEG profiles were determined with the use of heparinase, an enzyme that degrades heparin but has little effect on other coagulation factors. The most commonly encountered complication was hemorrhaging which was diagnosed by laboratory and clinical assessment in 11 of 17 patients. Transfusion requirements (measured in ml/kg/ECMO hour) were the following: packed red blood cells--1.34 +/- 0.5; platelets--0.71 +/- 0.57; fresh frozen plasma--0.09 +/- 0.12; cryoprecipitate 0.05 +/- 0.05. Thrombelastograph profiles reflected hemostatic conditions that ranged from severe coagulopathies (DIC) to hypercoagulability. Interpretation of TEG profiles identified hemostatic abnormalities in 57 of 101 profiles (46.5%), with the most common etiology related to platelet dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

An in vitro analysis of the effect of acidosis on coagulation in chronic disease states - a thromboelastograph study.

PubMed

White, Hayden; Bird, Robert; Sosnowski, Kellie; Jones, Mark

2016-06-01

Thrombosis is a complication of many chronic illnesses. Chronic obstructive pulmonary disease (COPD) and diabetes mellitus are common medical conditions frequently associated with a hypercoagulable state. Acidaemia has been shown to reduce coagulation. COPD and diabetes mellitus during acute deterioration can present with a severe acidaemia. The impact of this acidaemia on coagulation is poorly studied. Patients presenting with a diagnosis of diabetic ketoacidosis or type II respiratory failure from COPD and a pH of less than 7.2 were included in our study. A coagulation screen and a thromboelastograph (TEG) were performed on admission and 24 hours later. The mean pH on admission was 7.07 and mean base excess was -16.3. The activated partial thromboplastin time was associated with pH change but remained within the normal range (26-41 s). All other coagulation and TEG parameters failed to show evidence of association (p>0.05). In the two models of non-haemorrhagic acidosis investigated, coagulation was not altered by the changes in pH. More work is needed to understand the complex relationship between factors affecting coagulation in individual disease processes. © 2016 Royal College of Physicians.

Biological Systems of Vitamin K: A Plasma Nutriproteomics Study of Subclinical Vitamin K Deficiency in 500 Nepalese Children.

PubMed

Lee, Sun Eun; Schulze, Kerry J; Cole, Robert N; Wu, Lee S F; Yager, James D; Groopman, John; Christian, Parul; West, Keith P

2016-04-01

Vitamin K (VK) is a fat-soluble vitamin whose deficiency disrupts coagulation and may disturb bone and cardiovascular health. However, the scale and systems affected by VK deficiency in pediatric populations remains unclear. We conducted a study of the plasma proteome of 500 Nepalese children 6-8 years of age (male/female ratio = 0.99) to identify proteins associated with VK status. We measured the concentrations of plasma lipids and protein induced by VK absence-II (PIVKA-II) and correlated relative abundance of proteins quantified by mass spectrometry with PIVKA-II. VK deficiency (PIVKA-II>2 μg/L) was associated with a higher abundance of low-density lipoproteins, total cholesterol, and triglyceride concentrations (p<0.01). Among 978 proteins observed in >10% of the children, five proteins were associated with PIVKA-II and seven proteins were differentially abundant between VK deficient versus sufficient children, including coagulation factor-II, hemoglobin, and vascular endothelial cadherin, passing a false discovery rate (FDR) threshold of 10% (q<0.10). Among 27 proteins associated with PIVKA-II or VK deficiency at a less stringent FDR (q<0.20), a network comprised of hemoglobin subunits and erythrocyte anti-oxidative enzymes were highly and positively correlated each other (all r>0.7). Untargeted proteomics offers a novel systems approach to elucidating biological processes of coagulation, vascularization, and erythrocyte oxidative stress related to VK status. The results may help elucidate subclinical metabolic disturbances related to VK deficiency in populations.

Porcine endothelium induces DNA-histone complex formation in human whole blood: a harmful effect of histone on coagulation and endothelial activation.

PubMed

Yoo, Hyun Ju; Kim, Ji-Eun; Gu, Ja Yoon; Lee, Sae Bom; Lee, Hyun Joo; Hwang, Ho Young; Hwang, Yoohwa; Kim, Young Tae; Kim, Hyun Kyung

2016-11-01

Neutrophils play a role in xenograft rejection. When neutrophils are stimulated, they eject the DNA-histone complex into the extracellular space, called neutrophil extracellular traps (NET). We investigated whether NET formation actively occurs in the xenograft and contributes to coagulation and endothelial activation. Human whole blood was incubated with porcine aortic endothelial cells (pEC) from wild-type or α1,3-galactosyltransferase gene-knockout (GTKO) pigs. In the supernatant plasma from human blood, the level of the DNA-histone complex was measured by ELISA, and thrombin generation was measured using a calibrated automated thrombogram. Histone-induced tissue factor and adhesion molecule expression were measured by flow cytometry. pEC from both wild-type and GTKO pigs significantly induced DNA-histone complex formation in human whole blood. The DNA-histone complex produced shortened the thrombin generation time and clotting time. Histone alone dose-dependently induced tissue factor and adhesion molecule expression in pEC. Aurintricarboxylic acid pretreatment partially inhibited pEC-induced DNA-histone complex formation. DNA-histone complex actively generated upon xenotransplantation is a novel target to inhibit coagulation and endothelial activation. To prevent tissue factor and adhesion molecule expression, a strategy to block soluble histone may be required in xenotransplantation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function

PubMed Central

Ivaskevicius, Vytautas; Biswas, Arijit; Bevans, Carville; Schroeder, Verena; Kohler, Hans Peter; Rott, Hannelore; Halimeh, Susan; Petrides, Petro E.; Lenk, Harald; Krause, Manuele; Miterski, Bruno; Harbrecht, Ursula; Oldenburg, Johannes

2010-01-01

Background Severe hereditary coagulation factor XIII deficiency is a rare homozygous bleeding disorder affecting one person in every two million individuals. In contrast, heterozygous factor XIII deficiency is more common, but usually not associated with severe hemorrhage such as intracranial bleeding or hemarthrosis. In most cases, the disease is caused by F13A gene mutations. Causative mutations associated with the F13B gene are rarer. Design and Methods We analyzed ten index patients and three relatives for factor XIII activity using a photometric assay and sequenced their F13A and F13B genes. Additionally, structural analysis of the wild-type protein structure from a previously reported X-ray crystallographic model identified potential structural and functional effects of the missense mutations. Results All individuals except one were heterozygous for factor XIIIA mutations (average factor XIII activity 51%), while the remaining homozygous individual was found to have severe factor XIII deficiency (<5% of normal factor XIII activity). Eight of the 12 heterozygous patients exhibited a bleeding tendency upon provocation. Conclusions The identified missense (Pro289Arg, Arg611His, Asp668Gly) and nonsense (Gly390X, Trp664X) mutations are causative for factor XIII deficiency. A Gly592Ser variant identified in three unrelated index patients, as well as in 200 healthy controls (minor allele frequency 0.005), and two further Tyr167Cys and Arg540Gln variants, represent possible candidates for rare F13A gene polymorphisms since they apparently do not have a significant influence on the structure of the factor XIIIA protein. Future in vitro expression studies of the factor XIII mutations are required to confirm their pathological mechanisms. PMID:20179087

Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function.

PubMed

Ivaskevicius, Vytautas; Biswas, Arijit; Bevans, Carville; Schroeder, Verena; Kohler, Hans Peter; Rott, Hannelore; Halimeh, Susan; Petrides, Petro E; Lenk, Harald; Krause, Manuele; Miterski, Bruno; Harbrecht, Ursula; Oldenburg, Johannes

2010-06-01

Severe hereditary coagulation factor XIII deficiency is a rare homozygous bleeding disorder affecting one person in every two million individuals. In contrast, heterozygous factor XIII deficiency is more common, but usually not associated with severe hemorrhage such as intracranial bleeding or hemarthrosis. In most cases, the disease is caused by F13A gene mutations. Causative mutations associated with the F13B gene are rarer. We analyzed ten index patients and three relatives for factor XIII activity using a photometric assay and sequenced their F13A and F13B genes. Additionally, structural analysis of the wild-type protein structure from a previously reported X-ray crystallographic model identified potential structural and functional effects of the missense mutations. All individuals except one were heterozygous for factor XIIIA mutations (average factor XIII activity 51%), while the remaining homozygous individual was found to have severe factor XIII deficiency (<5% of normal factor XIII activity). Eight of the 12 heterozygous patients exhibited a bleeding tendency upon provocation. The identified missense (Pro289Arg, Arg611His, Asp668Gly) and nonsense (Gly390X, Trp664X) mutations are causative for factor XIII deficiency. A Gly592Ser variant identified in three unrelated index patients, as well as in 200 healthy controls (minor allele frequency 0.005), and two further Tyr167Cys and Arg540Gln variants, represent possible candidates for rare F13A gene polymorphisms since they apparently do not have a significant influence on the structure of the factor XIIIA protein. Future in vitro expression studies of the factor XIII mutations are required to confirm their pathological mechanisms.

Monopolar soft-mode coagulation using hemostatic forceps for peptic ulcer bleeding.

PubMed

Yamasaki, Yasushi; Takenaka, Ryuta; Nunoue, Tomokazu; Kono, Yoshiyasu; Takemoto, Koji; Taira, Akihiko; Tsugeno, Hirofumi; Fujiki, Shigeatsu

2014-01-01

Upper gastrointestinal hemorrhage from bleeding peptic ulcer is sometimes difficult to treat by conventional endoscopic methods. Recently, monopolar electrocoagulation using a soft-coagulation system and hemostatic forceps (soft coagulation) has been used to prevent bleeding during endoscopic submucosal dissection. The aim of this study was to assess the safety and efficacy of soft coagulation in the treatment of bleeding peptic ulcer. A total of 39 patients with peptic ulcers were treated using soft coagulation at our hospital between January 2005 and March 2010. Emergency treatment employed an ERBE soft-mode coagulation system using hemostatic forceps. Second-look endoscopy was performed to evaluate the efficacy of prior therapy. Initial hemostasis was defined as accomplished by soft coagulation, with or without other endoscopic therapy prior to soft coagulation. The rate of initial hemostasis, rebleeding, and ultimate hemostasis were retrospectively analyzed. The study subjects were 31 men and 8 women with a mean age of 68.3±13.7 years, with 29 gastric ulcers and 10 duodenal ulcers. Initial hemostasis was achieved in 37 patients (95%). During follow-up, bleeding recurred in two patients, who were retreated with soft coagulation. The monopolar soft coagulation is feasible and safe for treating bleeding peptic ulcers.

Administration of tissue plasminogen activator without coagulation results in a Chinese population.

PubMed

Qin, Xiaoming; Zhao, Songyao; Yin, Liujie; Dou, Hailing; Chen, Jie; Wang, Yifan; Li, Mingzhe; Chen, Ruifang; Fu, Jing; Liu, Wei; Liu, Xin; Yang, Gaiqing; Wang, Runqing; Jia, Xinzhou; Bu, Shufang; Ma, Dongpu; Wang, Baoyu; Li, Shize

2018-03-01

Routine coagulation test before intravenous tissue plasminogen activator (tPA) use increases the door to needle time (DNT). We sought to evaluate the safety of tPA use without coagulation results and its impact on prognosis. In our stroke registry, tPA was delivered with coagulation results from December 2015 to April 2016 and without coagulation results from May 2016 to December 2016. Differences of demographics, clinical characteristic, and prognosis between these two groups were analyzed. In addition, logistic regression analysis was conducted to identify predictors for DNT of over 60 min. A total of 201 stroke patients were included in the final analysis. Of these, 81 patients received tPA with coagulation results and 120 patients without coagulation results. Only one (0.8%) patient with abnormal coagulation results met the exclusion criteria of tPA use in patients without coagulation results. The difference of DNT between groups with (mean, 61.7 min) and without (mean, 41.9 min) coagulation results was significant (P = 0.00). The group without coagulation results had a higher rate of favorable 90-day outcome (74.2 vs 70.4%) and lower rates of symptomatic intracranial hemorrhage/nonintracranial hemorrhage (4.9 and 22.2% vs 1.7 and 19.2%) than the group with coagulation results did; these differences were not statistically significant. In multivariate analysis, only tPA use with coagulation results was the predictor for DNT of over 60 min (P = 0.0030, OR = 2.44, 95% CI 1.28-4.65). The present study suggests that tPA could be delivered safely without coagulation results in patients without suspected coagulopathy, and avoiding coagulation tests reduces significantly the DNT interval.

Coagulation cascade and complement system in systemic lupus erythematosus

PubMed Central

Liang, Yan; Xie, Shang-Bo; Wu, Chang-Hao; Hu, Yuan; Zhang, Qin; Li, Si; Fan, Yin-Guang; Leng, Rui-Xue; Pan, Hai-Feng; Xiong, Hua-Bao; Ye, Dong-Qing

2018-01-01

This study was conducted to (1) characterize coagulation cascade and complement system in systemic lupus erythematosus (SLE); (2) evaluate the associations between coagulation cascade, complement system, inflammatory response and SLE disease severity; (3) test the diagnostic value of a combination of D-dimer and C4 for lupus activity. Transcriptomics, proteomics and metabolomics were performed in 24 SLE patients and 24 healthy controls. The levels of ten coagulations, seven complements and three cytokines were measured in 112 SLE patients. Clinical data were collected from 2025 SLE patients. The analysis of multi-omics data revealed the common links for the components of coagulation cascade and complement system. The results of ELISA showed coagulation cascade and complement system had an interaction effect on SLE disease severity, this effect was pronounced among patients with excess inflammation. The analysis of clinical data revealed a combination of D-dimer and C4 provided good diagnostic performance for lupus activity. This study suggested that coagulation cascade and complement system become ‘partners in crime’, contributing to SLE disease severity and identified the diagnostic value of D-dimer combined with C4for lupus activity. PMID:29599912

Effects of low temperature on coagulation of kaolinite suspensions.

PubMed

Xiao, Feng; Ma, Jun; Yi, Peng; Huang, Ju-Chang Howard

2008-06-01

In this study, coagulation of kaolinite suspensions at low temperatures is compared with that at an ambient temperature of 22 degrees C, and the process is examined with regard to the coagulation rate (CR) and chemical aspects of coagulation. Experiments using a photometric dispersion analyzer (PDA) show that coagulation of kaolinite suspensions can be taken as a two-phase process. Low temperature greatly reduces the CR of the first phase but not that of the second one. On the other hand, results show that low temperature did not serve to impede the hydrolysis of aluminum [Al(III)] within 1 min of alum addition. The measurements of electrophoretic mobility (EM) indicate that destabilization of kaolinite particles by hydrolyzed Al species was not hindered by low temperature within 1 min of alum addition. Slow coagulation at low temperature is due to the lowered CR but not the altered chemistry aspect of Al(III). Furthermore, the change in settled turbidity after 20-min flocculation as a function of coagulant dosage was more severe in the cold because of the low CR. Elongating floc-growth time, as observed, was able to counterbalance the retarded CR at low temperature and improve turbidity removal efficiency.

Applying the cell-based coagulation model in the management of critical bleeding.

PubMed

Ho, K M; Pavey, W

2017-03-01

The cell-based coagulation model was proposed 15 years ago, yet has not been applied commonly in the management of critical bleeding. Nevertheless, this alternative model may better explain the physiological basis of current coagulation management during critical bleeding. In this article we describe the limitations of the traditional coagulation protein cascade and standard coagulation tests, and explain the potential advantages of applying the cell-based model in current coagulation management strategies. The cell-based coagulation model builds on the traditional coagulation model and explains many recent clinical observations and research findings related to critical bleeding unexplained by the traditional model, including the encouraging results of using empirical 1:1:1 fresh frozen plasma:platelets:red blood cells transfusion strategy, and the use of viscoelastic and platelet function tests in patients with critical bleeding. From a practical perspective, applying the cell-based coagulation model also explains why new direct oral anticoagulants are effective systemic anticoagulants even without affecting activated partial thromboplastin time or the International Normalized Ratio in a dose-related fashion. The cell-based coagulation model represents the most cohesive scientific framework on which we can understand and manage coagulation during critical bleeding.

Performance of ultrafiltration membrane process combined with coagulation/sedimentation.

PubMed

Jang, N Y; Watanabe, Y; Minegishi, S

2005-01-01

Effects of coagulation/sedimentation as a pre-treatment on the dead-end ultrafiltration (UF) membrane process were studied in terms of membrane fouling and removal efficiency of natural dissolved organic matter, using Chitose River water. Two types of experiment were carried out. One was a bench scale membrane filtration with jar-test and the other was membrane filtration pilot plant combined with the Jet Mixed Separator (JMS) as a pre-coagulation/sedimentation unit. In the bench scale experiment, the effects of coagulant dosage, pH and membrane operating pressure on the membrane fouling and removal efficiency of natural dissolved organic matter were investigated. In the pilot plant experiment, we also investigated the effect of pre-coagulation/sedimentation on the membrane fouling and the removal efficiency of natural dissolved organic matter. Coagulation/sedimentation prior to membrane filtration process controlled the membrane fouling and increased the removal efficiency of natural dissolved organic matter.

Coagulant plus ballast technique provides a rapid mitigation of cyanobacterial nuisance

PubMed Central

de Magalhães, Leonardo; Miranda, Marcela; Mucci, Maíra; van Oosterhout, Frank; Huszar, Vera L. M.; Marinho, Marcelo M.; Lima, Eduardo R. A.; Lürling, Miquel

2017-01-01

Cyanobacteria blooms are a risk to environmental health and public safety due to the potent toxins certain cyanobacteria can produce. These nuisance organisms can be removed from water bodies by biomass flocculation and sedimentation. Here, we studied the efficacy of combinations of a low dose coagulant (poly-aluminium chloride—PAC—or chitosan) with different ballast compounds (red soil, bauxite, gravel, aluminium modified zeolite and lanthanum modified bentonite) to remove cyanobacterial biomass from water collected in Funil Reservoir (Brazil). We tested the effect of different cyanobacterial biomass concentrations on removal efficiency. We also examined if zeta potential was altered by treatments. Addition of low doses of PAC and chitosan (1–8 mg Al L-1) to the cyanobacterial suspensions caused flock formation, but did not settle the cyanobacteria. When those low dose coagulants were combined with ballast, effective settling in a dose-dependent way up to 99.7% removal of the flocks could be achieved without any effect on the zeta potential and thus without potential membrane damage. Removal efficacy was influenced by the cyanobacterial biomass and at higher biomass more ballast was needed to achieve good removal. The combined coagulant-ballast technique provides a promising alternative to algaecides in lakes, ponds and reservoirs. PMID:28598977

Implementation of a microcontroller-based semi-automatic coagulator.

PubMed

Chan, K; Kirumira, A; Elkateeb, A

2001-01-01

The coagulator is an instrument used in hospitals to detect clot formation as a function of time. Generally, these coagulators are very expensive and therefore not affordable by a doctors' office and small clinics. The objective of this project is to design and implement a low cost semi-automatic coagulator (SAC) prototype. The SAC is capable of assaying up to 12 samples and can perform the following tests: prothrombin time (PT), activated partial thromboplastin time (APTT), and PT/APTT combination. The prototype has been tested successfully.

Removal and transformation of effluent organic matter (EfOM) in biotreated textile wastewater by GAC/O3 pre-oxidation and enhanced coagulation.

PubMed

Qian, Feiyue; Sun, Xianbo; Liu, Yongdi; Xu, Hongyong

2013-01-01

GAC/O3 (ozonation in the presence of granular activated carbon) combined with enhanced coagulation was employed to process biotreated textile wastewater for possible reuse. The doses of ozone, GAC and coagulant were the variables studied for optimization. The effects of different treatment processes on effluent organic matter (EfOM) characteristics, including biodegradability, hydrophobic and hydrophilic nature, and apparent molecular weight (AMW) distribution were also investigated. Compared with ozonation, GAC/O3 not only presented a higher pre-oxidation efficiency, but also improved the treatability of hydrophobic and high molecular weight compounds by enhanced coagulation. After treatment by GAC/O3 pre-oxidation (0.6 mg O3 x mg(-1) COD and 20 g x L(-1) GAC) and enhanced coagulation (25 mg x L(-1) Al3+ at pH 5.5), the removal efficiencies of chemical oxygen demand (COD), dissolved organic carbon (DOC) and colour were higher than those for coagulation alone by 17.3%, 12.0% and 25.6%, respectively. Residual organic matter consisted mainly of hydrophobic acids and hydrophilic compounds of AMW < 1 kDa, which were colourless and of limited biological availability. The combination of GAC/O3 and enhanced coagulation was proved to be a simple and effective treatment strategy for removing EfOM from biotreated textile wastewater.

The clouds of Venus. II - An investigation of the influence of coagulation on the observed droplet size distribution

NASA Technical Reports Server (NTRS)

Rossow, W. B.

1977-01-01

An approximate numerical technique is used to investigate the influence of coagulation, sedimentation and turbulent motions on the observed droplet size distribution in the upper layers of the Venus clouds. If the cloud mass mixing ratio is less than 0.000001 at 250 K or the eddy diffusivity throughout the cloud is greater than 1,000,000 sq cm per sec, then coagulation is unimportant. In this case, the observed droplet size distribution is the initial size distribution produced by the condensation of the droplets. It is found that all cloud models with droplet formation near the cloud top (e.g., a photochemical model) must produce the observed droplet size distribution by condensation without subsequent modification by coagulation. However, neither meteoritic or surface dust can supply sufficient nucleating particles to account for the observed droplet number density. If the cloud droplets are formed near the cloud bottom, the observed droplet size distribution can be produced solely by the interaction of coagulation and dynamics; all information about the initial size distribution is lost. If droplet formation occurs near the cloud bottom, the lower atmosphere of Venus is oxidizing rather than reducing.

Coagulation mechanism of salt solution-extracted active component in Moringa oleifera seeds.

PubMed

Okuda, T; Baes, A U; Nishijima, W; Okada, M

2001-03-01

This study focuses on the coagulation mechanism by the purified coagulant solution (MOC-SC-PC) with the coagulation active component extracted from M. oleifera seeds using salt solution. The addition of MOC-SC-PC tap water formed insoluble matters. This formation was responsible for kaolin coagulation. On the other hand, insoluble matters were not formed when the MOC-SC-PC was added into distilled water. The formation was affected by Ca2+ or other bivalent cations which may connect each molecule of the active coagulation component in MOC-SC-PC and form a net-like structure. The coagulation mechanism of MOC-SC-PC seemed to be an enmeshment of Kaolin by the insoluble matters with the net-like structure. In case of Ca2+ ion (bivalent cations), at least 0.2 mM was necessary for coagulation at 0.3 mgC l-1 dose of MOC-SC-PC. Other coagulation mechanisms like compression of double layer, interparticle bridging or charge neutralization were not responsible for the coagulation by MOC-SC-PC.

Form factors and differential branching ratio of B →K μ+μ- in AdS/QCD

NASA Astrophysics Data System (ADS)

Momeni, S.; Khosravi, R.

2018-03-01

The holographic distribution amplitudes (DAs) for the K pseudoscalar meson are derived. For this aim, the light-front wave function (LFWF) of the K meson is extracted within the framework of the anti-de Sitter/quantum chromodynamics (AdS/QCD) correspondence. We consider a momentum-dependent (dynamical) helicity wave function that contains the dynamical spin effects. We use the LFWF to predict the radius and the electromagnetic form factor of the kaon and compare them with the experimental values. Then, the holographic twist-2 DA of K meson ϕK(α ,μ ) is investigated and compared with the result of the light-cone sum rules (LCSR). The transition form factors of the semileptonic B →K ℓ+ℓ- decays are derived from the holographic DAs of the kaon. With the help of these form factors, the differential branching ratio of the B →K μ+μ- on q2 is plotted. A comparison is made between our prediction in AdS/QCD and the results obtained from two models including the LCSR and the lattice QCD as well as the experimental values.

Micro- and mesoscopic process interactions in protein coagulation

NASA Astrophysics Data System (ADS)

San Biagio, P. L.; Martorana, V.; Emanuele, A.; Vaiana, S. M.; Manno, M.; Bulone, D.; Palma-Vittorelli, M. B.; Palma, M. U.

2000-04-01

It has recently been recognized that pathological protein coagulation is responsible for lethal pathologies as diverse as amyloidosis, Alzheimer and TSE. Understanding the coagulation mechanisms is therefore stirring great interest. In previous studies we have shown that on profoundly different systems coagulation is the result of a strong interaction between two processes on different length scales (mesoscopic and microscopic). Here we report experiments on bovine serum albumin (BSA) showing that the overall mechanism is the result of at least 3 distinct and strongly intertwined processes, on both length scales: molecular conformational changes, solution demixing and intermolecular crosslinking. This mechanism involves the statistical mechanics of protein-solvent interaction, its relation to the protein's landscape of configurational free energy and to the solution's thermodynamic stability, and its relation to the topological problem of crosslink-percolation, responsible for coagulation.

Increased thrombin generation in a mouse model of cancer cachexia is partially interleukin-6 dependent.

PubMed

Reddel, C J; Allen, J D; Ehteda, A; Taylor, R; Chen, V M Y; Curnow, J L; Kritharides, L; Robertson, G

2017-03-01

Essentials Cancer cachexia and cancer-associated thrombosis have not previously been mechanistically linked. We assessed thrombin generation and coagulation parameters in cachectic C26 tumor-bearing mice. C26 mice are hypercoagulable, partially corrected by blocking tumor derived interleukin-6. Coagulability and anti-inflammatory interventions may be clinically important in cancer cachexia. Background Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer, which have not previously been mechanistically linked. The colon 26 (C26) carcinoma is a well-established mouse model of complications of advanced cancer cachexia, partially dependent on high levels of interleukin-6 (IL-6) produced by the tumor. Objectives To assess if cancer cachexia altered the coagulation state and if this was attributable to tumor IL-6 production. Methods In male BALB/c*DBA2 (F1 hybrid) mice with a C26 tumor we used modified calibrated automated thrombogram and fibrin generation (based on overall hemostatic potential) assays to assess the functional coagulation state, and also examined fibrinogen, erythrocyte sedimentation rate (ESR), platelet count, tissue factor pathway inhibitor (TFPI) and hepatic expression of coagulation factors by microarray. C26 mice were compared with non-cachectic NC26, pair-fed and sham control mice. IL-6 expression in C26 cells was knocked down by lentiviral shRNA constructs. Results C26 mice with significant weight loss and highly elevated IL-6 had elevated thrombin generation, fibrinogen, ESR, platelets and TFPI compared with all control groups. Fibrin generation was elevated compared with pair-fed and sham controls but not compared with NC26 tumor mice. Hepatic expression of coagulation factors and fibrinolytic inhibitors was increased. Silencing IL-6 in the tumor significantly, but incompletely, attenuated the increased thrombin generation, fibrinogen and TFPI. Conclusions Cachectic C26 tumor-bearing mice are in a

Fever as a risk factor for increased response to vitamin K antagonists: a review of the evidence and potential mechanisms.

PubMed

Self, Timothy H; Oliphant, Carrie S; Reaves, Anne B; Richardson, Amy M; Sands, Christopher W

2015-01-01

Numerous factors affect the response to vitamin K antagonists (VKA) including age, dietary vitamin K, other drugs, pharmacogenetics, and disease states. In antithrombotic guidelines, fever is mentioned as a factor that may increase response to VKA. The purpose of this article is to review the available evidence regarding the effect of fever on response to VKA, and to discuss possible mechanisms of this effect. We performed a search of the English literature from 1943 to June 2014, using the key words fever AND warfarin, acenocoumarol, phenprocoumon, coumarin anticoagulants and VKA; fever AND vitamin K dependent clotting factors II, VII, IX, and X. One animal investigation and 6 studies in humans suggest fever increases response to VKA, but one study did not find a significant effect. The magnitude of this effect is variable. Possible mechanisms for the increased effect of VKA associated with fever are increased catabolism of vitamin K dependent clotting factors, decreased vitamin K intake, and inhibition of VKA metabolism. More rigorous studies are needed to confirm that fever increases response to warfarin and other VKA. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical coagulation of combined sewer overflow: heavy metal removal and treatment optimization.

PubMed

El Samrani, A G; Lartiges, B S; Villiéras, F

2008-02-01

The coagulation of combined sewer overflow (CSO) was investigated by jar-testing with two commercial coagulants, a ferric chloride solution (CLARFER) and a polyaluminium chloride (WAC HB). CSO samples were collected as a function of time during various wet-weather events from the inlet of Boudonville retention basin, Nancy, France. Jar-tests showed that an efficient turbidity removal can be achieved with both coagulants, though lower optimum dosages and higher re-stabilization concentrations were obtained with the aluminum-based coagulant. Optimum turbidity removal also yielded effective heavy metal elimination. However, the evolution with coagulant dosage of Cu, Zn, Pb, Cr, soluble and suspended solids contents followed various patterns. The removal behaviors can be explained by a selective aggregation of heavy metal carriers present in CSO and a specific interaction between hydrolyzed coagulant species and soluble metals. Stoichiometric relationships were established between optimal coagulant concentration, range of optimal dosing, and CSO conductivity, thus providing useful guidelines to adjust the coagulant demand during the course of CSO events.

A Uniqueness Result for Self-Similar Profiles to Smoluchowski's Coagulation Equation Revisited

NASA Astrophysics Data System (ADS)

Niethammer, B.; Throm, S.; Velázquez, J. J. L.

2016-07-01

In this note we indicate how to correct the proof of a uniqueness result in [6] for self-similar solutions to Smoluchowski's coagulation equation for kernels K=K(x,y) that are homogeneous of degree zero and close to constant in the sense that begin{aligned} -\\varepsilon le K(x,y)-2 le \\varepsilon Big ( Big (x/yBig )^{α } + Big (y/xBig )^{α }Big ) for α in [0,1/2). Under the additional assumption, in comparison to [6], that K has an analytic extension to mathbb {C}{setminus } (-infty ,0] and that the precise asymptotic behaviour of K at the origin is prescribed, we prove that self-similar solutions with given mass are unique if \\varepsilon is sufficiently small. The complete details of the proof are available in [4]. In addition, we give here the proof of a uniqueness result for a related but simpler problem that appears in the description of self-similar solutions for x → infty.

Proposal of the Coagulation Score as a Predictor for Short-Term and Long-Term Outcomes of Patients with Resectable Gastric Cancer.

PubMed

Kanda, Mitsuro; Tanaka, Chie; Kobayashi, Daisuke; Mizuno, Akira; Tanaka, Yuri; Takami, Hideki; Iwata, Naoki; Hayashi, Masamichi; Niwa, Yukiko; Yamada, Suguru; Fujii, Tsutomu; Sugimoto, Hiroyuki; Murotani, Kenta; Fujiwara, Michitaka; Kodera, Yasuhiro

2017-02-01

Systemic hemostasis and thrombosis activation has been implicated in tumor progression and metastasis. This study aimed to investigate the use of coagulation factors as a novel prediction method for postoperative outcomes after curative gastrectomy in patients with stage II/III gastric cancer (GC). Overall, 126 patients with stage II/III GC who underwent gastrectomy between May 2003 and February 2016 were eligible for inclusion in the study. We retrospectively evaluated the predictive value of preoperative platelet count and plasma fibrinogen and d-dimer levels, and coagulation score (0: fibrinogen and d-dimer both below upper limits; 1: either fibrinogen or d-dimer over upper limits; 2: both fibrinogen and d-dimer over upper limits) for short- and long-term outcomes. Postoperative complications were significantly more frequent in patients with elevated preoperative d-dimer levels compared with those with normal d-dimer levels (26 vs. 10 %; p = 0.032). The prevalence of postoperative complications showed a stepwise increase in proportion to the coagulation score. Patients with a coagulation score of 2 had significantly larger tumors (p = 0.013) and significantly greater intraoperative blood loss (p = 0.004) than those who scored 0 or 1. Coagulation score showed the highest values distinguished high-risk patients in overall and disease-free survival, and a coagulation score of 2 was an independent prognostic factor for recurrence. Patients with a coagulation score of 2 experienced a significantly higher prevalence of liver metastasis as an initial recurrence than those who scored 0 or 1 (p = 0.019). The coagulation score is a simple and promising predictor for postoperative complications and recurrence after gastrectomy in stage II/III GC patients.

Interplay between coagulation and vascular inflammation in sickle cell disease

PubMed Central

Sparkenbaugh, Erica; Pawlinski, Rafal

2013-01-01

Sickle cell disease is the most common inherited hematologic disorder that leads to the irreversible damage of multiple organs. Although sickling of red blood cells and vaso-occlusion are central to the pathophysiology of sickle cell disease the importance of hemolytic anemia and vasculopathy has been recently recognized. Hypercoagulation state is another prominent feature of sickle cell disease and is mediated by activation of both intrinsic and extrinsic coagulation pathways. Growing evidence demonstrates that coagulation may not only contribute to the thrombotic complications, but also to vascular inflammation associated with this disease. This article summarizes the role of vascular inflammation and coagulation activation, discusses potential mechanisms responsible for activation of coagulation and reviews recent data demonstrating the crosstalk between coagulation and vascular inflammation in sickle cell disease. PMID:23593937

Neprilysin Inhibits Coagulation through Proteolytic Inactivation of Fibrinogen

PubMed Central

Burrell, Matthew; Henderson, Simon J.; Ravnefjord, Anna; Schweikart, Fritz; Fowler, Susan B.; Witt, Susanne; Hansson, Kenny M.; Webster, Carl I.

2016-01-01

Neprilysin (NEP) is an endogenous protease that degrades a wide range of peptides including amyloid beta (Aβ), the main pathological component of Alzheimer’s disease (AD). We have engineered NEP as a potential therapeutic for AD but found in pre-clinical safety testing that this variant increased prothrombin time (PT) and activated partial thromboplastin time (APTT). The objective of the current study was to investigate the effect of wild type NEP and the engineered variant on coagulation and define the mechanism by which this effect is mediated. PT and APTT were measured in cynomolgus monkeys and rats dosed with a human serum albumin fusion with an engineered variant of NEP (HSA-NEPv) as well as in control plasma spiked with wild type or variant enzyme. The coagulation factor targeted by NEP was determined using in vitro prothrombinase, calibrated automated thrombogram (CAT) and fibrin formation assays as well as N-terminal sequencing of fibrinogen treated with the enzyme. We demonstrate that HSA-NEP wild type and HSA-NEPv unexpectedly impaired coagulation, increasing PT and APTT in plasma samples and abolishing fibrin formation from fibrinogen. This effect was mediated through cleavage of the N-termini of the Aα- and Bβ-chains of fibrinogen thereby significantly impairing initiation of fibrin formation by thrombin. Fibrinogen has therefore been identified for the first time as a substrate for NEP wild type suggesting that the enzyme may have a role in regulating fibrin formation. Reductions in NEP levels observed in AD and cerebral amyloid angiopathy may contribute to neurovascular degeneration observed in these conditions. PMID:27437944