[Case report. Phenprocoumon (Marcumar, Falithrom) as an unusual reason for coumarin poisoning in a dog].

PubMed

Lutze, G; Römhild, W; Elwert, J; Leppelt, J; Kutschmann, K

2003-01-01

Coumarin poisoning in dogs is not unusual and is in most cases caused by warfarin, a coumarin derivative which is used as a rodenticide. Competitive inhibition of vitamin K with an incomplete synthesis of the coagulation factors II, VII, IX and X can lead to a significant bleeding tendency. We observed a 3-year old male West Highland White Terrier with a reduced general condition and dyspnoea together with a massive haemothorax. Administration of vitamin K1 (3 mg/kg) led to a rapid improvement of the condition. Coagulation analysis revealed a prolonged activated recalcification time (ARCT), prothrombin time (PT) and aPTT with uncharacteristic thrombin time (TT); factor II, VII and X activities were reduced while factor V activity was normal, all of which are characteristic for coumarin poisoning. HPLC did not reveal the presence of warfarin but of phenoprocoumon, a drug used for thromboembolic prophylaxis in humans. This observation has not been described for dogs to date.

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.

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.

Ambient hemolysis and activation of coagulation is different between HeartMate II and HeartWare left ventricular assist devices.

PubMed

Birschmann, Ingvild; Dittrich, Marcus; Eller, Thomas; Wiegmann, Bettina; Reininger, Armin J; Budde, Ulrich; Strüber, Martin

2014-01-01

Thromboembolic and bleeding events in patients with a left ventricular assist device (LVAD) are still a major cause of complications. Therefore, the balance between anti-coagulant and pro-coagulant factors needs to be tightly controlled. The principle hypothesis of this study is that different pump designs may have an effect on hemolysis and activation of the coagulation system. Referring to this, the HeartMate II (HMII; Thoratec Corp, Pleasanton, CA) and the HeartWare HVAD (HeartWare International Inc, Framingham, MA) were investigated. For 20 patients with LVAD support (n = 10 each), plasma coagulation, full blood count, and clinical chemistry parameters were measured. Platelet function was monitored using platelet aggregometry, platelet function analyzer-100 system ( Siemens, Marburg, Germany), vasodilator-stimulated phosphoprotein phosphorylation assay, immature platelet fraction, platelet-derived microparticles, and von Willebrand diagnostic. Acquired von Willebrand syndrome could be detected in all patients. Signs of hemolysis, as measured by lactate dehydrogenase levels (mean, 470 U/liter HMII, 250 U/liter HVAD; p < 0.001), were more pronounced in the HMII patients. In contrast, D-dimer analysis indicated a significantly higher activation of the coagulation system in HVAD patients (mean, 0.94 mg/liter HMII, 2.01 mg/liter HVAD; p < 0.01). The efficacy of anti-platelet therapy using clopidogrel was not sufficient in more than 50% of the patients. Our results support the finding that all patients with rotary blood pumps suffered from von Willebrand syndrome. In addition, a distinct footprint of effects on hemolysis and the coagulation system can be attributed to different devices. As a consequence, the individual status of the coagulation system needs to be controlled in long-term patients. © 2013 Published by International Society for the Heart and Lung Transplantation on behalf of International Society for Heart and Lung Transplantation.

Microcystis aeruginosa-laden water treatment using enhanced coagulation by persulfate/Fe(II), ozone and permanganate: Comparison of the simultaneous and successive oxidant dosing strategy.

PubMed

Liu, Bin; Qu, Fangshu; Chen, Wei; Liang, Heng; Wang, Tianyu; Cheng, Xiaoxiang; Yu, Huarong; Li, Guibai; Van der Bruggen, Bart

2017-11-15

In this study, the application of enhanced coagulation with persulfate/Fe(II), permanganate and ozone for Microcystis-laden water treatment was investigated. Two oxidant dosage strategies were compared in terms of the organic removal performance: a simultaneous dosing strategy (SiDS) and a successive dosing strategy (SuDS). To optimize the oxidant species, oxidant doses and oxidant dosage strategy, the zeta potential, floc size and dimension fraction, potassium release and organic removal efficiency during the coagulation of algae-laden water were systematically investigated and comprehensively discussed. Ozonation causes most severe cell lysis and reduces organic removal efficiency because it releases intracellular organics. Moreover, ozonation can cause the release of odor compounds such as 2-methylisoborneol (2-MIB) and geosmin (GSM). With increasing doses, the performance of pollutant removal by coagulation enhanced by persulfate/Fe(II) or permanganate did not noticeably improve, which suggests that a low dosage of persulfate/Fe(II) and permanganate is the optimal strategy to enhance coagulation of Microcystis-laden water. The SiDS performs better than the SuDS because more Microcystis cell lysis occurs and less DOC is removed when oxidants are added before the coagulants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prolonged Prothrombin Time After Recombinant Activated Factor VII Therapy in Critically Bleeding Trauma Patients Is Associated With Adverse Outcomes

DTIC Science & Technology

2010-07-01

using the FVII coagulant activity (FVII:C) assay, a one- stage assay using thromboplastin tissue factor , which quantifies FVII clotting activity in...and the resultant production of dysfunctional factors II, VII, and X. This study focused on PT specifically because this measure examines the TF...ORIGINAL ARTICLE Prolonged Prothrombin Time After Recombinant Activated Factor VII Therapy in Critically Bleeding Trauma Patients Is Associated With

Influence of class I and II HLA alleles on inhibitor development in severe haemophilia A patients from the south of Brazil.

PubMed

De Barros, M F; Herrero, J C M; Sell, A M; De Melo, F C; Braga, M A; Pelissari, C B; Machado, J; De Souza Schiller, S; De Souza Hirle, L; Visentainer, J E L

2012-05-01

Congenital haemophilia A is a chromosome-linked recessive disorder caused by the deficiency or reduction of factor VIII (FVIII) pro-coagulant activity. During treatment, some patients develop alloantibodies (FVIII inhibitors) that neutralize the action of exogenously administered FVIII. Currently, the presence of these inhibitors is the most serious adverse event found in replacement therapy. Some studies have suggested that genetic factors influence the development of the FVIII coagulation inhibitors. To identify the class I and II alleles that may be influencing the formation of inhibitors in severe haemophilic patients. Genotyping of the class I (HLA-A, -B and -C) and class II (HLA-DRB1, -DQA1 and -DQB1) alleles of 122 patients with severe haemophilia A, including 36 who had developed antibodies to factor VIII, was performed. After the comparison of the group without inhibitors and the group with inhibitors, HLA-C*16 [Odds ratio (OR) = 7.73; P = 0.0092] and HLA-DRB1*14 (OR = 4.52; P = 0.0174) were found to be positively associated with the formation of the inhibitors. These results confirm that HLA alleles are involved in inhibitor production and could be used as a tool for recognition of groups at high risk of possible inhibitor development in Southern Brazilian haemophilic patients. © 2011 Blackwell Publishing Ltd.

A new manufacturing process to remove thrombogenic factors (II, VII, IX, X, and XI) from intravenous immunoglobulin gamma preparations.

PubMed

Park, Dong Hwarn; Kang, Gil Bu; Kang, Dae Eun; Hong, Jeung Woon; Lee, Min Gyu; Kim, Ki Yong; Han, Jeung Whan

2017-01-01

Coagulation factors (II, VII, IX, X, and particularly XIa) remaining in high concentrations in intravenous immunoglobulin (IVIG) preparations can form thrombi, causing thromboembolic events, and in serious cases, result in death. Therefore, manufacturers of biological products must investigate the ability of their production processes to remove procoagulant activities. Previously, we were able to remove coagulation factors II, VII, IX, and X from our IVIG preparation through ethanol precipitation, but factor XIa, which plays an important role in thrombosis, remained in the intermediate products. Here, we used a chromatographic process using a new resin that binds with high capacity to IgG and removes procoagulant activities. The procoagulant activities were reduced to low levels as determined by the thrombin generation assay: <1.56 mIU/mL, chromogenic FXIa assay: <0.16 mIU/mL, non-activated partial thromboplastin time (NaPTT): >250 s, FXI/FXIa ELISA: <0.31 ng/mL. Even after spiking with FXIa at a concentration 32.5 times higher than the concentration in normal specimens, the procoagulant activities were below the detection limit (<0.31 ng/mL). These results demonstrate the ability of our manufacturing process to remove procoagulant activities to below the detection limit (except by NaPTT), suggesting a reduced risk of thromboembolic events that maybe potentially caused by our IVIG preparation. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Computational Analysis of Intersubject Variability and Thrombin Generation in Dilutional Coagulopathy

DTIC Science & Technology

2012-11-01

proteins: Factor (F)II, FV, FVII , FVIII, F IX, and FX, as well as the anticoagulants antithrombin (AT) and TF pathway inhibi- tor (TFPI). The results...coagulation factors FII, FV, FVII , FVIIa, FVIII, F IX and FX, as well as the anticoagulants TFPI and AT and the throm- bin generation inducer TF. The model...scenario and tissue factor concentration. CONCLUSION: Dilutional effects on thrombin genera- tion in a human population can be predicted from trends

Measurement of Blood Coagulation Factor Synthesis in Cultures of Human Hepatocytes.

PubMed

Heinz, Stefan; Braspenning, Joris

2015-01-01

An important function of the liver is the synthesis and secretion of blood coagulation factors. Within the liver, hepatocytes are involved in the synthesis of most blood coagulation factors, such as fibrinogen, prothrombin, factor V, VII, IX, X, XI, XII, as well as protein C and S, and antithrombin, whereas liver sinusoidal endothelial cells produce factor VIII and von Willebrand factor. Here, we describe methods for the detection and quantification of most blood coagulation factors in hepatocytes in vitro. Hepatocyte cultures indeed provide a valuable tool to study blood coagulation factors. In addition, the generation and expansion of hepatocytes or hepatocyte-like cells may be used in future for cell-based therapies of liver diseases, including blood coagulation factor deficiencies.

[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.

The Carmat Bioprosthetic Total Artificial Heart Is Associated With Early Hemostatic Recovery and no Acquired von Willebrand Syndrome in Calves.

PubMed

Smadja, David M; Susen, Sophie; Rauch, Antoine; Cholley, Bernard; Latrémouille, Christian; Duveau, Daniel; Zilberstein, Luca; Méléard, Denis; Boughenou, Marie-Fazia; Belle, Eric Van; Gaussem, Pascale; Capel, Antoine; Jansen, Piet; Carpentier, Alain

2017-10-01

To determine hemostasis perturbations, including von Willebrand factor (VWF) multimers, after implantation of a new bioprosthetic and pulsatile total artificial heart (TAH). Preclinical study SETTING: Single-center biosurgical research laboratory. Female Charolais calves, 2-to-6 months old, weighing 102-to-122 kg. Surgical implantation of TAH through a mid-sternotomy approach. Four of 12 calves had a support duration of several days (4, 4, 8, and 10 days), allowing for the exploration of early steps of hemostasis parameters, including prothrombin time; coagulation factor levels (II, V, VII+X, and fibrinogen); and platelet count. Multimeric analysis of VWF was performed to detect a potential loss of high-molecular weight (HMW) multimers, as previously described for continuous flow rotary blood pumps. Despite the absence of anticoagulant treatment administered in the postoperative phase, no signs of coagulation activation were detected. Indeed, after an immediate postsurgery decrease of prothrombin time, platelet count, and coagulation factor levels, most parameters returned to baseline values. HMW multimers of VWF remained stable either after initiation or during days of support. Coagulation parameters and platelet count recovery in the postoperative phase of the Carmat TAH (Camat SA, Velizy Villacoublay Cedex, France) implantation in calves, in the absence of anticoagulant treatment and associated with the absence of decrease in HMW multimers of VWF, is in line with early hemocompatibility that is currently being validated in human clinical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative trial of the use of antiplatelet and oral anticoagulant in thrombosis prophylaxis in patients undergoing total cavopulmonary operation with extracardiac conduit: echocardiographic, tomographic, scintigraphic, clinical and laboratory analysis.

PubMed

Pessotti, Cristiane Felix Ximenes; Jatene, Marcelo Biscegli; Jatene, Ieda Biscegli; Oliveira, Patrícia Marques; Succi, Fabiana Moreira Passos; Moreira, Valeria de Melo; Lopes, Rafael Willain; Pedra, Simone Rolim Fernandes Fontes

2014-01-01

To compare the efficacy of aspirin and warfarin for prophylaxis of thrombosis in patients undergoing total cavopulmonary anastomosis. Evaluate whether coagulation factors (VII, VIII and protein C), clinical data, fenestration or hemodynamic factors, interfere with postoperative thrombosis. A prospective, randomized study of 30 patients, randomized into Group I (Warfarin) and Group II (AAS), underwent total cavopulmonary shunt with extracardiac conduit, between 2008 and 2011, with follow-up by clinical visits to evaluate side effects and adhesion. Performed transesophageal echocardiography in post operatory time, 3, 6,12 and 24 months; angiotomography at 6, 12 and 24 months to evaluate changes in the internal tube wall or thrombi and pulmonary scintigraphy to evaluate possible PTE. Two deaths in group I; 33.3% of patients had thrombus (46.7% in Group II). The previous occurrence of thrombus and low levels of coagulation protein C were the only factors that influenced the time free of thrombus (P=0.035 and 0.047). Angiotomographic evaluation: 35.7% in group II presented material accumulation greater than 2 mm (P=0.082). Scintigraphy: two patients had PTE in group II. Five patients had difficulty to comply with the treatment, 4 in group I with INR ranging from 1 to 6.4. The previous occurrence of thrombus is a risk factor for thrombosis in the postoperative period. Patients using AAS tend to deposit material in the tube wall. The small sample size did not allow to conclude which is the most effective drug in the prevention of thrombosis in this population.

The effects of proton radiation on the prothrombin and partial thromboplastin times of irradiated ferrets

PubMed Central

Krigsfeld, Gabriel S.; Sanzari, Jenine K.; Kennedy, Ann R.

2013-01-01

Purpose To determine whether proton radiation affects coagulation. Material and methods Ferrets were exposed to solar particle event-like proton radiation at doses of 0, 25, 100, or 200 centigray (cGy), and dose rates of 50 cGy/minute (high dose rate or HDR) or 50 cGy/hour (low dose rate or LDR). Plasma was isolated from blood collected prior to radiation exposure and at 3–7 h post-radiation. Prothrombin time (PT) assays and activated partial thromboplastin time (aPTT) assays were performed as were mixing studies to determine the coagulation factors involved. Results HDR and LDR exposure led to statistically significant increases in PT values. It was determined that the HDR-induced increase in PT was due to Factor VII, while Factors II, V, and VII contributed to the LDR-induced increase in PT values. Only acute LDR exposure caused an increase in aPTT values, which remained elevated for 48 h post-irradiation (which was the latest time assayed in these studies). Mixing studies revealed that Factor IX contributed to the increased aPTT values. A majority of the animals exposed at the LDR had an International Normalized Ratio approaching or surpassing 2.0. Conclusions PT/aPTT assays resulted in increased clotting times due to different coagulation factors, indicating potential radiation-induced coagulopathy. PMID:22221163

Two distinct forms of Factor VIII coagulant protein in human plasma. Cleavage by thrombin, and differences in coagulant activity and association with von Willebrand factor.

PubMed Central

Weinstein, M J; Chute, L E

1984-01-01

We have characterized Factor VIII coagulant protein, present in normal human plasma, that reacts with a specific human 125I-labeled anti-human VIII:C antigen Fab antibody fragment. Two major Factor VIII coagulant antigen populations were present. The first, approximately 85% of the total antigen, was bound to von Willebrand factor and when tested in a standard one-stage assay had Factor VIII coagulant activity. The second antigenic population, eluting near fibrinogen when plasma was gel filtered, was not bound to von Willebrand protein, did not have Factor VIII coagulant activity unless activated, but did block anti-VIII:C Fab neutralization of clotting activity. The two antigenic populations were separable by cryoprecipitation and agarose gel electrophoresis. Although the two antigenic populations differed in their Factor VIII coagulant activity and in their binding to von Willebrand factor, the principal member of both populations is of mol wt 2.4 X 10(5). Both antigens, when proteolyzed by thrombin, were quickly converted to a 1 X 10(5)-mol wt form in association with the appearance of VIII:C activity. The 1 X 10(5)-mol wt antigen was further slowly degraded to an 8 X 10(4)-mol wt form while Factor VIII coagulant activity declined. These results demonstrate the presence of an inactive Factor VIII coagulant protein in plasma, not associated with von Willebrand factor, that can react with thrombin to yield Factor VIII coagulant activity. Images PMID:6421875

Successful synthesis of active human coagulation factor VII by co-expression of mammalian gamma-glutamyl carboxylase and modification of vit.K cycle in Drosophila Schneider S2 cells.

PubMed

Nagahashi, Kotomi; Umemura, Kazuo; Kanayama, Naohiro; Iwaki, Takayuki

2017-04-01

Mammalian gamma-glutamyl carboxylase and reduced vitamin K are indispensable for synthesis of mature mammalian vitamin K dependent proteins including some of blood coagulation factors (factors II, VII, IX, and X). It was well known that Drosophila melanogaster expressed gamma-glutamyl carboxylase and possessed a vit.K cycle although native substrates for them have not been identified yet. Despite the potential capability of gamma carboxylation in D. melanogaster derived cells such as S2 cells, Drosophila gamma-glutamyl carboxylase failed to gamma carboxylate a peptide fused to the human coagulation factor IX propeptide. Thus, it had been believed that the Drosophila system was not adequate to synthesize mammalian vit.K dependent proteins. Indeed, we previously attempted to synthesize biologically active factor VII in S2 cells although we were not able to obtain it. However, recently, a successful transient expression of biologically active human factor IX from S2 cells was reported. In the present study, several expression vectors which enable expressing mammalian GGCX, VKORC1, and/or PDIA2 along with F7 were developed. S2 cells transfected with pMKA85, pMAK86, and pMAK219 successfully synthesized active FVII. Thus, mammalian GGCX was indispensable to synthesize active FVII while mammalian VKORC1 and PDIA2 were not critical but supportive factors for S2 cells.

Oral and parenteral anticoagulants: new kids on the block.

PubMed

Aditya, S

2012-01-01

Well-documented drawbacks of traditional anticoagulants have lead to the quest for an ideal anticoagulant resulting in a surge of novel anticoagulant molecules. These newer agents directly target specific steps in coagulation cascade and include newer low molecular weight heparins (adomiparin), ultra low molecular weight heparins (semuloparin, RO-14), inhibitors of activated factor II (dabigatran, AZD0837), X (rivaroxaban, apixaban, edoxaban, betrixaban), IX (REG1,2), XI (antisense oligonucleotides, BMS 262084, clavatadine A), VII/tissue factor (tifacogin, PCI 274836, and BMS 593214), V (recomodulin, solulin), VIII (TB402), dual thrombin/factor X inhibitors (EP21709, tanogitran), and newer vitamin K antagonists (tecarfarin). Direct thrombin inhibitors and Factor X inhibitors are the most clinically advanced. This article discusses the recent advances in the development of novel targets of anticoagulants. Medline, EMBASE, cochrane database, medscape, SCOPUS, and clinicaltrials.gov were searched using terms "anticoagulants", "blood coagulation inhibitors", "anticoagulants and venous thromboembolism", "anticoagulants and atrial fibrillation", and "'antithrombins." Journal articles published from 2007 to 2012 discussing pharmacology and/or clinical trials were screened.

In Vivo Bleeding Time and In Vitro Thrombelastography Measurements are Better Indicators of Dilutional Hypothermic Coagulopathy Than Prothrombin Time

DTIC Science & Technology

2007-06-01

of increased bruising, hematomas, and oozing from the recent surgical sites, or in massive hemorrhage from silent, pre-existing lesions such as peptic ... ulcers . Severe reduction of the vitamin K-dependent coagulation factors II, VII, IX, and X prolongs both PT and aPTT tests. Treatment with sodium

The Impact of Potassium Manganate (VII) on the Effectiveness of Coagulation in the Removal of Iron and Manganese from Groundwater with an Increased Content of Organic Substances

NASA Astrophysics Data System (ADS)

Krupińska, Izabela

2017-12-01

The article presents the results of studies concerning the impact of the method of Fe(II) ion oxidisation (dissolved oxygen and potassium manganate (VII)) on the effectiveness of coagulation in the removal of iron and manganese from groundwater with an increased content of organic substances. The efficiencies of two coagulants were compared: aluminium sulphate (VI) and polyaluminium chloride (Flokor 1.2A). Among the used methods of iron (II) oxidisation, the best effects have been achieved by potassium manganate (VII) because one of the oxidation products was manganese oxide (IV) precipitating from water. Better results in purifying the water were obtained with the use of a prehydrolysed coagulant Flokor 1.2 A than aluminium sulphate (VI).

Fibrinogen Vicenza and Genova II: two new cases of congenital dysfibrinogenemia with isolated defect of fibrin monomer polymerization and inhibitory activity on normal coagulation.

PubMed

Rodeghiero, F; Castaman, G C; Dal Belin Peruffo, A; Dini, E; Galletti, A; Barone, E; Gastaldi, G

1987-06-03

Two new cases of congenital dysfibrinogenemia are presented in which defective fibrin monomer polymerization and inhibitory activity on normal coagulation were observed. They have been tentatively called fibrinogen Vicenza and Genova II. The first was discovered in a family with mild bleeding diathesis, the second in an asymptomatic family. In almost all reported cases of fibrinogens with defective fibrin monomer polymerization, additional functional or structural defects have been detected. In our cases, on the contrary, detailed investigations failed to show any other abnormality. Fibrinogen Genova II is apparently identical to fibrinogen Baltimore IV, whereas fibrinogen Vicenza is similar to fibrinogen Troyes and Genova I, but also exerts an evident inhibitory activity on normal coagulation and differs from fibrinogen Genova II and Baltimore IV showing a different kinetic pattern of fibrin monomer polymerization.

Preparation of factor VII concentrate using CNBr-activated Sepharose 4B immunoaffinity chromatography

PubMed Central

Mousavi Hosseini, Kamran; Nasiri, Saleh

2015-01-01

Background: Factor VII concentrates are used in patients with congenital or acquired factor VII deficiency or treatment of hemophilia patients with inhibitors. In this research, immunoaffinity chromatography was used to purify factor VII from prothrombin complex (Prothrombin- Proconvertin-Stuart Factor-Antihemophilic Factor B or PPSB) which contains coagulation factors II, VII, IX and X. The aim of this study was to improve purity, safety and tolerability as a highly purified factor VII concentrate. Methods: PPSB was prepared using DEAE-Sephadex and was used as the starting material for purification of coagulation factor VII. Prothrombin complex was treated by solvent/detergent at 24°C for 6 h with constant stirring. The mixture of PPSB in the PBS buffer was filtered and then chromatographed using CNBr-activated Sepharose 4B coupled with specific antibody. Factors II, IX, VII, X and VIIa were assayed on the fractions. Fractions of 48-50 were pooled and lyophilized as a factor VII concentrate. Agarose gel electrophoresis was performed and Tween 80 was measured in the factor VII concentrate. Results: Specific activity of factor VII concentrate increased from 0.16 to 55.6 with a purificationfold of 347.5 and the amount of activated factor VII (FVIIa) was found higher than PPSB (4.4-fold). Results of electrophoresis on agarose gel indicated higher purity of Factor VII compared to PPSB; these finding revealed that factor VII migrated as alpha-2 proteins. In order to improve viral safety, solvent-detergent treatment was applied prior to further purification and nearly complete elimination of tween 80 (2 μg/ml). Conclusion: It was concluded that immuonoaffinity chromatography using CNBr-activated Sepharose 4B can be a suitable choice for large-scale production of factor VII concentrate with higher purity, safety and activated factor VII. PMID:26034723

Preparation of factor VII concentrate using CNBr-activated Sepharose 4B immunoaffinity chromatography.

PubMed

Mousavi Hosseini, Kamran; Nasiri, Saleh

2015-01-01

Factor VII concentrates are used in patients with congenital or acquired factor VII deficiency or treatment of hemophilia patients with inhibitors. In this research, immunoaffinity chromatography was used to purify factor VII from prothrombin complex (Prothrombin- Proconvertin-Stuart Factor-Antihemophilic Factor B or PPSB) which contains coagulation factors II, VII, IX and X. The aim of this study was to improve purity, safety and tolerability as a highly purified factor VII concentrate. PPSB was prepared using DEAE-Sephadex and was used as the starting material for purification of coagulation factor VII. Prothrombin complex was treated by solvent/detergent at 24°C for 6 h with constant stirring. The mixture of PPSB in the PBS buffer was filtered and then chromatographed using CNBr-activated Sepharose 4B coupled with specific antibody. Factors II, IX, VII, X and VIIa were assayed on the fractions. Fractions of 48-50 were pooled and lyophilized as a factor VII concentrate. Agarose gel electrophoresis was performed and Tween 80 was measured in the factor VII concentrate. Specific activity of factor VII concentrate increased from 0.16 to 55.6 with a purificationfold of 347.5 and the amount of activated factor VII (FVIIa) was found higher than PPSB (4.4-fold). RESULTS of electrophoresis on agarose gel indicated higher purity of Factor VII compared to PPSB; these finding revealed that factor VII migrated as alpha-2 proteins. In order to improve viral safety, solvent-detergent treatment was applied prior to further purification and nearly complete elimination of tween 80 (2 μg/ml). It was concluded that immuonoaffinity chromatography using CNBr-activated Sepharose 4B can be a suitable choice for large-scale production of factor VII concentrate with higher purity, safety and activated factor VII.

Interstitial deletion of chromosome 1q [del(1)(q24q25.3)] identified by fluorescence in situ hybridization and gene dosage analysis of apolipoprotein A-II, coagulation factor V, and antithrombin III

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

Takano, Takako; Yamanouchi, Yasuko; Mori, Yosuke

We report on a 12-month-old Japanese boy with an interstitial deletion of the long-arm of chromosome 1 and meningomyelocele, hydrocephalus, anal atresia, atrial septal defect, left renal agenesis, bilateral cryptorchidism, talipes equinovarus, low birth weight, growth/developmental retardation, and many minor anomalies. By conventional GTG-banding, his karyotype was first interpreted as 46,XY,de1(1)(q23q24), but it was corrected as 46,XY.ish del(1)(q24q25.3) by fluorescence in situ hybridization using 11 known cosmid clones as probes. His serum levels of apolipoprotein A-II (gene symbol: APOA2, previously assigned to 1q21-q23) and coagulation factor V (F5, 1q21-q25) were normal, while serum concentration and activity of antithrombin III (AT3,more » 1q23-q25.1) was low. The results indicated that localization of APOA2 and F5 are proximal to the deleted region and AT3 is located within the deletion extent in the patient. 16 refs., 4 figs.« less

Clinical Significance of Tissue Factor and CD13 Double-Positive Microparticles in Sirs Patients with Trauma and Severe Sepsis.

PubMed

Matsumoto, Hisatake; Yamakawa, Kazuma; Ogura, Hiroshi; Koh, Taichin; Matsumoto, Naoya; Shimazu, Takeshi

2017-04-01

Activated immune cells such as monocytes are key factors in systemic inflammatory response syndrome (SIRS) following trauma and sepsis. Activated monocytes induce almost all tissue factor (TF) expression contributing to inflammation and coagulation. TF and CD13 double-positive microparticles (TF/CD13MPs) are predominantly released from these activated monocytes. This study aimed to evaluate TF/CD13MPs and assess their usefulness as a biomarker of pathogenesis in early SIRS following trauma and sepsis. This prospective study comprising 24 trauma patients, 25 severe sepsis patients, and 23 healthy controls was conducted from November 2012 to February 2015. Blood samples were collected from patients within 24 h after injury and diagnosis of severe sepsis and from healthy controls. Numbers of TF/CD13MPs were measured by flow cytometry immediately thereafter. Injury Severity Score (ISS) and Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were calculated at patient enrollment. APACHE II and SOFA scores and International Society of Thrombosis and Haemostasis (ISTH) overt disseminated intravascular coagulation (DIC) diagnostic criteria algorithm were calculated at the time of enrollment of severe sepsis patients. Numbers of TF/CD13MPs were significantly increased in both trauma and severe sepsis patients versus controls and correlated significantly with ISS and APACHE II score in trauma patients and with APACHE II and ISTH DIC scores in severe sepsis patients. Increased numbers of TF/CD13MPs correlated significantly with severities in the acute phase in trauma and severe sepsis patients, suggesting that TF/CD13MPs are important in the pathogenesis of early SIRS following trauma and sepsis.

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

Ferrous iron/peroxymonosulfate oxidation as a pretreatment for ceramic ultrafiltration membrane: Control of natural organic matter fouling and degradation of atrazine.

PubMed

Cheng, Xiaoxiang; Liang, Heng; Ding, An; Tang, Xiaobin; Liu, Bin; Zhu, Xuewu; Gan, Zhendong; Wu, Daoji; Li, Guibai

2017-04-15

Ferrous iron/peroxymonosulfate (Fe(II)/PMS) oxidation was employed as a pretreatment method for ultrafiltration process to control membrane fouling caused by natural organic matter, including humic acid (HA), sodium alginate (SA), bovine serum albumin (BSA), and their mixture (HA-SA-BSA). To evaluate the mechanism of fouling mitigation, the effects of Fe(II)/PMS pretreatment on the characteristics of feed water were examined. The degradation of atrazine (ATZ) was also investigated and the species of generated radicals were preliminarily determined. Under the test exposure (15 and 50 μM), Fe(II)/PMS pretreatment effectively mitigated membrane fouling caused by HA, SA and HA-SA-BSA mixture, and the performance improved with the increase of Fe(II) or PMS dose; whereas aggravated BSA fouling at lower doses and fouling alleviation was observed only at a higher dose (50/50 μΜ). The fouling mitigation was mainly attributed to the effective reduction of organic loadings by coagulation with in-situ formed Fe(III). Its performance was comparable or even slightly higher than single coagulation with Fe(III), most likely due to the oxidation by Fe(II)/PMS process. Fe(II)/PMS oxidation showed better performance in reducing DOC and UV 254 , fluorescence intensities of fluorescent components and UV-absorbing compounds than single coagulation. In addition, Fe(II)/PMS pretreatment was efficient in ATZ degradation due to the generation of sulfate and hydroxyl radicals, whereas coagulation was ineffective to remove it. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Differential action of medically important Indian BIG FOUR snake venoms on rodent blood coagulation.

PubMed

Hiremath, Vilas; Nanjaraj Urs, A N; Joshi, Vikram; Suvilesh, K N; Savitha, M N; Urs Amog, Prathap; Rudresha, G V; Yariswamy, M; Vishwanath, B S

2016-02-01

Snakebite is a global health problem affecting millions of people. According to WHO, India has the highest mortality and/or morbidity due to snakebite. In spite of commendable research on Indian BIG FOUR venomous species; Naja naja and Bungarus caeruleus (elapid); Daboia russelii and Echis carinatus (viperid), no significant progress has been achieved in terms of diagnosis and management of biting species with appropriate anti-snake venom. Major hurdle is identification of offending species. Present study aims at differentiation of Indian BIG FOUR snake venoms based on their distinguish action on rodent blood coagulation. Assessment of coagulation alterations by elapid venoms showed negligible effect on re-calcification time, prothrombin time, activated partial thromboplastin time and factors assay (I, II, V, VIII and X) both in vitro and in vivo. However, viperid venoms demonstrated significant anticoagulant status due to their remarkable fibrinogen degradation potentials as supported by fibrinogenolytic activity, fibrinogen zymography and rotational thromboelastometry. Though results provide hint on probable alterations of Indian BIG FOUR snake venoms on blood coagulation, the study however needs validation from human victim's samples to ascertain its reliability for identification of biting snake species. Copyright © 2015 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

[Coagulation factor VII levels in uremic patients and theirs influence factors].

PubMed

Fang, Jun; Xia, Ling-Hui; Wei, Wen-Ning; Song, Shan-Jun

2004-12-01

This study was aimed to investigate coagulation factor VII level in uremic patients with chronic renal failure and to explore theirs influence factors. The plasma levels of coagulation factor VII were detected in 30 uremic patients with chronic renal failure before and after hemodialysis for 1 month, the factor VII activity (FVII:C) was determined by one-stage coagulation method, while activated factor VII (FVIIa) was measured by one-stage coagulation method using recombinant soluble tissue factor, and factor VII antigen was detected by ELISA. The results showed that: (1) The FVIIa, FVII:C and FVIIAg levels in chronic uremic patients before hemodialysis were 4.00 +/- 0.86 microg/L, (148.5 +/- 40.4)% and (99.8 +/- 21.1)% respectively, which were significantly increased, as compared with healthy controls [2.77 +/- 1.02 microg/L, (113.1 +/- 33.0)% and (73.7 +/- 18.3)% respectively, P < 0.05]. (2) After hemodialysis the FVIIa, FVII:C and FVIIAg levels in uremic patients significantly enhanced to 5.56 +/- 1.45 microg/L, (200.8 +/- 68.7)% and (124.1 +/- 19.3)% respectively (P < 0.05). (3) The abnormal increase of coagulation factor VII was positively correlated with levels of blood uria nitrogen and serum creatinine before hemodialysis but not after hemodialysis. It is concluded that the enhanced levels of coagulation factor VII in chronic uremic patients suggested abnormal activated state, herperactivity and elevated production of factor VII which correlated with renal functional injury. The abnormality of factor VII in uremia may be aggravated by hemodialysis. Coagulation factor (FVII) may be a risk factor for cardiovascular events in uremic patients who especially had been accepted long-term hemodialysis.

[Effects of various adsorbants on coagulation factors (author's transl)].

PubMed

Soulier, J P; Prou-Wartelle, O

1975-01-01

Adsorption of clotting factors by various adsorbants is studied (tricalcium phosphate, baryum sulfate or carbonate or citrate, calcium oxalate, aluminium hydroxyde and several silicate such as: kaolin, celite, bentonite, attapulgite, beidellite, asbestos). The main properties of each adsorbant are listed as well as several applications such as: selective adsorption of fibrinogen, separation between fibrinogen and factor VIII, separation of factor II from the other components of the prothrombin complex. Activation of factors XII and XI by the various silicates, as well as the activation of factor V by attapulgite are studied. Finally, the action of such adsorbants on the fibrinolytic system is summarized.

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.

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.

Direct bone morphogenetic protein 2 and Indian hedgehog gene transfer for articular cartilage repair using bone marrow coagulates.

PubMed

Sieker, J T; Kunz, M; Weißenberger, M; Gilbert, F; Frey, S; Rudert, M; Steinert, A F

2015-03-01

Bone morphogenetic protein 2 (BMP-2, encoded by BMP2) and Indian hedgehog protein (IHH, encoded by IHH) are well known regulators of chondrogenesis and chondrogenic hypertrophy. Despite being a potent chondrogenic factor BMP-2 was observed to induce chondrocyte hypertrophy in osteoarthritis (OA), growth plate cartilage and adult mesenchymal stem cells (MSCs). IHH might induce chondrogenic differentiation through different intracellular signalling pathways without inducing subsequent chondrocyte hypertrophy. The primary objective of this study is to test the efficacy of direct BMP2 and IHH gene delivery via bone marrow coagulates to influence histological repair cartilage quality in vivo. Vector-laden autologous bone marrow coagulates with 10(11) adenoviral vector particles encoding BMP2, IHH or the Green fluorescent protein (GFP) were delivered to 3.2 mm osteochondral defects in the trochlea of rabbit knees. After 13 weeks the histological repair cartilage quality was assessed using the ICRS II scoring system and the type II collagen positive area. IHH treatment resulted in superior histological repair cartilage quality than GFP controls in all of the assessed parameters (with P < 0.05 in five of 14 assessed parameters). Results of BMP2 treatment varied substantially, including severe intralesional bone formation in two of six joints after 13 weeks. IHH gene transfer is effective to improve repair cartilage quality in vivo, whereas BMP2 treatment, carried the risk intralesional bone formation. Therefore IHH protein can be considered as an attractive alternative candidate growth factor for further preclinical research and development towards improved treatments for articular cartilage defects. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

An interactive mutation database for human coagulation factor IX provides novel insights into the phenotypes and genetics of hemophilia B.

PubMed

Rallapalli, P M; Kemball-Cook, G; Tuddenham, E G; Gomez, K; Perkins, S J

2013-07-01

Factor IX (FIX) is important in the coagulation cascade, being activated to FIXa on cleavage. Defects in the human F9 gene frequently lead to hemophilia B. To assess 1113 unique F9 mutations corresponding to 3721 patient entries in a new and up-to-date interactive web database alongside the FIXa protein structure. The mutations database was built using MySQL and structural analyses were based on a homology model for the human FIXa structure based on closely-related crystal structures. Mutations have been found in 336 (73%) out of 461 residues in FIX. There were 812 unique point mutations, 182 deletions, 54 polymorphisms, 39 insertions and 26 others that together comprise a total of 1113 unique variants. The 64 unique mild severity mutations in the mature protein with known circulating protein phenotypes include 15 (23%) quantitative type I mutations and 41 (64%) predominantly qualitative type II mutations. Inhibitors were described in 59 reports (1.6%) corresponding to 25 unique mutations. The interactive database provides insights into mechanisms of hemophilia B. Type II mutations are deduced to disrupt predominantly those structural regions involved with functional interactions. The interactive features of the database will assist in making judgments about patient management. © 2013 International Society on Thrombosis and Haemostasis.

Determinants of drug costs in hopitalised patients with haemophilia: impact of recombinant activated factor VII.

PubMed

Galanaud, Jean Philippe; Pelletier-Fleury, Nathalie; Logerot-Lebrun, Hélène; Lambert, Thierry

2003-01-01

To analyse the determinants of anti-haemophilic drug costs in hospitalised patients with haemophilia and to estimate the impact of recombinant activated factor VII (rFVIIa) therapy on this expenditure. The perspective of the study was from the viewpoint of the hospital. A prospective study was carried out. All patients with haemophilia who were hospitalised in 1999 in Bicêtre public hospital, Paris, France were included in the cohort. For each of the 96 patients (154 hospital stays), we estimated the costs of anti-haemophilic drugs (coagulation concentrates) used. Costs were then stratified by different variables (severity of the disease, presence of a circulating inhibitor to coagulation factors, etc.) and a multivariate model was developed to determine the relationship between these variables and total anti-haemophilic drug costs, while controlling for potential confounders. Our study revealed: (i) the independent role of the five following variables in contributing to high anti-haemophilic drug expenditure: presence of a circulating inhibitor to coagulation factors, odds ratio (OR) = 16.9 (95% CI: 4.3-66); severity of the disease (factor VIII or factor IX < or =0.01 IU/mL), OR = 3.7 (95% CI: 1.6-8.6); length of hospital stay >4 days, OR = 8 (95% CI: 2.2-29.4); age >18 years old, OR = 6.2 (95% CI: 1.6-24.5); and surgical reasons for hospitalisation (whether surgery was haemophilia related [OR = 35.7 (95% CI: 7.3-175)] or not [OR = 5.4 (95% CI: 1.3-22.5)]); (ii) the large share that rFVIIa represented in this expenditure on medicines: rFVIIa was used in 20.1% of hospital stays and accounted for 56.2% of the total anti-haemophilic drug costs, which were estimated at 4,384,732 Euros (2000 values). Our data underline the heavy cost of the treatment of haemophilic patients with an inhibitor to coagulation factors. But, to the question of whether the high expenditure linked to rFVIIa utilisation will be balanced out by later benefits, it is not yet possible to reply with any certainty; further cost-benefit evaluation should be carried out.

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.

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.

[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.

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.

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

Haemostatic profile of healthy premature small for gestational age neonates.

PubMed

Mitsiakos, George; Giougi, Evaggelia; Chatziioannidis, Ilias; Karagianni, Paraskevi; Papadakis, Emmanouil; Tsakalidis, Christos; Papaioannou, Georgia; Malindretos, Pavlos; Nikolaidis, Nikolaos

2010-08-01

The pathogenetic profile of premature Small for Gestational Age (SGA) neonates is strongly related to their haemostatic equilibrium, which is inadequately understood. To evaluate coagulation and fibrinolysis in premature SGA neonates before intervening with Vitamin K administration. We performed a comparison of coagulation, natural inhibitors and fibrinolysis between SGA and Appropriate for Gestational Age (AGA) infants born prematurely [gestational age (G.A.) <37 weeks]. Study population consisted of 139 preterm newborns, 68 of whom were SGA (25 males and 43 females), while 71 were AGA (37 males and 34 females) that consisted the control group. Blood samples were obtained within 30 minutes following birth and before the administration of vitamin K. Investigation included: PT, INR, APTT, fibrinogen, coagulation factors II, V, VII, VIII, IX, X, XI, XII, von Willebrand factor, protein C and free protein S, antithrombin (AT), APCR, tPA and PAI-1. The independent t-test and the Mann-Whitney U test were used to compare the differences between the values of haemostatic parameters. Premature SGA infants presented significantly lower levels of fibrinogen (p<0.029) and higher levels of VIIIc factor, APCR, tPA and PAI-1 (p<0.041, 0.017, 0.021 and 0.019 respectively). The two groups had similar demographic characteristics (except from birth weight), without significant differences in the values of other haemostatic parameters. Despite the statistically significant differentiation in the levels of fibrinogen, VIIIc factor, APCR, tPA and PAI-1, the rest of haemostatic parameters have similar values between SGA and AGA preterms. (c) 2010 Elsevier Ltd. All rights reserved.

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.

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 are slightly enhanced in blood ex vivo and suppression of thrombin generation is not observed. A decrease in antithrombin reactivity is one potential mechanism contributing to these outcomes. © 2016 International Society on Thrombosis and Haemostasis.

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.

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.

Polymorphisms of the factor VII gene associated with the low activities of vitamin K-dependent coagulation factors in one-month-old infants.

PubMed

Ito, Koichi; Goto, Kenji; Sugiura, Tokio; Muramatsu, Kanji; Ando, Toshihiro; Maniwa, Hiroko; Yokoyama, Takao; Sugiyama, Kohachiro; Togari, Hajime

2007-01-01

Despite administration of vitamin K (VK), some infants show lower activity of VK-dependent coagulation factors and they could develop intracranial hemorrhage. For preventing VK deficiency bleeding (VKDB) in infants, oral administration of VK and a screening test for VK deficiency are carried out in Japan. For the screening, the total activity of VK-dependent coagulation factors is measured using a commercial product, Normotest. This study was undertaken to clarify the importance of the following genetic and environmental factors on the coagulation status in one-month-old infants: two polymorphisms in the factor VII gene, -323P0/10 (a 10-bp insertion in the promoter region at position -323) and R353Q (the replacement of arginine [R] with glutamine [Q] at residue 353) and sex, age, gestational age, birth weight, and feeding regimen. Two hundred Japanese infants (34.6 +/- 4.0 days old) were screened for VK-dependent coagulation activity with Normotest and were genotyped for the two polymorphisms. Among the subjects screened, 18 infants (9%) carried the P10 allele and 26 (13%) carried the R353Q allele. Multiple regression analysis showed that the 10-bp inserted (P10) allele or the Q allele was associated with the lower coagulation activities. The coagulation activities for the R/Q genotype were significantly lower than those for the R/R genotype and those for the P0/P10 genotype were significantly lower than those for the P0/P0 genotype. Therefore, infants who carry the P10 allele or the Q allele show lower activity of VK-dependent coagulation factors. These infants may have a higher risk of VKDB manifestation.

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 Authors.

Fe(II)-regulated moderate pre-oxidation of Microcystis aeruginosa and formation of size-controlled algae flocs for efficient flotation of algae cell and organic matter.

PubMed

Qi, Jing; Lan, Huachun; Liu, Ruiping; Liu, Huijuan; Qu, Jiuhui

2018-06-15

The coagulation/flocculation/flotation (C/F/F) process is becoming a popular method for algae-laden water treatment. However, the efficiency of flotation is highly dependent on the ability of the preceding coagulation/flocculation process to form flocculated algae flocs. This study aims to improve the Microcystis aeruginosa flotation efficiency from algae cell and organic matter aspects by applying Fe(II)-regulated pretreatment enhanced Al coagulation process. The ability of the C/F/F process to remove cyanobacterial cells can be enhanced from 8% to 99% at a Fe(II) dose of 30 μM. The Al dose needed can be reduced by more than half while achieving successful flotation. The introduced Fe(II) after KMnO 4 can not only realize moderate pre-oxidation of cyanobacterial cells, but also form in-situ Fe(III). The DOC value can also be decreased significantly due to the formation of in-situ Fe(III), which is more efficient in dissolved organic matter (DOM) removal compared with pre-formed Fe(III). In addition, the gradually hydrolyzed in-situ Fe(III) can facilitate the hydrolysis of Al as a dual-coagulant and promote the clustering and cross-linking of Al hydrolyzates, which can enhance the formation of size-controlled algae flocs. Finally, the size-controlled algae flocs can be effectively floated by the bubbles released in the flotation process due to the efficient collision and attachment between flocs and bubbles. Therefore, the efficient flotation of algae cell and organic matter can be realized by the Fe(II) regulated moderate pre-oxidation of M. aeruginosa and formation of size-controlled algae flocs. Copyright © 2018 Elsevier Ltd. All rights reserved.

A retrospective discussion of the prognostic value of combining prothrombin time(PT) and fibrinogen(Fbg) in patients with Hepatocellular carcinoma.

PubMed

Wang, Xue-Ping; Mao, Min-Jie; He, Zhong-Lian; Zhang, Lin; Chi, Pei-Dong; Su, Jia-Rui; Dai, Shu-Qin; Liu, Wan-Li

2017-01-01

Aims: The levels of coagulation system tests have been studied in various cancers. In this study, our aim is to evaluate the prognostic value of pretreatment plasma coagulation tests in hepatocellular carcinoma (HCC) patients. Patient and methods: A retrospective study was performed in 539 patients with HCC, and follow-up period was at least 60 months until recurrence or death. The prognostic significance of coagulation system tests (prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen) were determined by univariate and multivariate Cox hazard models. Then, according to the results of the multivariate analyses, we proposed the coagulation-Based Stage, which combined the independent risk factors (prothrombin time and fibrinogen). Results: Coagulation system tests including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fbg) were analyzed. Patients with prolonged PT (≥12.1 sec) levels had significantly poor overall survival (OS) and disease-free survival (DFS), not only in the entire cohort (HR: 1.661, 95%CI: 1.125-2.451, p= 0.011 vs. HR: 1.660, 95%CI: 1.125-2.451, p= 0.011), but also in the subgroups stratified by pathological stage (stage I-II and stage III-IV). Additionally, high Fbg (≥2.83 g/L) levels experienced significantly decreased OS and DFS (HR: 2.158, 95%CI: 1.427-3.263, p< 0.001 vs. HR: 2.161, 95%CI: 1.429-3.267, p< 0.001), not only in the entire cohort but also in the subgroups stratified by pathological stage (stage I-II and stage III-IV). All the patients were then stratified (based on combined PT and Fbg) into three groups, The OS for HCC patients were (41.37±17.76), (31.83±19.84) and (18.68±18.41) months, and the DFS for HCC patients were (41.15±17.88), (31.65±19.81) and (18.66±18.39) months. Conclusions: Our findings suggest that the combination of plasma PT and Fbg levels should be evaluated as the valuable predictor of survival in patients with HCC.

Exosites in the substrate specificity of blood coagulation reactions.

PubMed

Bock, P E; Panizzi, P; Verhamme, I M A

2007-07-01

The specificity of blood coagulation proteinases for substrate, inhibitor, and effector recognition is mediated by exosites on the surfaces of the catalytic domains, physically separated from the catalytic site. Some thrombin ligands bind specifically to either exosite I or II, while others engage both exosites. The involvement of different, overlapping constellations of exosite residues enables binding of structurally diverse ligands. The flexibility of the thrombin structure is central to the mechanism of complex formation and the specificity of exosite interactions. Encounter complex formation is driven by electrostatic ligand-exosite interactions, followed by conformational rearrangement to a stable complex. Exosites on some zymogens are in low affinity proexosite states and are expressed concomitant with catalytic site activation. The requirement for exosite expression controls the specificity of assembly of catalytic complexes on the coagulation pathway, such as the membrane-bound factor Xa*factor Va (prothrombinase) complex, and prevents premature assembly. Substrate recognition by prothrombinase involves a two-step mechanism with initial docking of prothrombin to exosites, followed by a conformational change to engage the FXa catalytic site. Prothrombin and its activation intermediates bind prothrombinase in two alternative conformations determined by the zymogen to proteinase transition that are hypothesized to involve prothrombin (pro)exosite I interactions with FVa, which underpin the sequential activation pathway. The role of exosites as the major source of substrate specificity has stimulated development of exosite-targeted anticoagulants for treatment of thrombosis.

Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees

PubMed Central

1994-01-01

The role of interleukin 6 (IL-6) in the toxic sequelae of sepsis is controversial. To assess the part of IL-6 in inflammatory responses to endotoxin, we investigated eight chimpanzees after either a bolus intravenous injection of Escherichia coli endotoxin (n = 4; 4 ng/kg) or after the same dose of endotoxin with a simultaneous bolus intravenous injection of an anti-IL-6 mAb (30 mg; n = 4). Anti-IL-6 did not affect the induction of the cytokine network (tumor necrosis factor [TNF], soluble TNF receptors types I and II, and IL-8) by endotoxin, nor did it influence the occurrence of a neutrophilic leukocytosis and neutrophil degranulation, as monitored by the measurement of elastase- alpha 1-antitrypsin complexes. In contrast, anti-IL-6 markedly attenuated endotoxin-induced activation of coagulation, monitored with the plasma levels of the prothrombin fragment F1+2 and thrombin- antithrombin III complexes, whereas activation of fibrinolysis, determined with the plasma concentrations of plasmin-alpha 2- antiplasmin complexes, remained unaltered. We conclude that IL-6 does not have a feedback effect on the release of other cytokines after injection of endotoxin, and that it is not involved in endotoxin- induced neutrophilia or neutrophil degranulation. IL-6 is, however, an important intermediate factor in activation of coagulation in low grade endotoxemia in chimpanzees. PMID:8145042

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

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.

Enzymatically oxidized phospholipids restore thrombin generation in coagulation factor deficiencies.

PubMed

Slatter, David A; Percy, Charles L; Allen-Redpath, Keith; Gajsiewicz, Joshua M; Brooks, Nick J; Clayton, Aled; Tyrrell, Victoria J; Rosas, Marcela; Lauder, Sarah N; Watson, Andrew; Dul, Maria; Garcia-Diaz, Yoel; Aldrovandi, Maceler; Heurich, Meike; Hall, Judith; Morrissey, James H; Lacroix-Desmazes, Sebastien; Delignat, Sandrine; Jenkins, P Vincent; Collins, Peter W; O'Donnell, Valerie B

2018-03-22

Hemostatic defects are treated using coagulation factors; however, clot formation also requires a procoagulant phospholipid (PL) surface. Here, we show that innate immune cell-derived enzymatically oxidized phospholipids (eoxPL) termed hydroxyeicosatetraenoic acid-phospholipids (HETE-PLs) restore hemostasis in human and murine conditions of pathological bleeding. HETE-PLs abolished blood loss in murine hemophilia A and enhanced coagulation in factor VIII- (FVIII-), FIX-, and FX-deficient human plasma . HETE-PLs were decreased in platelets from patients after cardiopulmonary bypass (CPB). To explore molecular mechanisms, the ability of eoxPL to stimulate individual isolated coagulation factor/cofactor complexes was tested in vitro. Extrinsic tenase (FVIIa/tissue factor [TF]), intrinsic tenase (FVIIIa/FIXa), and prothrombinase (FVa/FXa) all were enhanced by both HETE-PEs and HETE-PCs, suggesting a common mechanism involving the fatty acid moiety. In plasma, 9-, 15-, and 12-HETE-PLs were more effective than 5-, 11-, or 8-HETE-PLs, indicating positional isomer specificity. Coagulation was enhanced at lower lipid/factor ratios, consistent with a more concentrated area for protein binding. Surface plasmon resonance confirmed binding of FII and FX to HETE-PEs. HETE-PEs increased membrane curvature and thickness, but not surface charge or homogeneity, possibly suggesting increased accessibility to cations/factors. In summary, innate immune-derived eoxPL enhance calcium-dependent coagulation factor function, and their potential utility in bleeding disorders is proposed.

Enzymatically oxidized phospholipids restore thrombin generation in coagulation factor deficiencies

PubMed Central

Slatter, David A.; Percy, Charles L.; Allen-Redpath, Keith; Gajsiewicz, Joshua M.; Brooks, Nick J.; Tyrrell, Victoria J.; Lauder, Sarah N.; Watson, Andrew; Dul, Maria; Garcia-Diaz, Yoel; Aldrovandi, Maceler; Heurich, Meike; Hall, Judith; Lacroix-Desmazes, Sebastien; Delignat, Sandrine; Jenkins, P. Vincent; Collins, Peter W.; O’Donnell, Valerie B.

2018-01-01

Hemostatic defects are treated using coagulation factors; however, clot formation also requires a procoagulant phospholipid (PL) surface. Here, we show that innate immune cell–derived enzymatically oxidized phospholipids (eoxPL) termed hydroxyeicosatetraenoic acid–phospholipids (HETE-PLs) restore hemostasis in human and murine conditions of pathological bleeding. HETE-PLs abolished blood loss in murine hemophilia A and enhanced coagulation in factor VIII- (FVIII-), FIX-, and FX-deficient human plasma . HETE-PLs were decreased in platelets from patients after cardiopulmonary bypass (CPB). To explore molecular mechanisms, the ability of eoxPL to stimulate individual isolated coagulation factor/cofactor complexes was tested in vitro. Extrinsic tenase (FVIIa/tissue factor [TF]), intrinsic tenase (FVIIIa/FIXa), and prothrombinase (FVa/FXa) all were enhanced by both HETE-PEs and HETE-PCs, suggesting a common mechanism involving the fatty acid moiety. In plasma, 9-, 15-, and 12-HETE-PLs were more effective than 5-, 11-, or 8-HETE-PLs, indicating positional isomer specificity. Coagulation was enhanced at lower lipid/factor ratios, consistent with a more concentrated area for protein binding. Surface plasmon resonance confirmed binding of FII and FX to HETE-PEs. HETE-PEs increased membrane curvature and thickness, but not surface charge or homogeneity, possibly suggesting increased accessibility to cations/factors. In summary, innate immune-derived eoxPL enhance calcium-dependent coagulation factor function, and their potential utility in bleeding disorders is proposed. PMID:29563336

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.

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.

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

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.

Comparison of inclined plate sedimentation and dissolved air flotation for the minimisation of subsequent nitrogenous disinfection by-product formation.

PubMed

Chu, Wen-Hai; Gao, Nai-Yun; Templeton, Michael R; Yin, Da-Qiang

2011-04-01

The formation of disinfection by-products (DBPs), including both nitrogenous disinfection by-products (N-DBPs) and carbonaceous disinfection by-products (C-DBPs), was investigated upon chlorination of water samples following two treatment processes: (i) coagulation-inclined plate sedimentation (IPS)-filtration and (ii) coagulation-dissolved air flotation (DAF)-filtration. The removal of algae, dissolved organic nitrogen (DON), dissolved organic carbon (DOC) and UV(254) by coagulation-DAF-filtration was superior to coagulation-IPS-filtration. On average, 53%, 53% and 31% of DOC, DON and UV(254) were removed by coagulation-DAF-filtration process, which were higher than 47%, 31% and 27% of that by coagulation-IPS-filtration process. Additionally, coagulation-IPS-filtration performed less well at removing the low molecular weight organics than coagulation-DAF-filtration process. The concentrations of chloroform, dichloroacetamide (DCAcAm) and dichloroacetonitrile (DCAN) formed during chlorination after coagulation-DAF-filtration reached their maximum values of 13, 1.5 and 4.7μgL(-1), respectively, and were lower than those after coagulation-IPS-filtration with the maximum detected levels of 17, 2.9 and 6.3μgL(-1). However, the trichloronitromethane (TCNM) concentration after the two processes was similar, suggesting that DON may have less of a contribution to TCNM formation than DCAcAm and DCAN. Copyright © 2011 Elsevier Ltd. All rights reserved.

Review on Vitamin K Deficiency and its Biomarkers: Focus on the Novel Application of PIVKA-II in Clinical Practice.

PubMed

Dong, Rui; Wang, Nianyue; Yang, Yongfeng; Ma, Li; Du, Qiang; Zhang, Wei; Tran, Anh H; Jung, Haiyoung; Soh, Andrew; Zheng, Yijie; Zheng, Shan

2018-04-01

Vitamin K (VK) is a co-factor of the γ-glutamyl carboxylase that catalyzes the conversion of glutamate residues to γ-carboxyglutamate in VK-dependent proteins. The carboxylation reaction imparts the essential calcium-binding residues for the biological function of several proteins involved in the process of coagulation and bone metabolism. VK deficiency is frequently encountered in newborns and can lead to fatal hemorrhagic complications. This review describes and discusses the clinical application of VK deficiency testing. References and data were researched in PubMed and reviewed. In adults, VK deficiency is associated with uncontrolled bleeding, liver dysfunction, osteoporosis, and coronary diseases. An improved understanding of the role of VK deficiency in health and illness can be achieved by setting a gold-standard in the inter-laboratory estimations of VK. However, conventional methods used to measure the VK deficiency based upon the coagulation time lack sensitivity and specificity. Recently, the alterations in proteins induced by VK absence or antagonism (PIVKA) have proven to be suitable biomarkers for detecting VK deficiency. The measurement of PIVKA-II exhibits an enhanced sensitivity and specificity in comparison to other methods conventionally used for the assessment of VK deficiency in newborns and adults. PIVKA-II could potentially be employed as an effective biomarker in the diagnosis of VK deficiency.

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.

Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia.

PubMed

Pawlinski, Rafal; Pedersen, Brian; Schabbauer, Gernot; Tencati, Michael; Holscher, Todd; Boisvert, William; Andrade-Gordon, Patricia; Frank, Rolf Dario; Mackman, Nigel

2004-02-15

Sepsis is associated with a systemic activation of coagulation and an excessive inflammatory response. Anticoagulants have been shown to inhibit both coagulation and inflammation in sepsis. In this study, we used both genetic and pharmacologic approaches to analyze the role of tissue factor and protease-activated receptors in coagulation and inflammation in a mouse endotoxemia model. We used mice expressing low levels of the procoagulant molecule, tissue factor (TF), to analyze the effects of TF deficiency either in all tissues or selectively in hematopoietic cells. Low TF mice had reduced coagulation, inflammation, and mortality compared with control mice. Similarly, a deficiency of TF expression by hematopoietic cells reduced lipopolysaccharide (LPS)-induced coagulation, inflammation, and mortality. Inhibition of the down-stream coagulation protease, thrombin, reduced fibrin deposition and prolonged survival without affecting inflammation. Deficiency of either protease activated receptor-1 (PAR-1) or protease activated receptor-2 (PAR-2) alone did not affect inflammation or survival. However, a combination of thrombin inhibition and PAR-2 deficiency reduced inflammation and mortality. These data demonstrate that hematopoietic cells are the major pathologic site of TF expression during endotoxemia and suggest that multiple protease-activated receptors mediate crosstalk between coagulation and inflammation.

Effect of circulating tissue factor on hypercoagulability in type 2 diabetes mellitus studied by rheometry and dielectric blood coagulometry.

PubMed

Uchimura, Isao; Kaibara, Makoto; Nagasawa, Masayuki; Hayashi, Yoshihito

2016-01-01

Hypercoagulability in type 2 diabetes mellitus (T2DM) patients increases their risk of cardiovascular diseases. The aim of this work was to investigate the hypercoagulation mechanism in T2DM patients in terms of circulating tissue factor (TF). Whole blood coagulation tests by damped oscillation rheometry and dielectric blood coagulometry (DBCM) were performed. The average coagulation time was significantly shorter for T2DM patients than for healthy controls. In vitro addition of either anti-TF or anti-activated factor VII (FVIIa) antibody to hypercoagulable blood samples prolonged coagulation times for one group of patients, while coagulation times remained short for another group. The levels of circulating TF were estimated in the former group by measuring the coagulation times for blood samples from healthy subjects with addition of various concentrations of TF and comparing them with the coagulation times for the group. The results indicated that the levels of circulating TF were on the order of subpicomolar at most. Circulating TF is at least partially responsible for a hypercoagulable group of T2DM patients, while an abnormality in the intrinsic coagulation pathway probably occurs in the other group.

[Abnormality of blood coagulation indexes in patients with de novo acute leukemia and its clinical significance].

PubMed

Xiao, Fang-Fang; Hu, Kai-Xun; Guo, Mei; Qiao, Jian-Hui; Sun, Qi-Yun; Ai, Hui-Sheng; Yu, Chang-Lin

2013-04-01

To explore hemorrhage risk and the clinical significance of abnormal change of prothrombin time (PT), activated partial thromboplastin time (APTT), plasma fibrinogen (FIB), plasma thrombin time (TT) and d-dimer (D-D) in de novo acute leukemia (except for APL), the different bleeding manifestations of 114 cases of de novo acute leukemia with different coagulation indexes were analyzed retrospectively. The correlation between these blood coagulation indexes and the possible correlative clinical characteristics were analysed, including age, sex, type of acute leukemia, initial white blood cell(WBC) and platelet(Plt) count, the proportion of blast cells in bone marrow and cytogenetic abnormality of patients at diagnosis. The results indicated that the incidence of abnormal blood coagulation was as high as 78.1% for de novo AL patients. These patients with 5 normal blood coagulation indexes may have mild bleeding manifestation, but the more abnormal indexes, the more severe bleeding. Both PT and D-D were sensitive indexes for diagnosis of level II bleeding. Incidence of abnormal blood coagulation significantly correlates with the proportion of blast cells in bone marrow (χ(2) = 4.184, OR = 1.021, P < 0.05) and more with D-D (P < 0.01), while age, sex, type of AL, WBC count, Plt count and abnormality of cytogenetics did not correlate with abnormal blood coagulation. It is concluded that the coagulation and fibrinolysis are abnormal in most patients with de novo acute leukemia. More abnormal indexes indicate more severe bleeding, and both PT and D-D are sensitive indexes for diagnosis of level II bleeding. Higher proportion of blast cells in bone marrow predicts higher incidence of abnormal blood clotting. Acute leukemia with elderly age, high white blood cell count and adverse cytogenetics do not predict severer abnormal blood clotting. Detection of PT, APTT, TT, FIB, and D-D may help to judge whether the patients are in a state of hypercoagulability or disseminated intravenous coagulation, which will provide experiment evidences for early intervention and medication.

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.

Acute Coagulopathy of Trauma in the Rat

DTIC Science & Technology

2013-01-01

coagulation and include prothrombin complex con- centrate, recombinant activated FVII , tranexamic acid, and fibrinogen (13, 14). The degree of coagulopathy...extrinsic pathway using tissue factor to initiate coagulation as would be expected following tissue injury. Cytochalasin D (inhibit platelet function in...chalasin D. ! Angle was elevated, and clotting time was shortened, suggesting that coagulation factors were activated and adequate to support thrombin

21 CFR 864.7750 - Prothrombin time test.

Code of Federal Regulations, 2010 CFR

2010-04-01

... the detection of possible clotting factor deficiencies in the extrinsic coagulation pathway, which involves the reaction between coagulation factors III and VII, and to monitor patients receiving coumarin...

PubMed Central

Baillargeon, L.; Drouin, J.; Desjardins, L.; Leroux, D.; Audet, D.

1993-01-01

The purpose of this study, which took the form of a two-period cross-over clinical trial, was to determine whether a homeopathic substance, Arnica Montana, significantly decreased bleeding time (Simplate II) and to describe its impact on various blood coagulation tests. It was not shown that this substance had a significant impact on various parameters of blood coagulation in healthy volunteers in the period immediately following administration [corrected]. PMID:7903572

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.

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.

Analysis of aggregation of platelets in thrombosis

NASA Astrophysics Data System (ADS)

Ahuja, Suresh

Platelets are key players in thrombus formation by first rolling over collagen bound von Willebrand factor followed by formation of a stable interaction with collagen. The first adhered platelets bind additional platelets until the whole injury is sealed off by a platelet aggregate. The coagulation system stabilizes the formed platelet plug by creating a tight fibrin network, and then wound contraction takes place because of morphological changes in platelets. Coagulation takes place by platelet activation and aggregation mainly through fibrinogen polymerization into fibrin fibers. The process includes multiple factors, such as thrombin, plasmin, and local shear-rate which regulate and control the process. Coagulation can be divided into two pathways: the intrinsic pathway and the extrinsic pathway. The intrinsic pathway is initiated by the exposure of a negatively charged. It is able to activate factor XII, using a complex reaction that includes prekallikrein and high-molecular-weight kininogen as cofactors.. Thrombin is the final enzyme that is needed to convert fibrinogen into fibrin. The extrinsic pathway starts with the exposure of tissue factor to the circulating blood, which is the major initiator of coagulation. There are several feedback loops that reinforce the coagulation cascade, resulting in large amounts of thrombin. It is dependent on the presence of pro-coagulant surfaces of cells expressing negatively charged phospholipids--which include phosphatidylserine (PS)--on their outer membrane. PS-bearing surfaces are able to increase the efficiency of the reactions by concentrating and co-localizing coagulation factors.. Aggregation of platelets are analyzed and compared to adhesion of platelet to erythrocyte and to endothelial cells. This abstract is replacing MAR16-2015-020003.

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

Effect of circulating tissue factor on hypercoagulability in type 2 diabetes mellitus studied by rheometry and dielectric blood coagulometry

PubMed Central

Uchimura, Isao; Kaibara, Makoto; Nagasawa, Masayuki; Hayashi, Yoshihito

2016-01-01

Background: Hypercoagulability in type 2 diabetes mellitus (T2DM) patients increases their risk of cardiovascular diseases. Objective: The aim of this work was to investigate the hypercoagulation mechanism in T2DM patients in terms of circulating tissue factor (TF). Methods: Whole blood coagulation tests by damped oscillation rheometry and dielectric blood coagulometry (DBCM) were performed. Results: The average coagulation time was significantly shorter for T2DM patients than for healthy controls. In vitro addition of either anti-TF or anti-activated factor VII (FVIIa) antibody to hypercoagulable blood samples prolonged coagulation times for one group of patients, while coagulation times remained short for another group. The levels of circulating TF were estimated in the former group by measuring the coagulation times for blood samples from healthy subjects with addition of various concentrations of TF and comparing them with the coagulation times for the group. The results indicated that the levels of circulating TF were on the order of subpicomolar at most. Conclusions: Circulating TF is at least partially responsible for a hypercoagulable group of T2DM patients, while an abnormality in the intrinsic coagulation pathway probably occurs in the other group. PMID:27858671

Elementary sulfur in effluent from denitrifying sulfide removal process as adsorbent for zinc(II).

PubMed

Chen, Chuan; Zhou, Xu; Wang, Aijie; Wu, Dong-hai; Liu, Li-hong; Ren, Nanqi; Lee, Duu-Jong

2012-10-01

The denitrifying sulfide removal (DSR) process can simultaneously convert sulfide, nitrate and organic compounds into elementary sulfur (S(0)), di-nitrogen gas and carbon dioxide, respectively. However, the S(0) formed in the DSR process are micro-sized colloids with negatively charged surface, making isolation of S(0) colloids from other biological cells and metabolites difficult. This study proposed the use of S(0) in DSR effluent as a novel adsorbent for zinc removal from wastewaters. Batch and continuous tests were conducted for efficient zinc removal with S(0)-containing DSR effluent. At pH<7.5, removal rates of zinc(II) were increased with increasing pH. The formed S(0) colloids carried negative charge onto which zinc(II) ions could be adsorbed via electrostatic interactions. The zinc(II) adsorbed S(0) colloids further enhanced coagulation-sedimentation efficiency of suspended solids in DSR effluents. The DSR effluent presents a promising coagulant for zinc(II) containing wastewaters. Copyright © 2012 Elsevier Ltd. All rights reserved.

The polyphosphate–factor XII pathway drives coagulation in prostate cancer-associated thrombosis

PubMed Central

Nickel, Katrin F.; Ronquist, Göran; Langer, Florian; Labberton, Linda; Fuchs, Tobias A.; Bokemeyer, Carsten; Sauter, Guido; Graefen, Markus; Mackman, Nigel; Stavrou, Evi X.; Ronquist, Gunnar

2015-01-01

Cancer is a leading cause of thrombosis. We identify a new procoagulant mechanism that contributes to thromboembolism in prostate cancer and allows for safe anticoagulation therapy development. Prostate cancer-mediated procoagulant activity was reduced in plasma in the absence of factor XII or its substrate of the intrinsic coagulation pathway factor XI. Prostate cancer cells and secreted prostasomes expose long chain polyphosphate on their surface that colocalized with active factor XII and initiated coagulation in a factor XII-dependent manner. Polyphosphate content correlated with the procoagulant activity of prostasomes. Inherited deficiency in factor XI or XII or high-molecular-weight kininogen, but not plasma kallikrein, protected mice from prostasome-induced lethal pulmonary embolism. Targeting polyphosphate or factor XII conferred resistance to prostate cancer-driven thrombosis in mice, without increasing bleeding. Inhibition of factor XII with recombinant 3F7 antibody reduced the increased prostasome-mediated procoagulant activity in patient plasma. The data illustrate a critical role for polyphosphate/factor XII-triggered coagulation in prostate cancer-associated thrombosis with implications for anticoagulation without therapy-associated bleeding in malignancies. PMID:26153520

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.

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.

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.

[Factor XIII-guided treatment algorithm reduces blood transfusion in burn surgery].

PubMed

Carneiro, João Miguel Gonçalves Valadares de Morais; Alves, Joana; Conde, Patrícia; Xambre, Fátima; Almeida, Emanuel; Marques, Céline; Luís, Mariana; Godinho, Ana Maria Mano Garção; Fernandez-Llimos, Fernando

Major burn surgery causes large hemorrhage and coagulation dysfunction. Treatment algorithms guided by ROTEM ® and factor VIIa reduce the need for blood products, but there is no evidence regarding factor XIII. Factor XIII deficiency changes clot stability and decreases wound healing. This study evaluates the efficacy and safety of factor XIII correction and its repercussion on transfusion requirements in burn surgery. Randomized retrospective study with 40 patients undergoing surgery at the Burn Unit, allocated into Group A those with factor XIII assessment (n = 20), and Group B, those without assessment (n = 20). Erythrocyte transfusion was guided by a hemoglobin trigger of 10g.dL -1 and the other blood products by routine coagulation and ROTEM ® tests. Analysis of blood product consumption included units of erythrocytes, fresh frozen plasma, platelets, and fibrinogen. The coagulation biomarker analysis compared the pre- and post-operative values. Group A (with factor XIII study) and Group B had identical total body surface area burned. All patients in Group A had a preoperative factor XIII deficiency, whose correction significantly reduced units of erythrocyte concentrate transfusion (1.95 vs. 4.05, p = 0.001). Pre- and post-operative coagulation biomarkers were similar between groups, revealing that routine coagulation tests did not identify factor XIII deficiency. There were no recorded thromboembolic events. Correction of factor XIII deficiency in burn surgery proved to be safe and effective for reducing perioperative transfusion of erythrocyte units. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

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.

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 coagulation status, it may be necessary to confirm a coagulation defect through an additional coagulation factor assay.

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.

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

[Endothelial microparticles (EMP) in physiology and pathology].

PubMed

Sierko, Ewa; Sokół, Monika; Wojtukiewicz, Marek Z

2015-08-18

Endothelial microparticles (EMP) are released from endothelial cells (ECs) in the process of activation and/or apoptosis. They harbor adhesive molecules, enzymes, receptors and cytoplasmic structures and express a wide range of various constitutive antigens, typical for ECs, at their surface. Under physiological conditions the concentration of EMP in the blood is clinically insignificant. However, it was reported that under pathological conditions EMP concentration in the blood might slightly increase and contribute to blood coagulation, angiogenesis and inflammation. It has been shown that EMP directly and indirectly contribute to the activation of blood coagulation. Endothelial microparticles directly participate in blood coagulation through their surface tissue factor (TF) - a major initiator of blood coagulation. Furthermore, EMP exhibit procoagulant potential via expression of negatively charged phospholipids at their surface, which may promote assembly of coagulation enzymes (TF/VII, tenases and prothrombinase complexes), leading to thrombus formation. In addition, they provide a binding surface for coagulation factors: IXa, VIII, Va and IIa. Moreover, it is possible that EMP transfer TF from TF-bearing EMP to activated platelets and monocytes by binding them through adhesion molecules. Also, EMP express von Willebrand factor, which may facilitate platelet aggregation. Apart from their procoagulant properties, it was demonstrated that EMP may express adhesive molecules and metalloproteinases (MMP-2, MMP-9) at their surface and release growth factors, which may contribute to angiogenesis. Additionally, surface presence of C3 and C4 - components of the classical pathway - suggests pro-inflammatory properties of these structures. This article contains a summary of available data on the biology and pathophysiology of endothelial microparticles and their potential role in blood coagulation, angiogenesis and inflammation.

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

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.

Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

PubMed

Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric

2016-06-23

The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.

Sodium citrate vacuum tubes validation: preventing preanalytical variability in routine coagulation testing.

PubMed

Lima-Oliveira, Gabriel; Lippi, Giuseppe; Salvagno, Gian Luca; Montagnana, Martina; Picheth, Geraldo; Guidi, Gian Cesare

2013-04-01

Sometimes in-vitro diagnostic devices (e.g. blood collection tubes) are not validated before use or when the producer's brand is changed. The aim of this study was to validate five brands of sodium citrate vacuum tubes. Blood specimens from 50 volunteers were collected in five different tube brands (I: Venosafe, II: VACUETTE, III: BD Vacutainer, IV: LABOR IMPORT and V: S-Monovette). Routine coagulation tests [activated partial thromboplastin time (aPTT), prothrombin time (PT), and fibrinogen (FIB)] were performed on ACL TOP instrument using HemosIL reagents. The significance of the differences between samples was assessed by paired Student's t-test, set at P < 0.005. Significant differences were observed for: PT when comparing I vs. II, I vs. III, I vs. V, II vs. III, II vs. IV, II vs. V, III vs. IV, III vs. V and IV vs. V; aPTT when comparing I vs. II, I vs. III, I vs. IV, II vs. IV, III vs. IV and IV vs. V. No differences were observed among brands for FIB determination. We suggest that every laboratory management should both standardize the procedures and frequently evaluate the quality of in-vitro diagnostic devices.

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

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.

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...

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

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.

HEPATIC FUNCTION AFTER GENETICALLY-ENGINEERED PIG LIVER TRANSPLANTATION IN BABOONS

PubMed Central

Ekser, Burcin; Echeverri, Gabriel J.; Hassett, Andrea Cortese; Yazer, Mark H.; Long, Cassandra; Meyer, Michael; Ezzelarab, Mohamed; Lin, Chih Che; Hara, Hidetaka; van der Windt, Dirk J.; Dons, Eefje M.; Phelps, Carol; Ayares, David; Cooper, David K.C.; Gridelli, Bruno

2010-01-01

Background If ‘bridging’ to allotransplantation is to be achieved by a pig liver xenograft, adequate hepatic function needs to be assured. Methods We have studied hepatic function in baboons after transplantation of livers from α1,3-galactosyltransferase gene-knockout (GTKO,n=1) or GTKO pigs transgenic for CD46 (GTKO/CD46,n=5). Monitoring was by liver function tests and coagulation parameters. Pig-specific proteins in the baboon serum/plasma were identified by Western blot. In 4 baboons, coagulation factors were measured. The results were compared with values from healthy humans, baboons, and pigs. Results Recipient baboons died or were euthanized after 4-7 days following internal bleeding associated with profound thrombocytopenia. However, parameters of liver function, including coagulation, remained in the near-normal range, except for some cholestasis. Western blot demonstrated that pig proteins (albumin, fibrinogen, haptoglobin, plasminogen) were produced by the liver from day 1. Production of several pig coagulation factors was confirmed. Conclusions After the transplantation of genetically-engineered pig livers into baboons (1) many parameters of hepatic function, including coagulation, were normal or near-normal; (2) there was evidence for production of pig proteins, including coagulation factors, and (3) these appeared to function adequately in baboons, though inter-species compatibility of such proteins remains to be confirmed. PMID:20606605

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

X-ray Studies of Regenerated Cellulose Fibers Wet Spun from Cotton Linter Pulp in NaOH/Thiourea Aqueous Solutions

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

Chen,X.; Burger, C.; Fang, D.

Regenerated cellulose fibers were fabricated by dissolution of cotton linter pulp in NaOH (9.5 wt%) and thiourea (4.5 wt%) aqueous solution followed by wet-spinning and multi-roller drawing. The multi-roller drawing process involved three stages: coagulation (I), coagulation (II) and post-treatment (III). The crystalline structure and morphology of regenerated cellulose fiber was investigated by synchrotron wide-angle X-ray diffraction (WAXD) and small-angle X-ray scattering (SAXS) techniques. Results indicated that only the cellulose II crystal structure was found in regenerated cellulose fibers, proving that the cellulose crystals were completely transformed from cellulose I to II structure during spinning from NaOH/thiourea aqueous solution. Themore » crystallinity, orientation and crystal size at each stage were determined from the WAXD analysis. Drawing of cellulose fibers in the coagulation (II) bath (H{sub 2}SO{sub 4}/H{sub 2}O) was found to generate higher orientation and crystallinity than drawing in the post-treatment (III). Although the post-treatment process also increased crystal orientation, it led to a decrease in crystallinity with notable reduction in the anisotropic fraction. Compared with commercial rayon fibers fabricated by the viscose process, the regenerated cellulose fibers exhibited higher crystallinity but lower crystal orientation. SAXS results revealed a clear scattering maximum along the meridian direction in all regenerated cellulose fibers, indicating the formation of lamellar structure during spinning.« less

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.

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

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).

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

Differential procoagulant activity of microparticles derived from monocytes, granulocytes, platelets and endothelial cells: impact of active tissue factor.

PubMed

Shustova, Olga N; Antonova, Olga A; Golubeva, Nina V; Khaspekova, Svetlana G; Yakushkin, Vladimir V; Aksuk, Svetlana A; Alchinova, Irina B; Karganov, Mikhail Y; Mazurov, Alexey V

2017-07-01

: Microparticles released by activated/apoptotic cells exhibit coagulation activity as they express phosphatidylserine and some of them - tissue factor. We compared procoagulant properties of microparticles from monocytes, granulocytes, platelets and endothelial cells and assessed the impact of tissue factor in observed differences. Microparticles were sedimented (20 000g, 30 min) from the supernatants of activated monocytes, monocytic THP-1 cells, granulocytes, platelets and endothelial cells. Coagulation activity of microparticles was examined using plasma recalcification assay. The size of microparticles was evaluated by dynamic light scattering. Tissue factor activity was measured by its ability to activate factor X. All microparticles significantly accelerated plasma coagulation with the shortest lag times for microparticles derived from monocytes, intermediate - for microparticles from THP-1 cells and endothelial cells, and the longest - for microparticles from granulocytes and platelets. Average diameters of microparticles ranged within 400-600 nm. The largest microparticles were produced by endothelial cells and granulocytes, smaller - by monocytes, and the smallest - by THP-1 cells and platelets. The highest tissue factor activity was detected in microparticles from monocytes, lower activity - in microparticles from endothelial cells and THP-1 cells, and no activity - in microparticles from platelets and granulocytes. Anti-tissue factor antibodies extended coagulation lag times for microparticles from monocytes, endothelial cells and THP-1 cells and equalized them with those for microparticles from platelets and granulocytes. Higher coagulation activity of microparticles from monocytes, THP-1 cells and endothelial cells in comparison with microparticles from platelets and granulocytes is determined mainly by the presence of active tissue factor.

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 50% at D2 compared to the basal levels, and these reductions in plasma activity for both factors were consistent with our RT-PCR findings. In contrast, the plasma activities of the other coagulation factors (fibrinogen, factors V, VII, XIII, and VWF) were not significantly reduced, despite the reduction in the liver mRNA levels. Unlike the other factors, FX showed a temporal increase in its plasma activity, with significant increases (P<0.05) detected at D1. Investigating the coagulation cascade protein profiles during liver regeneration by DH may help to better understand the basic biology of the liver under normal and pathological conditions.

21 CFR 864.7340 - Fibrinogen determination system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... disseminated intravascular coagulation (nonlocalized clotting within the blood vessels) and primary fibrinolysis (the dissolution of fibrin in a blood clot). (b) Classification. Class II (performance standards...

21 CFR 864.7340 - Fibrinogen determination system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... disseminated intravascular coagulation (nonlocalized clotting within the blood vessels) and primary fibrinolysis (the dissolution of fibrin in a blood clot). (b) Classification. Class II (performance standards...

21 CFR 864.7340 - Fibrinogen determination system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... disseminated intravascular coagulation (nonlocalized clotting within the blood vessels) and primary fibrinolysis (the dissolution of fibrin in a blood clot). (b) Classification. Class II (performance standards...

21 CFR 864.7340 - Fibrinogen determination system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... disseminated intravascular coagulation (nonlocalized clotting within the blood vessels) and primary fibrinolysis (the dissolution of fibrin in a blood clot). (b) Classification. Class II (performance standards...

21 CFR 864.7340 - Fibrinogen determination system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... disseminated intravascular coagulation (nonlocalized clotting within the blood vessels) and primary fibrinolysis (the dissolution of fibrin in a blood clot). (b) Classification. Class II (performance standards...

Flomoxef, a new oxacephem antibiotic, does not cause hemostatic defects.

PubMed

Cazzola, M; Brancaccio, V; De Giglio, C; Paternò, E; Matera, M G; Rossi, F

1993-03-01

Antibiotics of the beta-lactam class may cause coagulation defects and bleeding. It has been suggested that N-methyltetrazolethiol (NMTT), a common side chain group at the 3'-position of the cephem or 1-oxacephem frame, could be responsible for the hypoprothrombinemic effect of the antibiotics and that it could inhibit the liver vitamin K-epoxide reductase activity. Flomoxef (6315-S) is a new oxacephem antibiotic which differs from latamoxef because it has [1-(2-hydroxethyl)-1H-tetrazol-5-yl] thiomethyl (HTT) as a side chain at the 3'-position of cephem group instead of NMTT and an extensive modification of 7 beta-acylamino side chain. The present study was carried out to study its effects on vitamin K-dependent blood coagulation parameters in human volunteers. Ten adult patients (6 men and 4 women), suffering from chronic bronchitis, entered into the study. Each patient received ten 1 g i.m. injections of flomoxef at 12-hourly intervals. Apparently, the treatment with this oxacephem antibiotic had no significant effect. PT, PTT and fibrinogen remained in the normal range in all patients and factors II+VII+X, protein C, protein S and AT III were not depleted. The trend was similar both in men and women. Based on the results of the present study, we conclude that flomoxef is an antibiotic that does not exhibit an effect on blood coagulation, even in males.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Probe measurements and numerical model predictions of evolving size distributions in premixed flames

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

De Filippo, A.; Sgro, L.A.; Lanzuolo, G.

2009-09-15

Particle size distributions (PSDs), measured with a dilution probe and a Differential Mobility Analyzer (DMA), and numerical predictions of these PSDs, based on a model that includes only coagulation or alternatively inception and coagulation, are compared to investigate particle growth processes and possible sampling artifacts in the post-flame region of a C/O = 0.65 premixed laminar ethylene-air flame. Inputs to the numerical model are the PSD measured early in the flame (the initial condition for the aerosol population) and the temperature profile measured along the flame's axial centerline. The measured PSDs are initially unimodal, with a modal mobility diameter ofmore » 2.2 nm, and become bimodal later in the post-flame region. The smaller mode is best predicted with a size-dependent coagulation model, which allows some fraction of the smallest particles to escape collisions without resulting in coalescence or coagulation through the size-dependent coagulation efficiency ({gamma}{sub SD}). Instead, when {gamma} = 1 and the coagulation rate is equal to the collision rate for all particles regardless of their size, the coagulation model significantly under predicts the number concentration of both modes and over predicts the size of the largest particles in the distribution compared to the measured size distributions at various heights above the burner. The coagulation ({gamma}{sub SD}) model alone is unable to reproduce well the larger particle mode (mode II). Combining persistent nucleation with size-dependent coagulation brings the predicted PSDs to within experimental error of the measurements, which seems to suggest that surface growth processes are relatively insignificant in these flames. Shifting measured PSDs a few mm closer to the burner surface, generally adopted to correct for probe perturbations, does not produce a better matching between the experimental and the numerical results. (author)« less

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.

Complement Activation Alters Platelet Function

DTIC Science & Technology

2015-12-01

haemostatic and coagulation properties of platelets. 15. SUBJECT TERMS Platelets, Complement, Trauma, Tissue Damage 16. SECURITY CLASSIFICATION... coagulation , there is mounting evidence that they may also be important in the development and progression of inflammatory processes (Coppinger et al...receptor-ligand interactions and/or through exposure to cytokines including IL-6, other acute-phase reactants, and pro- coagulant factors such as thrombin

Venom Protein C activators as diagnostic agents for defects of protein C System.

PubMed

Ramzan, Faiqah; Asmat, Andleeb

2018-06-18

Background Protein C is a vitamin K dependent plasma zymogen. It prevents clotting by inhibiting clotting by inactivating factor V and factor VIII. Protein C activation pathway involves three steps: (i) Activation of protein C; (ii) Inhibition of coagulation through inactivating factor V and VIII by activated protein C and (iii) Inhibition of activated protein C by plasma protease inhibitors specific for this enzyme. Proteinases converts the zymogen Protein C (PC) of vertebrates into activated PC, which has been detected in several snake venoms. Most PC activators have been purified from venom of snake species belonging to the genera of the Agkistrodon complex. Unlike the physiological thrombin-catalyzed PC activation reaction which requires thrombomodulin as a cofactor, most snake venom activators directly convert the zymogen PC into the catalytically active form which can easily be determined by means of coagulation or chromogenic substrate techniques. Conclusion The fast-acting PC activator Protac® from Agkistrodon contortrix (southern copperhead snake) venom has been found to have broad application in diagnostic practice for the determination of disorders in the PC pathway. Recently, screening assays for the PC pathway have been introduced, based on the observation that the PC pathway is probably the most important physiological barrier against thrombosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

A survey of coagulation laboratory practices and satisfaction ratings of member laboratories of the Thailand National External Quality Assessment Scheme for blood coagulation.

PubMed

Chuntarut, A; Tientadakul, P; Wongkrajang, P

2016-06-01

The Thailand National External Quality Assessment Scheme (NEQAS) for blood coagulation was established in 2005. The objective of this study was to collect data of coagulation laboratory practices and satisfaction of NEQAS member. Two hundred seventy-six questionnaires were sent to laboratories that are members of NEQAS to obtain data relating to coagulation laboratory practice and satisfaction in 2014. Data from this survey were compared with data from the survey conducted in 2005 to evaluate levels of improvement. Of 276 questionnaires sent, 212 (76.8%) were returned. Improvements were characterized by the number of laboratories that (i) decreased use of 3.8% sodium citrate as anticoagulant; (ii) implemented use of at least two control levels for internal quality control; and (iii) implemented reporting of reference values with results, as well as establishing their own reference range and using geometric mean as the denominator for international normalized ratio calculation. For overall satisfaction, 179 of 206 (86.9%) participant laboratories reported being satisfied or very satisfied. Improvements in coagulation laboratory practices in Thailand were observed in every step of the total testing process. However, additional improvements are still needed, such as determination and use of a local reference range. © 2016 John Wiley & Sons Ltd.

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

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.

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

Systemic hyperfibrinolysis after trauma: a pilot study of targeted proteomic analysis of superposed mechanisms in patient plasma.

PubMed

Banerjee, Anirban; Silliman, Christopher C; Moore, Ernest E; Dzieciatkowska, Monika; Kelher, Marguerite; Sauaia, Angela; Jones, Kenneth; Chapman, Michael P; Gonzalez, Eduardo; Moore, Hunter B; D'Alessandro, Angelo; Peltz, Erik; Huebner, Benjamin E; Einerson, Peter; Chandler, James; Ghasabayan, Arsen; Hansen, Kirk

2018-06-01

Viscoelastic measurements of hemostasis indicate that 20% of seriously injured patients exhibit systemic hyperfibrinolysis, with increased early mortality. These patients have normal clot formation with rapid clot lysis. Targeted proteomics was applied to quantify plasma proteins from hyperfibrinolytic (HF) patients to elucidate potential pathophysiology. Blood samples were collected in the field or at emergency department arrival and thrombelastography (TEG) was used to characterize in vitro clot formation under native and tissue plasminogen activator (tPA)-stimulated conditions. Ten samples were taken from injured patients exhibiting normal lysis time at 30 min (Ly30), "eufibrinolytic" (EF), 10 from HF patients, defined as tPA-stimulated TEG Ly30 >50%, and 10 from healthy controls. Trauma patient samples were analyzed by targeted proteomics and ELISA assays for specific coagulation proteins. HF patients exhibited increased plasminogen activation. Thirty-three proteins from the HF patients were significantly decreased compared with healthy controls and EF patients; 17 were coagulation proteins with anti-protease consumption (p < 0.005). The other 16 decreased proteins indicate activation of the alternate complement pathway, depletion of carrier proteins, and four glycoproteins. CXC7 was elevated in all injured patients versus healthy controls (p < 0.005), and 35 proteins were unchanged across all groups (p > 0.1 and fold change of concentrations of 0.75-1.3). HF patients had significant decreases in specific proteins and support mechanisms known in trauma-induced hyperfibrinolysis and also unexpected decreases in coagulation factors, factors II, X, and XIII, without changes in clot formation (SP, R times, or angle). Decreased clot stability in HF patients was corroborated with tPA-stimulated TEGs. Prognostic, level III.

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.

Testing of Intravenous Hemostatic Agents in a Novel Swine Model of Bleeding: Preliminary Results With FXa-PCPs

DTIC Science & Technology

2005-08-01

proceeds through a prothrombinase complex (prothrombin, factor Va, calcium, and phospholipid). Thrombin is the final product in the coagulation cascade...we report preliminary data on the efficacy of mixtures of highly purified blood coagulation factors (FVIIa and FXa) and phospholipids vesicles (PCPS...testing. Further study of these drugs for the use of traumatic hemorrhage is not warranted. 15. SUBJECT TERMS Recombinant Factor VI~a, factor Xa

The Potential Role of Recombinant Activated Factor VIIa (rFVIIa) in Military Pre-Hospital Setting

DTIC Science & Technology

2004-09-01

coagulation factors and platelets by crystalloids, colloids, or blood products The severity of dilutional coagulopathy is determined by both volume and...RTO-MP-HFM-109 3 - 1 The Potential Role of Recombinant Activated Factor VIIa (rFVIIa) in Military Pre-Hospital Setting LTC (ret.) Uri...decrease mortality from exsanguinations. Recombinant factor VIIa (rFVIIa) has been shown to overcome a variety of coagulation and platelet disorders

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.

Laboratory assessment of Activated Protein C Resistance/Factor V-Leiden and performance characteristics of a new quantitative assay.

PubMed

Amiral, Jean; Vissac, Anne Marie; Seghatchian, Jerard

2017-12-01

Activated Protein C Resistance is mainly associated to a factor V mutation (RQ506), which induces a deficient inactivation of activated factor V by activated protein C, and is associated to an increased risk of venous and arterial thrombosis in affected individuals, caused by the prolonged activated factor V survival. Its prevalence is mainly in Caucasians (about 5%), and this mutation is absent in Africans and Asians. Presence of Factor V-Leiden is usually evidenced with clotting methods, using a two-step APTT assay performed without or with APC: prolongation of blood coagulation time is decreased if this factor is present. The R506Q Factor V-Leiden mutation is now usually characterized using molecular biology, and this technique tends to become the first intention assay for characterization of patients. Both techniques are qualitative, and allow classifying tested individuals as heterozygotes or homozygotes for the mutation, when present. A new quantitative assay for Factor V-Leiden, using a one-step clotting method, has been developed, and designed with highly purified human coagulation proteins. Clotting is triggered with human Factor Xa, in presence of calcium and phospholipids (mixture which favours APC action over clotting process). Diluted tested plasma, is supplemented with a clotting mixture containing human fibrinogen, prothrombin, and protein S at a constant concentration. APC is added, and clotting is initiated with calcium. Calibration is performed with a pool of plasmas from patients carrying the R506Q Factor V mutation, and its mixtures with normal plasma. Homozygous patients have clotting times of about <40sec; heterozygous patients have clotting times of about 40-60sec and normal individuals yield clotting times >70sec. Factor V-Leiden concentration is usually >75% in homozygous patients, 30-60% in heterozygous patients and below 5% in normal. The assay is insensitive to clotting factor deficiencies (II, VII, VIII: C, IX, X), dicoumarol or heparin therapies, and has no interference with lupus anticoagulant (LA). This new assay for Factor V-Leiden can be easily used in any coagulation laboratory, is performed as a single test, and is quantitative. This assay has a high robustness, is accurate and presents a good intra- (<3%) and inter-assay (<5%) variability. It contributes solving most of the laboratory issues faced when testing factor V-Leiden. Quantitation of Factor V-L could contribute to a better assessment of thrombotic risk in affected patients, as this complication is first associated to and caused by the presence of a defined amount of FVa. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Hereditary heterozygous factor VII deficiency in patients undergoing surgery : Clinical relevance].

PubMed

Woehrle, D; Martinez, M; Bolliger, D

2016-10-01

A hereditary deficiency in coagulation factor VII (FVII) may affect the international normalized ratio (INR) value. However, FVII deficiency is occasionally associated with a tendency to bleed spontaneously. We hypothesized that perioperative substitution with coagulation factor concentrates might not be indicated in most patients. In this retrospective data analysis, we included all patients with hereditary heterozygous FVII deficiency who underwent surgical procedures at the University Hospital Basel between December 2010 and November 2015. In addition, by searching the literature, we identified publications reporting patients with FVII deficiency undergoing surgical procedures without perioperative substitution. We identified 22 patients undergoing 46 surgical procedures, resulting in a prevalence of 1:1500-2000. Coagulation factor concentrates were administered during the perioperative period in 15 procedures (33 %), whereas in the other 31 procedures (66 %), FVII deficiency was not substituted. No postoperative bleeding or thromboembolic events were reported. In addition, we found no differences in pre- and postoperative hemoglobin and coagulation parameters, with the exception of an improved postoperative INR value in the substituted group. In the literature review, we identified five publications, including 125 patients with FVII deficiency, undergoing 213 surgical procedures with no perioperative substitution. Preoperative substitution using coagulation factor concentrates does not seem to be mandatory in patients with an FVII level ≥15 %. For decision-making on preoperative substitution, patient history of an increased tendency to bleed may be more important than the FVII level or increased INR value.

Improved removal performance and mechanism investigation of papermaking wastewater treatment using manganese enhanced Fenton reaction.

PubMed

Wang, Yingcai; Wang, Can; Shi, Shuai; Fang, Shuai

2018-06-01

The effects of Mn(II) on Fenton system to treat papermaking wastewater and the mechanism of Mn(II) enhanced Fenton reaction were investigated in this study. The chemical oxygen demand (COD) removal efficiency was enhanced in the presence of Mn(II), which increased by 19% compared with that of the Fenton system alone. The pseudo-first order reaction kinetic rate constant of Mn(II)/Fenton system was 2.11 times higher than that of Fenton system. 67%-81% COD were removed with the increasing Mn(II) concentration from 0 to 0.8 g/L. COD removal efficiency was also enhanced in a wider pH range (3-7), which indicated the operation parameters of Fenton technology could be broadened to a milder condition. The study of the mechanism showed that Mn(II) participated in the oxidation and coagulation stages in Fenton system. In the oxidation stage, Mn(II) promotes the production of HO 2 •/ O 2 • - , then HO 2 •/ O 2 • - reacts with Fe(III) to accelerate the formation of Fe(II), and finally accelerates the production of HO•. Meantime MnMnO 3 and Fe(OH) 3 forms in the coagulation stage, facilitating the removal of suspended substances and a large amount of COD, which enhances the overall COD removal of papermaking wastewater. This study provided a detailed mechanism to improve practical applications of Fenton technology.

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.

Moderate KMnO4-Fe(II) pre-oxidation for alleviating ultrafiltration membrane fouling by algae during drinking water treatment.

PubMed

Ma, Baiwen; Qi, Jing; Wang, Xing; Ma, Min; Miao, Shiyu; Li, Wenjiang; Liu, Ruiping; Liu, Huijuan; Qu, Jiuhui

2018-05-21

Although ultrafiltration (UF) membranes are highly beneficial for removing algae, the removal process causes serious UF membrane fouling. To avoid the unfavorable effects of algal cells that have been damaged by oxidants, our previous study reported a novel, moderate pre-oxidation method (KMnO 4 -Fe(II) process) that aimed to achieve a balance between the release of intracellular organic matter and enhanced algae removal. This study further investigated the performance of a UF membrane with KMnO 4 -Fe(II) pretreatment in the presence of algae-laden reservoir water after a long running time. We found that algae could be completely removed, membrane fouling was significantly alleviated, and the overall performance was much better than that of Fe(III) coagulation alone. The transmembrane pressure (TMP) during Fe(III) coagulation increased to 42.8 kPa, however, that of the KMnO 4 -Fe(II) process only increased to 25.1 kPa for after running for 90 d. The slower transmembrane pressure was attributed to the larger floc size, higher surface activity, and inactivation of algae. Although there was little effect on microorganism development, lower microorganism abundance (20.7%) was observed during the KMnO 4 -Fe(II) process than during coagulation alone (44.9%) due to the release of extracellular polymeric substances. We also found that the floc cake layer was easily removed by washing, and many of the original membrane pores were clearly observed. Further analysis demonstrated that the effluent quality was excellent, especially its turbidity, chromaticity, and Mn and Fe concentrations. Based on the outstanding UF membrane performance, it may be concluded that the KMnO 4 -Fe(II) process exhibits considerable potential for application in the treatment of algae-laden water. Copyright © 2018. Published by Elsevier Ltd.

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.

21 CFR 864.7300 - Fibrin monomer paracoagulation test.

Code of Federal Regulations, 2011 CFR

2011-04-01

... clotting within a blood vessel) or in the differential diagnosis between disseminated intravascular coagulation and primary fibrinolysis (dissolution of the fibrin in a blood clot). (b) Classification. Class II...

21 CFR 864.7300 - Fibrin monomer paracoagulation test.

Code of Federal Regulations, 2012 CFR

2012-04-01

... clotting within a blood vessel) or in the differential diagnosis between disseminated intravascular coagulation and primary fibrinolysis (dissolution of the fibrin in a blood clot). (b) Classification. Class II...

21 CFR 864.7320 - Fibrinogen/fibrin degradation products assay.

Code of Federal Regulations, 2014 CFR

2014-04-01

... dissolution of the fibrin in a blood clot) and in monitoring therapy for disseminated intravascular coagulation (nonlocalized clotting in the blood vessels). (b) Classification. Class II (performance standards...

21 CFR 864.7300 - Fibrin monomer paracoagulation test.

Code of Federal Regulations, 2010 CFR

2010-04-01

... clotting within a blood vessel) or in the differential diagnosis between disseminated intravascular coagulation and primary fibrinolysis (dissolution of the fibrin in a blood clot). (b) Classification. Class II...

21 CFR 864.7320 - Fibrinogen/fibrin degradation products assay.

Code of Federal Regulations, 2013 CFR

2013-04-01

... dissolution of the fibrin in a blood clot) and in monitoring therapy for disseminated intravascular coagulation (nonlocalized clotting in the blood vessels). (b) Classification. Class II (performance standards...

21 CFR 864.7320 - Fibrinogen/fibrin degradation products assay.

Code of Federal Regulations, 2012 CFR

2012-04-01

... dissolution of the fibrin in a blood clot) and in monitoring therapy for disseminated intravascular coagulation (nonlocalized clotting in the blood vessels). (b) Classification. Class II (performance standards...

21 CFR 864.7300 - Fibrin monomer paracoagulation test.

Code of Federal Regulations, 2014 CFR

2014-04-01

... clotting within a blood vessel) or in the differential diagnosis between disseminated intravascular coagulation and primary fibrinolysis (dissolution of the fibrin in a blood clot). (b) Classification. Class II...

21 CFR 864.7320 - Fibrinogen/fibrin degradation products assay.

Code of Federal Regulations, 2011 CFR

2011-04-01

... dissolution of the fibrin in a blood clot) and in monitoring therapy for disseminated intravascular coagulation (nonlocalized clotting in the blood vessels). (b) Classification. Class II (performance standards...

21 CFR 864.7300 - Fibrin monomer paracoagulation test.

Code of Federal Regulations, 2013 CFR

2013-04-01

... clotting within a blood vessel) or in the differential diagnosis between disseminated intravascular coagulation and primary fibrinolysis (dissolution of the fibrin in a blood clot). (b) Classification. Class II...

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.

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.

In vitro anti-thrombotic and anti-coagulant properties of blacklip abalone (Haliotis rubra) viscera hydrolysate.

PubMed

Suleria, Hafiz Ansar Rasul; Masci, Paul P; Addepalli, Rama; Chen, Wei; Gobe, Glenda C; Osborne, Simone A

2017-07-01

Abalone viscera contain sulphated polysaccharides with anti-thrombotic and anti-coagulant activities. In this study, a hydrolysate was prepared from blacklip abalone (Haliotis rubra) viscera using papain and bromelain and fractionated using ion exchange and size exclusion chromatography. Hydrolysates and fractions were investigated for in vitro thrombin inhibition mediated through heparin cofactor II (HCII) as well as anti-coagulant activity in plasma and whole blood. On the basis of sulphated polysaccharide concentration, the hydrolysate inhibited thrombin through HCII with an inhibitor concentration at 50% (IC50) of 16.5 μg/mL compared with 2.1 μg/mL for standard heparin. Fractionation concentrated HCII-mediated thrombin inhibition down to an IC50 of 1.8 μg/mL and improved anti-coagulant activities by significantly delaying clotting time. This study confirmed the presence of anti-thrombotic and anti-coagulant molecules in blacklip abalone viscera and demonstrated that these activities can be enriched with a simple chromatography regime. Blacklip abalone viscera warrant further investigation as a source of nutraceutical or functional food ingredients. Graphical abstract Schematic showing preparation of bioactive extracts and fractions from blacklip abalone.

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.

Mutation in the factor VII hepatocyte nuclear factor 4α-binding site contributes to factor VII deficiency.

PubMed

Zheng, Xing-Wu; Kudaravalli, Rama; Russell, Theresa T; DiMichele, Donna M; Gibb, Constance; Russell, J Eric; Margaritis, Paris; Pollak, Eleanor S

2011-10-01

Severe coagulant factor VII (FVII) deficiency in postpubertal dizygotic twin males results from two point mutations in the FVII gene, a promoter region T→C transition at -60 and a His-to-Arg substitution at amino acid 348; both mutations prevent persistence of plasma functional FVII. This report documents longitudinal laboratory measurements from infancy to adulthood of FVII coagulant activity (FVII:C) in the twin FVII-deficient patients; it also details specific biochemical analyses of the -60 T→C mutation. The results revealed FVII:C levels of less than 1% in infancy that remain severely decreased through puberty and into adulthood. In-vitro analyses utilizing hepatocyte nuclear factor 4α (HNF4α) co-transfection and a chromatin immunoprecipitation assay indicate that the -60 T→C mutation severely diminishes functional interaction between the FVII promoter and transcription factor HNF4α. The importance of interaction between the FVII gene and HNF4α in normal FVII expression provides an in-vivo illustration of the regulated expression of an autosomal gene encoding a coagulation protein. The constancy of FVII:C and peripubertal patient symptomatology reported here illustrates androgen-independent expression in contrast to expression with an analogous mutation in the promoter region of the gene encoding coagulation FIX.

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.

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

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.

New models of hemostasis.

PubMed

McMichael, Maureen

2012-05-01

Hemostasis is an essential protective mechanism that depends on a delicate balance of procoagulant and anticoagulant processes. The waterfall/cascade models of coagulation are useful for understanding several essential steps of coagulation in vitro. These have resulted in the creation of the plasma-based tests used commonly and the ability to identify deficiencies in the extrinsic, intrinsic, and common pathways of coagulation. The model was also essential in elucidating the role of several of the inhibitors of coagulation and is currently used to demonstrate coagulation as it occurs in plasma in a static environment that is devoid of endothelial interactions. The intrinsic pathway originally described by these models does not appear to be essential for in vivo hemostasis but may play a role in pathologic thrombosis. The waterfall/cascade models' lack of cellular elements sets the stage for the cell-based model of coagulation. The cell-based model of blood coagulation, which includes the varied, complicated network of factors necessary for appropriate in vivo coagulation to occur, was the next step in the evolution of our understanding of coagulation. Recently, researchers have focused on real-time, in vivo models of hemostasis and this research reveals unexpected phenomena. Copyright © 2012 Elsevier Inc. All rights reserved.

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

Risk factors associated with short-term outcome and development of perioperative complications in dogs undergoing surgery because of gastric dilatation-volvulus: 166 cases (1992-2003).

PubMed

Beck, Jennifer J; Staatz, Andrew J; Pelsue, Davyd H; Kudnig, Simon T; MacPhail, Catriona M; Seim, Howard B; Monnet, Eric

2006-12-15

To evaluate risk factors associated with death and development of perioperative complications in dogs undergoing surgery for treatment of gastric dilatation-volvulus (GDV). Retrospective case series. 166 dogs. Records of dogs with confirmed GDV that underwent surgery were reviewed. Logistic regression was performed to identify factors associated with development of complications (ie, hypotension, arrhythmias, gastric necrosis necessitating gastrectomy, disseminated intravascular coagulation, peritonitis, sepsis, postoperative dilatation, postoperative vomiting, and incisional problems) and with short-term outcome (ie, died vs survived to the time of suture removal). Short-term mortality rate was 16.2% (27/166). Risk factors significantly associated with death prior to suture removal were clinical signs for > 6 hours prior to examination, combined splenectomy and partial gastrectomy, hypotension at any time during hospitalization, peritonitis, sepsis, and disseminated intravascular coagulation. Partial gastrectomy was not a significant risk factor for death but was for peritonitis, disseminated intravascular coagulation, sepsis, and arrhythmias. Age, gastrectomy, and disseminated intravascular coagulation were risk factors for development of hypotension. Use of a synthetic colloid or hypertonic saline solution was associated with a significantly decreased risk of hypotension. Results suggest that the prognosis for dogs undergoing surgery because of GDV is good but that certain factors are associated with an increased risk that dogs will develop perioperative complications or die.

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.

Analysis of rhG-CSF-effects on platelets by in vitro bleeding test and transcranial Doppler ultrasound examination.

PubMed

Söhngen, D; Wienen, S; Siebler, M; Boogen, C; Scheid, C; Schulz, A; Kobbe, G; Diehl, V; Heyll, A

1998-12-01

Experimental evidence suggests a stimulatory effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on both platelets and coagulation. RhG-CSF is increasingly used to stimulate healthy volunteer donors for blood stem cell mobilization. We therefore assessed 25 healthy donors receiving rhG-CSF for changes in in vitro bleeding test (IVBT), coagulation parameters and cerebral microembolism by transcranial Doppler (TCD) ultrasound. A significant shortening of IVBT was found on day 4 of rhG-CSF administration together with increased levels of fibrinogen and factor VIII and reduced activities of protein C and protein S. Although these changes are quite small it is possible that they may lead to a hypercoagulable state especially in donors with other risk factors for thromboembolism. However, TCD examination failed to detect any signs of microembolism. We therefore conclude that rhG-CSF leads to significant changes in coagulation parameters, but has no effect on TCD detectable microembolism as a stroke risk factor. However donors receiving rhG-CSF should be examined carefully to detect pre-existing changes in the coagulation system and we would like to suggest a routine thrombophilia screen.

Nitric oxide-generating silicone as a blood-contacting biomaterial

PubMed Central

Amoako, Kagya A.; Cook, Keith E.

2011-01-01

Coagulation upon blood-contacting biomaterials remains a problem for short and long-term clinical applications. This study examined the ability of copper(II)-doped silicone surfaces to generate nitric oxide (NO) and locally inhibit coagulation. Silicone was doped with 3-micron copper (Cu(0)) particles yielding 3 to 10 weight percent (wt%) Cu in 70-μm thick Cu/Silicone polymeric matrix composites (Cu/Si PMCs). At 3, 5, 8 and 10 wt% Cu doping, the surface expression of Cu was 12.1 ± 2.8%, 19.7 ± 5.4%, 29.0 ± 3.8%, and 33.8 ± 6.5% respectively. After oxidizing Cu(0) to Cu(II) by spontaneous corrosion, NO flux, JNO (mol*cm−2*min−1), as measured by chemiluminescence, increased with surface Cu expression according to the relationship JNO =(1.63 %SACu −0.81) ×10−11, R2 = 0.98 where %SACu is the percentage of surface occupied by Cu. NO flux at 10 wt% Cu was 5.35± 0.74 ×10−10 mol*cm−2*min−1. The clotting time of sheep blood exposed to these surfaces was 80 ± 13s with pure silicone and 339 ± 44s when 10 wt% Cu(II) was added. SEMs of coatings showed clots occurred away from exposed Cu-dendrites. In conclusion, Cu/Si PMCs inhibit coagulation in a dose-dependent fashion related to the extent of copper exposure on the coated surface. PMID:22036723

Factor VIII-bypassing activity of bovine tissue factor using the canine hemophilic model.

PubMed Central

O'Brien, D P; Giles, A R; Tate, K M; Vehar, G A

1988-01-01

The bleeding disorder of hemophilia A currently treated by replacement therapy of the missing coagulation factor, factor VIII, is frequently complicated by the development of neutralizing antibodies. The therapeutic potential of attenuated forms of the lipid-associated glycoprotein tissue factor, a known initiator of coagulation, was investigated as a factor VIII-by-passing activity. The protein moiety of tissue factor (Apo-TF) was partially purified and exhibited minimal procoagulant activity before relipidation in vitro. In pilot studies, Apo-TF injection into rabbits previously anticoagulated with an antibody to factor VIII was found to have a procoagulant effect. The efficacy of the material was further demonstrated when injection of Apo-TF in hemophilic dogs resulted in a normalization of the cuticle bleeding time. Little or no change in the blood parameters associated with disseminated intravascular coagulation was observed at lower doses, although mild to moderate effects were seen at higher doses. These data suggest a novel role for Apo-TF preparations as a potential therapeutic agent for hemophiliacs with antibodies to factor VIII once the potential thrombogenicity of such materials is evaluated. Images PMID:3134399

Tissue factor-dependent coagulation activation by heme: A thromboelastometry study.

PubMed

de Souza, Gleice Regina; Hounkpe, Bidossessi Wilfried; Fiusa, Maiara Marx Luz; Colella, Marina Pereira; Annichino-Bizzacchi, Joyce M; Traina, Fabiola; Costa, Fernando Ferreira; De Paula, Erich Vinicius

2017-01-01

Heme has been characterized as potent trigger of inflammation. In hemostasis, although heme has been shown to both induce and inhibit different compartments of hemostasis, its net effect on the hemostatic balance, and the biological relevance of these effects remain to be determined. Herein we evaluated the effect of heme on hemostasis using a global assay able to generate clinically relevant data in several other complex hemostatic diseases. Citrated whole blood samples from healthy participants were stimulated by heme or vehicle and incubated for 4h at 37°C. Rotational thromboelastometry was immediately performed. The participation of tissue factor in coagulation activation was evaluated using inhibitory antibody. Heme was able of inducing ex vivo coagulation activation in whole blood, affecting predominantly parameters associated with the initial phases of clot formation. This activation effect was at least partially dependent on hematopoietic tissue factor, since the effects of heme were partially abrogated by the inhibition of human tissue factor. In conclusion, using a global hemostasis assay, our study confirmed that heme is able to activate coagulation in whole blood, in a tissue factor-dependent way. These findings could explain the disturbance in hemostatic balance observed in conditions associated with the release of heme such as sickle cell disease.

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.

Simultaneous decomplexation in blended Cu(II)/Ni(II)-EDTA systems by electro-Fenton process using iron sacrificing electrodes.

PubMed

Zhao, Zilong; Dong, Wenyi; Wang, Hongjie; Chen, Guanhan; Tang, Junyi; Wu, Yang

2018-05-15

This research explored the application of electro-Fenton (E-Fenton) technique for the simultaneous decomplexation in blended Cu(II)/Ni(II)-EDTA systems by using iron sacrificing electrodes. Standard discharge (0.3 mg L -1 for Cu and 0.1 mg L -1 for Ni in China) could be achieved after 30 min reaction under the optimum conditions (i.e. initial solution pH of 2.0, H 2 O 2 dosage of 6 mL L -1  h -1 , current density of 20 mA/cm 2 , inter-electrode distance of 2 cm, and sulfate electrolyte concentration of 2000 mg L -1 ). The distinct differences in apparent kinetic rate constants (k app ) and intermediate removal efficiencies corresponding to mere and blended systems indicated the mutual promotion effect toward the decomplexation between Cu(II) and Ni(II). Massive accumulation of Fe(Ⅲ) favored the further removal of Cu(II) and Ni(II) by metal ion substitution. Species distribution results demonstrated that the decomplexation of metal-EDTA in E-Fenton process was mainly contributed to the combination of various reactions, including Fenton reaction together with the anodic oxidation, electro-coagulation (E-coagulation) and electrodeposition. Unlike hypophosphite and citrate, the presence of chlorine ion displayed favorable effects on the removal efficiencies of Cu(II) and Ni(II) at low dosage, but facilitated the ammonia nitrogen (NH 4 + -N) removal only at high dosage. Copyright © 2018 Elsevier B.V. All rights reserved.

Contact Activation of Blood Plasma and Factor XII by Ion-exchange Resins

PubMed Central

Yeh, Chyi-Huey Josh; Dimachkie, Ziad O.; Golas, Avantika; Cheng, Alice; Parhi, Purnendu; Vogler, Erwin A.

2011-01-01

Sepharose ion-exchange particles bearing strong Lewis acid/base functional groups (sulfopropyl, carboxymethyl, quarternary ammonium, dimethyl aminoethyl, and iminodiacetic acid) exhibiting high plasma protein adsorbent capacities are shown to be more efficient activators of blood factor XII in neat-buffer solution than either hydrophilic clean-glass particles or hydrophobic octyl sepharose particles ( FXII→surfaceactivatorFXIIa; a.k.a autoactivation, where FXII is the zymogen and FXIIa is a procoagulant protease). In sharp contrast to the clean-glass standard of comparison, ion-exchange activators are shown to be inefficient activators of blood plasma coagulation. These contrasting activation properties are proposed to be due to the moderating effect of plasma-protein adsorption on plasma coagulation. Efficient adsorption of blood plasma proteins unrelated to the coagulation cascade impedes FXII contacts with ion-exchange particles immersed in plasma, reducing autoactivation, and causing sluggish plasma coagulation. By contrast, plasma proteins do not adsorb to hydrophilic clean glass and efficient autoactivation leads directly to efficient activation of plasma coagulation. It is also shown that competitive-protein adsorption can displace FXIIa adsorbed to the surface of ion-exchange resins. As a consequence of highly-efficient autoactivation and FXIIa displacement by plasma proteins, ion-exchange particles are slightly more efficient activators of plasma coagulation than hydrophobic octyl sepharose particles that do not bear strong Lewis acid/base surface functionalities but to which plasma proteins adsorb efficiently. Plasma proteins thus play a dual role in moderating contact activation of the plasma coagulation cascade. The principal role is impeding FXII contact with activating surfaces but this same effect can displace FXIIa from an activating surface into solution where the protease can potentiate subsequent steps of the plasma coagulation cascade. PMID:21982294

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, thereby improving neurocognitive outcomes. PMID:28099190

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 neurocognitive outcomes.

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.

Black Carbon Aging from SOA Coatings and Coagulation with Diesel BC Emissions during SAAS at the PNNL Environmental Chamber

NASA Astrophysics Data System (ADS)

Aiken, A. C.; Liu, S.; Dubey, M. K.; Zaveri, R. A.; Shilling, J. E.; Gourihar, K.; Pekour, M. S.; Subramanian, R.; Zelenyuk, A.; Wilson, J. M.; Mazzoleni, C.; China, S.; Sharma, N.

2014-12-01

Black carbon (BC) is considered to be potentially the 2nd most important global warming factor behind CO2 (Bond et al., 2013). Uncertainties exist due to BC morphology and mixing state on the extent of the warming that it causes, e.g. Cappa et al., 2012. Core-shell BC is expected to enhance absorption by up to a factor of 2, but has yet to be observed to this extent from ambient data. Experiments were conducted during the Soot Aerosol Aging Study (SAAS) Laboratory Campaign at Pactific Northwest National Laboratory's Environmental Chamber in the winter of 2013-2014 to investigate the relationship between coatings and enhancements from diesel emissions. Direct on-line measurements were made with the single particle soot photometer (SP2) from fresh and aged BC from coating and coagulation experiments with secondary organic aerosol (SOA) formed in the chamber. BC measurements are coupled with photoactoustic measurements spanning the visible region to probe BC enhancements when mixed with SOA. Here we focus on the enhancements at 781 nm, that are tracked throughout SOA growth on BC, as determined from SP2 coating thicknesses. Thermal denuder (TD) experiments are conducted and enhancements are calculated from two different methods that agree well with each other, confirming the observed results. BC measurements are also compared with co-located measurements from SPLAT-II and filter analysis using SEM and TEM. BC coagulated with SOA produces minimal absorption enhancement values, whereas coatings are observed to have significant enhancement values at 300 degrees C, e.g. 1.3 for thickly coated BC. BC particles were coagulated with SOA in the chamber since this morphology has been observed in wildfire emissions (Sedlacek et al., 2012). Since we did not observe appreciable enhancements for the coagulated BC, we expect that ambient emissions dominated by this particle type to have enhancements due to other sources, such as brown carbon (BrC) that is often co-emitted (Saleh et al., 2014). We also observed thickly coated BC that is not detected by the SP2 when the coatings are too thick for the laser to evaporate the coating and for the BC core to receive enough energy from the laser to incandesce. This noted caveat warrants more research to determine how prevalent this BC particle type is and how it would be expected to impact climate.

A Phase Ib/II Dose-finding Study to Assess the Safety and Efficacy of LDE225 + INC424 in Patients With MF

ClinicalTrials.gov

2017-07-24

Primary Myelofibrosis; Thrombocythemia, Essential; Thrombocytosis; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Blood Coagulation Disorders; Blood Platelet Disorders; Hemorrhagic Disorders

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.

Recombinant α1-Antitrypsin Pittsburgh Attenuates Experimental Gram-Negative Septicemia

PubMed Central

Colman, Robert W.; Flores, Daniel N.; De La Cadena, Raul A.; Scott, Cheryl F.; Cousens, Laurence; Barr, Philip J.; Hoffman, Ian B.; Kueppers, Friedrich; Fisher, Donald; Idell, Steven; Pisarello, Jorge

1988-01-01

Alpha1-antitrypsin-Pittsburgh (AT-P), a naturally occurring lethal mutation (358Met → Arg), has been genetically engineered (rAT-P). The protein has been shown to be a potent active site-directed inhibitor of thrombin and the contact enzymes Factor XIIf, Factor XIa, and kallikrein. Because activation of the contact system is known to occur in gram-negative septicemia, the authors have hypothesized that the administration of rAT-P might modulate the course of this syndrome. Yorkshire piglets anesthetized with pentobarbital and infused with viable Pseudomonas aeruginosa (2 X 108 CFU) were untreated (Group I) or treated with rAT-P (Group II) and studied in a 6-hour protocol. Coagulation studies revealed that rAT-P significantly inhibited the rapid decrease in the functional concentrations of Antithrombin III, Factor XI, and fibrinogen. In addition, rAT-P markedly reduced the serum levels of fibrinogen degradation products. Survival in Group II was significantly increased during 2-5 hours but not at 6 hours when the functional levels of rAT-P in plasma were the lowest. These results indicate that this recombinant inhibitor, even at low concentrations, affords protection in experimental gram-negative septicemia. PMID:3257651

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.

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.

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

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.

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.

Initial Resuscitation with Plasma and Other Blood Components Reduced Bleeding Compared to Hetastarch in Anesthetized Swine with Uncontrolled Splenic Hemorrhage

DTIC Science & Technology

2011-04-01

products and Hextend. The fluid with the highest amount of coagulation factors , FFP resulted in the lowest blood loss. The FFP treatment had the highest...compared to humans and have higher concentrations of many of the clotting factors (FV, FVII , FVIII, F IX, and FXII).44 Although we have confirmed the higher...utilizing plasma early in treatment is to prevent dilution of remaining coagulation factors or reverse the coagulopathy that has been observed in

Effects of In Vitro Hemodilution, Hypothermia and rFVIIa Addition on Coagulation in Human Blood

DTIC Science & Technology

2012-03-30

primary fluids used by many trauma units and the US Army for pre-hospital resuscitation [17]. HX, a hetastarch-based product in a balanced electro...and has been associated with dilution of coagulation factors and hypothermia. Recombinant activated Factor VII (rFVIIa) has been used, often as a...of rFVIIa results in an enhancement of thrombin generation on the platelet surface at the site of injury independent of the presence of Factor VIII

The Hag-protease-II is a fibrin(ogen)ase from Hippasa agelenoides spider venom gland extract: purification, characterization and its role in hemostasis.

PubMed

Devaraja, S; Girish, K S; Gowtham, Y N J; Kemparaju, K

2011-02-01

The current study describes the biochemical, biophysical and pharmacological properties of Hag-protease-II from Hippasa agelenoides spider venom gland extract. The Hag-protease-II was purified to homogeneity using gel filtration and ion-exchange chromatography. The molecular mass was found to be 28.749 kDa by MALDI-TOF mass spectrometry. PMSF abolished the activity while EDTA, EGTA, IAA and 1, 10-phenanthrolene did not. Hag-protease-II hydrolyzed casein, fibrinogen and fibrin, however it did not hydrolyze gelatin, fibronectin and collagen types- I and IV. It was non-lethal and devoid of hemorrhagic, myotoxic and edema forming activities. It dose dependently reduced re-calcification time of citrated human plasma. Strikingly; the Hag-protease-II coagulated the factor X deficient congenital human plasma. It hydrolyzed Bβ-chain but, did not degrade Aα- and γ-chains of fibrinogen while, it hydrolyzed α-polymer and α-chain but not the β-chain and γ-γ dimers of partially cross-linked fibrin clot. The Hag-protease-II induced aggregation of human platelets in PRP dose dependently, however it did not interfere in collagen induced aggregation of PRP and washed human platelets. Copyright © 2010 Elsevier Ltd. All rights reserved.

Soluble Proteins Form Film by the Treatment of Low Temperature Plasma

NASA Astrophysics Data System (ADS)

Ikehara, Sanae; Sakakita, Hajime; Ishikawa, Kenji; Akimoto, Yoshihiro; Nakanishi, Hayao; Shimizu, Nobuyuki; Hori, Masaru; Ikehara, Yuzuru

2015-09-01

It has been pointed out that low temperature plasma in atmosphere was feasible to use for hemostasis without heat injury. Indeed, earlier studies demonstrated that low temperature plasma played an important role to stimulate platelets to aggregate and turned on the proteolytic activities of coagulation factors, resulting in the acceleration of the natural blood coagulation process. On the other hands, our developed equips could immediately form clots upon the contact with plasma flair, while the histological appearance was different from natural coagulation. Based on these findings in formed clots, we sought to determine if plasma flair supplied by our devices was capable of forming film using a series of soluble proteins Following plasma treatment, films were formed from bovine serum albumin, and the other plasma proteins at physiological concentration. Analysis of trans-electron microscope demonstrated that plasma treatment generated small protein particles and made them fuse to be larger aggregations The combined results demonstrated that plasma are capable of aggregating soluble proteins and that platelets and coagulation factors are not necessary for plasma induced blood coagulation. Supported in part by Grants-in-Aid for Scientific Research on Priority Area (21590454, 24590498, and 24108006 to Y. I.).

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.

Isolation and partial purification of anticoagulant fractions from the venom of the Iranian snake Echis carinatus.

PubMed

Babaie, Mahdi; Zolfagharian, Hossein; Salmanizadeh, Hossein; Mirakabadi, Abbas Zare; Alizadeh, Hafezeh

2013-01-01

Many snake venoms comprise different factors, which can either promote or inhibit the blood coagulation pathway. Coagulation disorders and hemorrhage belong to the most prominent features of bites of the many vipers. A number of these factors interact with components of the human blood coagulation. This study is focused on the effect of Echis carinatus snake venom on blood coagulation pathway. Anticoagulant factors were purified from the Iranian Echis carinatus venom by two steps: gel filtration (Sephadex G-75) and ion-exchange (DEAE-Sephadex) chromatography, in order to study the anticoagulant effect of crude venom and their fractions. The prothrombin time was estimated on human plasma for each fraction. Our results showed that protrombin time value was increase from 13.4 s to 170 s for F2C and to 280 s for F2D. Our study showed that these fractions of the venom delay the prothrombine time and thus can be considered as anticoagulant factors. They were shown to exhibit proteolytic activity. The molecular weights of these anticoagulants (F2C, F2D) were estimated by SDS/PAGE electrophoresis. F2C comprises two protein bands with molecular weights of 50 and 79 kDa and F2D a single band with a molecular weight of 42 kDa.

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 of the functional coagulation activity of FV in human plasma.

How Frequency of Electrosurgical Current and Electrode Size Affect the Depth of Electrocoagulation.

PubMed

Taheri, Arash; Mansoori, Parisa; Bahrami, Naeim; Alinia, Hossein; Watkins, Casey E; Feldman, Steven R

2016-02-01

Many factors affect the depth of electrocoagulation. To evaluate the effect of current frequency and electrode size on the depth of electrocoagulation. In this in vitro study, 4 cylindrical electrodes (2, 2.3, 3, and 4 mm) were used to apply 3 electrosurgical currents (0.4, 1.5, and 3 MHz) to bovine liver. Each electrode was placed at different points on the surface of the liver, and energy at various levels and frequencies was delivered to the tissue. Subsequently, cross-sections of the liver were analyzed. Coagulation started at the periphery of the electrode-tissue contact area. With higher energy levels, coagulation spreads to involve the remainder of the contact area. Neither the frequency nor the electrode size had any effect on this coagulation pattern. The frequency of the current also did not show any relation with depth of coagulation; however, there was a direct correlation between the size of the electrode and the depth of coagulation. Larger-tip electrodes provided deeper coagulation compared with finer-tip electrodes.

Life-threatening urethral hemorrhage after placement of a Foley catheter in a patient with uroseptic disseminated intravascular coagulation due to chronic urinary retention induced by untreated benign prostatic hyperplasia.

PubMed

Ikegami, Yukihiro; Yoshida, Keisuke; Imaizumi, Tsuyoshi; Isosu, Tsuyoshi; Kurosawa, Shin; Murakawa, Masahiro

2016-10-01

A 77-year-old man with severe septic disseminated intravascular coagulation following urinary infection was transported to our hospital. He had developed urinary retention induced by untreated prostatic hyperplasia. Immediate drainage with a Foley catheter was successfully carried out, but the hematuria progressed to life-threatening hemorrhage. Complete hemostasis was impossible by surgical treatment because the tissue around the prostatic urethra was very fragile and hemorrhagic. Organized treatments (continuous hemodiafiltration combined with polymyxin-B immobilized fiber column hemoperfusion and systemic treatment with antibiotics and coagulation factors) were commenced soon after the operation. The patient eventually recovered from the septic disseminated intravascular coagulation. This case report illustrates the risk of placement of Foley catheters in patients with severe septic disseminated intravascular coagulation.

In Vitro and In Vivo Investigation of High-Intensity Focused Ultrasound (HIFU) Hat-Type Ablation Mode

PubMed Central

Dai, Hongya; Chen, Fei; Yan, Sijing; Ding, Xiaoya; Ma, Dazhao; Wen, Jing; Xu, Die; Zou, Jianzhong

2017-01-01

Background The aim of this study was to investigate the feasibility of the application of high-intensity focused ultrasound (HIFU) hat-type ablation mode in in vitro and in vivo models, and to compare the ablation effects of different parameter combinations. Material/Methods HIFU hat-type ablation was performed in isolated bovine liver tissue and in the liver tissue in living rabbits, and the coagulative necrosis for different parameter combinations (plane angles and irradiation order) was investigated. We also analyzed and compared the ablation effects of traditional ablation and hat-type ablation modes. Coagulative necrosis morphology was detected with TTC staining, and the coagulative necrosis volume and energy efficiency factor (EEF) were calculated and compared. Results Coagulative necrosis was observed in all the ablated groups, and the coagulative necrosis volume was much larger than the irradiation area. The coagulative necrosis induced by the hat-type ablation was more regular and controllable than the traditional ablation. The angles between the ablation planes determined the coagulative necrosis morphology, but did not affect the coagulative necrosis volume. Moreover, the irradiation order significantly influenced the coagulative necrosis. Importantly, under certain conditions, hat-type ablation achieved higher efficiency compared with the traditional ablation mode. Conclusions Compared with the traditional ablation mode, HIFU hat-type ablation effectively shortened the irradiation time, reduced the over-accumulation of energy, and increased the HIFU ablation efficiency. PMID:28699626

In Vitro and In Vivo Investigation of High-Intensity Focused Ultrasound (HIFU) Hat-Type Ablation Mode.

PubMed

Dai, Hongya; Chen, Fei; Yan, Sijing; Ding, Xiaoya; Ma, Dazhao; Wen, Jing; Xu, Die; Zou, Jianzhong

2017-07-12

BACKGROUND The aim of this study was to investigate the feasibility of the application of high-intensity focused ultrasound (HIFU) hat-type ablation mode in in vitro and in vivo models, and to compare the ablation effects of different parameter combinations. MATERIAL AND METHODS HIFU hat-type ablation was performed in isolated bovine liver tissue and in the liver tissue in living rabbits, and the coagulative necrosis for different parameter combinations (plane angles and irradiation order) was investigated. We also analyzed and compared the ablation effects of traditional ablation and hat-type ablation modes. Coagulative necrosis morphology was detected with TTC staining, and the coagulative necrosis volume and energy efficiency factor (EEF) were calculated and compared. RESULTS Coagulative necrosis was observed in all the ablated groups, and the coagulative necrosis volume was much larger than the irradiation area. The coagulative necrosis induced by the hat-type ablation was more regular and controllable than the traditional ablation. The angles between the ablation planes determined the coagulative necrosis morphology, but did not affect the coagulative necrosis volume. Moreover, the irradiation order significantly influenced the coagulative necrosis. Importantly, under certain conditions, hat-type ablation achieved higher efficiency compared with the traditional ablation mode. CONCLUSIONS Compared with the traditional ablation mode, HIFU hat-type ablation effectively shortened the irradiation time, reduced the over-accumulation of energy, and increased the HIFU ablation efficiency.

Epsilon-aminocaproic Acid for Treatment of Fibrinolysis during Liver Transplantation

PubMed Central

Kang, Yoogoo; Lewis, Jessica H.; Navalgund, Ashok; Russell, Michael W.; Bontempo, Franklin A.; Niren, Lawrence S.; Starzl, Thomas E.

2010-01-01

In 97 adult patients receiving liver transplants, the coagulation system was monitored by thrombelastography and by coagulation profile including PT; aPTT; platelet count; level of factors I, II, V, VII, VIII, IX, X, XI, and XII; fibrin degradation products; ethanol gel test; protamine gel test; and euglobulin lysis time. Preoperatively, fibrinolysis defined as a whole blood clot lysis index of less than 80% was present in 29 patients (29.9%), and a euglobulin lysis time of less than 1 h was present in 13 patients. Fibrinolysis increased progressively during surgery in 80 patients (82.5%) and was most severe on reperfusion of the graft liver in 33 patients (34%). When whole blood clot lysis (F < 180 min) was observed during reperfusion of the graft liver, blood coagulability was tested by thrombelastography using both a blood sample treated in vitro with ε-aminocaproic acid (0.09%) and an untreated sample. Blood treated with ε-aminocaproic acid showed improved coagulation without fibrinolytic activity in all 74 tests. When whole blood clot lysis time was less than 120 min, generalized oozing occurred, and the effectiveness of ε-aminocaproic acid was demonstrated in vitro during the pre-anhepatic and post-anhepatic stages, ε-aminocaproic acid (1 g, single intravenous dose) was administered. In all 20 patients treated with ε-aminocaproic acid, fibrinolytic activity disappeared; whole blood clot lysis was not seen on thrombelastography during a 5-h observation period, and whole blood clot lysis index improved from 28.5 ± 29.5% to 94.8 ± 7.4% (mean ± SD, P < 0.001). None of the treated patients had hemorrhagic or thrombotic complications. In patients undergoing liver transplantation, the judicious use of a small dose of ε-aminocaproic acid, when its efficacy was confirmed in vitro, effectively treated the severe fibrinolysis without clinical thrombotic complications. PMID:3296855

Microvesicle Tissue Factor Activity and Interleukin-8 Levels are Associated with Mortality in Patients with Influenza A/H1N1 Infection.

PubMed

Rondina, Matthew T; Tatsumi, Kohei; Bastarache, Julie A; Mackman, Nigel

2016-07-01

To identify plasma biomarkers that can be early predictors of mortality in critically ill patients with primary influenza A/H1N1. A prospective, multicenter, case-cohort pilot study. Three academic ICUs. Fifteen patients with primary influenza A/H1N1 that included seven survivors and eight nonsurvivors. For comparison, age- and gender-matched healthy controls (n = 27) were also studied. Plasma was prepared from whole blood drawn on ICU admission in patients with influenza (ICU day 1). Microvesicle tissue factor activity, thrombin-antithrombin complexes, and D-dimers were measured as procoagulant markers and markers of activation of coagulation. Plasma cytokine levels were measured on the same blood samples in a subset of 12 patients with influenza using the Luminex Multi-Analyte Profiling system (Luminex Corporation, DeSoto, TX). Patients were followed up for the primary outcome of 28-day mortality. The average admission Acute Physiology and Chronic Health Evaluation II score of the patients was 25.5 ± 9.3, 60% of patients had shock, and the 28-day mortality rate was 53.3% (n = 8/15). Patients with influenza had dysregulated indices of coagulation and inflammation compared with controls. Among the markers of activation of coagulation measured on ICU day 1, only increased microvesicle tissue factor activity was significantly associated with subsequent influenza-related mortality (5.6 ± 1.2 pg/mL in nonsurvivors vs 1.8 ± 0.8 pg/mL in survivors; p < 0.05). Interleukin-8 was significantly higher in nonsurvivors compared with survivors (71.8 ± 29.1 pg/mL, n = 5 vs 17.3 ± 3.7 pg/mL, n = 7; p < 0.05). In addition, microvesicle tissue factor activity and interleukin-8 levels were significantly and positively correlated (r = 0.60; p = 0.003). Other cytokines, thrombin-antithrombin complexes, and D-dimer were not different between nonsurvivors and survivors and did not correlate with illness severity or mortality. This study identifies an association between plasma interleukin-8 and microvesicle tissue factor activity measured on admission in patients with severe, primary influenza A/H1N1 infection and subsequent mortality. Thus, these biomarkers may serve as very early prognostic markers for patients with influenza A/H1N1.

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

Hemostasis in Overt and Subclinical Hyperthyroidism

PubMed Central

Ordookhani, Arash; Burman, Kenneth D.

2017-01-01

Context There are contradictory results on the effect of hyperthyroidism on hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). The present review focuses on hemostatic changes in overt and subclinical hyperthyroidism. Methods A systematic literature search was conducted employing MEDLINE database. The following words were used for the search: Hyperthyroidism; thyrotoxicosis; Graves disease; goiter, nodular; hemostasis; blood coagulation factors; blood coagulation disorders; venous thromboembolism; bleeding; fibrinolysis. The articles that were related to hyperthyroidism and hemostasis are used in this manuscript. Results Hyperthyroidism, either overt or subclinical, renders a hypercoagulable state, although there are several studies with contradictory findings in the literature. Hypercoagulability may be caused by an increase in the level of various coagulation factors such as factor (F) VIII, FX, FIX, von Willebrand F (vWF), and fibrinogen, while hypofibrinolysis by changes in coagulation parameters such as a decrease in plasmin and plasmin activator or an increase in α2-antiplasmin, plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor Conclusions Although many reports are in favor of a hypercoagulable state in overt hyperthyroidism but this finding at the biochemical level and its clinical implication, on the occurrence of VTE, has yet to be confirmed. PMID:29201071

Effect of N-acetylcysteine on the accuracy of the prothrombin time assay of plasma coagulation factor II+VII+X activity in subjects infused with the drug. Influence of time and temperature.

PubMed

Thorsen, Sixtus; Teisner, Ane; Jensen, Søren Astrup; Philips, Malou; Dalhoff, Kim; Bendtsen, Flemming

2009-01-01

The prothrombin time (PT) assay of factor II+VII+X activity is an important predictor of liver damage in paracetamol poisoned patients. It complicates interpretation of results that the antidote, acetylcysteine (NAC) depresses this activity. The aim was to investigate if NAC influences the accuracy of the plasma PT assay. The accuracy of Nycotest PT was studied using plasma added NAC in vitro and plasma from subjects infused with NAC. The latter results were compared with those obtained by analysis of PT by CoaguChek S. Therapeutic NAC concentrations added to plasma in vitro decreased factor II+VII+X activity at 37 degrees C in a time-dependent manner. This effect was quenched at temperatures <24 degrees C. Activity lost at 37 degrees C could partly be recovered by subsequent incubation at 5 or 20 degrees C. Incubation at 37 degrees C prior to assay led to a significant additional depression of factor II+VII+X activity in plasma from subjects infused with NAC during the first 3h of infusion indicating that it contained reactive NAC. The risk that this NAC interfered with the accuracy of the PT assay was considered minimal with samples stored below 24 degrees C. This was supported by similarity of results obtained by analysis of appropriately stored plasma and simultaneously drawn blood by CoaguChek S. Residual reactive NAC does not interfere with the accuracy of the PT assay of plasma stored below 24 degrees C, but NAC-induced loss in activity at 37 degrees C may be partly recovered during subsequent storage below 24 degrees C.

Factor XI as a target for antithrombotic therapy

PubMed Central

Bane, Charles E.; Gailani, David

2014-01-01

Anticoagulants currently used in clinical practice to treat thromboembolic disorders are effective but increase the risk of severe bleeding because they target proteins that are essential for normal coagulation (hemostasis). Drugs with better safety profiles are required for prevention and treatment of thromboembolic disease. Coagulation factor XIa has emerged as a novel target for safer anticoagulant therapy because of its role in thrombosis and its relatively small contribution to hemostasis. PMID:24886766

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.

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.

[Clinical characteristics and prognosis in patients with high plasma level of procalcitonin: an analysis in 188 patients].

PubMed

Pan, Chuli; Cui, Wei; Zhou, Feifei; Tu, Junwei; Lin, Xiuhui; Li, Libin; Zhang, Gensheng

2017-07-01

To investigate the clinical characteristics and prognosis of patients with high level of plasma procalcitonin (PCT > 100 μg/L), and to improve the clinician's understanding, diagnosis and treatment of this kind of patients. A retrospective study was conducted. The clinical data of patients with plasma PCT over 100 μg/L within 48 hours of admission admitted to Second Affiliated Hospital of Zhejiang University School of Medicine from February 2013 to December 2016 were collected, and the clinical characteristics were analyzed. The patients were divided into survival and death groups according to 28-day prognosis. The general data and laboratory parameters including vital signs, 24-hour urine output, routine blood test, blood biochemical tests, coagulation parameters, myocardial enzymes and arterial blood gas analysis were collected. The risk factors of mortality were analyzed using multi-logistic regression analysis. 188 patients with high level of plasma PCT were enrolled. There were 128 male patients (68.1%) with the average age of 62 (49, 75) years. Most patients were admitted in intensive care unit (ICU, 70.7%, 133/188). Major diagnosis was sepsis (91.0%), followed by multiple organ dysfunction syndrome (MODS, 57.4%), post large operation of thorax and abdomen (20.7%), trauma/burns (13.8%) and post-cardiopulmonary resuscitation (CPR, 6.4%). Of all the 188 patients, 115 patients survived and 73 died with a mortality of 38.8%. The parameters in the death group, including the percentages of MODS (84.9% vs. 40.0%), trauma/burns (26.0% vs. 6.1%), post-CPR (13.7% vs. 1.7%), ventilator support (82.2% vs. 40.9%) and shock (100.0% vs. 60.0%), the numbers of principal diagnosis [2.0 (2.0, 3.0) vs. 2.0 (1.0, 2.0)], acute physiology and chronic health evaluation II score [APACHE II score: 24 (19, 28) vs. 14 (10, 16)] and sequential organ failure assessment (SOFA) score [16.0 (12.5, 18.0) vs. 9.0 (6.0, 12.0)], as well as liver function, coagulation parameters, myocardial enzymes and lactic acid (Lac) levels were significantly higher than those in the survival group, but the platelet (PLT) count in the death group was significantly lower than that in the survival group [×10 9 /L: 62.00 (21.50, 111.00) vs. 93.00 (53.00, 136.00), all P < 0.05]. The parameters with statistical significance in the univariate analysis were enrolled in the multiple factor logistic regression analysis, which showed that patient with a high score of APACHE II [odds ratio (OR) = 1.290, 95% confidence interval (95%CI) = 1.121-1.484, P = 0.000] or the occurrence of MODS (OR = 7.264, 95%CI = 1.762-29.941, P = 0.006) at admission had a poor prognosis. The primary patients with high levels of plasma PCT (> 100 μg/L) were diagnosed with sepsis, MODS, trauma and post-CPR, complicated with respiratory and circulatory insufficiency. These factors of trauma, MODS and cardiac arrest, and some laboratory parameters including PLT, Lac, liver function, coagulation spectrum, and cardiac enzymes were correlated with the prognosis of the patients with high levels of plasma PCT. High APACHE II score and the incidence of MODS might be independent predictors of poor prognosis in the patients with high levels of plasma PCT.

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.

[Evaluation of selected parameters of blood coagulation and fibrinolysis system in patients undergoing total hip replacement surgery with normovolemic hemodilution procedure and standard enoxaparine prophylaxis].

PubMed

Piecuch, Wiesław; Sokołowska, Bozena; Dmoszyńska, Anna; Furmanik, Franciszek

2003-01-01

The aim of the study was to evaluate selected blood coagulation and fibrinolysis parameters in patients undergoing total hip replacement surgery with normovolemic hemodilution and standard enoksaparine profilaxis. The study included 66 patients undergoing hip replacement surgery. The group consisted of 51 women and 15 men, within the age range of 47-78, the mean age was 64. In 32 (subgroup II) patients the surgery was performed with the use of normovolemic hemodilution, in 34 (subgroup I) the hemodilution procedure was not applied. The enoksaparine as prophylaxis started 12 hours prior to surgery and continued during hospitalisation. The examination of the coagulation system was performed: on the day of the operation in the morning, on the day of the operation in the evening and on the first day after operation. We determined the concentrations of TAT and PAP complexes, prothrombin fragments 1 + 2 (F1 + 2) and d-dimers (DD). 1) during total hip replacement surgery and particularly in the period of the first 12 hours after the procedure marked activation of coagulation and fibrinolysis occurRed; 2) the application of the hemodilution procedure does not influence significantly the degree of coagulation and fibrinolysis disorders in the perioperative period, but could reduced incidence of thromboembolic complications in the postoperative period.

Neonatal Plasma Transfusion: An Evidence-Based Review.

PubMed

Keir, Amy K; Stanworth, Simon J

2016-10-01

Several clinical scenarios for plasma transfusion are repeatedly identified in audits, including treatment of bleeding in association with laboratory evidence of coagulopathy, correction of disseminated intravascular coagulation, prevention of intraventricular hemorrhage, management of critically ill neonates (eg, during sepsis or as a volume expander), or correction of markers of prolonged coagulation in the absence of bleeding. The findings of at least one national audit of transfusion practice indicated that almost half of plasma transfusions are given to neonates with abnormal coagulation values with no evidence of active bleeding, despite the limited evidence base to support the effectiveness of this practice. Plasma transfusions to neonates should be considered in the clinical context of bleeding (eg, vitamin K dependent), disseminated intravascular coagulation, and very rare inherited deficiencies of coagulation factors. There seems to be no role for prophylactic plasma to prevent intraventricular hemorrhage or for use as a volume expander. Copyright © 2016 Elsevier Inc. All rights reserved.

Investigating the characteristic strength of flocs formed from crude and purified Hibiscus extracts in water treatment.

PubMed

Jones, Alfred Ndahi; Bridgeman, John

2016-10-15

The growth, breakage and re-growth of flocs formed using crude and purified seed extracts of Okra (OK), Sabdariffa (SB) and Kenaf (KE) as coagulants and coagulant aids was assessed. The results showed floc size increased from 300 μm when aluminium sulphate (AS) was used as a coagulant to between 696 μm and 722 μm with the addition of 50 mg/l of OK, KE and SB crude samples as coagulant aids. Similarly, an increase in floc size was observed when each of the purified proteins was used as coagulant aid at doses of between 0.123 and 0.74 mg/l. The largest floc sizes of 741 μm, 460 μm and 571 μm were obtained with a 0.123 mg/l dose of purified Okra protein (POP), purified Sabdariffa (PSP) and purified Kenaf (PKP) respectively. Further coagulant aid addition from 0.123 to 0.74 mg/l resulted in a decrease in floc size and strength in POP and PSP. However, an increase in floc strength and reduced d50 size was observed in PKP at a dose of 0.74 mg/l. Flocs produced when using purified and crude extract samples as coagulant aids exhibited high recovery factors and strength. However, flocs exhibited greater recovery post-breakage when the extracts were used as a primary coagulant. It was observed that the combination of purified proteins and AS improved floc size, strength and recovery factors. Therefore, the applications of Hibiscus seeds in either crude or purified form increases floc growth, strength, recoverability and can also reduce the cost associated with the import of AS in developing countries. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Effect of two oral doses of 17beta-estradiol associated with dydrogesterone on thrombin generation in healthy menopausal women: a randomized double-blind placebo-controlled study.

PubMed

Rousseau, Alexandra; Robert, Annie; Gerotziafas, Grigoris; Torchin, Dahlia; Zannad, Faiez; Lacut, Karine; Libersa, Christian; Dasque, Eric; Démolis, Jean-Louis; Elalamy, Ismail; Simon, Tabassome

2010-04-01

Oral hormone therapy is associated with an increased risk of venous thrombosis. Drug agencies recommend the use of the lowest efficient dose to treat menopausal symptoms for a better risk/ratio profile, although this profile has not been totally investigated yet. The aim of the study was to compare the effect of the standard dose of 17beta-estradiol to a lower one on thrombin generation (TG). In a 2-month study, healthy menopausal women were randomized to receive daily 1mg or 2 mg of 17beta-estradiol (E1, n = 24 and E2, n = 26; respectively) with 10 mg dydrogesterone or placebo (PL, n = 22). Plasma levels factors VII, X, VIII and II were assessed before and after treatment as well as Tissue factor triggered TG, which allows the investigation of the different phases of coagulation process. The peak of thrombin was higher in hormone therapy groups (E1: 42.39 +/- 50.23 nm, E2: 31.08 +/- 85.86 nm vs. 10.52 +/- 40.63 nm in PL, P = 0.002 and P = 0.01). Time to reach the peak was also shortened (PL: 0.26 +/- 0.69 min vs. E1: -0.26 +/- 0.80 min, E2: -0.55 +/- 0.79 min, P <10(-3) for both comparisons) and mean rate index of the propagation phase of TG was significantly increased. Among the studied clotting factors, only the levels of FVII were significantly increased after treatment administration. The two doses of 17beta-estradiol induced in a similar degree an acceleration of the initiation and propagation phase of tissue factor triggered thrombin generation and a significant increase of FVII coagulant activity.

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 Elsevier Ltd. All rights reserved.

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

Comparison of two methods for blood lead analysis in cattle: graphite-furnace atomic absorption spectrometry and LeadCare(R) II system.

PubMed

Bischoff, Karyn; Gaskill, Cynthia; Erb, Hollis N; Ebel, Joseph G; Hillebrandt, Joseph

2010-09-01

The current study compared the LeadCare(R) II test kit system with graphite-furnace atomic absorption spectrometry for blood lead (Pb) analysis in 56 cattle accidentally exposed to Pb in the field. Blood Pb concentrations were determined by LeadCare II within 4 hr of collection and after 72 hr of refrigeration. Blood Pb concentrations were determined by atomic absorption spectrometry, and samples that were coagulated (n = 12) were homogenized before analysis. There was strong rank correlation (R(2) = 0.96) between atomic absorption and LeadCare II (within 4 hr of collection), and a conversion formula was determined for values within the observed range (3-91 mcg/dl, although few had values >40 mcg/dl). Median and mean blood pb concentrations for atomic absorption were 7.7 and 15.9 mcg/dl, respectively; for LeadCare II, medians were 5.2 mcg/dl at 4 hr and 4.9 mcg/dl at 72 hr, and means were 12.4 and 11.7, respectively. LeadCare II results at 4 hr strongly correlated with 72 hr results (R(2) = 0.96), but results at 72 hr were lower (P < 0.01). There was no significant difference between coagulated and uncoagulated samples run by atomic absorption. Although there have been several articles that compared LeadCare with other analytical techniques, all were for the original system, not LeadCare II. The present study indicated that LeadCare II results correlated well with atomic absorption over a wide range of blood Pb concentrations and that refrigerating samples for up to 72 hr before LeadCare II analysis was acceptable for clinical purposes.

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

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.

Identifying coagulopathies in the pathophysiology of cold stress syndrome in the Florida manatee Trichechus manatus latirostris.

PubMed

Barratclough, Ashley; Conner, Bobbi J; Brooks, Marjory B; Pontes Stablein, Alyssa; Gerlach, Trevor J; Reep, Roger L; Ball, Ray L; Floyd, Ruth Francis

2017-08-09

Cold stress syndrome (CSS) in the Florida manatee Trichechus manatus latirostris has been defined as morbidity and mortality resulting from prolonged exposure to water temperatures <20°C. The pathophysiology is described as multifactorial, involving nutritional, immunological and metabolic disturbances; however, the exact mechanisms are unknown. We hypothesized that thromboembolic complications contribute to the pathophysiology of CSS in addition to the previously described factors. During the winter of 2014-2015, 10 Florida manatees with clinical signs of CSS were presented to Lowry Park Zoo, Tampa, FL, USA. Thromboelastography (TEG) and coagulation panels were performed at admission. In addition, coagulation panel data from 23 retrospective CSS cases were included in the analyses. There were numerous differences between mean values of TEG and coagulation parameters for healthy manatees and those for CSS cases. Among TEG parameters, reaction time (R), clot formation time (K) and percentage of clot lysed after 30 min (LY30) values were significantly different (p < 0.05) between the 2 groups. CSS cases also had significantly higher mean D-dimer concentration and coagulation factor XI activity, prolonged mean activated partial thromboplastin time (aPTT) and significantly decreased mean antithrombin activity. These combined abnormalities include clinicopathologic criteria of disseminated intravascular coagulation, indicating an increased risk of thromboembolic disease associated with manatee CSS.

Hemostasis in Hypothyroidism and Autoimmune Thyroid Disorders.

PubMed

Ordookhani, Arash; Burman, Kenneth D

2017-04-01

There are contradictory results on the effect of hypothyroidism on the changes in hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). This paper reviews the studies on laboratory and population-based findings regarding hemostatic changes and risk of VTE in hypothyroidism and autoimmune thyroid disorders. A comprehensive literature search was conducted employing MEDLINE database. The following words were used for the search: Hypothyroidism; thyroiditis, autoimmune; blood coagulation factors; blood coagulation tests; hemostasis, blood coagulation disorders; thyroid hormones; myxedema; venous thromboembolism; fibrinolysis, receptors thyroid hormone. The papers that were related to hypothyroidism and autoimmune thyroid disorder and hemostasis are used in this review. Overt hypothyroidism is more associated with a hypocoagulable state. Decreased platelet count, aggregation and agglutination, von Willebrand factor antigen and activity, several coagulation factors such as factor VIII, IX, XI, VII, and plasminogen activator-1 are detected in overt hypothyrodism. Increased fibrinogen has been detected in subclinical hypothyroidism and autoimmune thyroid disease rendering a tendency towards a hypercoagulability state. Increased factor VII and its activity, and plasminogen activator inhibitor-1 are among several findings contributing to a prothrombotic state in subclinical hypothyroidism. Overt hypothyroidism is associated with a hypocoagulable state and subclinical hypothyroidism and autoimmune thyroid disorders may induce a prothrombotic state. However, there are contradictory findings for the abovementioned thyroid disorders. Prospective studies on the risk of VTE in various levels of hypofunctioning of the thyroid and autoimmune thyroid disorders are warranted.

Hemostasis in Hypothyroidism and Autoimmune Thyroid Disorders

PubMed Central

Ordookhani, Arash; Burman, Kenneth D.

2017-01-01

Context There are contradictory results on the effect of hypothyroidism on the changes in hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). This paper reviews the studies on laboratory and population-based findings regarding hemostatic changes and risk of VTE in hypothyroidism and autoimmune thyroid disorders. Evidence Acquisition A comprehensive literature search was conducted employing MEDLINE database. The following words were used for the search: Hypothyroidism; thyroiditis, autoimmune; blood coagulation factors; blood coagulation tests; hemostasis, blood coagulation disorders; thyroid hormones; myxedema; venous thromboembolism; fibrinolysis, receptors thyroid hormone. The papers that were related to hypothyroidism and autoimmune thyroid disorder and hemostasis are used in this review. Results Overt hypothyroidism is more associated with a hypocoagulable state. Decreased platelet count, aggregation and agglutination, von Willebrand factor antigen and activity, several coagulation factors such as factor VIII, IX, XI, VII, and plasminogen activator-1 are detected in overt hypothyrodism. Increased fibrinogen has been detected in subclinical hypothyroidism and autoimmune thyroid disease rendering a tendency towards a hypercoagulability state. Increased factor VII and its activity, and plasminogen activator inhibitor-1 are among several findings contributing to a prothrombotic state in subclinical hypothyroidism. Conclusions Overt hypothyroidism is associated with a hypocoagulable state and subclinical hypothyroidism and autoimmune thyroid disorders may induce a prothrombotic state. However, there are contradictory findings for the abovementioned thyroid disorders. Prospective studies on the risk of VTE in various levels of hypofunctioning of the thyroid and autoimmune thyroid disorders are warranted. PMID:29026409

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 more sensitive to the perturbation of coagulation protein concentrations. Conclusions A QSP model for non-bleeding baseline coagulation activity was established with data from clinically relevant in vivo biomarkers at baseline and changes in response to rFVIIa treatment. This model will provide future mechanistic insights into this system. © 2016 International Society on Thrombosis and Haemostasis.

Vitamin K: from coagulation to calcification.

PubMed

Paakkari, Ilari

Vitamin K is not only essential for the synthesis of coagulation factors in the liver, but it also strengthens the bones and prevents calcification of the arteries. These effects are mediated through the same mechanism, i.e. carboxylation of Gla target proteins. The discovery of novel Gla proteins that are not associated with blood coagulation or calcium metabolism indicates that vitamin K has additional effects in the pancreas and the central nervous system, for example. As dietary supplements, vitamin K1 of plant origin and vitamins K2 of bacterial origin may exert different effects.

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

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 hypercoagulable state, which is partly attributable to IL-6 release by the tumor. The findings support the importance of the coagulation state in cancer cachexia and the clinical utility of anti-inflammatory interventions. © 2017 International Society on Thrombosis and Haemostasis.

PbO2(s, plattnerite) reductive dissolution by natural organic matter: reductant and inhibitory subfractions.

PubMed

Shi, Zhi; Stone, Alan T

2009-05-15

Natural organic matter (NOM) is a diverse collection of molecules, each possessing its own reductant, complexant, and adsorption properties. Here, we are interested in the ability of NOM to bring about the reductive dissolution of Pb(IV)O2(s). Adding the coagulants FeCl3 or Al2(SO4)3 followed by membrane filtration is one way to remove a subset of NOM molecules from surface water samples. Another is to pass water samples through a granular activated carbon (GAC) column. Results from applying these treatments to Great Dismal Swamp water (DSW) and Nequasset Bog Water (NBW) can best be explained as follows: (i) GAC column treatment is more efficient at removing the NOM fraction most responsible for reductive dissolution. (ii) Coagulation/filtration, with either coagulant, is most efficient at removing a second, inhibitory fraction. Inhibition may arise from (i) adsorption at the mineral/water interface, which blocks approach of reductant molecules and (ii) a micelle-like aggregate nature, which provides hydrophobic pockets that capture reductantmolecules, again keeping them away from the mineral/water interface. Hypotheses regarding reductant and inhibitory fractions are further evaluated using representative low-molecular-weight compounds. Substituted hydroquinones are used as mimics of the reductant fraction, and malonic acid, quinic acid, trehalose, alginic acid, and polygalacturonic acid are used as mimics of the inhibitory fraction.

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

Tissue Factor Pathway Inhibitor: Multiple Anticoagulant Activities for a Single Protein.

PubMed

Mast, Alan E

2016-01-01

Tissue factor (TF) pathway inhibitor (TFPI) is an anticoagulant protein that inhibits early phases of the procoagulant response. Alternatively spliced isoforms of TFPI are differentially expressed by endothelial cells and human platelets and plasma. The TFPIβ isoform localizes to the endothelium surface where it is a potent inhibitor of TF-factor VIIa complexes that initiate blood coagulation. The TFPIα isoform is present in platelets. TFPIα contains a stretch of 9 amino acids nearly identical to those found in the B-domain of factor V that are well conserved in mammals. These amino acids provide exosite binding to activated factor V, which allows for TFPIα to inhibit prothrombinase during the initiation phase of blood coagulation. Endogenous inhibition at this point in the coagulation cascade was only recently recognized and has provided a biochemical rationale to explain the pathophysiological mechanisms underlying several clinical disorders. These include the east Texas bleeding disorder that is caused by production of an altered form of factor V with high affinity for TFPI and a paradoxical procoagulant effect of heparins. In addition, these findings have led to ideas for pharmacological targeting of TFPI that may reduce bleeding in hemophilia patients. © 2015 American Heart Association, Inc.

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.

Factor XII (Hageman factor) deficiency

MedlinePlus

... disorders: coagulation factor deficiencies. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. ... Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

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

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.

Increased thromboplastic potential in diabetes: a multifactorial phenomenon.

PubMed

Landgraf-Leurs, M M; Ladik, T; Smolka, B; Bock, T; Schramm, W; Spannagl, M; Landgraf, R

1987-07-01

Coagulation parameters, platelet aggregation, and thromboxane production as well as metabolic parameters were measured in 31 diabetic patients, 12 without and 19 with clinically manifest late complications, and in 14 healthy control subjects. Spontaneous in vitro aggregation as well as ADP, collagen, and arachidonic acid induced aggregation were higher in both groups of diabetic patients, without an increase in thromboxane B2 production. In diabetic patients with late complications an increase in fibrinogen, fibrinogen cyanogen bromide peptide, factor VIII related antigen, C1-esterase inhibitor, and antithrombin III was observed in comparison to healthy subjects. Fibrinogen, C1-esterase inhibitor, and factor VIII related antigen were already elevated in diabetic patients without clinically manifest late vascular complications. No strict correlations were found between serum glucose, glycosylated hemoglobin, and glycosylated albumin, on the one hand, and coagulation promoting or inhibiting factors, aggregation or thromboxane B2 production, on the other, in either control or diabetic subjects. Also no correlations existed between the coagulation parameters and the aggregation results. In vitro incubation of pooled normal plasma with different glucose concentrations had no influence on the methods by which the coagulation parameters were measured. These data indicate that rather early in the diabetic state many changes take place in different phases of the thrombostatic process, all resulting in an increased hemostatic diathesis.

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.

Hemostatic abnormalities in Noonan syndrome.

PubMed

Artoni, Andrea; Selicorni, Angelo; Passamonti, Serena M; Lecchi, Anna; Bucciarelli, Paolo; Cerutti, Marta; Cianci, Paola; Gianniello, Francesca; Martinelli, Ida

2014-05-01

A bleeding diathesis is a common feature of Noonan syndrome, and various coagulation abnormalities have been reported. Platelet function has never been carefully investigated. The degree of bleeding diathesis in a cohort of patients with Noonan syndrome was evaluated by a validated bleeding score and investigated with coagulation and platelet function tests. If ratios of prothrombin time and/or activated partial thromboplastin time were prolonged, the activity of clotting factors was measured. Individuals with no history of bleeding formed the control group. The study population included 39 patients and 28 controls. Bleeding score was ≥2 (ie, suggestive of a moderate bleeding diathesis) in 15 patients (38.5%) and ≥4 (ie, suggestive of a severe bleeding diathesis) in 7 (17.9%). Abnormal coagulation and/or platelet function tests were found in 14 patients with bleeding score ≥2 (93.3%) but also in 21 (87.5%) of those with bleeding score <2. The prothrombin time and activated partial thromboplastin time were prolonged in 18 patients (46%) and partial deficiency of factor VII, alone or in combination with the deficiency of other vitamin K-dependent factors, was the most frequent coagulation abnormality. Moreover, platelet aggregation and secretion were reduced in 29 of 35 patients (82.9%, P < .01 for all aggregating agents). Nearly 40% of patients with the Noonan syndrome had a bleeding diathesis and >90% of them had platelet function and/or coagulation abnormalities. Results of these tests should be taken into account in the management of bleeding or invasive procedures in these patients. Copyright © 2014 by the American Academy of Pediatrics.

Reversal of dabigatran anticoagulation ex vivo: Porcine study comparing prothrombin complex concentrates and idarucizumab.

PubMed

Honickel, Markus; Treutler, Stefanie; van Ryn, Joanne; Tillmann, Sabine; Rossaint, Rolf; Grottke, Oliver

2015-04-01

Urgent surgery or life-threatening bleeding requires prompt reversal of the anticoagulant effects of dabigatran. This study assessed the ability of three- and four-factor prothrombin complex concentrate (PCC) and idarucizumab (specific antidote for dabigatran) to reverse the anticoagulant effects of dabigatran in a porcine model of trauma. Twelve animals were given dabigatran etexilate (DE) orally and dabigatran intravenously, before infliction of trauma. Six animals received tranexamic acid plus fibrinogen concentrate 12 minutes post-injury. Six PCCs (each 30 and 60 U/kg) and idarucizumab (30 and 60 mg/kg) were added to blood samples ex vivo. Coagulation was assessed by several coagulation assays. All coagulation parameters were altered after dabigatran infusion (plasma level: 442 ± 138 ng/ml). Both three- and four-factor PCCs mostly or completely reversed the effects of dabigatran on thromboelastometry variables and PT but not on aPTT. Idarucizumab neutralised plasma concentrations of dabigatran, and reversed the effects of the drug on coagulation variables. Thrombin generation showed dose-dependent over-correction following the addition of PCC, implying that elevated levels of thrombin are required to overcome dabigatran-induced coagulopathy. In contrast, treatment with idarucizumab returned thrombin generation to baseline levels. Following trauma, therapy with tranexamic acid plus fibrinogen improved correction of coagulation parameters by PCC, and thromboelastometry parameters by idarucizumab. All investigated PCCs improved dabigatran- and trauma-induced coagulopathy to a similar degree. In conclusion, this study shows that three- and four-factor PCCs are similarly effective for dabigatran reversal. Idarucizumab also reversed the effects of dabigatran and, unlike PCCs, was not associated with over-correction of thrombin generation.

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 can be utilized to simulate FVIII activity-time profiles for various dosing scenarios. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Hemostatic Changes Associated With Increased Mortality Rates in Hospitalized Patients With HIV-Associated Tuberculosis: A Prospective Cohort Study

PubMed Central

Schutz, Charlotte; Ward, Amy M.; Huson, Mischa A. M.; Wilkinson, Robert J.; Burton, Rosie; Maartens, Gary; Wilkinson, Katalin A.; Meijers, Joost C. M.; Lutter, René; Grobusch, Martin P.; Meintjes, Graeme; van der Poll, Tom

2017-01-01

Background Mortality rates remain high for human immunodeficiency virus (HIV)–associated tuberculosis, and our knowledge of contributing mechanisms is limited. We aimed to determine whether hemostatic changes in HIV-tuberculosis were associated with mortality or decreased survival time and the contribution of mycobacteremia to these effects. Methods We conducted a prospective study in Khayelitsha, South Africa, in hospitalized HIV-infected patients with CD4 cell counts <350/µL and microbiologically proved tuberculosis. HIV-infected outpatients without tuberculosis served as controls. Plasma biomarkers reflecting activation of procoagulation and anticoagulation, fibrinolysis, endothelial cell activation, matricellular protein release, and tissue damage were measured at admission. Cox proportional hazard models were used to assess variables associated with 12-week mortality rates. Results Of 59 patients with HIV-tuberculosis, 16 (27%) died after a median of 12 days (interquartile range, 0–24 days); 29 (64%) of the 45 not receiving anticoagulants fulfilled criteria for disseminated intravascular coagulation. Decreased survival time was associated with higher concentrations of markers of fibrinolysis, endothelial activation, matricellular protein release, and tissue damage and with decreased concentrations for markers of anticoagulation. In patients who died, coagulation factors involved in the common pathway were depleted (factor II, V, X), which corresponded to increased plasma clotting times. Mycobacteremia modestly influenced hemostatic changes without affecting mortality. Conclusions Patients with severe HIV-tuberculosis display a hypercoagulable state and activation of the endothelium, which is associated with mortality. PMID:28363198

Sequential organ failure assessment (SOFA) scores differ between genders in a sepsis cohort: cause or effect?

PubMed

Jacobson, Sofie; Liedgren, Eva; Johansson, Göran; Ferm, Martin; Winsö, Ola

2012-11-01

Controversy exists regarding the influence of gender on sepsis events and outcome. Epidemiological data from other countries may not always apply to local circumstances. The aim of this study was to identify gender differences in patient characteristics, treatment, and outcome related to the occurrence of sepsis at admission to the ICU. A prospective observational cohort study on patients admitted to the ICU over a 3-year period fulfilling sepsis criteria during the first 24 hours. Demographic data, APACHE II score, SOFA score, TISS 76, aetiology, length of stay (LOS), mortality rate, and aspects of treatment were collected and then analysed with respect to gender differences. There were no gender-related differences in mortality or length of stay. Early organ dysfunction assessed as SOFA score at admission was a stronger risk factor for hospital mortality for women than for men. This discrepancy was mainly associated with the coagulation sub-score. CRP levels differed between genders in relation to hospital mortality. Infection from the abdominopelvic region was more common among women, whereas infection from skin or skin structures were more common in men. In this cohort, gender was not associated with increased mortality during a 2-year follow-up period. SOFA score at ICU admission was a stronger risk factor for hospital mortality for women than for men. The discrepancy was mainly related to the coagulation SOFA sub-score. Together with differences in CRP levels this may suggest differences in inflammatory response patterns between genders.

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 clinical laboratories to provide measurement of the functional coagulation activity of FV in human plasma. PMID:21711555

Prolonged Activated Clotting Time after Protamine Administration Does Not Indicate Residual Heparinization after Cardiopulmonary Bypass in Pediatric Open Heart Surgery.

PubMed

Yamamoto, Tomohiro; Wolf, Hans-Gerd; Sinzobahamvya, Nicodème; Asfour, Boulos; Hraska, Victor; Schindler, Ehrenfried

2015-08-01

In open heart surgery, heparinization is commonly neutralized using an empirical heparin:protamine ratio ranging between 1:1 and 1:1.5. However, these ratios may result in protamine overdose that should be avoided for its negative side effects on the coagulation system. This study aimed to indicate the appropriate treatment for prolonged activated clotting time (ACT) after protamine administration following cardiopulmonary bypass (CPB) in pediatric open heart surgery by investigating the underlying reasons for it. Twenty-seven children (<10 kg) undergoing open heart surgery were included. Heparin was administered only before CPB (400 IU/kg) and in the pump priming volume for CPB (2,000 IU) and was neutralized by 1:1 protamine after CPB. The blood heparin concentration was measured using anti-Xa assay. ACT and blood concentrations of heparin, coagulation factors, thrombin-antithrombin complex, and prothrombin fragment 1 + 2 were assessed. A rotational thromboelastometry (ROTEM; Tem International GmbH, München, Bayern, Germany) was used to confirm the coagulation status and residual heparin after protamine administration. Anti-Xa assay showed that there is no residual heparin in the blood after 1:1 protamine administration. Nevertheless, ACT (128.89 ± 3.09 seconds before heparin administration) remained prolonged (177.14 ± 5.43 seconds at 10 minutes after protamine, 182.00 ± 5.90 seconds at 30 minutes after protamine). The blood concentrations of coagulation factors were significantly lower than those before heparin administration (p < 0.01). The low FIBTEM MCF of ROTEM (4.43 ± 0.32 mm) at 10 minutes after protamine indicated low fibrinogen concentration. Prolonged ACT after heparin neutralization by 1:1 protamine administration does not necessarily indicate residual heparin, but low blood concentrations of coagulation factors should be considered as a reason as well. Accordingly, supply of coagulation factors instead of additional protamine should be considered. Georg Thieme Verlag KG Stuttgart · New York.

Studies on a family with combined functional deficiencies of vitamin K-dependent coagulation factors.

PubMed Central

Goldsmith, G H; Pence, R E; Ratnoff, O D; Adelstein, D J; Furie, B

1982-01-01

Two siblings with m ild hemorrhagic symptoms had combined functional deficiencies of vitamin K-dependent clotting factors. Prothrombin (0.18-0.20 U/ml) and Stuart factor (Factor X, 0.18-0.20 U/ml) and Stuart factor (Factor X, 0.18-0.20 U/ml) were most severely affected. Antigenic amounts of affected coagulation factors were normal and normal generation of thrombin activity occurred in the patients' plasmas after treatment with nonophysiologic activators that do not require calcium for prothrombin activation. Hepatobilary disease, malabsorptive disorders, and plasma warfarin were not present. Both parents had normal levels of all coagulation factors. The patients' plasmas contained prothrombin that reacted both with antibody directed against des-gamma-carboxyprothrombin and native prothrombin. Crossed immunoelectrophoresis of patients' plasmas and studies of partially purified patient prothrombin suggested the presence of a relatively homogeneous species of dysfunctional prothrombin, distinct from the heterologous species found in the plasma of warfarin-treated persons. These studies are most consistent with a posttranslational defect in hepatic carboxylation of vitamin K-dependent factors. This kindred uniquely possesses an autosomal recessive disorder of vitamin K-dependent factor formation that causes production of an apparently homogeneous species of dysfunctional prothrombin; the functional deficiencies in clotting factors are totally corrected by oral or parenteral administration of vitamin K1. Images PMID:7085873

Quantitative evaluation of plasma after methylene blue and white light treatment in four Chinese blood centers.

PubMed

Chunhui, Yang; Guohui, Bian; Hong, Yang; Xiaopu, Xiao; Zherong, Bai; Mingyuan, Wang; Xinsheng, Zhang; Juanjuan, Wang; Changqing, Li; Wuping, Li

2013-12-01

Pathogen reduction technology is an important process in the blood safety system, including solvent/detergent treatment, filtration and methylene blue-photochemical technology (MB-PCT). To investigate the quality of MB-PCT-treated plasma, plasma samples from four Chinese blood centers were analyzed over 12 months of storage to determine the recovery of activities and levels of various plasma proteins. Ten plasma units each from the Suzhou, Yancheng, Chongqing and Shandong blood centers were divided into two aliquots. One was subjected to treatment with one of two methylene blue-photochemical technology instruments and the other was used as control. The treated and untreated sample pairs were stored at -30°C. The recovery rates of coagulation factors, inhibitor proteins, total protein, immunoglobulins, and complement proteins were measured at different time points after storage. The mean recovery of most proteins exceeded 80% after MB treatment. The exceptions were factor XI and fibrinogen, of which only 71.3-74% and 69.0-92.3% were retained during storage. The two equipment types differed in terms of residual MB concentration in the plasma samples (0.18 μM and 0.29 μM, respectively). They had similar protein recovery rates at 0.5 month but differed at later time points. The four blood centers differed significantly with regard to factor II, V, VIII and fibrinogen activities. Only the samples from the Shandong blood center met the methylene blue treated fresh frozen plasma requirement. The major factor that influenced the quality of the MB-FFP samples was the time taken between blood collection and storage. Methylene blue treated plasma showed reduced coagulation factor (CF) activity and protein levels. The MB treatment-induced damage to the proteins was acceptable at the four Chinese blood centers, but the quality of the MB-treated plasma in general was not satisfactory. The main factor affecting plasma quality may be the duration of the collection and processing. Copyright © 2013 Elsevier Ltd. All rights reserved.

DEVELOPMENT AND APPLICATION OF A NEW AIR POLLUTION MODELING SYSTEM--II. AEROSOL MODULE STRUCTURE AND DESIGN (R823186)

EPA Science Inventory

The methods used for simulating aerosol physical and chemical processes in a new air pollution modeling system are discussed and analyzed. Such processes include emissions, nucleation, coagulation, reversible chemistry, condensation, dissolution, evaporation, irreversible chem...

(Evaluation of neutralizing ability of four commercially available antivenoms against the venom of Bothrops asper from Costa Rica)

PubMed

Bogarín, G; Segura, E; Durán, G; Lomonte, B; Rojas, G; Gutiérrez, J M

1995-09-01

We studied the ability of four commercially available antivenoms to neutralize several toxic and enzymatic activities of Bothrops asper (terciopelo) venom from Costa Rica. Experiments with preincubation of venom and antivenom were carried out to test the neutralization of lethal, hemorrhagic, coagulant and indirect hemolytic activities. In addition, antibody titers against crude venom and myotoxin II purified from this venom were determined by enzyme immunoassay (ELISA). Results indicate that polyvalent antivenom from Instituto Clodomiro Picado (Costa Rica) has the highest neutralizing ability against lethal, coagulant and indirect hemolytic activities, whereas MYN polyvalent antivenom (México) has the highest neutralization against hemorrhagic activity. Antivenom from Instituto Clodomiro Picado also has the highest antibody titers against crude B. asper venom and against myotoxin II. Antivenoms from Universidad Central de Venezuela (Venezuela), Vencofarma (Brazil) and MYN (México) failed to neutralize the lethal effect of this venom. These results stress the need for rigorous quality control systems to evaluate the neutralizing ability of antivenoms in Central America.

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.

Topical application of recombinant activated factor VII during cesarean delivery for placenta previa.

PubMed

Schjoldager, Birgit T B G; Mikkelsen, Emmeli; Lykke, Malene R; Præst, Jørgen; Hvas, Anne-Mette; Heslet, Lars; Secher, Niels J; Salvig, Jannie D; Uldbjerg, Niels

2017-06-01

During cesarean delivery in patients with placenta previa, hemorrhaging after removal of the placenta is often challenging. In this condition, the extraordinarily high concentration of tissue factor at the placenta site may constitute a principle of treatment as it activates coagulation very effectively. The presumption, however, is that tissue factor is bound to activated factor VII. We hypothesized that topical application of recombinant activated factor VII at the placenta site reduces bleeding without affecting intravascular coagulation. We included 5 cases with planned cesarean delivery for placenta previa. After removal of the placenta, the surgeon applied a swab soaked in recombinant activated factor VII containing saline (1 mg in 246 mL) to the placenta site for 2 minutes; this treatment was repeated once if the bleeding did not decrease sufficiently. We documented the treatment on video recordings and measured blood loss. Furthermore, we determined hemoglobin concentration, platelet count, international normalized ratio, activated partial thrombin time, fibrinogen (functional), factor VII:clot, and thrombin generation in peripheral blood prior to and 15 minutes after removal of the placenta. We also tested these blood coagulation variables in 5 women with cesarean delivery planned for other reasons. Mann-Whitney test was used for unpaired data. In all 5 cases, the uterotomy was closed under practically dry conditions and the median blood loss was 490 (range 300-800) mL. There were no adverse effects of recombinant activated factor VII and we did not measure factor VII to enter the circulation. Neither did we observe changes in thrombin generation, fibrinogen, activated partial thrombin time, international normalized ratio, and platelet count in the peripheral circulation (all P values >.20). This study indicates that in patients with placenta previa, topical recombinant activated factor VII may diminish bleeding from the placenta site without initiation of systemic coagulation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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.

[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.

Near fatal spontaneous intraperitoneal bleeding: A rare manifestation in a congenital factor X deficiency carrier.

PubMed

Vinod, K V; Hitha, B; Kaaviya, R; Dutta, T K

2015-03-01

Congenital factor X (FX) deficiency is a rare coagulation disorder of autosomal recessive inheritance, characterized by bleeding of variable severity. Bleeding severity generally correlates with the level of FX functional activity and severe bleeding usually occurs in moderate and severe deficiency, when FX coagulant activity is <5%. FX activity above 10% is infrequently associated with severe bleeding. Here we report the rare occurrence of life-threatening massive spontaneous intraperitoneal bleeding with hypovolemic shock, resulting from spontaneous rupture of an ovarian luteal cyst in a 25-year-old FX deficiency carrier woman, with a FX activity of 26%. She was managed successfully conservatively, with fresh frozen plasma and packed red blood cell transfusions and she showed gradual improvement. The case is being reported to discuss the diagnosis and management of this rare inherited coagulation disorder.

Chronic urticaria in adults: state-of-the-art in the new millennium*

PubMed Central

Criado, Paulo Ricardo; Criado, Roberta Facchini Jardim; Maruta, Celina Wakisaka; dos Reis, Vitor Manoel Silva

2015-01-01

Chronic urticaria has been explored in several investigative aspects in the new millennium, either as to its pathogenesis, its stand as an autoimmune or auto-reactive disease, the correlation with HLA-linked genetic factors, especially with class II or its interrelation with the coagulation and fibrinolysis systems. New second-generation antihistamines, which act as good symptomatic drugs, emerged and were commercialized over the last decade. Old and new drugs that may interfere with the pathophysiology of the disease, such as cyclosporine and omalizumab have been developed and used as treatments. The purpose of this article is to describe the current state of knowledge on aspects of chronic urticaria such as, pathophysiology, diagnosis and the current therapeutic approach proposed in the literature. PMID:25672302

Blind Pose Prediction, Scoring, and Affinity Ranking of the CSAR 2014 Dataset.

PubMed

Martiny, Virginie Y; Martz, François; Selwa, Edithe; Iorga, Bogdan I

2016-06-27

The 2014 CSAR Benchmark Exercise was focused on three protein targets: coagulation factor Xa, spleen tyrosine kinase, and bacterial tRNA methyltransferase. Our protocol involved a preliminary analysis of the structural information available in the Protein Data Bank for the protein targets, which allowed the identification of the most appropriate docking software and scoring functions to be used for the rescoring of several docking conformations datasets, as well as for pose prediction and affinity ranking. The two key points of this study were (i) the prior evaluation of molecular modeling tools that are most adapted for each target and (ii) the increased search efficiency during the docking process to better explore the conformational space of big and flexible ligands.

The influence of prophylactic factor VIII in severe hemophilia A

PubMed Central

Gissel, Matthew; Whelihan, Matthew F; Ferris, Lauren A; Mann, Kenneth G; Rivard, Georges E; Brummel-Ziedins, Kathleen E

2013-01-01

Introduction Hemophilia A individuals displaying a similar genetic defect have heterogeneous clinical phenotypes. Aim To evaluate the underlying effect of exogenous factor (f)VIII on tissue factor (Tf)-initiated blood coagulation in severe hemophilia utilizing both empirical and computational models. Methods We investigated twenty-five clinically severe hemophilia A patients. All individuals were on fVIII prophylaxis and had not received fVIII from 0.25 to 4 days prior to phlebotomy. Coagulation was initiated by the addition of Tf to contact-pathway inhibited whole blood ± an anti-fVIII antibody. Aliquots were quenched over 20 min and analyzed for thrombin generation and fibrin formation. Coagulation factor levels were obtained and used to computationally predict thrombin generation with fVIII set to either zero or its value at the time of the draw. Results Due to prophylactic fVIII, at the time of the blood draw, the individuals had fVIII levels that ranged from <1% to 22%. Thrombin generation (maximum level and rate) in both empirical and computational systems increased as the level of fVIII increased. FXIII activation rates also increased as the fVIII level increased. Upon suppression of fVIII, thrombin generation became comparable in both systems. Plasma composition analysis showed a negative correlation between bleeding history and computational thrombin generation in the absence of fVIII. Conclusion Residual prophylactic fVIII directly causes an increase in thrombin generation and fibrin cross-linking in individuals with clinically severe hemophilia A. The combination of each individual's coagulation factors (outside of fVIII) determine each individual's baseline thrombin potential and may affect bleeding risk. PMID:21899664

Haemostatic monitoring during postpartum haemorrhage and implications for management

PubMed Central

Solomon, C.; Collis, R. E.; Collins, P. W.

2012-01-01

Summary Postpartum haemorrhage (PPH) is a major risk factor for maternal morbidity and mortality. PPH has numerous causative factors, which makes its occurrence and severity difficult to predict. Underlying haemostatic imbalances such as consumptive and dilutional coagulopathies may develop during PPH, and can exacerbate bleeding and lead to progression to severe PPH. Monitoring coagulation status in patients with PPH may be crucial for effective haemostatic management, goal-directed therapy, and improved outcomes. However, current PPH management guidelines do not account for the altered baseline coagulation status observed in pregnant patients, and the appropriate transfusion triggers to use in PPH are unknown, due to a lack of high-quality studies specific to this area. In this review, we consider the evidence for the use of standard laboratory-based coagulation tests and point-of-care viscoelastic coagulation monitoring in PPH. Many laboratory-based tests are unsuitable for emergency use due to their long turnaround times, so have limited value for the management of PPH. Emerging evidence suggests that viscoelastic monitoring, using thrombelastography- or thromboelastometry-based tests, may be useful for rapid assessment and for guiding haemostatic therapy during PPH. However, further studies are needed to define the ranges of reference values that should be considered ‘normal’ in this setting. Improving awareness of the correct application and interpretation of viscoelastic coagulation monitoring techniques may be critical in realizing their emergency diagnostic potential. PMID:23075633

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.

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 but also to predict a proper dosage for coagulant amounts and to project the quality of the output water under real conditions.

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.

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.

Analysis of clinical risk factors associated with the prognosis of severe multiple-trauma patients with acute lung injury.

PubMed

Wu, Junsong; Sheng, Lei; Wang, Shenhua; Li, Qiang; Zhang, Mao; Xu, Shaowen; Gan, Jianxin

2012-09-01

Several clinical risk factors have been reported to be associated with the prognosis of acute lung injury (ALI). However, these studies have included a general trauma patient population, without singling out the severely injured multiple-trauma patient population. To identify the potential risk factors that could affect the prognosis of ALI in multiple-trauma patients and investigate the prognostic effects of certain risk factors among different patient subpopulations. In this retrospective cohort study, severely injured multiple-trauma patients with early onset of ALI from several trauma centers were studied. Potential risk factors affecting the prognosis of ALI were examined by univariate and multivariate logistic analyses. There were 609 multiple-trauma patients with ALI admitted to the emergency department and emergency intensive care unit during the study period. The nine risk factors that affected prognosis, as indicated by the unadjusted odds ratios with 95% confidence intervals, were the APACHE II (Acute Physiology and Chronic Health Evaluation II) score, duration of trauma, age, gastrointestinal hemorrhage, pulmonary contusion, disseminated intravascular coagulation (DIC), multiple blood transfusions in 6 h, Injury Severity Score (ISS), and aspiration of gastric contents. Specific risk factors also affected different patient subpopulations in different ways. Patients older than 65 years and with multiple (> 10 units) blood transfusions in the early stage after multiple trauma were found to be independent risk factors associated with deterioration of ALI. The other factors studied, including pulmonary contusion, APACHE II score ≥ 20, ISS ≥ 16, gastrointestinal hemorrhage, and aspiration of gastric contents, may predict the unfavorable prognosis of ALI in the early stage of trauma, with their effects attenuating in the later stage. Duration of trauma ≥ 1 h and the presence of DIC may also indicate unfavorable prognosis during the entire treatment period. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

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. These kinetic profiles are consistent with a 1:1 stoichiometry for the functional interaction between cofactor and enzyme on the surface of monocytes and platelets. Taken together, these results indicate that autocatalytic pathways connecting the extrinsic, intrinsic, and common coagulation pathways can operate efficiently on the monocyte membrane. PMID:1613461

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.

Quality of Clotting Factor Activity in Fresh Frozen Plasma at Thaw with a Microwave System and after Storage at 4 degrees C for 48 Hours.

PubMed

Kuta, Piotr; Hauck-Dlimi, Barbara; Strobel, Julian; Zimmermann, Robert; Eckstein, Reinhold

2016-01-01

Uncontrolled hemorrhage in polytrauma patients usually results in rapid need of blood products. Despite the shorter thawing times of microwave devices for heating fresh frozen plasma (FFP), their use has remained controversial, and just a few laboratory analyses have been published on this topic. The aim of this study was to analyse the quality of clotting factors immediately after thawing FFP with a microwave device and after 48-hour post thaw storage at 4 degrees C. 24 FFP units of all four ABO blood groups (six of each blood group) were thawed with a Transfusio-therm 2000 and later stored at 4 degrees C for 48 hours. Samples were drawn aseptically and investigated on various clotting factors and protein proteases (fibrinogen, antithrombin, FII, FV, FVII, FVIII, FIX, FX, FXI, FXIII, vWF antigen and activity, protein S, and protein C) using standard coagulation and chromogenic assays immediately after thawing and again after a 48-hour storage period at 4 degrees C. All units were tested for both anaerobic and aerobic microbial contamination using standard operating procedures immediately after thawing. After thawing, all coagulation factors and protein protease activities were within normal ranges. Blood group O individuals had approximately 25% lower plasma levels of vWF antigen and activity. After a 48-hour storage period at 4 degrees C, FVIII and FIX activities declined significantly in all blood groups, whereas the remaining clotting factors remained comparably stable. Immediately after rapid thawing using a microwave system, all FFP units contained adequate coagulation factor activities to maintain hemostatic activity at the time of product thaw. The post thaw refrigerated storage caused an anticipated decrease in factor VIII and IX activities, but retained normal coagulation factor levels of many plasma proteins. Therefore we conclude that the Transfusio-therm 2000 has no clinically significant influence on the activity of clotting factors and plasma proteases in FFP units.

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.

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.

Polymer Latex Stability Modification by Exposure to Hydrophobic Solvents.

PubMed

de Oliveira Cardoso A; Galembeck

1998-08-01

The stability of latex particles toward coagulation in the presence of salt is modified by swelling the latex with toluene and chloroform vapors. Short-term stability was determined by turbidimetric titrations, and the long-term stability was evaluated by adding latex and salt solutions, allowing the mixture to age for 24 or 48 h and determining the characteristics of the supernatant and of the sediment. Nine different latexes were examined, with variable results: in some cases, both apolar solvents stabilize the latex; in other cases, increased stability is induced by only one of the solvents, either toluene or chloroform. There is also coherence, but not a strict correlation, between the solvent effects on short- and long-term stability. For instance, in the case of a core-and-shell styrene-butyl methacrylate latex, chloroform has a small stabilizing effect in the titration experiment, but it prevents the formation of a coagulated latex sediment even 48 h after mixing latex and salt. Two hypotheses are discussed to account for these observations: (i) swelling solvents decrease the particles ability to dissipate the collision kinetic energy, so that particles collide but without joining each other; (ii) the solvents induce the release of trapped charged groups from the particle interior to the interface, enhancing the usual (electrostatic, steric, hydration) stability factors. Copyright 1998 Academic Press.

Development of a lectin binding assay to differentiate between recombinant and endogenous proteins in pharmacokinetic studies of protein-biopharmaceuticals.

PubMed

Weber, Alfred; Minibeck, Eva; Scheiflinger, Friedrich; Turecek, Peter L

2015-04-10

Human glycoproteins, expressed in hamster cell lines, show similar glycosylation patterns to naturally occurring human molecules except for a minute difference in the linkage of terminal sialic acid: both cell types lack α2,6-galactosyl-sialyltransferase, abundantly expressed in human hepatocytes and responsible for the α2,6-sialylation of circulating glycoproteins. This minute difference, which is currently not known to have any physiological relevance, was the basis for the selective measurement of recombinant glycoproteins in the presence of their endogenous counterparts. The assay is based on using the lectin Sambucus nigra agglutinin (SNA), selectively binding to α2,6-sialylated N-glycans. Using von Willebrand factor (VWF), factor IX (FIX), and factor VIIa (FVIIa), it was demonstrated that (i) the plasma-derived proteins, but not the corresponding recombinant proteins, specifically bind to SNA and (ii) this binding can be used to deplete the plasma-derived proteins. The feasibility of this approach was confirmed in spike-recovery studies for all three recombinant coagulation proteins in human plasma and for recombinant VWF (rVWF) in macaque plasma. Analysis of plasma samples from macaques after administration of recombinant and a plasma-derived VWF demonstrated the suitability and robustness of this approach. Data showed that rVWF could be selectively measured without changing the ELISAs and furthermore revealed the limitations of baseline adjustment using a single measurement of the predose concentration only. The SNA gel-based depletion procedure can easily be integrated in existing procedures as a specific sample pre-treatment step. While ELISA-based methods were used to measure the recombinant coagulation proteins in the supernatants obtained by depletion, this procedure is applicable for all biochemical analyses. Copyright © 2015 Elsevier B.V. All rights reserved.

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).

Factor X deficiency

MedlinePlus

... disorders: coagulation factor deficiencies. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. ... Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

Factor VII deficiency

MedlinePlus

... disorders: coagulation factor deficiencies. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. ... Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

Gynaecological and obstetric management of women with inherited bleeding disorders.

PubMed

Demers, Christine; Derzko, Christine; David, Michèle; Douglas, Joanne

2006-10-01

The prevalence of bleeding disorders, notably von Willebrand disease (vWD), among adult women with objectively documented menorrhagia is consistently reported to be 10% to 20% and is even higher in adolescents presenting with menorrhagia. This consensus document has been developed by a multidisciplinary committee consisting of an anesthesiologist, 2 hematologists, and an obstetrician/gynaecologist and has been endorsed by their relevant specialty bodies. It has been prepared with the express purpose of providing guidelines for both women with inherited bleeding disorders and for their caregivers regarding the gynaecological and obstetric management of these women, including appropriate anesthesia support where indicated. Diagnostic tools and specific medical and, where appropriate, surgical alternatives to management are reviewed and evidence-based recommendations presented. A MEDLINE search of the English literature between January 1975 and November 2003 was performed using the following key words: menorrhagia, uterine bleeding, pregnancy, von Willebrand, congenital bleeding disorder, desmopressin/DDAVP, tranexamic acid, oral contraceptives, medroxyprogesterone, therapy, hysterectomy, anesthesia, epidural, spinal. Recommendations from other society guidelines were reviewed. 1. Inherited bleeding disorders should be considered in the differential diagnosis of all patients presenting with menorrhagia (II-2B). The graphical scoring system presented is a validated tool which offers a simple yet practical method that can be used by patients to quantify their blood loss (II-2B). 2. Because underlying bleeding disorders are frequent in women with menorrhagia, physicians should consider performing a hemoglobin/hematocrit, platelet count, ferritin, PT (INR) and APTT in women with menorrhagia. In women who have a personal history of other bleeding or a family history of bleeding, further investigation should be considered, including a vWD workup (factor VIII, vWF antigen, and vWF functional assay) (II-2B). 3. Treatment of menorrhagia in women with inherited bleeding disorders should be individualized (III-B). 4. An inherited bleeding disorder is not a contraindication to hormonal therapy (oral contraceptives [II-1B], depot medroxyprogesterone acetate (DMPA) [II-3B], danazol [II-2B], GnRH analogs [II-3B]) or local treatments (levonorgestrel-releasing IUS [II-1B]) and non-hormonal therapy (antifibrinolytic drug tranexamic acid [II-1B]) as well as desmopressin (II-1B). These therapies represent first line treatment. Blood products should not be used for women with mild bleeding disorders (III-A). 5. In women who no longer want to preserve their fertility, conservative surgical therapy (ablation) and hysterectomy may be options (III-B). Clinicians may consult the "SOGC Clinical Practice Guideline: Guidelines for the Management of Abnormal Uterine Bleeding" for an in-depth discussion of the available therapeutic modalities, both medical and surgical. To minimize the risk of intraoperative and post-operative hemorrhage, coagulation factors should be corrected preoperatively with post-operative monitoring (II-1B). 6. Girls growing up in families with a history of vWD or other inherited bleeding disorders should be tested pre-menarchally to determine whether or not they have inherited the disease to allow both the patient and her family to prepare for her first and subsequent menstrual periods (III-C). 7. In adolescents presenting with menorrhagia, an inherited bleeding disorder should be excluded (III-B). When possible, investigation should be undertaken before oral contraceptive therapy is instituted, as the hormonally induced increase in factor VIII and vWF may mask the diagnosis (II-B). 8. Pregnancy in women with inherited bleeding disorders may require a multidisciplinary approach. A copy of their recommendations should be given to the patient and she should be instructed to present it to the health care provider admitting her to the birthing centre. Women with severe bleeding disorders or with a fetus at risk for a severe bleeding disorder should deliver in a hospital (level three) or where there is access to consultants in obstetrics, anesthesiology, hematology, and pediatrics (III-C). 9. Vacuum extraction, forceps, fetal scalp electrodes, and fetal scalp blood sampling should be avoided if the fetus is known or thought to be at risk for a congenital bleeding disorder. A Caesarean section should be performed for obstetrical indications only (II-2C). 10. Epidural and spinal anesthesia are contraindicated if there is a coagulation defect. There is no contraindication to regional anesthesia if coagulation is normalized. The decision to use regional anesthesia should be made on an individual basis (III-C). 11. The risk of early and late postpartum hemorrhage is increased in women with bleeding disorders. Women with inherited bleeding disorders should be advised about the possibility of excessive postpartum bleeding and instructed to report this immediately (III-B). 12. Intramuscular injections, surgery, and circumcision should be avoided in neonates at risk for a severe hereditary bleeding disorder until adequate workup/preparation are possible (III-B). The quality of evidence reported in this document has been described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on the Periodic Health Exam (Table 1).

Gynaecological and obstetric management of women with inherited bleeding disorders.

PubMed

Demers, Christine; Derzko, Christine; David, Michèle; Douglas, Joanne

2005-07-01

The prevalence of bleeding disorders, notably von Willebrand disease (vWD), among adult women with objectively documented menorrhagia is consistently reported to be 10% to 20% and is even higher in adolescents presenting with menorrhagia. This consensus document has been developed by a multidisciplinary committee consisting of an anesthesiologist, 2 hematologists, and an obstetrician/gynaecologist and has been endorsed by their relevant specialty bodies. It has been prepared with the express purpose of providing guidelines for both women with inherited bleeding disorders and for their caregivers regarding the gynaecological and obstetric management of these women, including appropriate anesthesia support where indicated. Diagnostic tools and specific medical and, where appropriate, surgical alternatives to management are reviewed and evidence-based recommendations presented. A MEDLINE search of the English literature between January 1975 and November 2003 was performed using the following key words: menorrhagia, uterine bleeding, pregnancy, von Willebrand, congenital bleeding disorder, desmopressin/DDAVP, tranexamic acid, oral contraceptives, medroxyprogesterone, therapy, hysterectomy, anesthesia, epidural, spinal. Recommendations from other society guidelines were reviewed. 1. Inherited bleeding disorders should be considered in the differential diagnosis of all patients presenting with menorrhagia (II-2B). The graphical scoring system presented is a validated tool which offers a simple yet practical method that can be used by patients to quantify their blood loss (II-2B). 2. Because underlying bleeding disorders are frequent in women with menorrhagia, physicians should consider performing a hemoglobin/hematocrit, platelet count, ferritin, PT (INR) and APTT in women with menorrhagia. In women who have a personal history of other bleeding or a family history of bleeding, further investigation should be considered, including a vWD workup (factor VIII, vWF antigen, and vWF functional assay) (II-2B). 3. Treatment of menorrhagia in women with inherited bleeding disorders should be individualized (III-B). 4. An inherited bleeding disorder is not a contraindication to hormonal therapy (oral contraceptives [II-1B], depot medroxyprogesterone acetate (DMPA) [II-3B], danazol [II-2B], GnRH analogs [II-3B]) or local treatments (levonorgestrel-releasing IUS [II-1B]) and non-hormonal therapy (antifibrinolytic drug tranexamic acid [II-1B]) as well as desmopressin (II-1B). These therapies represent first line treatment. Blood products should not be used for women with mild bleeding disorders (III-A). 5. In women who no longer want to preserve their fertility, conservative surgical therapy (ablation) and hysterectomy may be options (III-B). Clinicians may consult the "SOGC Clinical Practice Guideline: Guidelines for the Management of Abnormal Uterine Bleeding" for an in-depth discussion of the available therapeutic modalities, both medical and surgical. To minimize the risk of intraoperative and post-operative hemorrhage, coagulation factors should be corrected preoperatively with post-operative monitoring (II-1B). 6. Girls growing up in families with a history of vWD or other inherited bleeding disorders should be tested pre-menarchally to determine whether or not they have inherited the disease to allow both the patient and her family to prepare for her first and subsequent menstrual periods (III-C). 7. In adolescents presenting with menorrhagia, an inherited bleeding disorder should be excluded (III-B). When possible, investigation should be undertaken before oral contraceptive therapy is instituted, as the hormonally induced increase in factor VIII and vWF may mask the diagnosis (II-B). 8. Pregnancy in women with inherited bleeding disorders may require a multidisciplinary approach. A copy of their recommendations should be given to the patient and she should be instructed to present it to the health care provider admitting her to the birthing centre. Women with severe bleeding disorders or with a fetus at risk for a severe bleeding disorder should deliver in a hospital (level three) or where there is access to consultants in obstetrics, anesthesiology, hematology, and pediatrics (III-C). 9. Vacuum extraction, forceps, fetal scalp electrodes, and fetal scalp blood sampling should be avoided if the fetus is known or thought to be at risk for a congenital bleeding disorder. A Caesarean section should be performed for obstetrical indications only (II-2C). 10. Epidural and spinal anesthesia are contraindicated if there is a coagulation defect. There is no contraindication to regional anesthesia if coagulation is normalized. The decision to use regional anesthesia should be made on an individual basis (III-C). 11. The risk of early and late postpartum hemorrhage is increased in women with bleeding disorders. Women with inherited bleeding disorders should be advised about the possibility of excessive postpartum bleeding and instructed to report this immediately (III-B). 12. Intramuscular injections, surgery, and circumcision should be avoided in neonates at risk for a severe hereditary bleeding disorder until adequate workup/preparation are possible (III-B). The quality of evidence reported in this document has been described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on the Periodic Health Exam (Table 1).

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.

Interval and continuous exercise regimens suppress neutrophil-derived microparticle formation and neutrophil-promoted thrombin generation under hypoxic stress.

PubMed

Chen, Yi-Ching; Ho, Ching-Wen; Tsai, Hsing-Hua; Wang, Jong-Shyan

2015-04-01

Acute hypoxic exposure increases vascular thrombotic risk. The release of procoagulant-rich microparticles from neutrophils accelerates the pathogenesis of inflammatory thrombosis. The present study explicates the manner in which interval and continuous exercise regimens affect neutrophil-derived microparticle (NDMP) formation and neutrophil/NDMP-mediated thrombin generation (TG) under hypoxic condition. A total of 60 sedentary males were randomized to perform either aerobic interval training [AIT; 3-min intervals at 40% and 80% V̇O2max (maximal O2 consumption)] or moderate continuous training (MCT; sustained 60% V̇O2max) for 30 min/day, 5 days/week for 5 weeks, or to a control (CTL) group who did not receive any form of training. At rest and immediately after hypoxic exercise test (HE, 100 W under 12% O2 for 30 min), the NDMP characteristics and dynamic TG were measured by flow cytometry and thrombinography respectively. Before the intervention, HE (i) elevated coagulant factor VIII/fibrinogen concentrations and shortened activated partial thromboplastin time (aPTT), (ii) increased total and tissue factor (TF)-rich/phosphatidylserine (PS)-exposed NDMP counts and (iii) enhanced the peak height and rate of TG promoted by neutrophils/NDMPs. Following the 5-week intervention, AIT exhibited higher enhancement of V̇O2max than did MCT. Notably, both MCT and AIT attenuated the extents of HE-induced coagulant factor VIII/fibrinogen elevations and aPTT shortening. Furthermore, the two exercise regimens significantly decreased TF-rich/PS-exposed NDMP formation and depressed neutrophil/NDMP-mediated dynamic TG at rest and following HE. Hence, we conclude that AIT is superior to MCT for enhancing aerobic capacity. Moreover, either AIT or MCT effectively ameliorates neutrophil/NDMP-promoted TG by down-regulating expression of procoagulant factors during HE, which may reduce thrombotic risk evoked by hypoxia. Moreover, either AIT or MCT effectively ameliorates neutrophil/NDMP-promoted TG by down-regulating expression of procoagulant factors during HE, which may reduce thrombotic risk evoked by hypoxia.

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.

Stability of colloidal gold and determination of the Hamaker constant

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

Demirci, S.; Enuestuen, B.V.; Turkevich, J.

1978-12-14

Previous computation of stability factors of colloidal gold from coagulation data was found to be in systematic error due to an underestimation of the particle concentration by electron microscopy. A new experimental technique was developed for determination of this concentration. Stability factors were recalculated from the previous data using the correct concentration. While most of the previously reported conclusions remain unchanged, the absolute rate of fast coagulation is found to agree with that predicted by the theory. A value of the Hamaker constant was determined from the corrected data.

6-Methylsulfinylhexyl isothiocyanate modulates endothelial cell function and suppresses leukocyte adhesion.

PubMed

Okamoto, Takayuki; Akita, Nobuyuki; Nagai, Masashi; Hayashi, Tatsuya; Suzuki, Koji

2014-01-01

6-Methylsulfinylhexyl isothiocyanate (6-MSITC) is an active compound in wasabi (Wasabia japonica Matsum.), which is one of the most popular spices in Japan. 6-MSITC suppresses lipopolysaccharide-induced macrophage activation, arachidonic- or adenosine diphosphate-induced platelet activation, and tumor cell proliferation. These data indicate that 6-MSITC has several biological activities involving anti-inflammatory, anti-coagulant, and anti-apoptosis properties. Endothelial cells (ECs) maintain vascular homeostasis and play crucial roles in crosstalk between blood coagulation and vascular inflammation. In this study, we determined the anti-coagulant and anti-inflammatory effects of 6-MSITC on human umbilical vein endothelial cells (HUVECs). 6-MSITC slightly reduced tissue factor expression, but did not alter von Willebrand factor release in activated HUVECs. 6-MSITC modulated the generation of activated protein C, which is essential for negative regulation of blood coagulation, on normal ECs. In addition, 6-MSITC reduced tumor necrosis factor-α (TNF-α)-induced interleukin-6 and monocyte chemoattractant protein-1 expression. 6-MSITC markedly attenuated TNF-α-induced adhesion of human monoblast U937 cells to HUVECs and reduced vascular cell adhesion molecule-1 and E-selectin mRNA expression in activated ECs. These results showed that 6-MSITC modulates EC function and suppresses cell adhesion. This study provides new insight into the mechanism of the anti-inflammatory effect of 6-MSITC, suggesting that 6-MSITC has therapeutic potential as a treatment for vasculitis and vascular inflammation.

IgMk paraprotein from gammopathy patient can bind to cardiolipin and interfere with coagulation assay: a case report.

PubMed

Wu, Xin-Yao; Yin, Yu-Feng; Teng, Jia-Lin; Zhang, Li-Wei; Yang, Cheng-de

2017-06-23

The monoclonal gammopathies are a group of plasma-cell proliferative disorders characterized by the secretion of monoclonal immunoglobulin (M protein or paraprotein). Some rare cases have revealed the specific affinity of paraprotein as autoantibody. Here we report a patient with monoclonal gammopathy of undetermined significance (MGUS) accompanied by a remarkable increase of anticardiolipin antibody (aCL) and an extensively decreased coagulation factor activity, however, without any clinical signs of antiphospholipid syndrome (APS) and bleeding. Our further investigation indicated that IgMκ paraprotein of this patient possessed an antibody activity against phospholipids so as to bind to cardiolipin and interfere with coagulation assay in vitro. This case might be indicative that an abnormality of coagulation tests, disturbed by IgMκ paraprotein, does not predict a risk of bleeding in this patient.

Antithrombin, an Important Inhibitor in Blood Clots.

PubMed

Zhu, Ying; Cong, Qing-Wei; Liu, Yue; Wan, Chun-Ling; Yu, Tao; He, Guang; He, Lin; Cai, Lei; Chou, Kuo-Chen

2016-01-01

Blood coagulation is healthy and lifesaving because it can stop bleeding. It can, however, be a troublemaker as well, causing serious medical problems including heart attack and stroke. Body has complex blood coagulation cascade to modulate the blood clots. In the environment of plasma, the blood coagulation cascade is regulated by antithrombin, which is deemed one of the most important serine protease inhibitors. It inhibits thrombin; it can inhibit factors IXa and Xa as well. Interestingly, its inhibitory ability will be significantly increased with the existence of heparin. In this minireview paper, we are to summarize the structural features of antithrombin, as well as its heparin binding modes and anti-coagulation mechanisms, in hopes that the discussion and analysis presented in this paper can stimulate new strategies to find more effective approaches or compounds to modulate the antithrombin.

21 CFR 864.7140 - Activated whole blood clotting time tests.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class II...

21 CFR 864.7140 - Activated whole blood clotting time tests.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class II...

21 CFR 864.7140 - Activated whole blood clotting time tests.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class II...

21 CFR 864.7140 - Activated whole blood clotting time tests.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class II...

21 CFR 864.7140 - Activated whole blood clotting time tests.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class II...

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 expressed. In this study, it is still shown that DM2 is a multifactor disease and its physiopathologic mechanisms are not completely known today.

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.

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

Polyacrylamide grafted cellulose as an eco-friendly flocculant: Key factors optimization of flocculation to surfactant effluent.

PubMed

Zhu, Hangcheng; Zhang, Yong; Yang, Xiaogang; Shao, Lan; Zhang, Xiumei; Yao, Juming

2016-01-01

The discharge of effluents from surfactant manufacturers is giving rise to increasingly serious environmental problems. In order to develop the eco-friendly flocculation materials to achieve effective removal of pollutants from the surfactant effluents, the bamboo pulp cellulose from Phyllostachys heterocycla is employed as the skeleton material to synthesize an eco-friendly bamboo pulp cellulose-g-polyacrylamide (BPC-g-PAM) for flocculation. The BPC-g-PAM is used with the metal ions as the coagulant to treat the effluent from a surfactant manufacturer. The response surface methodology coupled with Box-behnken design is employed to optimize the key factors of coagulation-flocculation. The results show that the combination of Fe(3+) with BPC-g-PAM achieves the best coagulation-flocculation performance like, the fast treatment time, minimum coagulant and BPC-g-PAM dosages compared with the other two combinations of Al(3+) with BPC-g-PAM and Ca(2+) with BPC-g-PAM. Therefore, the combination of Fe(3+) with BPC-g-PAM is expected to promote its application for the pollution control in the surfactant manufacturers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hyper-coagulable profile with elevated pro-thrombotic biomarkers and increased cerebro- and cardio-vascular disease risk exist among healthy dyslipidemic women.

PubMed

Ferreira, Cláudia N; Carvalho, Maria G; Reis, Helton J; Gomes, Karina B; Sousa, Marinez O; Palotás, András

2014-05-01

Dyslipidemia is one of the pathognomonic elements of athero-genesis, as well as cerebro- and cardio-vascular disease (CCVD). Hemostatic factors are also involved in athero-sclerosis and ischemic changes, however their relationship with disrupted lipid homeostasis is not well characterized. The aim of this study was to determine the coagulation state of dyslipidemic patients and to evaluate their association with CCVD risk factors. Biochemical and hematological parameters, as well as neuro-psychiatric profile of 109 dyslipidemic subjects and 107 normo-lipidic healthy volunteers were assessed. Serum bio-marker levels and cognitive performance generally did not differ in the groups, but prothrombin fragment 1+2 (F1+2) and D-dimer concentrations were markedly higher among women. Hyper-coagulability was not associated with dyslipidemia, but was correlated with the female gender, which might pose an increased thromboembolic risk in asymptomatic women.

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.

Venom Concentrations and Clotting Factor Levels in a Prospective Cohort of Russell's Viper Bites with Coagulopathy.

PubMed

Isbister, Geoffrey K; Maduwage, Kalana; Scorgie, Fiona E; Shahmy, Seyed; Mohamed, Fahim; Abeysinghe, Chandana; Karunathilake, Harendra; O'Leary, Margaret A; Gnanathasan, Christeine A; Lincz, Lisa F

2015-01-01

Russell's viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy. This study aimed to investigate the kinetics and dynamics of venom and clotting function in Russell's viper envenoming. In a prospective cohort of 146 patients with Russell's viper envenoming, we measured venom concentrations, international normalised ratio [INR], prothrombin time (PT), activated partial thromboplastin time (aPTT), coagulation factors I, II, V, VII, VIII, IX and X, and von Willebrand factor antigen. The median age was 39 y (16-82 y) and 111 were male. The median peak INR was 6.8 (interquartile range [IQR]: 3.7 to >13), associated with low fibrinogen [median,<0.01 g/L; IQR: <0.01-0.9 g/L), low factor V levels [median,<5%; IQR: <5-4%], low factor VIII levels [median,40%; IQR: 12-79%] and low factor X levels [median, 48%; IQR: 29-67%]. There were smaller reductions in factors II, IX and VII over time. All factors recovered over 48 h post-antivenom. The median INR remained >3 at 6 h post-antivenom but had reduced to <2, by 24 h. The aPTT had also returned to close to normal (<50 sec) at 24 h. Factor VII, VIII and IX levels were unusually high pre-antivenom, median peak concentrations of 393%, 307% and 468% respectively. Pre-antivenom venom concentrations and the INR (r = 0.20, p = 0.02) and aPTT (r = 0.19, p = 0.03) were correlated (non-parametric Spearman analysis). Russell's viper coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and X which recover over 48 h. Severity of clotting abnormalities was associated with venom concentrations.

[Reference values for the blood coagulation tests in Mexico: usefulness of the pooled plasma from blood donors].

PubMed

Calzada-Contreras, Adriana; Moreno-Hernández, Manuel; Castillo-Torres, Noemi Patricia; Souto-Rosillo, Guadalupe; Hernández-Juárez, Jesús; Ricardo-Moreno, María Tania; Sánchez-Fernández, Maria Guadalupe de Jesús; García-González, América; Majluf-Cruz, Abraham

2012-01-01

The blood coagulation system maintains the blood in a liquid state and bleeding and thrombosis are the manifestations of its malfunction. Blood coagulation laboratory evaluates the physiology of this system. To establish both, the reference values for several tests performed at the blood coagulation laboratory as well as the utility of the pooled plasma to perform these assays. MATERIAL AND: In this descriptive, cross-sectional, randomized study, we collected plasma from Mexican Mestizos. Each pooled plasma was prepared with the plasma from at least 20 blood donors. We performed screening and special tests and the Levey-Jennings graphs were built and interpreted after each pass. Results of the tests were analyzed and their distribution was established using the Kolmogorov-Smirnov test. To establish the reference values we used 95% confidence intervals. We collected 72 pooled plasmas. The distribution for PT, APTT, and TT tests was abnormal. Although the PT test showed a bimodal distribution it was normal for factor VII. The reference values for the hemostatic, anticoagulant, and fibrinolytic factors were different from those suggested by the manufacturers. We established the reference values for the blood coagulation tests in the adult Mexican population. We have shown that the pooled plasma must be used for the screening tests. We suggest that each clinical laboratory should establish its own reference values (at least for the screening tests). To reach this objective, we encourage the use of the pooled plasma.

Thromboelastographic evaluation of dogs with congenital portosystemic shunts.

PubMed

Kelley, D; Lester, C; DeLaforcade, A; Webster, C R L

2013-01-01

On plasma-based assays, dogs with congenital portosystemic shunts (CPSS) have changes in serum concentrations of both pro- and anticoagulant proteins, but how these abnormalities affect whole blood coagulation assays (eg, thromboelastography) are unknown. To conduct kaolin-activated thromboelastography (TEG) analysis in dogs with CPSS and to compare TEG coagulation status with clinical presentation, routine serum biochemistry, and plasma-based coagulation tests. Twenty-one client-owned dogs with CPSS confirmed by ultrasound examination or nuclear scintigraphy. In a prospective study, signalment, clinical presentation, TEG analysis, CBC, serum biochemistry, and hemostatic tests (platelet count, prothrombin time [PT], activated partial thromboplastin time [aPTT], quantitative fibrinogen, antithrombin [AT] activity, protein C [PC] activity, d-dimers, and factor VIII activity) were analyzed in dogs with CPSS. Dogs with CPSS had significantly shorter K values and increased angle, maximum amplitude (MA), and G values compared with the reference population. On plasma-based coagulation testing, dogs with CPSS had significantly prolonged PT, lower platelet counts, lower AT and PC activities, and increased d-dimers and factor VIII activity. Evaluation of G value defined 9/21 dogs with CPSS as hypercoagulable. These dogs were more likely to have hepatic encephalopathy (HE) than CPSS dogs that had normal coagulation. TEG analysis detected hemostatic abnormalities consistent with a hypercoagulable state in some dogs with CPSS. The presence of a hypercoagulable state was 40 times more likely in dogs with symptomatic HE. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk.

PubMed

Cugno, Massimo; Tedeschi, Alberto; Borghi, Alessandro; Bucciarelli, Paolo; Asero, Riccardo; Venegoni, Luigia; Griffini, Samantha; Grovetti, Elena; Berti, Emilio; Marzano, Angelo Valerio

2015-01-01

Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease.

Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk

PubMed Central

Cugno, Massimo; Tedeschi, Alberto; Borghi, Alessandro; Bucciarelli, Paolo; Asero, Riccardo; Venegoni, Luigia; Griffini, Samantha; Grovetti, Elena; Berti, Emilio; Marzano, Angelo Valerio

2015-01-01

Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease. PMID:26057532

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)

Differentiating disseminated intravascular coagulation (DIC) with the fibrinolytic phenotype from coagulopathy of trauma and acute coagulopathy of trauma-shock (COT/ACOTS).

PubMed

Gando, S; Wada, H; Thachil, J

2013-05-01

Two concepts have been proposed for the hemostatic changes occurring early after trauma. Disseminated intravascular coagulation (DIC) with the fibrinolytic phenotype is characterized by activation of the coagulation pathways, insufficient anticoagulant mechanisms and increased fibrinolysis. Coagulopathy of trauma and acute coagulopathy of trauma-shock (COT/ACOTS) occurs as a result of increased activation of the thrombomodulin and protein C pathways, leading to the suppression of coagulation and activation of fibrinolysis. Despite the differences between these two conditions, independent consideration of COT/ACOTS from DIC with the fibrinolytic phenotype is probably incorrect. Robust diagnostic criteria based on its pathophysiology are required to establish COT/ACOTS as a new independent disease concept. In addition, the independency of its characteristics, laboratory data, time courses and prognosis from DIC should be confirmed. Confusion between two concepts may be based on studies of trauma lacking the following: (i) a clear distinction of the properties of blood between the inside and outside of vessels, (ii) a clear distinction between physiologic and pathologic hemostatic changes, (iii) attention to the time courses of the changes in hemostatic parameters, (iv) unification of the study population, and (v) recognition that massive bleeding is not synonymous with coagulation disorders. More information is needed to elucidate the pathogenesis of these two entities, DIC with the fibrinolytic phenotype and COT/ACOTS after trauma. However, available data suggest that COT/ACOTS is not a new concept but a disease entity similar to or the same as DIC with the fibrinolytic phenotype. © 2013 International Society on Thrombosis and Haemostasis.

Protein Z efficiently depletes thrombin generation in disseminated intravascular coagulation with poor prognosis.

PubMed

Lee, Nuri; Kim, Ji-Eun; Gu, Ja-Yoon; Yoo, Hyun Ju; Kim, Inho; Yoon, Sung-Soo; Park, Seonyang; Han, Kyou-Sup; Kim, Hyun Kyung

2016-01-01

Disseminated intravascular coagulation (DIC) is characterized by consumption of coagulation factors and anticoagulants. Thrombin generation assay (TGA) gives useful information about global hemostatic status. We developed a new TGA system that anticoagulant addition can deplete thrombin generation in plasma, which may reflect defective anticoagulant system in DIC. TGAs were measured on the calibrated automated thrombogram with and without thrombomodulin or protein Z in 152 patients who were suspected of having DIC, yielding four parameters including lag time, endogenous thrombin potential, peak thrombin and time-to-peak in each experiment. Nonsurvivors showed significantly prolonged lag time and time-to-peak in TGA-protein Z system, which was performed with added protein Z. In multivariate Cox regression analysis, lag time and time-to-peak in TGA system were significant independent prognostic factors. In TGA-protein Z system, lag time and time-to-peak were revealed as independent prognostic factors of DIC. Protein Z addition could potentiate its anticoagulant effect in DIC with poor prognosis, suggesting the presence of defective protein Z system. The prolonged lag time and time-to-peak in both TGA and TGA-protein Z systems are expected to be used as independent prognostic factors of DIC.

Coagulopathy induced by acidosis, hypothermia and hypocalcaemia in severe bleeding.

PubMed

De Robertis, E; Kozek-Langenecker, S A; Tufano, R; Romano, G M; Piazza, O; Zito Marinosci, G

2015-01-01

Acidosis, hypothermia and hypocalcaemia are determinants for morbidity and mortality during massive hemorrhages. However, precise pathological mechanisms of these environmental factors and their potential additive or synergistic anticoagulant and/or antiplatelet effects are not fully elucidated and are at least in part controversial. Best available evidences from experimental trials indicate that acidosis and hypothermia progressively impair platelet aggregability and clot formation. Considering the cell-based model of coagulation physiology, hypothermia predominantly prolongs the initiation phase, while acidosis prolongs the propagation phase of thrombin generation. Acidosis increases fibrinogen breakdown while hypothermia impairs its synthesis. Acidosis and hypothermia have additive effects. The effect of hypocalcaemia on coagulopathy is less investigated but it appears that below the cut-off of 0.9 mmol/L, several enzymatic steps in the plasmatic coagulation system are blocked while above that cut-off effects remain without clinical sequalae. The impact of environmental factor on hemostasis is underestimated in clinical practice due to our current practice of using routine coagulation laboratory tests such as partial thromboplastin time or prothrombin time, which are performed at standardized test temperature, after pH correction, and upon recalcification. Temperature-adjustments are feasible in viscoelastic point-of-care tests such as thrombelastography and thromboelastometry which may permit quantification of hypothermia-induced coagulopathy. Rewarming hypothermic bleeding patients is highly recommended because it improves patient outcome. Despite the absence of high-quality evidence, calcium supplementation is clinical routine in bleeding management. Buffer administration may not reverse acidosis-induced coagulopathy but may be essential for the efficacy of coagulation factor concentrates such as recombinant activated factor VII.

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

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 independent risk factor for organ space SSI (OR = 5.4, P = 0.01), pneumonia (OR = 3.0, P = 0.023), and sepsis (OR = 4.4, P < 0.001). Abnormal coagulation profile was an independent predictor of morbidity and mortality in patients undergoing PLF. As such, it should be considered in preoperative optimization and risk stratification.

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.

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?

Fat high in stearic acid favorably affects blood lipids and factor VII coagulant activity in comparison with fats high in palmitic acid or high in myristic and lauric acids.

PubMed

Tholstrup, T; Marckmann, P; Jespersen, J; Sandström, B

1994-02-01

The effect of fats high in individual, prevalent saturated dietary fatty acids on lipoproteins and hemostatic variables in young healthy subjects was evaluated in a randomized strictly controlled metabolic feeding study. Three experimental diets: shea butter (S; 42% stearic acid), palm oil (P; 43% palmitic palmitic acid), and palm-kernel oil with high-oleic sunflower oil (ML; 10% myristic acid, 30% lauric acid) were served to 15 men for 3 wk each, separated by washout periods. Diet S compared with diet P resulted in significant reduction in plasma cholesterol (22%) LDL cholesterol (26%), apolipoprotein B (18%), HDL cholesterol (12%), apolipoprotein A-I (13%), and a 13% lower factor VII coagulant activity (P = 0.001). Similar differences were observed between diets S and ML. In conclusion, intake of shea butter high in stearic acid favorably affects blood lipids and factor VII coagulant activity in young men, compared with fats high in saturated fatty acids with 12-16 carbons.

Removal of binary dyes mixtures with opposite and similar charges by adsorption, coagulation/flocculation and catalytic oxidation in the presence of CeO2/H2O2 Fenton-like system.

PubMed

Issa Hamoud, Houeida; Finqueneisel, Gisèle; Azambre, Bruno

2017-06-15

In this study, the removal of binary mixtures of dyes with similar (Orange II/Acid Green 25) or opposite charges (Orange II/Malachite Green) was investigated either by simple adsorption on ceria or by the heterogeneous Fenton reaction in presence of H 2 O 2 . First, the CeO 2 nanocatalyst with high specific surface area (269 m 2 /g) and small crystal size (5 nm) was characterized using XRD, Raman spectroscopy and N 2 physisorption at 77 K. The adsorption of single dyes was studied either from thermodynamic and kinetic viewpoints. It is shown that the adsorption of dyes on ceria surface is highly pH-dependent and followed a pseudo-second order kinetic model. Adsorption isotherms fit well the Langmuir model with a complete monolayer coverage and higher affinity towards Orange II at pH 3, compared to other dyes. For the (Orange II/Acid Green 25) mixture, both the amounts of dyes adsorbed on ceria surface and discoloration rates measured from Fenton experiments were decreased by comparison with single dyes. This is due to the adsorption competition existing onto the same surface Ce x+ sites and the reaction competition with hydroxyl radicals, respectively. The behavior of the (Orange II/Malachite Green) mixture is markedly different. Dyes with opposite charges undergo paired adsorption on ceria as well as homogeneous and heterogeneous coagulation/flocculation processes, but can also be removed by heterogeneous Fenton process. Copyright © 2016 Elsevier Ltd. All rights reserved.

Confinement regulates complex biochemical networks: initiation of blood clotting by "diffusion acting".

PubMed

Shen, Feng; Pompano, Rebecca R; Kastrup, Christian J; Ismagilov, Rustem F

2009-10-21

This study shows that environmental confinement strongly affects the activation of nonlinear reaction networks, such as blood coagulation (clotting), by small quantities of activators. Blood coagulation is sensitive to the local concentration of soluble activators, initiating only when the activators surpass a threshold concentration, and therefore is regulated by mass transport phenomena such as flow and diffusion. Here, diffusion was limited by decreasing the size of microfluidic chambers, and it was found that microparticles carrying either the classical stimulus, tissue factor, or a bacterial stimulus, Bacillus cereus, initiated coagulation of human platelet-poor plasma only when confined. A simple analytical argument and numerical model were used to describe the mechanism for this phenomenon: confinement causes diffusible activators to accumulate locally and surpass the threshold concentration. To interpret the results, a dimensionless confinement number, Cn, was used to describe whether a stimulus was confined, and a Damköhler number, Da(2), was used to describe whether a subthreshold stimulus could initiate coagulation. In the context of initiation of coagulation by bacteria, this mechanism can be thought of as "diffusion acting", which is distinct from "diffusion sensing". The ability of confinement and diffusion acting to change the outcome of coagulation suggests that confinement should also regulate other biological "on" and "off" processes that are controlled by thresholds.

The Loss of Homeostasis in Hemostasis: New Approaches in Treating and Understanding Acute Disseminated Intravascular Coagulation in Critically Ill Patients*

PubMed Central

Abrams, Charles S.

2012-01-01

Abstract Disseminated intravascular coagulation (DIC) profoundly increases the morbidity and mortality of patients who have sepsis. Both laboratory and clinical research advanced the understanding of the biology and pathophysiology of DIC. This, in turn, gave rise to improved therapies and patient outcomes. Beginning with a stimulus causing disruption of vascular integrity, cytokines and chemokines cause activation of systemic coagulation and inflammation. Seemingly paradoxically, the interplay between coagulation and inflammation also inhibits endogenous anticoagulants, fibrinolytics, and antiinflammatory pathways. The earliest documented and best‐studied microbial cause of DIC is the lipopolysaccharide endotoxin of Gram‐negative bacteria. Extensive microvascular thrombi emerge in the systemic vasculature due to dysregulation of coagulation. The result of this unrestrained, widespread small vessel thromboses multiorgan system failure. Consumption of platelets and coagulation factors during this process can lead to an elevated risk of hemorrhage. The management of these patients with simultaneous hemorrhage and thrombosis is complex and challenging. Definitive treatment of DIC, and attenuation of end‐organ damage, requires control of the inciting cause. Currently, activated protein C is the only approved therapy in the United States for sepsis complicated by DIC. Further research is needed in this area to improve clinical outcomes for patients with sepsis. Clin Trans Sci 2012; Volume 5: 85–92 PMID:22376264

Coagulation Abnormalities of Sickle Cell Disease: Relationship with Clinical Outcomes and the Effect of Disease Modifying Therapies

PubMed Central

Noubouossie, Denis; Key, Nigel S.; Ataga, Kenneth I.

2015-01-01

Sickle cell disease (SCD) is a hypercoagulable state. Patients exhibit increased platelet activation, high plasma levels of markers of thrombin generation, depletion of natural anticoagulant proteins, abnormal activation of the fibrinolytic system, and increased tissue factor expression, even in the non-crisis “steady state.” Furthermore, SCD is characterized by an increased risk of thrombotic complications. The pathogenesis of coagulation activation in SCD appears to be multi-factorial, with contributions from ischemia-reperfusion injury and inflammation, hemolysis and nitric oxide deficiency, and increased sickle RBC phosphatidylserine expression. Recent studies in animal models suggest that activation of coagulation may contribute to the pathogenesis of SCD, but the data on the contribution of coagulation and platelet activation to SCD-related complications in humans are limited. Clinical trials of new generations of anticoagulants and antiplatelet agents, using a variety of clinical endpoints are warranted. PMID:26776344

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

Role of plasma kallikrein in diabetes and metabolism.

PubMed

Feener, E P; Zhou, Q; Fickweiler, W

2013-09-01

Plasma kallikrein (PK) is a serine protease generated from plasma prekallikrein, an abundant circulating zymogen expressed by the Klkb1 gene. The physiological actions of PK have been primarily attributed to its production of bradykinin and activation of coagulation factor XII, which promotes inflammation and the intrinsic coagulation pathway. Recent genetic, molecular, and pharmacological studies of PK have provided further insight into its role in physiology and disease. Genetic analyses have revealed common Klkb1 variants that are association with blood metabolite levels, hypertension, and coagulation. Characterisation of animal models with Klkb1 deficiency and PK inhibition have demonstrated effects on inflammation, vascular function, blood pressure regulation, thrombosis, haemostasis, and metabolism. These reports have also identified a host of PK substrates and interactions, which suggest an expanded physiological role for this protease beyond the bradykinin system and coagulation. The review summarises the mechanisms that contribute to PK activation and its emerging role in diabetes and metabolism.

Sequential Organ Failure Assessment (SOFA) scores differ between genders in a sepsis cohort: Cause or effect?

PubMed Central

Liedgren, Eva; Johansson, Göran; Ferm, Martin; Winsö, Ola

2012-01-01

Background. Controversy exists regarding the influence of gender on sepsis events and outcome. Epidemiological data from other countries may not always apply to local circumstances. The aim of this study was to identify gender differences in patient characteristics, treatment, and outcome related to the occurrence of sepsis at admission to the ICU. Methods. A prospective observational cohort study on patients admitted to the ICU over a 3-year period fulfilling sepsis criteria during the first 24 hours. Demographic data, APACHE II score, SOFA score, TISS 76, aetiology, length of stay (LOS), mortality rate, and aspects of treatment were collected and then analysed with respect to gender differences. Results. There were no gender-related differences in mortality or length of stay. Early organ dysfunction assessed as SOFA score at admission was a stronger risk factor for hospital mortality for women than for men. This discrepancy was mainly associated with the coagulation sub-score. CRP levels differed between genders in relation to hospital mortality. Infection from the abdominopelvic region was more common among women, whereas infection from skin or skin structures were more common in men. Conclusion. In this cohort, gender was not associated with increased mortality during a 2-year follow-up period. SOFA score at ICU admission was a stronger risk factor for hospital mortality for women than for men. The discrepancy was mainly related to the coagulation SOFA sub-score. Together with differences in CRP levels this may suggest differences in inflammatory response patterns between genders. PMID:22793786

The role of protease-activated receptors PAR-1 and PAR-2 in the repair of 16HBE 14o(-) epithelial cell monolayers in vitro.

PubMed

Ewen, D; Clarke, S L; Smith, J R; Berger, C; Salmon, G; Trevethick, M; Shute, J K

2010-03-01

We recently reported that repair following mechanical wounding of epithelial cell layers in vitro is dependent on fibrin formation and the activity of locally expressed coagulation cascade proteins. Serine proteases of the coagulation cascade are an important group of protease-activated receptor (PAR) activators and PAR-1 to 4 are expressed by the normal bronchial epithelium. We tested the hypothesis that activation of PAR-1 and PAR-2 by coagulation cascade proteases stimulates epithelial repair via effects on fibrin formation. Using mechanically wounded 16HBE 14o(-) epithelial cell layers in culture, we investigated the effect of PAR-1 and PAR-2 agonist peptides, control partially scrambled peptides and PAR-neutralizing antibodies on the rate of repair and fibrin formation. Coagulation factors in culture supernatants were measured by immunoblot. RT-PCR was used to investigate PAR-1, PAR-2 and PGE2 receptor (EP-1 to EP-4) expression in this model and qRT-PCR to quantify responses to wounding. Additionally, we investigated the effect of exogenously added factor Xa (FXa) and neutrophil elastase and the influence of PGE2 and indomethacin on the repair response. PAR-1 and PAR-2 peptide agonists stimulated the rate of repair and enhanced the formation of a fibrin provisional matrix to support the repair process. Conversely, PAR-neutralizing antibodies inhibited repair. Under serum-free culture conditions, 16HBE 14o(-) cells expressed EP-2 and EP-3, but not EP-1 or EP-4, receptors. Wounding induced an increased expression of EP-3 but did not alter EP-2, PAR-1 or PAR-2 expression. In the absence of PAR agonists, there was no evidence for a role for PGE2 in fibrin formation or the repair process. Indomethacin attenuated fibrin formation in wounded cultures only in the presence of the PAR-2 peptide. FXa stimulated epithelial repair while neutrophil elastase reduced the levels of coagulation factors and inhibited repair. Locally expressed serine proteases of the coagulation cascade activate PAR-1 and PAR-2 to enhance fibrin formation and bronchial epithelial repair.

Coagulation removal of humic acid-stabilized carbon nanotubes from water by PACl: influences of hydraulic condition and water chemistry.

PubMed

Ma, Si; Liu, Changli; Yang, Kun; Lin, Daohui

2012-11-15

Discharged carbon nanotubes (CNTs) can adsorb the widely-distributed humic acid (HA) in aquatic environments and thus be stabilized. HA-stabilized CNTs can find their way into and challenge the potable water treatment system. This study investigated the efficiency of coagulation and sedimentation techniques in the removal of the HA-stabilized multi-walled carbon nanotubes (MWCNTs) using polyaluminum chloride (PACl) as a coagulant, with a focus on the effects of hydraulic conditions and water chemistry. Stirring speeds in the mixing and reacting stages were gradually changed to examine the effect of the hydraulic conditions on the removal rate. The stirring speed in the reacting stage affected floc formation and thereby had a greater impact on the removal rate than the stirring speed in the mixing stage. Water chemistry factors such as pH and ionic strength had a significant effect on the stability of MWCNT suspension and the removal efficiency. Low pH (4-7) was favorable for saving the coagulant and maintaining high removal efficiency. High ionic strength facilitated the destabilization of the HA-stabilized MWCNTs and thereby lowered the required PACl dosage for the coagulation. However, excessively high ionic strength (higher than the critical coagulation concentration) decreased the maximum removal rate, probably by inhibiting ionic activity of PACl hydrolyzate in water. These results are expected to shed light on the potential improvement of coagulation removal of aqueous stabilized MWCNTs in water treatment systems. Copyright © 2012 Elsevier B.V. All rights reserved.

[Effects on phenol removal in the process of enhanced coagulation by manganese dioxide formed in situ].

PubMed

Zhang, Li-Zhu; Chen, Xiao-Dong; Ma, Jun; Yu, Min; Li, Xin

2011-10-01

Phenol was selected as a model compound. Factors, such as Ca2+, tannic acid, dose of kaolinite, dose of manganese dioxide formed in situ and pH, were invested on phenol removal in the process of enhanced coagulation by manganese dioxide formed in situ. Results showed that the addition of Ca2+ is beneficial for phenol removal. In the range of Ca2+ varied from 0 to 1.0 mmol x L(-1), the efficiency of phenol removal was enhanced more than 10%. Tannic acid can enhance phenol removal significantly when they are coexisted in water. As tannic acid was added to 10 mg x L(-1), phenol removal can be increased about 30% and 50% in the process of coagulation by AlCl3 and enhanced coagulation by manganese dioxide formed in situ, respectively. The dose of coagulant can be reduced in the process of enhanced coagulation with the addition of manganese dioxide formed in situ. The point of 1 mg x L(-1) manganese dioxide formed in situ linked with 30 mg x L(-1) AlCl3 can have the same phenol removal efficiency as the addition of 50 mg x L(-1) AlCl3. In the range of pH varied from 5 to 9, phenol can be removed with the high efficiency in the process of enhanced coagulation by manganese dioxide formed in situ. While under the strong acid condition and strong basic condition, phenol has lower removal efficiency.

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.

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.

Activation of coagulation and endothelium with concurrent impairment of anticoagulant mechanisms in patients with typhoid fever.

PubMed

de Jong, Hanna K; Parry, Chris M; van der Vaart, Thomas W; Kager, Liesbeth M; van den Ende, Stannie J; Maude, Rapeephan R; Wijedoru, Lalith; Ghose, Aniruddha; Hassan, Mohammed U; Hossain, Mohammed A; Dondorp, Arjan M; Baker, Steve; Faiz, M Abul; Meijers, Joost C M; Wiersinga, W Joost

2018-05-07

Typhoid fever caused by Salmonella Typhi remains a major burden worldwide. Gastrointestinal bleeding can be seen in up to 10 percent of patients and may be fatal. The coagulopathy, which may be the driver of this severe complication in patients with typhoid fever, however is ill defined. The aim of this study was to evaluate the activation of coagulation, anticoagulation, and fibrinolysis in patients with acute typhoid fever. Parameters of coagulation and fibrinolysis were measured in 28 hospitalized patients with culture-confirmed or PCR-confirmed typhoid fever and compared to 38 age- and sex-matched healthy volunteers. Patients demonstrated activation of the coagulation system, as reflected by elevated in vitro thrombin generation and high plasma levels of fibrinogen, D-dimer and prothrombin fragment F1 + 2 in concert with consumption of coagulation factors resulting in a prolonged prothrombin-time and activated-partial-thromboplastin-time. Concurrently, the anticoagulant proteins, protein C and antithrombin, were significantly lower in comparison to healthy controls. Patients also demonstrated evidence of activation and inhibition of fibrinolysis and a marked activation of endothelial cells. The extent of coagulation activation was associated with the course of the disease, repeated testing during convalescence showed a return toward normal values. Activation of coagulation is an important clinical feature of typhoid fever and is associated with severity of disease. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Waste Water Management and Infectious Disease. Part II: Impact of Waste Water Treatment

ERIC Educational Resources Information Center

Cooper, Robert C.

1975-01-01

The ability of various treatment processes, such as oxidation ponds, chemical coagulation and filtration, and the soil mantle, to remove the agents of infectious disease found in waste water is discussed. The literature concerning the efficiency of removal of these organisms by various treatment processes is reviewed. (BT)

Short communication: Prediction of milk coagulation and acidity traits in Mediterranean buffalo milk using Fourier-transform mid-infrared spectroscopy.

PubMed

Manuelian, C L; Visentin, G; Boselli, C; Giangolini, G; Cassandro, M; De Marchi, M

2017-09-01

Milk coagulation and acidity traits are important factors to inform the cheesemaking process. Those traits have been deeply studied in bovine milk, whereas scarce information is available for buffalo milk. However, the dairy industry is interested in a method to determine milk coagulation and acidity features quickly and in a cost-effective manner, which could be provided by Fourier-transform mid-infrared (FT-MIR) spectroscopy. The aim of this study was to evaluate the potential of FT-MIR to predict coagulation and acidity traits of Mediterranean buffalo milk. A total of 654 records from 36 herds located in central Italy with information on milk yield, somatic cell score, milk chemical composition, milk acidity [pH, titratable acidity (TA)], and milk coagulation properties (rennet coagulation time, curd firming time, and curd firmness) were available for statistical analysis. Reference measures of milk acidity and coagulation properties were matched with milk spectral information, and FT-MIR prediction models were built using partial least squares regression. The data set was divided into a calibration set (75%) and a validation set (25%). The capacity of FT-MIR spectroscopy to correctly classify milk samples based on their renneting ability was evaluated by a canonical discriminant analysis. Average values for milk coagulation traits were 13.32 min, 3.24 min, and 39.27 mm for rennet coagulation time, curd firming time, and curd firmness, respectively. Milk acidity traits averaged 6.66 (pH) and 7.22 Soxhlet-Henkel degrees/100 mL (TA). All milk coagulation and acidity traits, except for pH, had high variability (17 to 46%). Prediction models of coagulation traits were moderately to scarcely accurate, whereas the coefficients of determination of external validation were 0.76 and 0.66 for pH and TA, respectively. Canonical discriminant analysis indicated that information on milk coagulating ability is present in the MIR spectra, and the model correctly classified as noncoagulating the 91.57 and 67.86% of milk samples in the calibration and validation sets, respectively. In conclusion, our results can be relevant to the dairy industry to classify buffalo milk samples before processing. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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 [1.1, 4.1], P = 0.032), reoperation (OR = 3.6 [1.4, 9.3], P = 0.008), and sepsis (OR = 3.4 [1.1, 10.4], P = 0.031). This is the first large study to document abnormal coagulation profile as an independent predictor of outcomes following PCLF. Abnormal coagulation profile represents a predictor of complications that can be medically mitigated, and is therefore a valuable parameter to assess preoperatively. Coagulation profile should continue to play a role in targeting patients for risk stratification, preoperative optimization, and quality improvement initiatives. 3.

Immobilized rennin in TC/SG composite in cheese production.

PubMed

Barouni, Eleftheria; Petsi, Theano; Kolliopoulos, Dionysios; Vasileiou, Dimitrios; Panas, Panagiotis; Bekatorou, Argyro; Kanellaki, Maria; Koutinas, Athanasios A

2016-06-01

The object of the current study was to develop a new process for continuous Feta-type cheese production using a biocatalyst consisting of immobilized rennin on a tubular cellulose/starch gel (TC/SG) composite, which has been proven to be an appropriate carrier for enzyme immobilization. Different methodologies were used in order to prepare four biocatalysts. The most effective was selected for cheese production in a 1L continuous system, providing two economically useful results for the dairy industries: (i) increase of productivity by the continuous coagulation of milk, and (ii) saving of the rennin enzyme expenses of the batch coagulation of milk. The criteria used to choose the appropriate biocatalyst was based on the time of coagulation in successive batches, the concentration of immobilized rennin combined with the filter efficiency and its application in the continuous system. Physicochemical analyses of the cheeses at various stages of the ripening were performed. No significant differences compared to cheeses prepared with the traditional method were found. Aroma compounds were determined by SPME GC-MS. Copyright © 2016 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.

Coagulation effect on the activity size distributions of long lived radon progeny aerosols and its application to atmospheric residence time estimation techniques.

PubMed

Anand, S; Mayya, Y S

2015-03-01

The long lived naturally occurring radon progeny species in the atmosphere, namely (210)Pb, (210)Bi and (210)Po, have been used as important tracers for understanding the atmospheric mixing processes and estimating aerosol residence times. Several observations in the past have shown that the activity size distribution of these species peaks at larger particle sizes as compared to the short lived radon progeny species - an effect that has been attributed to the process of coagulation of the background aerosols to which they are attached. To address this issue, a mathematical equation is derived for the activity-size distribution of tracer species by formulating a generalized distribution function for the number of tracer atoms present in coagulating background particles in the presence of radioactive decay and removal. A set of these equations is numerically solved for the progeny chain using Fuchs coagulation kernel combined with a realistic steady-state aerosol size spectrum that includes nucleation, accumulation and coarse mode components. The important findings are: (i) larger shifts in the modal sizes of (210)Pb and (210)Po at higher aerosol concentrations such as that found in certain Asian urban regions (ii) enrichment of tracer specific activity on particles as compared to that predicted by pure attachment laws (iii) sharp decline of daughter-to-parent activity ratios for decreasing particle sizes. The implication of the results to size-fractionated residence time estimation techniques is highlighted. A coagulation corrected graphical approach is presented for estimating the residence times from the size-segregated activity ratios of (210)Bi and (210)Po with respect to (210)Pb. The discrepancy between the residence times predicted by conventional formula and the coagulation corrected approach for specified activity ratios increases at higher atmospheric aerosol number concentrations (>10(10) #/m(3)) for smaller sizes (<1 μm). The results are further discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Two-dimensional correlation spectroscopic analysis on the interaction between humic acids and aluminum coagulant.

PubMed

Jin, Pengkang; Song, Jina; Wang, Xiaochang C; Jin, Xin

2018-02-01

In this study, two-dimensional correlation spectroscopy integrated with synchronous fluorescence and infrared absorption spectroscopy was employed to investigate the interaction between humic acids and aluminum coagulant at slightly acidic and neutral pH. Higher fluorescence quenching was produced for fulvic-like and humic-like fractions at pH5. At pH5, the humic-like fractions originating from the carboxylic acid, carboxyl and polysaccharide compounds were bound to aluminum first, followed by the fulvic-like fractions originating from the carboxyl and polysaccharide compounds. This finding also demonstrated that the activated functional groups of HA were involved in forming the Al-HA complex, which was accompanied by the removal of other groups by co-precipitation. Meanwhile, at pH7, almost no fluorescence quenching occurred, and surface complexation was observed to occur, in which the activated functional groups were absorbed on the amorphous Al(OH) 3 . Two-dimensional FT-IR correlation spectroscopy indicated the sequence of HA structural change during coagulation with aluminum, with IR bands affected in the order of COOH>COO - >NH deformation of amide II>aliphatic hydroxyl COH at pH5, and COO - >aliphatic hydroxyl COH at pH7. This study provides a promising pathway for analysis and insight into the priority of functional groups in the interaction between organic matters and metal coagulants. Copyright © 2017. Published by Elsevier B.V.

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.

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

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.

Response surface methodology investigation into the interactions between arsenic and humic acid in water during the coagulation process.

PubMed

Watson, Malcolm Alexander; Tubić, Aleksandra; Agbaba, Jasmina; Nikić, Jasmina; Maletić, Snežana; Molnar Jazić, Jelena; Dalmacija, Božo

2016-07-15

Interactions between arsenic and natural organic matter (NOM) are key limiting factors during the optimisation of drinking water treatment when significant amounts of both must be removed. This work uses Response Surface Methodology (RSM) to investigate how they interact during their simultaneous removal by iron chloride coagulation, using humic acid (HA) as a model NOM substance. Using a three factor Box-Behnken experimental design, As and HA removals were modelled, as well as a combined removal response. ANOVA results showed the significance of the coagulant dose for all three responses. At high initial arsenic concentrations (200μg/l), As removal was significantly hindered by the presence of HA. In contrast, the HA removal response was found to be largely independent of the initial As concentration, with the optimum coagulant dose increasing at increasing HA concentrations. The combined response was similar to the HA removal response, and the interactions evident are most interesting in terms of optimising treatment processes during the preparation of drinking water, highlighting the importance of utilizing RSM for such investigations. The combined response model was successfully validated with two different groundwaters used for drinking water supply in the Republic of Serbia, showing excellent agreement under similar experimental conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Increased circulating procoagulant and anticoagulant factors as TF and TFPI according to severity or infecting serotypes in human dengue infection.

PubMed

Leal de Azeredo, Elzinandes; Solórzano, Victor Edgar Fiestas; de Oliveira, Débora Batista; Marinho, Cintia Ferreira; de Souza, Luiz José; da Cunha, Rivaldo Venâncio; Damasco, Paulo Vieira; Kubelka, Claire Fernandes; de-Oliveira-Pinto, Luzia Maria

2017-01-01

Tissue Factor (TF) is the initiator of coagulation and Tissue Factor Inhibitor (TFPI) is the physiological inhibitor of the TF/FVIIa complex. Circulating levels of TF and TFPI were quantified in dengue patients and the relationships with disease severity and infecting serotype analysed. A significant decrease in TF and TPFI plasma levels was observed in mild DF patients compared with severe dengue. Furthermore, both factors were associated with haemorrhagic manifestations. Finally, TF levels were significantly increased in DENV-1/2 infected patients as compared with DENV-4. These findings suggest that activation of TF-pathway is an important component of DENV -related coagulation disorders. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Identification and Mechanistic Analysis of a Novel Tick-Derived Inhibitor of Thrombin

PubMed Central

Jablonka, Willy; Kotsyfakis, Michalis; Mizurini, Daniella M.; Monteiro, Robson Q.; Lukszo, Jan; Drake, Steven K.; Ribeiro, José M. C.; Andersen, John F.

2015-01-01

A group of peptides from the salivary gland of the tick Hyalomma marginatum rufipes, a vector of Crimean Congo hemorrhagic fever show weak similarity to the madanins, a group of thrombin-inhibitory peptides from a second tick species, Haemaphysalis longicornis. We have evaluated the anti-serine protease activity of one of these H. marginatum peptides that has been given the name hyalomin-1. Hyalomin-1 was found to be a selective inhibitor of thrombin, blocking coagulation of plasma and inhibiting S2238 hydrolysis in a competitive manner with an inhibition constant (Ki) of 12 nM at an ionic strength of 150 mM. It also blocks the thrombin-mediated activation of coagulation factor XI, thrombin-mediated platelet aggregation, and the activation of coagulation factor V by thrombin. Hyalomin-1 is cleaved at a canonical thrombin cleavage site but the cleaved products do not inhibit coagulation. However, the C-terminal cleavage product showed non-competitive inhibition of S2238 hydrolysis. A peptide combining the N-terminal parts of the molecule with the cleavage region did not interact strongly with thrombin, but a 24-residue fragment containing the cleavage region and the C-terminal fragment inhibited the enzyme in a competitive manner and also inhibited coagulation of plasma. These results suggest that the peptide acts by binding to the active site as well as exosite I or the autolysis loop of thrombin. Injection of 2.5 mg/kg of hyalomin-1 increased arterial occlusion time in a mouse model of thrombosis, suggesting this peptide could be a candidate for clinical use as an antithrombotic. PMID:26244557

[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.

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

Pluripotency and a secretion mechanism of Drosophila transglutaminase.

PubMed

Shibata, Toshio; Kawabata, Shun-Ichiro

2018-03-01

Transglutaminase (TG) catalyses the formation of an isopeptide bond between glutamine and lysine residues and amine incorporation into specific glutamine residues. TG is conserved in all metazoans and functions both intracellularly and extracellularly. Here we review the existing knowledge of Drosophila TG with an emphasis on its pluripotency: Drosophila TG (i) plays a key role in cuticular morphogenesis, haemolymph coagulation, and entrapment against invading pathogens, (ii) suppresses the immune deficiency pathway to enable immune tolerance against commensal bacteria through the incorporation of polyamines into the nuclear factor-κB-like transcription factor Relish as well as through the protein-protein cross-linking of Relish, (iii) forms a physical matrix in the gut through cross-linking of chitin-binding proteins and (iv) is involved in the maintenance of homeostasis in microbiota in the gut. Moreover, we review the evidence that TG-A, one of alternative splicing-derived isoforms of Drosophila TG, is secreted through an endoplasmic reticulum/Golgi-independent pathway involving exosomes and fatty acylations.

Losac, the First Hemolin that Exhibits Procogulant Activity through Selective Factor X Proteolytic Activation*

PubMed Central

Alvarez-Flores, Miryam Paola; Furlin, Daniel; Ramos, Oscar H. P.; Balan, Andrea; Konno, Katsuhiro; Chudzinski-Tavassi, Ana Marisa

2011-01-01

Envenoming by the contact of human skin with Lonomia obliqua caterpillars promotes a hemorrhagic syndrome characterized by a consumptive coagulopathy. Losac (Lonomia obliqua Stuart factor activator) is a component of the bristle of L. obliqua that is probably partially responsible for the observed syndrome because it activates factor X and is recognized by an effective antilonomic serum. Here we unveil the proteolytic activity of Losac and demonstrate the feasibility of its recombinant production. On the other hand, Losac has no homology to known proteases, but it can be inhibited by PMSF, a serine protease inhibitor. Instead, it shows closer homology to members of the hemolin family of proteins, a group of cell adhesion molecules. The recombinant protein (rLosac) shortened the coagulation time of normal and deficient plasmas, whereas it was ineffective in factor X-deficient plasma unless reconstituted with this protein. rLosac was able to activate factor X in a dose- and time-dependent manner but not γ-carboxyglutamic acid domainless factor X. Moreover, phospholipids and calcium ions increased rLosac activity. Also, rLosac had no effect on fibrin or fibrinogen, indicating its specificity for blood coagulation activation. Linear double reciprocal plots indicate that rLosac follows a Michaelis-Menten kinetics. Cleavage of factor X by rLosac resulted in fragments that are compatible with those generated by RVV-X (a well known factor X activator). Together, our results validate Losac as the first protein from the hemolin family exhibiting procoagulant activity through selective proteolysis on coagulation factor X. PMID:21177860

Confinement Regulates Complex Biochemical Networks: Initiation of Blood Clotting by “Diffusion Acting”

PubMed Central

Shen, Feng; Pompano, Rebecca R.; Kastrup, Christian J.; Ismagilov, Rustem F.

2009-01-01

Abstract This study shows that environmental confinement strongly affects the activation of nonlinear reaction networks, such as blood coagulation (clotting), by small quantities of activators. Blood coagulation is sensitive to the local concentration of soluble activators, initiating only when the activators surpass a threshold concentration, and therefore is regulated by mass transport phenomena such as flow and diffusion. Here, diffusion was limited by decreasing the size of microfluidic chambers, and it was found that microparticles carrying either the classical stimulus, tissue factor, or a bacterial stimulus, Bacillus cereus, initiated coagulation of human platelet-poor plasma only when confined. A simple analytical argument and numerical model were used to describe the mechanism for this phenomenon: confinement causes diffusible activators to accumulate locally and surpass the threshold concentration. To interpret the results, a dimensionless confinement number, Cn, was used to describe whether a stimulus was confined, and a Damköhler number, Da2, was used to describe whether a subthreshold stimulus could initiate coagulation. In the context of initiation of coagulation by bacteria, this mechanism can be thought of as “diffusion acting”, which is distinct from “diffusion sensing”. The ability of confinement and diffusion acting to change the outcome of coagulation suggests that confinement should also regulate other biological “on” and “off” processes that are controlled by thresholds. PMID:19843446

A case control study on the structural equation model of the mechanism of coagulation and fibrinolysis imbalance in chronic schistosomiasis.

PubMed

Le, Aiping; Zhang, Lunli; Liu, Wei; Li, Xiaopeng; Ren, Jianwei; Ning, An

2017-02-01

A structural equation model was used for verification with chronic schistosomiasis to investigate the coagulation-anticoagulation system imbalance and to deduce the mechanism of D-dimer (D-D) level elevation in patients with advanced schistosome hepatic disease. We detected the plasma levels of tissue-type fiber plasminogen activator (tPA), urokinase type plasminogen activator (uPA), plasmin-antiplasmin complex (PAP), plasminogen (PLG), antithrombin (AT), plasminogen activator inhibitor 1 (PAI1), D-D, factor VIII: C (FVIII:C), antithrombin-III (AT-III), PLG, protein S (PS), and protein C (PC) in the healthy people as control (69), patients with chronic schistosomiasis (150) or advanced chronic schistosomiasis (90). FVIII, PAP, D-D, tPA, and uPA plasma levels were significantly higher in the chronic group than in the control group and were also significantly higher in the advanced group. However, AT-III, PC, PS, AT, PLG, and PAI1 plasma levels in the advanced and chronic groups were significantly lower than those in the control group. With progression of disease in patients with schistosomiasis japonica, a hypercoagulable state is induced by the coagulation-anticoagulation imbalance, eventually leading to patients with high levels of D-D. Furthermore, we established a structural equation model path of a "chronic schistosomiasis disease stage-(coagulation-anticoagulation-fibrinolysis)-D-D." By using analysis of moment structures (AMOS), it was shown that the chronic schistosomiasis stage was positively related to factor VIII and had negative correlation with AT-III; a good positive correlation with PAP, tPA, and uPA; and a good negative correlation with PLG and PAI1. In addition, our results show that the path coefficient of anticoagulation-fibrinolysis system to the chronic stage of schistosomiasis or D-D levels was significantly higher than that of the coagulation system. In conclusion, the coagulation and fibrinolysis imbalance in patients with chronic schistosomiasis, especially with advanced schistosomiasis, is due to the progression of disease stages.

Tissue factor expression by endothelial cells in sickle cell anemia.

PubMed

Solovey, A; Gui, L; Key, N S; Hebbel, R P

1998-05-01

The role of the vascular endothelium in activation of the coagulation system, a fundamental homeostatic mechanism of mammalian biology, is uncertain because there is little evidence indicating that endothelial cells in vivo express tissue factor (TF), the system's triggering mechanism. As a surrogate for vessel wall endothelium, we examined circulating endothelial cells (CEC) from normals and patients with sickle cell anemia, a disease associated with activation of coagulation. We find that sickle CEC abnormally express TF antigen (expressed as percent CEC that are TF-positive), with 66+/-13% positive in sickle patients in steady-state, 83+/-19% positive in sickle patients presenting with acute vasoocclusive episodes, and only 10+/-13% positive in normal controls. Repeated samplings confirmed this impression that TF expression is greater when sickle patients develop acute vasoocclusive episodes. Sickle CEC are also positive for TF mRNA, with excellent concurrence between antigen and mRNA expression. The TF expressed on the antigen-positive CEC is functional, as demonstrated by a binding assay for Factor VIIa and a chromogenic assay sensitive to generation of Factor Xa. By establishing that endothelial cells in vivo can express TF, these data imply that the vast endothelial surface area does provide an important pathophysiologic trigger for coagulation activation.

Amorphous nanosilicas induce consumptive coagulopathy after systemic exposure

NASA Astrophysics Data System (ADS)

Nabeshi, Hiromi; Yoshikawa, Tomoaki; Matsuyama, Keigo; Nakazato, Yasutaro; Arimori, Akihiro; Isobe, Masaaki; Tochigi, Saeko; Kondoh, Sayuri; Hirai, Toshiro; Akase, Takanori; Yamashita, Takuya; Yamashita, Kohei; Yoshida, Tokuyuki; Nagano, Kazuya; Abe, Yasuhiro; Yoshioka, Yasuo; Kamada, Haruhiko; Imazawa, Takayoshi; Itoh, Norio; Kondoh, Masuo; Yagi, Kiyohito; Mayumi, Tadanori; Tsunoda, Shin-ichi; Tsutsumi, Yasuo

2012-02-01

We previously reported that well-dispersed amorphous nanosilicas with particle size 70 nm (nSP70) penetrate skin and produce systemic exposure after topical application. These findings underscore the need to examine biological effects after systemic exposure to nanosilicas. The present study was designed to examine the biological effects. BALB/c mice were intravenously injected with amorphous nanosilicas of sizes 70, 100, 300, 1000 nm and then assessed for survival, blood biochemistry, and coagulation. As a result, injection of nSP70 caused fatal toxicity, liver damage, and platelet depletion, suggesting that nSP70 caused consumptive coagulopathy. Additionally, nSP70 exerts procoagulant activity in vitro associated with an increase in specific surface area, which increases as diameter reduces. In contrast, nSP70-mediated procoagulant activity was absent in factor XII-deficient plasma. Collectively, we revealed that interaction between nSP70 and intrinsic coagulation factors such as factor XII, were deeply related to nSP70-induced harmful effects. In other words, it is suggested that if interaction between nSP70 and coagulation factors can be suppressed, nSP70-induced harmful effects may be avoided. These results would provide useful information for ensuring the safety of nanomaterials (NMs) and open new frontiers in biological fields by the use of NMs.

Edible bird’s nest attenuates procoagulation effects of high-fat diet in rats

PubMed Central

Yida, Zhang; Imam, Mustapha Umar; Ismail, Maznah; Ismail, Norsharina; Hou, Zhiping

2015-01-01

Edible bird’s nest (EBN) is popular in Asia, and has long been used traditionally as a supplement. There are, however, limited evidence-based studies on its efficacy. EBN has been reported to improve dyslipidemia, which is closely linked to hypercoagulation states. In the present study, the effects of EBN on high-fat diet- (HFD-) induced coagulation in rats were evaluated. Rats were fed for 12 weeks with HFD alone or in combination with simvastatin or EBN. Food intake was estimated, and weight measurements were made during the experimental period. After sacrifice, serum oxidized low-density lipoprotein (oxLDL), adiponectin, leptin, von willibrand factor, prostacyclin, thromboxane and lipid profile, and whole blood coagulation indices (bleeding time, prothrombin time, activated partial thromboplastin time, red blood count count, and platelet count) were estimated. Furthermore, hepatic expression of coagulation-related genes was evaluated using multiplex polymerase chain reaction. The results indicated that EBN could attenuate HFD-induced hypercholesterolemia and coagulation similar to simvastatin, partly through transcriptional regulation of coagulation-related genes. The results suggested that EBN has the potential for lowering the risk of cardiovascular disease-related hypercoagulation due to hypercholesterolemia. PMID:26251574

Complement component 5 promotes lethal thrombosis

PubMed Central

Mizuno, Tomohiro; Yoshioka, Kengo; Mizuno, Masashi; Shimizu, Mie; Nagano, Fumihiko; Okuda, Tomoyuki; Tsuboi, Naotake; Maruyama, Shoichi; Nagamatsu, Tadashi; Imai, Masaki

2017-01-01

Extracellular histones promote platelet aggregation and thrombosis; this is followed by induction of coagulation disorder, which results in exhaustion of coagulation factors. Complement component 5 (C5) is known to be associated with platelet aggregation and coagulation system activation. To date, the pathological mechanism underlying liver injury has remained unclear. Here, we investigated whether C5 promotes liver injury associated with histone-induced lethal thrombosis. C5-sufficient and C5-deficient mice received single tail vein injections of purified, unfractionated histones obtained from calf thymus (45–75 μg/g). Subsequently, the mice were monitored for survival for up to 72 h. Based on the survival data, the 45 μg/g dose was used for analysis of blood cell count, liver function, blood coagulation ability, and promotion of platelet aggregation and platelet/leukocyte aggregate (PLA) production by extracellular histones. C5-deficient mice were protected from lethal thrombosis and had milder thrombocytopenia, consumptive coagulopathy, and liver injury with embolism and lower PLA production than C5-sufficient mice. These results indicate that C5 is associated with coagulation disorders, PLA production, and embolism-induced liver injury. In conclusion, C5 promotes liver injury associated with histone-induced lethal thrombosis. PMID:28205538

Host defense peptides of thrombin modulate inflammation and coagulation in endotoxin-mediated shock and Pseudomonas aeruginosa sepsis.

PubMed

Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; Mörgelin, Matthias; van der Plas, Mariena J A; Rydengård, Victoria; Malmsten, Martin; Albiger, Barbara; Schmidtchen, Artur

2012-01-01

Gram-negative sepsis is accompanied by a disproportionate innate immune response and excessive coagulation mainly induced by endotoxins released from bacteria. Due to rising antibiotic resistance and current lack of other effective treatments there is an urgent need for new therapies. We here present a new treatment concept for sepsis and endotoxin-mediated shock, based on host defense peptides from the C-terminal part of human thrombin, found to have a broad and inhibitory effect on multiple sepsis pathologies. Thus, the peptides abrogate pro-inflammatory cytokine responses to endotoxin in vitro and in vivo. Furthermore, they interfere with coagulation by modulating contact activation and tissue factor-mediated clotting in vitro, leading to normalization of coagulation responses in vivo, a previously unknown function of host defense peptides. In a mouse model of Pseudomonas aeruginosa sepsis, the peptide GKY25, while mediating a modest antimicrobial effect, significantly inhibited the pro-inflammatory response, decreased fibrin deposition and leakage in the lungs, as well as reduced mortality. Taken together, the capacity of such thrombin-derived peptides to simultaneously modulate bacterial levels, pro-inflammatory responses, and coagulation, renders them attractive therapeutic candidates for the treatment of invasive infections and sepsis.

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-existing pathology 15. The assay was used to show that in 9 patients with DIC, the FV 1-stage, 2-stage, and total activities were decreased, on average, by 54%, 44%, and 42%, respectively, compared with normal pooled human reference plasma (NHP). The FV microplate assay is easily adaptable to measure the activity of any coagulation factor. This assay will increase our understanding of FV biochemistry through a more accurate and complete measurement of its activity in research and clinical settings. This information will positively impact healthcare environments through earlier diagnosis and development of more effective treatments for coagulation disorders, such as DIC. PMID:22987015

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 above the pre-existing pathology (15). The assay was used to show that in 9 patients with DIC, the FV 1-stage, 2-stage, and total activities were decreased, on average, by 54%, 44%, and 42%, respectively, compared with normal pooled human reference plasma (NHP). The FV microplate assay is easily adaptable to measure the activity of any coagulation factor. This assay will increase our understanding of FV biochemistry through a more accurate and complete measurement of its activity in research and clinical settings. This information will positively impact healthcare environments through earlier diagnosis and development of more effective treatments for coagulation disorders, such as DIC.

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.

Increased coagulation and fibrinolytic potential of solvent-detergent plasma: a comparative study between Omniplasma and fresh frozen plasma.

PubMed

van Beers, J J B C; van Egmond, L T; Wetzels, R J H; Verhezen, P W M; Beckers, E A M; van Oerle, R; Spronk, H M H; Straat, R J M H E; Henskens, Y M C

2016-07-01

In this study, differences in levels of proteins involved in coagulation and fibrinolysis were compared between fresh frozen (quarantine plasma) and Omniplasma. Furthermore, thawing conditions and plasma stability after thawing were studied. 10 Omniplasma and 10 quarantine plasma units were used to study different procoagulation, anticoagulation and fibrinolytic parameters. Analysis took place at different time-points during plasma storage at 2-6°C. At baseline, significant reduced levels of factor V, free protein S, α2-antiplasmin and tPA-induced ROTEM lysis time were observed in Omniplasma as compared to quarantine plasma. Moreover, thrombin generation, IXa-AT complex levels and factor XIa were significantly increased in Omniplasma. The majority of the parameters studied remained stable in Omniplasma 48 h after thawing, with the exception of factor VIII (decrease) and IXa-AT (increase). Our results suggest an increased coagulation potential, presumingly as a result of contact activation during the production process and also, an increased fibrinolytic potential in Omniplasma. The stability of Omniplasma, based upon the different parameters studied, is comparable to Q-plasma. A maximum post-thawing time of 48 hfor Omniplasma can be suggested. © 2016 International Society of Blood Transfusion.

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

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.

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

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.

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).

Telangiectatic Matting is Associated with Hypersensitivity and a Bleeding Tendency.

PubMed

Kadam, Pooja; Lim, Jerrick; Paver, Ian; Connor, David E; Parsi, Kurosh

2018-04-01

The aim was to investigate the pathogenesis of telangiectatic matting (TM) and identify possible risk factors. This study had two parts. The clinical records of consecutive patients were retrospectively analysed to identify risk factors for TM. In the second part, the haemostatic and coagulation profile of the subset of patients with TM were analysed and compared with controls using standard coagulation tests, platelet function and a global assay of coagulation (rotational thromboelastometry, ROTEM). In 352 consecutive patients presenting to a phlebology practice, 25 patients had TM (7.1%). All 25 patients were female with the median age of 45 (27-57) years. A comprehensive medical history was taken. Among 27 possible risk factors assessed, statistically significant associations included recurrent epistaxis, easy bruising, hypersensitivity (eczema, hives, hay fever, and rhinitis), previous treatment with sclerotherapy or endovenous laser for lower limb veins, and a family history of telangiectasias. Variables not associated with TM included oral contraceptive intake, hormone replacement therapy, and age. The haemostatic and coagulation profile of 12 patients (6 male and 6 female) with TM did not differ significantly from those without TM. TM is associated with both hypersensitivity and a bleeding tendency. This study revealed no significant increase in the incidence of haemostatic abnormalities in patients with TM compared with the control group. Given the significant association with hypersensitivity disorders, the underlying mast cell hyper-reactivity may contribute to both hypersensitivity and a bleeding tendency and predispose patients to TM. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Alteration of Antithrombin III and D-dimer Levels in Clinically Localized Prostate Cancer

PubMed Central

Ko, Dong Woo; Park, Juhyun; Kim, In Sung; Doo, Seung Hwan; Yoon, Cheol Yong; Park, Hongzoo; Lee, Won Ki; Kim, Dae Sung; Jeong, Seong Jin; Byun, Seok-Soo; Lee, Sang Eun

2010-01-01

Purpose We performed a comparative analysis of the plasma levels of antithrombin (AT) III, plasminogen, fibrinogen, and D-dimer among patients with and without clinically localized prostate cancer to investigate the clinical significance of the coagulation profile in prostate cancer. Materials and Methods A prospective study was performed in which plasma levels of AT III, plasminogen, fibrinogen, and D-dimer were assessed in patients before they underwent prostate biopsy. According to the results of the biopsy, the patients were categorized into the cancer group or the control group. Levels of the four coagulation factors were then compared between the cancer and control groups. Also, levels of the four coagulation factors were correlated with tumor stage and grade in the cancer group. Results The cancer group had significantly lower levels of AT III activity and higher plasma D-dimer levels than did the control group (p=0.007 and p=0.018, respectively). Within the cancer group, no significant differences were observed in the levels of AT III, plasminogen, fibrinogen, or D-dimer between those with a pathological Gleason score of ≥7 and otherwise. Regarding pathologic stage of prostate cancer, the subjects with organ-confined disease and those with extraprostatic extension of a tumor demonstrated no significant differences in the preoperative levels of the four coagulation factors analyzed. Conclusions Our results suggest that plasma levels of AT III and D-dimer are altered in patients with prostate cancer. Further study is needed to elucidate the underlying mechanism and clinical significances of such a phenomenon among patients with clinically localized prostate cancer. PMID:20414406

Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy

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

Schechter, Melissa E.; Andrade, Bruno B.; He, Tianyu

In HIV infection, persistent inflammation despite effective antiretroviral therapy is linked to increased risk of noninfectious chronic complications such as cardiovascular and thromboembolic disease. Thus, a better understanding of inflammatory and coagulation pathways in HIV infection is needed to optimize clinical care. Markers of monocyte activation and coagulation independently predict morbidity and mortality associated with non-AIDS events. We identified a specific subset of monocytes that express tissue factor (TF), persist after virological suppression, and trigger the coagulation cascade by activating factor X. This subset of monocytes expressing TF had a distinct gene signature with up-regulated innate immune markers and evidencemore » of robust production of multiple proinflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor–α (TNF-α), and IL-6, ex vivo and in vitro upon lipopolysaccharide stimulation. We validated our findings in a nonhuman primate model, showing that TF-expressing inflammatory monocytes were associated with simian immunodeficiency virus (SIV)–related coagulopathy in the progressive [pigtail macaques (PTMs)] but not in the nonpathogenic (African green monkeys) SIV infection model. Last, Ixolaris, an anticoagulant that inhibits the TF pathway, was tested and potently blocked functional TF activity in vitro in HIV and SIV infection without affecting monocyte responses to Toll-like receptor stimulation. Strikingly, in vivo treatment of SIV-infected PTMs with Ixolaris was associated with significant decreases in D-dimer and immune activation. These data suggest that TF-expressing monocytes are at the epicenter of inflammation and coagulation in chronic HIV and SIV infection and may represent a potential therapeutic target.« less

Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy

DOE PAGES

Schechter, Melissa E.; Andrade, Bruno B.; He, Tianyu; ...

2017-08-30

In HIV infection, persistent inflammation despite effective antiretroviral therapy is linked to increased risk of noninfectious chronic complications such as cardiovascular and thromboembolic disease. Thus, a better understanding of inflammatory and coagulation pathways in HIV infection is needed to optimize clinical care. Markers of monocyte activation and coagulation independently predict morbidity and mortality associated with non-AIDS events. We identified a specific subset of monocytes that express tissue factor (TF), persist after virological suppression, and trigger the coagulation cascade by activating factor X. This subset of monocytes expressing TF had a distinct gene signature with up-regulated innate immune markers and evidencemore » of robust production of multiple proinflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor–α (TNF-α), and IL-6, ex vivo and in vitro upon lipopolysaccharide stimulation. We validated our findings in a nonhuman primate model, showing that TF-expressing inflammatory monocytes were associated with simian immunodeficiency virus (SIV)–related coagulopathy in the progressive [pigtail macaques (PTMs)] but not in the nonpathogenic (African green monkeys) SIV infection model. Last, Ixolaris, an anticoagulant that inhibits the TF pathway, was tested and potently blocked functional TF activity in vitro in HIV and SIV infection without affecting monocyte responses to Toll-like receptor stimulation. Strikingly, in vivo treatment of SIV-infected PTMs with Ixolaris was associated with significant decreases in D-dimer and immune activation. These data suggest that TF-expressing monocytes are at the epicenter of inflammation and coagulation in chronic HIV and SIV infection and may represent a potential therapeutic target.« less

Human Cells as Platform to Produce Gamma-Carboxylated Proteins.

PubMed

de Sousa Bomfim, Aline; de Freitas, Marcela Cristina Corrêa; Covas, Dimas Tadeu; de Sousa Russo, Elisa Maria

2018-01-01

The gamma-carboxylated proteins belong to a family of proteins that depend on vitamin K for normal biosynthesis. The major representative gamma-carboxylated proteins are the coagulation system proteins, for example, factor VII, factor IX, factor X, prothrombin, and proteins C, S, and Z. These molecules have harbored posttranslational modifications, such as glycosylation and gamma-carboxylation, and for this reason they need to be produced in mammalian cell lines. Human cells lines have emerged as the most promising alternative to the production of gamma-carboxylated proteins. In this chapter, the methods to generate human cells as a platform to produce gamma-carboxylated proteins, for example the coagulation factors VII and IX, are presented. From the cell line modification up to the vitamin K adaptation of the produced cells is described in the protocols presented in this chapter.

Mechanism of the protective effects of the combined treatment with rhynchophylla total alkaloids and sinapine thiocyanate against a prothrombotic state caused by vascular endothelial cell inflammatory damage

PubMed Central

Li, Yunlun; Zhang, Xinya; Yang, Wenqing; Li, Chao; Chu, Yanjun; Jiang, Haiqiang; Shen, Zhenzhen

2017-01-01

The aim of the present study was to investigate the effect and the underlying mechanism of the combined treatment of rhynchophylla total alkaloids (RTA) and sinapine thiocyanate for protection against a prothrombotic state (PTS) associated with the tumor necrosis factor-alpha (TNF-α)-induced inflammatory injury of vascular endothelial cells (VECs). A TNF-α-induced VEC inflammatory injury model was established, and cell morphology of VECs was evaluated using scanning electron microscopy. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to examine the mRNA and protein expression of coagulation-related factors, including nuclear factor-κB (NF-κB), transforming growth factor-β1 (TGF-β1), tissue factor (TF), plasminogen activator inhibitor (PAI-1), protease-activation receptors (PAR-1) and protein kinase C (PKC-α) in VECs. Combined treatment with RTA and sinapine thiocyanate was demonstrated to reduce, to a varying extent, the mRNA and protein expression of NF-κB, TGF-β1, TF, PAR-1, PKC-α and PAI-1. Furthermore, combined treatment with RTA and sinapine thiocyanate was able to downregulate the expression of coagulation-related factors in injured VECs, thereby inhibiting the PTS induced by vascular endothelial injury. The underlying mechanism is partially associated with the TF-mediated activation of the thrombin-receptor signaling pathway that suppresses coagulation during inflammation and balances fibrinolysis in order to inhibit fibrin generation and deposition. PMID:28587383

Mechanism of the protective effects of the combined treatment with rhynchophylla total alkaloids and sinapine thiocyanate against a prothrombotic state caused by vascular endothelial cell inflammatory damage.

PubMed

Li, Yunlun; Zhang, Xinya; Yang, Wenqing; Li, Chao; Chu, Yanjun; Jiang, Haiqiang; Shen, Zhenzhen

2017-06-01

The aim of the present study was to investigate the effect and the underlying mechanism of the combined treatment of rhynchophylla total alkaloids (RTA) and sinapine thiocyanate for protection against a prothrombotic state (PTS) associated with the tumor necrosis factor-alpha (TNF-α)-induced inflammatory injury of vascular endothelial cells (VECs). A TNF-α-induced VEC inflammatory injury model was established, and cell morphology of VECs was evaluated using scanning electron microscopy. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to examine the mRNA and protein expression of coagulation-related factors, including nuclear factor-κB (NF-κB), transforming growth factor-β1 (TGF-β1), tissue factor (TF), plasminogen activator inhibitor (PAI-1), protease-activation receptors (PAR-1) and protein kinase C (PKC-α) in VECs. Combined treatment with RTA and sinapine thiocyanate was demonstrated to reduce, to a varying extent, the mRNA and protein expression of NF-κB, TGF-β1, TF, PAR-1, PKC-α and PAI-1. Furthermore, combined treatment with RTA and sinapine thiocyanate was able to downregulate the expression of coagulation-related factors in injured VECs, thereby inhibiting the PTS induced by vascular endothelial injury. The underlying mechanism is partially associated with the TF-mediated activation of the thrombin-receptor signaling pathway that suppresses coagulation during inflammation and balances fibrinolysis in order to inhibit fibrin generation and deposition.

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.

Some Important Milestones in the Field of Blood Clotting.

PubMed

Doolittle, Russell F

2016-01-01

Several different kinds of 'milestone' in the field of blood coagulation are described from the middle decades of the 20th century. Although viewed from the standpoint of clotting per se, attention is also given to implications for innate immunity. The first milestone considered is the protracted saga of clotting dependence on vitamin K, an adventure that spanned more than five decades beginning in the 1920s. The second has to do with the discovery of a half-dozen 'new' clotting factors during the period immediately following World War II. A third pursues a narrower focus and examines the once mysterious transformation of fibrinogen into fibrin. Finally, the clinical treatment of classical hemophilia had a remarkable turning point in the 1960s as the result of simple but sensible measures. © 2015 S. Karger AG, Basel.

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.

Extracellular proteases as targets for drug development

PubMed Central

Cudic, Mare

2015-01-01

Proteases constitute one of the primary targets in drug discovery. In the present review, we focus on extracellular proteases (ECPs) because of their differential expression in many pathophysiological processes, including cancer, cardiovascular conditions, and inflammatory, pulmonary, and periodontal diseases. Many new ECP inhibitors are currently under clinical investigation and a significant increase in new therapies based on protease inhibition can be expected in the coming years. In addition to directly blocking the activity of a targeted protease, one can take advantage of differential expression in disease states to selectively deliver therapeutic or imaging agents. Recent studies in targeted drug development for the metalloproteases (matrix metalloproteinases, adamalysins, pappalysins, neprilysin, angiotensin-converting enzyme, metallocarboxypeptidases, and glutamate carboxypeptidase II), serine proteases (elastase, coagulation factors, tissue/urokinase plasminogen activator system, kallikreins, tryptase, dipeptidyl peptidase IV), cysteine proteases (cathepsin B), and renin system are discussed herein. PMID:19689354

Study of coagulation processes of selected humic acids under copper ions influence*

NASA Astrophysics Data System (ADS)

Boguta, Patrycja; Sokolowska, Zofia

2013-04-01

Humic acids have limited sorption capacity and big dose of metal or other mineral component which can be sorbed on humic acids, can cause saturation of negative, surface charge of humic acids leading to destabilization of dissolved humic acids compounds. Destabilisation can be observed as coagulation and floculation proces of humic acids. However there are a lot of mechanisms which causing precipitation of humic acids. Thereby, in order to full description of coagulation process, different methods should be applied. Ordinarily, humic acids coagulation is studied by measurement of absorbance, transmittance or carbon loss in solution. Meanwhile, very significant information is also variation of metal content in soil solution and information whether metal goes to precipitate together with humic acids or stays in dissolved form in solution. So, that, from one side, processes of stronger accumulation of metal can lead to soil degradation and micronutrient deficiency for plants. However, there is also possibility to stay metal in solution in toxic and bioavailable form for plants. Main aim of this paper was to study coagulation process of different humic acids extracted from mucking peats under copper ions influence at adjusted pH to 5. In order to this, four peaty-muck soils were taken from selected places in east part of Poland (meadows and river valleys). These soils differed by humification degree, secondary transformation, density and pH. At next step, humic acids were extracted from soils using sodium hydroxide (NaOH) extractant. After exact purification by washing with HF-HCl mixture and water, humic acids were liofilized. Solutions of humic acids were prepared at concentration 40 mg/dm3 with addition of different amount of copper ions to obtain final concentration of Cu(II) ranged from 0-40mg/dm3. After 24 hours solutions were investigated using measurements of absorbance at 470nm (UV-VIS spectrometer Jasco V-530), measurements of organic carbon in solution (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.

[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

Objective: To determine the levels of coagulation and inflammatory factors in women with moderate and severe ovarian endometriosis so as to investigate the possible role of coagulation and inflammatory factors in the pathogenesis, diagnosis and treatment of this disease. Methods: From June 2015 and June 2017, clinical data of 366 patients with pathologically diagnosed moderate and severe ovarian endometriosis (case group) and 244 patients with pathologically diagnosed benign ovarian cysts (control group) in Women's Hospital of Zhejiang University School of Medicine were retrospectively analyzed. The levels of coagulation indicators, inflammatory factors and serum tumor markers were measured. Then, the values of these indicators in diagnosis of endometriosis were analyzed. Results: (1) The levels of plasma prothrombin time (PT) and thrombin time (TT) in patients with ovarian endometriosis [median: 12.8 s (range: 12.4-13.2 s) and 15.5 s (range: 15.1-15.9 s), respectively] were significantly shorter than those with benign ovarian cysts [median: 13.0 s (range: 12.5-13.4 s) and 15.7 s (range: 15.3-16.1 s), respectively; all P <0.01]. The levels of plasma fibrinogen (FIB) and D-dimer [D-D; median: 3.1 g/L (range: 2.8-3.5 g/L) and 0.9 mg/L (range: 0.6-2.1 mg/L) , respectively] in patients with ovarian endometriosis were significantly higher than those with benign ovarian cysts [median: 2.8 g/L (range: 2.6-3.2 g/L) and 0.6 mg/L (range: 0.4-1.2 mg/L), respectively; P =0.000]. Moreover, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio [PLR; median: 2.3 (range: 1.8-3.1) and 144 (range: 113-179), respectively] in patients with ovarian endometriosis were significantly higher than those with benign ovarian cysts [median: 2.1 (range: 1.6-2.8) and 128 (range: 104-165), respectively; P <0.01]. Furthermore, in patients with ovarian endometriosis, the levels of PT were significantly shorter in stage Ⅳ endometriosis than that in stage Ⅲ endometriosis ( P <0.05). 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.

Sample-to-SNP kit: a reliable, easy and fast tool for the detection of HFE p.H63D and p.C282Y variations associated to hereditary hemochromatosis.

PubMed

Nielsen, Peter B; Petersen, Maja S; Ystaas, Viviana; Andersen, Rolf V; Hansen, Karin M; Blaabjerg, Vibeke; Refstrup, Mette

2012-10-01

Classical hereditary hemochromatosis involves the HFE-gene and diagnostic analysis of the DNA variants HFE p.C282Y (c.845G>A; rs1800562) and HFE p.H63D (c.187C>G; rs1799945). The affected protein alters the iron homeostasis resulting in iron overload in various tissues. The aim of this study was to validate the TaqMan-based Sample-to-SNP protocol for the analysis of the HFE-p.C282Y and p.H63D variants with regard to accuracy, usefulness and reproducibility compared to an existing SNP protocol. The Sample-to-SNP protocol uses an approach where the DNA template is made accessible from a cell lysate followed by TaqMan analysis. Besides the HFE-SNPs other eight SNPs were used as well. These SNPs were: Coagulation factor II-gene F2 c.20210G>A, Coagulation factor V-gene F5 p.R506Q (c.1517G>A; rs121917732), Mitochondria SNP: mt7028 G>A, Mitochondria SNP: mt12308 A>G, Proprotein convertase subtilisin/kexin type 9-gene PCSK9 p.R46L (c.137G>T), Plutathione S-transferase pi 1-gene GSTP1 p.I105V (c313A>G; rs1695), LXR g.-171 A>G, ZNF202 g.-118 G>T. In conclusion the Sample-to-SNP kit proved to be an accurate, reliable, robust, easy to use and rapid TaqMan-based SNP detection protocol, which could be quickly implemented in a routine diagnostic or research facility. Copyright © 2012. Published by Elsevier B.V.

Hemorrhage under veno-venous extracorporeal membrane oxygenation in acute respiratory distress syndrome patients: a retrospective data analysis

PubMed Central

Muders, Thomas; Theuerkauf, Nils; Spitzhüttl, Juliane; Schellhaas, Torsten; Schewe, Jens-Christian; Guenther, Ulf; Wrigge, Hermann; Putensen, Christian

2017-01-01

Background Despite being still invasive and challenging, technical improvement has resulted in broader and more frequent application of extracorporeal membrane oxygenation (ECMO), to prevent hypoxemia and to reduce invasiveness of mechanical ventilation (MV). Heparin-coated ECMO-circuits are currently standard of care, in addition to heparin based anticoagulation (AC) regimen guided by activated clotting time (ACT) or activated partial thromboplastin time (aPTT). Despite these advances, a reliable prediction of hemorrhage is difficult and the risk of hemorrhagic complication remains unfortunately high. We hypothesized, that there are coagulation parameters that are indices for a higher risk of hemorrhage under veno-venous (VV)-ECMO therapy. Methods Data from 36 patients with severe respiratory failure treated with VV-ECMO at a University Hospital intensive care unit (ICU) were analyzed retrospectively. Patients were separated into two groups based on severity of hemorrhagic complications and transfusion requirements. The following data were collected: demographics, hemodynamic data, coagulation samples, transfusion requirements, change of ECMO-circuit during treatment and adverse effects, including hemorrhage and thrombosis. Results In this study 74 hemorrhagic events were observed, one third of which were severe. Patients suffering from severe hemorrhage had a lower survival rate on VV-ECMO (43% vs. 91%; P=0.002) and in ICU (36% vs. 86%; P=0.002). SAPS II, factor VII and X were different between mild and severe hemorrhage group. Conclusions Severe hemorrhage under VV-ECMO is associated with higher mortality. Only factor VII and X differed between groups. Further clinical studies are required to determine the timing of initiation and targets for AC therapies during VV-ECMO. PMID:29312706

Low protein Z plasma level is a risk factor for acute myocardial infarction in coronary atherosclerosis disease patients.

PubMed

Liu, Baoxin; Li, Yong; Luo, Jiachen; Dai, Liming; Zhao, Jinlong; Li, Hongqiang; Jie, Qiqiang; Wang, Dongzhi; Huang, Xin; Wei, Yidong

2016-12-01

To examine plasma protein Z (PZ) levels in acute myocardial infarction (AMI) and chronic coronary atherosclerosis disease (CCAD) patients without history of AMI and explore its potential clinical significance. Plasma PZ concentrations were measured in 90 AMI patients (Group A), 87 CCAD patients without AMI history who remained free of major clinical events at least one year (Group B), and 88 clinically healthy controls (Group C). PZ was found to be significantly lower (P<0.001) in Group A (1508.5±486.2ng/mL) compared with Group B (1823.0±607.8ng/mL) and C (2001.7±733.0ng/mL) and in Group A+B compared with Group C (Group A+B 1663.1±570.0 ng/mL, P<0.001). No statistically significant difference was reached between Group B and C (P=0.081). PZ level was significantly correlated with concentration of creatine kinase MB, high sensitive-cardiac troponin T, high sensitive C reactive protein, D-dimer and coagulation factor II and may be a useful predictor for AMI (OR: 1.38, 95% CI: 1.13-1.77, P=0.03). Subgroup analysis showed PZ concentration below the lowest tertile (<1398ng/mL) had a significantly increased risk for AMI and CCAD (OR: 3.39; 95% CI: 1.12-10.31; P=0.03 and OR: 7.39; 95% CI: 2.62-20.79; P<0.001 respectively). PZ deficiency is found in AMI patients and could potentially reflect the myocardium injury, local coagulation activation and inflammation response during the acute phase of coronary atherosclerosis disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Low protein Z plasma level is a risk factor for acute myocardial infarction in coronary atherosclerosis disease patients

PubMed Central

Liu, Baoxin; Li, Yong; Luo, Jiachen; Dai, Liming; Zhao, Jinlong; Li, Hongqiang; Jie, Qiqiang; Wang, Dongzhi; Huang, Xin; Wei, Yidong

2016-01-01

Objectives To examine plasma protein Z (PZ) levels in acute myocardial infarction (AMI) and chronic coronary atherosclerosis disease (CCAD) patients without history of AMI and explore its potential clinical significance. Methods Plasma PZ concentrations were measured in 90 AMI patients (Group A), 87 CCAD patients without AMI history who remained free of major clinical events at least one year (Group B), and 88 clinically healthy controls (Group C). Results PZ was found to be significantly lower (P<0.001) in A (1508.5 ± 486.2 ng/mL) compared with B (1823.0 ± 607.8 ng/mL) and C (2001.7 ± 733.0 ng/mL) groups and in A+B compared with C Group (A+B 1663.1±570.0, P<0.001). No statistically significant difference was reached between B and C groups (P=0.081). PZ level was significantly correlated with concentration of creatine kinase MB, high sensitive-cardiac troponin T, high sensitive C reactive protein, D-dimer and coagulation factor II and may be a useful predictor for AMI (OR: 1.38, 95% CI: 1.13-1.77, P=0.03). Subgroup analysis showed PZ concentration below the lowest tertile (< 1398 ng/mL) had a significantly increased risk for AMI and CCAD (OR: 3.39; 95% CI: 1.12-10.31; P=0.03 and OR: 7.39; 95% CI: 2.62-20.79; P<0.001 respectively). Conclusions PZ deficiency is found in AMI patients and could potentially reflect the myocardium injury, local coagulation activation and inflammation response during the acute phase of coronary atherosclerosis disease. PMID:27770663

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.

Coagulation Profile in Patients with Different Etiologies for Cushing Syndrome: A Prospective Observational Study.

PubMed

Tirosh, Amit; Lodish, Maya; Lyssikatos, Charalampos; Belyavskaya, Elena; Feelders, Richard A; Stratakis, Constantine A

2017-05-01

Previous studies reported a higher prevalence of venous-thromboembolic events among patients with Cushing disease (CD) compared to those with ACTH-independent Cushing syndrome (CS) from adrenal sources. The objective of the current study was to evaluate the coagulation profile of patients with CS from different etiologies. A prospective observational study was conducted at a clinical research center. The study included adult patients admitted for evaluation of suspected CS (n=85), that were divided into 3 groups: CD (n=22), ACTH-independent CS from an adrenal tumor/hyperplasia (adrenal CS, n=21), and a control group consisting of subjects with negative screening for CS (rule-out CS, n=42). Coagulation profiles were drawn before and 8.5±4.3 months after surgery (trans-sphenoidal or adrenalectomy, n=18), and included fibrinogen, Factor VIII (FVIII), von Willebrand factor antigen (vWF:Ag), plasminogen activator inhibitor-1 (PAI-1), antithrombin III (ATIII), Protein C (PC), Protein S (PS), α2-antiplasmin (α2AP), and aPTT measurements. Patients with CD had higher baseline mean cortisol levels, ATIII activity and vWF:Ag levels compared with adrenal CS. Differences in ATIII activity and vWF:Ag levels remained even after controlling for BMI, and ATIII after also controlling for 24-h urinary free cortisol collections. Our study showed for the first time the differences in coagulation profiles between various etiologies of CS. We assume that the higher cortisol burden among CD patients may explain the differences found in the coagulation profile as well as the higher risk for VTE compared with primary adrenal CS patients. © Georg Thieme Verlag KG Stuttgart · New York.

Early-Stage Estimated Value of Blend Sign on the Prognosis of Patients with Intracerebral Hemorrhage

PubMed Central

Zhou, Ningquan; Wang, Chao

2018-01-01

Background and Purpose This study aimed to explore the relationship between blend sign and prognosis of patients with intracerebral hemorrhage (ICH). Methods Between January 2014 and December 2016, the results of cranial computed tomography imaging within 24 h after the onset of symptoms from 275 patients with ICH were retrospectively analyzed. The patients with or without blend sign were compared to observe and analyze the difference in coagulation function abnormality, rebleeding, mortality, and bad prognosis rates in the early stages. Results Of the 275 patients with ICH, 47 patients had Blend Sign I (17.09%) and 17 patients had Blend Sign II (6.18%). The coagulation function abnormality rate had no statistical difference among Blend Sign I, Blend Sign II, and conventional groups (P > 0.05). In the Blend Sign I group, the rebleeding rate was 4.26%, bad prognosis rate was 25.53%, and mortality rate was 6.38%, which were not statistically significantly different compared with those in the conventional group (P > 0.05). The rebleeding rate in the Blend Sign II group was 47.06%, bad prognosis rate was 82.35%, and mortality rate was 47.06%, which were statistically significantly different compared with those in the conventional and Blend Sign I groups (P < 0.05). Conclusions For the patients associated with Blend Sign I, the prognosis was equivalent to that in the conventional group, with no statistically significant difference. The rebleeding, bad prognosis, and mortality rates were higher in the Blend Sign II group than in the conventional group and deserved more attention.

Study on the blood compatibility and biodegradation properties of magnesium alloys.

PubMed

Mochizuki, Akira; Kaneda, Hideki

2015-02-01

Lately, several magnesium alloys have been investigated as a new class of biomaterials owing to their excellent biodegradability in living tissues. In this study, we considered AZ series of Mg alloy containing aluminum (3% to 9%) and zinc (1%) as a model magnesium alloy, and investigated their biodegradation in whole blood and blood compatibility in vitro. The results of the elution property of metal ions determined using chromogenic assay and the associated pH change show that the degradation resistance of the AZ series alloys in blood is improved by alloying aluminum. Furthermore, the blood compatibility of the alloys was investigated in terms of their hemolysis, factor Xa-like activity, using spectrophotometry and chromogenic assay, respectively, and coagulation time measurements (prothrombin time and activated partial thromboplastin time). The results indicated that the blood compatibility of the AZ series alloys is excellent, irrespective of the alloy composition. The excellent blood compatibility with the coagulation system could be attributed to the eluted Mg(2+) ion, which suppresses the activation of certain coagulation factors in the intrinsic and/or extrinsic coagulation pathways. In terms of the degradation resistance of the AZ series alloys in blood, the results of pH change in blood and the amount of the eluted metal ions indicate that the performance is markedly improved with an increase in aluminum content. Copyright © 2014 Elsevier B.V. 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.

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.

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

[Arsenic removal by coagulation process and the field expanding experiments for Yangzonghai Lake].

PubMed

Chen, Jing; Zhang, Shu; Yang, Xiang-jun; Huang, Zhang-jie; Wang, Shi-xiong; Wang, Chong; Wei, Qun-yan; Zhang, Gen-lin; Xiao, Jun

2015-01-01

Yangzonghai Lake is the third largest plateau lake in Yunnan province. In June 2008, arsenic contamination was detected in Yangzonghai Lake and the water quality worsens dramatically from standard grade II to worse than grade V. Since Yongzonghai Lake is so large with the area of 31 km2 and the storage capacity of 6.04 x 10(8) m3, those pretreatment operations of the traditional arsenic removal methods, such as pre oxidation, adjusting pH value, are not applicable. In this study, a facile remediation strategy for arsenic removal by coagulation process, in which ferric chloride was directly sprayed into the contaminated water without any pretreatment, was reported. The results showed that the arsenic removal percentage was up to 95.1%-96.7% for 50 L raw water with reagent dosage of 1.62-3.20 mg x L(-1). Furthermore, the pH value of the lake kept constant in the coagulation process, which was beneficial for fish survival. Re-dissolved arsenic from precipitation was not detected in 954 days. The strategy of ferric chloride coagulation were applied to field experiments for lake water with volumes of 1 x 10(4) m3 and 25 x 10(4) m3, in which arsenic was also removed effectively. The reported strategy was of great advantage for simple operation, low cost and ecological safety, therefore it provides a representative example for arsenic contamination treatment of large lake.

Determinants of impaired renal and vascular function are associated with elevated levels of procoagulant factors in the general population.

PubMed

Dekkers, I A; de Mutsert, R; de Vries, A P J; Rosendaal, F R; Cannegieter, S C; Jukema, J W; le Cessie, S; Rabelink, T J; Lamb, H J; Lijfering, W M

2018-03-01

Essentials Why venous thrombosis is more prevalent in chronic kidney disease is unclear. We investigated whether renal and vascular function are associated with hypercoagulability. Coagulation factors showed a procoagulant shift with impaired renal and vascular function. This suggests that renal and vascular function play a role in the etiology of thrombosis. Background Impaired renal and vascular function have been associated with venous thrombosis, but the mechanism is unclear. Objectives We investigated whether estimated glomerular filtration rate (eGFR), urinary albumin-creatinine ratio (UACR), and pulse wave velocity (PWV) are associated with a procoagulant state. Methods In this cross-sectional analysis of the NEO Study, eGFR, UACR, fibrinogen, and coagulation factors (F)VIII, FIX and FXI were determined in all participants (n = 6536), and PWV was assessed in a random subset (n = 2433). eGFR, UACR and PWV were analyzed continuously and per percentile: per six categories for eGFR (> 50 th [reference] to < 1st) and UACR (< 50 th [reference] to > 99th), and per four categories (< 50 th [reference] to > 95th percentile) for PWV. Linear regression was used and adjusted for age, sex, total body fat, smoking, education, ethnicity, total cholesterol, C-reactive protein (CRP) and vitamin K antagonists use (FIX). Results Mean age was 55.6 years, mean eGFR 86.0 (12SD) mL 1.73 m - ² and median UACR 0.4 mg mmol -1 (25th, 75th percentile; 0.3, 0.7). All coagulation factors showed a procoagulant shift with lower renal function and albuminuria. For example, FVIII was 22 IU dL -1 (95% CI, 13-32) higher in the eGFR < 1st percentile compared with the > 50th percentile, and FVIII was 12 IU dL -1 (95% CI, 3-22) higher in the UACR > 99th percentile compared with the < 50th percentile. PWV was positively associated with coagulation factors FIX and FXI in continuous analysis; per m/s difference in PWV, FIX was 2.0 IU dL -1 (95% CI, 0.70-3.2) higher. Conclusions Impaired renal and vascular function was associated with higher levels of coagulation factors, underlining the role of renal function and vascular function in the development of venous thrombosis. © 2017 International Society on Thrombosis and Haemostasis.

[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.

[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.

Determination of dabigatran, rivaroxaban and apixaban by ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) and coagulation assays for therapy monitoring of novel direct oral anticoagulants.

PubMed

Schmitz, E M H; Boonen, K; van den Heuvel, D J A; van Dongen, J L J; Schellings, M W M; Emmen, J M A; van der Graaf, F; Brunsveld, L; van de Kerkhof, D

2014-10-01

Three novel direct oral anticoagulants (DOACs) have recently been registered by the Food and Drug Administration and European Medicines Agency Commission: dabigatran, rivaroxaban, and apixaban. To quantify DOACs in plasma, various dedicated coagulation assays have been developed. To develop and validate a reference ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) method and to evaluate the analytical performance of several coagulation assays for quantification of dabigatran, rivaroxaban, and apixaban. The developed UPLC-MS/MS method was validated by determination of precision, accuracy, specificity, matrix effects, lower limits of detection, carry-over, recovery, stability, and robustness. The following coagulation assays were evaluated for accuracy and precision: laboratory-developed (LD) diluted thrombin time (dTT), Hemoclot dTT, Pefakit PiCT, ECA, Liquid anti-Xa, Biophen Heparin (LRT), and Biophen DiXal anti-Xa. Agreement between the various coagulation assays and UPLC-MS/MS was determined with random samples from patients using dabigatran or rivaroxaban. The UPLC-MS/MS method was shown to be accurate, precise, sensitive, stable, and robust. The dabigatran coagulation assay showing the best precision, accuracy and agreement with the UPLC-MS/MS method was the LD dTT test. For rivaroxaban, the anti-factor Xa assays were superior to the PiCT-Xa assay with regard to precision, accuracy, and agreement with the reference method. For apixaban, the Liquid anti-Xa assay was superior to the PiCT-Xa assay. Statistically significant differences were observed between the various coagulation assays as compared with the UPLC-MS/MS reference method. It is currently unknown whether these differences are clinically relevant. When DOACs are quantified with coagulation assays, comparison with a reference method as part of proficiency testing is therefore pivotal. © 2014 International Society on Thrombosis and Haemostasis.

A data-driven approach for the study of coagulation phenomena in waste lubricant oils and its relevance in alkaline regeneration treatments.

PubMed

Pinheiro, C T; Ascensão, V R; Reis, M S; Quina, M J; Gando-Ferreira, L M

2017-12-01

Coagulation phenomena can occur in certain types of waste lubricant oils (WLO) during regeneration processes involving alkaline treatments, causing plant shutdowns. In this context, this study addresses the nature of the compounds responsible for the coagulation phenomena after the alkaline treatment. For such, an empirical test was developed to assess the coagulation behaviour of WLO, consisting in the addition of KOH to the WLO followed by heating under stirring conditions. This test was performed on 133 samples and four coagulation classes were identified: A; B1; B2 and C. Moreover, a physicochemical characterization of WLO was carried out regarding viscosity at 40°C, saponification number (SN), total acid number (TAN), surface tension, water content, elemental analysis and functional groups (FTIR). 56 samples of fresh lubricant oils for different applications were also characterized and their properties assessed and compared. Multivariate methods were applied to WLO to discriminate among coagulation classes based on FTIR spectra. It was found that coagulation classes A and B1 exhibit statistically similar patterns for all properties determined. Spectral discriminating analysis did not reveal discriminant peaks for class B1 samples, and the presence of specific additives was pointed as the possible factor underlying the increase in viscosity in this oils. Class B2 presents the absence of additives and oxidation products as differentiating features. In addition, B2 samples showed lower TAN SN, and lower concentration of some elements. Lubricants from gear or hydraulic applications can give rise to this class of WLO. Oils of Class C are mainly composed by synthetic ester type base oils, which hamper regeneration processes using alkaline pretreatments. In future studies, WLO type A and B1 can be classified as a single class. The coagulation phenomena classification becomes A - negative, B - precipitate formation and C - positive. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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

Hemophilia

MedlinePlus

... disorders: coagulation factor deficiencies. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. ... Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

Haemostaseome-associated SNPs: has the thrombotic phenotype a greater influence than ethnicity? GMT study from Aquitaine including Basque individuals.

PubMed

Freyburger, Geneviève; Labrouche, Sylvie; Hubert, Christophe; Bauduer, Frédéric

2015-01-01

The Genetic Markers for Thrombosis (GMT) study compared the relative influence of ethnicity and thrombotic phenotype regarding the distribution of SNPs implicated in haemostasis pathophysiology ("haemostaseome"). We assessed 384 SNPs in three groups, each of 480 subjects: 1) general population of Aquitaine region (Southwestern France) used as control; 2) patients with venous thromboembolism from the same area; and 3) autochthonous Basques, a genetic isolate, who demonstrate unusual characteristics regarding the coagulation system. This study sought to evaluate i) the value of looking for a large number of genes in order to identify new genetic markers of thrombosis, ii) the value of investigating low risk factors and potential preferential associations, iii) the impact of ethnicity on the characterisation of markers for thrombosis. We did not detect any previously unrecognised SNP significantly associated with thrombosis risk or any preferential associations of low-risk factors in patients with thrombosis. The sum of ϰ² values for our 110 significant SNPs demonstrated a smaller genetic distance between patients and controls (321 cumulated ϰ² value) than between Basques and controls (1,570 cumulated ϰ² value). Hence, our study confirms the genetic particularity of Basques especially regarding a significantly lower expression of the non-O blood group (p< 0.0004). This is mitigated by a higher prevalence of factor II Leiden (p< 0.02) while factor V Leiden prevalence does not differ. Numerous other differences covering a wide range of proteins of the haemostaseome may result in an overall different genetic risk for venous thromboembolism.

Phosphorothioate oligonucleotides inhibit the intrinsic tenase complex.

PubMed

Sheehan, J P; Lan, H C

1998-09-01

Systemic administration of ISIS 2302, a 20-mer antisense phosphorothioate oligonucleotide targeting human intercellular adhesion molecule-1 mRNA, causes prolongation of plasma clotting times in both monkey and human studies. The anticoagulant effects of ISIS 2302 were investigated with both in vitro coagulation assays in human plasma and purified enzyme systems. At high oligonucleotide plasma concentrations (>100 microgram/mL), prolongation of the prothrombin and thrombin times was observed. In a thrombin time assay using purified components, high concentrations of ISIS 2302 inhibited thrombin clotting activity both by stimulating inhibition by heparin cofactor II and directly competing with fibrinogen for binding to anion binding exosite I. In contrast, low concentrations of ISIS 2302 (<100 microgram/mL) showed a selective, linear prolongation of the activated partial thromboplastin time (PTT). The rate limiting effect of 50 microgram/mL ISIS 2302, which prolonged the PTT to 1.5 times control, was identified by sequential modification of the clotting assay. Delaying addition of oligonucleotide until after contact activation failed to correct prolongation of the PTT. The calcium-dependent steps of the intrinsic pathway were individually assessed by adding sufficient activated coagulation factor to correct the PTT in plasma deficient in that specific factor. Addition of factor XIa, IXa, VIIIa, or Va failed to correct the PTT in the presence of ISIS 2302. In contrast, 0.2 nmol/L factor Xa corrected prolongation of the PTT in factor X-deficient plasma with or without oligonucleotide present. ISIS 2302 (50 microgram/mL) did not prolong a modified Russel viper venom time, suggesting no significant inhibition of prothrombinase. Thus, 50 microgram/mL ISIS 2302 prolonged the PTT by selectively inhibiting intrinsic tenase activity. ISIS 2302 showed partial inhibition of intrinsic tenase activity (to approximately 35% of control) at clinically relevant oligonucleotide concentrations in a chromogenic assay. This activity was oligonucleotide sequence-independent but required the phosphorothioate backbone, suggesting that inhibition of intrinsic tenase is a general property of this class of oligonucleotides. These results are relevant to both the therapeutic use of phosphorothioate oligonucleotides and the potential design of inhibitors of the intrinsic tenase complex, a novel target for anticoagulation. Copyright 1998 by The American Society of Hematology.

Low-level lasers: their role in the mechanisms of the stimulation of the reparative processes

NASA Astrophysics Data System (ADS)

Yeliseenko, Vladimir I.

1994-08-01

The transformation of light energy into thermal energy with extremely high temperatures, the evaporation of interstitial and intracellular fluids, and the cytoplasmic proteins coagulation are the most important factors in the mechanism of high-power lasers effect on biological tissues. A set of dystrophic disorders develops in tissues as a result, up to the coagulative necrosis, which lays in the basis of the laser thermal crust at incised edges. With CO2 laser the damage is evident from the first cell layers. Its size is in the linear correlation with exposure time. The Nd:YAG and argon lasers' light penetrates the superficial cell layers without damage practically and realizes in deeper well vascularized tissue layers, the submucous layer of the gastrointestinal hollow organs, in particular. It depends on the closeness of the irradiation spectrum of absorption of hemoglobin and result in blood coagulation in the vascular lumine with formation of the `coagulative laser thrombi.' That explains a wide use of laser irradiation in urgent endoscopy for arresting acute gastrointestinal hemorrhages. For these reasons Nd:YAG laser `contact scalpel' technique with sapphire tips is used for incisions on parenchymatous organs with simultaneous blood coagulation in vessels lumina with good hemostasis and holestasis (hepatobiliar surgery), and for pancreas and thyroid surgery, in gynecology and other surgical areas.

A method for the inline measurement of milk gel firmness using an optical sensor.

PubMed

Arango, O; Castillo, M

2018-05-01

At present, selection of cutting time during cheesemaking is made based on subjective methods, which has effects on product homogeneity and has prevented complete automation of cheesemaking. In this work, a new method for inline monitoring of curd firmness is presented. The method consisted of developing a model that correlates the backscatter ratio of near infrared light during milk coagulation with the rheological storage modulus. The model was developed through a factorial design with 2 factors: protein concentration (3.4 and 5.1%) and coagulation temperature (30 and 40°C). Each treatment was replicated 3 times; the model was calibrated with the first replicate and validated using the remaining 2 replicates. The coagulation process was simultaneously monitored using an optical sensor and small-amplitude oscillatory rheology. The model was calibrated and successfully validated at the different protein concentrations and coagulation temperatures studied, predicting the evolution of storage modulus during milk coagulation with coefficient of determination values >0.998 and standard error of prediction values <3.4 Pa. The results demonstrated that the proposed method allows inline monitoring of curd firming in cheesemaking and cutting the curd at a proper firmness to each type of cheese. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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).

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.

Congenital afibrinogenemia

MedlinePlus

... disorders: coagulation factor deficiencies. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. ... Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

Bleeding disorders

MedlinePlus

... disorders: coagulation factor deficiencies. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. ... Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

Pelvic adhesion and gonadotropin-releasing hormone analogue: effects of triptorelin acetate depot on coagulation and fibrinolytic activities.

PubMed

Di Nardo, Maria Antonietta; Annunziata, Maria Laura; Ammirabile, Massimiliano; Di Minno, Matteo Nicola Dario; Ruocco, Anna Lilia; De Falco, Marianna; Di Lieto, Andrea

2012-06-01

The study investigated the impact of gonadotropin-releasing hormone analogue (GnRH-a) on coagulation and fibrinolytic activities and its effectiveness in the prevention of pelvic adhesion after myomectomy. Thirty-two infertile women underwent myomectomy followed by adhesion evaluation surgery with a second-look laparoscopy. Before myomectomy, 15 women were treated with triptorelin acetate for 3 months and 17 received no treatment. Plasminogen activator inhibitor (PAI), thrombin activatable fibrinolysis inhibitor (TAFI), protein C (PC), plasminogen, α2-antiplasmin were determined by enzyme-linked immunosorbent assays and the activity of coagulation factors V and VIII by coagulometric methods. Patients treated with GnRH-a showed significant decrease in PAI, TAFI, factors V, and VIII (P < .05) and increased PC (P < .05), but no significant change in plasminogen and α2-antiplasmin levels compared with control group. The incidence, extent, and severity of adhesions were significantly lower in GnRH-a-treated patients compared with control group (P < .05), suggesting a possible critical role of the GnRH-a therapy in preventing postoperative adhesion development.

Role of hepsin in factor VII activation in zebrafish.

PubMed

Khandekar, Gauri; Jagadeeswaran, Pudur

2014-01-01

Factor VII, the initiator of the extrinsic coagulation cascade, circulates in human plasma mainly in its zymogen form, factor VII and in small amounts in its activated form, factor VIIa. However, the mechanism of initial generation of factor VIIa is not known despite intensive research using currently available model systems. Earlier findings suggested serine proteases factor VII activating protease and hepsin play a role in activating factor VII, however, it has remained controversial. In this paper we estimated the levels of factor VIIa and factor VII for the first time in zebrafish adult population and also reevaluated the role of the above two serine proteases in activating factor VII in vivo using zebrafish as a model system. Knockdown of factor VII activating protease and hepsin was performed followed by assaying for their effect on factor VIIa concentration and extrinsic coagulation as measured by the kinetic prothrombin time. Factor VII activating protease knockdown showed no change in kinetic prothrombin time and no effect on factor VIIa levels while hepsin knockdown increased the kinetic prothrombin time and significantly reduced the factor VIIa plasma levels. Our results thus indicate that hepsin plays a physiologically important role in factor VII activation and hemostasis in zebrafish. © 2013.

Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock

PubMed Central

2010-01-01

Background Lactate clearance, a surrogate for the magnitude and duration of global tissue hypoxia, is used diagnostically, therapeutically and prognostically. This study examined the association of early lactate clearance with selected inflammatory, coagulation, apoptosis response biomarkers and organ dysfunction scores in severe sepsis and septic shock. Methods Measurements of serum arterial lactate, biomarkers (interleukin-1 receptor antagonist, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha, intercellular adhesion molecule-1, high mobility group box-1, D-Dimer and caspase-3), and organ dysfunction scores (Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score II, Multiple Organ Dysfunction Score, and Sequential Organ Failure Assessment) were obtained in conjunction with a prospective, randomized study examining early goal-directed therapy in severe sepsis and septic shock patients presenting to the emergency department (ED). Lactate clearance was defined as the percent change in lactate levels after six hours from a baseline measurement in the ED. Results Two-hundred and twenty patients, age 65.0 +/- 17.1 years, were examined, with an overall lactate clearance of 35.5 +/- 43.1% and in-hospital mortality rate of 35.0%. Patients were divided into four quartiles of lactate clearance, -24.3 +/- 42.3, 30.1 +/- 7.5, 53.4 +/- 6.6, and 75.1 +/- 7.1%, respectively (p < 0.01). The mean levels of all biomarkers and organ dysfunction scores over 72 hours were significantly lower with higher lactate clearance quartiles (p < 0.01). There was a significant decreased in-hospital, 28-day, and 60-day mortality in the higher lactate clearance quartiles (p < 0.01). Conclusions Early lactate clearance as a surrogate for the resolution of global tissue hypoxia is significantly associated with decreased levels of biomarkers, improvement in organ dysfunction and outcome in severe sepsis and septic shock. PMID:20181046

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.

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

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.

Tissue factor deficiency increases alveolar hemorrhage and death in influenza A virus-infected mice.

PubMed

Antoniak, S; Tatsumi, K; Hisada, Y; Milner, J J; Neidich, S D; Shaver, C M; Pawlinski, R; Beck, M A; Bastarache, J A; Mackman, N

2016-06-01

Essentials H1N1 Influenza A virus (IAV) infection is a hemostatic challenge for the lung. Tissue factor (TF) on lung epithelial cells maintains lung hemostasis after IAV infection. Reduced TF-dependent activation of coagulation leads to alveolar hemorrhage. Anticoagulation might increase the risk for hemorrhages into the lung during severe IAV infection. Background Influenza A virus (IAV) infection is a common respiratory tract infection that causes considerable morbidity and mortality worldwide. Objective To investigate the effect of genetic deficiency of tissue factor (TF) in a mouse model of IAV infection. Methods Wild-type mice, low-TF (LTF) mice and mice with the TF gene deleted in different cell types were infected with a mouse-adapted A/Puerto Rico/8/34 H1N1 strain of IAV. TF expression was measured in the lungs, and bronchoalveolar lavage fluid (BALF) was collected to measure extracellular vesicle TF, activation of coagulation, alveolar hemorrhage, and inflammation. Results IAV infection of wild-type mice increased lung TF expression, activation of coagulation and inflammation in BALF, but also led to alveolar hemorrhage. LTF mice and mice with selective deficiency of TF in lung epithelial cells had low basal levels of TF and failed to increase TF expression after infection; these two strains of mice had more alveolar hemorrhage and death than controls. In contrast, deletion of TF in either myeloid cells or endothelial cells and hematopoietic cells did not increase alveolar hemorrhage or death after IAV infection. These results indicate that TF expression in the lung, particularly in epithelial cells, is required to maintain alveolar hemostasis after IAV infection. Conclusion Our study indicates that TF-dependent activation of coagulation is required to limit alveolar hemorrhage and death after IAV infection. © 2016 International Society on Thrombosis and Haemostasis.

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.

Anticoagulant Effect of Sugammadex: Just an In Vitro Artifact.

PubMed

Dirkmann, Daniel; Britten, Martin W; Pauling, Henning; Weidle, Juliane; Volbracht, Lothar; Görlinger, Klaus; Peters, Jürgen

2016-06-01

Sugammadex prolongs activated partial thromboplastin time (aPTT) and prothrombin time (PT) suggestive of anticoagulant effects. To pinpoint its presumed anticoagulant site of action, the authors assessed Sugammadex's impact on a panel of coagulation assays. Sugammadex, Rocuronium, Sugammadex and Rocuronium combined, or saline were added to blood samples from healthy volunteers and analyzed using plasmatic (i.e., aPTT, thrombin time, and fibrinogen concentration) (n = 8 each), PT (quick), activities of plasmatic coagulation factors, and whole blood (extrinsically and intrinsically activated thromboelastometry) assays (n = 18 each). Furthermore, dose-dependent effects of Sugammadex were also assessed (n = 18 each) in diluted Russel viper venom time (DRVVT) assays with low (DRVVT1) and high (DRVVT2) phospholipid concentrations and in a highly phospholipid-sensitive aPTT assay. Sugammadex increased PT (+9.1%; P < 0.0001), aPTT (+13.1%; P = 0.0002), and clotting time in extrinsically (+33.1%; P = 0.0021) and intrinsically (+22.4%; P < 0.0001) activated thromboelastometric assays. Furthermore, activities of factors VIII, IX, XI, and XII decreased (-7%, P = 0.009; -7.8%, P < 0.0001; -6.9%, P < 0.0001; and -4.3%, P = 0.011, respectively). Sugammadex dose-dependently prolonged both DRVVT1 and the highly phospholipid-sensitive aPTT assays, but additional phospholipids in the DRVVT2 assay almost abolished these prolongations. Thrombin time, a thromboelastometric thrombin generation assay, clot firmness, clot lysis, fibrinogen concentration, and activities of other coagulation factors were unaltered. Rocuronium, Sugammadex and Rocuronium combined, and saline exerted no effects. Sugammadex significantly affects various coagulation assays, but this is explainable by an apparent phospholipid-binding effect, suggesting that Sugammadex`s anticoagulant effects are likely an in vitro artifact.

A comparative study of tissue factor and kaolin on blood coagulation assays using rotational thromboelastometry and thromboelastography.

PubMed

Peng, Henry T; Grodecki, Richard; Rizoli, Sandro; Shek, Pang N

2016-01-01

Rotational thromboelastometry (ROTEM) and thromboelastography (TEG) have been increasingly used to diagnose acute coagulopathy and guide blood transfusion. The tests are routinely performed using different triggering activators such as tissue factor and kaolin, which activate different pathways yielding different results. To optimize the global blood coagulation assays using ROTEM and TEG, we conducted a comparative study on the activation methods employing tissue factor and kaolin at different concentrations as well as standard reagents as recommended by the manufacturer of each device. Key parameter values were obtained at various assay conditions to evaluate and compare coagulation and fibrinolysis profiles of citrated whole blood collected from healthy volunteers. It was found that tissue factor reduced ROTEM clotting time and TEG R, and increased ROTEM clot formation time and TEG K in a concentration-dependent manner. In addition, tissue factor affected ROTEM alpha angle, and maximum clot firmness, especially in the absence of kaolin activation, whereas both ROTEM and TEG clot lysis (LI30, CL30, and LY30) remained unaffected. Moreover, kaolin reduced ROTEM clotting time and TEG R and K, but to a lesser extent than tissue factor, in-tem and ex-tem. Correlations in all corresponding parameters between ROTEM and TEG were observed, when the same activators were used in the assays compared with lesser correlations between standard kaolin TEG and ROTEM (INTEM/EXTEM). The two types of viscoelastic point-of-care devices provide different results, depending on the triggering reagent used to perform the assay. Optimal assay condition was obtained to reduce assay time and improve assay accuracy.

Separation of whole blood into plasma and red cells by using a hollow-fibre filtration system.

PubMed

Hornsey, V S; McColl, K; Drummond, O; Prowse, C V

2005-08-01

The aim of this study was to assess the separation of whole blood into red cells and plasma by using the Sangofer device, which is a gravity-fed, hollow-fibre system. The components would then be compared with those produced by the use of more elaborate technical equipment. Ten whole-blood units were leucoreduced by using a WBF2 filter and immediately separated into red cells and plasma by using the Sangofer blood-separation device. Red cells were stored in additive solution and tested on days 1 and 42. The plasma was assayed for levels of various coagulation factors and for markers of both coagulation and complement activation. The red-cell parameters were similar to those obtained when routine centrifugation methods were used. The filter did not cause haemolysis. Levels of plasma factor VIII and factor XI were lower than those seen in routinely produced leucoreduced plasma units but there was no evidence of activation of the coagulation and complement systems. The Sangofer device is simple and straightforward to use and eliminates the need for both centrifugation and automated separation steps during the processing of whole blood into red cells and plasma components. Minor changes are required to make the procedure easier to incorporate into routine use.

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.

Electrocoagulation efficiency of the tannery effluent treatment using aluminium electrodes.

PubMed

Espinoza-Quiñones, Fernando R; Fornari, Marilda M T; Módenes, Aparecido N; Palácio, Soraya M; Trigueros, Daniela E G; Borba, Fernando H; Kroumov, Alexander D

2009-01-01

An electro-coagulation laboratory scale system using aluminium plates electrodes was studied for the removal of organic and inorganic pollutants as a by-product from leather finishing industrial process. A fractional factorial 2(3) experimental design was applied in order to obtain optimal values of the system state variables. The electro-coagulation (EC) process efficiency was based on the chemical oxygen demand (COD), turbidity, total suspended solid, total fixed solid, total volatile solid, and chemical element concentration values. Analysis of variance (ANOVA) for final pH, total fixed solid (TFS), turbidity and Ca concentration have confirmed the predicted models by the experimental design within a 95% confidence level. The reactor working conditions close to real effluent pH (7.6) and electrolysis time in the range 30-45 min were enough to achieve the cost effective reduction factors of organic and inorganic pollutants' concentrations. An appreciable improvement in COD removal efficiency was obtained for electro-coagulation treatment. Finally, the technical-economical analysis results have clearly shown that the electro-coagulation method is very promising for industrial application.

Plume-exit modeling to determine cloud condensation nuclei activity of aerosols from residential biofuel combustion

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

Mena, Francisco; Bond, Tami C.; Riemer, Nicole

Residential biofuel combustion is an important source of aerosols and gases in the atmosphere. The change in cloud characteristics due to biofuel burning aerosols is uncertain, in part, due to the uncertainty in the added number of cloud condensation nuclei (CCN) from biofuel burning. We provide estimates of the CCN activity of biofuel burning aerosols by explicitly modeling plume dynamics (coagulation, condensation, chemical reactions, and dilution) in a young biofuel burning plume from emission until plume exit, defined here as the condition when the plume reaches ambient temperature and specific humidity through entrainment. We found that aerosol-scale dynamics affect CCNmore » activity only during the first few seconds of evolution, after which the CCN efficiency reaches a constant value. Homogenizing factors in a plume are co-emission of semi-volatile organic compounds (SVOCs) or emission at small particle sizes; SVOC co-emission can be the main factor determining plume-exit CCN for hydrophobic or small particles. Coagulation limits emission of CCN to about 10 16 per kilogram of fuel. Depending on emission factor, particle size, and composition, some of these particles may not activate at low supersaturation ( s sat). Hygroscopic Aitken-mode particles can contribute to CCN through self-coagulation but have a small effect on the CCN activity of accumulation-mode particles, regardless of composition differences. Simple models (monodisperse coagulation and average hygroscopicity) can be used to estimate plume-exit CCN within about 20 % if particles are unimodal and have homogeneous composition, or when particles are emitted in the Aitken mode even if they are not homogeneous. On the other hand, if externally mixed particles are emitted in the accumulation mode without SVOCs, an average hygroscopicity overestimates emitted CCN by up to a factor of 2. This work has identified conditions under which particle populations become more homogeneous during plume processes. This homogenizing effect requires the components to be truly co-emitted, rather than sequentially emitted.« less

Plume-exit modeling to determine cloud condensation nuclei activity of aerosols from residential biofuel combustion

NASA Astrophysics Data System (ADS)

Mena, Francisco; Bond, Tami C.; Riemer, Nicole

2017-08-01

Residential biofuel combustion is an important source of aerosols and gases in the atmosphere. The change in cloud characteristics due to biofuel burning aerosols is uncertain, in part, due to the uncertainty in the added number of cloud condensation nuclei (CCN) from biofuel burning. We provide estimates of the CCN activity of biofuel burning aerosols by explicitly modeling plume dynamics (coagulation, condensation, chemical reactions, and dilution) in a young biofuel burning plume from emission until plume exit, defined here as the condition when the plume reaches ambient temperature and specific humidity through entrainment. We found that aerosol-scale dynamics affect CCN activity only during the first few seconds of evolution, after which the CCN efficiency reaches a constant value. Homogenizing factors in a plume are co-emission of semi-volatile organic compounds (SVOCs) or emission at small particle sizes; SVOC co-emission can be the main factor determining plume-exit CCN for hydrophobic or small particles. Coagulation limits emission of CCN to about 1016 per kilogram of fuel. Depending on emission factor, particle size, and composition, some of these particles may not activate at low supersaturation (ssat). Hygroscopic Aitken-mode particles can contribute to CCN through self-coagulation but have a small effect on the CCN activity of accumulation-mode particles, regardless of composition differences. Simple models (monodisperse coagulation and average hygroscopicity) can be used to estimate plume-exit CCN within about 20 % if particles are unimodal and have homogeneous composition, or when particles are emitted in the Aitken mode even if they are not homogeneous. On the other hand, if externally mixed particles are emitted in the accumulation mode without SVOCs, an average hygroscopicity overestimates emitted CCN by up to a factor of 2. This work has identified conditions under which particle populations become more homogeneous during plume processes. This homogenizing effect requires the components to be truly co-emitted, rather than sequentially emitted.

Plume-exit modeling to determine cloud condensation nuclei activity of aerosols from residential biofuel combustion

DOE PAGES

Mena, Francisco; Bond, Tami C.; Riemer, Nicole

2017-08-07

Residential biofuel combustion is an important source of aerosols and gases in the atmosphere. The change in cloud characteristics due to biofuel burning aerosols is uncertain, in part, due to the uncertainty in the added number of cloud condensation nuclei (CCN) from biofuel burning. We provide estimates of the CCN activity of biofuel burning aerosols by explicitly modeling plume dynamics (coagulation, condensation, chemical reactions, and dilution) in a young biofuel burning plume from emission until plume exit, defined here as the condition when the plume reaches ambient temperature and specific humidity through entrainment. We found that aerosol-scale dynamics affect CCNmore » activity only during the first few seconds of evolution, after which the CCN efficiency reaches a constant value. Homogenizing factors in a plume are co-emission of semi-volatile organic compounds (SVOCs) or emission at small particle sizes; SVOC co-emission can be the main factor determining plume-exit CCN for hydrophobic or small particles. Coagulation limits emission of CCN to about 10 16 per kilogram of fuel. Depending on emission factor, particle size, and composition, some of these particles may not activate at low supersaturation ( s sat). Hygroscopic Aitken-mode particles can contribute to CCN through self-coagulation but have a small effect on the CCN activity of accumulation-mode particles, regardless of composition differences. Simple models (monodisperse coagulation and average hygroscopicity) can be used to estimate plume-exit CCN within about 20 % if particles are unimodal and have homogeneous composition, or when particles are emitted in the Aitken mode even if they are not homogeneous. On the other hand, if externally mixed particles are emitted in the accumulation mode without SVOCs, an average hygroscopicity overestimates emitted CCN by up to a factor of 2. This work has identified conditions under which particle populations become more homogeneous during plume processes. This homogenizing effect requires the components to be truly co-emitted, rather than sequentially emitted.« less

Anticoagulants and the propagation phase of thrombin generation.

PubMed

Orfeo, Thomas; Gissel, Matthew; Butenas, Saulius; Undas, Anetta; Brummel-Ziedins, Kathleen E; Mann, Kenneth G

2011-01-01

The view that clot time-based assays do not provide a sufficient assessment of an individual's hemostatic competence, especially in the context of anticoagulant therapy, has provoked a search for new metrics, with significant focus directed at techniques that define the propagation phase of thrombin generation. Here we use our deterministic mathematical model of tissue-factor initiated thrombin generation in combination with reconstructions using purified protein components to characterize how the interplay between anticoagulant mechanisms and variable composition of the coagulation proteome result in differential regulation of the propagation phase of thrombin generation. Thrombin parameters were extracted from computationally derived thrombin generation profiles generated using coagulation proteome factor data from warfarin-treated individuals (N = 54) and matching groups of control individuals (N = 37). A computational clot time prolongation value (cINR) was devised that correlated with their actual International Normalized Ratio (INR) values, with differences between individual INR and cINR values shown to derive from the insensitivity of the INR to tissue factor pathway inhibitor (TFPI). The analysis suggests that normal range variation in TFPI levels could be an important contributor to the failure of the INR to adequately reflect the anticoagulated state in some individuals. Warfarin-induced changes in thrombin propagation phase parameters were then compared to those induced by unfractionated heparin, fondaparinux, rivaroxaban, and a reversible thrombin inhibitor. Anticoagulants were assessed at concentrations yielding equivalent cINR values, with each anticoagulant evaluated using 32 unique coagulation proteome compositions. The analyses showed that no anticoagulant recapitulated all features of warfarin propagation phase dynamics; differences in propagation phase effects suggest that anticoagulants that selectively target fXa or thrombin may provoke fewer bleeding episodes. More generally, the study shows that computational modeling of the response of core elements of the coagulation proteome to a physiologically relevant tissue factor stimulus may improve the monitoring of a broad range of anticoagulants.

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.

Combinatorial Enzyme Design Probes Allostery and Cooperativity in the Trypsin Fold

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

Page, Michael J.; Di Cera, Enrico; St. Louis-MED)

2010-06-14

Converting one enzyme into another is challenging due to the uneven distribution of important amino acids for function in both protein sequence and structure. We report a strategy for protein engineering allowing an organized mixing and matching of genetic material that leverages lower throughput with increased quality of screens. Our approach successfully tested the contribution of each surface-exposed loop in the trypsin fold alone and the cooperativity of their combinations towards building the substrate selectivity and Na{sup +}-dependent allosteric activation of the protease domain of human coagulation factor Xa into a bacterial trypsin. As the created proteases lack additional proteinmore » domains and protein co-factor activation mechanism requisite for the complexity of blood coagulation, they are stepping-stones towards further understanding and engineering of artificial clotting factors.« less

Factor XII (Hageman factor) is a missing link between stress and hypercoagulability and plays an important role in the pathophysiology of ischemic stroke.

PubMed

Eggers, Arnold E

2006-01-01

A new hypothesis is presented on the function of factor XII, which is postulated to be a "missing link" between acute stress and transient hypercoagulability. The implications of this idea are developed to show how chronic stress, which involves activation of hypertension and migraine as well as hypercoagulability, can cause of cerebrovascular disease. "Acute stress" is defined as "the normal short-term physiological response to the perception of major threats or demands". "Chronic stress" is "the abnormal ongoing physiological response to the continuing perception of unresolvable major threats or demands". The factor XII hypothesis is as follows: Acute stress includes release of epinephrine by the adrenal medulla. Epinephrine activates platelets by binding to alpha-2A adrenergic receptors. Activated platelets convert pre-bound factor XII to its active form, which then initiates the intrinsic coagulation cascade. This can be called the "activated platelet initiation pathway" for coagulation. Neither tissue factor nor pre-formed thrombin is required. Thrombosis proceeds to completion, but only a minute amount of thrombin is formed, and the process normally stops at this point. In people who lapse into a state of chronic stress, essential hypertension, which is also a manifestation of stress, synergizes with hypercoagulability: there is both a baseline rise in blood pressure and systemic platelet activation as well as superimposed labile rises of both. Upregulation of these two stress parameters is atherogenic: epinephrine-activated platelets stimulating thrombin formation interact with endothelial cells activated by angiotensin II to cause, first, smooth muscle cell proliferation, which is a histological hallmark of atherosclerosis, and, lastly, a symptomatic thrombotic occlusion-the stroke. The migraine symptoms which often accompany this process are a marker of chronic stress and ongoing pathophysiologic damage. Therapeutic predictions are made regarding novel ways of blocking stress-induced hypercoagulability and hypertension. Hypercoagulability could be targeted by monoclonal antibodies directed against the platelet-specific alpha-2 adrenergic receptor or the (putative) platelet receptor for Factor XII; hypertension could be treated with monoclonal antibodies directed against the beta-adrenergic receptor in the juxtaglomerular apparatus or by surgical denervation of the kidneys, either of which would decrease the renin release which helps drive the hypertension.

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.

Biomaterials trigger endothelial cell activation when co-incubated with human whole blood.

PubMed

Herklotz, Manuela; Hanke, Jasmin; Hänsel, Stefanie; Drichel, Juliane; Marx, Monique; Maitz, Manfred F; Werner, Carsten

2016-10-01

Endothelial cell activation resulting from biomaterial contact or biomaterial-induced blood activation may in turn also affect hemostasis and inflammatory processes in the blood. Current in vitro hemocompatibility assays typically ignore these modulating effects of the endothelium. This study describes a co-incubation system of human whole blood, biomaterial and endothelial cells (ECs) that was developed to overcome this limitation. First, human endothelial cells were characterized in terms of their expression of coagulation- and inflammation-relevant markers in response to various activators. Subsequently, their capacity to regulate hemostasis as well as complement and granulocyte activation was monitored in a hemocompatibility assay. After blood contact, quiescent ECs exhibited anticoagulant and anti-inflammatory properties. When they were co-incubated with surfaces exhibiting pro-coagulant or pro-inflammatory characteristics, the ECs down-regulated coagulation but not complement or leukocyte activation. Analysis of intracellular levels of the endothelial activation markers E-selectin and tissue factor showed that co-incubation with model surfaces and blood significantly increased the activation state of ECs. Finally, the coagulation- and inflammation-modulating properties of the ECs were tested after blood/biomaterial exposure. Pre-activation of ECs by biomaterials in the blood induced a pro-coagulant and pro-inflammatory state of the ECs, wherein the pro-coagulant response was higher for biomaterial/blood pre-activated ECs than for TNF-α-pre-activated cells. This work provides evidence that biomaterials, even without directly contacting the endothelium, affect the endothelial activation state with and have consequences for plasmatic and cellular reactions in the blood. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bacillus anthracis Cell Wall Peptidoglycan but Not Lethal or Edema Toxins Produces Changes Consistent With Disseminated Intravascular Coagulation in a Rat Model

PubMed Central

Qiu, Ping; Li, Yan; Shiloach, Joseph; Cui, Xizhong; Sun, Junfeng; Trinh, Loc; Kubler-Kielb, Joanna; Vinogradov, Evgeny; Mani, Haresh; Al-Hamad, Mariam; Fitz, Yvonne; Eichacker, Peter Q.

2013-01-01

Background. Disseminated intravascular coagulation (DIC) appears to be important in the pathogenesis of Bacillus anthracis infection, but its causes are unclear. Although lethal toxin (LT) and edema toxin (ET) could contribute, B. anthracis cell wall peptidoglycan (PGN), not the toxins, stimulates inflammatory responses associated with DIC. Methods and Results. To better understand the pathogenesis of DIC during anthrax, we compared the effects of 24-hour infusions of PGN, LT, ET, or diluent (control) on coagulation measures 6, 24, or 48 hours after infusion initiation in 135 rats. No control recipient died. Lethality rates (approximately 30%) did not differ among PGN, LT, and ET recipients (P = .78). Thirty-three of 35 deaths (94%) occurred between 6 and 24 hours after the start of challenge. Among challenge components, PGN most consistently altered coagulation measures. Compared with control at 6 hours, PGN decreased platelet and fibrinogen levels and increased prothrombin and activated partial thromboplastin times and tissue factor, tissue factor pathway inhibitor, protein C, plasminogen activator inhibitor (PAI), and thrombin-antithrombin complex levels, whereas LT and ET only decreased the fibrinogen level or increased the PAI level (P ≤ .05). Nearly all effects associated with PGN infusion significantly differed from changes associated with toxin infusion (P ≤ .05 for all comparisons except for PAI level). Conclusion. DIC during B. anthracis infection may be related more to components such as PGN than to LT or ET. PMID:23737601

Reproducing a Prospective Clinical Study as a Computational Retrospective Study in MIMIC-II.

PubMed

Kury, Fabrício S P; Huser, Vojtech; Cimino, James J

2015-01-01

In this paper we sought to reproduce, as a computational retrospective study in an EHR database (MIMIC-II), a recent large prospective clinical study: the 2013 publication, by the Japanese Association for Acute Medicine (JAAM), about disseminated intravascular coagulation, in the journal Critical Care (PMID: 23787004). We designed in SQL and Java a set of electronic phenotypes that reproduced the study's data sampling, and used R to perform the same statistical inference procedures. All produced source code is available online at https://github.com/fabkury/paamia2015. Our program identified 2,257 eligible patients in MIMIC-II, and the results remarkably agreed with the prospective study. A minority of the needed data elements was not found in MIMIC-II, and statistically significant inferences were possible in the majority of the cases.

Fibrinogen Nový Jicín and Praha II: cases of hereditary Aalpha 16 Arg-->Cys and Aalpha 16 Arg-->His dysfibrinogenemia.

PubMed

Kotlín, Roman; Chytilová, Martina; Suttnar, Jirí; Riedel, Tomás; Salaj, Peter; Blatný, Jan; Santrůcek, Jirí; Klener, Pavel; Dyr, Jan E

2007-01-01

Various dysfibrinogenemias have been described worldwide. This paper describes two new cases of dysfibrinogenemia identified in the Czech Republic. The proposita of fibrinogen Nový Jicín, a 12-year-old girl, presented with hemorrhagic complications, low Clauss fibrinogen level (0.3 g/l) and prolonged both thrombin (70.8 s) and reptilase (>180 s) time. Her mother and sister both presented with normal coagulation tests, normal fibrinogen level and reported no history of bleeding. The carriers of the fibrinogen Praha II were a 31-year-old man and his 11-year-old daughter. They both presented with low fibrinogen Clauss level (0.88 g/l) and prolonged thrombin and reptilase time. To identify the genetic mutation responsible for these dysfibrinogens, genomic DNA extracted from the blood was analyzed. The presence of the mutant chains in the circulation was determined by MALDI-TOF mass spectroscopy. Scanning electron micrographs of the patients' fibrin clots were obtained. The kinetics of fibrinopeptide release and fibrin polymerization were impaired for both fibrinogen Nový Jicín and Praha II. DNA sequencing showed heterogeneous fibrinogen Aalpha R16C mutation in the fibrinogen Nový Jicín case and heterogeneous fibrinogen Aalpha R16H in the fibrinogen Praha II case. The mutant chains were found to be expressed to the circulation by MALDI-TOF mass spectroscopy. Scanning electron micrographs of the patient's fibrin clot were found to be abnormal. The case of dysfibrinogenemia Aalpha R16C-fibrinogen Nový Jicín and the case of dysfibrinogenemia Aalpha R16H were found by routine coagulation testing and were genetically identified.

A Fast and Efficient Version of the TwO-Moment Aerosol Sectional (TOMAS) Global Aerosol Microphysics Model

NASA Technical Reports Server (NTRS)

Lee, Yunha; Adams, P. J.

2012-01-01

This study develops more computationally efficient versions of the TwO-Moment Aerosol Sectional (TOMAS) microphysics algorithms, collectively called Fast TOMAS. Several methods for speeding up the algorithm were attempted, but only reducing the number of size sections was adopted. Fast TOMAS models, coupled to the GISS GCM II-prime, require a new coagulation algorithm with less restrictive size resolution assumptions but only minor changes in other processes. Fast TOMAS models have been evaluated in a box model against analytical solutions of coagulation and condensation and in a 3-D model against the original TOMAS (TOMAS-30) model. Condensation and coagulation in the Fast TOMAS models agree well with the analytical solution but show slightly more bias than the TOMAS-30 box model. In the 3-D model, errors resulting from decreased size resolution in each process (i.e., emissions, cloud processing wet deposition, microphysics) are quantified in a series of model sensitivity simulations. Errors resulting from lower size resolution in condensation and coagulation, defined as the microphysics error, affect number and mass concentrations by only a few percent. The microphysics error in CN70CN100 (number concentrations of particles larger than 70100 nm diameter), proxies for cloud condensation nuclei, range from 5 to 5 in most regions. The largest errors are associated with decreasing the size resolution in the cloud processing wet deposition calculations, defined as cloud-processing error, and range from 20 to 15 in most regions for CN70CN100 concentrations. Overall, the Fast TOMAS models increase the computational speed by 2 to 3 times with only small numerical errors stemming from condensation and coagulation calculations when compared to TOMAS-30. The faster versions of the TOMAS model allow for the longer, multi-year simulations required to assess aerosol effects on cloud lifetime and precipitation.

Glial reactions to argon laser photocoagulation injury in rabbit and rat retinas

NASA Astrophysics Data System (ADS)

Humphrey, Martin F.; Chu, Yi; Sharp, Claudia; Moore, Stephen; Mann, Krishna; Rakoczy, Piroska; Constable, Ian J.

1996-04-01

Argon laser photocoagulation is a standard and effective clinical technique for a variety of disease conditions. However there is evidence that coagulation produces more widespread alterations in the retina than the local scarring at the injury site. For example, in diabetic retinopathy multiple photocoagulations in the retinal periphery can control blood vessel growth in the central retina. Therefore we have studied the changes in retinal glial cells following photocoagulation using immunocytochemical techniques with an emphasis on the spread of cellular reactions by using whole, flatmounted retinal preparations. Muller glial cells do not normally express the cytoskeletal protein GFAP (glial fibrillary acidic protein) but do so after a variety of injuries. We found that there is a very widespread expression of GFAP by Muller cells even after very focal coagulations and that this persists for 1 - 1.5 months after coagulation. The microglial cells are primed to react to injury and can release very powerful effector molecules and we therefore also examined the microglial reaction to see whether it correlated with the Muller cell reaction. However, we found that the microglial response, in terms of anatomical changes, was very focally confined to regions of direct cellular injury. We also examined MHC II expression to see whether microglia expressed this activity related protein without anatomical changes but we found no evidence of wide spread changes. In summary we find that inflammatory reactions are very localized after coagulation but the macroglial changes are more widespread and therefore the distant effects of photocoagulation may be more related to macroglial reactions.

Newly-recognized roles of factor XIII in thrombosis

PubMed Central

Byrnes, James R.; Wolberg, Alisa S.

2017-01-01

Arterial and venous thrombosis are major contributors to coagulation-associated morbidity and mortality. Greater understanding of mechanisms leading to thrombus formation and stability is expected to lead to improved treatment strategies. Factor XIII (FXIII) is a transglutaminase found in plasma and platelets. During thrombosis, activated FXIII crosslinks fibrin and promotes thrombus stability. Recent studies have provided new information about FXIII activity during coagulation and its effects on clot composition and function. These findings reveal newly-recognized roles for FXIII in thrombosis. Herein, we review published literature on FXIII biology and effects on fibrin structure and stability, epidemiologic data associating FXIII with thrombosis, and evidence from animal models indicating FXIII has an essential role in determining thrombus stability, composition, and size. PMID:27056150

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.

Wound shock: a history of its study and treatment by military surgeons.

PubMed

Hardaway, Robert M

2004-04-01

The treatment of wounds has received considerable attention from the time of the Trojan War. However, it was not until the American Civil War that shock was described as an entity distinct from the wounds themselves and that efforts were directed at more than just treatment of the wound. The need for fluid resuscitation in the treatment of hemorrhagic shock was first recognized in the Spanish American War, as was the association of sepsis with shock. World War I showed the need for blood in the treatment of "wound shock," a lesson that had to be relearned in World War II through bitter experience. Studies in the Korean War described the concept of disseminated intravascular coagulation and multiple organ failure, and the existence of disseminated intravascular coagulation was confirmed by studies in Vietnam. The treatment of hemorrhagic shock is now very effective, but the treatment of traumatic and septic shock remains unsatisfactory.

VSDMIP: virtual screening data management on an integrated platform

NASA Astrophysics Data System (ADS)

Gil-Redondo, Rubén; Estrada, Jorge; Morreale, Antonio; Herranz, Fernando; Sancho, Javier; Ortiz, Ángel R.

2009-03-01

A novel software (VSDMIP) for the virtual screening (VS) of chemical libraries integrated within a MySQL relational database is presented. Two main features make VSDMIP clearly distinguishable from other existing computational tools: (i) its database, which stores not only ligand information but also the results from every step in the VS process, and (ii) its modular and pluggable architecture, which allows customization of the VS stages (such as the programs used for conformer generation or docking), through the definition of a detailed workflow employing user-configurable XML files. VSDMIP, therefore, facilitates the storage and retrieval of VS results, easily adapts to the specific requirements of each method and tool used in the experiments, and allows the comparison of different VS methodologies. To validate the usefulness of VSDMIP as an automated tool for carrying out VS several experiments were run on six protein targets (acetylcholinesterase, cyclin-dependent kinase 2, coagulation factor Xa, estrogen receptor alpha, p38 MAP kinase, and neuraminidase) using nine binary (actives/inactive) test sets. The performance of several VS configurations was evaluated by means of enrichment factors and receiver operating characteristic plots.

Warfarin hypersensitivity due to gluten-sensitive enteropathy: a case study.

PubMed

Kwolek, Sara; Deming, Paula

2012-01-01

A 53 year old female who was maintained on long-term warfarin therapy due to history of pulmonary embolism, repeatedly presents with an abnormally prolonged Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT). After many asymptomatic episodes were corrected with Vitamin K therapy to temporarily reverse the effects of the warfarin, the cause of the apparent coagulopathy was further investigated. Factor Activity Assays of the common pathway factors II, IX, and X all revealed critically low values; below the threshold even a loading dose of warfarin is typically capable of eliciting. The patient tested strongly positive for Tissue Transglutaminase IgA, which is highly suggestive of a gluten-sensitive enteropathy. One effect of this condition is malabsorption due to flattened intestinal villi. The patient was determined to have an acquired vitamin K deficiency secondary to gluten-sensitive enteropathy. Her condition was exacerbated by the long-term warfarin therapy, resulting in the prolonged PT and PTT. The patient was treated with vitamin K therapy, which reversed the deficiency and corrected her abnormal coagulation results.

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 immediate and late effects of thyroid hormone (triiodothyronine) on murine coagulation gene transcription.

PubMed

Salloum-Asfar, Salam; Boelen, Anita; Reitsma, Pieter H; van Vlijmen, Bart J M

2015-01-01

Thyroid dysfunction is associated with changes in coagulation. The aim of our study was to gain more insight into the role of thyroid hormone in coagulation control. C57Black/6J mice received a low-iodine diet and drinking water supplemented with perchlorate to suppress endogenous triiodothyronine (T3) and thyroxine (T4) production. Under these conditions, the impact of exogenous T3 on plasma coagulation, and hepatic and vessel-wall-associated coagulation gene transcription was studied in a short- (4 hours) and long-term (14 days) setting. Comparing euthyroid conditions (normal mice), with hypothyroidism (conditions of a shortage of thyroid hormone) and those with replacement by incremental doses of T3, dosages of 0 and 0.5 μg T3/mouse/day were selected to study the impact of T3 on coagulation gene transcription. Under these conditions, a single injection of T3 injection increased strongly hepatic transcript levels of the well-characterized T3-responsive genes deiodinase type 1 (Dio1) and Spot14 within 4 hours. This coincided with significantly reduced mRNA levels of Fgg, Serpinc1, Proc, Proz, and Serpin10, and the reduction of the latter three persisted upon daily treatment with T3 for 14 days. Prolonged T3 treatment induced a significant down-regulation in factor (F) 2, F9 and F10 transcript levels, while F11 and F12 levels increased. Activity levels in plasma largely paralleled these mRNA changes. Thbd transcript levels in the lung (vessel-wall-associated coagulation) were significantly up-regulated after a single T3 injection, and persisted upon prolonged T3 exposure. Two-week T3 administration also resulted in increased Vwf and Tfpi mRNA levels, whereas Tf levels decreased. These data showed that T3 has specific effects on coagulation, with Fgg, Serpinc1, Proc, Proz, Serpin10 and Thbd responding rapidly, making these likely direct thyroid hormone receptor targets. F2, F9, F10, F11, F12, Vwf, Tf and Tfpi are late responding genes and probably indirectly modulated by T3.

Platelet Glycoprotein lb-1X and Malignancy

DTIC Science & Technology

2011-09-01

Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. Proc Natl Acad Sci...JM, Hakim J, de Prost D. Vascular endothelial growth factor production by fibroblasts in response to factor VIIa binding to tissue factor involves...interactions in vitro. (14) The extrinsic pathway of coagulation triggered by factor VII ( FVII ) and tissue factor can be activated in cancer patients. (15

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

The impact of irrigating fluid absorption on blood coagulation in patients undergoing transurethral resection of the prostate

PubMed Central

Shin, Hyun-Jung; Na, Hyo-Seok; Jeon, Young-Tae; Park, Hee-Pyoung; Nam, Sun-Woo; Hwang, Jung-Won

2017-01-01

Abstract Although endoscopic transurethral resection of the prostate (TURP) is a well-established procedure as a treatment for benign prostatic hyperplasia, its complications remain a concern. Among these, coagulopathy may be caused by the absorption of irrigating fluid. This study aimed to evaluate such phenomenon using a rotational thromboelastometry (ROTEM). A total of 20 patients undergoing TURP participated in this study. A mixture of 2.7% sorbitol–0.54% mannitol solution and 1% ethanol was used as an irrigating fluid, and fluid absorption was measured via the ethanol concentration in expired breath. The effects on coagulation were assessed by pre- and postoperative laboratory blood tests, including hemoglobin, hematocrit, platelet count, international normalized ratio of prothrombin time (PT-INR), activated partial thromboplastin time, electrolyte, and ROTEM. INTEM-clotting time (INTEM-CT) was significantly lengthened by 14% (P = 0.001). INTEM-α-angle was significantly decreased by 3% (P = 0.011). EXTEM-clot formation time was significantly prolonged by 18% (P = 0.008), and EXTEM-maximum clot firmness (EXTEM-MCF) was significantly decreased by 4% (P = 0.010). FIBTEM-MCF was also significantly decreased by 13% (P = 0.015). Moreover, hemoglobin (P < 0.001), hematocrit (P < 0.001), platelet counts (P < 0.001), potassium (P = 0.024), and ionized calcium (P = 0.004) were significantly decreased, while PT-INR (P = 0.001) was significantly increased after surgery. The amount of irrigating fluid absorbed was significantly associated with the weight of resected prostatic tissue (P = 0.001) and change of INTEM-CT (P < 0.001). As shown by the ROTEM analysis, the irrigating fluid absorbed during TURP impaired the blood coagulation cascade by creating a disruption in the coagulation factor activity or by lowering the coagulation factor concentration via dilution. PMID:28079789

The impact of irrigating fluid absorption on blood coagulation in patients undergoing transurethral resection of the prostate: A prospective observational study using rotational thromboelastometry.

PubMed

Shin, Hyun-Jung; Na, Hyo-Seok; Jeon, Young-Tae; Park, Hee-Pyoung; Nam, Sun-Woo; Hwang, Jung-Won

2017-01-01

Although endoscopic transurethral resection of the prostate (TURP) is a well-established procedure as a treatment for benign prostatic hyperplasia, its complications remain a concern. Among these, coagulopathy may be caused by the absorption of irrigating fluid. This study aimed to evaluate such phenomenon using a rotational thromboelastometry (ROTEM).A total of 20 patients undergoing TURP participated in this study. A mixture of 2.7% sorbitol-0.54% mannitol solution and 1% ethanol was used as an irrigating fluid, and fluid absorption was measured via the ethanol concentration in expired breath. The effects on coagulation were assessed by pre- and postoperative laboratory blood tests, including hemoglobin, hematocrit, platelet count, international normalized ratio of prothrombin time (PT-INR), activated partial thromboplastin time, electrolyte, and ROTEM.INTEM-clotting time (INTEM-CT) was significantly lengthened by 14% (P = 0.001). INTEM-α-angle was significantly decreased by 3% (P = 0.011). EXTEM-clot formation time was significantly prolonged by 18% (P = 0.008), and EXTEM-maximum clot firmness (EXTEM-MCF) was significantly decreased by 4% (P = 0.010). FIBTEM-MCF was also significantly decreased by 13% (P = 0.015). Moreover, hemoglobin (P < 0.001), hematocrit (P < 0.001), platelet counts (P < 0.001), potassium (P = 0.024), and ionized calcium (P = 0.004) were significantly decreased, while PT-INR (P = 0.001) was significantly increased after surgery. The amount of irrigating fluid absorbed was significantly associated with the weight of resected prostatic tissue (P = 0.001) and change of INTEM-CT (P < 0.001).As shown by the ROTEM analysis, the irrigating fluid absorbed during TURP impaired the blood coagulation cascade by creating a disruption in the coagulation factor activity or by lowering the coagulation factor concentration via dilution.

Removal of copper (II) from aqueous solutions by flotation using polyaluminum chloride silicate (PAX-XL60 S) as coagulant and carbonate ion as activator.

PubMed

Ghazy, S E; Mahmoud, I A; Ragab, A H

2006-01-01

Flotation is a separation technology for removing toxic heavy metal ions from aqueous solutions. Here a simple and rapid flotation procedure is presented for the removal of copper(II) from aqueous solutions. It is based on the use of polyaluminum chloride silicate (PAX-XL60 S) as coagulant and flocculent, carbonate ion as activator and oleic acid (HOL) as surfactant. Both ion and precipitate flotation are included depending on the solution pH. Ion and precipitate flotation in the aqueous HOL-PAX-XL60 S-Cu2+-CO3(2-) system gave powerful preferential removal of Cu2+ (F -100%) over the HOL-PAX-XL60 S-Cu2+ system containing no CO3(2+) ion (F approximately 86%). The role of CO3(2-) ion is also evident from decreasing the dose of PAX-XL60 S from 700 mg l(-1) to 200 mg l(-1). The other parameters, influencing the flotation process, namely: metal ion, surfactant and PAX-XL60 S concentrations, ionic strength, temperature and foreign ions were examined. Moreover, the procedure was successfully applied to recover Cu2+ ions from different volumes up to 11 and from natural water samples.

Endoscopic monopolar coagulation of internal haemorrhoids: a surgeon's experience of the first 100 cases.

PubMed

Loh, W-L; Tan, S; Ngooi, M S; Ong, Z K; Ngoi, S S

2017-01-01

The purpose of this study was to evaluate one surgeon's initial experience with a novel technique of retroflexed endoscopic coagulation of internal haemorrhoids. Patients who presented with symptoms and signs indicating Grade II-III haemorrhoids were counselled before the procedure. Those who were assessed to require an examination of their colon, based on their age and symptoms, underwent a full colonoscopy before treatment of the haemorrhoids. After the procedure, patients were routinely prescribed nonsteroidal anti-inflammatory drugs, antibiotics and laxatives. The first 100 patients of median age 52.0 (20.8-78.5) years included 65 (65%) women. Five (5%) patients suffered from postprocedural complications, of which three (3%) were postprocedural bleeding and two (2%) were postprocedural pain, all treated conservatively. The recurrence rate was 6% at a median follow-up time of 36 (6-76) months. The median duration of follow-up was 36.5 (8.5-57.0) months. This novel technique appears to be safe and effective for the treatment of Grade II-III internal haemorrhoids, and can be incorporated seamlessly into the end of a colonoscopy for the evaluation of haematochezia. Comparative trials should be performed. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

Dominant von Willebrand disease type 2A groups I and II due to missense mutations in the A2 domain of the von Willebrand factor gene: diagnosis and management.

PubMed

Michiels, Jan Jacques; van Vliet, Huub H D M

2009-01-01

Pertinent findings in patients with von Willebrand disease (VWD) type 2A include prolonged bleeding time (BT), consistently low von Willebrand factor (VWF):ristocetin cofactor activity (RCo)/antigen concentration (Ag) and VWF:collagen binding (CB)/Ag ratios, absence of high, and (depending on severity) intermediate and large VWF multimers, the presence of pronounced triplet structure of individual bands and increased VWF degradation products due to increased proteolysis caused by mutations in the A2 domain of VWF. Two categories of VWD type 2A can be distinguished: group I with severe and group II with mild VWD. A minority of VWD type 2A have mild VWD characterized by near normal to prolonged BT, normal factor VIII coagulant activity and VWF:Ag, low VWF:RCo and VWF:CB, a normal ristocetin-induced platelet aggregation and complete but transient correction of BT and functional VWF parameters to normal levels for only a few hours due to short half-lives for VWF:RCo and CWF:CB. Such transient complete responses to desmopressin (DDAVP) lasting only a few hours may facilitate treatment and prophylaxis of minor bleedings, but may not be able to prevent bleeding during minor and major surgery. Most VWD type 2A patients have pronounced VWD with very low VWF:RCo, prolonged BT, PFA-100 closure times >250 s, and response to DDAVP is only transient, minor, poor or absent, with no correction of the BT despite some increase in VWF:RCo, thus being candidates for factor VIII-VWF concentrate substitution for the acute and prophylactic treatment of bleeding symptoms. Copyright (c) 2009 S. Karger AG, Basel.

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.

Role of altered coagulation-fibrinolytic system in the pathophysiology of diabetic retinopathy.

PubMed

Behl, Tapan; Velpandian, Thirumurthy; Kotwani, Anita

2017-05-01

The implications of altered coagulation-fibrinolytic system in the pathophysiology of several vascular disorders, such as stroke and myocardial infarction, have been well researched upon and established. However, its role in the progression of diabetic retinopathy has not been explored much. Since a decade, it is known that hyperglycemia is associated with a hypercoagulated state and the various impairments it causes are well acknowledged as independent risk factors for the development of cardiovascular diseases. But recent studies suggest that the hypercoagulative state and diminished fibrinolytic responses might also alter retinal homeostasis and induce several deleterious molecular changes in retinal cells which aggravate the already existing hyperglycemia-induced pathological conditions and thereby lead to the progression of diabetic retinopathy. The major mediators of coagulation-fibrinolytic system whose concentration or activity get altered during hyperglycemia include fibrinogen, antithrombin-III (AT-III), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF). Inhibiting the pathways by which these altered mediators get involved in the pathophysiology of diabetic retinopathy can serve as potential targets for the development of an adjuvant novel alternative therapy for diabetic retinopathy. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterization of a microbial polysaccharide-based bioflocculant and its anti-inflammatory and pro-coagulant activity.

PubMed

Zhong, Chunying; Cao, Gang; Rong, Kuan; Xia, Zhengwu; Peng, Ting; Chen, Honggao; Zhou, Jiangang

2018-01-01

We describe a novel bioflocculant, MBF-15, which is an exopolysaccharide extracted from the alkaliphilic bacterium Paenibacillus jamilae. The biophysical characteristics of MBF-15 were determined using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. MBF-15 was also evaluated for its biocompatibility by examining its inflammatory, coagulant, and hemostatic properties in vitro and in vivo. Pretreatment of peripheral blood mononuclear cells with MBF-15 inhibited lipopolysaccharide-stimulated expression of inducible nitric oxide synthase, production of nitric oxide, and secretion of pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-6. In addition, MBF-15 increased both mRNA and protein levels of the anti-inflammatory cytokines transforming growth factor-β and IL-10. The hemocompatibility of MBF-15 was investigated by measuring the hemolysis ratio and clotting times. MBF-15 had high pro-thrombogenic activity but was not hemolytic. In a rat model, MBF-15 showed superior hemostatic properties compared with chitosan. Thus, MBF-15 offers a promising combination of anti-inflammatory and pro-coagulant properties that may be useful for hemostasis in a variety of clinical settings. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

Short-term chamber exposure to low doses of two kinds of wood smoke does not induce systemic inflammation, coagulation or oxidative stress in healthy humans

PubMed Central

Sallsten, Gerd; Almerud, Pernilla; Basu, Samar; Barregard, Lars

2013-01-01

Introduction: Air pollution increases the risk of cardiovascular diseases. A proposed mechanism is that local airway inflammation leads to systemic inflammation, affecting coagulation and the long-term risk of atherosclerosis. One major source of air pollution is wood burning. Here we investigate whether exposure to two kinds of wood smoke, previously shown to cause airway effects, affects biomarkers of systemic inflammation, coagulation and lipid peroxidation. Methods: Thirteen healthy adults were exposed to filtered air followed by two sessions of wood smoke for three hours, one week apart. One session used smoke from the start-up phase of the wood-burning cycle, and the other smoke from the burn-out phase. Mean particle mass concentrations were 295 µg/m3 and 146 µg/m3, and number concentrations were 140 000/cm3 and 100 000/cm3, respectively. Biomarkers were analyzed in samples of blood and urine taken before and several times after exposure. Results after wood smoke exposure were adjusted for exposure to filtered air. Results: Markers of systemic inflammation and soluble adhesion molecules did not increase after wood smoke exposure. Effects on markers of coagulation were ambiguous, with minor decreases in fibrinogen and platelet counts and mixed results concerning the coagulation factors VII and VIII. Urinary F2-isoprostane, a consistent marker of in vivo lipid peroxidation, unexpectedly decreased after wood smoke exposure. Conclusions: The effects on biomarkers of inflammation, coagulation and lipid peroxidation do not indicate an increased risk of cardiovascular diseases in healthy adults by short-term exposure to wood smoke at these moderate doses, previously shown to cause airway effects. PMID:23808634

Functionalization of single-walled carbon nanotubes regulates their effect on hemostasis

NASA Astrophysics Data System (ADS)

Sokolov, A. V.; Aseychev, A. V.; Kostevich, V. A.; Gusev, A. A.; Gusev, S. A.; Vlasova, I. I.

2011-04-01

Applications of single-walled carbon nanotubes (SWNTs) in medical field imply the use of drug-coupled carbon nanotubes as well as carbon nanotubes functionalized with different chemical groups that change nanotube surface properties and interactions between nanotubes and cells. Covalent attachment of polyethylene glycol (PEG) to carboxylated single-walled carbon nanotubes (c-SWNT) is known to prevent the nanotubes from interaction with macrophages. Here we characterized nanotube's ability to stimulate coagulation processes in platelet-poor plasma (PPP), and evaluated the effect of SWNTs on platelet aggregation in platelet-rich plasma (PRP). Our study showed that PEG-SWNT did not affect the rate of clotting in PPP, while c-SWNT shortened the clot formation time five times compared to the control PPP. Since c-SWNT failed to accelerate coagulation in plasma lacking coagulation factor XI, it may be suggested that c-SWNT affects the contact activation pathway. In PRP, platelets responded to both SWNT types with irreversible aggregation, as evidenced by changes in the aggregate mean radius. However, the rate of aggregation induced by c-SWNT was two times higher than it was with PEG-SWNT. Cytological analysis also showed that c-SWNT was two times more efficient when compared to PEG-SWNT in aggregating platelets in PRP. Taken together, our results show that functionalization of nanoparticles can diminish their negative influence on blood cells. As seen from our data, modification of c-SWNT with PEG, when only a one percent of carbon atoms is bound to polymer (70 wt %), decreased the nanotube-induced coagulation in PRP and repelled the accelerating effect on the coagulation in PPP. Thus, when functionalized SWNTs are used for administration into bloodstream of laboratory animals, their possible pro-coagulant and pro-aggregating properties must be taken into account.

Tissue Factor-Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes.

PubMed

Koizume, Shiro; Miyagi, Yohei

2015-01-01

Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF-fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF-fVII complex. Here, we discuss the roles of the TF-fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF-fVII function.

Source of Chronic Inflammation in Aging.

PubMed

Sanada, Fumihiro; Taniyama, Yoshiaki; Muratsu, Jun; Otsu, Rei; Shimizu, Hideo; Rakugi, Hiromi; Morishita, Ryuichi

2018-01-01

Aging is a complex process that results from a combination of environmental, genetic, and epigenetic factors. A chronic pro-inflammatory status is a pervasive feature of aging. This chronic low-grade inflammation occurring in the absence of overt infection has been defined as "inflammaging" and represents a significant risk factor for morbidity and mortality in the elderly. The low-grade inflammation persists even after reversing pro-inflammatory stimuli such as LDL cholesterol and the renin-angiotensin system (RAS). Recently, several possible sources of chronic low-grade inflammation observed during aging and age-related diseases have been proposed. Cell senescence and dysregulation of innate immunity is one such mechanism by which persistent prolonged inflammation occurs even after the initial stimulus has been removed. Additionally, the coagulation factor that activates inflammatory signaling beyond its role in the coagulation system has been identified. This signal could be a new source of chronic inflammation and cell senescence. Here, we summarized the factors and cellular pathways/processes that are known to regulate low-grade persistent inflammation in aging and age-related disease.

Effects of pentastarch and albumin infusion on cardiorespiratory function and coagulation in patients with severe sepsis and systemic hypoperfusion.

PubMed

Rackow, E C; Mecher, C; Astiz, M E; Griffel, M; Falk, J L; Weil, M H

1989-05-01

Twenty consecutive patients with severe sepsis were randomized to fluid challenge with 5% albumin or 10% low MW hydroxyethyl starch (pentastarch) solutions. Fluid challenge was administered iv as 250 ml of test colloid every 15 min until the pulmonary artery wedge pressure (WP) was greater than or equal to 15 mm Hg or a maximum dose of 2000 ml was infused. Hemodynamic, respiratory, and coagulation profiles were measured before and after fluid infusion. The amount of colloid required to achieve a WP of 15 mm Hg was comparable between groups. Both colloid infusions resulted in similar increases in cardiac output, stroke output, and stroke work. The effect of fluid infusion with pentastarch on coagulation was not significantly different from albumin, although pentastarch was associated with a 45% decrease in factor VIII:c. We conclude that pentastarch is equivalent to albumin for fluid resuscitation of patients with severe sepsis.

Removal of sodium lauryl sulphate by coagulation/flocculation with Moringa oleifera seed extract.

PubMed

Beltrán-Heredia, J; Sánchez-Martín, J

2009-05-30

Among other natural flocculant/coagulant agents, Moringa oleifera seed extract ability to remove an anionic surfactant has been evaluated and it has been found to be very interesting. Sodium lauryl sulphate was removed from aqueous solutions up to 80% through coagulation/flocculation process. pH and temperature were found to be not very important factors in removal efficiency. Freundlich (F), Frumkin-Fowler-Guggenheim (FFG) and Gu-Zhu (GZ) models were used to adjust experimental data in a solid-liquid adsorption hypothesis. Last one resulted to be the most accurate one. Several data fit parameters were determined, as Freundlich order, which was found to be 1.66, Flory-Huggins interaction parameter from FFG model, which was found to be 4.87; and limiting Moringa surfactant adsorption capacity from GZ model, which was found to be 2.13 x 10(-3)mol/g.

An ecoimmunological approach to study evolutionary and ancient links between coagulation, complement and Innate immunity

PubMed Central

Kasetty, Gopinath; Alyafei, Saud; Smeds, Emanuel; Salo-Ahen, Outi M. H.; Hansson, Stefan R.; Egesten, Arne; Herwald, Heiko

2018-01-01

ABSTRACT Coagulation, complement, and innate immunity are tightly interwoven and form an alliance that can be traced back to early eukaryotic evolution. Here we employed an ecoimmunological approach using Tissue Factor Pathway Inhibitor (TFPI)-1-derived peptides from the different classes of vertebrates (i.e. fish, reptile, bird, and mammals) and tested whether they can boost killing of various human bacterial pathogens in plasma. We found signs of species-specific conservation and diversification during evolution in these peptides that significantly impact their antibacterial activity. Though all peptides tested executed bactericidal activity in mammalian plasma (with the exception of rodents), no killing was observed in plasma from birds, reptiles, and fish, pointing to a crucial role for the classical pathway of the complement system. We also observed an interference of these peptides with the human intrinsic pathway of coagulation though, unlike complement activation, this mechanism appears not to be evolutionary conserved. PMID:29473457

ACUTE CARDIOVASCULAR EFFECTS OF FIREFIGHTING AND ACTIVE COOLING DURING REHABILITATION

PubMed Central

Burgess, Jefferey L.; Duncan, Michael D.; Hu, Chengcheng; Littau, Sally R.; Caseman, Delayne; Kurzius-Spencer, Margaret; Davis-Gorman, Grace; McDonagh, Paul F.

2012-01-01

Objectives To determine the cardiovascular and hemostatic effects of fire suppression and post-exposure active cooling. Methods Forty-four firefighters were evaluated prior to and after a 12 minute live-fire drill. Next, 50 firefighters undergoing the same drill were randomized to post-fire forearm immersion in 10°C water or standard rehabilitation. Results In the first study, heart rate and core body temperature increased and serum C-reactive protein decreased but there were no significant changes in fibrinogen, sE-selectin or sL-selectin. The second study demonstrated an increase in blood coagulability, leukocyte count, factors VIII and X, cortisol and glucose, and a decrease in plasminogen and sP-selectin. Active cooling reduced mean core temperature, heart rate and leukocyte count. Conclusions Live-fire exposure increased core temperature, heart rate, coagulability and leukocyte count; all except coagulability were reduced by active cooling. PMID:23090161

Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage.

PubMed

Green, F W; Kaplan, M M; Curtis, L E; Levine, P H

1978-01-01

In a series of in vitro studies, both the soluble (plasmatic) coagulation system and the cellular (platelet-mediated) aspect of coagulation were shown to be extremely sensitive to relatively minor increases in hydrogen ion concentration. All studies became abnormal at pH 6.8. At pH 6.4, assays of the intrinsic and extrinsic coaglution systems, the polymerization of fibrinogen, and assay of the availability of platelet phospholipid (platelet factor 3) were twice prolonged over control values. Platelet aggregation was reduced by more than 50%. At pH 5.4 in vitro, platelet aggregation and plasma coagulation were both virtually abolished. Furthermore, previously formed platelet aggregates disaggregated at a slightly acid pH. Pepsin further enhanced platelet disaggregation. Because gastric acidity is normally two to four orders of magnitude greater than that which abolishes platelet aggregation and plasma clotting in vitro, and pepsin is present in abundance, we call attention to the probable antihemostatic effect of hydrocloric acid and pepsin in the upper gastrointestinal tract. This in vitro study may provide a rationale for meticulous regulation of intragastric pH in an effort to control upper gastrointestinal hemorrhage.

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.

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)

Effect of pH and glucose on cultured human peritoneal mesothelial cells.

PubMed

Shao, J C; Yorioka, N; Nishida, Y; Yamakido, M

1999-08-01

We investigated the effects of various pH and glucose concentrations on the growth of human peritoneal mesothelial cells and on coagulation and fibrinolytic factors. Cells were cultured at various pH values in Ham's F-12 medium containing 1.0% foetal calf serum and supplemented with D-glucose or D-mannitol at various concentrations. After 4-48 h, cell proliferation and 3H-thymidine incorporation were determined. Coagulation and fibrinolytic factors were measured after 48 h. Glucose caused concentration-dependent inhibition of cell growth at all pH values, but the deleterious effect of low pH on cell proliferation was faster and stronger than that of high glucose. At a similar osmolality, mannitol caused less inhibition of cell proliferation than glucose. There was a glucose concentration-dependent increase of thrombin-antithrombin III complex production at all pH values. At pH 5.2, tissue-type plasminogen activator production was far lower than at higher pH values, and production of the plasminogen activator inhibitor showed a glucose concentration-dependent increase. At pH 6.5 or 7.3, however, the plasminogen activator inhibitor production decreased and tissue-type plasminogen activator production increased in a glucose concentration-dependent manner. Low pH and/or high glucose culture medium had an inhibitory effect on peritoneal mesothelial cells, with the effect of high glucose being partially related to hyperosmolality. These cells may modulate peritoneal coagulant and fibrinolytic activity, with the balance between coagulation and fibrinolysis being disturbed by low pH and/or high glucose.

Contrasting effects of photochemical and microbial degradation on Cu(II) binding with fluorescent DOM from different origins.

PubMed

Xu, Huacheng; Guan, Dong-Xing; Zou, Li; Lin, Hui; Guo, Laodong

2018-08-01

Effects of photochemical and microbial degradation on variations in composition and molecular-size of dissolved organic matter (DOM) from different sources (algal and soil) and the subsequent influence on Cu(II) binding were investigated using UV-Vis, fluorescence excitation-emission matrices coupled with parallel factor analysis, flow field-flow fractionation (FlFFF), and metal titration. The degradation processes resulted in an initial rapid decline in the bulk dissolved organic carbon and chromophoric and fluorescent DOM components, followed by a small or little decrease. Specifically, photochemical reaction decreased the aromaticity, humification and apparent molecular weights of all DOM samples, whereas a reverse trend was observed during microbial degradation. The FlFFF fractograms revealed that coagulation of both protein- and humic-like DOM induced an increase in molecular weights for algal-DOM, while the molecular weight enhancement for allochthonous soil samples was mainly attributed to the self-assembly of humic-like components. The Cu(II) binding capacity of algal-derived humic-like and fulvic-like DOM consistently increased during photo- and bio-degradation, while the soil-derived DOM exhibited a slight decline in Cu(II) binding capacity during photo-degradation but a substantial increase during microbial degradation, indicating source- and degradation-dependent metal binding heterogeneities. Pearson correlation analysis demonstrated that the Cu(II) binding potential was mostly related with aromaticity and molecular size for allochthonous soil-derived DOM, but was regulated by both DOM properties and specific degradation processes for autochthonous algal-derived DOM. This study highlighted the coupling role of inherent DOM properties and external environmental processes in regulating metal binding, and provided new insights into metal-DOM interactions and the behavior and fate of DOM-bound metals in aquatic environments. Copyright © 2018 Elsevier Ltd. All rights reserved.

Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality.

PubMed

Mauri, Tommaso; Bellani, Giacomo; Patroniti, Nicolo'; Coppadoro, Andrea; Peri, Giuseppe; Cuccovillo, Ivan; Cugno, Massimo; Iapichino, Gaetano; Gattinoni, Luciano; Pesenti, Antonio; Mantovani, Alberto

2010-04-01

Pentraxin 3 (PTX3) is an inflammatory mediator produced by neutrophils, macrophages, myeloid dendritic and endothelial cells. During sepsis a massive inflammatory activation and coagulation/fibrinolysis dysfunction occur. PTX3, as a mediator of inflammation, may represent an early marker of severity and outcome in sepsis. This study is based on a prospective trial regarding the impact of glycemic control on coagulation in sepsis. Ninety patients admitted to three general intensive care units were enrolled when severe sepsis or septic shock was diagnosed. At enrollment, we recorded sepsis signs, disease severity, coagulation activation [prothrombin fragments 1 + 2 (F(1+2))] and fibrinolysis inhibition [plasminogen activator inhibitor-1 (PAI-1)]. We measured plasma PTX3 levels at enrollment, everyday until day 7, then at days 9, 11, 13, 18, 23 and 28. Mortality was recorded at day 90. Although not different on day 1, PTX3 remained significantly higher in non-survivors than in survivors over the first 5 days (p = 0.002 by general linear model). On day 1, PTX3 levels were higher in septic shock than in severely septic patients (p = 0.029). Day 1 PTX3 was significantly correlated with platelet count (p < 0.001), SAPS II score (p = 0.006) and SOFA score (p < 0.001). Day 1 PTX3 was correlated with F(1+2) concentration and with PAI-1 activity and concentration (p < 0.05 for all). Persisting high levels of circulating PTX3 over the first days from sepsis onset may be associated with mortality. PTX3 correlates with severity of sepsis and with sepsis-associated coagulation/fibrinolysis dysfunction.

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-firming rate constant (k(CF)). Season of sampling was found to be very important, yielding higher values during winter for all traits except k(CF) and k(SR). All CFt traits were affected by individual cow factors. For parity, milk produced by first-lactation cows showed higher k(CF) and k(SR), but delays in achieving CF(max). With respect to stage of lactation, RCT(eq) and potential asymptotic CF increased during the middle of lactation and stabilized thereafter, whereas the 2 instant rate constants presented the opposite pattern, with the lowest (k(CF)) and highest (k(SR)) values occurring in mid lactation. The new challenge offered by prolonging the test interval and individual modeling of milk technological properties allowed us to study the effects of parameters related to the environment and to individual cows. This novel strategy may be useful for investigating the genetic variability of these new coagulation traits. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Intrapartum anti-disseminated intravascular coagulation therapy leading to successful vaginal delivery following intrauterine fetal death caused by placental abruption: a case report.

PubMed

Honda, Michiko; Matsunaga, Shigetaka; Era, Sumiko; Takai, Yasushi; Baba, Kazunori; Seki, Hiroyuki

2014-12-23

Disseminated intravascular coagulation due to placental abruption with intrauterine fetal death is not uncommon. It can result in increased maternal mortality rates and the need for hysterectomy or greater transfusion volumes if the delivery is not completed within six to eight hours. However, consensus is lacking regarding the delivery approach for cases in which delivery is prolonged. A 37-year-old Japanese woman was transported to our tertiary center two and a half hours after the onset of labor because of a diagnosis of placental abruption with intrauterine fetal death at 40 weeks and three days' gestation. On arrival, although severe hypofibrinogenemia was observed, there was no external hemorrhage. Because her cervical canal dilation was good (Bishop score, 7), labor was induced using oxytocin. Anti-disseminated intravascular coagulation therapy was simultaneously started via transfusion. After her hypofibrinogenemia resolved, delivery progressed rapidly, and the fetus was delivered approximately 10 hours after the onset. To reduce postpartum hemorrhage, 6g of fibrinogen concentrate and tranexamic acid, an antifibrinolytic agent, were administered immediately before extraction of the dead fetus and placenta. Although the amount of intrapartum hemorrhage was 1824g, there was no abnormal bleeding after delivery, and our patient was discharged three days later. In cases of placental abruption complicated with disseminated intravascular coagulation, intrapartum administration of coagulation factors can simultaneously promote effective labor and correct hypofibrinogenemia, enabling minimally invasive vaginal delivery.

Application of alum and chickpea (cicer arietinum) in removing color from leachate

NASA Astrophysics Data System (ADS)

Zin, N. S. M.; Awang, N. H.; Akbar, N. A.

2018-04-01

Dual coagulant has the potential to improve the coagulation process. In leachate treatment coagulation/flocculation can be used as a main treatment method or as a polishing/tertiary treatment step. Application of natural coagulant as coagulant aids able to increase the formation of floc and the removal ability of the coagulation process. This study was focusing on the ability of dual coagulants made from chemical coagulant (Alum) and natural coagulant (Cicer Arietinum (CA)) in removing colour from leachate. Jar test was carried out to investigate the effect of dose and pH on the removal ability of the dual coagulant. The optimum pH and dose for dual coagulant were obtained at pH 6.0 with dose of Alum at 4 g/L and dose of CA at 0.6 g/L with 94% removal of colour. While the optimum removal of colour for single Alum (4 g/L) and single CA (1.4 g/L) were recorded as 88% and 22%, respectively. The removals obtained using single natural and chemical coagulants were not as good as those obtained by dual coagulant. Thus, addition of CA as a coagulant aid for alum, able to increase the removal of color from leachate and has the potential to be applied as a treatment method for leachate.

Microphysics-based black carbon aging in a global CTM: constraints from HIPPO observations and implications for global black carbon budget

NASA Astrophysics Data System (ADS)

He, Cenlin; Li, Qinbin; Liou, Kuo-Nan; Qi, Ling; Tao, Shu; Schwarz, Joshua P.

2016-03-01

We develop and examine a microphysics-based black carbon (BC) aerosol aging scheme that accounts for condensation, coagulation, and heterogeneous chemical oxidation processes in a global 3-D chemical transport model (GEOS-Chem) by interpreting the BC measurements from the HIAPER Pole-to-Pole Observations (HIPPO, 2009-2011) using the model. We convert aerosol mass in the model to number concentration by assuming lognormal aerosol size distributions and compute the microphysical BC aging rate (excluding chemical oxidation aging) explicitly from the condensation of soluble materials onto hydrophobic BC and the coagulation between hydrophobic BC and preexisting soluble particles. The chemical oxidation aging is tested in the sensitivity simulation. The microphysical aging rate is ˜ 4 times higher in the lower troposphere over source regions than that from a fixed aging scheme with an e-folding time of 1.2 days. The higher aging rate reflects the large emissions of sulfate-nitrate and secondary organic aerosol precursors hence faster BC aging through condensation and coagulation. In contrast, the microphysical aging is more than 5-fold slower than the fixed aging in remote regions, where condensation and coagulation are weak. Globally, BC microphysical aging is dominated by condensation, while coagulation contribution is largest over eastern China, India, and central Africa. The fixed aging scheme results in an overestimate of HIPPO BC throughout the troposphere by a factor of 6 on average. The microphysical scheme reduces this discrepancy by a factor of ˜ 3, particularly in the middle and upper troposphere. It also leads to a 3-fold reduction in model bias in the latitudinal BC column burden averaged along the HIPPO flight tracks, with largest improvements in the tropics. The resulting global annual mean BC lifetime is 4.2 days and BC burden is 0.25 mg m-2, with 7.3 % of the burden at high altitudes (above 5 km). Wet scavenging accounts for 80.3 % of global BC deposition. We find that, in source regions, the microphysical aging rate is insensitive to aerosol size distribution, condensation threshold, and chemical oxidation aging, while it is the opposite in remote regions, where the aging rate is orders of magnitude smaller. As a result, global BC burden and lifetime show little sensitivity (< 5 % change) to these three factors.

Microphysics-based black carbon aging in a global CTM: constraints from HIPPO observations and implications for global black carbon budget

NASA Astrophysics Data System (ADS)

He, C.; Li, Q.; Liou, K. N.; Qi, L.; Tao, S.; Schwarz, J. P.

2015-11-01

We develop and examine a microphysics-based black carbon (BC) aerosol aging scheme that accounts for condensation and coagulation processes in a global 3-D chemical transport model (GEOS-Chem) by interpreting the BC measurements from the HIAPER Pole-to-Pole Observations (HIPPO, 2009-2011) using the model. We convert aerosol mass in the model to number concentration by assuming lognormal aerosol size distributions and compute the microphysical BC aging rate explicitly from the condensation of soluble materials onto hydrophobic BC and the coagulation between hydrophobic BC and preexisting soluble particles. The resulting aging rate is ∼ 4 times higher in the lower troposphere over source regions than that from a fixed aging scheme with an e-folding time of 1.2 days. The higher aging rate reflects the large emissions of sulfate-nitrate and secondary organic aerosol precursors hence faster BC aging through condensation and coagulation. In contrast, the microphysical aging is more than fivefold slower than the fixed aging in remote regions, where condensation and coagulation are weak. Globally BC microphysical aging is dominated by condensation, while coagulation contribution is largest over East China, India, and Central Africa. The fixed aging scheme results in an overestimate of HIPPO BC throughout the troposphere by a factor of 6 on average. The microphysical scheme reduces this discrepancy by a factor of ∼ 3, particularly in the middle and upper troposphere. It also leads to a threefold reduction in model bias in the latitudinal BC column burden averaged along the HIPPO flight tracks, with largest improvements in the tropics. The resulting global annual mean BC lifetime is 4.2 days and BC burden is 0.25 mg m-2, with 7.3 % of the burden at high altitudes (above 5 km). Wet scavenging accounts for 80.3 % of global BC deposition. We find that in source regions the microphysical aging rate is insensitive to aerosol size distribution, condensation threshold, and chemical oxidation aging, while it is the opposite in remote regions, where the aging rate is orders of magnitude smaller. As a result, global BC burden and lifetime show little sensitivity (< 5 % change) to these three factors.

Electric injury, Part II: Specific injuries.

PubMed

Fish, R M

2000-01-01

Electric injury can cause disruption of cardiac rhythm and breathing, burns, fractures, dislocations, rhabdomyolysis, eye and ear injury, oral and gastrointestinal injury, vascular damage, disseminated intravascular coagulation, peripheral and spinal cord injury, and Reflex Sympathetic Dystrophy. Secondary trauma from falls, fires, flying debris, and inhalation injury can complicate the clinical picture. Diagnostic and treatment considerations for electric injuries are described in this article, which is the second part of a three-part series on electric injuries.

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

A global quantitative survey of hemostatic assessment in postpartum hemorrhage and experience with associated bleeding disorders.

PubMed

James, Andra H; Cooper, David L; Paidas, Michael J

2017-01-01

Coagulopathy may be a serious complicating or contributing factor to postpartum hemorrhage (PPH), and should be promptly recognized to ensure proper bleeding management. This study aims to evaluate the approaches of obstetrician-gynecologists worldwide towards assessing massive PPH caused by underlying bleeding disorders. A quantitative survey was completed by 302 obstetrician-gynecologists from 6 countries (the UK, France, Germany, Italy, Spain, and Japan). The survey included questions on the use of hematologic laboratory studies, interpretation of results, laboratory's role in coagulation assessments, and experience with bleeding disorders. Overall, the most common definitions of "massive" PPH were >2,000 mL (39%) and >1,500 mL (34%) blood loss. The most common criteria for rechecking a "stat" complete blood count and for performing coagulation studies were a drop in blood pressure (73%) and ongoing visible bleeding (78%), respectively. Laboratory coagulation (prothrombin time/activated partial thromboplastin time [PT/aPTT]) and factor VIII/IX assays were performed on-site more often than were mixing studies (laboratory coagulation studies, 93%; factor VIII/IX assays, 63%; mixing studies, 22%). Most commonly consulted sources of additional information were colleagues within one's own specialty (68%) and other specialists (67%). Most respondents had consulted with a hematologist (78%; least, Germany [56%]; greatest, UK [98%]). The most common reason for not consulting was hematologist unavailability (44%). The most commonly reported thresholds for concern with PT and aPTT were 13 to 20 seconds (36%) and 30 to 45 seconds (50%), respectively. Most respondents reported having discovered an underlying bleeding disorder (58%; least, Japan [35%]; greatest, Spain [74%]). Global survey results highlight similarities and differences between countries in how PPH is assessed and varying levels of obstetrician-gynecologist experience with identification of underlying bleeding disorders and engagement of hematology consultants. Opportunities to improve patient management of PPH associated with bleeding disorders include greater familiarity with interpreting PT/aPTT test results and identification of and consistent consultation with hematologists with relevant expertise.

Recurrence of cervical intraepithelial lesions after thermo-coagulation in HIV-positive and HIV-negative Nigerian women.

PubMed

Oga, Emmanuel A; Brown, Jessica P; Brown, Clayton; Dareng, Eileen; Adekanmbi, Victor; Odutola, Michael; Olaniyan, Olayinka; Offiong, Richard; Obende, Kayode; Adewole, Ayodele Stephen; Peter, Achara; Dakum, Patrick; Adebamowo, Clement

2016-05-11

The burden of cervical cancer remains huge globally, more so in sub-Saharan Africa. Effectiveness of screening, rates of recurrence following treatment and factors driving these in Africans have not been sufficiently studied. The purpose of this study therefore was to investigate factors associated with recurrence of cervical intraepithelial lesions following thermo-coagulation in HIV-positive and HIV-negative Nigerian women using Visual Inspection with Acetic Acid (VIA) or Lugol's Iodine (VILI) for diagnosis. A retrospective cohort study was conducted, recruiting participants from the cervical cancer "see and treat" program of IHVN. Data from 6 sites collected over a 4-year period was used. Inclusion criteria were: age ≥18 years, baseline HIV status known, VIA or VILI positive and thermo-coagulation done. Logistic regression was performed to examine the proportion of women with recurrence and to examine factors associated with recurrence. Out of 177 women included in study, 67.8 % (120/177) were HIV-positive and 32.2 % (57/177) were HIV-negative. Recurrence occurred in 16.4 % (29/177) of participants; this was 18.3 % (22/120) in HIV-positive women compared to 12.3 % (7/57) in HIV-negative women but this difference was not statistically significant (p-value 0.31). Women aged ≥30 years were much less likely to develop recurrence, adjusted OR = 0.34 (95 % CI = 0.13, 0.92). Among HIV-positive women, CD4 count <200cells/mm(3) was associated with recurrence, adjusted OR = 5.47 (95 % CI = 1.24, 24.18). Recurrence of VIA or VILI positive lesions after thermo-coagulation occurs in a significant proportion of women. HIV-positive women with low CD4 counts are at increased risk of recurrent lesions and may be related to immunosuppression.

Safety of recombinant human factor XIII in a cynomolgus monkey model of extracorporeal blood circulation.

PubMed

Ponce, R; Armstrong, K; Andrews, K; Hensler, J; Waggie, K; Heffernan, J; Reynolds, T; Rogge, M

2005-01-01

Factor XIII (FXIII) is a thrombin-activated plasma coagulation factor critical for blood clot stabilization and longevity. Administration of exogenous FXIII to replenish depleted stores after major surgery, including cardiopulmonary bypass, may reduce bleeding complications and transfusion requirements. Thus, a model of extracorporeal circulation (ECC) was developed in adult male cynomolgus monkeys (Macaca fascicularis) to evaluate the nonclinical safety of recombinant human FXIII (rFXIII). The hematological and coagulation profile in study animals during and after 2 h of ECC was similar to that reported for humans during and after cardiopulmonary bypass, including observations of anemia, thrombocytopenia, and activation of coagulation and platelets. Intravenous slow bolus injection of 300 U/kg (2.1 mg/kg) or 1000 U/kg (7 mg/kg) rFXIII after 2 h of ECC was well tolerated in study animals, and was associated with a dose-dependent increase in FXIII activity. No clinically significant effects in respiration, ECG, heart rate, blood pressure, body temperature, clinical chemistry, hematology (including platelet counts), or indicators of thrombosis (thrombin:anti-thrombin complex and D-Dimer) or platelet activation (platelet factor 4 and beta-thromboglobulin) were related to rFXIII administration. Specific examination of brain, heart, lung, liver, and kidney from rFXIII-treated animals provided no evidence of histopathological alterations suggestive of subclinical hemorrhage or thrombosis. Taken as a whole, the results demonstrate the ECC model suitably replicated the clinical presentation reported for humans during and after cardiopulmonary bypass surgery, and do not suggest significant concerns regarding use of rFXIII in replacement therapy after extracorporeal circulation.

Anticoagulant activity in salivary glands of the insect vector Culicoides variipennis sonorensis by an inhibitor of factor Xa.

PubMed

Pérez de León, A A; Valenzuela, J G; Tabachnick, W J

1998-02-01

Blood feeding by the insect vector Culicoides variipennis sonorensis involves laceration of superficial host tissues, an injury that would be expected to trigger the coagulation cascade. Accordingly, the salivary glands of C.v. sonorensis were examined for the presence of an antihemostatic that prevents blood coagulation. Assays using salivary gland extracts showed a delay in the recalcification time of plasma devoid of platelets, indicating the presence of anticoagulant activity. Retardation in the formation of a fibrin clot was also observed after the addition of tissue factor to plasma that was preincubated with salivary gland extracts. Similarly, an inhibitory effect by salivary gland extracts was detected in assays that included factors of the intrinsic pathway. Inhibition of the catalytic activity of purified factor Xa toward its chromogenic substrate suggested that it was the target of the salivary anticoagulant of C.v. sonorensis. This was corroborated by the coincidence of anticoagulant and anti-FXa activities obtained by reverse-phase HPLC. The depletion of anti-FXa activity from salivary glands during blood feeding suggests that the FXa inhibitor functions as anticoagulant. Molecular sieving HPLC yielded an apparent molecular mass of 28 kDa for the salivary FXa inhibitor of C.v. sonorensis. Preventing the formation of thrombin through the inhibition of FXa likely facilitates blood feeding by maintaining the pool of blood fluid at the feeding site. The salivary FXa inhibitor of C.v. sonorensis could impair the network of host-defense mechanisms in the skin microenvironment by avoiding blood coagulation at the site of feeding.

Hemostatic properties and protein expression profile of therapeutic apheresis plasma treated with amotosalen and ultraviolet A for pathogen inactivation.

PubMed

Ohlmann, Philippe; Hechler, Béatrice; Chafey, Philippe; Ravanat, Catherine; Isola, Hervé; Wiesel, Marie-Louise; Cazenave, Jean-Pierre; Gachet, Christian

2016-09-01

The INTERCEPT Blood System (IBS) using amotosalen-HCl and ultraviolet (UV)A inactivates a large spectrum of microbial pathogens and white blood cells in therapeutic plasma. Our aim was to evaluate to what extent IBS modifies the capacity of plasma to generate thrombin and induces qualitative or quantitative modifications of plasma proteins. Plasma units from four donors were collected by apheresis. Samples were taken before (control [CTRL]) and after IBS treatment and stored at -80°C until use. The activities of plasma coagulation factors and inhibitors and the thrombin generation potential were determined using assays measuring clotting times and the calibrated automated thrombogram (CAT), respectively. The proteomic profile of plasma proteins was examined using a two-dimensional differential in-gel electrophoresis (2D-DIGE) method. Nearly all of the procoagulant and antithrombotic factors tested retained at least 78% of their initial pre-IBS activity. Only FVII and FVIII displayed a lower level of conservation (67%), which nevertheless remained within the reference range for conventional plasma coagulation factors. The thrombin generation profile of plasma was conserved after IBS treatment. Among the 1331 protein spots revealed by 2D-DIGE analysis, only four were differentially expressed in IBS plasma compared to CTRL plasma and two were identified by mass spectrometric analysis as transthyretin and apolipoprotein A1. The IBS technique for plasma moderately decreases the activities of plasma coagulation factors and antithrombotic proteins, with no impact on the thrombin generation potential of plasma and very limited modifications of the proteomic profile. © 2016 AABB.

Pharmacogenomics of Anti-platelet and Anti-coagulation Therapy

PubMed Central

Fisch, Adam S.; Perry, Christina G.; Stephens, Sarah H.; Horenstein, Richard B.; Shuldiner, Alan R.

2013-01-01

Arterial thrombosis is a major component of vascular disease, especially myocardial infarction (MI) and stroke. Current anti-thrombotic therapies such as warfarin and clopidogrel are effective in inhibiting cardiovascular events; however, there is great inter-individual variability in response to these medications. In recent years, it has been recognized that genetic factors play a significant role in drug response, and, subsequently, common variants in genes responsible for metabolism and drug action have been identified. These discoveries along with the new diagnostic targets and therapeutic strategies on the horizon hold promise for more effective individualized anti-coagulation and anti-platelet therapy. PMID:23797323

Moringa oleifera-mediated coagulation of textile wastewater and its biodegradation using novel consortium-BBA grown on agricultural waste substratum.

PubMed

Bedekar, Priyanka A; Bhalkar, Bhumika N; Patil, Swapnil M; Govindwar, Sanjay P

2016-10-01

Generation of secondary sludge is a major concern of textile dye removal by coagulation process. Combinatorial coagulation-biodegradation treatment system has been found efficient in degradation of coagulated textile dye sludge. Moringa oleifera seed powder (700 mg L -1 ) was able to coagulate textile dyestuff from real textile wastewater with 98 % color removal. Novel consortium-BBA was found to decolorize coagulated dye sludge. Parameters that significantly affect coagulation process were optimized using response surface methodology. The bench-scale stirred tank reactor (50-L capacity) designed with optimized parameters for coagulation process could efficiently remove 98, 89, 78, and 67 % of American Dye Manufacturer's Institute (ADMI) in four repetitive cycles, respectively. Solid-state fermentation composting reactor designed to treat coagulated dye sludge showed 96 % removal of dye within 10 days. Coagulation of dyes from textile wastewater and degradation of coagulated dye sludge were confirmed by Fourier transform infrared spectroscopy (FTIR) analysis. Cell morphology assay, comet assay, and phytotoxicity confirmed the formation of less toxic products after coagulation and degradation mechanism.

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 repartitioning in dairy cows exposed to HS. Our findings expand our current knowledge on the effects of HS on plasma proteomics in dairy cows and offer a new perspective for future research. Copyright © 2016 Elsevier B.V. All rights reserved.

Blood coagulation system in patients with chronic kidney disease: a prospective observational study

PubMed Central

Huang, Meng-Jie; Wei, Ri-bao; Wang, Yang; Su, Ting-yu; Di, Ping; Li, Qing-ping; Yang, Xi; Li, Ping; Chen, Xiang-mei

2017-01-01

Objectives Thromboembolic events are the major factor affecting the prognosis of patients with chronic kidney disease (CKD). Haemostatic alterations are possible causes of these complications, but their roles remain poorly characterised. In the prospective observational study, we investigated the entire coagulation process in patients with CKD to elucidate the mechanisms of their high thromboembolic risk. Methods A total of 95 patients with CKD and 20 healthy controls who met the inclusion criteria were consecutively recruited from September 2015 to March 2016. The platelet count, platelet aggregation, von Willebrand factor antigen (vWF:Ag), vWF ristocetin cofactor activity (vWF:RCo), fibrinogen, factor V (FV), FVII, FVIII, antithrombin III, protein C, protein S, D-dimer, standard coagulation tests and thromboelastography were measured in patients with CKD and controls. Associations between the estimated glomerular filtration rate (eGFR) and haemostatic biomarkers were tested using multivariable linear regression. Results The adjusted and unadjusted levels of vWF:Ag, vWF:RCo, fibrinogen, FVII, FVIII and D-dimer were significantly higher in patients with CKD than that in the healthy controls, and were elevated with CKD progression. However, after adjustment for baseline differences, platelet aggregation and thromboelastography parameters showed no significant differences between patients with CKD and healthy controls. In the correlation analysis, vWF:Ag, vWF:RCo and FVIII were inversely associated with eGFR (r=−0.359, p<0.001; r=−0.391, p<0.001; r=−0.327, p<0.001, respectively). During the 1-year of follow-up, one cardiovascular event occurred in patients with CKD 5 stage, whereas no thromboembolic event occurred in the CKD 3 and 4 and control groups. Conclusions Patients with CKD are characterised by endothelial dysfunction and increased coagulation, especially FVIII activity. The abnormal haemostatic profiles may contribute to the elevated risk of thrombotic events but further longer-term study with large samples is still required to more precisely determine the relationship between the elevation of procoagulant factors and clinical outcomes. PMID:28576889

Blood coagulation system in patients with chronic kidney disease: a prospective observational study.

PubMed

Huang, Meng-Jie; Wei, Ri-Bao; Wang, Yang; Su, Ting-Yu; Di, Ping; Li, Qing-Ping; Yang, Xi; Li, Ping; Chen, Xiang-Mei

2017-06-01

Thromboembolic events are the major factor affecting the prognosis of patients with chronic kidney disease (CKD). Haemostatic alterations are possible causes of these complications, but their roles remain poorly characterised. In the prospective observational study, we investigated the entire coagulation process in patients with CKD to elucidate the mechanisms of their high thromboembolic risk. A total of 95 patients with CKD and 20 healthy controls who met the inclusion criteria were consecutively recruited from September 2015 to March 2016. The platelet count, platelet aggregation, von Willebrand factor antigen (vWF:Ag), vWF ristocetin cofactor activity (vWF:RCo), fibrinogen, factor V (FV), FVII, FVIII, antithrombin III, protein C, protein S, D-dimer, standard coagulation tests and thromboelastography were measured in patients with CKD and controls. Associations between the estimated glomerular filtration rate (eGFR) and haemostatic biomarkers were tested using multivariable linear regression. The adjusted and unadjusted levels of vWF:Ag, vWF:RCo, fibrinogen, FVII, FVIII and D-dimer were significantly higher in patients with CKD than that in the healthy controls, and were elevated with CKD progression. However, after adjustment for baseline differences, platelet aggregation and thromboelastography parameters showed no significant differences between patients with CKD and healthy controls. In the correlation analysis, vWF:Ag, vWF:RCo and FVIII were inversely associated with eGFR (r=-0.359, p<0.001; r=-0.391, p<0.001; r=-0.327, p<0.001, respectively). During the 1-year of follow-up, one cardiovascular event occurred in patients with CKD 5 stage, whereas no thromboembolic event occurred in the CKD 3 and 4 and control groups. Patients with CKD are characterised by endothelial dysfunction and increased coagulation, especially FVIII activity. The abnormal haemostatic profiles may contribute to the elevated risk of thrombotic events but further longer-term study with large samples is still required to more precisely determine the relationship between the elevation of procoagulant factors and clinical outcomes. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Ischemic Stroke Is Associated with the ABO Locus: The EuroCLOT Study

PubMed Central

Williams, Frances M K; Carter, Angela M; Hysi, Pirro G; Surdulescu, Gabriela; Hodgkiss, Dylan; Soranzo, Nicole; Traylor, Matthew; Bevan, Steve; Dichgans, Martin; Rothwell, Peter M W; Sudlow, Cathie; Farrall, Martin; Silander, Kaisa; Kaunisto, Mari; Wagner, Peter; Saarela, Olli; Kuulasmaa, Kari; Virtamo, Jarmo; Salomaa, Veikko; Amouyel, Philippe; Arveiler, Dominique; Ferrieres, Jean; Wiklund, Per-Gunnar; Arfan Ikram, M; Hofman, Albert; Boncoraglio, Giorgio B; Parati, Eugenio A; Helgadottir, Anna; Gretarsdottir, Solveig; Thorsteinsdottir, Unnur; Thorleifsson, Gudmar; Stefansson, Kari; Seshadri, Sudha; DeStefano, Anita; Gschwendtner, Andreas; Psaty, Bruce; Longstreth, Will; Mitchell, Braxton D; Cheng, Yu-Ching; Clarke, Robert; Ferrario, Marco; Bis, Joshua C; Levi, Christopher; Attia, John; Holliday, Elizabeth G; Scott, Rodney J; Fornage, Myriam; Sharma, Pankaj; Furie, Karen L; Rosand, Jonathan; Nalls, Mike; Meschia, James; Mosely, Thomas H; Evans, Alun; Palotie, Aarno; Markus, Hugh S; Grant, Peter J; Spector, Tim D

2013-01-01

Objective End-stage coagulation and the structure/function of fibrin are implicated in the pathogenesis of ischemic stroke. We explored whether genetic variants associated with end-stage coagulation in healthy REFVIDunteers account for the genetic predisposition to ischemic stroke and examined their influence on stroke subtype. Methods Common genetic variants identified through genome-wide association studies of coagulation factors and fibrin structure/function in healthy twins (n = 2,100, Stage 1) were examined in ischemic stroke (n = 4,200 cases) using 2 independent samples of European ancestry (Stage 2). A third clinical collection having stroke subtyping (total 8,900 cases, 55,000 controls) was used for replication (Stage 3). Results Stage 1 identified 524 single nucleotide polymorphisms (SNPs) from 23 linkage disequilibrium blocks having significant association (p < 5 × 10–8) with 1 or more coagulation/fibrin phenotypes. The most striking associations included SNP rs5985 with factor XIII activity (p = 2.6 × 10–186), rs10665 with FVII (p = 2.4 × 10–47), and rs505922 in the ABO gene with both von Willebrand factor (p = 4.7 × 10–57) and factor VIII (p = 1.2 × 10–36). In Stage 2, the 23 independent SNPs were examined in stroke cases/noncases using MOnica Risk, Genetics, Archiving and Monograph (MORGAM) and Wellcome Trust Case Control Consortium 2 collections. SNP rs505922 was nominally associated with ischemic stroke (odds ratio = 0.94, 95% confidence interval = 0.88–0.99, p = 0.023). Independent replication in Meta-Stroke confirmed the rs505922 association with stroke, beta (standard error, SE) = 0.066 (0.02), p = 0.001, a finding specific to large-vessel and cardioembolic stroke (p = 0.001 and p = < 0.001, respectively) but not seen with small-vessel stroke (p = 0.811). Interpretation ABO gene variants are associated with large-vessel and cardioembolic stroke but not small-vessel disease. This work sheds light on the different pathogenic mechanisms underpinning stroke subtype. Ann Neurol 2013 PMID:23381943

Discovery of novel aminobenzisoxazole derivatives as orally available factor IXa inhibitors

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

Sakurada, Isao; Endo, Toshiya; Hikita, Katsuyoshi

2017-06-01

Using structure based drug design, novel aminobenzisoxazoles as coagulation factor IXa inhibitors were designed and synthesized. Highly selective inhibition of FIXa over FXa was demonstrated. Anticoagulation profile of selected compounds was evaluated by aPTT and PT tests. In vitro ADMET and pharmacokinetic (PK) profiles were also evaluated.

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.

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 acids might partially ameliorate SCD-associated chronic coagulopathic state.

A Drosophila haemocyte-specific protein, hemolectin, similar to human von Willebrand factor.

PubMed Central

Goto, A; Kumagai, T; Kumagai, C; Hirose, J; Narita, H; Mori, H; Kadowaki, T; Beck, K; Kitagawa, Y

2001-01-01

We identified a novel Drosophila protein of approximately 400 kDa, hemolectin (d-Hml), secreted from haemocyte-derived Kc167 cells. Its 11.7 kbp cDNA contains an open reading frame of 3843 amino acid residues, with conserved domains in von Willebrand factor (VWF), coagulation factor V/VIII and complement factors. The d-hml gene is located on the third chromosome (position 70C1-5) and consists of 26 exons. The major part of d-Hml consists of well-known motifs with the organization: CP1-EG1-CP2-EG2-CP3-VD1-VD2-VD'-VD3-VC1-VD"-VD"'-FC1-FC2-VC2-LA1-VD4-VD5-VC3-VB1-VB2-VC4-VC5-CK1 (CP, complement-control protein domain; EG, epidermal-growth-factor-like domain; VB, VC, VD, VWF type B-, C- and D-like domains; VD', VD", VD"', truncated C-terminal VDs; FC, coagulation factor V/VIII type C domain; LA, low-density-lipoprotein-receptor class A domain; CK, cysteine knot domain). The organization of VD1-VD2-VD'-VD3, essential for VWF to be processed by furin, to bind to coagulation factor VIII and to form interchain disulphide linkages, is conserved. The 400 kDa form of d-Hml was sensitive to acidic cleavage near the boundary between VD2 and VD', where the cleavage site of pro-VWF is located. Agarose-gel electrophoresis of metabolically radiolabelled d-Hml suggested that it is secreted from Kc167 cells mainly as dimers. Resembling VWF, 7.9% (305 residues) of cysteine residues on the d-Hml sequence had well-conserved positions in each motif. Coinciding with the development of phagocytic haemocytes, d-hml transcript was detected in late embryos and larvae. Its low-level expression in adult flies was induced by injury at any position on the body. PMID:11563973

Severe coagulation factor VII deficiency caused by a novel homozygous mutation (p. Trp284Gly) in loop 140s.

PubMed

Hao, Xiuping; Cheng, XiaoLi; Ye, Jiajia; Wang, Yingyu; Yang, LiHong; Wang, Mingshan; Jin, Yanhui

2016-06-01

Congenital coagulation factor VII (FVII) deficiency is a rare disorder caused by mutation in F7 gene. Herein, we reported a patient who had unexplained hematuria and vertigo with consanguineous parents. He has been diagnosed as having FVII deficiency based on the results of reduced FVII activity (2.0%) and antigen (12.8%). The thrombin generation tests verified that the proband has obstacles in producing thrombin. Direct sequencing analysis revealed a novel homozygous missense mutation p.Trp284Gly. Also noteworthy is the fact that the mutational residue belongs to structurally conserved loop 140s, which majorly undergo rearrangement after FVII activation. Model analysis indicated that the substitution disrupts these native hydrophobic interactions, which are of great importance to the conformation in the activation domain of FVIIa.

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

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.

Biomass fly ashes as low-cost chemical agents for Pb removal from synthetic and industrial wastewaters.

PubMed

Barbosa, Rui; Lapa, Nuno; Lopes, Helena; Günther, Annika; Dias, Diogo; Mendes, Benilde

2014-06-15

The main aim of this work was to study the removal efficiency of Pb from synthetic and industrial wastewaters by using biomass fly ashes. The biomass fly ashes were produced in a biomass boiler of a pulp and paper industry. Three concentrations of Pb(2+) were tested in the synthetic wastewater (1, 10 and 1000 mg Pb/L). Moreover, two different wastewaters were collected in an industrial wastewater treatment plant (IWWTP) of an industry of lead-acid batteries: (i) wastewater of the equalization tank, and (ii) IWWTP effluent. All the wastewaters were submitted to coagulation-flocculation tests with a wide range of biomass fly ashes dosage (expressed as Solid/Liquid - S/L - ratios). All supernatants were characterized for chemical and ecotoxicological parameters. The use of biomass fly ashes has reduced significantly the Pb concentration in the synthetic wastewater and in the wastewaters collected in the IWWTP. For example, the definitive coagulation-flocculation assays performed over the IWWTP effluent presented a very low concentration of Pb (0.35 mg/L) for the S/L ratio of 1.23 g/L. Globally, the ecotoxicological characterization of the supernatants resulting from the coagulation-flocculation assays of all wastewaters has indicated an overall reduction on the ecotoxicity of the crude wastewaters, due to the removal of Pb. Copyright © 2014 Elsevier Inc. All rights reserved.

[Coagulation and adsorption on treating the Yellow River and the impact on chlorine decay during chlorination process].

PubMed

Zhan, Xiao; Gao, Bao-yu; Liu, Bin; Xu, Chun-hua; Yue, Qin-yan

2010-05-01

Two types of inorganic polymer coagulants, polyferric chloride (PFC) and polyaluminum chloride (PAC), were chosen to treat the Yellow River water. Different dosages were investigated in order to investigate the turbidity, UV24, DOC and permanganate index removal efficiency and their coagulation mechanisms based on the Zeta potentials. The natural organic matter removal by the combination of coagulation and adsorption with powder activated carbon were analyzed based on different coagulant and adsorbent dosages and dosing orders. The effects of combination of coagulation and adsorption on the residual chlorine decay were analyzed. The results showed that the two coagulants had high turbidity removal efficiency ( > 90%). The UV254, DOC, permanganate index removal efficiency were 29.2%, 26.1% and 27.9% respectively for PAC coagulation and were 32.3%, 23.3% and 32.9% respectively for PFC. Electric neutralization played an important role in the PAC coagulation process while both adsorption bridging and electric neutralization performed when PFC was used. The removal percentage of organic matter increased with the increase coagulant and adsorbent. The adsorption after coagulation process gave the better UV254 and DOC removal efficiency than the coagulation after adsorption. The UV254 and DOC removal efficiency were 95.2% and 99.9% for PAC coagulation after adsorption and were 90.1% and 99.9% for PFC coagulation first. But adding powder activated carbon can improve floc settlement performance and maintained persistent disinfection effect.

A Computational Chemo-Fluidic Modeling for the Investigation of Patient-Specific Left Ventricle Thrombogenesis

NASA Astrophysics Data System (ADS)

Mittal, Rajat; Seo, Jung Hee; Abd, Thura; George, Richard T.

2015-11-01

Patients recovering from myocardial infarction (MI) are considered at high-risk for cardioembolic stroke due to the formation of left ventricle thrombus (LVT). The formation of LVT is the result of a complex interplay between the fluid dynamics inside the ventricle and the chemistry of coagulation, and the role of LV flow pattern on the thrombogenesis was not well understood. The previous computational study performed with the model ventricles suggested that the local flow residence time is the key variable governing the accumulation of coagulation factors. In the present study, a coupled, chemo-fluidic computational modeling is applied to the patient-specific cases of infracted ventricles to investigate the interaction between the LV hemodynamics and thrombogensis. In collaboration with the Johns Hopkins hospital, patient-specific LV models are constructed using the multi-modality medical imaging data. Blood flow in the left ventricle is simulated by solving the incompressible Navier-Stokes equations and the biochemical reactions for the thrombus formation are modeled with convection-diffusion-reaction equations. The formation and deposition of key coagulation chemical factors are then correlated with the hemodynamic flow metrics to explore the biophysics underlying LVT risk. Supported by the Johns Hopkins Medicine Discovery Fund and NSF Grant: CBET-1511200, Computational resource by XSEDE NSF grant TG-CTS100002.

Leishmania amazonensis exhibits phosphatidylserine-dependent procoagulant activity, a process that is counteracted by sandfly saliva

PubMed Central

Rochael, Natalia Cadaxo; Lima, Luize Gonçalves; de Oliveira, Sandra Maria Pereira; Barcinski, Marcello André; Saraiva, Elvira Maria; Monteiro, Robson Queiroz; Pinto-da-Silva, Lucia Helena

2013-01-01

Leishmania parasites expose phosphatidylserine (PS) on their surface, a process that has been associated with regulation of host's immune responses. In this study we demonstrate that PS exposure by metacyclic promastigotes of Leishmania amazonensis favours blood coagulation. L. amazonensis accelerates in vitro coagulation of human plasma. In addition, L. amazonensis supports the assembly of the prothrombinase complex, thus promoting thrombin formation. This process was reversed by annexin V which blocks PS binding sites. During blood meal, Lutzomyia longipalpis sandfly inject saliva in the bite site, which has a series of pharmacologically active compounds that inhibit blood coagulation. Since saliva and parasites are co-injected in the host during natural transmission, we evaluated the anticoagulant properties of sandfly saliva in counteracting the procoagulant activity of L. amazonensis . Lu. longipalpis saliva reverses plasma clotting promoted by promastigotes. It also inhibits thrombin formation by the prothrombinase complex assembled either in phosphatidylcholine (PC)/PS vesicles or in L. amazonensis . Sandfly saliva inhibits factor X activation by the intrinsic tenase complex assembled on PC/PS vesicles and blocks factor Xa catalytic activity. Altogether our results show that metacyclic promastigotes of L. amazonensis are procoagulant due to PS exposure. Notably, this effect is efficiently counteracted by sandfly saliva. PMID:24037188

Determinants of the Thrombogenic Potential of Multiwalled Carbon Nanotubes

PubMed Central

Burke, Andrew; Singh, Ravi; Carroll, David L.; Owen, John; Kock, Nancy D.; D’Agostino, Ralph; Torti, Frank M.; Torti, Suzy V.

2011-01-01

Multiwalled carbon nanotubes (MWCNTs) are cylindrical tubes of graphitic carbon with unique physical and electrical properties. MWCNTs are being explored for a variety of diagnostic and therapeutic applications. Successful biomedical application of MWCNTs will require compatibility with normal circulatory components, including constituents of the hemostatic cascades. In this manuscript, we compare the thrombotic activity of MWCNTs in vitro and in vivo. We also assess the influence of functionalization of MWCNTs on thrombotic activity. In vitro, MWCNT activate the intrinsic pathway of coagulation as measured by activated partial thromboplastin time (aPTT) assays. Functionalization by amidation or carboxylation enhances this procoagulant activity. Mechanistic studies demonstrate that MWCNTs enhance propagation of the intrinsic pathway via a non-classical mechanism strongly dependent on factor IX. MWCNTs preferentially associate with factor IXa and may provide a platform for its activation. In addition to their effects on the coagulation cascade, MWCNTs activate platelets in vitro, with amidated MWCNTs exhibiting greater platelet activation than carboxylated or pristine MWCNTs. However, contrasting trends are obtained in vivo, where functionalization tends to diminish rather than enhance pro-coagulant activity. Thus, following systemic injection of MWCNTs in mice, pristine MWCNTs decreased platelet counts, increased vWF, and increased D-dimers. In contrast, carboxylated MWCNTS exhibited little procoagulant tendency in vivo, eliciting only a mild and transient decrease in platelets. Amidated MWCNTs elicited no statistically significant change in platelet count. Further, neither carboxylated nor amidated MWCNTs increased vWF or D-dimers in mouse plasma. We conclude that the pro-coagulant tendencies of MWCNTs observed in vitro are not necessarily recapitulated in vivo. Further, functionalization can markedly attenuate the procoagulant activity of MWCNTs in vivo. This work will inform the rational development of biocompatible MWCNTs for systemic delivery. PMID:21663954

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

A prospective multicenter cohort study of the association between global tissue hypoxia and coagulation abnormalities during early sepsis resuscitation.

PubMed

Trzeciak, Stephen; Jones, Alan E; Shapiro, Nathan I; Pusateri, Anthony E; Arnold, Ryan C; Rizzuto, Michael; Arora, Tanisha; Parrillo, Joseph E; Dellinger, R Phillip

2010-04-01

Coagulation activation is an integral part of sepsis pathogenesis. Experimental data suggest that endothelial exposure to hypoxia activates coagulation. We aimed to test the hypothesis that the quantity of exposure to global tissue hypoxia is associated with the degree of coagulation activation during early sepsis resuscitation. Prospective, multicenter cohort study. Emergency department and intensive care unit of three academic hospitals. Inclusion criteria were age older than 17, acute infection with two or more signs of systemic inflammation, hypotension despite fluid challenge (or lactate >4 mM), and continuous central venous oxygen saturation (Scvo2) monitoring for quantitative resuscitation. Exclusion criteria were anticoagulant or blood product administration. We recorded central venous oxygen saturation continuously for 0 to 6 hrs of resuscitation and calculated the area under the curve for central venous oxygen saturation <70%. We defined hypoxia exposure as exceeding the median area under the curve for the entire cohort. At 0, 6, and 24 hrs, we measured conventional coagulation biomarkers plus thrombin-antithrombin complex, plasmin-antiplasmin complex, tissue plasminogen activator, plasminogen activator inhibitor-1, protein C, antithrombin, and endothelial markers (E-selectin, intracellular adhesion molecule-1, thrombomodulin). We compared changes during 0 to 6 hrs and 0 to 24 hrs in biomarkers between hypoxia exposure and nonexposure groups. We enrolled 40 patients (60% requiring vasopressors; 30% mortality). We found that exposure to hypoxia alone was not associated with a significant degree of coagulation activation. However, in secondary analyses we found that exposure to arterial hypotension induced E-selectin and thrombin-antithrombin complex, whereas concomitant exposure to both hypotension and hypoxia was associated with amplification of E-selectin and thrombomodulin, and a reduction in protein C. In this sample of patients undergoing quantitative resuscitation for sepsis, we found that exposure to global tissue hypoxia (as quantified by low central venous oxygen saturation) was not associated with major coagulation activation. Further investigation to elucidate the clinical factors that trigger or intensify the procoagulant response to sepsis is warranted.

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 and the PT or aPTT are repeated on the 1:1 mix. Factor activity assays are most commonly performed as a one-stage assay. The patient's citrated plasma is diluted and mixed 1-to-1 with a single factor-deficient substrate plasma. A PT or aPTT is performed on the above mix, depending on the factor being tested.Factor inhibitors are antibodies that are most commonly diagnosed in male patients with severe hemophilia A (FVIII deficiency) where they are induced by factor replacement therapy.Factor inhibitors can also appear in the form of spontaneous autoantibodies in both male and female individuals who were previously well. This is an autoimmune condition called "acquired hemophilia."Most coagulation laboratories can measure the plasma concentration of VWF protein (VWF antigen) by an immunoturbidimetric technique. Testing the functional activity of VWF, utilizes the drug ristocetin.The state of multimerization of VWF is important and is assessed by electrophoresis on agarose gels. Type 2a and 2b VWD are associated with the lack of intermediate- and high molecular weight multimers.The antiphospholipid syndrome (APLS) is an acquired autoimmune phenomenon associated with an increased incidence of both venous and arterial thromboses, as well as fetal loss. Typically, there is a paradoxical prolongation of the aPTT in the absence of any clinical features of bleeding. This is the so-called "lupus anticoagulant (LA) effect." The laboratory definition of the APLS requires the presence of either a "lupus anticoagulant" or a persistent titer of antiphospholipid antibodies.There are now 2 broad classes of direct-acting oral anticoagulants (DOACs): [1] The oral direct thrombin inhibitors (DTIs) such as dabigatran; and [2] The oral direct factor Xa inhibitors such as rivaroxaban and apixaban. The PT and aPTT are variably affected by the DOACs and are generally unhelpful in monitoring their concentrations. Most importantly, a normal PT or aPTT does NOT exclude the presence of any of the DOACs. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

Inactivation of Pathogenic Microorganisms in Infectious Medical Waste. A Literature Review of Current On-Site Treatment Technologies.

DTIC Science & Technology

1992-01-01

by thermal inactivation, removal in soil, and dilution in ground and surface waters . 0 18 Chapter II: Treatment Technologies Kinetics of Thermal...reaction with water in which the proteins coagulate or precipitate. This is analogous to heat transforming the raw egg medium into a rigid egg white...to either allow germination and outgrowth after adsorption and diffusion of nutrients and water , or penetration of high energy levels of heat which

Immunogenicity and immune tolerance coagulation Factors VIII and IX.

PubMed

Rup, B

2003-01-01

Some of the major issues related to the development and control of antibodies that occur during treatment of haemophilia with replacement factors (Factor VIII and Factor IX) are reviewed. Information on analytical issues, immunogenicity, and immune tolerance may be applicable to the study of other therapeutic proteins. Conversely, new information obtained from evaluation of other therapeutic protein products may address issues that remain unresolved for Factor VIII and FIX replacement therapy.

A randomized, double-blind, phase I/II trial of tumor necrosis factor and interferon-gamma for treatment of AIDS-related complex (Protocol 025 from the AIDS Clinical Trials Group).

PubMed

Agosti, J M; Coombs, R W; Collier, A C; Paradise, M A; Benedetti, J K; Jaffe, H S; Corey, L

1992-05-01

To determine safety and efficacy of tumor necrosis factor (TNF) and interferon-gamma (IFN gamma) in the treatment of patients with acquired immunodeficiency syndrome (AIDS)-related complex, a randomized, double-blind study was conducted. Twenty-five patients with AIDS-related complex and CD4 lymphocytes less than or equal to 500 x 10(6)/L attended an AIDS Clinical Trials Unit of a tertiary referral center. Patients were administered tumor necrosis factor (TNF) (10 micrograms/m2) or IFN gamma (10 micrograms/m2), or both intramuscularly three times weekly for 16 weeks. Side effects from all three preparations included fever, constitutional symptoms, and local reactions. No significant hematologic, hepatic, renal, or coagulation abnormalities were observed. CD4 lymphocyte counts, beta 2-microglobulin, p24 antigen levels, and anti-p24 antibody did not change significantly during therapy. Similarly, no significant change was noted in rates of HIV isolation from peripheral blood mononuclear cells or plasma. TNF and IFN gamma were tolerable after premedication with acetaminophen; however, no significant change in markers of human immunodeficiency virus infection was demonstrated. These cytokines alone do not appear to be of benefit, nor do they appear to hasten the progression of HIV infection.

Protein C and protein S deficiencies: similarities and differences between two brothers playing in the same game.

PubMed

Bereczky, Zsuzsanna; Kovács, Kitti B; Muszbek, László

2010-12-01

Protein C (PC) and protein S (PS) are vitamin K-dependent glycoproteins that play an important role in the regulation of blood coagulation as natural anticoagulants. PC is activated by thrombin and the resulting activated PC (APC) inactivates membrane-bound activated factor VIII and factor V. The free form of PS is an important cofactor of APC. Deficiencies in these proteins lead to an increased risk of venous thromboembolism; a few reports have also associated these deficiencies with arterial diseases. The degree of risk and the prevalence of PC and PS deficiency among patients with thrombosis and in those in the general population have been examined by several population studies with conflicting results, primarily due to methodological variability. The molecular genetic background of PC and PS deficiencies is heterogeneous. Most of the mutations cause type I deficiency (quantitative disorder). Type II deficiency (dysfunctional molecule) is diagnosed in approximately 5%-15% of cases. The diagnosis of PC and PS deficiencies is challenging; functional tests are influenced by several pre-analytical and analytical factors, and the diagnosis using molecular genetics also has special difficulties. Large gene segment deletions often remain undetected by DNA sequencing methods. The presence of the PS pseudogene makes genetic diagnosis even more complicated.

Fluid loss does not explain coagulation activation during air travel.

PubMed

Schreijer, Anja J M; Cannegieter, Suzanne C; Caramella, Marianna; Meijers, Joost C M; Krediet, Raymond T; Simons, Ries M; Rosendaal, Frits R

2008-06-01

The mechanism of air travel-related venous thrombosis is unclear. Although immobility plays a pivotal role, other factors such as fluid loss may contribute. We investigated whether fluid loss occurred more in individuals with coagulation activation after air travel than in subjects without. As a secondary aim, we investigated whether fluid loss per se occurred during air travel. In this crossover study, 71 healthy volunteers were exposed to eight hours of air travel, eight hours immobilization in a cinema, and a daily-life control situation. Markers of fluid loss (haematocrit, serum osmolality and albumin) and of coagulation activation were measured before and after each exposure. The study included 11 volunteers with and 55 volunteers without coagulation activation during the flight. The change in parameters of fluid loss was not different in volunteers with an activated clotting system from those without (difference between groups in haematocrit: -0.6%, 95% confidence interval [CI]: -1.9 to 0.6). On a group level, mean haematocrit values decreased during all three exposures. However, in some individuals it increased, which occurred in more participants during the flight (34%; 95% CI 22 to 46) than during the daily-life situation (19%; 95% CI 10 to 28). These findings do not support the hypothesis that fluid loss contributes to thrombus formation during air travel.

Aspects of platelet disturbances in haemodialysis patients

PubMed Central

Schoorl, Marianne; Grooteman, Muriel P.C.; Bartels, Piet C.M.; Nubé, Menso J.

2013-01-01

Patients with mild-to-chronic kidney disease (CKD) exhibit a variety of haemostatic disorders, ranging from an increased clotting tendency and reductions in the levels of natural inhibitors of coagulation to defective fibrinolysis. In addition, platelet (PLT) abnormalities are common. In this minireview, we report on aspects of haemodialysis (HD)-induced PLT activation. It is demonstrated that PLTs from HD patients are exhausted due to repeated stimulation of HD treatment and recurrent release of PLT degranulation products. During HD, additional aberrations of the haemostatic process occur. Besides deviations of coagulation and fibrinolysis, PLT activation and a reduction in their granule content have been observed during HD treatment. As HD treatment is carried out three times per week, month after month, chronic HD patients may suffer persistently from coagulation defects and PLT disorders on top of the alterations induced by the uraemic state itself. PLT activation occurs together with thrombin and fibrin generation. However, macro fibrin depositions in clot devices are not demonstrated, microaggregates occur not only in the extracorporeal circuit (ECC) but are also present in the blood circulation. As vascular access thrombosis is a frequent complication in patients with HD treatment, it is believed that hypercoagulability could result from vascular changes combined with PLTs and activation of coagulation factors. PMID:24596657

Realtime temperature determination during retinal photocoagulation on patients

NASA Astrophysics Data System (ADS)

Brinkmann, Ralf; Koinzer, Stefan; Schlott, Kerstin; Ptaszynski, Lars; Bever, Marco; Baade, Alex; Miura, Yoko; Birngruber, Reginald; Roider, Johann

2011-03-01

Retinal photocoagulation is a long time established treatment for a variety of retinal diseases, most commonly applied for diabetic macular edema and diabetic retinopathy. The damage extent of the induced thermal coagulations depend on the temperature increase and the time of irradiation. So far, the induced temperature rise is unknown due to intraocular variations in light transmission and scattering and RPE/choroidal pigmentation, which can vary inter- and intraindividually by more than a factor of four. Thus in clinical practice, often stronger and deeper coagulations are applied than therapeutically needed, which lead to extended retinal damage and strong pain perception. The final goal of this project focuses on a dosimetry control, which automatically generates a desired temperature profile and thus coagulation strength for every individual coagulation spot, ideally unburden the ophthalmologist from any laser settings. In this paper we present the first realtime temperature measurements achieved on patients during retinal photocoagulation by means of an optoacoustic method, making use of the temperature dependence of the thermal expansion coefficient of retinal tissue. Therefore, nanosecond probe laser pulses are repetitively and simultaneously applied with the treatment radiation in order to excite acoustic waves, which are detected at the cornea with an ultrasonic transducer embedded in the contact lens and then are processed by PC.

Innovative physico-chemical treatment of wastewater incorporating Moringa oleifera seed coagulant.

PubMed

Bhuptawat, Hitendra; Folkard, G K; Chaudhari, Sanjeev

2007-04-02

Moringa oleifera is a pan tropical, multipurpose tree whose seeds contain a high quality edible oil (up to 40% by weight) and water soluble proteins that act as effective coagulants for water and wastewater treatment. The use of this natural coagulant material has not yet realised its potential. A water extract of M. oleifera seed was applied to a wastewater treatment sequence comprising coagulation-flocculation-sedimentation-sand filtration. The study was laboratory based using an actual wastewater. Overall COD removals of 50% were achieved at both 50 and 100mg/l M. oleifera doses. When 50 and 100mg/l seed doses were applied in combination with 10mg/l of alum, COD removal increased to 58 and 64%, respectively. The majority of COD removal occurred during the filtration process. In the tests incorporating alum, sludge generation and filter head loss increased by factors of 3 and 2, respectively. These encouraging treatment results indicate that this may be the first treatment application that can move to large scale adoption. The simple water extract may be obtained at minimal cost from the presscake residue remaining after oil extraction from the seed. The regulatory compliance issues of adopting 'new materials' for wastewater treatment are significantly less stringent than those applying to the production of potable water.

A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.

PubMed

Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F; Hamaoka, Takafumi

2015-06-25

Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously.

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.

Comparison of single-step and two-step purified coagulants from Moringa oleifera seed for turbidity and DOC removal.

PubMed

Sánchez-Martín, J; Ghebremichael, K; Beltrán-Heredia, J

2010-08-01

The coagulant proteins from Moringa oleifera purified with single-step and two-step ion-exchange processes were used for the coagulation of surface water from Meuse river in The Netherlands. The performances of the two purified coagulants and the crude extract were assessed in terms of turbidity and DOC removal. The results indicated that the optimum dosage of the single-step purified coagulant was more than two times higher compared to the two-step purified coagulant in terms of turbidity removal. And the residual DOC in the two-step purified coagulant was lower than in single-step purified coagulant or crude extract. (c) 2010 Elsevier Ltd. All rights reserved.