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Sample records for blood coagulation activation

  1. Contact activation of blood-plasma coagulation.

    PubMed

    Vogler, Erwin A; Siedlecki, Christopher A

    2009-04-01

    This opinion identifies inconsistencies in the generally-accepted surface biophysics involved in contact activation of blood-plasma coagulation, reviews recent experimental work aimed at resolving inconsistencies, and concludes that this standard paradigm requires substantial revision to accommodate new experimental observations. Foremost among these new findings is that surface-catalyzed conversion of the blood zymogen factor XII (FXII, Hageman factor) to the enzyme FXIIa (FXII [surface] --> FXIIa, a.k.a. autoactivation) is not specific for anionic surfaces, as proposed by the standard paradigm. Furthermore, it is found that surface activation is moderated by the protein composition of the fluid phase in which FXII autoactivation occurs by what appears to be a protein-adsorption-competition effect. Both of these findings argue against the standard view that contact activation of plasma coagulation is potentiated by the assembly of activation-complex proteins (FXII, FXI, prekallikrein, and high-molecular weight kininogen) directly onto activating surfaces (procoagulants) through specific protein/surface interactions. These new findings supplement the observation that adsorption behavior of FXII and FXIIa is not remarkably different from a wide variety of other blood proteins surveyed. Similarity in adsorption properties further undermines the idea that FXII and/or FXIIa are distinguished from other blood proteins by unusual adsorption properties resulting in chemically-specific interactions with activating anionic surfaces. IMPACT STATEMENT: This review shows that the consensus biochemical mechanism of contact activation of blood-plasma coagulation that has long served as a rationale for poor hemocompatibility is an inadequate basis for surface engineering of advanced cardiovascular biomaterials.

  2. Contact activation of blood-plasma coagulation

    NASA Astrophysics Data System (ADS)

    Golas, Avantika

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

  3. Systemic blood coagulation activation in acute coronary syndromes

    PubMed Central

    Undas, Anetta; Szułdrzyński, Konstanty; Brummel-Ziedins, Kathleen E.; Tracz, Wiesława; Zmudka, Krzysztof

    2009-01-01

    We evaluated systemic alterations to the blood coagulation system that occur during a coronary thrombotic event. Peripheral blood coagulation in patients with acute coronary thrombosis was compared with that in people with stable coronary artery disease (CAD). Blood coagulation and platelet activation at the microvascular injury site were assessed using immunochemistry in 28 non-anticoagulated patients with acute myocardial infarction (AMI) versus 28 stable CAD patients matched for age, sex, risk factors, and medications. AMI was associated with increased maximum rates of thrombin-antithrombin complex generation (by 93.8%; P < .001), thrombin B-chain formation (by 57.1%; P < .001), prothrombin consumption (by 27.9%; P = .012), fibrinogen consumption (by 27.0%; P = .02), factor (f) Va light chain generation (by 44.2%; P = .003), and accelerated fVa inactivation (by 76.1%; P < .001), and with enhanced release of platelet-derived soluble CD40 ligand (by 44.4%; P < .001). FVa heavy chain availability was similar in both groups because of enhanced formation and activated protein C (APC)–mediated destruction. The velocity of coagulant reactions in AMI patients showed positive correlations with interleukin-6. Heparin treatment led to dampening of coagulant reactions with profiles similar to those for stable CAD. AMI-induced systemic activation of blood coagulation markedly modifies the pattern of coagulant reactions at the site of injury in peripheral vessels compared with that in stable CAD patients. PMID:18931343

  4. Blood coagulation activation and fibrinolysis during a downhill marathon run.

    PubMed

    Sumann, Günther; Fries, Dietmar; Griesmacher, Andrea; Falkensammer, Gerda; Klingler, Anton; Koller, Arnold; Streif, Werner; Greie, Sven; Schobersberger, Beatrix; Schobersberger, Wolfgang

    2007-07-01

    Prolonged physical exercise is associated with multiple changes in blood hemostasis. Eccentric muscle activation induces microtrauma of skeletal muscles, inducing an inflammatory response. Since there is a link between inflammation and coagulation we speculated that downhill running strongly activates the coagulation system. Thirteen volunteers participated in the Tyrolean Speed Marathon (42,195 m downhill race, 795 m vertical distance). Venous blood was collected 3 days (T1) and 3 h (T2) before the run, within 30 min after finishing (T3) and 1 day thereafter (T4). We measured the following key parameters: creatine kinase, myoglobin, thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen, plasminogen-activator-inhibitor-1 antigen and thrombelastography with ROTEM [intrinsic pathway (InTEM) clotting time, clot formation time, maximum clot firmness, alpha angle]. Thrombin generation was evaluated by the Thrombin Dynamic Test and the Technothrombin TGA test. Creatine kinase and myoglobin were elevated at T3 and further increased at T4. Thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen and plasminogen-activator-inhibitor-1 antigen were significantly increased at T3. ROTEM analysis exhibited a shortening of InTEM clotting time and clot formation time after the marathon, and an increase in InTEM maximum clot firmness and alpha angle. Changes in TGA were indicative for thrombin generation after the marathon. We demonstrated that a downhill marathon induces an activation of coagulation, as measured by specific parameters for coagulation, ROTEM and thrombin generation assays. These changes were paralleled by an activation of fibrinolysis indicating a preserved hemostatic balance.

  5. Blood Coagulation, Inflammation and Malaria

    PubMed Central

    Francischetti, Ivo M. B.; Seydel, Karl B.; Monteiro, Robson Q.

    2010-01-01

    I. ABSTRACT Malaria remains a highly prevalent disease in more than 90 countries and accounts for at least 1 million deaths every year. Plasmodium falciparum infection is often associated with a procoagulant tonus characterized by thrombocytopenia and activation of the coagulation cascade and fibrinolytic system; however, bleeding and hemorrhage are uncommon events, suggesting that a compensated state of blood coagulation activation occurs in malaria. This article i) reviews the literature related to blood coagulation and malaria in a historic perspective, ii) describes basic mechanisms of coagulation, anticoagulation, and fibrinolysis, iii) explains the laboratory changes in acute and compensated disseminated intravascular coagulation (DIC), iv) discusses the implications of tissue factor (TF) expression in the endothelium of P. falciparum-infected patients, and v) emphasizes the pro-coagulant role of parasitized erythrocytes (pRBC) and activated platelets in the pathogenesis of malaria. This article also presents the ‘Tissue Factor Model’ (TFM) for malaria pathogenesis, which places TF as the interface between sequestration, endothelial cell activation, blood coagulation disorder and inflammation often associated with the disease. The relevance of the coagulation-inflammation cycle for the multiorgan dysfunction and coma is discussed in the context of malaria pathogenesis. PMID:18260002

  6. [Diagnostic of blood coagulation].

    PubMed

    Barthels, M

    2008-12-01

    A survey is given on the peculiar characteristics of laboratory methods for analyzing the blood coagulation system with special regard to the preanalytical, analytical and postanalytical phase. Routinely used methods are described.

  7. Inherited disorders of blood coagulation.

    PubMed

    Lippi, Giuseppe; Franchini, Massimo; Montagnana, Martina; Favaloro, Emmanuel J

    2012-08-01

    Hemostasis is traditionally defined as a physiological response to blood vessel injury and bleeding, which entails a co-ordinated process involving the blood vessel, platelets, and blood clotting proteins (i.e. coagulation factors). Hemostasis can be divided into primary and secondary components. The former rapidly initiates after endothelial damage and is characterized by vascular contraction, platelet adhesion, and formation of a soft aggregate plug. The latter is initiated following the release of tissue factor and involves a complex sequence of events known as the blood coagulation cascade, encompassing serial steps where each coagulation factor activates another in a chain reaction that culminates in the conversion of fibrinogen to fibrin. Patients carrying abnormalities of the coagulation cascade (i.e. deficiencies of coagulation factors) have an increased bleeding tendency, where the clinical severity is mostly dependent upon the type and the plasma level of the factor affected. These disorders also impose a heavy medical and economic burden on individual patients and society in general. The aim of this article is to provide a general overview on the pathophysiology, clinics, diagnostics, and therapy of inherited disorders of coagulation factors.

  8. Whole blood coagulation analyzers.

    PubMed

    1997-08-01

    Whole blood Coagulation analyzers (WBCAs) are widely used point-of-care (POC) testing devices found primarily in cardiothoracic surgical suites and cardia catheterization laboratories. Most of these devices can perform a number of coagulation tests that provide information about a patient's blood clotting status. Clinicians use the results of the WBCA tests, which are available minutes after applying a blood sample, primarily to monitor the effectiveness of heparin therapy--an anticoagulation therapy used during cardiopulmonary bypass (CPB) surgery, angioplasty, hemodialysis, and other clinical procedures. In this study we evaluated five WBCAs from four suppliers. Our testing focused on the applications for which WBCAs are primarily used: Monitoring moderate to high heparin levels, as would be required, for example, during CPB are angioplasty. For this function, WCBAs are typically used to perform an activated clotting time (ACT) test or, as one supplier refers to its test, a heparin management test (HMT). All models included in this study offered an ACT test or an HMT. Monitoring low heparin levels, as would be required, for example,during hemodialysis. For this function, WBCAs would normally be used to perform either a low-range ACT (LACT) test or a whole blood activated partial thromboplastin time (WBAPTT) test. Most of the evaluated units could perform at least one of these tests; one unit did not offer either test and was therefore not rated for this application. We rated and ranked each evaluated model separately for each of these two applications. In addition, we provided a combined rating and ranking that considers the units' appropriateness for performing both application. We based our conclusions on a unit's performance and humans factor design, as determined by our testing, and on its five-year life-cycle cost, as determined by our net present value (NPV) analysis. While we rated all evaluated units acceptable for each appropriate category, we did

  9. [Condition setting for the measurement of blood coagulation factor XIII activity using a fully automated blood coagulation analyzer, COAGTRON-350].

    PubMed

    Kanno, Nobuko; Kaneko, Makoto; Tanabe, Kumiko; Jyona, Masahiro; Yokota, Hiromitsu; Yatomi, Yutaka

    2012-12-01

    The automated laboratory analyzer COAGTRON-350 (Trinity Biotech) is used for routine and specific coagulation testing for the detection of fibrin formation utilizing either mechanical principles (ball method) or photo-optical principles, chromogenic kinetic enzyme analysis, and immune-turbidimetric detection systems in one benchtop unit. In this study, we demonstrated and established a parameter for the measurement of factor XIII (FXIII) activity using Berichrom FXIII reagent and the COAGTRON-350 analyzer. The usual protocol used for this reagent, based on the handling method, was slightly modified for this device. The analysis showed that fundamental study for the measurement of FXIII activity under our condition setting was favorable in terms of reproducibility, linearity, and correlation with another assays. Since FXIII is the key enzyme that plays important roles in hemostasis by stabilizing fibrin formation, the measurement of FXIII is essential for the diagnosis of bleeding disorders. Therefore, FXIII activity assessment as well as a routine coagulation testing can be conducted simultaneously with one instrument, which is useful in coagulopathy assessment.

  10. [Monitoring of blood coagulation in perioperative care].

    PubMed

    Ishii, Hisanari

    2012-01-01

    Coagulation disorders often occur perioperatively and monitoring of blood coagulation should be fast and adequate to treat these disorders to protect patients from massive bleeding. Control of hemostasis is one of the main issues in major surgeries. Coagulation test results from a central laboratory may delay making such a perioperative decision. Recently, point-of-care monitoring (POCM), which is able to examine coagulation disorder in an operation theater with short waiting time, has become important. Both prothrombin time (PT) and activated clotting time (ACT) are very useful and popular, but also criticized because they can be monitored only until fibrin formation. On the other hand, viscoelastic monitorings of whole blood, are able to estimate fibrin formation, clot fixation, platelet function and fibrinolysis. In this review article, among variable perioperative POCMs of blood coagulation, three thromboelastographic monitorings, such as TEG ROTEM, and Sonoclot as well as PT and ACT, are described along with their utilities and limits to examine perioperative coagulation.

  11. Coagulating activity of the blood, vascular wall, and myocardium under hypodynamia conditions

    NASA Technical Reports Server (NTRS)

    Petrovskiy, B. V. (Editor); Chazov, E. I. (Editor); Andreyev, S. V. (Editor)

    1980-01-01

    In order to study the effects of hypodynamia on the coagulating properties of the blood, vascular wall, and myocardium, chinchilla rabbits were kept for varying periods in special cages which restricted their movements. At the end of the experiment, blood samples were taken and the animals were sacrificed. Preparations were made from the myocardium venae cavae, and layers of the aorta. Two resultant interrelated and mutually conditioned syndromes were discovered: thrombohemorrhagic in the blood and hemorrago-thrombotic in the tissues.

  12. Fluorescence-based blood coagulation assay device for measuring activated partial thromboplastin time.

    PubMed

    Dudek, Magdalena M; Kent, Nigel; Gustafsson, Kerstin M; Lindahl, Tomas L; Killard, Anthony J

    2011-01-01

    The measurement of blood clotting time is important in a range of clinical applications such as assessing coagulation disorders and controlling the effect of various anticoagulant drug therapies. Clotting time tests essentially measure the onset of clot formation which results from the formation of fibrin fibers in the blood sample. However, such assays are inherently imprecise due to the highly variable nature of the clot formation process and the sample matrix. This work describes a clotting time measurement assay which uses a fluorescent probe to very precisely detect the onset of fibrin clot formation. It uses a microstructured surface which enhances the formation of multiple localized clot loci and which results in the abrupt redistribution of the fluorescent label at the onset of clot formation in both whole blood and plasma. This methodology was applied to the development of an activated partial thromboplastin time (aPTT) test in a lateral flow microfluidic platform and used to monitor the effect of heparin dosage where it showed linearity from 0 to 2 U/mL in spiked plasma samples (R(2)=0.996, n = 3), correlation against gold standard coagulometry of 0.9986, and correlation against standard hospital aPTT in 32 patient samples of 0.78.

  13. Contact activation of blood coagulation on a defined kaolin/collagen surface in a microfluidic assay.

    PubMed

    Zhu, Shu; Diamond, Scott L

    2014-12-01

    Generation of active Factor XII (FXIIa) triggers blood clotting on artificial surfaces and may also enhance intravascular thrombosis. We developed a patterned kaolin (0 to 0.3 pg/μm(2))/type 1 collagen fibril surface for controlled microfluidic clotting assays. Perfusion of whole blood (treated only with a low level of 4 μg/mL of the XIIa inhibitor, corn trypsin inhibitor) drove platelet deposition followed by fibrin formation. At venous wall shear rate (100 s(-1)), kaolin accelerated onset of fibrin formation by ~100 sec when compared to collagen alone (250 sec vs. 350 sec), with little effect on platelet deposition. Even with kaolin present, arterial wall shear rate (1000 s(-1)) delayed and suppressed fibrin formation compared to venous wall shear rate. A comparison of surfaces for extrinsic activation (tissue factor TF/collagen) versus contact activation (kaolin/collagen) that each generated equal platelet deposition at 100 s(-1) revealed: (1) TF surfaces promoted much faster fibrin onset (at 100 sec) and more endpoint fibrin at 600 sec at either 100 s(-1) or 1000 s(-1), and (2) kaolin and TF surfaces had a similar sensitivity for reduced fibrin deposition at 1000 s(-1) (compared to fibrin formed at 100 s(-1)) despite differing coagulation triggers. Anti-platelet drugs inhibiting P2Y1, P2Y12, cyclooxygenase-1 or activating IP-receptor or guanylate cyclase reduced platelet and fibrin deposition on kaolin/collagen. Since FXIIa or FXIa inhibition may offer safe antithrombotic therapy, especially for biomaterial thrombosis, these defined collagen/kaolin surfaces may prove useful in drug screening tests or in clinical diagnostic assays of blood under flow conditions.

  14. In vitro and in vivo evaluation of blood coagulation activation of polyvinyl alcohol hydrogel plus dextran-based vascular grafts.

    PubMed

    Alexandre, Nuno; Costa, Elísio; Coimbra, Susana; Silva, Alice; Lopes, Ascensão; Rodrigues, Miguel; Santos, Marta; Maurício, Ana Colette; Santos, José Domingos; Luís, Ana Lúcia

    2015-04-01

    Polyvinyl alcohol hydrogel (PVA) is a water-soluble synthetic polymer that is commonly used in biomedical applications including vascular grafting. It was argued that the copolymerization of PVA with dextran (Dx) can result in improvement of blood-biomaterial interactions. The focus of this experimental study was to assess that interaction through an in vivo and in vitro evaluation of the coagulation system activation. The thrombogenicity of the copolymer was determined by quantification of platelet adhesion through the lactate dehydrogenase assay, determination of whole blood clotting time, and by quantification of platelet activation by flow cytometry. The thrombin-antithrombin complex blood levels were also determined. The obtained results for the in vitro assays suggested a non-thrombogenic profile for PVA/Dx. Additionally in vivo coagulation and hematological parameters were determined in an animal model after PVA/Dx vascular graft implantation. For coagulation homeostasis assessment, the intrinsic and extrinsic pathway's activation was determined by measuring prothrombin time (PT) and activated partial thromboplastin time (aPTT). Other markers of coagulation and inflammation activation including d-dimers, interleukin-6, and C-reactive protein were also assessed. The PVA/Dx copolymer tended to inhibit platelet adhesion/activation process and the contact activation process for coagulation. These results were also confirmed with the in vivo experiments where the measurements for APTT, interleukin-6, and C-reactive protein parameters were normal considering the species normal range of values. The response to those events is an indicator of the in vitro and in vivo hemocompatibility of PVA/Dx and it allows us to select this biomaterial for further preclinical trials in vascular reconstruction.

  15. Novel aspects of blood coagulation factor XIII. I. Structure, distribution, activation, and function

    SciTech Connect

    Muszbek, L.; Adany, R.; Mikkola, H.

    1996-10-01

    Blood coagulation factor XIII (FXIII) is a protransglutaminase that becomes activated by the concerted action of thrombin and Ca{sup 2+} in the final stage of the clotting cascade. In addition to plasma, FXIII also occurs in platelets, monocytes, and monocyte-derived macrophages. While the plasma factor is a heterotetramer consisting of paired A and B subunits (A{sub 2}B{sub 2}), its cellular counterpart lacks the B subunits and is a homodimer of potentially active A subunits (A{sub 2}). The gene coding for the A and B subunits has been localized to chromosomes 6p24-25 and 1q31-32.1, respectively. The genomic as well as the primary protein structure of both subunits has been established. Plasma FXIII circulates in association with its substrate precursor, fibrinogen. Fibrin(ogen) has an important regulatory role in the activation of plasma FXIII, for instance the proteolytic removal of activation peptide by thrombin, the dissociation of subunits A and B, and the exposure of the originally buried active site on the free A subunits. The end result of this process is the formation of an active transglutaminase, which crosslinks peptide chains through {epsilon}({gamma}-glutamyl)lysyl isopeptide bonds. The protein substrates of activated FXIII include components of the clotting-fibrinolytic system, adhesive and contractile proteins. The main physiological function of plasma FXIII is to cross-link fibrin and protect it from the fibrinolytic enzyme plasmin. The latter effect is achieved mainly by covalently linking {alpha}{sub 2} antiplasmin, the most potent physiological inhibitor of plasmin, to fibrin. Plasma FXIII seems to be involved in wound healing and tissue repair, and it is essential to maintaining pregnancy. Cellular FXIII, if exposed to the surface of the cells, might support or perhaps take over the hemostatic functions of plasma FXIII; however, its intracellular role has remained mostly unexplored. 328 refs., 4 figs.

  16. Erythrocyte-derived microparticles supporting activated protein C-mediated regulation of blood coagulation.

    PubMed

    Koshiar, Ruzica Livaja; Somajo, Sofia; Norström, Eva; Dahlbäck, Björn

    2014-01-01

    Elevated levels of erythrocyte-derived microparticles are present in the circulation in medical conditions affecting the red blood cells. Erythrocyte-derived microparticles expose phosphatidylserine thus providing a suitable surface for procoagulant reactions leading to thrombin formation via the tenase and prothrombinase complexes. Patients with elevated levels of circulating erythrocyte-derived microparticles have increased thrombin generation in vivo. The aim of the present study was to investigate whether erythrocyte-derived microparticles are able to support the anticoagulant reactions of the protein C system. Erythrocyte-derived microparticles were isolated using ultracentrifugation after incubation of freshly prepared erythrocytes with the ionophore A23187 or from outdated erythrocyte concentrates, the different microparticles preparations yielding similar results. According to flow cytometry analysis, the microparticles exposed phoshatidylserine and bound lactadherin, annexin V, and protein S, which is a cofactor to activated protein C. The microparticles were able to assemble the tenase and prothrombinase complexes and to stimulate the formation of thrombin in plasma-based thrombin generation assay both in presence and absence of added tissue factor. The addition of activated protein C in the thrombin generation assay inhibited thrombin generation in a dose-dependent fashion. The anticoagulant effect of activated protein C in the thrombin generation assay was inhibited by a monoclonal antibody that prevents binding of protein S to microparticles and also attenuated by anti-TFPI antibodies. In the presence of erythrocyte-derived microparticles, activated protein C inhibited tenase and prothrombinase by degrading the cofactors FVIIIa and FVa, respectively. Protein S stimulated the Arg306-cleavage in FVa, whereas efficient inhibition of FVIIIa depended on the synergistic cofactor activity of protein S and FV. In summary, the erythrocyte-derived microparticle

  17. 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.

  18. Interactions of PLGA nanoparticles with blood components: protein adsorption, coagulation, activation of the complement system and hemolysis studies.

    PubMed

    Fornaguera, Cristina; Calderó, Gabriela; Mitjans, Montserrat; Vinardell, Maria Pilar; Solans, Conxita; Vauthier, Christine

    2015-04-14

    The intravenous administration of poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been widely reported as a promising alternative for delivery of drugs to specific cells. However, studies on their interaction with diverse blood components using different techniques are still lacking. Therefore, in the present work, the interaction of PLGA nanoparticles with blood components was described using different complementary techniques. The influence of different encapsulated compounds/functionalizing agents on these interactions was also reported. It is worth noting that all these techniques can be simply performed, without the need for highly sophisticated apparatus or skills. Moreover, their transference to industries and application of quality control could be easily performed. Serum albumin was adsorbed onto all types of tested nanoparticles. The saturation concentration was dependent on the nanoparticle size. In contrast, fibrinogen aggregation was dependent on nanoparticle surface charge. The complement activation was also influenced by the nanoparticle functionalization; the presence of a functionalizing agent increased complement activation, while the addition of an encapsulated compound only caused a slight increase. None of the nanoparticles influenced the coagulation cascade at low concentrations. However, at high concentrations, cationized nanoparticles did activate the coagulation cascade. Interactions of nanoparticles with erythrocytes did not reveal any hemolysis. Interactions of PLGA nanoparticles with blood proteins depended both on the nanoparticle properties and the protein studied. Independent of their loading/surface functionalization, PLGA nanoparticles did not influence the coagulation cascade and did not induce hemolysis of erythrocytes; they could be defined as safe concerning induction of embolization and cell lysis.

  19. Group D prothrombin activators from snake venom are structural homologues of mammalian blood coagulation factor Xa.

    PubMed Central

    Rao, Veena S; Joseph, Jeremiah S; Kini, R Manjunatha

    2003-01-01

    Procoagulant venoms of several Australian elapids contain proteinases that specifically activate prothrombin; among these, Group D activators are functionally similar to coagulation factor Xa (FXa). Structural information on this class of prothrombin activators will contribute significantly towards understanding the mechanism of FXa-mediated prothrombin activation. Here we present the purification of Group D prothrombin activators from three Australian snake venoms (Hoplocephalus stephensi, Notechis scutatus scutatus and Notechis ater niger) using a single-step method, and their N-terminal sequences. The N-terminal sequence of the heavy chain of hopsarin D (H. stephensi) revealed that a fully conserved Cys-7 was substituted with a Ser residue. We therefore determined the complete amino acid sequence of hopsarin D. Hopsarin D shows approximately 70% similarity with FXa and approximately 98% similarity with trocarin D, a Group D prothrombin activator from Tropidechis carinatus. It possesses the characteristic Gla domain, two epidermal growth factor-like domains and a serine proteinase domain. All residues important for catalysis are conserved, as are most regions involved in interactions with factor Va and prothrombin. However, there are some structural differences. Unlike FXa, hopsarin D is glycosylated in both its chains: in light-chain residue 52 and heavy-chain residue 45. The glycosylation on the heavy chain is a large carbohydrate moiety adjacent to the active-site pocket. Overall, hopsarin D is structurally and functionally similar to mammalian coagulation FXa. PMID:12403650

  20. The effect of surface roughness on activation of the coagulation system and platelet adhesion in rotary blood pumps.

    PubMed

    Linneweber, Jörg; Dohmen, Pascal Maria; Kertzscher, Ulrich; Kerzscher, Ullrich; Affeld, Klaus; Nosé, Yukihiko; Konertz, Wolfgang

    2007-05-01

    The surface roughness of left ventricular assist devices (LVADs) is important for the biocompatibility of blood pumps. However, little is known about the effect of surface roughness on the antithrombogenicity of the device. The present study investigated the effect of surface roughness on the activation of the coagulation system and platelet adhesion in an impeller-type blood pump. Three identical Baylor Gyro 710 centrifugal blood pumps (Baylor College of Medicine, Houston, TX, USA) were manufactured with impeller surface roughness of 0.05, 0.2, and 0.4 microm, respectively, as determined by a stylus profilometer and by scanning electron microscopy. Whole blood was anticoagulated (1-IU heparin/mL, ACT 250 s) and circulated for 60 min in an artificial circulatory system, simulating LVAD perfusion (5-L/min flow against 100 mm Hg). Enzyme-linked immunosorbent assays were developed to quantify fibrinogen- and von Willebrand factor (vWf) adsorption as well as platelet adhesion directly on the impellers of the pumps. Levels of prothrombin fragment F1.2 and thrombin-antithrombin (TAT) complex were measured in order to quantify activation of coagulation. Compared with the 0.05-microm surface, platelet adhesion was 40 and 76% higher on the 0.2- and 0.4-microm surface, respectively (P < 0.01). The evaluation of adsorbed fibrinogen and vWf showed significant higher protein antigen levels on the rougher surfaces (P < 0.01). Furthermore, nonpulsatile perfusion activated the coagulation system. By contrast, the surface roughness had no significant influence on plasma prothrombin F1.2 fragment- and TAT concentrations. Antithrombogenicity was significantly reduced in pumps with inferior metal-finishing quality.

  1. Interactions of PLGA nanoparticles with blood components: protein adsorption, coagulation, activation of the complement system and hemolysis studies

    NASA Astrophysics Data System (ADS)

    Fornaguera, Cristina; Calderó, Gabriela; Mitjans, Montserrat; Vinardell, Maria Pilar; Solans, Conxita; Vauthier, Christine

    2015-03-01

    The intravenous administration of poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been widely reported as a promising alternative for delivery of drugs to specific cells. However, studies on their interaction with diverse blood components using different techniques are still lacking. Therefore, in the present work, the interaction of PLGA nanoparticles with blood components was described using different complementary techniques. The influence of different encapsulated compounds/functionalizing agents on these interactions was also reported. It is worth noting that all these techniques can be simply performed, without the need for highly sophisticated apparatus or skills. Moreover, their transference to industries and application of quality control could be easily performed. Serum albumin was adsorbed onto all types of tested nanoparticles. The saturation concentration was dependent on the nanoparticle size. In contrast, fibrinogen aggregation was dependent on nanoparticle surface charge. The complement activation was also influenced by the nanoparticle functionalization; the presence of a functionalizing agent increased complement activation, while the addition of an encapsulated compound only caused a slight increase. None of the nanoparticles influenced the coagulation cascade at low concentrations. However, at high concentrations, cationized nanoparticles did activate the coagulation cascade. Interactions of nanoparticles with erythrocytes did not reveal any hemolysis. Interactions of PLGA nanoparticles with blood proteins depended both on the nanoparticle properties and the protein studied. Independent of their loading/surface functionalization, PLGA nanoparticles did not influence the coagulation cascade and did not induce hemolysis of erythrocytes; they could be defined as safe concerning induction of embolization and cell lysis.The intravenous administration of poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been widely reported as a promising

  2. Whole blood coagulation and platelet activation in the athlete: A comparison of marathon, triathlon and long distance cycling

    PubMed Central

    2010-01-01

    Introduction Serious thrombembolic events occur in otherwise healthy marathon athletes during competition. We tested the hypothesis that during heavy endurance sports coagulation and platelets are activated depending on the type of endurance sport with respect to its running fraction. Materials and Methods 68 healthy athletes participating in marathon (MAR, running 42 km, n = 24), triathlon (TRI, swimming 2.5 km + cycling 90 km + running 21 km, n = 22), and long distance cycling (CYC, 151 km, n = 22) were included in the study. Blood samples were taken before and immediately after completion of competition to perform rotational thrombelastometry. We assessed coagulation time (CT), maximum clot firmness (MCF) after intrinsically activation and fibrin polymerization (FIBTEM). Furthermore, platelet aggregation was tested after activation with ADP and thrombin activating peptide 6 (TRAP) by using multiple platelet function analyzer. Results Complete data sets were obtained in 58 athletes (MAR: n = 20, TRI: n = 19, CYC: n = 19). CT significantly decreased in all groups (MAR -9.9%, TRI -8.3%, CYC -7.4%) without differences between groups. In parallel, MCF (MAR +7.4%, TRI +6.1%, CYC +8.3%) and fibrin polymerization (MAR +14.7%, TRI +6.1%, CYC +8.3%) were significantly increased in all groups. However, platelets were only activated during MAR and TRI as indicated by increased AUC during TRAP-activation (MAR +15.8%) and increased AUC during ADP-activation in MAR (+50.3%) and TRI (+57.5%). Discussion While coagulation is activated during physical activity irrespective of type we observed significant platelet activation only during marathon and to a lesser extent during triathlon. We speculate that prolonged running may increase platelet activity, possibly, due to mechanical alteration. Thus, particularly prolonged running may increase the risk of thrombembolic incidents in running athletes. PMID:20452885

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

    PubMed

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

    2013-08-01

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

  4. Influence of red algal sulfated polysaccharides on blood coagulation and platelets activation in vitro.

    PubMed

    Sokolova, Ekaterina V; Byankina, Anna O; Kalitnik, Alexandra A; Kim, Yong H; Bogdanovich, Larisa N; Solov'eva, Tamara F; Yermak, Irina M

    2014-05-01

    The influence of sulfated polysaccharides (λ-, κ-, and κ/β-carrageenan and porphyran) - on platelet activation was studied. Carrageenans were much weaker inhibitors of a coagulation process than heparin, while porphyran had not that effect. Results of the aPTT and PT assays suppose that carrageenans affected mostly intrinsic pathway of coagulation, while their effect on the extrinsic pathway is extremely low (λ and κ/β) or absent (κ, LMW derivative of κ-carrageenan). λ-Carrageenan was the most potent anticoagulant agent in TT, aPTT, PT, and anti-factor Xa activity. This sample was also the strongest inhibitor of collagen-induced platelet aggregation in PRP. Generally, the correlation of anticoagulant and antithrombotic action in PRP is preserved for carrageenans but not for heparin. Carrageenans and porphyran affected platelet adhesion to collagen by influencing glycoprotein VI. Low molecular weight κ-carrageenan had a similar effect on platelet adhesion mediated with both major collagen receptors: integrin α2 β1 and glycoprotein VI as native polysaccharide had. Carrageenans resulted in activation of platelets under platelet adhesion mediated by integrin αIIb β3 with less degree than heparin. The least sulfated κ/β-carrageenan that possessed an inhibiting effect on thrombin- and collagen-induced aggregation of washed platelets and on the PT test but it had no significant effect on TT was the weakest promoter of integrin αIIb β3 mediated platelet activation. In summary, our study showed that the polysaccharide action was complex, since it depended on its molecular mass, sulfation degree, and monosaccharide contents (3,6-anhydrogalactose).

  5. 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

  6. Systems Biology of Coagulation Initiation: Kinetics of Thrombin Generation in Resting and Activated Human Blood

    PubMed Central

    Chatterjee, Manash S.; Denney, William S.; Jing, Huiyan; Diamond, Scott L.

    2010-01-01

    Blood function defines bleeding and clotting risks and dictates approaches for clinical intervention. Independent of adding exogenous tissue factor (TF), human blood treated in vitro with corn trypsin inhibitor (CTI, to block Factor XIIa) will generate thrombin after an initiation time (Ti) of 1 to 2 hours (depending on donor), while activation of platelets with the GPVI-activator convulxin reduces Ti to ∼20 minutes. Since current kinetic models fail to generate thrombin in the absence of added TF, we implemented a Platelet-Plasma ODE model accounting for: the Hockin-Mann protease reaction network, thrombin-dependent display of platelet phosphatidylserine, VIIa function on activated platelets, XIIa and XIa generation and function, competitive thrombin substrates (fluorogenic detector and fibrinogen), and thrombin consumption during fibrin polymerization. The kinetic model consisting of 76 ordinary differential equations (76 species, 57 reactions, 105 kinetic parameters) predicted the clotting of resting and convulxin-activated human blood as well as predicted Ti of human blood under 50 different initial conditions that titrated increasing levels of TF, Xa, Va, XIa, IXa, and VIIa. Experiments with combined anti-XI and anti-XII antibodies prevented thrombin production, demonstrating that a leak of XIIa past saturating amounts of CTI (and not “blood-borne TF” alone) was responsible for in vitro initiation without added TF. Clotting was not blocked by antibodies used individually against TF, VII/VIIa, P-selectin, GPIb, protein disulfide isomerase, cathepsin G, nor blocked by the ribosome inhibitor puromycin, the Clk1 kinase inhibitor Tg003, or inhibited VIIa (VIIai). This is the first model to predict the observed behavior of CTI-treated human blood, either resting or stimulated with platelet activators. CTI-treated human blood will clot in vitro due to the combined activity of XIIa and XIa, a process enhanced by platelet activators and which proceeds in the

  7. Blood coagulation disorders in septic patients.

    PubMed

    Knoebl, Paul

    2010-03-01

    Host defense and blood coagulation are tightly connected and interacting systems, necessary for the integrity of an organism. Complex mechanisms regulate the intensity of a host response to invading pathogens or other potentially dangerous situations. Under regular conditions, this response is limited in time and located to the site of injury. Sometimes, however, systemic host response is overwhelming and disproportional and causes damage, not cure. Dependent on the genetical predisposition of the host, its current immunocompetence, or the type of injury, the reaction leads to the clinical picture of the different degrees of sepsis. Septic organ dysfunction is caused by intravascular fibrin deposition as a result of coagulation activation, anticoagulant breakdown, and shut down of fibrinolysis. This article describes the major pathophysiologic reactions in these situations and presents www.SepDIC.eu, an online tool on sepsis and associated coagulopathy.

  8. Reaction-diffusion waves of blood coagulation.

    PubMed

    Galochkina, Tatiana; Bouchnita, Anass; Kurbatova, Polina; Volpert, Vitaly

    2017-03-24

    One of the main characteristics of blood coagulation is the speed of clot growth. In the current work we consider a mathematical model of the coagulation cascade and study existence, stability and speed of propagation of the reaction-diffusion waves of blood coagulation. We also develop a simplified one-equation model that reflects the main features of the thrombin wave propagation. For this equation we estimate the wave speed analytically. The resulting formulas provide a good approximation for the speed of wave propagation in a more complex model as well as for the experimental data.

  9. [Proteins influencing the blood coagulation].

    PubMed

    Alberio, Lorenzo

    2011-11-01

    This review describes some natural proteins, which can be employed, either as factor concentrates derived from human plasma or as recombinant drug, to modulate the coagulation system. I will address some biochemical characteristics and the physiological role of von Willebrand factor, the coagulation factors of the extrinsic and intrinsic pathways, and the physiological anticoagulant protein C. In addition, I will detail the pharmacological compounds, which are available for influencing or substituting the coagulation proteins: desmopressin (DDAVP), single coagulation factor concentrates, prothrombin complex concentrates, and protein C concentrate. In particular, I will address some treatment topics of general medical interest, such as the treatment of massive bleeding, the correction of the coagulopathy induced by vitamin K-antagonists in patients with cerebral haemorrhage, and of the coagulopathy of meningococcemia. Finally, I will describe some properties and practical clinical applications of the recombinant anticoagulans lepirudin and bivalirudin, which are derived from hirudin, the natural anticoagulant of the medical leech.

  10. Isolation and properties of a blood coagulation factor X activator from the venom of king cobra (Ophiophagus hannah).

    PubMed

    Lee, W H; Zhang, Y; Wang, W Y; Xiong, Y L; Gao, R

    1995-10-01

    A specific blood coagulation factor X activator was purified from the venom of Ophiophagus hannah by gel filtration and two steps of FPLC Mono-Q column ion-exchange chromatography. It showed a single protein band both in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and alkaline polyacrylamide gel electrophoresis. The mol. wt was estimated to be 62,000 in non-reducing conditions and 64,500 in reducing conditions by SDS-PAGE. The isoelectric point was found to be pH 5.6. The enzyme had weak amidolytic activities toward CBS 65-25, but it showed no activities on S-2266, S-2302, thrombin substrate S-2238, plasmin substrate S-2251 or factor Xa substrate S-2222. It had no arginine esterase activity toward substrate benzoylarginine ethylester (BAEE). The enzyme activated factor X in vitro and the effect was absolutely Ca2+ dependent, with a Hill coefficient of 6.83. It could not activate prothrombin nor had any effect on fibrinogen and thus appeared to act specifically on factor X. The procoagulant activity of the enzyme was almost completely inhibited by serine protease inhibitors like PMSF, TPCK and soybean trypsin inhibitor; partially inhibited by L-cysteine. Metal chelator EDTA did not inhibit its procoagulant activity. These results suggest that the factor X activator from O. hannah venom is a serine protease.

  11. Does whole blood coagulation analysis reflect developmental haemostasis?

    PubMed

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

    2016-07-27

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

  12. Magnetic particle imaging of blood coagulation

    SciTech Connect

    Murase, Kenya Song, Ruixiao; Hiratsuka, Samu

    2014-06-23

    We investigated the feasibility of visualizing blood coagulation using a system for magnetic particle imaging (MPI). A magnetic field-free line is generated using two opposing neodymium magnets and transverse images are reconstructed from the third-harmonic signals received by a gradiometer coil, using the maximum likelihood-expectation maximization algorithm. Our MPI system was used to image the blood coagulation induced by adding CaCl{sub 2} to whole sheep blood mixed with magnetic nanoparticles (MNPs). The “MPI value” was defined as the pixel value of the transverse image reconstructed from the third-harmonic signals. MPI values were significantly smaller for coagulated blood samples than those without coagulation. We confirmed the rationale of these results by calculating the third-harmonic signals for the measured viscosities of samples, with an assumption that the magnetization and particle size distribution of MNPs obey the Langevin equation and log-normal distribution, respectively. We concluded that MPI can be useful for visualizing blood coagulation.

  13. 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.

  14. Structural investigation of zymogenic and activated forms of human blood coagulation factor VIII: a computational molecular dynamics study

    PubMed Central

    2010-01-01

    Background Human blood coagulation factor VIII (fVIII) is a large plasma glycoprotein with sequential domain arrangement in the order A1-a1-A2-a2-B-a3-A3-C1-C2. The A1, A2 and A3 domains are interconnected by long linker peptides (a1, a2 and a3) that possess the activation sites. Proteolysis of fVIII zymogen by thrombin or factor Xa results in the generation of the activated form (fVIIIa) which serves as a critical co-factor for factor IXa (fIXa) enzyme in the intrinsic coagulation pathway. Results In our efforts to elucidate the structural differences between fVIII and fVIIIa, we developed the solution structural models of both forms, starting from an incomplete 3.7 Å X-ray crystal structure of fVIII zymogen, using explicit solvent MD simulations. The full assembly of B-domainless single-chain fVIII was built between the A1-A2 (Ala1-Arg740) and A3-C1-C2 (Ser1669-Tyr2332) domains. The structural dynamics of fVIII and fVIIIa, simulated for over 70 ns of time scale, enabled us to evaluate the integral motions of the multi-domain assembly of the co-factor and the possible coordination pattern of the functionally important calcium and copper ion binding in the protein. Conclusions MD simulations predicted that the acidic linker peptide (a1) between the A1 and A2 domains is largely flexible and appears to mask the exposure of putative fIXa enzyme binding loop (Tyr555-Asp569) region in the A2 domain. The simulation of fVIIIa, generated from the zymogen structure, predicted that the linker peptide (a1) undergoes significant conformational reorganization upon activation by relocating completely to the A1-domain. The conformational transition led to the exposure of the Tyr555-Asp569 loop and the surrounding region in the A2 domain. While the proposed linker peptide conformation is predictive in nature and warrants further experimental validation, the observed conformational differences between the zymogen and activated forms may explain and support the large body of

  15. Mathematical Modeling of Intravascular Blood Coagulation under Wall Shear Stress

    PubMed Central

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

    2015-01-01

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

  16. Acoustic determination of early stages of intravascular blood coagulation.

    PubMed

    Uzlova, Svetlana G; Guria, Konstantin G; Guria, Georgy Th

    2008-10-13

    The blood coagulation system (BCS) is a complex biological system playing a principal role in the maintenance of haemostasis. Insufficient activity of the BCS may lead to bleeding and blood loss (e.g. in the case of haemophilia). On the other hand, excessive activity may cause intravascular blood coagulation, thromboses and embolization. Most of the methods currently used for BCS monitoring suffer from the major disadvantage of being invasive. The purpose of the present work is to demonstrate the feasibility of using ultrasonic methods for non-invasive registration of the early stages of blood coagulation processes in intensive flows. With this purpose, a special experimental set-up was designed, facilitating the simultaneous detection of optical and acoustic signals during the clotting process. It was shown that (i) as microemboli appear in the flow during the early stage of blood coagulation, the intensity of the Doppler signal increases twofold, and (ii) microemboli formation in the early stages of blood clotting always reveals itself through an acoustic contrast. Both of these effects are well defined, so we hope that they may be used for non-invasive BCS monitoring in clinical practice.

  17. Oxidation inhibits iron-induced blood coagulation.

    PubMed

    Pretorius, Etheresia; Bester, Janette; Vermeulen, Natasha; Lipinski, Boguslaw

    2013-01-01

    Blood coagulation under physiological conditions is activated by thrombin, which converts soluble plasma fibrinogen (FBG) into an insoluble clot. The structure of the enzymatically-generated clot is very characteristic being composed of thick fibrin fibers susceptible to the fibrinolytic degradation. However, in chronic degenerative diseases, such as atherosclerosis, diabetes mellitus, cancer, and neurological disorders, fibrin clots are very different forming dense matted deposits (DMD) that are not effectively removed and thus create a condition known as thrombosis. We have recently shown that trivalent iron (ferric ions) generates hydroxyl radicals, which subsequently convert FBG into abnormal fibrin clots in the form of DMDs. A characteristic feature of DMDs is their remarkable and permanent resistance to the enzymatic degradation. Therefore, in order to prevent thrombotic incidences in the degenerative diseases it is essential to inhibit the iron-induced generation of hydroxyl radicals. This can be achieved by the pretreatment with a direct free radical scavenger (e.g. salicylate), and as shown in this paper by the treatment with oxidizing agents such as hydrogen peroxide, methylene blue, and sodium selenite. Although the actual mechanism of this phenomenon is not yet known, it is possible that hydroxyl radicals are neutralized by their conversion to the molecular oxygen and water, thus inhibiting the formation of dense matted fibrin deposits in human blood.

  18. Kinetics of the Factor XIa catalyzed activation of human blood coagulation Factor IX

    SciTech Connect

    Walsh, P.N.; Bradford, H.; Sinha, D.; Piperno, J.R.; Tuszynski, G.P.

    1984-05-01

    The kinetics of activation of human Factor IX by human Factor XIa was studied by measuring the release of a trichloroacetic acid-soluble tritium-labeled activation peptide from Factor IX. Initial rates of trichloroacetic acid-soluble /sup 3/H-release were linear over 10-30 min of incubation of Factor IX (88 nM) with CaCl/sub 2/ (5 mM) and with pure (greater than 98%) Factor XIa (0.06-1.3 nM), which was prepared by incubating human Factor XI with bovine Factor XIIa. Release of /sup 3/H preceded the appearance of Factor IXa activity, and the percentage of /sup 3/H released remained constant when the mole fraction of /sup 3/H-labeled and unlabeled Factor IX was varied and the total Factor IX concentration remained constant. A linear correlation (r greater than 0.98, P less than 0.001) was observed between initial rates of /sup 3/H-release and the concentration of Factor XIa, measured by chromogenic assay and by radioimmunoassay and added at a Factor IX:Factor XIa molar ratio of 70-5,600. Kinetic parameters, determined by Lineweaver-Burk analysis, include K/sub m/ (0.49 microM) of about five- to sixfold higher than the plasma Factor IX concentration, which could therefore regulate the reaction. The catalytic constant (k/sub cat/) (7.7/s) is approximately 20-50 times higher than that reported by Zur and Nemerson for Factor IX activation by Factor VIIa plus tissue factor. Therefore, depending on the relative amounts of Factor XIa and Factor VIIa generated in vivo and other factors which may influence reaction rates, these kinetic parameters provide part of the information required for assessing the relative contributions of the intrinsic and extrinsic pathways to Factor IX activation, and suggest that the Factor XIa catalyzed reaction is physiologically significant.

  19. A hitherto undescribed plasma factor acting at the contact phase of blood coagulation (Flaujeac factor): case report and coagulation studies.

    PubMed

    Lacombe, M J; Varet, B; Levy, J P

    1975-11-01

    This paper reports an asymptomatic coagulation defect responsible for an abnormality at the contact phase of blood coagulation in vitro, distinct from Hageman factor and Fletcher factor deficiencies. Coagulation studies in a 50-yr-old French woman without bleeding tendency revealed the following results: whole-blood clotting time in glass tubes and activated partial thromboplastin time with kaolin and ellagic acid were greatly prolonged; one-stage prothrombin was normal; no circulating anticoagulant was detected, and the infusion of normal plasma corrected the coagulation defect with an estimated half-life of 6.5 days; the levels of factor VIII, IX, XI, and XII were normal; mutual correction was obtained with a Fletcher factor-deficient plasma; the level of whole complement was normal. Studies of the contact phase of blood coagulation and contact-induced fibrinolysis showed the same abnormalities as in Hageman factor- and Fletcher-deficient plasmas. These results indicate that the patient's plasma is deficient in a previously undescribed coagulation factor, which participates in the initial stage of the blood coagulation process in vitro. Family studies revealed consanguinity in the propositus' parents. The assay of this newly described factor in the propositus' children revealed a partial defect, compatible with a heterozygous state, in three of the four tested children. This indicates a recessive inheritance of this new blood coagulation defect.

  20. Hydroxyapatite formed on/in agarose gel induces activation of blood coagulation and platelets aggregation.

    PubMed

    Arimura, Shin-ichiro; Kawahara, Ko-ichi; Biswas, Kamal Krishna; Abeyama, Kazuhiro; Tabata, Masashi; Shimoda, Toru; Ogomi, Daisuke; Matsusaki, Michiya; Kato, Shinya; Ito, Takashi; Sugihara, Kazumasa; Akashi, Mitsuru; Hashiguchi, Teruto; Maruyama, Ikuro

    2007-05-01

    We reported earlier that hydroxyapatite (HA) formed on/in agarose gels (HA/agarose) produced by alternate soaking process is a bone-filling material possessing osteoconductive and hemostatic effects. This process could allow us to make bone-like apatite that was formed on/in organic polymer hydrogel matrices. Here, we investigated the mechanism of hemostasis induced by HA/agarose and found that HA/agarose, but not agarose or HA powder, significantly shortened activated partial thromboplastin time (APTT). While HA/agarose did not show significant platelet aggregation, it markedly enhanced adenosine diphosphate (ADP)-induced platelet aggregation. Moreover, Western blot analysis revealed selective adsorption of vitronectin onto HA/agarose. We also observed marked differences between HA powder and HA/agarose in their XRD patterns. The crystallinity of HA powder was much higher compared to that of HA/agarose. Furthermore, 50-100 nm of tube-form aggregations was observed in HA powder on the other hand 100-200 nm of particles was observed in HA/agarose by SEM observation. Thus 100-200 nm of low crystallized particles on the surface structure of HA/agarose may play an important role in hemostasis. Our results demonstrated a crucial role of HA/agarose in the mechanism of hemostasis and suggested a potential role for HA/agarose as a bone-grafting material.

  1. Markers of inflammation, activation of blood platelets and coagulation disorders in inflammatory bowel diseases.

    PubMed

    Matowicka-Karna, Joanna

    2016-04-13

    Inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn's disease. It is a group of chronic disorders characterized by inflammation of the gastrointestinal track with unknown etiology. Currently applied biomarkers include CRP, ESR, pANCA, ASCA, and fecal calprotectin. The etiopathogenesis of IBD is multifactorial. In patients with IBD in inflamed alimentary tract mucosa the number of recruited monocytes and activated macrophages which are source of cytokines. In IBD, the exacerbation is accompanied by thrombocytosis. Platelets play a crucial role in the hemostasis and inflammatory response. Selectins, which regulates the hemostasis and inflammatory response, stimulates the secretion of many inflammatory mediators such as β-thromboglobuline, CD40L, fibrinogen, IL-1β, platelet factor-4. In the course of IBD the following changes are observed: an increase in the number of platelets (reactive thrombocytosis), PDW and PCT, reduction in MPV, increased production and excretion of granular content products (P-selectin, GP53, β-TG, PF-4, vWF, fibrinolytic inhibitors).

  2. Fibrinolysis and the control of blood coagulation.

    PubMed

    Chapin, John C; Hajjar, Katherine A

    2015-01-01

    Fibrin plays an essential role in hemostasis as both the primary product of the coagulation cascade and the ultimate substrate for fibrinolysis. Fibrinolysis efficiency is greatly influenced by clot structure, fibrinogen isoforms and polymorphisms, the rate of thrombin generation, the reactivity of thrombus-associated cells such as platelets, and the overall biochemical environment. Regulation of the fibrinolytic system, like that of the coagulation cascade, is accomplished by a wide array of cofactors, receptors, and inhibitors. Fibrinolytic activity can be generated either on the surface of a fibrin-containing thrombus, or on cells that express profibrinolytic receptors. In a widening spectrum of clinical disorders, acquired and congenital defects in fibrinolysis contribute to disease morbidity, and new assays of global fibrinolysis now have potential predictive value in multiple clinical settings. Here, we summarize the basic elements of the fibrinolytic system, points of interaction with the coagulation pathway, and some recent clinical advances.

  3. Fibrinolysis and the control of blood coagulation

    PubMed Central

    Chapin, John C.; Hajjar, Katherine A.

    2014-01-01

    Fibrin plays an essential role in hemostasis as both the primary product of the coagulation cascade and the ultimate substrate for fibrinolysis. Fibrinolysis efficiency is greatly influenced by clot structure, fibrinogen isoforms and polymorphisms, the rate of thrombin generation, the reactivity of thrombus-associated cells such as platelets, and the overall biochemical environment. Regulation of the fibrinolytic system, like that of the coagulation cascade, is accomplished by a wide array of cofactors, receptors, and inhibitors. Fibrinolytic activity can be generated either on the surface of a fibrin-containing thrombus, or on cells that express profibrinolytic receptors. In a widening spectrum of clinical disorders, acquired and congenital defects in fibrinolysis contribute to disease morbidity, and new assays of global fibrinolysis now have potential predictive value in multiple clinical settings. Here, we summarize the basic elements of the fibrinolytic system, points of interaction with the coagulation pathway, and some recent clinical advances. PMID:25294122

  4. Spatial localization of bacteria controls coagulation of human blood by 'quorum acting'.

    PubMed

    Kastrup, Christian J; Boedicker, James Q; Pomerantsev, Andrei P; Moayeri, Mahtab; Bian, Yao; Pompano, Rebecca R; Kline, Timothy R; Sylvestre, Patricia; Shen, Feng; Leppla, Stephen H; Tang, Wei-Jen; Ismagilov, Rustem F

    2008-12-01

    Blood coagulation often accompanies bacterial infections and sepsis and is generally accepted as a consequence of immune responses. Though many bacterial species can directly activate individual coagulation factors, they have not been shown to directly initiate the coagulation cascade that precedes clot formation. Here we demonstrated, using microfluidics and surface patterning, that the spatial localization of bacteria substantially affects coagulation of human and mouse blood and plasma. Bacillus cereus and Bacillus anthracis, the anthrax-causing pathogen, directly initiated coagulation of blood in minutes when bacterial cells were clustered. Coagulation of human blood by B. anthracis required secreted zinc metalloprotease InhA1, which activated prothrombin and factor X directly (not via factor XII or tissue factor pathways). We refer to this mechanism as 'quorum acting' to distinguish it from quorum sensing--it does not require a change in gene expression, it can be rapid and it can be independent of bacterium-to-bacterium communication.

  5. Blood coagulation and the risk of atherothrombosis: a complex relationship.

    PubMed

    Spronk, Henri Mh; van der Voort, Danielle; Ten Cate, Hugo

    2004-12-01

    The principles of Virchov's triad appear to be operational in atherothrombosis or arterial thrombosis: local flow changes and particularly vacular wall damage are the main pathophysiological elements. Furthermore, alterations in arterial blood composition are also involved although the specific role and importance of blood coagulation is an ongoing matter of debate. In this review we provide support for the hypothesis that activated blood coagulation is an essential determinant of the risk of atherothrombotic complications. We distinguish two phases in atherosclerosis: In the first phase, atherosclerosis develops under influence of "classical" risk factors, i.e. both genetic and acquired forces. While fibrinogen/fibrin molecules participate in early plaque lesions, increased activity of systemic coagulation is of no major influence on the risk of arterial thrombosis, except in rare cases where a number of specific procoagulant forces collide. Despite the presence of tissue factor - factor VII complex it is unlikely that all fibrin in the atherosclerotic plaque is the direct result from local clotting activity. The dominant effect of coagulation in this phase is anticoagulant, i.e. thrombin enhances protein C activation through its binding to endothelial thrombomodulin.The second phase is characterized by advancing atherosclerosis, with greater impact of inflammation as indicated by an elevated level of plasma C-reactive protein, the result of increased production influenced by interleukin-6. Inflammation overwhelms protective anticoagulant forces, which in itself may have become less efficient due to down regulation of thrombomodulin and endothelial cell protein C receptor (EPCR) expression. In this phase, the inflammatory drive leads to recurrent induction of tissue factor and assembly of catalytic complexes on aggregated cells and on microparticles, maintaining a certain level of thrombin production and fibrin formation. In advanced atherosclerosis systemic and

  6. A plasma proteolysis pathway comprising blood coagulation proteases.

    PubMed

    Yang, Lu; Li, Yun; Bhattacharya, Arup; Zhang, Yuesheng

    2016-07-05

    Coagulation factors are essential for hemostasis. Here, we show that these factors also team up to degrade plasma proteins that are unrelated to hemostasis. Prolidase, SRC and amyloid β1-42 (Aβ1-42) are used as probes. Each probe, upon entering the blood circulation, binds and activates factor XII (FXII), triggering the intrinsic and common coagulation cascades, which in turn activate factor VII, a component of the extrinsic coagulation cascade. Activated factor VII (FVIIa) rapidly degrades the circulating probes. Therefore, FXII and FVIIa serve as the sensor/initiator and executioner, respectively, for the proteolysis pathway. Moreover, activation of this pathway by one probe leads to the degradation of all three probes. Significant activation of this pathway follows tissue injury and may also occur in other disorders, e.g., Alzheimer's disease, of which Aβ1-42 is a key driver. However, enoxaparin, a clinically used anticoagulant, inhibits the proteolysis pathway and elevates plasma levels of the probes. Enoxaparin may also mitigate potential impact of activators of the proteolysis pathway on coagulation. Our results suggest that the proteolysis pathway is important for maintaining low levels of various plasma proteins. Our finding that enoxaparin inhibits this pathway provides a means to control it. Inhibition of this pathway may facilitate the development of disease biomarkers and protein therapeutics, e.g., plasma Aβ1-42 as a biomarker of Alzheimer's disease or recombinant human prolidase as an antitumor agent.

  7. 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

  8. Mathematical models of blood coagulation and platelet adhesion: clinical applications.

    PubMed

    Panteleev, M A; Ananyeva, N M; Ataullakhanov, F I; Saenko, E L

    2007-01-01

    At present, computer-assisted molecular modeling and virtual screening have become effective and widely-used tools for drug design. However, a prerequisite for design and synthesis of a therapeutic agent is determination of a correct target in the metabolic system, which should be either inhibited or stimulated. Solution of this extremely complicated problem can also be assisted by computational methods. This review discusses the use of mathematical models of blood coagulation and platelet-mediated primary hemostasis and thrombosis as cost-effective and time-saving tools in research, clinical practice, and development of new therapeutic agents and biomaterials. We focus on four aspects of their application: 1) efficient diagnostics, i.e. theoretical interpretation of diagnostic data, including sensitivity of various clotting assays to the changes in the coagulation system; 2) elucidation of mechanisms of coagulation disorders (e.g. hemophilias and thrombophilias); 3) exploration of mechanisms of action of therapeutic agents (e.g. recombinant activated factor VII) and planning rational therapeutic strategy; 4) development of biomaterials with non-thrombogenic properties in the design of artificial organs and implantable devices. Accumulation of experimental knowledge about the blood coagulation system and about platelets, combined with impressive increase of computational power, promises rapid development of this field.

  9. Influence of solar activity on fibrinolysis and fibrinogenolysis. [statistical correlation between solar flare and blood coagulation indices

    NASA Technical Reports Server (NTRS)

    Marchenko, V. I.

    1974-01-01

    During periods of high solar activity fibrinolysis and fibrinogenolysis are increased. A direct correlative relationship is established between the indices of fibrinolysis, fibrinogenolysis and solar flares which were recorded two days before the blood was collected for analysis.

  10. Development of a User-Friendly App for Testing Blood Coagulation Status in Schizophrenia Patients.

    PubMed

    Vegt, Johannes; Guest, Paul C

    2017-01-01

    Blood coagulation time is an important factor to consider for postoperative and cardiac disorder patients who have been prescribed anticoagulant coagulant medications. The coagulation process is also known to be perturbed in some individuals with psychiatric disorders, such as schizophrenia. This chapter describes a patient self-management system for a functional assessment of blood coagulation activity, determining the appropriate anticoagulant dosages using a test strip device and the Coagu app. The app can also be used as a patient reminder of treatment times and to monitor treatment and effects over time.

  11. Hemophilia as a defect of the tissue factor pathway of blood coagulation: Effect of factors VIII and IX on factor X activation in a continuous-flow reactor

    SciTech Connect

    Repke, D.; Gemmell, C.H.; Guha, A.; Turitto, V.T.; Nemerson, Y. ); Broze, G.J. Jr. )

    1990-10-01

    The effect of factors VIII and IX on the ability of the tissue factor-factor VIIa complex to activate factor X was studied in a continuous-flow tubular enzyme reactor. Tissue factor immobilized in a phospholipid bilayer on the inner surface of the tube was exposed to a perfusate containing factors VIIa, VIII, IX, and X flowing at a wall shear rate of 57, 300, or 1130 sec{sup {minus}1}. The addition of factors VIII and IX at their respective plasma concentrations resulted in a further 2{endash}-to 3{endash}fold increase. The direct activation of factor X by tissue factor-factor VIIa could be virtually eliminated by the lipoprotein-associated coagulation inhibitor. These results suggest that the tissue factor pathway, mediated through factors VIII and IX, produces significant levels of factor Xa even in the presence of an inhibitor of the tissue factor-factor VIIa complex; moreover, the activation is dependent on local shear conditions. These findings are consistent both with a model of blood coagulation in which initiation of the system results from tissue factor and with the bleeding observed in hemophilia.

  12. Changes in the human blood coagulating system during prolonged hypokinesia

    NASA Technical Reports Server (NTRS)

    Filatova, L. M.; Anashkin, O. D.

    1978-01-01

    Changes in the coagulating system of the blood were studied in six subjects during prolonged hypokinesia. Thrombogenic properties of the blood rose in all cases on the 8th day. These changes are explained by stress reaction due to unusual conditions for a healthy person. Changes in the blood coagulating system in the group subjected to physical exercise and without it ran a practically parallel course. Apparently physical exercise is insufficient to prevent such changes that appear in the coagulating system of the blood during prolonged hypokinesia.

  13. In Vitro Effect of Activated Recombinant Factor VII (rFVIIa) on Coagulation Properties of Human Blood at Hypothermic Temperatures

    DTIC Science & Technology

    2007-11-01

    purified soy phosphatides in ellagic acid (Actin FS Activated PTT Reagent, Dade Behring, Marburg, Germany) was added to plasma samples in a 1:1 volume...acetylsali- cylic acid or any other nonsteroidal anti-inflammatory drugs for the 7 days before blood sampling. A smooth cubital venipuncture was...speed, and the plasma collected for the standard clotting assays. Prothrombin time (PT), activated partial thromboplastin time ( aPTT ), and fibrinogen

  14. Blood coagulation reactions on nanoscale membrane surfaces

    NASA Astrophysics Data System (ADS)

    Pureza, Vincent S.

    Blood coagulation requires the assembly of several membrane-bound protein complexes composed of regulatory and catalytic subunits. The biomembranes involved in these reactions not only provide a platform for these procoagulant proteins, but can also affect their function. Increased exposure of acidic phospholipids on the outer leaflet of the plasma membrane can dramatically modulate the catalytic efficiencies of such membrane-bound enzymes. Under physiologic conditions, however, these phospholipids spontaneously cluster into a patchwork of membrane microdomains upon which membrane binding proteins may preferentially assemble. As a result, the membrane composition surrounding these proteins is largely unknown. Through the development and use of a nanometer-scale bilayer system that provides rigorous control of the phospholipid membrane environment, I investigated the role of phosphatidylserine, an acidic phospholipid, in the direct vicinity (within nanometers) of two critical membrane-bound procoagulant protein complexes and their respective natural substrates. Here, I present how the assembly and function of the tissue factor˙factor VIIa and factor Va˙factor Xa complexes, the first and final cofactor˙enzyme complexes of the blood clotting cascade, respectively, are mediated by changes in their immediate phospholipid environments.

  15. Polymer Brushes Containing Sulfonated Sugar Repeat Units: Synthesis, Characterization and In Vitro Testing of Blood Coagulation Activation

    PubMed Central

    Ayres, N.; Holt, D. J.; Jones, C.F.; Corum, L. E.; Grainger, D. W.

    2009-01-01

    A new polymer brush chemistry containing sulfonated carbohydrate repeat units has been synthesized from silicon substrates using ATRP methods and characterized both in bulk and using surface analysis. The polymer brush was designed to act as a mimic for the naturally occurring sulfonated glycosaminoglycan, heparin, commonly used for modifying blood-contacting surfaces both in vitro and in vivo. Surface analysis showed conversion of brush saccharide precursor chemistry to the desired sulfonated polymer product. The sulfonated polymer brush surface was further analyzed using three conventional in vitro tests for blood compatibility -- plasma recalcification times, complement activation, and thrombin generation. The sulfonated polymer brush films on silicon oxide wafers exhibited better assay performance in these blood component assays than the unsulfonated sugar functionalized polymer brush in all tests performed. PMID:19859552

  16. Metals in airpollution particles decrease whole blood coagulation time

    EPA Science Inventory

    The mechanism underlying the pro-coagulative effect of air pollution particle exposure is not known. We tested the postulate that 1) the soluble fraction ofan air pollution particle can affect whole blood coagulation time and 2) metals included in the soluble fraction are respons...

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

    PubMed

    Casutt, M; Konrad, C; Schuepfer, G

    2012-11-01

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

  18. [Blood coagulation disorders in oncological patients].

    PubMed

    von Depka Prondzinski, M

    2005-01-01

    Patients with malignancies often experience acute disorders of coagulation. They may manifest as thromboembolism, disseminated intravascular coagulation or a tendency to bleed. Either disorder carries a high rate of complications and a difficult task in diagnosing and treating them. Some complications typical for patients with malignancies are discussed. Among these are tumor associated thrombophilia, acquired von Willebrand's disease, and thrombocytopenia.

  19. Effect of carryover of clot activators on coagulation tests during phlebotomy.

    PubMed

    Fukugawa, Yoko; Ohnishi, Hiroaki; Ishii, Takahiro; Tanouchi, Ayako; Sano, Junko; Miyawaki, Haruko; Kishino, Tomonori; Ohtsuka, Kouki; Yoshino, Hideaki; Watanabe, Takashi

    2012-06-01

    We investigated the effect of clot activators carried over from the serum tube on major coagulation tests during phlebotomy. First, blood specimens from 30 normal subjects were mixed with small amounts of fluid containing clot activators, and their effects on various coagulation tests were determined. Only the value of fibrin monomer complex displayed a remarkable change when thrombin-containing fluid was added to the blood specimens. Subsequently, 100 paired blood specimens (taken from 75 healthy volunteers and 25 patients taking warfarin) were collected in coagulation tubes before and after the serum tube using standard phlebotomy procedures. Various coagulation tests were performed to determine the effect of contamination of thrombin-containing blood on coagulation parameters. Differences between the 2 tubes were minimal but significant for some of the coagulation tests. Therefore, we conclude that the effect of clot activators in the serum tube on coagulation tests is minimal when standard phlebotomy procedures are used.

  20. [Clinical diagnosis of thrombosis and blood coagulation tests].

    PubMed

    Watanabe, K

    1998-03-01

    Blood coagulation tests are useful to diagnose some thrombotic diseases. Particularly, these tests are valuable for the diagnosis of familiar thrombophilia, antiphospholipid antibody syndrome (APS) and disseminated intravascular coagulation (DIC). For the diagnosis of thrombophilia, determinations of both biological activity and antigen level of antithrombin III, protein C and protein S are important for initial screening. Since activated protein C (APC) resistance is extremely rare in Japanese, APC resistant test that based on APTT, is unnecessary to include as one of the screening tests. Detection of activity and antigen level of either plasminogen or fibrinogen is recommended to screen the plasminogen deficiency or dysfibrinogenemia. Determination of lupus anticoagulant is needed for the diagnosis of APS. At this time, the dilute phospholipid APTT (dAPTT) or the dilute Russell viper venom time (dRVVT) may be useful as a screening test for LA because procedure of these tests are basically simple to perform in Japanese laboratory. In the next step, cross mixing test of dAPTT (or APTT) should be perform to make a diagnose of LA more solid. Final confirm tests can be conveniently carried out with kit of either STACLOT or LA-CONFIRM. Platelet count and FDP (or FDP D dimer) assay are two essential tests for the diagnosis of DIC. Criteria of diagnosis for DIC recommended by Blood Coagulation Research Group of Japanese Ministry of Health and Welfare is not unnecessarily appropriate for practical use. TAT and PIC can be a good laboratory tests for early detection of hypercoagulable state in patients with DIC.

  1. Effect of magnetic bracelets on the coagulation and anticoagulation systems of the blood of patients with hypertension

    NASA Technical Reports Server (NTRS)

    Bublis, V. V.; Zabrodina, L. V.; Platonova, A. T.; Meyerova, Y. A.

    1974-01-01

    The data which have been obtained on the influence of magnetic bracelets on the coagulation and anticoagulation systems of the blood indicate that the wearing of magnetic bracelets results in a decrease in the coagulation activity of the blood and an increase in the activity of the anticoagulation system. These changes must be viewed as favorable for patients with cardiovascular pathology.

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

    PubMed

    Ilinskaya, Anna N; Dobrovolskaia, Marina A

    2013-06-01

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

  3. The effects of oral administration of Yunnan Baiyao on blood coagulation in beagle dogs as measured by kaolin-activated thromboelastography and buccal mucosal bleeding times.

    PubMed

    Frederick, Jami; Boysen, Søren; Wagg, Catherine; Chalhoub, Serge

    2017-01-01

    We examined the effects of oral administration of Yunnan Baiyao (YB) on hemostasis by measuring buccal mucosal bleeding times (BMBTs) and doing citrated kaolin-activated whole-blood thromboelastography (TEG). In a randomized controlled crossover trial 8 beagle dogs were given either placebo or 1000 mg of YB orally every 12 h for 5 consecutive treatments. Blood was drawn 24 h before treatment and 2 and 24 h after the last treatment, and the BMBT was measured in each sample in duplicate. The TEG analysis was done in duplicate 60 ± 5 min after sample collection. There were no adverse effects of treatment and no significant differences between the control and treatment BMBTs or TEG parameters at any time point. Significant differences were found between baseline and 24 h after the last treatment within the treatment group for the TEG parameters LY30 and LY60 and within the control group for the TEG parameters MA, G, LY30, and LY60. Thus, at the dose and frequency of administration in this study YB did not appear to have any clinically significant effects on the measured coagulation parameters. The differences within the treatment group were likely due to analytic error since similar differences were seen in the control group. Further studies with a larger sample, as well as more direct measures of platelet function, are needed.

  4. Coagulation on biomaterials in flowing blood: some theoretical considerations.

    PubMed

    Basmadjian, D; Sefton, M V; Baldwin, S A

    1997-12-01

    Are truly inert biomaterials feasible? Recent mathematical models of coagulation which are reviewed here suggest that such materials are impossible. This conclusion, which is certainly consistent with our collective experimental evidence, arises from the calculation that conversion of Factor XI to XIa never drops to zero even at the highest flow rates and with virtually no Factor XIIa bound to a surface. Residual amounts of XIa are still formed which can in principle kick-off the coagulation cascade. Furthermore, if the flow rates and corresponding mass transfer coefficients are low and in spite of these near-vanishing levels of the initiating coagulants, the surprising result is that substantial amounts of thrombin are produced. On the contrary, under slightly higher flow conditions, there can be more substantial levels of initiating coagulants, yet paradoxically thrombin production is near zero. This article presents a theoretical understanding of the events which take place during the interaction of biomaterials with flowing blood. We follow these events from the time of first contact to the final production of thrombin. The effect of flow and surface activity on the contact phase reactions is examined in detail and the two are found to be intertwined. The common pathway is also examined and here the main feature is the existence of three flow dependent regions which produce either high or very low levels of thrombin, as well as multiple thrombin steady states. In a final analysis we link the two segments of the cascade and consider the events which result. In addition, we note that multiple steady states arise only in the presence of two (thrombin) feedback loops. Single loops or the bare cascade will produce only single steady states. With some imagination one can attribute to the feedback loops the role of providing the cascade with a mechanism to produce high thrombin levels in case of acute need (e.g. bleeding) or to allow levels to subside to 'stand

  5. Plasmin-induced procoagulant effects in the blood coagulation: a crucial role of coagulation factors V and VIII.

    PubMed

    Ogiwara, Kenichi; Nogami, Keiji; Nishiya, Katsumi; Shima, Midori

    2010-09-01

    Plasminogen activators provide effective treatment for patients with acute myocardial infarction. However, paradoxical elevation of thrombin activity associated with failure of clot lysis and recurrent thrombosis has been reported. Generation of thrombin in these circumstances appears to be owing to plasmin (Plm)-induced activation of factor (F) XII. Plm catalyzes proteolysis of several coagulant factors, but the roles of these factors on Plm-mediated procoagulant activity remain to be determined. Recently developed global coagulation assays were used in this investigation. Rotational thromboelastometry using whole blood, clot waveform analysis and thrombin generation tests using plasma, showed that Plm (> or =125 nmol/l) shortened the clotting times in similar dose-dependent manners. In particular, the thrombin generation test, which was unaffected by products of fibrinolysis, revealed the enhanced coagulation with an approximately two-fold increase of peak level of thrombin generation. Studies using alpha2-antiplasmin-deficient plasma revealed that much lower dose of Plm (> or =16 nmol/l) actually contributed to enhancing thrombin generation. The shortening of clotting time could be observed even in the presence of corn trypsin inhibitor, supporting that Plm exerted the procoagulant activity independently of FXII. In addition, using specific coagulation-deficient plasmas, the clot waveform analysis showed that Plm did not shorten the clotting time in only FV-deficient or FVIII-deficient plasma in prothrombin time-based or activated partial thromboplastin time-based assay, respectively. Our results indicated that Plm did possess procoagulant activity in the blood coagulation, and this effect was likely attributed by multicoagulation factors, dependent on FV and/or FVIII.

  6. Regulation of tissue factor coagulant activity on cell surfaces

    PubMed Central

    RAO, L.V.M.; PENDURTHI, U.R.

    2012-01-01

    Summary Tissue factor (TF) is a transmembrane glycoprotein and an essential component of factor VIIa-TF enzymatic complex that triggers activation of the coagulation cascade. Formation of TF-FVIIa complexes on cell surfaces not only trigger the coagulation cascade but also transduce cell signaling via activation of protease-activated receptors. Tissue factor is expressed constitutively on cell surfaces of a variety of extravascular cell types, including fibroblasts and pericytes in and surrounding blood vessel walls and epithelial cells but generally absent on cells that come in contact with blood directly. However, TF expression could be induced in some blood cells, such as monocytes and endothelial cells, following an injury or pathological stimuli. Tissue factor is essential for hemostasis, but aberrant expression of TF leads to thrombosis. Therefore, a proper regulation of TF activity is critical for the maintenance of hemostatic balance and health in general. TF-FVIIa coagulant activity at the cell surface is influenced not only by TF protein expression levels but also independently by a variety of mechanisms, including alterations in membrane phospholipid composition and cholesterol content, thiol-dependent modifications of TF allosteric disulfide bond, and other post-translational modifications of TF. In this article, we critically review key literature on mechanisms by which TF coagulant activity is regulated at the cell surface in the absence of changes in TF protein levels with specific emphasis on recently published data and provide the authors’ perspective on the subject. PMID:23006890

  7. [Effect of composition of reagents for activated partial thromboplastin time on their sensitivity during analysis of blood coagulation factors].

    PubMed

    Berkovskiĭ, A L; Vasil'ev, S A; Sergeeva, E V; Kozlov, A A

    2000-04-01

    Brain cephaline-based reagents for evaluating activated partial thromboplastin time (APTT) and soybean phosphatides with ellagic acid complex activator with intermediate metal ions have been studied. The sensitivity of these reagents to internal clotting factors (VIII and IX) and heparin is determined by phospholipid nature and type of metal. The results help obtain highly active and sensitive APTT reagents.

  8. Change in fibrinolytic activity under the influence of a constant magnetic field. [blood coagulation normilization in heart patients

    NASA Technical Reports Server (NTRS)

    Yepishina, S. G.

    1974-01-01

    The fibrinolytic activity of plasma changes under the influence of a constant magnetic field (CMF) with a strength of 250 or 2500 oersteds. CMF shows a tendency toward normalization of fibrinolytic processes in the presence of pathological disturbances in fibrinolysis activation.

  9. Blood coagulation and propagation of autowaves in flow.

    PubMed

    Ermakova, Elena A; Panteleev, Mikhail A; Shnol, Emmanuil E

    2005-01-01

    This study analyses the effect of flow and boundary reactions on spatial propagation of waves of blood coagulation. A simple model of coagulation in plasma consisting of three differential reaction-diffusion equations was used for numerical simulations. The vessel was simulated as a two-dimensional channel of constant width, and the anticoagulant influence of thrombomodulin present on the undamaged vessel wall was taken into account. The results of the simulations showed that this inhibition could stop the coagulation process in the absence of flow in narrow channels. For the used mathematical model of coagulation this was the case if the width was below 0.2 mm. In wider vessels, the process could be stopped by the rapid blood flow. The required flow rate increased with the increase of the damage region size. For example, in a 0.5-mm wide channel with 1-mm long damage region, the propagation of coagulation may be terminated at the flow rate of more than 20 mm/min.

  10. Cardiovascular and blood coagulative effects of pulmonary zinc exposure

    SciTech Connect

    Gilmour, Peter S.; Nyska, Abraham; Schladweiler, Mette C.; McGee, John K.; Wallenborn, J. Grace; Richards, Judy H.; Kodavanti, Urmila P. . E-mail: kodavanti.urmila@epa.gov

    2006-02-15

    Cardiovascular damage induced by pulmonary exposure to environmental chemicals can result from direct action or, secondarily from pulmonary injury. We have developed a rat model of pulmonary exposure to zinc to demonstrate cardiac, coagulative, and fibrinolytic alterations. Male Wistar Kyoto rats were instilled intratracheally with saline or zinc sulfate, 131 {mu}g/kg (2 {mu}mol/kg); the alterations were determined at 1, 4, 24, and 48 h postexposure. High-dose zinc enabled us to show changes in circulating levels of zinc above normal and induce significant pulmonary inflammation/injury such that cardiac impairments were likely. At 1-24 h postexposure, plasma levels of zinc increased to nearly 20% above the base line. Significant pulmonary inflammation and injury were determined by analysis of bronchoalveolar lavage fluid and histopathology in zinc-exposed rats at all time points. Starting at 4 h postexposure, pulmonary damage was accompanied by persistently increased gene expressions of tissue factor (TF) and plasminogen activator-inhibitor-1 (PAI-1), but not thrombomodulin (TM). Cardiac tissues demonstrated similar temporal increases in expressions of TF, PAI-1, and TM mRNA following pulmonary instillation of zinc. In contrast to extensive pulmonary edema and inflammation, only mild, and focal acute, myocardial lesions developed in a few zinc-exposed rats; no histological evidence showed increased deposition of fibrin or disappearance of troponin. At 24 and 48 h postexposure to zinc, increases occurred in levels of systemic fibrinogen and the activated partial thromboplastin time. These data suggest that cardiovascular blood coagulation impairments are likely following pulmonary zinc exposure and associated pulmonary injury and inflammation.

  11. Evaluation of whole blood coagulation process by optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Xu, Xiangqun; Lin, Jia

    2010-11-01

    This study was to investigate the feasibility of using optical coherence tomography (OCT) to evaluate whole blood coagulation process. Attenuation coefficients and 1/e light penetration depth (D1/e) against time of human whole blood during in vitro clot formation under static were measured from the OCT profiles of reflectance vs depth. The results obtained clearly showed that the optical parameters are able to identify three stages during the in vitro blood clotting process. It is concluded that D1/e measured by OCT is a potential parameter to quantify and follow the liquid-gel transition of blood during clotting.

  12. Multifrequency acoustics as a probe of mesoscopic blood coagulation dynamics

    NASA Astrophysics Data System (ADS)

    Ganesan, Adarsh; Rajendran, Gokulnath; Ercole, Ari; Seshia, Ashwin

    2016-08-01

    Coagulation is a complex enzymatic polymerisation cascade. Disordered coagulation is common in medicine and may be life-threatening yet clinical assays are typically bulky and/or provide an incomplete picture of clot mechanical evolution. We present the adaptation of an in-plane acoustic wave device: quartz crystal microbalance with dissipation at multiple harmonics to determine the time-evolution of mesoscale mechanical properties of clot formation in vitro. This approach is sensitive to changes in surface and bulk clot structure in various models of induced coagulopathy. Furthermore, we are able to show that clot formation at surfaces has different kinetics and mechanical strength to that in the bulk, which may have implications for the design of bioprosthetic materials. The "Multifrequency acoustics" approach thus enables unique capability to portray biological processes concerning blood coagulation.

  13. 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.

  14. Adaptive Force Sonorheometry for Assessment of Whole Blood Coagulation

    PubMed Central

    Mauldin, F. William; Viola, Francesco; Hamer, Theresa C.; Ahmed, Eman M.; Crawford, Shawna B.; Haverstick, Doris M.; Lawrence, Michael B.; Walker, William F.

    2010-01-01

    Background: Viscoelastic diagnostics that monitor the hemostatic function of whole blood (WB), such as thromboelastography, have been developed with demonstrated clinical utility. By measuring the cumulative effects of all components of hemostasis, viscoelastic diagnostics have circumvented many of the challenges associated with more common tests of blood coagulation. Methods: We describe a new technology, called sonorheometry, that adaptively applies acoustic radiation force to assess coagulation function in WB. The repeatability (precision) of coagulation parameters was assessed using citrated WB samples. A reference range of coagulation parameters, along with corresponding measurements from prothrombin time (PT) and partial thromboplastin time (PTT), were obtained from WB samples of 20 healthy volunteers. In another study, sonorheometry monitored anticoagulation with heparin (0 – 5 IU/ml) and reversal from varied dosages of protamine (0 – 10 IU/ml) in heparinized WB (2 IU/ml). Results: Sonorheometry exhibited low CVs for parameters: clot initiation time (TC1), < 7%; clot stabilization time (TC2), < 6.5%; and clotting angle (θ), < 3.5%. Good correlation was observed between clotting times, TC1 and TC2, and PTT (r = 0.65 and 0.74 respectively; n=18). Linearity to heparin dosage was observed with average linearity r > 0.98 for all coagulation parameters. We observed maximum reversal of heparin anticoagulation at protamine to heparin ratios of 1.4:1 from TC1 (P=0.6) and 1.2:1 from θ (P=0.55). Conclusions: Sonorheometry is a non-contact method for precise assessment of WB coagulation. PMID:20096680

  15. Micro-electromechanical film bulk acoustic sensor for plasma and whole blood coagulation monitoring.

    PubMed

    Chen, Da; Song, Shuren; Ma, Jilong; Zhang, Zhen; Wang, Peng; Liu, Weihui; Guo, Qiuquan

    2017-05-15

    Monitoring blood coagulation is an important issue in the surgeries and the treatment of cardiovascular diseases. In this work, we reported a novel strategy for the blood coagulation monitoring based on a micro-electromechanical film bulk acoustic resonator. The resonator was excited by a lateral electric field and operated under the shear mode with a frequency of 1.9GHz. According to the apparent step-ladder curves of the frequency response to the change of blood viscoelasticity, the coagulation time (prothrombin time) and the coagulation kinetics were measured with the sample consumption of only 1μl. The procoagulant activity of thromboplastin and the anticoagulant effect of heparin on the blood coagulation process were illustrated exemplarily. The measured prothrombin times showed a good linear correlation with R(2)=0.99969 and a consistency with the coefficient of variation less than 5% compared with the commercial coagulometer. The proposed film bulk acoustic sensor, which has the advantages of small size, light weight, low cost, simple operation and little sample consumption, is a promising device for miniaturized, online and automated analytical system for routine diagnostics of hemostatic status and personal health monitoring.

  16. 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

  17. Mesoscopic Modeling of Blood Clotting: Coagulation Cascade and Platelets Adhesion

    NASA Astrophysics Data System (ADS)

    Yazdani, Alireza; Li, Zhen; Karniadakis, George

    2015-11-01

    The process of clot formation and growth at a site on a blood vessel wall involve a number of multi-scale simultaneous processes including: multiple chemical reactions in the coagulation cascade, species transport and flow. To model these processes we have incorporated advection-diffusion-reaction (ADR) of multiple species into an extended version of Dissipative Particle Dynamics (DPD) method which is considered as a coarse-grained Molecular Dynamics method. At the continuum level this is equivalent to the Navier-Stokes equation plus one advection-diffusion equation for each specie. The chemistry of clot formation is now understood to be determined by mechanisms involving reactions among many species in dilute solution, where reaction rate constants and species diffusion coefficients in plasma are known. The role of blood particulates, i.e. red cells and platelets, in the clotting process is studied by including them separately and together in the simulations. An agonist-induced platelet activation mechanism is presented, while platelets adhesive dynamics based on a stochastic bond formation/dissociation process is included in the model.

  18. [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

  19. New method for detection of blood coagulation using fiber-optic sensor

    NASA Astrophysics Data System (ADS)

    Fediay, Sergey G.; Kuznetzov, Alexsey V.

    1991-07-01

    The detection of blood coagulation is very important in therapeutics and surgery. It is necessary to determine the overall time taken for blood clotting, production rate of thrombin, presence or absence of blood coagulation factors, etc. In this paper a new method for detection of blood coagulation is presented. This method is based on the fiber-optic sensor and allows for the study of different ways of blood clotting (such as blood coagulation and platelets aggregation) separately, thus enhancing the precision of determination. The method for determining the blood coagulation presented possesses high precision in monitoring the process of coagulation. An elaborate mathematical model of the process of blood coagulation has been developed to help the computer handle obtained data.

  20. Dynamic and quantitative assessment of blood coagulation using optical coherence elastography

    NASA Astrophysics Data System (ADS)

    Xu, Xiangqun; Zhu, Jiang; Chen, Zhongping

    2016-04-01

    Reliable clot diagnostic systems are needed for directing treatment in a broad spectrum of cardiovascular diseases and coagulopathy. Here, we report on non-contact measurement of elastic modulus for dynamic and quantitative assessment of whole blood coagulation using acoustic radiation force orthogonal excitation optical coherence elastography (ARFOE-OCE). In this system, acoustic radiation force (ARF) is produced by a remote ultrasonic transducer, and a shear wave induced by ARF excitation is detected by the optical coherence tomography (OCT) system. During porcine whole blood coagulation, changes in the elastic property of the clots increase the shear modulus of the sample, altering the propagating velocity of the shear wave. Consequently, dynamic blood coagulation status can be measured quantitatively by relating the velocity of the shear wave with clinically relevant coagulation metrics, including reaction time, clot formation kinetics and maximum shear modulus. The results show that the ARFOE-OCE is sensitive to the clot formation kinetics and can differentiate the elastic properties of the recalcified porcine whole blood, blood added with kaolin as an activator, and blood spiked with fibrinogen.

  1. Influence of a constant magnetic field on thrombocytes. [delay of blood coagulation time

    NASA Technical Reports Server (NTRS)

    Meyerova, Y. A.

    1974-01-01

    In an experiment on white mice it was found that a constant electromagnetic field with strength of 250-275 oersteds is biologically active at an exposure of 55 minutes. Qualitative and morphological changes in thrombocytes 1-3 days following exposure reduced their numbers, prolonged blood coagulation time and increased the number of leucocytes.

  2. Numerical simulations of a reduced model for blood coagulation

    NASA Astrophysics Data System (ADS)

    Pavlova, Jevgenija; Fasano, Antonio; Sequeira, Adélia

    2016-04-01

    In this work, the three-dimensional numerical resolution of a complex mathematical model for the blood coagulation process is presented. The model was illustrated in Fasano et al. (Clin Hemorheol Microcirc 51:1-14, 2012), Pavlova et al. (Theor Biol 380:367-379, 2015). It incorporates the action of the biochemical and cellular components of blood as well as the effects of the flow. The model is characterized by a reduction in the biochemical network and considers the impact of the blood slip at the vessel wall. Numerical results showing the capacity of the model to predict different perturbations in the hemostatic system are discussed.

  3. 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.

  4. In vitro thrombogenesis resulting from decreased shear rate and blood coagulability.

    PubMed

    Maruyama, Osamu; Kosaka, Ryo; Nishida, Masahiro; Yamane, Takashi; Tatsumi, Eisuke; Taenaka, Yoshiyuki

    2016-06-15

    In vitro antithrombogenic testing with mock circulation is a useful type of pre-evaluation in ex vivo testing of mechanical assist devices. For effective in vitro testing, we have been developing a clear quantitative thrombogenesis model based on shear stress and blood coagulability. Bovine blood was used as the test medium. The activating clotting time (ACT) was adjusted with trisodium citrate and calcium chloride from 200 to 1,000 seconds. The blood was then applied to a rheometer and subjected to shear at 50 to 2,880 s-1. Blood coagulation time and degree of thrombogenesis were measured by the torque sensor of the rheometer. Prothrombin time (PT) and activated partial thromboplastin time (APTT) of the test blood were also measured after the application of shear. Blood coagulation time increased, and the degree of thrombogenesis decreased, with increases in shear rate to between 50 and 2,880 s-1. for test bloods with ACTs of 200 to 250 seconds. An ACT of 200 to 250 seconds is thus appropriate for in vitro antithrombogenic testing under a shear rate of 2,880 s-1. APTT was prolonged, whereas PT did not change, with increasing shear rate: that is, increasing the shear rate reduced thrombogenesis related to the intrinsic clotting pathway. An ACT of 200 to 250 seconds was suitable for in vitro antithrombogenic testing, and increasing the shear stress generated in the mechanical assist device reduced thrombogenesis via the intrinsic clotting pathway.

  5. CpaA a novel protease from Acinetobacter baumannii clinical isolates deregulates blood coagulation.

    PubMed

    Tilley, Derek; Law, Robert; Warren, Sarah; Samis, John A; Kumar, Ayush

    2014-07-01

    Acinetobacter baumannii is an important nosocomial pathogen that displays high antibiotic resistance. It causes a variety of infections including pneumonias and sepsis which may result in disseminated intravascular coagulation. In this work, we identify and characterize a novel secreted, zinc-dependent, metallo-endopeptidase CpaA (coagulation targeting metallo-endopeptidase of Acinetobacter baumannii) which deregulates human blood coagulation in vitro and thus is likely to contribute to A. baumannii virulence. Three quarters of the clinical isolates tested (n = 16) had the cpaA gene; however, it was absent from two type strains, A. baumannii ATCC 17978 and A. baumannii ATCC 19606. The CpaA protein was purified from one clinical isolate and was able to cleave purified factor (F) V and fibrinogen and reduce the coagulation activity of FV in human plasma. CpaA-treated plasma showed reduced clotting activity in contact pathway-activated partial thromboplastin time (aPTT) assays, but increased clotting activity in tissue factor pathway prothrombin time (PT) assays. A significant portion of clinically relevant A. baumannii isolates secrete a protease which targets and deregulates the coagulation system.

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

    PubMed

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

    2015-04-01

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

  7. Assessing quality of life in individuals with hereditary blood coagulation disorders.

    PubMed

    Solovieva, S; Santavirta, N; Santavirta, S; Konttinen, Y T

    2004-06-01

    The aim of this study was to test the reliability and validity of the SF-36 questionnaire among the patients with hereditary blood coagulation disorders, to compare their quality of life (QoL) to that of healthy controls, and to identify the dimensions of life the patients consider most important. Results showed that the SF-36 questionnaire had good internal consistency reliability and construct and known group validity in individuals with hereditary blood coagulation disorders. Leisure activities/hobbies, availability of work/ study, followed by relationships with other people, own health and relationships with family/relatives appeared most frequently across the patients' and controls' priority ranks. The areas affected most by the disease were financial security, own health and relationships with family/relatives. A comparison of standardized scale scores suggests that blood coagulation disorders are diseases with a predominantly physical impact. Patients with blood coagulation disorders had health-related quality of life that was lower in most domains compared to healthy controls. However, when a wider concept of QoL was applied no differences between the patients' and controls' perceived QoL could be noted.

  8. Grow with the flow: a spatial–temporal model of platelet deposition and blood coagulation under flow

    PubMed Central

    Leiderman, Karin; Fogelson, Aaron L.

    2011-01-01

    The body's response to vascular injury involves two intertwined processes: platelet aggregation and coagulation. Platelet aggregation is a predominantly physical process, whereby platelets clump together, and coagulation is a cascade of biochemical enzyme reactions. Thrombin, the major product of coagulation, directly couples the biochemical system to platelet aggregation by activating platelets and by cleaving fibrinogen into fibrin monomers that polymerize to form a mesh that stabilizes platelet aggregates. Together, the fibrin mesh and the platelet aggregates comprise a thrombus that can grow to occlusive diameters. Transport of coagulation proteins and platelets to and from an injury is controlled largely by the dynamics of the blood flow. To explore how blood flow affects the growth of thrombi and how the growing masses, in turn, feed back and affect the flow, we have developed the first spatial–temporal mathematical model of platelet aggregation and blood coagulation under flow that includes detailed descriptions of coagulation biochemistry, chemical activation and deposition of blood platelets, as well as the two-way interaction between the fluid dynamics and the growing platelet mass. We present this model and use it to explain what underlies the threshold behaviour of the coagulation system's production of thrombin and to show how wall shear rate and near-wall enhanced platelet concentrations affect the development of growing thrombi. By accounting for the porous nature of the thrombus, we also demonstrate how advective and diffusive transport to and within the thrombus affects its growth at different stages and spatial locations. PMID:20439306

  9. The vulnerable blood. Coagulation and clot structure in diabetes mellitus.

    PubMed

    Hess, K

    2015-01-01

    Patients with diabetes are at increased risk of cardiovascular morbidity and mortality. While arteriosclerotic lesions have long been recognized as the underlying cause more recent studies suggest that alterations of the blood are also critically involved. Following plaque rupture, adherence of platelets is followed by the formation of a cross-linked fibrin clot. Patients with diabetes exhibit a prothrombotic milieu consisting of hyper reactive platelets, a tight and rigid clot structure which is due to up-regulation of coagulation factors and prolongation of clot lysis. Metabolic alterations as well as inflammatory processes, which are up-regulated in diabetes, are thought to be the main underlying causes. More recently, the complement cascade has emerged as a potential new player in this context with several complement components directly influencing both platelet function and coagulation. This review provides an overview concerning the changes that lead to alterations of platelet function and clot structure in diabetes.

  10. Coagulation changes during lower body negative pressure and blood loss in humans.

    PubMed

    van Helmond, Noud; Johnson, Blair D; Curry, Timothy B; Cap, Andrew P; Convertino, Victor A; Joyner, Michael J

    2015-11-01

    We tested the hypothesis that markers of coagulation activation are greater during lower body negative pressure (LBNP) than those obtained during blood loss (BL). We assessed coagulation using both standard clinical tests and thrombelastography (TEG) in 12 men who performed a LBNP and BL protocol in a randomized order. LBNP consisted of 5-min stages at 0, -15, -30, and -45 mmHg of suction. BL included 5 min at baseline and following three stages of 333 ml of blood removal (up to 1,000 ml total). Arterial blood draws were performed at baseline and after the last stage of each protocol. We found that LBNP to -45 mmHg is a greater central hypovolemic stimulus versus BL; therefore, the coagulation markers were plotted against central venous pressure (CVP) to obtain stimulus-response relationships using the linear regression line slopes for both protocols. Paired t-tests were used to determine whether the slopes of these regression lines fell on similar trajectories for each protocol. Mean regression line slopes for coagulation markers versus CVP fell on similar trajectories during both protocols, except for TEG α° angle (-0.42 ± 0.96 during LBNP vs. -2.41 ± 1.13°/mmHg during BL; P < 0.05). During both LBNP and BL, coagulation was accelerated as evidenced by shortened R-times (LBNP, 9.9 ± 2.4 to 6.2 ± 1.1; BL, 8.7 ± 1.3 to 6.4 ± 0.4 min; both P < 0.05). Our results indicate that LBNP models the general changes in coagulation markers observed during BL.

  11. Identification of the blood coagulation factor interacting sequences in staphylococcal superantigen-like protein 10.

    PubMed

    Itoh, Saotomo; Takii, Takemasa; Onozaki, Kikuo; Tsuji, Tsutomu; Hida, Shigeaki

    2017-03-25

    Staphylococcal superantigen-like proteins (SSLs) are a family of exoproteins of Staphylococcus aureus. We have shown that SSL10 binds to vitamin K-dependent coagulation factors and inhibits blood coagulation induced by recalcification of citrated plasma. SSL10 was revealed to bind to coagulation factors via their γ-carboxyglutamic acid (Gla) domain. In this study we attempted to identify the responsible sequence of SSL10 for the interaction with coagulation factors. We prepared a series of domain swap mutants between SSL10 and its paralog SSL7 that does not interact with coagulation factors, and examined their binding activity to immobilized prothrombin using ELISA-like binding assay. The domain swap mutants that contained SSL10β1-β3 ((23)MEMKN ISALK HGKNN LRFKF RGIKI QVL(60)) bound to immobilized prothrombin, and mutants that contained SSL10β10-β12 ((174)SFYNL DLRSK LKFKY MGEVI ESKQI KDIEV NLK(207)) also retained the binding activity. On the other hand, mutants that lacked these two regions did not bind to prothrombin. These sequences, each alone, bound to prothrombin as 33 amino acid length polypeptides. These results suggest that SSL10 has two responsible sequences for the binding to prothrombin. These prothrombin-binding peptides would contribute to the development of new anticoagulants.

  12. Hereditary blood coagulation disorders: management and dental treatment.

    PubMed

    Gómez-Moreno, G; Cutando-Soriano, A; Arana, C; Scully, C

    2005-11-01

    Patients with hereditary hemostatic disorders, characterized by a tendency to bleeding or thrombosis, constitute a serious challenge in the dental practice. Advances in the medical diagnosis of hemostatic disorders have exposed dental professionals to new patients not amenable to the application of the management protocols associated with other, more well-known, disorders. It is the aim of this paper to review the evidence, to highlight the areas of major concern, and to suggest management regimens for patients with hereditary hemostatic disorders. An extensive review has been made (PubMed, Science Direct, Web of Knowledge, etc.) of literature pertaining to hereditary disorders affecting blood coagulation factors and how they affect the practice of dentistry. Several aspects relating to the care of such patients must be recognized and taken into consideration when dental treatment is planned. Replacement of deficient coagulation factors ensures that safe dental treatment will be carried out. However, the half-life of such coagulation factors requires that dental treatment be specifically planned and adapted to the type of pathology involved.

  13. Synthetic oligopeptide substrates: their diagnostic application in blood coagulation, fibrinolysis, and other pathologic states

    SciTech Connect

    Huseby, R.M.; Smith, R.E.

    1980-01-01

    This review article with 522 references, focuses on the use of synthetic oligopepide substrates to measure the activity of proteoytic enzymes in human physiology and pathology. A classification of proteinases based on their mechanism of action is presented. The application of these synthetic oligopeptide substrates to understand the disorders of the blood coagulation and fibrinolytic system is reviewed. Intracellular functioning proteinases were also assessed in relation to certain pathologies where their abnormal activity is recognized.

  14. Surface-mediated molecular events in material-induced blood-plasma coagulation

    NASA Astrophysics Data System (ADS)

    Chatterjee, Kaushik

    Coagulation and thrombosis persist as major impediments associated with the use of blood-contacting medical devices. We are investigating the molecular mechanism underlying material-induced blood-plasma coagulation focusing on the role of the surface as a step towards prospective development of improved hemocompatible biomaterials. A classic observation in hematology is that blood/blood-plasma in contact with clean glass surface clots faster than when in contact with many plastic surfaces. The traditional biochemical theory explaining the underlying molecular mechanism suggests that hydrophilic surfaces, like that of glass, are specific activators of the coagulation cascade because of the negatively-charged groups on the surface. Hydrophobic surfaces are poor procoagulants or essentially "benign" because they lack anionic groups. Further, these negatively-charged surfaces are believed to not only activate blood factor XII (FXII), the key protein in contact activation, but also play a cofactor role in the amplification and propagation reactions that ultimately lead to clot formation. In sharp contrast to the traditional theory, our investigations indicate a need for a paradigm shift in the proposed sequence of contact activation events to incorporate the role of protein adsorption at the material surfaces. These studies have lead to the central hypothesis for this work proposing that protein adsorption to hydrophobic surfaces attenuates the contact activation reactions so that poorly-adsorbent hydrophilic surfaces appear to be stronger procoagulants relative to hydrophobic surfaces. Our preliminary studies measuring the plasma coagulation response of activated FXII (FXIIa) on different model surfaces suggested that the material did not play a cofactor role in the processing of this enzyme dose through the coagulation pathway. Therefore, we focused our efforts on studying the mechanism of initial production of enzyme at the procoagulant surface. Calculations for the

  15. Using a Systems Pharmacology Model of the Blood Coagulation Network to Predict the Effects of Various Therapies on Biomarkers

    PubMed Central

    Nayak, S; Lee, D; Patel-Hett, S; Pittman, DD; Martin, SW; Heatherington, AC; Vicini, P; Hua, F

    2015-01-01

    A number of therapeutics have been developed or are under development aiming to modulate the coagulation network to treat various diseases. We used a systems model to better understand the effect of modulating various components on blood coagulation. A computational model of the coagulation network was built to match in-house in vitro thrombin generation and activated Partial Thromboplastin Time (aPTT) data with various concentrations of recombinant factor VIIa (FVIIa) or factor Xa added to normal human plasma or factor VIII-deficient plasma. Sensitivity analysis applied to the model revealed that lag time, peak thrombin concentration, area under the curve (AUC) of the thrombin generation profile, and aPTT show different sensitivity to changes in coagulation factors’ concentrations and type of plasma used (normal or factor VIII-deficient). We also used the model to explore how variability in concentrations of the proteins in coagulation network can impact the response to FVIIa treatment. PMID:26312163

  16. Spatial Propagation and Localization of Blood Coagulation Are Regulated by Intrinsic and Protein C Pathways, Respectively

    PubMed Central

    Panteleev, Mikhail A.; Ovanesov, Mikhail V.; Kireev, Dmitrii A.; Shibeko, Aleksei M.; Sinauridze, Elena I.; Ananyeva, Natalya M.; Butylin, Andrey A.; Saenko, Evgueni L.; Ataullakhanov, Fazoil I.

    2006-01-01

    Blood coagulation in vivo is a spatially nonuniform, multistage process: coagulation factors from plasma bind to tissue factor (TF)-expressing cells, become activated, dissociate, and diffuse into plasma to form enzymatic complexes on the membranes of activated platelets. We studied spatial regulation of coagulation using two approaches: 1), an in vitro experimental model of clot formation in a thin layer of plasma activated by a monolayer of TF-expressing cells; and 2), a computer simulation model. Clotting in factor VIII- and factor XI-deficient plasmas was initiated normally, but further clot elongation was impaired in factor VIII- and, at later stages, in factor XI-deficient plasma. The data indicated that clot elongation was regulated by factor Xa formation by intrinsic tenase, whereas factor IXa was formed by extrinsic tenase on activating cells and diffused into plasma, thus sustaining clot growth. Far from the activating cells, additional factor IXa was produced by factor XIa. Exogenously added TF had no effect on the clot growth rate, suggesting that plasma TF does not contribute significantly to the clot propagation process in a reaction-diffusion system without flow. Addition of thrombomodulin at 3–100 nM caused dose-dependent termination of clot elongation with a final clot size of 2–0.2 mm. These results identify roles of specific coagulation pathways at different stages of spatial clot formation (initiation, elongation, and termination) and provide a possible basis for their therapeutic targeting. PMID:16326897

  17. Coagulation competence and fluid recruitment after moderate blood loss in young men.

    PubMed

    Zaar, Morten; Mørkeberg, Jakob; Pott, Frank C; Johansson, Pär I; Secher, Niels H

    2014-09-01

    The coagulation system is activated by a reduction of the central blood volume during orthostatic stress and lower body negative pressure suggesting that also a blood loss enhances coagulation. During bleeding, however, the central blood volume is supported by fluid recruitment to the circulation and redistribution of the blood volume. In eight supine male volunteers (24 ± 3 years, blood volume of 6.9 ± 0.7 l; mean ± SD), 2 × 450 ml blood was withdrawn over ∼ 30 min while cardiovascular variables were monitored. Coagulation was evaluated by thrombelastography, and fluid recruitment was estimated by red blood cell count. Withdrawing 900 ml blood increased heart rate (62 ± 7 to 69 ± 13 bpm, P < 0.05; mean ± SD) and reduced stroke volume (113 ± 12 to 96 ± 14 ml, P < 0.05) leaving cardiac output, mean arterial pressure, and total peripheral resistance unchanged and, furthermore, reduced red blood cell count (4.80 ± 0.33 to 4.64 ± 0.37 × 10(12) cells l(-1), P < 0.05) indicating that 218 ± 173 ml fluid was recruited to the circulation. Withdrawing 450 ml blood reduced the time until initial fibrin formation (R: 6.5 ± 0.9 to 5.1 ± 1.0 min, P < 0.01), whereas the rate of clot formation increased after withdrawal of 900 ml blood (α-Angle: 66 ± 4 to 70 ± 3 deg, P < 0.01). Clot strength (maximal amplitude: 57 ± 4 mm), clot lysis 30 min after maximal amplitude (LY30: 0.8% [0-3.5%] (median [range])), and platelet count (218 ± 25 × 10(9) l(-1)) were unaffected. For supine males, ∼ 25% of a moderate blood loss is compensated by fluid recruitment to the circulation, which may explain the minor cardiovascular response. Yet, a blood loss of 450 ml accelerates coagulation, and this is further accentuated when blood loss is 900 ml.

  18. Origin of Serpin-Mediated Regulation of Coagulation and Blood Pressure

    PubMed Central

    Wang, Yunjie; Köster, Katharina; Lummer, Martina; Ragg, Hermann

    2014-01-01

    Vertebrates evolved an endothelium-lined hemostatic system and a pump-driven pressurized circulation with a finely-balanced coagulation cascade and elaborate blood pressure control over the past 500 million years. Genome analyses have identified principal components of the ancestral coagulation system, however, how this complex trait was originally regulated is largely unknown. Likewise, little is known about the roots of blood pressure control in vertebrates. Here we studied three members of the serpin superfamily that interfere with procoagulant activity and blood pressure of lampreys, a group of basal vertebrates. Angiotensinogen from these jawless fish was found to fulfill a dual role by operating as a highly selective thrombin inhibitor that is activated by heparin-related glycosaminoglycans, and concurrently by serving as source of effector peptides that activate type 1 angiotensin receptors. Lampreys, uniquely among vertebrates, thus use angiotensinogen for interference with both coagulation and osmo- and pressure regulation. Heparin cofactor II from lampreys, in contrast to its paralogue angiotensinogen, is preferentially activated by dermatan sulfate, suggesting that these two serpins affect different facets of thrombin’s multiple roles. Lampreys also express a lineage-specific serpin with anti-factor Xa activity, which demonstrates that another important procoagulant enzyme is under inhibitory control. Comparative genomics suggests that orthologues of these three serpins were key components of the ancestral hemostatic system. It appears that, early in vertebrate evolution, coagulation and osmo- and pressure regulation crosstalked through antiproteolytically active angiotensinogen, a feature that was lost during vertebrate radiation, though in gnathostomes interplay between these traits is effective. PMID:24840053

  19. Using microfluidics to understand the effect of spatial distribution of tissue factor on blood coagulation.

    PubMed

    Shen, Feng; Kastrup, Christian J; Ismagilov, Rustem F

    2008-01-01

    Initiation of blood coagulation by tissue factor (TF) is a robust, highly regulated process. Both the spatial distribution of TF and the geometry of the vasculature may play important roles in regulating coagulation. As this review describes, microfluidic systems provide a unique opportunity for investigating the spatiotemporal dynamics of blood coagulation in vitro. Microfluidic systems with surfaces of phospholipid bilayers patterned with TF have been used to demonstrate experimentally the threshold responses of initiation of coagulation to the size and shape of surfaces presenting TF. These systems have also been used to demonstrate experimentally that propagation of coagulation is regulated by the shear rate of blood flow in microcapillaries and microchannels. By understanding these and other aspects of the spatial dynamics that regulate blood coagulation, many new methods for treating clotting disorders, such as venous thromboembolism (VTE) and sepsis, could arise.

  20. Effects of long and short carboxylated or aminated multiwalled carbon nanotubes on blood coagulation.

    PubMed

    Meng, Jie; Cheng, Xuelian; Liu, Jian; Zhang, Weiqi; Li, Xiaojin; Kong, Hua; Xu, Haiyan

    2012-01-01

    In this work the effects of four different multiwalled carbon nanotubes (MWCNTs), including long carboxylated (L-COOH), short carboxylated (S-COOH), long aminated (L-NH(2)) and short aminated (S-NH(2)) ones, on the integrity of red blood cells, coagulation kinetics and activation of platelets were investigated with human whole blood. We found that the four MWCNTs induced different degrees of red blood cell damage as well as a mild level of platelet activation (10-25%). L-COOH and L-NH(2) induced a higher level of platelet activation than S-COOH and S-NH(2) respectively; meanwhile L-NH(2) caused marked reductions in platelet viability. The presence of the four MWCNTs led to earlier fibrin formation, L-NH(2) increased the clots hardness significantly, while L-COOH and S-NH(2) made the clots become softer. It was concluded that the four MWCNTs affected blood coagulation process and the clots mechanical properties; they also altered the integrity of the red blood cells and the viability of the platelets, as well as induced platelets activation. The effects of MWCNTs depended on the size and chemistry of the nanotubes and the type of cells they contacted.

  1. Air quality improvement during 2010 Asian games on blood coagulability in COPD patients.

    PubMed

    Zhang, Zili; Wang, Jian; Guo, Meihua; Xiong, Mingmei; Zhou, Qipeng; Li, Defu; Shu, Jiaze; Lu, Wenju; Sun, Dejun

    2016-04-01

    2010 Asian game is associated with activation of blood coagulation with COPD patients. However, one step forward has been made on the gap between improved air pollution and blood coagulability. Meanwhile, our study also provides evidence for the presence of a hypercoagulative state in systemic circulation in COPD patients. Additional studies employing other susceptible populations and endpoints are pending.

  2. PF-04886847 (an inhibitor of plasma kallikrein) attenuates inflammatory mediators and activation of blood coagulation in rat model of lipopolysaccharide (LPS)-induced sepsis.

    PubMed

    Kolte, D; Bryant, J W; Gibson, G W; Wang, J; Shariat-Madar, Z

    2012-06-01

    The plasma kallikrein-mediated proteolysis regulates both thrombosis and inflammation. Previous study has shown that PF-04886847 is a potent and competitive inhibitor of kallikrein, suggesting that it might be useful for the treatment of kallikrein-kinin mediated inflammatory and thrombotic disorders. In the rat model of lipopolysaccharide (LPS) -induced sepsis used in this study, pretreatment of rats with PF-04886847 (1 mg/kg) prior to LPS (10 mg/kg) prevented endotoxin-induced increase in granulocyte count in the systemic circulation. PF-04886847 significantly reduced the elevated plasma 6-keto PGF1α levels in LPS treated rats, suggesting that PF-04886847 could be useful in preventing hypotensive shock during sepsis. PF-04886847 did not inhibit LPS-induced increase in plasma TNF-α level. Pretreatment of rats with PF-04886847 prior to LPS did not attenuate endotoxin-induced decrease in platelet count and plasma fibrinogen levels as well as increase in plasma D-dimer levels. PF-04886847 did not protect the animals against LPS-mediated acute hepatic and renal injury and disseminated intravascular coagulation (DIC). Since prekallikrein (the zymogen form of plasma kallikrein) deficient patients have prolonged activated partial thromboplastin time (aPTT) without having any bleeding disorder, the anti-thrombotic property and mechanism of action of PF-04886847 was assessed. In a rabbit balloon injury model designed to mimic clinical conditions of acute thrombotic events, PF-04886847 reduced thrombus mass dose-dependently. PF-04886847 (1 mg/kg) prolonged both aPTT and prothrombin time (PT) in a dose-dependent manner. Although the findings of this study indicate that PF-04886847 possesses limited anti-thrombotic and anti-inflammatory effects, PF-04886847 may have therapeutic potential in other kallikrein-kinin mediated diseases.

  3. 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.

  4. [Seasonal changes in the blood coagulating and anticoagulating system indices in men at the preclinical stage of ischemic heart disease].

    PubMed

    Andreenko, G V; Panchenko, V M; Liutova, L V; Lisina, A N; Karabasova, M A

    1980-03-01

    Examination of 52 males (aged 23 to 40 years) in the preclinical stage of ischemic heart disease revealed seasonal differences in the values of the blood coagulation and anticoagulation systems: in the spring, there was an increase in blood coagulation activity displayed by growth of the concentration of fibrinogen and soluble fibrin and a reduction in the amount of the plasminogen activator. The authors suggest conducting preventive treatment of patients in the spring, the most unfavourable season in respect of the effect of the pathogenetic factors.

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

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

    PubMed

    Golderman, Valery; Shavit-Stein, Efrat; Tamarin, Ilia; Rosman, Yossi; Shrot, Shai; Rosenberg, Nurit; Maggio, Nicola; Chapman, Joab; Eisenkraft, Arik

    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.

  7. 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

  8. Characterization of Blood Properties from Coagulating Blood of Different Hematocrits Using Ultrasonic Backscatter and Attenuation

    NASA Astrophysics Data System (ADS)

    Huang, Chih-Chung; Wang, Shyh-Hau

    2006-09-01

    The influence of hematocrit on the change of blood properties during coagulating was extensively investigated using ultrasonic integrated backscatter and attenuation. Measurements were performed with porcine blood at hematocrits ranging from 25 to 55% using a 10 MHz transducer. Results showed that both integrated backscatter and attenuation are able to sensitively differentiate various stages of blood properties during coagulating. The slopes of integrated backscatter (Sr, dB/S) and attenuation (αr, dB\\cdotcm-1\\cdotMHz-1\\cdotmS-1) are increased relative to hematocrit. The best fits for Sr and αr as a function of hematocrit (H) equal to Sr=0.0357+1.62e-0.108H and αr=0.0281+0.003H, respectively. Variations of clotting time (Ts) and reaction time (Tα), estimated respectively from ultrasonic integrated backscatter and attenuation, associated with clot formation are also increased with hematocrit. This study demonstrates that blood hematocrit is a substantial factor affecting viscosity and backscattering properties of blood during coagulation capable of being discerned by ultrasonic backscattering and attenuation.

  9. 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.

  10. Bromelain has paradoxical effects on blood coagulability: a study using thromboelastography.

    PubMed

    Kaur, Harmanpreet; Corscadden, Kathryn; Lott, Carlene; Elbatarny, Hisham S; Othman, Maha

    2016-10-01

    Bromelain is a crude extract from pineapple that is known for a wide array of pharmacological effects including protein digestion, fibrinolytic and anti-immune inflammatory effects and has been popularly used as a phytotherapeutic drug. However, its clinical values and applications remain understudied. The aim of this study was to investigate the effect of bromelain on the coagulability of blood using thromboelastography (TEG). We identified 0.4 U/ml as the minimum concentration of bromelain that results in modification of a normal TEG tracing. We studied the effects of this dose on whole blood samples obtained from normal and hypercoagulable individuals using TEG and evaluated their plasma using conventional tests including prothrombin time (PT) and activated partial thromboplastin time (APTT). We extended this analysis to investigate the effect of bromelain on platelet aggregation in normal blood and on the coagulability of mice blood in vivo in response to a clinically relevant dose injected intraperitoenally. The addition of bromelain ex vivo reduced coagulability of both normal and hypercoagulable blood significantly and resulted in 47 and 22% prolongation of PT and 20 and 10% prolongation of APTT in normal and hypercoagulable samples, respectively and inhibited adenosine di-phosphate (ADP)-induced platelet aggregation by 19%. In vivo, there was a considerable variation in TEG parameters in blood obtained from mice and unexpectedly a paradoxical effect toward hypercoagulability was shown in response to 1.5 mg/kg bromelain injected intraperitoneally into seven different animals. However, these results were not statistically significant when compared with the saline-injected animals. Although the in-vitro findings in this small study indicate a potential anticoagulant effect for bromelain, this needs to be interpreted with caution as neither an oral nor intravenous routes were evaluated. The paradoxical in-vivo data following intraperitoneal administration

  11. Purification of High Molecular Weight Kininogen and the Role of This Agent in Blood Coagulation

    PubMed Central

    Saito, Hidehiko

    1977-01-01

    Recent studies of individuals with high molecular weight (HMW) kininogen deficiency established the importance of this plasma protein for in vitro initiation of blood coagulation. In the present study, HMW-kininogen was highly purified from human plasma by monitoring its clot-promoting activity, using Fitzgerald trait plasma as a substrate. This preparation of HMW-kininogen revealed a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (mol wt: 120,000) and released 1% of its weight as bradykinin upon incubation with plasma kallikrein. HMW-kininogen specifically repaired impaired surface-mediated plasma reactions of Fitzgerald trait plasma, but did not affect those of Hageman trait and Fletcher trait plasma. Kinin release from HMW-kininogen by trypsin, but not by plasma kallikrein, resulted in total loss of clot-promoting activity. No inhibitors of coagulation were found when all kinin activity was removed from HMW-kininogen by trypsin. The roles of HMW-kininogen, Hageman factor (HF, Factor XII), plasma prekallikrein (Fletcher factor), and plasma thromboplastin antecedent (PTA, Factor XI) in blood coagulation were studied in a purified system. HMW-kininogen was absolutely required for activation of PTA by HF and ellagic acid. The yield of activated PTA was proportional to the amount of HF, HMW-kininogen, and PTA in the mixtures, suggesting that, to activate PTA, these three proteins might form a complex in the presence of ellagic acid. No fragmentation of HF was found under these conditions. In contrast to HF, HF-fragments (mol wt: 30,000) activated PTA in the absence of HMW-kininogen and ellagic acid. Thus, it appears that in the present study PTA was activated in two distinct ways. Which pathway is the major one in whole plasma remains to be determined. Images PMID:893664

  12. Analysis of the coagulation of human blood cells on diamond surfaces by atomic force microscopy

    NASA Astrophysics Data System (ADS)

    Baranauskas, V.; Fontana, M.; Guo, Zhao Jing; Ceragioli, H. J.; Peterlevitz, A. C.

    2004-11-01

    Atomic force microscopy (AFM) was used to study the morphology and coagulation of human blood cells in contact with solid surfaces. Blood was extracted from the veins of healthy adult donors and the samples were used immediately after extraction, deposited either on borosilicate glass or diamond substrates. Some blood samples were anti-coagulated by adding heparin for single cell AFM imaging. No chemicals were used for attaching or immobilizing the cells. The diamond substrates were produced by chemical vapour deposition (CVD diamond) using a hot-filament CVD system fed with ethanol highly diluted in hydrogen. AFM imaging of isolated cells (anti-coagulated by heparin) was only possible on the glass substrates due to the lack of adherence of the cells to the diamond surface. The coagulation results suggest that blood clotting on diamond produces a less rough surface than blood clotting on glass.

  13. Coagulation Factors Test

    MedlinePlus

    ... this page helpful? Also known as: Factor Assays; Blood Clotting Factors; Clotting Factors [or by the individual factor ... person has enough coagulation activity to control the blood clotting process. It is used by healthcare practitioners to ...

  14. Metalloproteases Affecting Blood Coagulation, Fibrinolysis and Platelet Aggregation from Snake Venoms: Definition and Nomenclature of Interaction Sites

    PubMed Central

    Kini, R. Manjunatha; Koh, Cho Yeow

    2016-01-01

    Snake venom metalloproteases, in addition to their contribution to the digestion of the prey, affect various physiological functions by cleaving specific proteins. They exhibit their activities through activation of zymogens of coagulation factors, and precursors of integrins or receptors. Based on their structure–function relationships and mechanism of action, we have defined classification and nomenclature of functional sites of proteases. These metalloproteases are useful as research tools and in diagnosis and treatment of various thrombotic and hemostatic conditions. They also contribute to our understanding of molecular details in the activation of specific factors involved in coagulation, platelet aggregation and matrix biology. This review provides a ready reference for metalloproteases that interfere in blood coagulation, fibrinolysis and platelet aggregation. PMID:27690102

  15. 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).

  16. Influence of a constant and variable magnetic field on the coagulation of human blood in vitro and in vivo

    NASA Technical Reports Server (NTRS)

    Degen, I. L.; Plaksenko, V. Y.

    1974-01-01

    The influence of constant and varying magnetic fields on the coagulation of the blood was studied in experiments performed in vitro and vivo. In the in vitro tests it was found that a constant magnetic field with a strength of 100 or 200 oersteds influences the coagulation of the blood, retarding it in some cases and speeding up the coagulation time in others. In the in vivo studies, both retarding and accelerating effects were likewise observed with respect to the coagulation of the blood, but the nature of the change was a function of the background. A normalizing effect of the magnetic field on the coagulation of the blood was observed.

  17. Seawater Immersion Aggravates Burn Injury Causing Severe Blood Coagulation Dysfunction.

    PubMed

    Yan, Hong; Mao, Qingxiang; Ma, Yongda; Wang, Li; Chen, Xian; Hu, Yi; Ge, Hengjiang

    2016-01-01

    This study aimed to investigate the endothelial function in a canine model of burn injury combined with seawater immersion. The model of burn injury was established. The dogs were randomly divided into four groups including dogs with burn injury (B group), or burn injury combined with seawater immersion (BI group), or only immersion in seawater (I group), or control animals with no injury or immersion (C group). The circulating endothelial cell (CEC) count and coagulation-fibrinolysis parameters were measured. The CEC count in B group increased at 4 h, 7 h, and 10 h after injury and then reduced, whereas it continuously increased to a greater extent in BI group (P < 0.05). The von Willebrand factor (vWF) activity, plasminogen activator inhibitor (PAI-1), and the ratio of thromboxane B2 (TXB2) to 6-keto-prostaglandin F1α (6-K-PGF1α ) in BI group had a marked increase after injury, and the tissue-type plasminogen activator (tPA) in the BI group decreased. Microscope observations revealed thrombus formation in lungs of the animals in BI group, but not in C, I, or B groups. Burn injury causes endothelial dysfunction, and seawater immersion lastingly aggravates this injury, leading to a higher risk of developing thrombosis.

  18. Blood coagulation and fibrinolysis in aortic valve stenosis: links with inflammation and calcification.

    PubMed

    Natorska, J; Undas, A

    2015-08-01

    Aortic valve stenosis (AS) increasingly afflicts our aging population. However, the pathobiology of the disease is still poorly understood and there is no effective pharmacotherapy for treating those at risk for clinical progression. The progression of AS involves complex inflammatory and fibroproliferative processes that resemble to some extent atherosclerosis. Accumulating evidence indicates that several coagulation proteins and its inhibitors, including tissue factor, tissue factor pathway inhibitor, prothrombin, factor XIII, von Willebrand factor, display increased expression within aortic stenotic valves, predominantly on macrophages and myofibroblasts around calcified areas. Systemic impaired fibrinolysis, along with increased plasma and valvular expression of plasminogen activator inhibitor-1, has also been observed in patients with AS in association with the severity of the disease. There is an extensive cross-talk between inflammation and coagulation in stenotic valve tissue which contributes to the calcification and mineralisation of the aortic valve leaflets. This review summarises the available data on blood coagulation and fibrinolysis in AS with the emphasis on their interactions with inflammation and calcification.

  19. Real-Time Electrical Impedimetric Monitoring of Blood Coagulation Process under Temperature and Hematocrit Variations Conducted in a Microfluidic Chip

    PubMed Central

    Lei, Kin Fong; Chen, Kuan-Hao; Tsui, Po-Hsiang; Tsang, Ngan-Ming

    2013-01-01

    Blood coagulation is an extremely complicated and dynamic physiological process. Monitoring of blood coagulation is essential to predict the risk of hemorrhage and thrombosis during cardiac surgical procedures. In this study, a high throughput microfluidic chip has been developed for the investigation of the blood coagulation process under temperature and hematocrit variations. Electrical impedance of the whole blood was continuously recorded by on-chip electrodes in contact with the blood sample during coagulation. Analysis of the impedance change of the blood was conducted to investigate the characteristics of blood coagulation process and the starting time of blood coagulation was defined. The study of blood coagulation time under temperature and hematocrit variations was shown a good agreement with results in the previous clinical reports. The electrical impedance measurement for the definition of blood coagulation process provides a fast and easy measurement technique. The microfluidic chip was shown to be a sensitive and promising device for monitoring blood coagulation process even in a variety of conditions. It is found valuable for the development of point-of-care coagulation testing devices that utilizes whole blood sample in microliter quantity. PMID:24116099

  20. CARDIOVASCULAR AND BLOOD COAGULATION EFFECTS OF PULMONARY ZINC EXPOSURE

    EPA Science Inventory

    Cardiovascular damage induced by pulmonary exposure to environmental chemicals can result from direct action or, secondarily, from pulmonary injury. We have developed a rat model of pulmonary exposure to zinc to demonstrate cardiac, coagulative, and fibrinolytic alterations. Mal...

  1. Misfolded proteins activate Factor XII in humans, leading to kallikrein formation without initiating coagulation

    PubMed Central

    Maas, Coen; Govers-Riemslag, José W.P.; Bouma, Barend; Schiks, Bettina; Hazenberg, Bouke P.C.; Lokhorst, Henk M.; Hammarström, Per; ten Cate, Hugo; de Groot, Philip G.; Bouma, Bonno N.; Gebbink, Martijn F.B.G.

    2008-01-01

    When blood is exposed to negatively charged surface materials such as glass, an enzymatic cascade known as the contact system becomes activated. This cascade is initiated by autoactivation of Factor XII and leads to both coagulation (via Factor XI) and an inflammatory response (via the kallikrein-kinin system). However, while Factor XII is important for coagulation in vitro, it is not important for physiological hemostasis, so the physiological role of the contact system remains elusive. Using patient blood samples and isolated proteins, we identified a novel class of Factor XII activators. Factor XII was activated by misfolded protein aggregates that formed by denaturation or by surface adsorption, which specifically led to the activation of the kallikrein-kinin system without inducing coagulation. Consistent with this, we found that Factor XII, but not Factor XI, was activated and kallikrein was formed in blood from patients with systemic amyloidosis, a disease marked by the accumulation and deposition of misfolded plasma proteins. These results show that the kallikrein-kinin system can be activated by Factor XII, in a process separate from the coagulation cascade, and point to a protective role for Factor XII following activation by misfolded protein aggregates. PMID:18725990

  2. Disequilibrium of Blood Coagulation and Fibrinolytic System in Patients With Coronary Artery Ectasia

    PubMed Central

    Wu, Wei; Liu, Ruifeng; Chen, Lianfeng; Chen, Houzao; Zhang, Shuyang

    2016-01-01

    Abstract Thrombus formation and myocardial infarction are not uncommon in patients with coronary artery ectasia (CAE). In light of this, the present study aims to systemically evaluate the blood coagulation and fibrinolytic systems in CAE patients. In this study, we enrolled 30 patients with CAE, 30 patients with coronary atherosclerosis disease (CAD), and 29 subjects with normal coronary arteries (control). The coagulation system was evaluated using a routine coagulation function test performed in the hospital laboratory before coronary angiography, and measurements included prothrombin time, international normalized ratio, activated partial thromboplastin time, fibrinogen time, and thrombin time. The evaluation of the fibrinolytic system included measurements of D-dimer, euglobulin lysis time, plasminogen activator inhibitor 1, plasminogen, plasminogen activity assay, α1-antitrypsin (α1-AT), α2 plasmin inhibitor (α2-PI), and α2-macroglobulin (α2-MG). Alpha1-AT, α2-PI, and α2-MG also inhibit activities of 3 neutrophil serine proteases, namely human neutrophil elastase (HNE), cathepsin G (CG), and proteinase 3 (PR3); therefore, the plasma levels of these 3 proteinases were also evaluated. In CAE patients, the circulating coagulation system was normal. For the fibrinolytic system, a decrease of plasminogen activity was observed (P = 0.029) when compared with CAD patients, and the concentrations of α1-AT (both P < 0.001), α2-PI (P = 0.002 and P = 0.025), and α2-MG (P = 0.034 and P < 0.001) were significantly elevated when compared with CAD patients and normal controls. Moreover, the plasma levels of HNE (both P < 0.001) and CG (P = 0.027 and 0.016) in CAE patients were also significantly higher than those of the CAD and control groups. There was no difference in plasma PR3 concentration among these 3 groups. Disequilibrium of the coagulation/fibrinolytic system may contribute to thrombus formation and clinical coronary

  3. Effects of haemodilution on the optical properties of blood during coagulation studied by optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Liu, B.; Liu, Y.; Wei, H.; Yang, X.; Wu, G.; Guo, Z.; Yang, H.; He, Y.; Xie, S.

    2016-11-01

    We report an investigation of the effects of blood dilution with hypertonic (7.5 %) and normal (0.9 %) saline on its optical properties during coagulation in vitro using optical coherence tomography. The light penetration depth and attenuation coefficient are obtained from the dependences of reflectance on the depth. Normal whole blood has served as the control group. The average coagulation time is equal to 420 +/- 16, 418 +/- 16 and 358 +/- 14 {\\text{s}} with blood volume replacement of 2 %, 11 %, and 20 % by 0.9 % normal saline, respectively. With 2 %, 11% and 20% blood volume replacement with 7.5 % hypertonic saline, the average coagulation time is 422 +/- 17, 1160 +/- 45 and 1730 +/- 69 {\\text{s}}, respectively. For normal whole blood, the average coagulation time amounts to 425 +/- 19 {\\text{s}}. it is shown that dilution with normal saline has a procoagulant effect when it replaces 20 % of blood volume, and hypertonic saline has an anticoagulant effect if it replaces 11 % or more of blood volume. It is concluded that optical coherence tomography is a potential technique to quantify and monitor the liquid - gel transition during the coagulation process of blood diluted by normal and hypertonic saline.

  4. Optical coherence tomography-guided laser microsurgery for blood coagulation with continuous-wave laser diode

    NASA Astrophysics Data System (ADS)

    Chang, Feng-Yu; Tsai, Meng-Tsan; Wang, Zu-Yi; Chi, Chun-Kai; Lee, Cheng-Kuang; Yang, Chih-Hsun; Chan, Ming-Che; Lee, Ya-Ju

    2015-11-01

    Blood coagulation is the clotting and subsequent dissolution of the clot following repair to the damaged tissue. However, inducing blood coagulation is difficult for some patients with homeostasis dysfunction or during surgery. In this study, we proposed a method to develop an integrated system that combines optical coherence tomography (OCT) and laser microsurgery for blood coagulation. Also, an algorithm for positioning of the treatment location from OCT images was developed. With OCT scanning, 2D/3D OCT images and angiography of tissue can be obtained simultaneously, enabling to noninvasively reconstruct the morphological and microvascular structures for real-time monitoring of changes in biological tissues during laser microsurgery. Instead of high-cost pulsed lasers, continuous-wave laser diodes (CW-LDs) with the central wavelengths of 450 nm and 532 nm are used for blood coagulation, corresponding to higher absorption coefficients of oxyhemoglobin and deoxyhemoglobin. Experimental results showed that the location of laser exposure can be accurately controlled with the proposed approach of imaging-based feedback positioning. Moreover, blood coagulation can be efficiently induced by CW-LDs and the coagulation process can be monitored in real-time with OCT. This technology enables to potentially provide accurate positioning for laser microsurgery and control the laser exposure to avoid extra damage by real-time OCT imaging.

  5. Optical coherence tomography-guided laser microsurgery for blood coagulation with continuous-wave laser diode.

    PubMed

    Chang, Feng-Yu; Tsai, Meng-Tsan; Wang, Zu-Yi; Chi, Chun-Kai; Lee, Cheng-Kuang; Yang, Chih-Hsun; Chan, Ming-Che; Lee, Ya-Ju

    2015-11-16

    Blood coagulation is the clotting and subsequent dissolution of the clot following repair to the damaged tissue. However, inducing blood coagulation is difficult for some patients with homeostasis dysfunction or during surgery. In this study, we proposed a method to develop an integrated system that combines optical coherence tomography (OCT) and laser microsurgery for blood coagulation. Also, an algorithm for positioning of the treatment location from OCT images was developed. With OCT scanning, 2D/3D OCT images and angiography of tissue can be obtained simultaneously, enabling to noninvasively reconstruct the morphological and microvascular structures for real-time monitoring of changes in biological tissues during laser microsurgery. Instead of high-cost pulsed lasers, continuous-wave laser diodes (CW-LDs) with the central wavelengths of 450 nm and 532 nm are used for blood coagulation, corresponding to higher absorption coefficients of oxyhemoglobin and deoxyhemoglobin. Experimental results showed that the location of laser exposure can be accurately controlled with the proposed approach of imaging-based feedback positioning. Moreover, blood coagulation can be efficiently induced by CW-LDs and the coagulation process can be monitored in real-time with OCT. This technology enables to potentially provide accurate positioning for laser microsurgery and control the laser exposure to avoid extra damage by real-time OCT imaging.

  6. Optical coherence tomography-guided laser microsurgery for blood coagulation with continuous-wave laser diode

    PubMed Central

    Chang, Feng-Yu; Tsai, Meng-Tsan; Wang, Zu-Yi; Chi, Chun-Kai; Lee, Cheng-Kuang; Yang, Chih-Hsun; Chan, Ming-Che; Lee, Ya-Ju

    2015-01-01

    Blood coagulation is the clotting and subsequent dissolution of the clot following repair to the damaged tissue. However, inducing blood coagulation is difficult for some patients with homeostasis dysfunction or during surgery. In this study, we proposed a method to develop an integrated system that combines optical coherence tomography (OCT) and laser microsurgery for blood coagulation. Also, an algorithm for positioning of the treatment location from OCT images was developed. With OCT scanning, 2D/3D OCT images and angiography of tissue can be obtained simultaneously, enabling to noninvasively reconstruct the morphological and microvascular structures for real-time monitoring of changes in biological tissues during laser microsurgery. Instead of high-cost pulsed lasers, continuous-wave laser diodes (CW-LDs) with the central wavelengths of 450 nm and 532 nm are used for blood coagulation, corresponding to higher absorption coefficients of oxyhemoglobin and deoxyhemoglobin. Experimental results showed that the location of laser exposure can be accurately controlled with the proposed approach of imaging-based feedback positioning. Moreover, blood coagulation can be efficiently induced by CW-LDs and the coagulation process can be monitored in real-time with OCT. This technology enables to potentially provide accurate positioning for laser microsurgery and control the laser exposure to avoid extra damage by real-time OCT imaging. PMID:26568136

  7. 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.

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

    NASA Astrophysics Data System (ADS)

    Xu, Xiangqun; Teng, Xiangshuai

    2015-05-01

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

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

    PubMed

    Xu, Xiangqun; Teng, Xiangshuai

    2015-05-21

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

  10. Metals in air pollution particles decrease whole-blood coagulation time.

    PubMed

    Sangani, Rahul G; Soukup, Joleen M; Ghio, Andrew J

    2010-07-01

    The mechanism underlying procoagulative effects of air pollution particle exposure is not known. The authors tested the postulate that (1) the water-soluble components of an air pollution particle could affect whole-blood coagulation time and (2) metals included in this fraction were responsible for this effect. Exposure to the water-soluble fraction of particulate matter (PM), at doses as low as 50 ng/ml original particle, significantly diminished the whole-blood coagulation time. Inclusion of deferoxamine prolonged coagulation time following the exposures to the water-soluble fraction, whereas equivalent doses of ferroxamine had no effect. Except for nickel, all metal sulfates shortened the whole-blood coagulation time. Iron and zinc were two metals with the greatest capacity to reduce the coagulation time, with an effect observed at 10 ng/ml. Finally, in contrast to the anticoagulants citrate and EDTA, their iron complexes were found to be procoagulative. The authors conclude that metals in the water-soluble fraction of air pollution particles decrease whole-blood coagulation time. These metals can potentially contribute to procoagulative effects observed following human exposures to air pollution particles.

  11. Coagulation defects associated with massive blood transfusion: A large multicenter study.

    PubMed

    Yang, Jiang-Cun; Sun, Yang; Xu, Cui-Xiang; Dang, Qian-Li; Li, Ling; Xu, Yong-Gang; Song, Yao-Jun; Yan, Hong

    2015-09-01

    The variations in the coagulation indices of patients receiving massive blood transfusion were investigated across 20 large‑scale general hospitals in China. The data of 1,601 surgical inpatients receiving massive transfusion were retrospectively collected and the trends in the platelet counts and coagulation indices prior to and at 16 different time points during packed red blood cell (pRBC; after 2‑40 units of pRBC) transfusion were evaluated by linear regression analysis. Temporal variations in the means of prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT) and fibrinogen (FIB) concentration were also assessed and the theoretical estimates and actual measurements of the platelet count were compared. The results demonstrated that the platelet count decreased linearly with an increase in the number of pRBC units transfused (Y=150.460‑3.041X; R2 linear=0.775). Following transfusion of 18 units of pRBC (0.3 units of pRBC transfused per kilogram of body weight), the average platelet count decreased to 71x10(9)/l (<75x10(9)/l). Furthermore, variations in the means of PT, INR, APTT and FIB did not demonstrate any pronounced trends and actual platelet counts were markedly higher than the theoretical estimates. In conclusion, no variations in the means of traditional coagulation indices were identified, however, the platelet count demonstrated a significant linear decrease with an increase in the number of pRBC units transfused. Furthermore, actual platelet counts were higher than theoretical estimates, indicating the requirement for close monitoring of actual platelet counts during massive pRBC transfusion.

  12. Fusaric acid, a mycotoxin, and its influence on blood coagulation and platelet function.

    PubMed

    Devaraja, Sannaningaiah; Girish, Kesturu S; Santhosh, Martin S; Hemshekhar, Mahadevappa; Nayaka, Siddaiah C; Kemparaju, Kempaiah

    2013-06-01

    The current study intended to explore the effect of fusaric acid on blood coagulation including plasma coagulation and platelet aggregation. Fusaric acid exhibited biphasic effects on citrated human plasma recalcification time. At concentrations below 50 ng, fusaric acid decreased the clotting time of plasma dose-dependently from 130 ± 3s control value to 32 ± 3s; however, above 50 ng, fusaric acid increased the clotting time from 32 ± 3s and reached a maximum of 152 s at 100 ng and remained unaltered thereafter for the increased dose of fusaric acid. Fusaric acid without damaging red blood cells and platelets, inhibited agonists such as collagen, ADP, thrombin, and epinephrine-induced aggregation of both platelet-rich plasma (PRP) and washed platelets preparations of human. Interestingly, fusaric acid showed biphasic effects only in thrombin-induced platelet aggregation of washed platelets, and at lower concentration (below 900 ng) it activated platelet aggregation; however, in increased concentration (above 900 ng) it inhibited the platelet aggregation of washed platelets. In addition, fusaric acid also inhibited the agonist ADP-induced platelet aggregation of washed platelet suspension but did not show biphasic effect. Further, fusaric acid did not induce the platelets to generate reactive oxygen species (ROS) that clearly suggests that the induction of platelet function could be the result of the fusaric acid-mediated receptor interaction but not through the morphological shape change.

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

    PubMed

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

    2011-04-22

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

  14. [Relation between biomarkers of the coagulation cascade, fibrinolytic system and lipid profiles in hypertensive patients with various coagulation potential of whole blood].

    PubMed

    Tolstopiatov, S M

    2009-01-01

    227 hypertensive patients, stage II-III have been investigated using new laboratory technology (patent of Ukraine), to reveal signs of coagulation potential and fibrinolytic tests of whole blood. 120 patients have been observed to detect definite markers of lipid profile. Obtained results revealed depression of fibrinolysis (from I to X degree) in 77.3%, hypercoagulation in 53.3%, and hypocoagulation in 25.6% of patients. These multidirectional changes proves the necessity of a laboratory control during administration of antiplatelets drugs. Besides, having coagulation module (CM) at VI-VIII degree, which corresponds to a high clinical risk factor of and urgent situation, the tactics of the treatment should be aggressive and parenteral. Lipid concentration was considerably higher at hypercoagulation state, although in 11-22% of cases, dislipidemia developed at hypocoagulation state. Total cholesterol (TC) and lipoprotein levels do not influence on formation of blood clot and considerably increase its density (P < 0.01), that complicates dissolving of blood clot by the fibrinolytic system, functional state of which goes down additionally during the increase of TC (r = -0.207; P < 0.05) and LDL (r = -0.197; P < 0.05). Fibrinolytic activity has strongly correlated with clot level (r = -0.465; P < 0.0001) and its density (r = -0.393; P < 0.0001). So, the algorithm of an individual treatment should include antihypertensive (under the control Blood Pressure), antiliplatelets (under the control MC) and hypolipidemic (under the laboratory control) agents.

  15. Untangling the complexity of blood coagulation network: use of computational modelling in pharmacology and diagnostics.

    PubMed

    Shibeko, Alexey M; Panteleev, Mikhail A

    2016-05-01

    Blood coagulation is a complex biochemical network that plays critical roles in haemostasis (a physiological process that stops bleeding on injury) and thrombosis (pathological vessel occlusion). Both up- and down-regulation of coagulation remain a major challenge for modern medicine, with the ultimate goal to correct haemostasis without causing thrombosis and vice versa. Mathematical/computational modelling is potentially an important tool for understanding blood coagulation disorders and their treatment. It can save a huge amount of time and resources, and provide a valuable alternative or supplement when clinical studies are limited, or not ethical, or technically impossible. This article reviews contemporary state of the art in the modelling of blood coagulation for practical purposes: to reveal the molecular basis of a disease, to understand mechanisms of drug action, to predict pharmacodynamics and drug-drug interactions, to suggest potential drug targets or to improve quality of diagnostics. Different model types and designs used for this are discussed. Functional mechanisms of procoagulant bypassing agents and investigations of coagulation inhibitors were the two particularly popular applications of computational modelling that gave non-trivial results. Yet, like any other tool, modelling has its limitations, mainly determined by insufficient knowledge of the system, uncertainty and unreliability of complex models. We show how to some extent this can be overcome and discuss what can be expected from the mathematical modelling of coagulation in not-so-far future.

  16. Blood coagulation screening using a paper-based microfluidic lateral flow device.

    PubMed

    Li, H; Han, D; Pauletti, G M; Steckl, A J

    2014-10-21

    A simple approach to the evaluation of blood coagulation using a microfluidic paper-based lateral flow assay (LFA) device for point-of-care (POC) and self-monitoring screening is reported. The device utilizes whole blood, without the need for prior separation of plasma from red blood cells (RBC). Experiments were performed using animal (rabbit) blood treated with trisodium citrate to prevent coagulation. CaCl2 solutions of varying concentrations are added to citrated blood, producing Ca(2+) ions to re-establish the coagulation cascade and mimic different blood coagulation abilities in vitro. Blood samples are dispensed into a paper-based LFA device consisting of sample pad, analytical membrane and wicking pad. The porous nature of the cellulose membrane separates the aqueous plasma component from the large blood cells. Since the viscosity of blood changes with its coagulation ability, the distance RBCs travel in the membrane in a given time can be related to the blood clotting time. The distance of the RBC front is found to decrease linearly with increasing CaCl2 concentration, with a travel rate decreasing from 3.25 mm min(-1) for no added CaCl2 to 2.2 mm min(-1) for 500 mM solution. Compared to conventional plasma clotting analyzers, the LFA device is much simpler and it provides a significantly larger linear range of measurement. Using the red colour of RBCs as a visible marker, this approach can be utilized to produce a simple and clear indicator of whether the blood condition is within the appropriate range for the patient's condition.

  17. Rapid evaluation of fibrinogen levels using the CG02N whole blood coagulation analyzer.

    PubMed

    Hayakawa, Mineji; Gando, Satoshi; Ono, Yuichi; Mizugaki, Asumi; Katabami, Kenichi; Maekawa, Kunihiko; Miyamoto, Daisuke; Wada, Takeshi; Yanagida, Yuichiro; Sawamura, Atsushi

    2015-04-01

    Rapid evaluation of fibrinogen (Fbg) levels is essential for maintaining homeostasis in patients with massive bleeding during severe trauma and major surgery. This study evaluated the accuracy of fibrinogen levels measured by the CG02N whole blood coagulation analyzer (A&T Corporation, Kanagawa, Japan) using heparinized blood drawn for blood gas analysis (whole blood-Fbg). A total of 100 matched pairs of heparinized blood samples and citrated blood samples were simultaneously collected from patients in the intensive care unit. Whole blood-Fbg results were compared with those of citrated plasma (standard-Fbg). The whole blood coagulation analyzer measured fibrinogen levels within 2 minutes. Strong correlations between standard-Fbg and whole blood-Fbg were observed (ρ = 0.91, p < 0.001). Error grid analysis showed that 88% of the values were clinically acceptable, and 12% were in a range with possible effects on clinical decision-making; none were in a clinically dangerous range without appropriate treatment. Using a fibrinogen cutoff value of 1.5 g/L for standard-Fbg, the area under the receiver operating characteristic curve of whole blood-Fbg was 0.980 (95% confidence interval 0.951-1.000, p < 0.001). The whole blood coagulation analyzer can rapidly measure fibrinogen levels in heparinized blood and could be useful in critical care settings where excessive bleeding is a concern.

  18. [Modern coagulation management reduces the transfusion rate of allogenic blood products].

    PubMed

    Weber, Christian Friedrich

    2012-06-01

    Evaluating the patient's individual bleeding history with a standardized questionnaire, using "point-of-care" - methods for coagulation analyses and providing autologous transfusion techniques are preconditions of a modern coagulation management. Therapy of coagulopathic patients should be based on structured hemotherapy algorithms. Surgical haemostasis and the maintenance of the basic conditions for haemostasis are elementary requirements for an effective therapy. In cases of diffuse bleeding, early antifibrinolytic therapy should be considered. Coagulation factor deficiencies should be corrected "goal-directed" using coagulation factor concentrates. Transfusion of fresh frozen plasma is only indicated in the clinical setting of massive transfusions. DDAVP and transfusion of platelet concentrates are options to optimize primary haemostasis. In cases of on-going bleeding, recombinant activated coagulation factor VII represents an option for "ultima-ratio" therapy.

  19. [Characteristics of the indicators of the blood coagulation and fibrinolysis systems in the pre-clinical stage of ischemic heart disease].

    PubMed

    Andreenko, G V; Panchenko, V M; Lisina, A N; Liutova, L V

    1978-10-01

    Signs of dysfunction of the coagulation system and fibrinolysis were determined in 45 healthy young individuals who had such risk factors in relation to ischemic heart disease as arterial hypertension, hypercholesterolemia, smoking, aggravated heredity, permanent emotional overstress, etc. These signs were manifested by a tendency to augmentation of blood coagulation and compensatory activation of fibrinolysis. Ischemic-type changes were detected on the ECG after a physical load. It is assumed that dysfunction of the coagulation system and fibrinolysis is an additional risk factor in relation to ischemic heart disease, while derangement of compensatory fibrinolysis tension with the subsequent tension of its components may lead to the development of coronary thrombosis.

  20. Coagulation Activation in Children with Sickle Cell Disease Is Associated with Cerebral Small Vessel Vasculopathy

    PubMed Central

    Colombatti, Raffaella; De Bon, Emiliano; Bertomoro, Antonella; Casonato, Alessandra; Pontara, Elena; Omenetto, Elisabetta; Saggiorato, Graziella; Steffan, Agostino; Damian, Tamara; Cella, Giuseppe; Teso, Simone; Manara, Renzo; Rampazzo, Patrizia; Meneghetti, Giorgio; Basso, Giuseppe; Sartori, Maria Teresa; Sainati, Laura

    2013-01-01

    Background Thrombotic complications in Sickle Cell Disease (SCD) arise since infancy, but the role of the coagulation system in children has been poorly explored. To determine its role in the development of clinical complications in childhood we measured coagulation and endothelial parameters in children with SCD at steady state. Methods Markers of thrombin generation, fibrin dissolution and endothelial activation were evaluated in 38 children with SS-Sβ°, 6 with SC disease and 50 age and blood group matched controls. Coagulation variables were correlated with markers of hemolysis and inflammation, with the presence of cerebral and lung vasculopathy and with the frequency of clinical complications. Results SS-Sβ° patients presented higher levels of factor VIII, von Willebrand factor antigen (VWF:Ag) and collagen binding activity, tissue plasminogen activator antigen (t-PA:Ag), D-dimer, p-selectin, prothrombin fragment1+2 (F1+2) and lower ADAMTS-13:activity/VWF:Ag (p<0.05) compared to controls and SC patients. In SS-Sβ° patients coagulation variables correlated positively with markers of inflammation, hemolysis, and negatively with HbF (p<0.05). Patients with cerebral silent infarcts showed significant decrease in t-PA:Ag and ADAMTS-13 Antigen and a tendency toward higher D-dimer, F1+2, TAT compared to patients without them. D-dimer was associated with a six fold increased risk of cerebral silent infarcts. No correlation was found between coagulation activation and large vessel vasculopathy or other clinical events except for decreased t-PA:Ag in patients with tricuspid Rigurgitant Velocity >2.5m/sec. Conclusions SS-Sβ° disease is associated with extensive activation of the coagulation system at steady state since young age. ADAMTS-13 and t-PA:Ag are involved in the development of cerebral silent infarcts. PMID:24205317

  1. Acetaminophen and meloxicam inhibit platelet aggregation and coagulation in blood samples from humans.

    PubMed

    Martini, Angela K; Rodriguez, Cassandra M; Cap, Andrew P; Martini, Wenjun Z; Dubick, Michael A

    2014-12-01

    Acetaminophen (Ace) and meloxicam (Mel) are the two types of analgesic and antipyretic medications. This study investigated the dose responses of acetaminophen and meloxicam on platelet aggregation and coagulation function in human blood samples. Blood samples were collected from six healthy humans and processed to make platelet-adjusted (100 × 10 cells/μl) blood samples. Acetaminophen (Tylenol, Q-PAP, 100 mg/ml) was added at the doses of 0 μg/ml (control), 214 μg/ml (the standard dose, 1 ×), 4 ×, 8 ×, 10 ×, 12 ×, 16 ×, and 20 ×. Similarly, meloxicam (Metacam, 5 mg/ml) was added at doses of 0 μg/ml (control), 2.85 μg/ml (the standard dose, 1 ×), 4 ×, 8 ×, 10 ×, 12 ×, 16 ×, and 20 ×. Fifteen minutes after the addition of acetaminophen and/or meloxicam, platelet aggregation was stimulated with collagen (2 μg/ml) or arachidonic acid (0.5 mmol/l) and assessed using a Chrono-Log 700 aggregometer. Coagulation function was assessed by prothrombin time (PT), activated partial thromboplastin time (aPTT), and using Rotem thrombelastogram. A robust inhibition by acetaminophen and/or meloxicam was observed in arachidonic acid-stimulated platelet aggregation starting at 1 × dose. Collagen-stimulated platelet aggregation was inhibited by ACE starting at 1 × (78 ± 10% of control), and by meloxicam starting at 4 × (72 ± 5% of control, both P < 0.05). The inhibitions by acetaminophen and meloxicam combined were similar to those by acetaminophen or meloxicam. aPTT was prolonged by meloxicam starting at 4 ×. No changes were observed in PT or any of Rotem measurements by acetaminophen and/or meloxicam. Acetaminophen and meloxicam compromised platelet aggregation and aPTT. Further effort is warranted to characterize the effects of acetaminophen and meloxicam on bleeding in vivo.

  2. Blood Coagulation and Platelet Economy in Subjects with Primary Gout

    PubMed Central

    Mustard, J. F.; Murphy, E. A.; Ogryzlo, M. A.; Smythe, H. A.

    1963-01-01

    Previous studies have suggested that there is an increased incidence of degenerative vascular disease in patients with gout and an increased rate of turnover of blood platelets in patients and animals with atherosclerosis. A disturbed uric acid metabolism and “secondary” gout have long been known to occur with bone marrow diseases. A study of platelet economy and blood clotting factors in subjects with primary gout was therefore undertaken. Twenty-two male subjects with gout but with no clinical evidence of vascular disease were studied. Half of these had a negative family history for vascular disease and half had less fortunate ancestors. The most striking differences were found when gouty patients with a negative family history for vascular disease were compared with similar control subjects. The mean platelet half-life was 2.85 days in the gouty subjects and 3.74 days in the controls. The mean platelet turnover (number/c.mm./day) was 58,750 in gouty subjects, 42,370 in controls. Platelet adhesiveness and plasma thromboplastic activity were correspondingly increased in the gouty subjects. Control subjects with a positive family history all showed relatively active clotting system and platelet turnover, similar to the values found in atherosclerotic subjects. The data indicated that there is increased platelet destruction and production in some patients with primary gout. The relation between this anomaly and the vascular disease, and disturbed urate metabolism in gouty subjects, remains to be investigated. PMID:14084698

  3. Influence of natural coagulants on isoflavones and antioxidant activity of tofu.

    PubMed

    Rekha, C R; Vijayalakshmi, G

    2010-08-01

    Tofu (instead of preparing using synthetic coagulant) was prepared using coagulants of plant origin (Citrus limonum, Garcinia indica, Tamarindus indica, Phyllanthus acidus and Passiflora edulis). Total crude protein and fat contents were highest in tofu prepared using G. indica and T. indica (72.5% dbw) compared to synthetic coagulant. Tofu prepared with natural coagulants had signifi cantly higher antioxidant activity compared to synthetic coagulant. Bioconversion of isoflavone glucosides (daidzin and genistin) into their corresponding bioactive aglycones (daidzein and genistein) was observed in tofu. The difference between glucosides and aglycones contents in soy milk was significant but there was not much difference in tofu coagulated with synthetic and natural coagulants.

  4. Detection of mild inherited disorders of blood coagulation: current options and personal recommendations.

    PubMed

    Lippi, Giuseppe; Pasalic, Leonardo; Favaloro, Emmanuel J

    2015-08-01

    Although assessment of prior personal and familial bleeding history is an important aspect of the diagnosis of bleeding disorders, patients with mild inherited bleeding disorders are sometimes clinically asymptomatic until presented with a hemostatic challenge. However, bleeding may occur after incursion of trauma or surgery, so detection of these conditions reflects an important facet of clinical and laboratory practice. Mild bleeding disorders may be detected as a result of family studies or following identification of abnormal values in first-line screening tests such as activated partial thromboplastin time, prothrombin time, fibrinogen and global platelet function screen testing, such as the platelet function analyzer. Following determination of abnormal screening tests, subsequent investigation should follow a systematic approach that targets specific diagnostic tests, and including factor assays, full platelet function assays and more extensive specialized hemostasis testing. The current report provides a personal overview on inherited disorders of blood coagulation and their detection.

  5. Nanoparticles and the blood coagulation system. Part I: benefits of nanotechnology.

    PubMed

    Ilinskaya, Anna N; Dobrovolskaia, Marina A

    2013-05-01

    Nanotechnology is proven to provide certain benefits in drug delivery by improving solubility, increasing uptake to target sites and changing pharmacokinetics profiles of traditional drugs. Since properties of many materials change tremendously at the nanoscale levels, nanotechnology is also being explored in various industrial applications. As such, nanoparticles are rapidly entering various areas of industry, biology and medicine. The benefits of using nanotechnology for industrial and biomedical applications are often tempered by concerns about the safety of these new materials. One such area of concern includes their effect on the immune system. While nanoparticle interactions with various constituents of the immune system have been reviewed before, little attention was given to nanoparticle effects on the blood coagulation system. Nanoparticle interface with the blood coagulation system may lead to either benefits to the host or adverse reactions. This article reviews recent advances in our understanding of nanoparticle interactions with plasma coagulation factors, platelets, endothelial cells and leukocytes. Part I is focused on desirable interactions between nanoparticles and the coagulation system, and discusses benefits of using nanotechnology to intervene in coagulation disorders. Undesirable interactions posing safety concerns are covered in part II, which will be published in the June issue of Nanomedicine.

  6. An analysis of the contact phase of blood coagulation: effects of shear rate and surface are intertwined.

    PubMed

    Gregory, K; Basmadjian, D

    1994-01-01

    This work analyzes, for the first time, the combined role of blood flow, protein transport and the reaction network of the contact phase up to the "common pathway" of the blood coagulation cascade. The model is comprised of a set of 20 dominant reactions with 11 components. Systems of ODEs reducible to 4 coupled equations describe rigorously the dynamic behavior, while systems of algebraic equations, reducible to a single polynomial equation, model the steady state concentrations of the coagulants. The analysis showed that there is never more than one stable steady state. This is in contrast to the analysis of common pathway that gives rise to multiple concentration states. It also revealed a general robustness of the system to changes in procoagulant concentrations, inhibition rates and most activation rate constants. The system is largely impervious to the level of activated Factor XII, given that a trace (non-zero) level is present. In contrast, the system displays a dual response to flow and surface activity: A change in either of these factors alone can promote, have no effect on, or (in the case of flow) impede the progress of coagulation, depending on the value of the other factor. Their effects must therefore be examined in unison. These results may help resolve contradictory findings attributed to one or the other factor alone.

  7. The effect of pre-eclampsia on the levels of coagulation and fibrinolysis factors in umbilical cord blood of newborns.

    PubMed

    Zanardo, Vincenzo; Savio, Valentina; Sabrina, Gavasso; Franzoi, Malida; Zerbinati, Patrizia; Fadin, Mariangela; Tognin, Giulio; Tormene, Daniela; Pagnan, Antonio; Simioni, Paolo

    2005-04-01

    The effect of pre-eclampsia on coagulation and fibrinolysis in newborns is still under investigation. We have evaluated several coagulation and fibrinolysis parameters in umbilical cord blood of 20 newborns from pre-eclamptic women and of 40 newborns from normotensive women with similar gestational age. Additionally, the presence of factor V Leiden and prothrombin G20210A mutation in cord blood has been assessed. Neonates from pre-eclamptic women exhibited significantly lower birth weight (2.48 +/- 0.92 versus 2.88 +/- 0.68 kg, P < 0.05) and were more frequently admitted to the neonatal intensive care unit (45 versus 20%, P < 0.01) as compared with neonates from normotensive women. Cord blood protein C antigen and activated protein C resistance mean levels were slightly higher in the group of neonates from pre-eclamptic mothers. Fibrinogen levels were lower in this group as compared with control newborns (132.17 +/- 46.97 versus 156.08 +/- 49.58 mg%, P < 0.02), and unrelated to birth weight. No significant differences between cases and controls were found in plasminogen activator inhibitor-1 or tissue plasminogen activator cord blood levels. Heterozygous prothrombin 20210A was found in three newborns from normotensive mothers, whereas no factor V Leiden mutation was found in either group. In conclusion, pre-eclampsia seems to have only mild effects on coagulation and fibrinolytic factors in the cord blood of newborns. Since no excess of common polymorphisms predisposing to thrombosis was found in newborns from pre-eclamptic mothers, it is unlikely that the carriership status of these genetic defects of newborns influences the adverse pregnancy/neonatal outcomes.

  8. Conditions of microvessel occlusion for blood coagulation in flow.

    PubMed

    Bouchnita, A; Galochkina, T; Kurbatova, P; Nony, P; Volpert, V

    2016-11-10

    Vessel occlusion is a perturbation of blood flow inside a blood vessel because of the fibrin clot formation. As a result, blood circulation in the vessel can be slowed down or even stopped. This can provoke the risk of cardiovascular events. In order to explore this phenomenon, we used a previously developed mathematical model of blood clotting to describe the concentrations of blood factors with a reaction-diffusion system of equations. The Navier-Stokes equations were used to model blood flow, and we treated the clot as a porous medium. We identify the conditions of partial or complete occlusion in a small vessel depending on various physical and physiological parameters. In particular, we were interested in the conditions on blood flow and diameter of the wounded area. The existence of a critical flow velocity separating the regimes of partial and complete occlusion was demonstrated through the mathematical investigation of a simplified model of thrombin wave propagation in Poiseuille flow. We observed different regimes of vessel occlusion depending on the model parameters both for the numerical simulations and in the theoretical study. Then, we compared the rate of clot growth in flow obtained in the simulations with experimental data. Both of them showed the existence of different regimes of clot growth depending on the velocity of blood flow.

  9. A mathematical model of thrombin production in blood coagulation, Part I: The sparsely covered membrane case.

    PubMed

    Baldwin, S A; Basmadjian, D

    1994-01-01

    This paper presents the first attempt to model the blood coagulation reactions in flowing blood. The model focuses on the common pathway and includes activation of factor X and prothrombin, including feedback activation of cofactors VIII and V by thrombin, and plasma inhibition of factor Xa and thrombin. In this paper, the first of two, the sparsely covered membrane (SCM) case is presented. This considers the limiting situation where platelet membrane binding sites are in excess, such that no membrane saturation or binding competition occurs. Under these conditions, the model predicts that the two positive feedback loops lead to multiple steady-state behavior in the range of intermediate mass transfer rates. It will be shown that this results in three parameter regions exhibiting very different thrombin production patterns. The model predicts the effect of flow on steady-state and dynamic thrombin production and attempts to explain the difference between venous and arterial thrombi. The reliance of thrombin production on precursor procoagulant protein concentrations is also assessed.

  10. Staphylococcal superantigen-like protein 10 (SSL10) inhibits blood coagulation by binding to prothrombin and factor Xa via their γ-carboxyglutamic acid (Gla) domain.

    PubMed

    Itoh, Saotomo; Yokoyama, Ryosuke; Kamoshida, Go; Fujiwara, Toshinobu; Okada, Hiromi; Takii, Takemasa; Tsuji, Tsutomu; Fujii, Satoshi; Hashizume, Hideki; Onozaki, Kikuo

    2013-07-26

    The staphylococcal superantigen-like protein (SSL) family is composed of 14 exoproteins sharing structural similarity with superantigens but no superantigenic activity. Target proteins of four SSLs have been identified to be involved in host immune responses. However, the counterparts of other SSLs have been functionally uncharacterized. In this study, we have identified porcine plasma prothrombin as SSL10-binding protein by affinity purification using SSL10-conjugated Sepharose. The resin recovered the prodomain of prothrombin (fragment 1 + 2) as well as factor Xa in pull-down analysis. The equilibrium dissociation constant between SSL10 and prothrombin was 1.36 × 10(-7) M in surface plasmon resonance analysis. On the other hand, the resin failed to recover γ-carboxyglutamic acid (Gla) domain-less coagulation factors and prothrombin from warfarin-treated mice, suggesting that the Gla domain of the coagulation factors is essential for the interaction. SSL10 prolonged plasma clotting induced by the addition of Ca(2+) and factor Xa. SSL10 did not affect the protease activity of thrombin but inhibited the generation of thrombin activity in recalcified plasma. S. aureus produces coagulase that non-enzymatically activates prothrombin. SSL10 attenuated clotting induced by coagulase, but the inhibitory effect was weaker than that on physiological clotting, and SSL10 did not inhibit protease activity of staphylothrombin, the complex of prothrombin with coagulase. These results indicate that SSL10 inhibits blood coagulation by interfering with activation of coagulation cascade via binding to the Gla domain of coagulation factor but not by directly inhibiting thrombin activity. This is the first finding that the bacterial protein inhibits blood coagulation via targeting the Gla domain of coagulation factors.

  11. Cord blood coagulation studies in infants of high-risk pregnant women.

    PubMed

    Hathaway, W E; Mahasandana, C; Makowski, E L

    1975-01-01

    A prospective study of cord blood for coagulability, evidence for disseminated intravascular coagulation (DIC), and hematocrit was done in 106 infants who were offspring of mothers with high-risk pregnancies (pre-eclampsia, diabets mellitus, third-trimester bleeders, severe erythroblastosis fetalis, maternal hypertension, fetal distress, and spontaneous premature labor). Significant changes of hypercoagulability (low AT-III and abnormal TEG) were seen in the third-trimester bleeder and premature labor groups which also had the highest incidence of IRDS and necrotizing. Infants undergoing "stress" (pre-eclampsia, fetal distress) had elevated levels of factors V and VIII but were not hypercoagulable or AT-III deficient. Except for mild thrombocytopenia, infants of the diabetic mothers, a group with increased thrombotic complications, did not show any cord blood abnormalities. Offspring of third-trimester bleeders were anemic. The EBF infants were also anemic, severely hypercoagulable, and showed coagulation changes compatible with severe liver disease and/or DIC. Mild changes compatible with intravascular coagulation were seen in six infants and were not related to the the development of IRDS.

  12. Quantification of sphingosine 1-phosphate by validated LC-MS/MS method revealing strong correlation with apolipoprotein M in plasma but not in serum due to platelet activation during blood coagulation.

    PubMed

    Frej, Cecilia; Andersson, Anders; Larsson, Benny; Guo, Li Jun; Norström, Eva; Happonen, Kaisa E; Dahlbäck, Björn

    2015-11-01

    Sphingosine 1-phosphate (S1P) is a signalling sphingolipid affecting multiple cellular functions of vascular and immune systems. It circulates at submicromolar levels bound to HDL-associated apolipoprotein M (apoM) or to albumin. S1P in blood is mainly produced by platelets and erythrocytes, making blood sampling for S1P quantification delicate. Standardisation of sampling is thereby of great importance to obtain robust data. By optimising and characterising the extraction procedure and the LC-MS/MS analysis, we have developed and validated a highly specific and sensitive method for S1P quantification. Blood was collected from healthy individuals (n = 15) to evaluate the effects of differential blood sampling on S1P levels. To evaluate correlation between S1P and apoM in different types of plasma and serum, apoM was measured by ELISA. The method showed good accuracy and precision in the range of 0.011 to 0.9 μM with less than 0.07 % carryover. We found that the methanol precipitation used to extract S1P co-extracted apoM and several other HDL-proteins from plasma. The platelet-associated S1P was released during coagulation, thus increasing the S1P concentration to double in serum as compared to that in plasma. Gel filtration chromatography revealed that the platelet-released S1P was mainly bound to albumin. This explains why the strong correlation between S1P and apoM levels in plasma is lost upon the clotting process and hence not observed in serum. We have developed, characterised and validated an efficient, highly sensitive and specific method for the quantification of S1P in biological material.

  13. Effects of plateletpheresis on blood coagulation parameters in healthy donors at National Blood Centre, Kuala Lumpur, Malaysia.

    PubMed

    Siti Nadiah, A K; Nor Asiah, M; Nur Syimah, A T; Normi, M; Anza, E; Aini, A Nor; Mohd Zahari, T H; Shahnaz, M; Faraizah, A K; Faisal, M A

    2013-12-01

    Plateletpheresis is a method used to remove platelet from the body either from random volunteer donors, patient's family members or HLA matched donors. A cross sectional study was carried out on 59 plateletpheresis donors aged between 18 and 55 years at National Blood Center (NBC), Kuala Lumpur. We compared the blood parameters before and after plateletpheresis and we found that the platelet count, FVIII, fibrinogen and thrombophilia markers anti-thrombin (AT), protein C and protein S were significantly reduced (p<0.05) with prolonged PT and APTT. There were significant changes in blood coagulation parameters but it is within acceptable range.

  14. Sulfated sericin is a novel anticoagulant influencing the blood coagulation cascade.

    PubMed

    Sano, Masanari; Tamada, Yasushi; Niwa, Kazuki; Morita, Toshisuke; Yoshino, Gen

    2009-01-01

    Sulfated sericin's influence on factors in the blood coagulation cascade was investigated to elucidate its anticoagulant mechanism. Prolongation of the prothrombin time (PT) and activated partial thromboplastin time (APTT) were observed in the presence of sulfated sericin. Fluorogenic peptide substrates on thrombin (factor IIa) and factor Xa were used to study the influence of sulfate sericin on their respective activities. Sulfated sericin inhibited neither thrombin nor factor Xa in the presence of antithrombin III (AT III). Gel electrophoresis was used to examine fibrinogen-fibrin conversion by thrombin in the presence of sulfated sericin. FPA and FPB release from fibrinogen by thrombin proceeded in the presence of sulfated sericin. The behavior of polymerization of fibrin monomer (FM) was affected by the presence of sulfated sericin. No initial lag time in the polymerization process was observed by addition of sulfated sericin to FM. This result means that sulfated sericin will interfere in the build-up of normal double-strand fibrils of FM during formation of fibrin fiber. Scanning electron microscopy (SEM) observations supported this inference. The anticoagulant mechanism of sulfated sericin is inferred to interfere with the initial polymerization process of FM.

  15. Contribution of a portable air plasma torch to rapid blood coagulation as a method of preventing bleeding

    NASA Astrophysics Data System (ADS)

    Kuo, S. P.; Tarasenko, O.; Chang, J.; Popovic, S.; Chen, C. Y.; Fan, H. W.; Scott, A.; Lahiani, M.; Alusta, P.; Drake, J. D.; Nikolic, M.

    2009-11-01

    The effectiveness and mechanism of a low temperature air plasma torch in clotting blood are explored. Both blood droplets and smeared blood samples were used in the tests. The treated droplet samples reveal how blood clotting depends on the distance at which the torch operated, and for how long the droplets have been exposed to the torch. Microscopy and cell count of smeared blood samples shed light on dependencies of erythrocyte and platelet counts on torch distance and exposure time. With an increase of torch distance, the platelet count of treated blood samples increases but is less than that of the control. The flux of reactive atomic oxygen (RAO) and the degree of blood clotting decreased. With an increase of exposure time, platelet count of treated samples decreased, while the degree of clot increased. The correlation among these dependencies and published data support a blood clotting mechanism that RAO as well as other likely reactive oxygen species generated by the plasma torch activate erythrocyte-platelets interactions and induces blood coagulation.

  16. Optical coherence tomography to investigate optical properties of blood during coagulation

    NASA Astrophysics Data System (ADS)

    Xu, Xiangqun; Lin, Jia; Fu, Feifei

    2011-09-01

    This study investigates the optical properties of human blood during the coagulation process under statics using optical coherence tomography (OCT). OCT signal slope (OCTSS) and 1/e light penetration depth (d1/e) were obtained from the profiles of reflectance versus depth. Results showed that both OCTSS and d1/e were able to sensitively differentiate various stages of blood properties during coagulating. After 1 h clotting, OCTSS decreased by 47.0%, 15.0%, 13.7%, and 8.5% and d1/e increased by 34.7%, 29.4%, 24.3%, and 22.9% for the blood samples at HCT of 25%, 35%, 45%, and 55%, respectively. The slope of d1/e versus time (Sr, ×10-4 mm/s), associated with clot formation rate decreased from 6.0+/-0.3, 3.7+/-0.5 to 2.3+/-0.4 with the increasing of HCT from 35%, 45%, to 55%. The clotting time (tc) from the d1/e evolution curves was estimated to be 1969+/-92 s, 375+/-12 s, 455+/-11 s, and 865+/-47 s for the blood of 25%, 35%, 45%, and 55%. This study demonstrates that the parameters (tc and Sr) from the variations in d1/e had better sensitivity and smaller standard deviation. Furthermore, blood hematocrit affecting backscattering properties of blood during coagulation was capable of being discerned by OCT parameters. It is concluded that OCT is a potential technique to quantify and follow the liquid-gel transition of blood during clotting.

  17. Optical coherence tomography to investigate optical properties of blood during coagulation.

    PubMed

    Xu, Xiangqun; Lin, Jia; Fu, Feifei

    2011-09-01

    This study investigates the optical properties of human blood during the coagulation process under statics using optical coherence tomography (OCT). OCT signal slope (OCTSS) and 1∕e light penetration depth (d(1∕e)) were obtained from the profiles of reflectance versus depth. Results showed that both OCTSS and d(1∕e) were able to sensitively differentiate various stages of blood properties during coagulating. After 1 h clotting, OCTSS decreased by 47.0%, 15.0%, 13.7%, and 8.5% and d(1∕e) increased by 34.7%, 29.4%, 24.3%, and 22.9% for the blood samples at HCT of 25%, 35%, 45%, and 55%, respectively. The slope of d(1∕e) versus time (S(r), ×10(-4) mm∕s), associated with clot formation rate decreased from 6.0 ± 0.3, 3.7 ± 0.5 to 2.3 ± 0.4 with the increasing of HCT from 35%, 45%, to 55%. The clotting time (t(c)) from the d(1∕e) evolution curves was estimated to be 1969 ± 92 s, 375 ± 12 s, 455 ± 11 s, and 865 ± 47 s for the blood of 25%, 35%, 45%, and 55%. This study demonstrates that the parameters (t(c) and S(r)) from the variations in d(1∕e) had better sensitivity and smaller standard deviation. Furthermore, blood hematocrit affecting backscattering properties of blood during coagulation was capable of being discerned by OCT parameters. It is concluded that OCT is a potential technique to quantify and follow the liquid-gel transition of blood during clotting.

  18. Alterations in Blood Coagulation and Viscosity Among Young Male Cigarette Smokers of Al-Jouf Region in Saudi Arabia.

    PubMed

    Almarshad, Hassan A; Hassan, Fathelrahman M

    2016-05-01

    Hemorheology, a measure of rheological properties of blood, is often correlated with cerebral blood flow and cardiac output; an increased blood viscosity may increase the risk of thrombosis or thromboembolic events. Previous studies have reported a large variation in hemorheological properties of blood among smokers. This prompted us to conduct coagulation experiments to evaluate the effect of cigarette smoking on hematological parameters, like cell counts, and coagulation parameters among young males in Al-Jouf region, Saudi Arabia. The hematological and coagulation parameters were used to relate the changes in viscosity and coagulation to smoking. A total of 321 male participants (126 nonsmokers and 195 smokers) were enrolled into the study as randomized sample. Complete blood count was measured by hematology analyzer, and coagulation tests were performed by coagulation analyzer. Thettest analysis was performed to compare the relationships of variables between the 2 groups. The results confirmed that smoking alters some hematology parameters leading to significant deterioration in blood flow properties. Smoking also increased the hematocrit (HCT), whole blood viscosity (WBV), and plasma viscosity (PV) but decreased the international normalized ratio (INR). The decrease in INR was found to be associated with the increase in WBV, PV, and HCT. Further investigations are necessary to assess the reversibility of such changes in cessation of smoking or other elements of influence.

  19. Effects of Hemoglobin-Based Oxygen Carriers on Blood Coagulation

    PubMed Central

    Roghani, Kimia; Holtby, Randall J.; Jahr, Jonathan S.

    2014-01-01

    For many decades, Hemoglobin-based oxygen carriers (HBOCs) have been central in the development of resuscitation agents that might provide oxygen delivery in addition to simple volume expansion. Since 80% of the world population lives in areas where fresh blood products are not available, the application of these new solutions may prove to be highly beneficial (Kim and Greenburg 2006). Many improvements have been made to earlier generation HBOCs, but various concerns still remain, including coagulopathy, nitric oxide scavenging, platelet interference and decreased calcium concentration secondary to volume expansion (Jahr et al. 2013). This review will summarize the current challenges faced in developing HBOCs that may be used clinically, in order to guide future research efforts in the field. PMID:25514567

  20. Coagulation Factor Concentrates Fail to Restore Alterations in Fibrin Formation Caused by Rivaroxaban or Dabigatran in Studies With Flowing Blood From Treated Healthy Volunteers.

    PubMed

    Arellano-Rodrigo, Eduardo; Lopez-Vilchez, Irene; Galan, Ana M; Molina, Patricia; Reverter, Joan Carles; Carné, Xavier; Villalta, Jaume; Tassies, Dolors; Lozano, Miguel; Díaz-Ricart, Maribel; Escolar, Gines

    2015-10-01

    We evaluated the hemostatic alterations in blood from healthy individuals treated for 5 days with direct oral anticoagulants (DOACs) rivaroxaban (20 mg/d) or dabigatran (150 mg/12 h) in a single-blind clinical trial with crossover assignment (NCT01478282). We assessed the potential of prothrombin complex concentrates, activated prothrombin complex concentrates, or recombinant activated factor VII, when added ex vivo, to reverse the alterations caused by these DOACs. Blood was drawn at maximum plasma concentration after the last dose of each DOAC, and modifications in coagulation biomarkers were evaluated using a series of tests performed under steady conditions including routine coagulation, thrombin generation, and thromboelastometry assays. Additional studies in standardized flow devices were applied to evaluate alterations on platelet deposition and fibrin formation on damaged vascular surfaces exposed to flowing blood. Both DOACs caused important modifications of all coagulation biomarkers and significantly reduced fibrin formation in flow studies. Alterations in biomarkers observed in steady laboratory tests were normalized and occasionally overcompensated by procoagulant strategies. In contrast, reductions in fibrin formation observed in studies with flowing blood were improved, although never completely restored to baseline levels. Effects of dabigatran in flow studies appeared more resistant to reversal strategies than those of rivaroxaban. Inconsistencies between results of coagulation studies in steady or flowing assays not only raise concerns about the adequacy of the earlier tests to predict the restoration of the coagulopathy induced by DOACs but also suggest limitations of nonspecific procoagulant strategies to control severe coagulopathy in patients inadvertently overexposed these agents.

  1. Interleukin-8 activates coagulation and correlates with survival after talc pleurodesis.

    PubMed

    Montes-Worboys, A; Rodriguez-Portal, J A; Arellano-Orden, E; Digón-Pereiras, J; Rodriguez-Panadero, F

    2010-01-01

    The aim of our study was to investigate whether interleukin (IL)-8 activates systemic coagulation after talc pleurodesis in malignant pleural effusion (MPE), and whether levels of IL-8 in plasma are related to early death after talc pleurodesis. IL-8 and tumour necrosis factor (TNF)-alpha were measured in samples from 231 MPE patients before and after talc pleurodesis. Whole blood from 31 healthy volunteers was incubated with IL-8, TNF-alpha and thromboplastin for 3 h in vitro, and thrombin-antithrombin (TAT) levels were measured. The same stimulation of blood samples was repeated using doses of calibrated talc. Nine, 12 and 17 patients died within 7, 10 and 15 days respectively. IL-8 was elevated in 102 patients within 48 h, and thrombotic events were observed in six of those patients. Survival correlated inversely with IL-8 at 24 and 48 h, and a significant correlation was also found between IL-8 and TAT. A positive dose-dependent correlation with TAT production was observed when blood was stimulated with IL-8 in vitro. However, there was no significant response to stimulation with talc, as compared with control blood samples. IL-8 is involved in the activation of coagulation that may occur after talc pleurodesis, and might also be implicated in early death of patients with MPE.

  2. Theories about blood coagulation in the writings of ancient Greek medico-philosophers.

    PubMed

    Tsoucalas, Gregory; Karamanou, Marianna; Papaioannou, Theodoros G; Sgantzos, Markos

    2016-12-05

    Anaxagoras and Empedocles both established during the Presocratic era a pioneering theory for the creation of everything in the universe. Macrocosmos' impact through the "Four Elements Theory" explained the conglomeration of the blood inside the vessels. Hippocrates, who instituted the "Four Humours theory", clearly understood blood's coagulation and introduced the term "thrombus". Plato, Aristotle and Galen, all engaged with the clotting phenomenon trying to interpret it. After eons of inquiry, it was the innovative thinking of the ancient Greek medico philosophers that set the scientific bases towards the understanding of a process that had been analyzing until our era.

  3. Effects of dimethylformamide (DMF) on coagulation and platelet activity

    SciTech Connect

    Imbriani, M.; Ghittori, S.; Prestinoni, A.; Longoni, P.; Cascone, G.; Gamba, G.

    1986-03-01

    The effects of dimethylformamide (DMF) on hemostatic functions, especially on platelet activity, were examined both in vitro and in vivo in 15 workers exposed to DMF (27 mg/m3, median value). Twenty-eight control subjects who were not exposed to DMF, but comparable for age, anthropometric data, and smoking habits, were also studied. Workers exposed to DMF showed a decrease in the number of platelets and had longer coagulation times, probably due to a change caused by DMF on the membrane receptor of platelets and on the phospholipid components of the clotting system.

  4. Effects on fibrinogen, fibrin, and blood coagulation of proteolytic extracts from fruits of Pseudananas macrodontes, Bromelia balansae, and B. hieronymi (Bromeliaceae) in comparison with bromelain.

    PubMed

    Errasti, María E; Prospitti, Anabela; Viana, Carolina A; Gonzalez, Mariana M; Ramos, Márcio V; Rotelli, Alejandra E; Caffini, Néstor O

    2016-06-01

    Extracts rich in cysteine proteases obtained from fruits of Pseudananas macrodontes (Pm), Bromelia balansae (Bb), and B. hieronymi (Bh) have previously shown an anti-inflammatory effect on animal models. Given the close relationship between hemostasis and inflammation, it is attractive to investigate therapeutic agents capable of modulating both systems. The aim of this work was to study the effect of Pm, Bb, and Bh on fibrin(ogen) and blood coagulation compared with stem bromelain (Bro). Action on fibrinogen was electrophoretically and spectrophotometrically evaluated, fibrinolytic activity was measured both electrophoretically and by the fibrin plate assay, and the effect on blood coagulation was studied by conventional coagulation tests (PT and APPT). All extracts showed the same proteolytic preference for fibrinogen subunits, that is Aα > Bβ, whereas γ was partially hydrolyzed by 100-fold concentration increase. Unlike Bro, cysteine proteases of Pm, Bb, and Bh increased absorbance at 540 nm of fibrinogen solution, suggesting thrombin-like activity, which was time-dependent and reached maximum values at lower concentration. All extracts showed the same proteolytic preference for fibrin subunits; however Pm, Bb, and Bh showed lower fibrinolytic activity than Bro at the assayed concentrations. Although Bb acted only as anticoagulant, Pm, Bh, and unexpectedly Bro showed dual action on blood coagulation: at low concentration showed procoagulant effect and at high concentration anticoagulant effect. Results reveal new plant species as potential sources of pharmacological agents for the treatment of a wide range of hemostatic disorders as well as to wound healing.

  5. Red blood cell coagulation induced by low-temperature plasma treatment.

    PubMed

    Miyamoto, Kenji; Ikehara, Sanae; Takei, Hikaru; Akimoto, Yoshihiro; Sakakita, Hajime; Ishikawa, Kenji; Ueda, Masashi; Ikeda, Jun-Ichiro; Yamagishi, Masahiro; Kim, Jaeho; Yamaguchi, Takashi; Nakanishi, Hayao; Shimizu, Tetsuji; Shimizu, Nobuyuki; Hori, Masaru; Ikehara, Yuzuru

    2016-09-01

    Low-temperature plasma (LTP) treatment promotes blood clot formation by stimulation of the both platelet aggregation and coagulation factors. However, the appearance of a membrane-like structure in clots after the treatment is controversial. Based on our previous report that demonstrated characteristics of the form of coagulation of serum proteins induced by LTP treatment, we sought to determine whether treatment with two plasma instruments, namely BPC-HP1 and PN-110/120TPG, formed clots only from red blood cells (RBCs). LTP treatment with each device formed clots from whole blood, whereas LTP treatment with BPC-HP1 formed clots in phosphate-buffered saline (PBS) containing 2 × 10(9)/mL RBCs. Light microscopic analysis results showed that hemolysis formed clots consisting of materials with membrane-like structures from both whole blood and PBS-suspended RBCs. Moreover, electron microscopic analysis results showed a monotonous material with high electron density in the formed clots, presenting a membrane-like structure. Hemolysis disappeared with the decrease in the current through the targets contacting with the plasma flare and clot formation ceased. Taken together, our results and those of earlier studies present two types of blood clot formation, namely presence or absence of hemolysis capability depending on the current through the targets.

  6. Haem-assisted dityrosine-cross-linking of fibrinogen under non-thermal plasma exposure: one important mechanism of facilitated blood coagulation

    PubMed Central

    Ke, Zhigang; Huang, Qing

    2016-01-01

    Although blood coagulation facilitated by non-thermal plasma has been reported several years ago, the insight to the involved mechanisms is still rather limited. In this work, we report our discovery of a new mechanism for the haem-promoted blood-coagulation caused by non-thermal plasma treatment. The reason for the haem role is due to that its oxidized form, namely, hematin, can promote the dityrosine cross-linking of fibrinogen, the most important coagulation protein, to form a membrane-like layer on the surface of the treated blood with plasma exposure. Both haem and non-thermal-plasma generated hydrogen peroxide are requisite for the cross-linking process. We confirmed that fibrinogen can coordinate with the haem iron to form a protein-haem complex which shows pseudo-peroxidase activity, and in the presence of hydrogen peroxide, the complex can induce the dityrosine formation between fibrinogen molecules, leading to the fibrin network necessary for the blood coagulation. Understanding of such an underlying mechanism can be useful to guide more efficient application of non-thermal plasma in the management of hemostasis, thrombosis and etc. PMID:27229173

  7. Platelet coagulation-protein interactions.

    PubMed

    Walsh, Peter N

    2004-08-01

    The biochemical mechanisms by which activated platelets participate in exposing receptors for the assembly of enzyme-cofactor-substrate complexes at all stages of the blood coagulation cascade are reviewed. Information derived from studies conducted during the last 30 years supports the concept that the initiation of blood coagulation is triggered by exposure of tissue factor at injury sites, leading to the generation of minute quantities of thrombin (limited by tissue factor pathway inhibitor), sufficient to activate platelets, factors XI, VIII, and V, and trigger the consolidation pathway (i.e., the sequential activation of factors XI, IX, X, and prothrombin on the activated platelet surface), leading to the generation of sufficient thrombin to convert fibrinogen to fibrin and effect hemostasis. Platelets localize coagulation to the hemostatic thrombus and protect coagulation enzymes from inhibition by both plasma and platelet inhibitors (e.g., protease nexin 2), thus preventing disseminated intravascular coagulation.

  8. The relationship between the antimicrobial effect of catheter coatings containing silver nanoparticles and the coagulation of contacting blood.

    PubMed

    Stevens, Kris N J; Crespo-Biel, Olga; van den Bosch, Edith E M; Dias, Aylvin A; Knetsch, Menno L W; Aldenhoff, Yvette B J; van der Veen, Frederik H; Maessen, Jos G; Stobberingh, Ellen E; Koole, Leo H

    2009-08-01

    It is well known that surface coatings for medical devices can be made antimicrobial through introduction of silver nanoparticles. By virtue of their extremely large surface-to-volume ratio, the silver particles serve as a depot for sustained release of silver ions, despite the fact that silver is not readily oxidized. Antimicrobial coatings are especially important in connection with indwelling catheters with a high risk of bacterial line infections, such as central venous catheters (CVCs). This study specifically addressed the question what the impact of silver nanoparticles (exposed at the coating's surface) and/or the release of silver ions would be on coagulation of contacting blood. Studies, performed in vitro with fresh platelet-rich blood plasma (PRP) from 5 different healthy volunteer donors, clearly pointed out that: (i) the presence of silver nanoparticles correlates with accelerated thrombin formation upon contact of the coating with PRP; (ii) platelet activation is stronger as a result from the contact with silver nanoparticle-containing coatings as compared to other coatings which are devoid of silver. A series of titration experiments, in which the potential effect of silver ions is mimicked, revealed that the observed activation of blood platelets can be best explained through a collision mechanism. The results suggest that platelets that collide with silver, exposed at the surface, become activated without adhering to the surface. These new results point, rather unexpectedly, at a double effect of the silver nanoparticles in the coating: a strong antimicrobial effect occurs simultaneously with acceleration of the coagulation of contacting blood. This new information is, evidently, most relevant for the development of improved surface coatings for indwelling catheters (such as CVCs) which should combine antimicrobial features and close-to-zero thrombogenicity.

  9. 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.

  10. Mast cell-restricted tetramer-forming tryptases and their beneficial roles in hemostasis and blood coagulation.

    PubMed

    Prieto-García, Alicia; Castells, Mariana C; Hansbro, Philip M; Stevens, Richard L

    2014-05-01

    Tetramer-forming tryptase (hTryptase-β) was recently discovered to have a prominent role in preventing the internal accumulation of life-threatening fibrin deposits and fibrin-platelet clots. The anticoagulant activity of hTryptase-β is an explanation for the presence of hemorrhagic disorders in some patients with anaphylaxis or mastocytosis. The fragments of hFibrinogen formed by the proteolysis of this prominent protein by hTryptase-β could be used as biomarkers in the blood and/or urine for the identification and monitoring of patients with mast cell-dependent disorders. Recombinant hTryptase-β has potential to be used in clinical settings where it is desirable to inhibit blood coagulation.

  11. Kinetic characterization of the protein Z-dependent protease inhibitor reaction with blood coagulation factor Xa.

    PubMed

    Huang, Xin; Swanson, Richard; Broze, George J; Olson, Steven T

    2008-10-31

    Protein Z-dependent protease inhibitor (ZPI) is a recently identified member of the serpin superfamily that functions as a cofactor-dependent regulator of blood coagulation factors Xa (FXa) and XIa. Here we show that ZPI and its cofactor, protein Z (PZ), inhibit procoagulant membrane-bound factor Xa by the branched pathway acyl-intermediate trapping mechanism used by other serpins, but with significant variations of this mechanism that are unique to ZPI. Rapid kinetic analyses showed that the reaction proceeded by the initial assembly of a membrane-associated PZ-ZPI-FXa Michaelis complex (K(M) 53+/-5 nM) followed by conversion to a stable ZPI-FXa complex (k(lim) 1.2+/-0.1 s(-1)). Cofactor premixing experiments together with independent kinetic analyses of ZPI-PZ and factor Xa-PZ-membrane complex formation suggested that assembly of the Michaelis complex through either ZPI-PZ-lipid or factor Xa-PZ-lipid intermediates was rate-limiting. Reaction stoichiometry analyses and native PAGE showed that for every factor Xa molecule inhibited by ZPI, two serpin molecules were cleaved. Native PAGE and immunoblotting showed that PZ dissociated from ZPI once ZPI forms a stable complex with FXa, and kinetic analyses confirmed that PZ acted catalytically to accelerate the membrane-dependent ZPI-factor Xa reaction. The ZPI-FXa complex was only transiently stable and dissociated with a rate constant that showed a bell-shaped pH dependence indicative of participation of factor Xa active-site residues. The complex was detectable by SDS-PAGE when denatured at low pH, consistent with it being a kinetically trapped covalent acyl-intermediate. Together our findings show that ZPI functions like other serpins to regulate the activity of FXa but in a manner uniquely dependent on protein Z, procoagulant membranes, and pH.

  12. Possibly propylthiouracil-induced antineutrophilic cytoplasmic antibody-associated vasculitis manifested as blood coagulation disorders

    PubMed Central

    Yi, Xiao-Yan; Wang, Yao; Li, Qi-Fu; Li, Rong; Yang, Shu-Min; Zhou, Guo-Qing; Wang, Zhi-Hong

    2016-01-01

    Abstract Background: Propylthiouracil is the most common drug used to treat hyperthyroidism. However, this drug could cause a severe disease, antineutrophilic cytoplasmic antibody-associated vasculitis (AAV), which was usually misdiagnosed. Methods: We reported a 60-year-old woman of propylthiouracil-induced AAV manifested as blood coagulation disorders. The patient was admitted because of hyperthyroidism and leukopenia. At the time of hospitalization, she suffered from dry cough, erythema and knee joints ache, and gradually became febrile. And then BP decreased and PLT was reduced with coagulation disorders. ANCA: c-ANCA positive (1:100), p-ANCA positive (1:320), MPO-IgG positive, PR3-IgG positive, GBM-IgG negative. Erythrocyte sedimentation rate and C-reactive protein increased markedly. Chest high-resolution computed tomography (HRCT) showed that scattered spots, patch and ground-glass opacity. Results: Finally, we made a terminal diagnosis of PTU-induced AAV possibly. After drug withdrawal and use of steroid, the patient recovered well and then accepted RAI therapy. As the patient was given imipenem-cilastatin before the reduction of PLT and coagulation disorders, we considered that the hematologic disorders might be caused by antibiotics or a clinical presentation of the vasculitis itself. Conclusion: Drug-induced vasculitis is relatively good prognosis, but early diagnosis and timely withdrawal of associated drugs are the key to the treatment. PMID:27741122

  13. Estimation of carboxyhemoglobin concentrations in thermo-coagulated blood on a CO-oximeter system: an experimental study.

    PubMed

    Oritani, S; Nagai, K; Zhu, B L; Maeda, H

    1996-12-27

    In order for forensic toxicological application of a CO-oximeter system to carboxyhemoglobin (CO-Hb) analysis of thermo-coagulated blood, an experimental study was performed. Blood samples containing varying concentrations of CO-Hb were gradually heated up to 70-80 degrees C in ca. 1-13 min, and the extracts (soluble fractions) were examined. CO-Hb contents in the extracts did not represent those in whole thermo-coagulated blood, showing a considerable increase especially for the samples with the initial CO-Hb levels of ca. 25-50%. Changes in CO-Hb % measurements depended little on the heating time but greatly on the final temperature of the blood. The apparent increase in CO-Hb measurements proved to be significantly related to the decrease in total soluble hemoglobin due to thermo-coagulation which depended on the CO-Hb contents, not due to CO-Hb formation by heat. Although gas chromatographic analysis of CO combined with appropriate measurement of total hemoglobin would be required for accurate CO-Hb determination of thermo-coagulated blood, a possible method for rough estimation (semiquantitative screening) of CO-Hb content in whole thermo-coagulated blood with the CO-oximeter was proposed on the basis of thermostability of CO-Hb. The estimated CO-Hb values correlated with the contents measured by a gas chromatographic method independently of the heating time or final temperature up to 80 degrees C.

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. Contribution of explicit solvent effects to the binding affinity of small-molecule inhibitors in blood coagulation factor serine proteases.

    PubMed

    Abel, Robert; Salam, Noeris K; Shelley, John; Farid, Ramy; Friesner, Richard A; Sherman, Woody

    2011-06-06

    The prevention of blood coagulation is important in treating thromboembolic disorders, and several serine proteases involved in the coagulation cascade have been classified as pharmaceutically relevant. Whereas structure-based drug design has contributed to the development of some serine protease inhibitors, traditional computational methods have not been able to fully describe structure-activity relationships (SAR). Here, we study the SAR for a number of serine proteases by using a method that calculates the thermodynamic properties (enthalpy and entropy) of the water that solvates the active site. We show that the displacement of water from specific subpockets (such as S1-4 and the ester binding pocket) of the active site by the ligand can govern potency, especially for cases in which small chemical changes (i.e., a methyl group or halogen) result in a substantial increase in potency. Furthermore, we describe how relative binding free energies can be estimated by combining the water displacement energy with complementary terms from an implicit solvent molecular mechanics description binding.

  20. 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

  1. Coagulopathy in patients with acute pulmonary embolism: a pilot study of whole blood coagulation and markers of endothelial damage.

    PubMed

    Lehnert, Per; Johansson, Pär I; Ostrowski, Sisse R; Møller, Christian H; Bang, Lia E; Olsen, Peter Skov; Carlsen, Jørn

    2017-02-01

    Whole blood coagulation and markers of endothelial damage were studied in patients with acute pulmonary embolism (PE), and evaluated in relation to PE severity. Twenty-five patients were enrolled prospectively each having viscoelastical analysis of whole blood done using thrombelastography (TEG) and Multiplate aggregometry. Fourteen of these patients were investigated for endothelial damage by ELISA measurements of Syndecan-1 (endothelial glycocalyx degradation), soluble endothelial Selectin (endothelial cell activation), soluble Thrombomodulin (endothelial cell injury) and Histone Complexed DNA fragments (endothelial cytotoxic histones). The mean values of TEG and Multiplate parameters were all within the reference levels, but a significant difference between patients with high and intermediate risk PE was observed for Ly30 (lytic activity) 1.5% [0-10] vs. 0.2% [0-2.2] p = .04, and ADP (platelet reactivity) 92 U [20-145] vs. 59 U [20-111] p = .03. A similar difference was indicated for functional fibrinogen 21 mm [17-29] vs. 18 mm [3-23] p = .05. Analysis of endothelial markers identified a significant difference in circulating levels between high and intermediate risk PE patients for Syndecan-1 118.6 ng/mL [76-133] vs. 36.3 ng/mL [11.8-102.9] p = .008. In conclusion, patients with acute PE had normal whole blood coagulation, but high risk PE patients had signs of increased activity of the haemostatic system and significantly increased level of endothelial glycocalyx degradation.

  2. Interaction of blood coagulation factor Va with phospholipid vesicles examined by using lipophilic photoreagents

    SciTech Connect

    Krieg, U.C.; Isaacs, B.S.; Yemul, S.S.; Esmon, C.T.; Bayley, H.; Johnson, A.E.

    1987-01-13

    Two different lipophilic photoreagents, (/sup 3/H)adamantane diazirine and 3-(trifluoromethyl)-3-(m-(/sup 125/I)iodophenyl)diazirine (TID), have been utilized to examine the interactions of blood coagulation factor Va with calcium, prothrombin, factor Xa, and, in particular, phospholipid vesicles. With each of these structurally dissimilar reagents, the extent of photolabeling of factor Va was greater when the protein was bound to a membrane surface than when it was free in solution. Specifically, the covalent photoreaction with Vl, the smaller subunit of factor Va, was 2-fold higher in the presence of phosphatidylcholine/phosphatidylserine (PC/PS, 3:1) vesicles, to which factor Va binds, than in the presence of 100% PC vesicles, to which the protein does not bind. However, the magnitude of the PC/PS-dependent photolabeling was much less than has been observed previously with integral membrane proteins. It therefore appears that the binding of factor Va to the membrane surface exposes Vl to the lipid core of the bilayer, but that only a small portion of the Vl polypeptide is exposed to, or embedded in, the bilayer core. Addition of either prothrombin or active-site-blocked factor Xa to PC/PS-bound factor Va had little effect on the photolabeling of Vl with TID, but reduced substantially the covalent labeling of Vh, the larger subunit of factor Va. This indicates that prothrombin and factor Xa each cover nonpolar surfaces on Vh when the macromolecules associate on the PC/PS surface. It therefore seems likely that the formation of the prothrombinase complex involves a direct interaction between Vh and factor Xa and between Vh and prothrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. 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

  4. [INFLUENCE OF THE INTRA-ABDOMINAL HYPERTENSION ON THE BLOOD COAGULATION SYSTEM (EXPERIMENTAL STUDY)].

    PubMed

    Turgunov, Y; Matyushko, D; Nurbekov, A; Kaliyeva, D; Alibekov, A

    2016-07-01

    The analysis of the influence of the intra-abdominal hypertension on the blood coagulation system by carrying out an experimental research with laboratory animals is presented in article. After simulating intra-abdominal hypertension with different degree and exposition we made the laboratory research of blood coagulation system (fibrinogen, PTI, SFMC, APTT) and ELISA research on the concentration of the modern marker of thrombozis - D-dimer. The results in article clearly demonstrate that there is a direct linear dependence of level of fibrinogen and SFMC on degree of intra-abdominal hypertension, and the multidirectional changes of indicators with increase of intra-abdominal hypertension duration - towards hypercoagulation for 3-12 hours, and then by 24 o'clock - in the opposite direction towards hypocoagulation. Perhaps, it is explained with development of organ dysfunction and a coagulopathy of consumption. Indicator D-dimer has also direct linear dependence on the intra-abdominal hypertension level with contents peak at 3 hour exposition, and at all intra-abdominal hypertension levels, more than 2-fold rise of D-dimer level is statistically significant.

  5. [Effect of rhG-CSF on blood coagulation in beagles irradiated by 2.3 Gy neutron].

    PubMed

    Li, Ming; Han, Qin-Fang; Liu, Xiao-Lan; Xing, Shuang; Xiong, Guo-Lin; Xie, Ling; Zhao, Yan-Fang; Yu, Zu-Yin; Ding, Yi-Bo; Zhao, Zhen-Hu; Cong, Yu-Wen; Luo, Qing-Liang

    2010-12-01

    The aim of this study was to investigate the effect of recombinant human granulocyte stimulating factor (rhG-CSF) on blood coagulation of beagles irradiated by 2.3 Gy neutron so as to provide new therapy for blood coagulation disorder after neutron irradiation. 10 beagles were exposed to 2.3 Gy neutron, and then randomly assigned into supportive care group and rhG-CSF-treated group. The rhG-CSF-treated cohorts were injected subcutaneously with rhG-CSF (10 µg/kg·d) beginning at the day of exposure for 21 consecutive days. Peripheral blood platelet counts were examined once every two days. In vitro platelet aggregation test, thromboelastography and blood clotting tetrachoric tests were also performed. The results indicated that the blood clotting system of irradiated dogs was in hypercoagulable state in the early days after 2.3 Gy neutron irradiation, and became hypocoagulable at crisis later and were mainly on intrinsic coagulation pathway. Blood fibrinogen increased markedly during the course of disease, while platelet counts and aggregation function were decreased remarkably. rhG-CSF administered daily could correct hypercoagulable state induced by 2.3 Gy neutron irradiation at the early time post exposure, shortened the thromboplastin generation time and clotting formation, down-regulated the abnormal high fibrinogen in blood, and improved platelet aggregation function. It is concluded that rhG-CSF can improve coagulation disorders of irradiated dogs.

  6. Reduced Blood Coagulation on Roll-to-Roll, Shrink-Induced Superhydrophobic Plastics.

    PubMed

    Nokes, Jolie M; Liedert, Ralph; Kim, Monica Y; Siddiqui, Ali; Chu, Michael; Lee, Eugene K; Khine, Michelle

    2016-03-09

    The unique antiwetting properties of superhydrophobic (SH) surfaces prevent the adhesion of water and bodily fluids, including blood, urine, and saliva. While typical manufacturable approaches to create SH surfaces rely on chemical and structural modifications, such approaches are expensive, require postprocessing, and are often not biocompatible. By contrast, it is demonstrated that purely structural SH features are easily formed using high throughput roll-to-roll (R2R) manufacturing by shrinking a prestressed thermoplastic with a thin, stiff layer of silver and calcium. These features are subsequently embossed into any commercially available and Food and Drug Administration (FDA)-approved plastic. The R2R SH surfaces have contact angles >150° and contact angle hysteresis <10°. Importantly, the surfaces minimize blood adhesion, leading to reduced blood coagulation without the need for anticoagulants. SH surfaces have >4200× reduction of blood residue area compared to the nonstructured controls of the same material. In addition, blood clotting is reduced >5× using whole blood directly from the patient. Furthermore, these surfaces can be easily configured into 3D shapes, as demonstrated with SH tubes. With the simple scale-up production and the eliminated need for anticoagulants to prevent clotting, the proposed conformable SH surfaces can be impactful for a wide range of medical tools, including catheters and microfluidic channels.

  7. Improved Coagulation and Blood Conservation in the Golden Hours After Cardiopulmonary Bypass

    PubMed Central

    Beckmann, Scott R.; Carlile, Dee; Bissinger, Randall C.; Burrell, M.; Winkler, Thomas; Shely, William W.

    2007-01-01

    Abstract: The Hemobag (HB) technique allows the open-heart team to safely concentrate the residual cardiopulmonary bypass (CPB) circuit contents and return a high volume of concentrated clotting factors and blood cells back to the patient as autotransfusion. Hematocrit, platelet count, fibrinogen concentration ([Fib]), prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratio (INR) were compared between two prospective convenience groups of cardiac surgical patients whose residual circuit blood was processed by the HB (n = 10) or by the Cell Saver (CS; n = 10) at two times after CPB: (a) after acute normovolemic hemodilution (ANH) infusion and protamine administration and (b) after admission to the intensive care unit (ICU), ∼1 hour after CPB and HB content infusion. Minimal cell processing was also used in the HB patients to conserve blood. “Golden hours” is defined as the first few hours after CPB and protamine sulfate administration and extend into the ICU, when maintaining hemostasis is vital during cardiac surgery and is the most susceptible period for blood product administration and the opportunity to improve patient outcome. Except for PTT, all parameters changed significantly from the ANH infusion and protamine administration to ∼1 hour after HB blood infusion and arrival in the ICU. Fibrinogen (p = .048) and hematocrit (p = .046) were significantly higher in the HB group compared with the CS group at the end of the golden hour despite infusion of significantly more allogeneic blood products (p = .070) and more washed red blood cells (RBCs; p = .001) in the CS group. All but one of the HB patients did not receive any allogeneic blood products during the golden hours. Use of the HB technique for salvaging blood is associated with significant increases in the patient’s protein and cellular concentrations and lowered coagulation times in the important, first few golden hours after CPB, and except for one patient

  8. Probing the coagulation pathway with aptamers identifies combinations that synergistically inhibit blood clot formation.

    PubMed

    Bompiani, Kristin M; Lohrmann, Jens L; Pitoc, George A; Frederiksen, James W; Mackensen, George B; Sullenger, Bruce A

    2014-08-14

    Coordinated enzymatic reactions regulate blood clot generation. To explore the contributions of various coagulation enzymes in this process, we utilized a panel of aptamers against factors VIIa, IXa, Xa, and prothrombin. Each aptamer dose-dependently inhibited clot formation, yet none was able to completely impede this process in highly procoagulant settings. However, several combinations of two aptamers synergistically impaired clot formation. One extremely potent aptamer combination was able to maintain human blood fluidity even during extracorporeal circulation, a highly procoagulant setting encountered during cardiopulmonary bypass surgery. Moreover, this aptamer cocktail could be rapidly reversed with antidotes to restore normal hemostasis, indicating that even highly potent aptamer combinations can be rapidly controlled. These studies highlight the potential utility of using sets of aptamers to probe the functions of proteins in molecular pathways for research and therapeutic ends.

  9. Laser speckle contrast imaging of skin blood perfusion responses induced by laser coagulation

    NASA Astrophysics Data System (ADS)

    Ogami, M.; Kulkarni, R.; Wang, H.; Reif, R.; Wang, R. K.

    2014-08-01

    We report application of laser speckle contrast imaging (LSCI), i.e., a fast imaging technique utilising backscattered light to distinguish such moving objects as red blood cells from such stationary objects as surrounding tissue, to localise skin injury. This imaging technique provides detailed information about the acute perfusion response after a blood vessel is occluded. In this study, a mouse ear model is used and pulsed laser coagulation serves as the method of occlusion. We have found that the downstream blood vessels lacked blood flow due to occlusion at the target site immediately after injury. Relative flow changes in nearby collaterals and anastomotic vessels have been approximated based on differences in intensity in the nearby collaterals and anastomoses. We have also estimated the density of the affected downstream vessels. Laser speckle contrast imaging is shown to be used for highresolution and fast-speed imaging for the skin microvasculature. It also allows direct visualisation of the blood perfusion response to injury, which may provide novel insights to the field of cutaneous wound healing.

  10. Laser speckle contrast imaging of skin blood perfusion responses induced by laser coagulation

    SciTech Connect

    Ogami, M; Kulkarni, R; Wang, H; Reif, R; Wang, R K

    2014-08-31

    We report application of laser speckle contrast imaging (LSCI), i.e., a fast imaging technique utilising backscattered light to distinguish such moving objects as red blood cells from such stationary objects as surrounding tissue, to localise skin injury. This imaging technique provides detailed information about the acute perfusion response after a blood vessel is occluded. In this study, a mouse ear model is used and pulsed laser coagulation serves as the method of occlusion. We have found that the downstream blood vessels lacked blood flow due to occlusion at the target site immediately after injury. Relative flow changes in nearby collaterals and anastomotic vessels have been approximated based on differences in intensity in the nearby collaterals and anastomoses. We have also estimated the density of the affected downstream vessels. Laser speckle contrast imaging is shown to be used for highresolution and fast-speed imaging for the skin microvasculature. It also allows direct visualisation of the blood perfusion response to injury, which may provide novel insights to the field of cutaneous wound healing. (laser biophotonics)

  11. Significantly different coagulation factor activities underlying the variability of 'normal' activated partial thromboplastin time.

    PubMed

    Park, Kyoung-Jin; Kwon, Eui-Hoon; Ma, Youngeun; Park, In-Ae; Kim, Seon-Woo; Kim, Sun-Hee; Kim, Hee-Jin

    2012-01-01

    The activated partial thromboplastin time (aPTT) is a widely used coagulation screening test in routine laboratories. The aPTT level in the control population varies and is reflected by the reference interval. However, there have been no studies to investigate the coagulation status determining the variability of the aPTT. The aim of this study was to investigate the coagulation factor activities underlying the variability of aPTT in the population. The study participants were reference individuals with prothrombin time and aPTT within reference intervals. The aPTT was determined using STA-PTT Automate (Diagnostica Stago, Asnieres, France; local reference interval, 29.1-41.9 s). Those with aPTT within the marginal ranges of reference interval were selected for factor assays. We defined the lower marginal group as the lowest 10 percentile of reference interval (29.1-30.9 s) and the upper marginal group as the highest 10 percentile (38.0-41.9 s). Activities of factor II, V, VIII, IX, X, XI, and XII were determined in both groups. The lower marginal and upper marginal groups consisted of 220 and 209 individuals, respectively. All coagulation factors were significantly higher in the lower marginal than in the upper marginal group (P = 0.0127 for factor II and P < 0.0001 for the others). Multiple logistic regression analyses revealed factor XII and VIII were two strongest contributors determining the aPTT level, whereas factor XI was not significantly different between the groups (P = 0.095). This study firstly demonstrated significantly different coagulation factor activities underlying the variability of aPTT in reference individuals. The results suggested the possibility of disease association or phenotypic contribution of variable coagulation activities in the population.

  12. Hepatocyte tissue factor activates the coagulation cascade in mice

    PubMed Central

    Sullivan, Bradley P.; Kopec, Anna K.; Joshi, Nikita; Cline, Holly; Brown, Juliette A.; Bishop, Stephanie C.; Kassel, Karen M.; Rockwell, Cheryl; Mackman, Nigel

    2013-01-01

    In this study, we characterized tissue factor (TF) expression in mouse hepatocytes (HPCs) and evaluated its role in mouse models of HPC transplantation and acetaminophen (APAP) overdose. TF expression was significantly reduced in isolated HPCs and liver homogenates from TFflox/flox/albumin-Cre mice (HPCΔTF mice) compared with TFflox/flox mice (control mice). Isolated mouse HPCs expressed low levels of TF that clotted factor VII-deficient human plasma. In addition, HPC TF initiated factor Xa generation without exogenous factor VIIa, and TF activity was increased dramatically after cell lysis. Treatment of HPCs with an inhibitory TF antibody or a cell-impermeable lysine-conjugating reagent prior to lysis substantially reduced TF activity, suggesting that TF was mainly present on the cell surface. Thrombin generation was dramatically reduced in APAP-treated HPCΔTF mice compared with APAP-treated control mice. In addition, thrombin generation was dependent on donor HPC TF expression in a model of HPC transplantation. These results suggest that mouse HPCs constitutively express cell surface TF that mediates activation of coagulation during hepatocellular injury. PMID:23305736

  13. Acute effects of calcium supplements on blood pressure and blood coagulation: secondary analysis of a randomised controlled trial in post-menopausal women.

    PubMed

    Bristow, Sarah M; Gamble, Greg D; Stewart, Angela; Horne, Anne M; Reid, Ian R

    2015-12-14

    Recent evidence suggests that Ca supplements increase the risk of cardiovascular events, but the mechanism(s) by which this occurs is uncertain. In a study primarily assessing the effects of various Ca supplements on blood Ca levels, we also investigated the effects of Ca supplements on blood pressure and their acute effects on blood coagulation. We randomised 100 post-menopausal women to 1 g/d of Ca or a placebo containing no Ca. Blood pressure was measured at baseline and every 2 h up to 8 h after their first dose and after 3 months of supplementation. Blood coagulation was measured by thromboelastography (TEG) in a subgroup of participants (n 40) up to 8 h only. Blood pressure declined over 8 h in both the groups, consistent with its normal diurnal rhythm. The reduction in systolic blood pressure was smaller in the Ca group compared with the control group by >5 mmHg between 2 and 6 h (P≤0·02), and the reduction in diastolic blood pressure was smaller at 2 h (between-groups difference 4·5 mmHg, P=0·004). Blood coagulability, assessed by TEG, increased from baseline over 8 h in the calcium citrate and control groups. At 4 h, the increase in the coagulation index was greater in the calcium citrate group compared with the control group (P=0·03), which appeared to be due to a greater reduction in the time to clot initiation. These data suggest that Ca supplements may acutely influence blood pressure and blood coagulation. Further investigation of this possibility is required.

  14. HIV Status, Burden of Comorbid Disease, and Biomarkers of Inflammation, Altered Coagulation, and Monocyte Activation

    PubMed Central

    Armah, Kaku A.; McGinnis, Kathleen; Baker, Jason; Gibert, Cynthia; Butt, Adeel A.; Bryant, Kendall J.; Goetz, Matthew; Tracy, Russell; Oursler, Krisann K.; Rimland, David; Crothers, Kristina; Rodriguez-Barradas, Maria; Crystal, Steve; Gordon, Adam; Kraemer, Kevin; Brown, Sheldon; Gerschenson, Mariana; Leaf, David A.; Deeks, Steven G.; Rinaldo, Charles; Kuller, Lewis H; Justice, Amy; Freiberg, Matthew

    2012-01-01

    Background. Biomarkers of inflammation, altered coagulation, and monocyte activation are associated with mortality and cardiovascular disease (CVD) in the general population and among human immunodeficiency virus (HIV)–infected people. We compared biomarkers for inflammation, altered coagulation, and monocyte activation between HIV-infected and uninfected people in the Veterans Aging Cohort Study (VACS). Methods. Biomarkers of inflammation (interleukin-6 [IL-6]), altered coagulation (d-dimer), and monocyte activation (soluble CD14 [sCD14]) were measured in blood samples from 1525 HIV-infected and 843 uninfected VACS participants. Logistic regression was used to determine the association between HIV infection and prevalence of elevated (>75th percentile) biomarkers, adjusting for confounding comorbidities. Results. HIV-infected veterans had less prevalent CVD, hypertension, diabetes, obesity, hazardous drinking, and renal disease, but more dyslipidemia, hepatitis C, and current smoking than uninfected veterans. Compared to uninfected veterans, HIV-infected veterans with HIV-1 RNA ≥500 copies/mL or CD4 count <200 cells/µL had a significantly higher prevalence of elevated IL-6 (odds ratio [OR], 1.54; 95% confidence interval [CI],1.14–2.09; OR, 2.25; 95% CI, 1.60–3.16, respectively) and d-dimer (OR, 1.97; 95% CI, 1.44–2.71, OR, 1.68; 95% CI, 1.22–2.32, respectively) after adjusting for comorbidities. HIV-infected veterans with a CD4 cell count <200 cells/µL had significantly higher prevalence of elevated sCD14 compared to uninfected veterans (OR, 2.60; 95% CI, 1.64–4.14). These associations still persisted after restricting the analysis to veterans without known confounding comorbid conditions. Conclusions. These data suggest that ongoing HIV replication and immune depletion significantly contribute to increased prevalence of elevated biomarkers of inflammation, altered coagulation, and monocyte activation. This contribution is independent of

  15. [Ischemic changes and blood coagulation abnormalities as complications of pneumococcal meningitis].

    PubMed

    Sugiyama, Takashi; Uchiyama, Tsuyoshi; Takashima, Hirotsugu; Yamamoto, Daisuke; Sato, Keishiro; Shimizu, Takako; Otsuki, Yoshiro; Ohashi, Toshihiko

    2015-01-01

    One explanation for cerebral infarctions that occur as a complication of pneumococcal meningitis is blood coagulation abnormalities. We investigated the clinical features, laboratory test results, magnetic resonance imaging (MRI) findings, and pathological features of 10 patients with pneumococcal meningitis between 2006 and 2013 to examine the abnormal findings that may be associated with prognosis. Five patients (50%) that had Glasgow Outcome Scale scores between 1 and 4 were classified as the poor outcome group. In this group, the MRI revealed a high signal intensity on the diffusion-weighted image (DWI), and there was an abnormal signal along the cerebral cortex and Virchow-Robin spaces, which were characterized pathologically by ischemic changes. The plasma thrombin-antithrombin complex (TAT) levels showed greater differences between the poor and good prognosis groups than platlet and D-dimer levels; this suggested that high plasma TAT levels indicate a poor prognosis.

  16. Investigation for role of tissue factor and blood coagulation system in severe acute pancreatitis and associated liver injury.

    PubMed

    Ou, Zhi-Bing; Miao, Chun-Mu; Ye, Ming-Xin; Xing, Ding-Pei; He, Kun; Li, Pei-Zhi; Zhu, Rong-Tao; Gong, Jian-Ping

    2017-01-01

    This study aims to investigate the molecular mechanisms underlying the pathogenesis of severe acute pancreatitis (SAP) and SAP-associated liver injury, we performed an association analysis of the functions of tissue factor (TF) and blood coagulation system in both SAP patients and mouse SAP model. Our results showed that serum TF and tissue factor-microparticle (TF-MP) levels were highly up-regulated in both SAP patients and SAP mouse model, which was accompanied by the dysfunction of blood coagulation system. Besides, TF expression was also highly up-regulated in the Kupffer cells (KCs) of SAP mouse model. After inhibiting KCs in SAP mouse model, the amelioration of blood coagulation system functions was associated with the decrease in serum TF and TF-MPs levels, and the reduction of SAP-associated liver injury was associated with the decrease of TF expression in KCs. In conclusion, the dis-regulated TF expression and associated dysfunction of blood coagulation system are critical factors for the pathogenesis of SAP and SAP-associated liver injury. TF may serve as a potential and effective target for treating SAP and SAP-associated liver injury.

  17. Short-term Effects of Air Temperature on Blood Markers of Coagulation and Inflammation in Potentially Susceptible Individuals

    EPA Science Inventory

    Objectives: Changes in air temperature are associated with an increase in cardiovascular events, but the role of pro-coagulant and pro-inflammatory blood markers is still poorly understood. We investigated the association between air temperature and fibrinogen, plasminogen act...

  18. Interest of ICG blood clearance monitoring for reproducible 810-nm diode laser coagulation of blood vessels

    NASA Astrophysics Data System (ADS)

    Desmettre, Thomas; Soulie-Begu, Sylvie; Devoisselle, Jean-Marie; Mordon, Serge R.

    1999-02-01

    Purpose: To evaluate a method of control of diode laser fluence leading to a reproducible ICG-enhanced selective photocoagulation of blood vessels. This method would use the chromophore clearance, i.e. ICG blood concentration decay to adapt the laser fluence. Materials and Methods: A skin flap window was used on hamsters. After a 15 mg/kg ICG solution injection, photocoagulation of vessels were performed. Results: Selective photocoagulation of blood vessels was obtained only during the first 10 minutes. The fluence required to obtain a selective photocoagulation of vessels (F) was modelized using a one compartment phamacokinetic equation: F equals Of(1-e-t/(tau )). The best fit was obtained for a time constant (tau) equals 4.8 min and Of equals 300 J/cm2 (correlation coefficient r2 equals 0.996). During the first 10 minutes, the fluence required for selective photocoagulation of vessels was increased by a factor 4.5. Conclusion: Fluence required for a selective photocoagulation of vessels was correlated to ICG blood concentration decay. The time constant was equivalent to ICG half-life time in human blood. These results demonstrate that diode laser ICG-enhanced photocoagulation can be controlled by monitoring the ICG blood clearance.

  19. The influence of joint application of arsenic trioxide and daunorubicin on primary acute promyelocytic leukaemia cells and apoptosis and blood coagulation of cell strain.

    PubMed

    Zhang, Xiaojuan; Qin, Na; Chen, Xinghua; Guo, Shuxia

    2015-05-01

    This test cultivated three groups of acute promyelocytic leukemia (APL) and NB4 cells in liquid in vitro, processed them with arsenic trioxide (ATO), daunorubicin (DNR), ATO+DNR respectively, and then set up blank control group. Apoptosis of cells in each group was observed using flow cytometry, procoagulant activity of APL and NB4 cells in each group was detected with recalcification time, and expressions of tissue factor (TF), thrombomodulin and annexin II of NB4 cells in each group were measured using ELISA method. The results showed that the apoptosis rate increased 4-8 times compared with blank control group after processing APL and NB4 cells with ATO and DNR; procoagulant activity decreased obviously; and expression of TF and annexin II of NB4 cells reduced significantly (P<0.05). We concluded that combination of ATO and DNR could promote APL and NB4 cell apoptosis effectively without aggravating blood coagulation disorders, which might improve coagulation function of APL by inhibiting coagulation and hyperfibrinolysis through reducing expression of TF and annexin II. This drug combination may be a safe and effective method in the treatment of APL of primary high white blood cells type.

  20. Obstructive sleep apnea syndrome: blood viscosity, blood coagulation abnormalities, and early atherosclerosis.

    PubMed

    Toraldo, Domenico Maurizio; Peverini, Francesco; De Benedetto, Michele; De Nuccio, Francesco

    2013-02-01

    Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for atherosclerosis and arterial thrombosis, which are associated with high cardiovascular (CV) morbidity and mortality. In studies performed in clinical populations with elevated CV event risk profiles, the occurrence of moderate to severe OSAS was very often accompanied by a worsened vascular function and increased prevalence of structural abnormalities. Recent investigations of atherosclerosis in OSAS have focused on thrombotic tendency and blood viscosity, providing new insight into mechanisms of the disease. Despite that knowledge about the mechanisms of development of CV disease in patients with OSAS is still incomplete, observations confirm a relationship between sleep-disordered breathing and the rheological properties (flow properties) of blood. While platelet dysfunction and hypercoagulability (PDMPs, PaI-1, and SF) play important roles in the pathogenesis of vascular disease, there are limited studies on the potential role of blood viscosity in the development of vascular disease in OSAS.

  1. New clotting disorders that cast new light on blood coagulation and may play a role in clinical practice.

    PubMed

    Girolami, A; Cosi, E; Ferrari, S; Lombardi, A M; Girolami, B

    2017-03-01

    Recently several variants of clotting factors have shown a peculiar behavior so that they appear as new defects. The factors involved are FII, FV and FIX. Prothrombin deficiency is usually associated with bleeding. Recently a few prothrombin abnormalities involving Arg396 mutations, have been demonstrated to show antithrombin resistance with the consequent appearance of a thrombophilic state and venous thromboses in young age. The same is true for an abnormal FIX (FIX Padua). The thrombotic manifestations in the latter condition are also venous. The abnormal FIX (FIX Padua) is characterized by a great increase in FIX activity whereas FIX antigen is only slightly increased. The condition is due to an Arg338Lys mutation. The increased intrinsic clotting activity of this abnormal FIX is being investigated as a useful therapeutic approach in homophile B patients. Another new clotting disorder is represented by two abnormal FV (FV East Texas and FV Amsterdam). These are characterized by a deletion of part of the B domain of FV resulting in a "short" FV. The condition is characterized by a mild bleeding tendency due to high levels of Tissue Factor pathway inhibitor. The "short" factor V is in fact resistant to the action of Tissue Factor pathway inhibitor which is sharply increased in these patients. These new clotting entities have again demonstrated that the study of patients who show a tendency to venous thrombosis or a mild bleeding condition that cannot be explained on the basis of our current concepts of blood coagulation, may represent "new" coagulation disorders. All persons interested in thrombotic or hemorrhagic disorders should be informed about these new clinical and laboratory conditions.

  2. Interference of iron as a coagulant on MIB removal by powdered activated carbon adsorption for low turbidity waters.

    PubMed

    Seckler, Ferreira Filho Sidney; Margarida, Marchetto; Rosemeire, Alves Laganaro

    2013-08-01

    Powered activated carbon (PAC) is widely used in water treatment plants to minimize odors in drinking water. This study investigated the removal of 2-methylisoborneol (MIB) by PAC adsorption, combined with coagulation using iron as a coagulant. The adsorption and coagulation process were studied through different case scenarios of jar tests. The analysis evaluated the effect of PAC dosing in the liquid phase immediately before or after the coagulant addition. Ferric sulphate was used as the coagulant with dosages from 10 to 30 mg/L, and PAC dosages varied from 10 to 40 mg/L. The highest MIB removal efficiency (about 70%) was achieved without the coagulant addition and with the highest PAC dosage (40 mg/L). Lower MIB removal efficiencies were observed in the presence of coagulant, showing a clear interference of the iron precipitate or coagulant in the adsorption process. The degree of interference of the coagulation process in the MIB removal was proportional to the ratio of ferric hydroxide mass to the PAC mass. For both cases of PAC dosing, upstream and downstream of the coagulant injection point, the MIB removal efficiency was similar. However, MIB removal efficiency was 15% lower when compared with experiments without the coagulant application. This interference in the MIB adsorption occurs potentially because the coagulant coats the surface of the carbon and interferes with the MIB coming in contact with the carbon's surface and pores. This constraint requires an increase of the PAC dosage to provide the same efficiency observed without coagulation.

  3. Ex vivo effects of low-dose rivaroxaban on specific coagulation assays and coagulation factor activities in patients under real life conditions.

    PubMed

    Mani, Helen; Hesse, Christian; Stratmann, Gertrud; Lindhoff-Last, Edelgard

    2013-01-01

    Global coagulation assays display variable effects at different concentrations of rivaroxaban. The aim of this study is to quantify the ex vivo effects of low-dose rivaroxaban on thrombophilia screening assays and coagulation factor activities based on the administration time, and to show how to mask possible interferences. Plasma samples from 40 patients receiving rivaroxaban 10 mg daily were investigated to measure activities of clotting factor II, V, VII, VIII, IX, XI, XII and XIII; protein C- and protein S-levels; lupus anticoagulants; anticardiolipin IgG and IgM; D-dimer, heparin-platelet factor 4 (HPF4) antibodies and screening tests for von Willebrand disease (VWD). Two hours after rivaroxaban administration, the activities of clotting factors were significantly decreased to different extents, except for factor XIII. Dilution of plasma samples resulted in neutralisation of these interferences. The chromogenic protein C activity assay was not affected by rivaroxaban. Depending on the timing of tablet intake in relation to blood sampling protein S activity was measured falsely high when a clotting assay was used. False-positive results for lupus anticoagulants were observed depending on the assay system used and the administration time of rivaroxaban. ELISA-based assays such as anticardiolipin IgG and IgM, D-dimer, HPF4-antibodies and the turbidimetric assays for VWD were not affected by rivaroxaban. Specific haemostasis clotting tests should be performed directly prior to rivaroxaban intake. Assay optimisation in the presence of rivaroxaban can be achieved by plasma dilution. Immunologic assays are not influenced by rivaroxaban, while chromogenic assays can be used, when they do not depend on factor Xa.

  4. Evaluation of coagulation factors and platelet function from an off-line modified ultrafiltration technique for post-cardiopulmonary bypass circuit blood recovery.

    PubMed

    Beckmann, S; Lynn, P; Miller, S; Harris, R; DiMarco, R F; Ross, J E

    2013-05-01

    Modified ultrafiltration (MUF) is a technique that hemoconcentrates residual CPB circuit blood and the patient at the same time. Hemoconcentration and MUF are Class 1-A recommendations in the anesthesia and surgical blood conservation guidelines. This study evaluated the off-line MUF process of the Hemobag (HB, Global Blood Resources, Somers, CT, USA) to quantitate coagulation factor levels, platelet (PLT) count and function in one facility and cellular growth factor concentrations of the final product that were transfused to the patient in another facility In two cardiac surgery facilities, after decannulation, the extracorporeal circuit (ECC) blood from 22 patients undergoing cardiac surgery was processed with the HB device. In eleven patients from the first facility by the study design, blood samples for coagulation factor levels and PLT aggregation were drawn from the reservoir of the MUF device pre- and post-processing. The samples (n = 11) were sent to a reference laboratory where testing for prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), reptilase time, fibrinogen, clotting factors II, V, VII, VIII, IX, X, ADAMTS-13, protein C, protein S, antithrombin III, von Willebrand Factor (vWF), and platelet (PLT) aggregation were performed. A portion of the final concentrated HB blood samples (n = 5-10) from the second facility by design were evaluated for transforming and platelet-derived cellular growth factor concentrations. On average, approximately 800 - 2000 mls of whole blood were removed from the ECC post-CPB for processing in the HB device. After processing, there was, on the average, approximately 300 - 950 mls of concentrated whole blood salvaged for reinfusion. The PT and INR were significantly lower in the post-processing product compared to the pre-processing samples while the aPTT times were not significantly different. All coagulation factors and natural anti-coagulants were significantly

  5. Effects of Aerobic Fitness and Adiposity on Coagulation Biomarkers in Men vs. Women with Elevated Blood Pressure

    PubMed Central

    Wilson, Kathleen L.; Tomfohr, Lianne; Edwards, Kate; Knott, Cindy; Hong, Suzi; Redwine, Laura; Calfas, Karen; Rock, Cheryl L.; von Känel, Roland; Mills, Paul J.

    2012-01-01

    A hypercoagulable state is a potential mechanism linking elevated blood pressure (BP), adiposity and a sedentary lifestyle to development of coronary heart disease (CHD). We examined relationships among aerobic fitness and adiposity in 76 sedentary subjects with elevated BP. Blood levels of plasminogen activator inhibitor-1 (PAI-1), D-dimer, von Willebrand factor (vWF) and thrombomodulin were assessed as biomarkers of coagulation. In individuals with elevated BP, percent body fat and fitness were associated with biomarkers indicative of a hypercoagulable state, even after demographic and metabolic factors were considered. D-dimer was positively associated with percent body fat (beta=0.37, p=0.003). PAI-1 was higher in men than in women (beta=−0.31, p=0.015) and associated with lower VO2peak (beta=−0.35, p=0.024). Thrombomodulin was positively associated with VO2peak (beta=0.56, p< 0.01). vWF was not significantly associated with fitness or adiposity. Our results emphasise that both percent body fat and physical fitness are important in the maintenance of haemostatic balance. PMID:23105963

  6. The Coagulative Profile of Cyanotic Children Undergoing Cardiac Surgery: The Role of Whole Blood Preoperative Thromboelastometry on Postoperative Transfusion Requirement.

    PubMed

    Vida, Vladimiro L; Spiezia, Luca; Bortolussi, Giacomo; Marchetti, Marta E; Campello, Elena; Pittarello, Demetrio; Gregori, Dario; Stellin, Giovanni; Simioni, Paolo

    2016-07-01

    The objective of this study is to evaluate the preoperative coagulation pattern and its association to postoperative blood products transfusion in children with congenital heart disease (CHD), focusing on cyanotic patients (oxygen saturation, SATO 2  < 85%). From January to August 2014, preoperative standard coagulation tests and rotational thromboelastometry assays were performed on 81 pediatric patients (<16 years old) who underwent surgery for CHD with the aid of cardiopulmonary bypass. Sixty patients (74%) were acyanotic and 21 (26%) cyanotic. Mean age at time of surgery was 7.9 months (interquartile range 2.9-43.6 months). Cyanotic patients had a significantly higher hematocrit (P < 0.001), a reduced prothrombin activity (PT) (P = 0.01) level, and a lower platelet count (P = 0.02) than acyanotic patients. An inverse linear association was found between patient's SATO2 and clot formation time (CFT) (INTEM, P = 0.001, and EXTEM, P < 0.0001). A direct linear association was found between patient's SATO2 and maximum clot firmness (MCF) (INTEM, P = 0.04, and EXTEM, P = 0.05). Preoperative cyanosis was also associated with a lower median MCF in FIBTEM (P = 0.02). Cyanotic patients required more frequent postoperative transfusions of fibrinogen (7/21 patients, 33% vs. 4/60 patients, 6.7%, P = 0.01) and fresh frozen plasma (14/21, 67% vs. 25/60, 42%, P = 0.08). Patients with a lower presurgery PT and platelet count subsequently required more fibrinogen transfusion P = 0.02 and P = 0.003, respectively); the same goes for patients with a longer CFT (INTEM, P = 0.01 and EXTEM, P = 0.03) and a reduced MCF (INTEM, P = 0.02 and FIBTEM, P = 0.01) as well. Cyanotic patients showed significant preoperative coagulation anomalies and required a higher postoperative fibrinogen supplementation. The preoperative MCF FIBTEM has become an important factor in our postoperative thromboelastometry-guided transfusion

  7. Moderation of prekallkrein-factor XII interactions in surface activation of coagulation by protein-adsorption competition.

    PubMed

    Chatterjee, Kaushik; Thornton, Jennifer L; Bauer, James W; Vogler, Erwin A; Siedlecki, Christopher A

    2009-10-01

    Traditional biochemistry of contact activation of blood coagulation suggesting that anionic hydrophilic surfaces are specific activators of the cascade is inconsistent with known trends in protein adsorption. To investigate contact activation reactions, a chromogenic assay was used to measure prekallkrein (PK) hydrolysis to kallikrein (Kal) by activated factor XII (FXIIa) at test hydrophilic (clean glass) and hydrophobic (silanized glass) surfaces in the presence of bovine serum albumin (BSA). Hydrolysis of PK by FXIIa is detected after contact of the zymogen FXII with a test hydrophobic surface only if putatively-adsorbed FXIIa is competitively displaced by BSA. By contrast, FXIIa activity is detected spontaneously following FXII activation by a hydrophilic surface and requires no adsorption displacement. These results (i) show that an anionic hydrophilic surface is not a necessary cofactor for FXIIa-mediated hydrolysis of PK, (ii) indicate that PK hydrolysis does not need to occur by an activation complex assembled directly on an anionic, activating surface, (iii) confirms that contact activation of FXII (autoactivation) is not specific to anionic hydrophilic surfaces, and (iv) demonstrates that protein-adsorption competition is an essential feature that must be included in any comprehensive mechanism of surface-induced blood coagulation.

  8. [Spatial aspects of the dynamics of blood coagulation. II. Phenomenological model].

    PubMed

    Ataullakhanov, F I; Guriia, G T; Safroshkina, A Iu

    1994-01-01

    Pattern formation dynamics of the blood clotting system was investigated using a reaction-diffusion model based on modern biochemical concepts. It is shown through analysis of the model that the pattern formation mechanism in the blood significantly differs from the well known fundamental Turing's mechanism. Within the mechanism discovered the human blood is treated as the specific new-type active medium, in which the pattern formation is determined by the interplay of two autowaves.

  9. The soluble recombinant form of a binding protein/receptor for the globular domain of C1q (gC1qR) enhances blood coagulation.

    PubMed

    Peerschke, E I; Jesty, J; Reid, K B; Ghebrehiwet, B

    1998-01-01

    The gC1qR is a ubiquitously expressed, 33 kDa cellular protein which recognizes the globular domains of C1q. Recent evidence suggests that the gC1qR also serves as the Zn(++)-dependent endothelial cell binding site for factor XII and high-molecular-weight kininogen, and activates intrinsic coagulation and kinin pathways in purified systems. In addition, activated lymphocytes have been reported to release soluble gC1qR. Thus, the present study investigated the procoagulant potential of soluble gC1qR in human plasma using the recombinant protein (rgC1qR). rgC1qR supported a dose-dependent shortening of extrinsic coagulation using the prothrombin time in the presence of diluted (1/50-1/500) thromboplastin. Maximum enhancement of the prothrombin time resulted in shortening of the clotting time from 78.8 +/- 0.4 s to 68.5 +/- 0.6 s (mean +/- SD, n = 8) in the presence of 50 micrograms/ml (1.5 mumol/l) rgC1qR. rgC1qR also enhanced the intrinsic pathway of coagulation evaluated in the absence of activators of the contact system, as demonstrated by a shortening of the plasma recalcification time from 348 +/- 66 s to 140 +/- 23 s (n = 4). rgC1qR, however, had no effect on intrinsic coagulation in the presence of undiluted kaolin or ellagic acid, and under these conditions failed to shorten the activated partial thromboplastin time of factor VIII or factor-IX-deficient plasma. rgC1qR further failed to affect thrombin and factor Xa generation assayed using chromogenic substrates, and did not enhance thrombin-induced conversion of fibrinogen to fibrin. Interestingly, the procoagulant activity of the rgC1qR was measurable in either factor-XII- or factor-XI-deficient plasma, suggesting that it was not exclusively focused on the contact system of coagulation. Although the mechanism of action of gC1qR on blood coagulation remains obscure, the data suggest a potential role for this protein in hemostatic and thrombotic events.

  10. [Combined use of active chlorine and coagulants for drinking water purification and disinfection].

    PubMed

    Rakhmanin, Iu A; Zholdakova, Z I; Poliakova, E E; Kir'ianova, L F; Miasnikov, I N; Tul'skaia, E A; Artemova, T Z; Ivanova, L V; Dmitrieva, R A; Doskina, T V

    2004-01-01

    The authors made an experimental study of the efficiency of water purification procedures based on the combined use of active chlorine and coagulants and hygienically evaluated the procedures. The study included the evaluation of water disinfection with various coagulants and active chlorine; the investigation of the processes of production of deleterious organic chlorine compounds; the assessment of the quality of water after its treatment. The coagulants representing aluminum polyoxychloride: RAX-10 (AQUA-AURATE 10) and RAX-18 (AQUA-AURATE 18), and aluminum sulfate, technically pure grade were tested. The treatment of river water with the coagulants RAX-10 and RAX-18, followed by precipitation, filtration, and chlorination under laboratory conditions, was shown to result in water disinfection to the levels complying with the requirements described in SanPiN 2.1.4.1074-01. RAX-18 showed the best disinfecting activity against total and heat-tolerant coliform bacteria, but also to the highly chlorine-resistant microrganisms--the spores of sulfite-reducing Clostridia, phages, and viruses. Since the coagulants have an increased sorptive capacity relative to humus and other organic substances, substitution of primary chlorination for coagulant treatment may induce a reduction in the risk of formation of oncogenically and mutagenically hazardous chlorinated hydrocarbons.

  11. Moojenactivase, a novel pro-coagulant PIIId metalloprotease isolated from Bothrops moojeni snake venom, activates coagulation factors II and X and induces tissue factor up-regulation in leukocytes.

    PubMed

    Sartim, Marco A; Costa, Tassia R; Laure, Helen J; Espíndola, Milena S; Frantz, Fabiani G; Sorgi, Carlos A; Cintra, Adélia C O; Arantes, Eliane C; Faccioli, Lucia H; Rosa, José C; Sampaio, Suely V

    2016-05-01

    Coagulopathies following snakebite are triggered by pro-coagulant venom toxins, in which metalloproteases play a major role in envenomation-induced coagulation disorders by acting on coagulation cascade, platelet function and fibrinolysis. Considering this relevance, here we describe the isolation and biochemical characterization of moojenactivase (MooA), a metalloprotease from Bothrops moojeni snake venom, and investigate its involvement in hemostasis in vitro. MooA is a glycoprotein of 85,746.22 Da, member of the PIIId group of snake venom metalloproteases, composed of three linked disulfide-bonded chains: an N-glycosylated heavy chain, and two light chains. The venom protease induced human plasma clotting in vitro by activating on both blood coagulation factors II (prothrombin) and X, which in turn generated α-thrombin and factor Xa, respectively. Additionally, MooA induced expression of tissue factor (TF) on the membrane surface of peripheral blood mononuclear cells (PBMC), which led these cells to adopt pro-coagulant characteristics. MooA was also shown to be involved with production of the inflammatory mediators TNF-α, IL-8 and MCP-1, suggesting an association between MooA pro-inflammatory stimulation of PBMC and TF up-regulation. We also observed aggregation of washed platelets when in presence of MooA; however, the protease had no effect on fibrinolysis. Our findings show that MooA is a novel hemostatically active metalloprotease, which may lead to the development of coagulopathies during B. moojeni envenomation. Moreover, the metalloprotease may contribute to the development of new diagnostic tools and pharmacological approaches applied to hemostatic disorders.

  12. Mathematical modeling of blood coagulation cascade: kinetics of intrinsic and extrinsic pathways in normal and deficient conditions.

    PubMed

    Zhu, Donghui

    2007-10-01

    A mathematical model has been developed to simulate the generation of thrombin through intrinsic and extrinsic pathways. The time course of clotting factor activation during coagulation was calculated, and the sensitivity of the kinetics due to a decrease or deficiency in the concentrations of coagulation proteins or their activities was studied. The model gives reasonable predictions without the adjustment of any parameter values. The calculated clotting time was approximately 44 s for the intrinsic pathway and approximately 8.6 s for the extrinsic pathway using normal protein concentrations in plasma. Various prolonged clotting times were observed in different factor-deficient disorders using this model.

  13. Coagulation Defects in Experimental Hepatic Injury in the Dog

    PubMed Central

    Osbaldiston, G. W.; Hoffman, Marcia W.

    1971-01-01

    Alteration in activity of blood coagulation factors in dogs with acute hepatic injury caused by oral carbon tetrachloride dosing was studied. Coagulation Factors II, VII and IX were dramatically reduced within 48 hours but recovered to normal in the next five days. Because surgery is rarely performed on dogs with hepatic necrosis, the use of fresh whole blood tranfusion to improve the coagulation defect in hepatic injury was also studied. Transfusion was found to have only a temporary beneficial effect. PMID:4253461

  14. Methodical aspects of blood coagulation measurements in birds applying commercial reagents--a pilot study.

    PubMed

    Guddorf, Vanessa; Kummerfeld, Norbert; Mischke, Reinhard

    2014-01-01

    The aim of this study was to examine the suitability of commercially available reagents for measurements of coagulation parameters in citrated plasma from birds. Therefore, plasma samples of 17 healthy donor birds of different species were used to determine prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT) applying various commercial reagents which are routinely used in coagulation diagnostics in humans and mammals. A PT reagent based on human placental thromboplastin yielded not only shorter clotting times than a reagent containing recombinant human tissue factor (median 49 vs. 84 s), but also showed a minor range of distribution of values (43-55 s vs. 30-147 s, minimum-maximum, n = 5 turkeys). An aPTT reagent containing kaolin and phospholipids of animal origin delivered the shortest clotting times and the lowest range of variation in comparison to three other reagents of different composition. However, even when this reagent was used, aPTTs were partially extremely long (> 200 s). Thrombin time was 38 s (28-57 s, n = 5 chicken) when measured with bovine thrombin at a final concentration of 2 IU thrombin/ ml. Coefficients of variation for within-run precision analysis (20 repetitions) of PT was 8.0% and 4.7% for aPTT measurements using selected reagents of mammalian origin. In conclusion, of the commercially available reagents tested, a PT reagent based on human placental thromboplastin and an aPTT reagent including rabbit brain phospholipid and kaolin, show some promise for potential use in birds.

  15. Hemolymph coagulation and phenoloxidase activity in Uca tangeri induced by Escherichia coli endotoxin.

    PubMed

    Salawu, Musa O; Oloyede, Hussein O B; Oladiji, Temidayo A; Yakubu, Musa T; Amuzat, Aliyu O

    2016-05-01

    Uca tangeri is a marine fiddler crab found commonly in the West African coast and is often exposed to Gram-negative pathogens upon injury. The aim of this study was to document the patterns of endotoxin-induced protein coagulation and phenoloxidase (PO) activity in hemolymph fractions of Uca tangeri. Hemolymph from live crabs was obtained by carapace puncture, pooled. and then separated into plasma, hemocyte Lysate (HL), hemocyte lysate supernatant (HLS) and hemocyte lysate debris (HLD). The effect of Escherichia coli (O1111:B4) endotoxin and calcium ion (Ca(2+)) on protein coagulation in the presence/absence of endotoxin and the endotoxin dose-dependence of coagulation and PO activity were each studied in the plasma, HL, HLS and HLD. The results showed Ca(2+) was required to induce coagulation, and was endotoxin concentration-dependent in the plasma. PO activity was highest in the HLS but PO specific activity was highest in HLD. PO activity remained relatively constant with increased LPS concentration in the range studied 0-10 EU/ml. From the data we conclude that endotoxin-induced protein coagulation occurs in the plasma alone and might be mediated by trans-glutaminases, while PO activity is localized inside hemocytes and cell membranes in Uca tangeri.

  16. Clinical utility of biomarkers of endothelial activation and coagulation for prognosis in HIV infection

    PubMed Central

    Graham, Susan M; Mwilu, Regina; Liles, W Conrad

    2013-01-01

    Introduction: HIV infection is associated with vascular dysfunction and adverse cardiovascular outcomes. Our objective was to review the evidence regarding the clinical utility of endothelial activation and coagulation biomarkers for the prognosis of HIV-infected patients. Methods: We searched PubMed and Embase for publications using the keywords “HIV” or “HIV infection” and “endothelium” or “coagulation”. We reviewed reference lists and hand-searched for additional relevant articles. All clinical studies that enrolled non-pregnant, HIV-infected adults, measured biomarkers reflecting endothelial activation or coagulation, and prospectively evaluated their associations with vascular dysfunction or clinical outcomes were included. Results: Seventeen studies were identified that fulfilled the inclusion criteria, of which 11 investigated endothelial activation biomarkers and 12 investigated coagulation biomarkers. Biomarkers and outcomes varied widely across studies. Overall, published studies support an association between P-selectin and venous thromboembolism in HIV-infected patients, an association between tissue-type plasminogen activator and death, and associations between D-dimer and several clinical outcomes, including venous thromboembolism, cardiovascular disease, and all-cause mortality. Conclusions: Several studies have demonstrated associations between biomarkers of endothelial activation and coagulation and clinically important outcomes in HIV-1 infection. Additional large-scale prospective investigations to determine the utility of endothelial activation and coagulation biomarkers for risk stratification and prediction of adverse outcomes are clearly warranted. PMID:23732995

  17. 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.

  18. [DNA extraction from coagulated human blood for application in genotyping techniques for human leukocyte antigen and immunoglobulin-like receptors].

    PubMed

    Cardozo, Daniela Maira; Guelsin, Gláucia Andréia; Clementino, Samaia Laface; Melo, Fabiano Cavalcante de; Braga, Marco Antônio; Souza, Cleonice de; Moliterno, Ricardo Alberto; Visentainer, Jeane Eliete Laguila

    2009-01-01

    The objective of this study was to standardize a method for extracting high-quality DNA from samples of coagulated blood. Forty-eight samples of human coagulated blood were used for DNA extraction by means of the EZ-DNA commercial kit (Biological Industries, Beit Haemek, Israel), the Neoscience column kit (One Lambda Inc., San Diego, CA, USA) and a modified salting-out method. Only the salting-out method was able to extract high concentrations of DNA (mean, 180 ng/(1/4)microl), which were measured using the Qubit fluorescence detector (Invitrogen, USA). This method enabled amplification of HLA (human leukocyte antigen) genes using the Luminex PCR-SSO (polymerase chain reaction - sequence-specific oligonucleotide) technology, which demands good quality DNA, and amplification of KIR (killer-cell immunoglobulin-like receptor) genes using an in-house PCR-SSP (polymerase chain reaction - sequence-specific primer) technique, which demands a specific concentration of DNA (10 ng/(1/4)microl). We concluded that the modified salting-out technique was very efficient, simple and fast for DNA extraction from human coagulated blood samples, with the aim of genotyping the HLA and KIR genes.

  19. Systems Biology of Coagulation

    PubMed Central

    Diamond, Scott L.

    2013-01-01

    Accurate computer simulation of blood function can inform drug target selection, patient-specific dosing, clinical trial design, biomedical device design, as well as the scoring of patient-specific disease risk and severity. These large-scale simulations rely on hundreds of independently measured physical parameters and kinetic rate constants. However, the models can be validated against large scale, patient-specific laboratory measurements. By validation with high dimensional data, modelling becomes a powerful tool to predict clinically complex scenarios. Currently, it is possible to accurately predict the clotting rate of plasma or blood in a tube as it is activated with a dose of tissue factor, even as numerous coagulation factors are altered by exogenous attenuation or potentiation. Similarly, the dynamics of platelet activation, as indicated by calcium mobilisation or inside-out signalling, can now be numerically simulated with accuracy in cases where platelets are exposed to combinations of agonists. Multiscale models have emerged to combine platelet function and coagulation kinetics into complete physics-based descriptions of thrombosis under flow. Blood flow controls platelet fluxes, delivery and removal of coagulation factors, adhesive bonding, and von Willebrand factor conformation. The field of Blood Systems Biology has now reached a stage that anticipates the inclusion of contact, complement, and fibrinolytic pathways along with models of neutrophil and endothelial activation. Along with “-omics” data sets, such advanced models seek to predict the multifactorial range of healthy responses and diverse bleeding and clotting scenarios, ultimately to understand and improve patient outcomes. PMID:23809126

  20. The Mechanisms of Coagulation.

    ERIC Educational Resources Information Center

    Kurtz, Richard; Jesty, Jolyon

    1994-01-01

    Several topics such as heart disease, strokes, biochemical reactions, blood components, and genetics can be related to blood clotting. Introduces a simple, safe and inexpensive hands-on demonstration using bovine (cattle) blood plasma of normal and abnormal coagulation. (ZWH)

  1. Comparison of the level of residual coagulant activity in different cheese varieties.

    PubMed

    Bansal, Nidhi; Fox, Patrick F; McSweeney, Paul L H

    2009-08-01

    The coagulant retained in cheese curd is a major contributor to proteolysis during ripening. The objective of this study was to quantify residual coagulant in 9 cheese varieties by measuring its activity on a synthetic heptapeptide (Pro-Thr-Glu-Phe-[NO2-Phe]-Arg-Leu) assayed using reversed-phase HPLC. The level of residual coagulant activity was highest in Camembert cheese, probably due to its low pH at whey drainage and the high moisture content of the cheese, followed in order by Feta=Port du Salut=Cheddar>Gouda>Emmental=Parmigiano Reggiano=low-moisture part-skim Mozzarella=Mozzarella di Bufala Campana. The high cooking temperature (50-54 degrees C) used during the manufacture of Emmental and Parmigiano Reggiano cheeses and the cooking and stretching step in hot water during the manufacture of Mozzarella cheese may be the reasons for the lowest residual coagulant activity in these cheeses. The level of residual coagulant activity was higher in Feta cheese made from milk concentrated by ultrafiltration than in conventional Feta.

  2. Effects of Blood Coagulate Removal Method on Aedes albopictus (Diptera: Culicidae) Life Table Characteristics and Vector Competence for Dengue Virus.

    PubMed

    van Dodewaard, Caitlin A M; Richards, Stephanie L; Harris, Jonathan W

    2016-01-01

    Commercially available blood can be used as an alternative to live animals to maintain mosquito colonies and deliver infectious bloodmeals during research studies. We analyzed the extent to which two methods for blood coagulate removal (defibrination or addition of sodium citrate) affected life table characteristics (i.e., fecundity, fertility, hatch rate, and adult survival) and vector competence (infection, dissemination, and transmission) of Aedes albopictus (Skuse) for dengue virus (DENV). Two types of bovine blood were tested at two extrinsic incubation temperatures (27 or 30°C) for DENV-infected and uninfected mosquitoes. Fully engorged mosquitoes were transferred to individual cages containing an oviposition cup and a substrate. Eggs (fecundity) and hatched larvae (fertility) were counted. At 14 and 21 d post feeding on a DENV-infected bloodmeal, 15 mosquitoes were sampled from each group, and vector competence was analyzed (bodies [infection], legs [dissemination], and saliva [transmission]). Differences in life table characteristics and vector competence were analyzed for mosquitoes fed blood processed using different methods for removal of coagulates. The method for removal of coagulates significantly impacted fecundity, fertility, and hatch time in the uninfected group, but not DENV-infected group. Infected mosquitoes showed significantly higher fecundity and faster hatch time than uninfected mosquitoes. We show no significant differences in infection or dissemination rates between groups; however, horizontal transmission rate was significantly higher in mosquitoes fed DENV-infected citrated compared with defibrinated blood. We expect the findings of this study to inform research using artificial blood delivery methods to assess vector competence.

  3. Coagulation factor XI promotes distal platelet activation and single platelet consumption in the bloodstream under shear flow

    PubMed Central

    Zilberman-Rudenko, Jevgenia; Itakura, Asako; Wiesenekker, Chantal P.; Vetter, Ralf; Maas, Coen; Gailani, David; Tucker, Erik I.; Gruber, András; Gerdes, Christoph; McCarty, Owen J. T.

    2016-01-01

    Objective Coagulation factor XI (FXI) has been shown to contribute to thrombus formation on collagen or tissue factor (TF)-coated surfaces in vitro and in vivo by enhancing thrombin generation. Whether the role of the intrinsic pathway of coagulation is restricted to the local site of thrombus formation is unknown. This study was aimed to determine whether FXI could promote both proximal and distal platelet activation and aggregate formation in the bloodstream. Approach and Results Pharmacological blockade of FXI activation or thrombin activity in blood did not affect local platelet adhesion, yet reduced local platelet aggregation, thrombin localization and fibrin formation on immobilized collagen and TF under shear flow, ex vivo. Downstream of the thrombus formed on immobilized collagen or collagen and 10 pM TF, platelet CD62P expression and microaggregate formation and progressive platelet consumption were significantly reduced in the presence of FXI-function blocking antibodies or a thrombin inhibitor in a shear rate- and time-dependent manner. In a non-human primate model of thrombus formation, we found that inhibition of FXI reduced single platelet consumption in the bloodstream distal to a site of thrombus formation. Conclusions This study demonstrates that the FXI-thrombin axis contributes to distal platelet activation and procoagulant microaggregate formation in the blood flow downstream of the site of thrombus formation. Our data highlights FXI as a novel therapeutic target for inhibiting distal thrombus formation without affecting proximal platelet adhesion. PMID:26769048

  4. Effect of high pressures on the enzymatic activity of commercial milk protein coagulants

    NASA Astrophysics Data System (ADS)

    Wiśniewska, Krystyna; Reps, Arnold; Jankowska, Agnieszka

    2014-04-01

    This study was aimed at determining the effect of high pressures in the range of 100-1000 MPa/15 min, applied in 100 MPa increments, on the coagulating and proteolytic activity of commercial coagulants produced with genetic engineering methods: Maxiren, Chymogen, Chymax and of a natural rennin preparation, Hala. The coagulating activity of Hala preparation differed compared with the other preparations, due to greater resistance to high pressures, especially in the range of 500-600 MPa. The preparations produced with genetic engineering methods lost their capability for milk protein coagulation by 500 MPa. Pressurization at 200 MPa contributed to their reduced capability for casein macroproteolysis. In contrast, an increase in Chymax, Chymogen, Maxiren and Hala preparations' hydrolytic capability for the macroproteolysis of isoelectric casein was observed upon pressure treatment at 100 and 400 MPa and for microproteolysis after pressure treatment at 200 MPa. Storage (48 h/5°C) of the pressurized preparations had an insignificant effect on their coagulating and proteolytic activities.

  5. [In vitro effects of hemocoagulase atrix and its effective components on blood coagulation of patients with bleeding disorders].

    PubMed

    Wang, Rui-Juan; Wang, Zhao-Yue; Jiang, Ming-Hua; Zhang, Wei; Cao, Li-Juan; Sun, Xiong-Hua; Zhang, Jian; Bai, Xia; Ruan, Chang-Geng

    2012-04-01

    This study was aimed to investigate the pro coagulation effects of hemocoagulase atrix and its effective components (batroxobin and factor X activator) on plasma of normal subjects and patients with bleeding disorders and their mechanisms. Activated partial thromboplastin time (APTT) and prothrombin time (PT) were measured. The factor (F)X activation and thrombin generation were analyzed by using chromogenic substrate method. The results showed that the plasma APTT of normal subjects was shortened by hemocoagulase atrix, batroxobin and FX activator, and the effect of FX activator was found to be concentration-dependent (r = 0.889, P < 0.05). The prolonged APTT of plasma from patients with bleeding disorders could be corrected by hemocoagulase atrix, batroxobin and FX activator, but PT showed no great changes resulted from the treatments. FX activator could promote FX activation and thrombin generation, while neither hemocoagulase atrix nor batroxobin showed such abilities. It is concluded that hemocoagulase atrix promotes coagulation process, and corrects coagulation abnormalities in patients with bleeding disorders, its main component batroxobin directly acts on fibrinogen, and FX activator promotes thrombin generation through activating FX.

  6. Activation of Markers of Inflammation, Coagulation and Fibrinolysis in Musculoskeletal Trauma

    PubMed Central

    Reikerås, Olav; Borgen, Pål

    2014-01-01

    Background Traumatic injury induces changes in mediators of inflammation and coagulation, but the pivotal roles of inflammation and coagulation has not been precisely clarified. Therefore we have studied markers of inflammation and coagulation after a standardized musculoskeletal trauma like total hip replacement surgery. Methods We allocated 21 patients aged 50 to 84 years who underwent total hip replacement surgery. Releases of TNF-α, IL-1β, IL-6, IL-8 and IL-10 and protrombin fragment F1.2 and plasmin-antiplasmin complex (PAP) were examined during surgery and up 6 days postoperatively, and systemic releases were compared to pre-operative values. Surgery induced significant increments in serum levels of IL-6 at 6 hours and at 1 day after surgery and in levels of IL-8 at 6 hours after surgery. There were no significant changes in serum levels of TNF-α, IL-1β or IL-10. There were significant increments in blood levels of F1.2 and PAP up to 6 days postoperatively with highest levels at 6 hours after surgery. There were only week correlations between IL-6 and IL-8 and F1.2 and PAP. Conclusion Major musculoskeletal surgery causes changes of the inflammatory, coagulatory and fibrinolytic cascades in stable patients, but with no correlations between inflammation and coagulation and fibrinolysis. PMID:25364904

  7. Endothelial cell injury and coagulation system activation during synergistic hepatotoxicity from monocrotaline and bacterial lipopolysaccharide coexposure.

    PubMed

    Yee, Steven B; Hanumegowda, Umesh M; Copple, Bryan L; Shibuya, Masabumi; Ganey, Patricia E; Roth, Robert A

    2003-07-01

    A small, noninjurious dose of bacterial lipopolysaccharide (LPS; 7.4 x 106 EU/kg) administered 4 h after a small, nontoxic dose of monocrotaline (MCT; 100 mg/kg) produces synergistic hepatotoxicity in rats within 6 to 12 h after MCT exposure. The resulting centrilobular (CL) and midzonal (MZ) liver lesions are characterized by hepatic parenchymal cell (HPC) necrosis. Pronounced hemorrhage, disruption of sinusoidal architecture, and loss of central vein intima suggest that an additional component to injury may be the liver vasculature. In the present investigation, the hypothesis that sinusoidal endothelial cell (SEC) injury and coagulation system activation occur in this model was tested. Plasma hyaluronic acid (HA) concentration, a biomarker for SEC injury, was significantly increased in cotreated animals before the onset of HPC injury and remained elevated through the time of maximal HPC injury (i.e., 18 h). SEC injury was confirmed by immunohistochemistry and electron microscopy. Pyrrolic metabolites were produced from MCT by SECs in vitro, which suggests that MCT may injure SECs directly through the formation of its toxic metabolite, monocrotaline pyrrole. Inasmuch as SEC activation and injury can promote hemostasis, activation of the coagulation system was evaluated. Coagulation system activation, as marked by a decrease in plasma fibrinogen, occurred before the onset of HPC injury. Furthermore, extensive fibrin deposition was observed immunohistochemically within CL and MZ regions after MCT/LPS cotreatment. Taken together, these results suggest that SEC injury and coagulation system activation are components of the synergistic liver injury resulting from MCT and LPS coexposure.

  8. 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.

  9. Synergistic effect of biological activated carbon and enhanced coagulation in secondary wastewater effluent treatment.

    PubMed

    Aryal, A; Sathasivan, A; Vigneswaran, S

    2012-01-01

    The use of secondary wastewater effluent (SWWE) is an essential strategy for making better use of limited water resources. However, a wide range of organic compounds eventually renders them unsuitable for recycling. In water treatment processes, biologically activated carbon (BAC) is adopted after physicochemical treatment. However, the effectiveness of such combination for SWWE remains poorly understood. This study investigates the effectiveness of various combinations: BAC/enhanced coagulation (EC) or EC/BAC, especially in terms of dissolved organic carbon (DOC) removal. The results showed that distinct advantage could be obtained by adopting BAC/EC combination rather than EC/BAC, as microbes in BAC not only remove non-coagulable compounds but also synergize the removal efficiency by releasing some coagulable humic substances.

  10. Hyperferritinaemia in Dengue Virus Infected Patients Is Associated with Immune Activation and Coagulation Disturbances

    PubMed Central

    Pannuti, Cláudio S.; Brouns, Rosalba M.; van den Berg, Riemsdijk W. A.; van den Ham, Henk-Jan; Martina, Byron E. E.; Osterhaus, Albert D. M. E.; Netea, Mihai G.; Meijers, Joost C. M.; van Gorp, Eric C. M.; Kallas, Esper G.

    2014-01-01

    Background During a dengue outbreak on the Caribbean island Aruba, highly elevated levels of ferritin were detected in dengue virus infected patients. Ferritin is an acute-phase reactant and hyperferritinaemia is a hallmark of diseases caused by extensive immune activation, such as haemophagocytic lymphohistiocytosis. The aim of this study was to investigate whether hyperferritinaemia in dengue patients was associated with clinical markers of extensive immune activation and coagulation disturbances. Methodology/Principal Findings Levels of ferritin, standard laboratory markers, sIL-2R, IL-18 and coagulation and fibrinolytic markers were determined in samples from patients with uncomplicated dengue in Aruba. Levels of ferritin were significantly increased in dengue patients compared to patients with other febrile illnesses. Moreover, levels of ferritin associated significantly with the occurrence of viraemia. Hyperferritinaemia was also significantly associated with thrombocytopenia, elevated liver enzymes and coagulation disturbances. The results were validated in a cohort of dengue virus infected patients in Brazil. In this cohort levels of ferritin and cytokine profiles were determined. Increased levels of ferritin in dengue virus infected patients in Brazil were associated with disease severity and a pro-inflammatory cytokine profile. Conclusions/Significance Altogether, we provide evidence that ferritin can be used as a clinical marker to discriminate between dengue and other febrile illnesses. The occurrence of hyperferritinaemia in dengue virus infected patients is indicative for highly active disease resulting in immune activation and coagulation disturbances. Therefore, we recommend that patients with hyperferritinaemia are monitored carefully. PMID:25299654

  11. Intranasal exposure to amorphous nanosilica particles could activate intrinsic coagulation cascade and platelets in mice

    PubMed Central

    2013-01-01

    Background Nanomaterials with particle sizes <100 nm have been already applied in various applications such as cosmetics, medicines, and foods. Therefore, ensuring the safety of nanomaterials is becoming increasingly important. Here we examined the localization and biological responses of intranasally administered amorphous nanosilica particles in mice, focusing on the coagulation system. Methods We used nanosilica particles with diameters of 30, 70, or 100 nm (nSP30, nSP70, or nSP100 respectively), and conventional microscale silica particles with diameters of 300 or 1000 nm (mSP300 or mSP1000, respectively). BALB/c mice were intranasally exposed to nSP30, nSP70, nSP100, mSP300, or mSP1000 at concentrations of 500 μg/mouse for 7 days. After 24 hours of last administration, we performed the in vivo transmission electron microscopy analysis, hematological examination and coagulation tests. Results In vivo transmission electron microscopy analysis showed that nanosilica particles with a diameter <100 nm were absorbed through the nasal cavity and were distributed into liver and brain. Hematological examination and coagulation tests showed that platelet counts decreased and that the activated partial thromboplastin time was prolonged in nSP30 or nSP70-treated groups of mice, indicating that nanosilica particles might have activated a coagulation cascade. In addition, in in vitro activation tests of human plasma, nanosilica particles had greater potential than did conventional microscale silica particles to activate coagulation factor XII. In nanosilica-particle-treated groups, the levels of soluble CD40 ligand, and von Willebrand factor which are involved in stimulating platelets tended to slightly increase with decreasing particle size. Conclusions These results suggest that intranasally administered nanosilica particles with diameters of 30 and 70 nm could induce abnormal activation of the coagulation system through the activation of an intrinsic coagulation cascade

  12. [Removal of DON in micro-polluted raw water by coagulation and adsorption using activated carbon].

    PubMed

    Liu, Bing; Yu, Guo-Zhong; Gu, Li; Zhao, Cheng-Mei; Li, Qing-Fei; Zhai, Hui-Min

    2013-04-01

    Dissolved organic nitrogen as a precursor of new type nitrogenous disinfection by-products in drinking water attracted gradually the attention of scholars all over the world. In order to explore the mechanism of DON removal in micro-polluted raw water by coagulation and adsorption, water quality parameters, such as DON, DOC, NH4(+) -N, UV254, pH and dissolved oxygen, were determined in raw water and the molecular weight distribution of the DON and DOC was investigated. The variations in DON, DOC and UV254 in the coagulation and adsorption tests were investigated, and the changes of DON in raw water were characterized using three-dimensional fluorescence spectroscopy. The results showed that DON, DOC and UV254 were 1.28 mg x L(-1), 8.56 mg x L(-1), 0.16 cm(-1), and DOC/DON and SUVA were 6.69 mg x mg(-1), 1.87 m(-1) x (mg x L(-1))(-1) in raw water, respectively. The molecular weight distribution of the DON in raw water showed a bimodal distribution. The small molecular weight (< 6 000) fractions accounted for a high proportion of 68% and the large (> 20 000) fractions accounted for about 22%. The removal of DON, DOC and UV254 was about 20%, 26% and 70%, respectively, in the coagulation test and the dosage of coagulant was 10 mg x L(-1). The removal of DON, DOC and UV254 was about 60%, 35% and 100%, respectively, in the adsorption test and the dosage of activated carbon was 1.0 g. In the combination of coagulation and adsorption, the removal of DON and DOC reached approximately 82% and 64%, respectively. 3DEEM revealed that the variation of DON in the coagulation and adsorption tests depended intimately on tryptophan protein-like substances, aromatic protein-like substances and fulvic acid-like substances.

  13. 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.

  14. Positive selection during the evolution of the blood coagulation factors in the context of their disease-causing mutations.

    PubMed

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

    2014-11-01

    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.

  15. 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

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

    PubMed Central

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

    2015-01-01

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

  17. Evidence for a prevalent dimorphism in the activation peptide of human coagulation factor IX.

    PubMed Central

    McGraw, R A; Davis, L M; Noyes, C M; Lundblad, R L; Roberts, H R; Graham, J B; Stafford, D W

    1985-01-01

    We have independently isolated and characterized cDNA and genomic clones for the human coagulation factor IX. Sequence analysis in both cases indicates that threonine is encoded by the triplet ACT as the third residue of the activation peptide. This is in agreement with some earlier reports but in disagreement with others that show the alanine triplet GCT at this position. The discrepancy can thus be accounted for by natural variation of a single nucleotide in the normal population. Amino acid sequence analyses of activated factor IX from plasma samples of four individuals yielded two cases of alanine and two cases of threonine at the third position of the activation peptide. In factor IX from pooled plasma and in factor IX from a heterozygous individual, however, both alanine and threonine were found. Taken together, the findings show that a prevalent nondeleterious dimorphism exists in the activation peptide of human coagulation factor IX. PMID:3857619

  18. Association of air pollution sources and aldehydes with biomarkers of blood coagulation, pulmonary inflammation, and systemic oxidative stress.

    PubMed

    Altemose, Brent; Robson, Mark G; Kipen, Howard M; Ohman Strickland, Pamela; Meng, Qingyu; Gong, Jicheng; Huang, Wei; Wang, Guangfa; Rich, David Q; Zhu, Tong; Zhang, Junfeng

    2016-07-20

    Using data collected before, during, and after the 2008 Summer Olympic Games in Beijing, this study examines associations between biomarkers of blood coagulation (vWF, sCD62P and sCD40L), pulmonary inflammation (EBC pH, EBC nitrite, and eNO), and systemic oxidative stress (urinary 8-OHdG) with sources of air pollution identified utilizing principal component analysis and with concentrations of three aldehydes of health concern. Associations between the biomarkers and the air pollution source types and aldehydes were examined using a linear mixed effects model, regressing through seven lag days and controlling for ambient temperature, relative humidity, gender, and day of week for the biomarker measurements. The biomarkers for pulmonary inflammation, particularly EBC pH and eNO, were most consistently associated with vehicle and industrial combustion, oil combustion, and vegetative burning. The biomarkers for blood coagulation, particularly vWF and sCD62p, were most consistently associated with oil combustion. Systemic oxidative stress biomarker (8-OHdG) was most consistently associated with vehicle and industrial combustion. The associations of the biomarkers were generally not significant or consistent with secondary formation of pollutants and with the aldehydes. The findings support policies to control anthropogenic pollution sources rather than natural soil or road dust from a cardio-respiratory health standpoint.Journal of Exposure Science and Environmental Epidemiology advance online publication, 20 July 2016; doi:10.1038/jes.2016.38.

  19. Plasmin and coagulant activities in a minicurd model system: Study of technological parameters.

    PubMed

    Vélez, M A; Perotti, M C; Candioti, M C; Bergamini, C V; Hynes, E R

    2016-09-01

    The effect of scalding temperature of the curd, the inclusion of a washing step, and the pH at whey drainage on plasmin and coagulant activities were assessed in a minicurd model of young hard cooked cheese. The variables were tested as follows: draining pH was assayed at 3 levels (4.6, 5.6, and 6.4), curd scalding temperature was tested at 50 and 56°C, and washing of the curd was examined at 2 levels (no washing step, and the replacement of the whey by water). Increase in pH at whey drainage and washing of the curd had a positive effect on plasmin activity, which was also evidenced by compatible changes in soluble peptide profiles. No effect of increased cooking temperature was found on plasmin activity. Plasminogen activation was not verified in any treatment. As for coagulant, lower pH values at whey drainage and a decrease in curd cooking temperature increased its activity; washing of the curd showed no influence on coagulant residual activity. These results were consistent with proteolysis described by peptide profiles, electrophoresis, and soluble nitrogen fractions.

  20. Selected parameters of blood coagulation and fibrinolysis prior to and after surgical treatment of squamous cell carcinoma of the oral cavity.

    PubMed

    Knapik, Jadwiga; Korabiowska, Monika; Hönig, Johannes F; Grohmann, Ulrike; Undas, Anetta; Bartkowski, Stanislaw B; Brinck, Ulrich

    2002-01-01

    Selected parameters of blood coagulation and fibrinolysis were evaluated in 20 patients with squamous cell carcinoma of the oral cavity (stages T2/4 N0/3 M0). The control group consisted of 10 healthy age-matched men. The clotting time, calcium plasma clotting time, prothrombin time index and fibrinogen levels in the patients were similar to those observed in the controls. Increased fibrin degradation products (FDP) to 480 and 80 microg/min were found in patients before and after surgical treatment, respectively. We conclude that, in patients treated surgically because of carcinoma of the oral cavity, there might be increased activity of the fibrinolytic system both prior to and after operation.

  1. Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

    NASA Astrophysics Data System (ADS)

    Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J. T.

    2013-06-01

    Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis.

  2. Network-Based Biomarkers for Cold Coagulation Blood Stasis Syndrome and the Therapeutic Effects of Shaofu Zhuyu Decoction in Rats

    PubMed Central

    Su, Shulan; Duan, Jinao; Cui, Wenxia; Shang, Erxing; Liu, Pei; Bai, Gang; Guo, Sheng; Qian, Dawei; Tang, Yuping

    2013-01-01

    In this study, the reverse docking methodology was applied to predict the action targets and pathways of Shaofu Zhuyu decoction (SFZYD) bioactive ingredients. Furthermore, Traditional Chinese Medicine (TCM) cold coagulation blood stasis (CCBS) syndrome was induced in female Sprague-Dawley rats with an ice-water bath and epinephrine, and SFZYD was used to treat CCBS syndrome. A metabolomic approach was used to evaluate changes in the metabolic profiles and to analyze the pharmacological mechanism of SFZYD actions. Twenty-three potential protein targets and 15 pathways were discovered, respectively; among these, pathways are associated with inflammation and immunological stress, hormone metabolism, coagulation function, and glycometabolism. There were also changes in the levels of endogenous metabolites of LysoPCs and glucuronides. Twenty endogenous metabolites were identified. Furthermore, the relative quantities of 6 endogenous metabolites in the plasma and 5 in the urine were significantly affected by SFZYD (P < 0.05). The pharmacological mechanism of SFZYD was partially associated with glycerophospholipid metabolism and pentose and glucuronate interconversions. In conclusion, our findings demonstrated that TCM CCBS pattern induced by ice water and epinephrine was complex and related to multiple metabolic pathways. SFZYD did regulate the TCM CCBS by multitargets, and biomarkers and SFZYD should be used for the clinical treatment of CCBS syndrome. PMID:24288569

  3. Carbon Nanotubes Activate Limulus Amebocyte Lysate Coagulation by Interface Adsorption.

    PubMed

    Yang, Man; Nie, Xin; Meng, Jie; Liu, Jian; Sun, Zhiwei; Xu, Haiyan

    2017-03-15

    Limulus amebocyte lysate (LAL) assay is worldwide requested in the assessment of endotoxin contamination for biomaterials. As carbon nanotubes are one major nanomaterial with multiple potentials in biomedical application, here we investigate whether oxidized multiwalled carbon nanotubes (O-MWCNT) interferes the assessment by LAL assays. We showed that the endotoxin free O-MWCNT dispersing in aqueous solutions could activate both the gel-clotting and the end-point chromogenic LAL assay by converting coagulogen into coagulin through interfacial interactions between O-MWCNT and enzymes in the assays. In conclusion, the O-MWCNT could induce false positive results by activating the enzyme cascade of LAL.

  4. Activation of coagulation in bullous pemphigoid and other eosinophil-related inflammatory skin diseases

    PubMed Central

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

    2011-01-01

    Bullous pemphigoid (BP) is a skin disease caused by autoantibodies to hemidesmosomal proteins BP180 and BP230, with eosinophils participating in blister formation. Tissue factor (TF), the initiator of coagulation, is embodied within the eosinophil granules and exposed upon activation. We evaluated the coagulation activation in patients with BP (63), chronic urticaria (CU; 20), atopic dermatitis (AD; 14), cutaneous drug reactions (CDRs; six), psoriasis (20), dermatitis herpetiformis (DH; four) and primary cutaneous T cell lymphoma (CTCL; five), and in 40 healthy controls. Prothrombin fragment F1+2 and d-dimer (coagulation markers) were measured by enzyme-linked immunosorbent assay (ELISA) in all plasma samples and BP blister fluid. Skin TF expression was evaluated immunohistochemically in the patients and 20 controls. F1+2 and d-dimer levels were higher in BP plasma than in control plasma (P = 0·0001 for both), and dramatically high in blister fluid; both correlated positively with disease severity, esinophil counts and anti-BP180 antibodies (P = 0·006–0·0001). Plasma F1+2 and d-dimer levels were higher in the CU, AD and CDR patients than in controls (P = 0·0001 for all), but normal in the psoriasis, DH and CTCL patients. Skin TF was expressed in the BP (P = 0·0001), CU (P = 0·0001), AD (P = 0·001) and CDR patients (P = 0·01), but not in the psoriasis, DH or CTCL patients. Co-localization confocal microscopy studies confirmed eosinophils as the source of TF in 10 BP patients. The coagulation cascade is activated in BP and other eosinophil-mediated skin disorders, but not in non-eosinophil driven conditions. This hypercoagulability may contribute to inflammation, tissue damage and, possibly, thrombotic risk. PMID:21488867

  5. Comparison of samples obtained from 3.2% sodium citrate glass and two 3.2% sodium citrate plastic blood collection tubes used in coagulation testing.

    PubMed

    Gosselin, Robert C; Janatpour, Kim; Larkin, Edward C; Lee, Yanlap P; Owings, John T

    2004-12-01

    We sought to compare coagulation test results obtained from patients using 2 plastic blood collection tubes and the traditional glass blood collection tube. Blood specimens were obtained from 241 patients in 3.2% buffered sodium citrate using standard glass tubes, in 3.2% buffered sodium citrate in plastic tubes, and in 3.2% sodium citrate "sandwich" tubes (plastic within plastic). All samples were obtained and processed contemporaneously and tested for prothrombin time (PT) and activated partial thromboplastin time (aPTT). Residual plasma was frozen at -70 degrees C for future testing, including fibrinogen, antithrombin, plasminogen, protein C and protein S (functional and antigenic), dilute Russell viper venom time (DRVVT), ristocetin cofactor, factor XIII, D dimer, anti-Xa activity, and prothrombin fragment. Although paired t test analysis revealed statistically significant differences (P < .05) between glass and plastic for PT, aPTT, fibrinogen, protein C (functional and antigenic), functional protein S, DRVVT and confirmation method, antithrombin, and factor XIII, these differences were not considered clinically significant.

  6. Impacts of coagulation on the adsorption of organic micropollutants onto powdered activated carbon in treated domestic wastewater.

    PubMed

    Altmann, Johannes; Zietzschmann, Frederik; Geiling, Eva-Linde; Ruhl, Aki Sebastian; Sperlich, Alexander; Jekel, Martin

    2015-04-01

    The application of powdered activated carbon (PAC) as an advanced wastewater treatment step for the removal of organic micropollutants (OMP) necessitates complete separation of the PAC particles, e.g. by coagulation. In this study, potential positive or negative indirect or direct effects of coagulation on the adsorption of OMPs onto PAC in treated wastewater were investigated. Although the concentration of dissolved organic matter (DOM) was significantly reduced by coagulation, the selective removal of mainly larger DOM components such as biopolymers and humic substances did not improve subsequent OMP adsorption onto PAC, demonstrating that coagulation has minor effects on DOM constituents that are relevant for direct competition or pore blocking. The combination of coagulation and adsorption yielded the sum of the individual removals, as adsorption predominantly affected smaller compounds. While the formation of flocs led to visible incorporation of PAC particles, no significant mass transfer limitations impeded the OMP adsorption. As a result, the dosing sequence of coagulant and PAC is not critical for efficient adsorption of OMPs onto PAC. The relationships between adsorptive OMP removal and corresponding reduction of UV absorption at 254 nm (UVA254) as a promising surrogate correlation for the real-time monitoring and PAC adjustment were affected by coagulation, leading to individual correlations depending on the water composition. Correcting for UVA254 reduction by coagulation produces adsorptive UVA254 removal, which correlates highly with OMP removal for different WWTP effluents and varying coagulant doses and can be applied in combined adsorption/coagulation processes to predict OMP removal and control PAC dosing.

  7. Minimum wound size for clotting: flowing blood coagulates on a single collagen fiber presenting tissue factor and von Willebrand factor.

    PubMed

    Zhu, Shu; Tomaiuolo, Maurizio; Diamond, Scott L

    2016-08-08

    It is unknown if a lower size limit exists for human blood coagulation under flow over physiological vessel wall triggers as small as a single collagen fiber. Prior determinations of the smallest sized surface stimuli necessary for clotting of human blood, defined as the patch size threshold, have not deployed whole blood, hemodynamic flow, and platelet adhesive stimuli. For whole blood perfused in microfluidic devices, we report that steady venous flow (wall shear rate, 100 s(-1)) was sufficient to drive platelet deposition on 20 micron long zones of collagen fibers or on a single fiber. With tissue factor (TF)-coated collagen, flowing blood generated robust platelet deposits, platelet-localized thrombin, and fibrin on a single collagen fiber, thus demonstrating the absence of a physiological patch size threshold under venous flow. In contrast, at arterial wall shear rate (1000 s(-1)) with TF present, essentially no platelet or fibrin deposition occurred on 20 micron collagen zones or on a single collagen fiber, demonstrating a patch threshold, which was overcome by pre-coating the collagen with von Willebrand factor (vWF). For venous flows, human blood can clot on one of the smallest biological units of a single collagen fiber presenting TF. For arterial flows, vWF together with TF allows human blood to generate thrombin and fibrin on a patch stimulus as limited as a single collagen fiber. vWF-dependent platelet adhesion represents a particle-based sensing mechanism of micron-scale stimuli that then allows amplification of the molecular components of TF-driven thrombin and fibrin production under arterial flow.

  8. Momordica charantia seed extract exhibits strong anticoagulant effect by specifically interfering in intrinsic pathway of blood coagulation and dissolves fibrin clot.

    PubMed

    Manjappa, Bhagyalakshmi; Gangaraju, Sowmyashree; Girish, Kesturu S; Kemparaju, Kempaiah; Gonchigar, Sathish J; Shankar, Rohit L; Shinde, Manohar; Sannaningaiah, Devaraja

    2015-03-01

    The current study explores the anticoagulant and fibrin clot-hydrolyzing properties of Momordica charantia seed extract (MCSE). MCSE hydrolyzed casein with the specific activity of 0.780 units/mg per min. Interestingly, it enhanced the clot formation process of citrated human plasma from control 146 to 432 s. In addition, the intravenous injection of MCSE significantly prolonged the bleeding time in a dose-dependent manner from control 150 to more than 800 s, and strengthened its anticoagulant activity. Interestingly, MCSE specifically prolonged the clotting time of only activated partial thromboplastin time, but not prothrombin time, and revealed the participation of MCSE in the intrinsic pathway of the blood coagulation cascade. Furthermore, MCSE completely hydrolyzed both Aα and Bβ chains of the human fibrinogen and partially hydrolyzed the γ chain. However, it hydrolyzed all the chains (α polymer, α chain, β chain and γ-γ dimmers) of partially cross-linked human fibrin clot. The proteolytic activity followed by the anticoagulant effect of the MCSE was completely abolished by the 1,10-phenanthroline and phenyl methyl sulphonyl fluoride, but iodoacetic acid, EDTA, and ethylene glycol-N,N,N',N'-tetra acetic acid did not. Curiously, MCSE did not hydrolyze any other plasma proteins except the plasma fibrinogen. Moreover, MCSE was devoid of RBC lysis, edema and hemorrhagic properties, suggesting its nontoxic nature. Taken together, MCSE may be a valuable candidate in the treatment of blood clot/thrombotic disorders.

  9. Endotoxin-induced coagulation reactions and phenoloxidase activity modulation in Sudanonautes africanus hemolymph fractions.

    PubMed

    Salawu, Musa Oyewole; Oloyede, Oyelola Bukoye

    2011-01-01

    Sudanonautes africanus is a freshwater crab local to Nigeria and West Africa that has no documentation of its innate immunity reactions. The objective of this study was to assess the effect of endotoxin (lipopolysaccharide [LPS]) on coagulation and on phenoloxidase (PO) activity in the hemolymph fractions of S. africanus. The hemolymph from each of 10 live crabs was obtained by carapace puncture and then fractionated into plasma and hemocytes. The hemocytes were then processed and then fractionated into hemocyte lysate (HL), hemocyte lysate supernatant (HLS), and hemocyte lysate debris (HLD). In one study, each fraction was then incubated with a fixed level of LPS in the presence or absence of exogenous calcium (Ca(2+)) ion. In another study, the LPS concentration was varied in order to study its effect on protein coagulation when an optimal ratio mixture of plasma:HLS was present as well as on PO activity in the plasma and HLS fractions. The results of the first set of studies demonstrated that a presence of Ca(2+) in the LPS-induced clotting reactions was essential. The next set of studies showed that a 7:1 plasma:HLS mixture yielded a higher level of coagulation than any other ratio tested in the presence of 1 EU LPS/ml. When this same plasma:HLS mixture ratio was used to ascertain the effect of varying LPS level on coagulation, the response trended higher up to a dose of 3.0 EU/ml., and decreased thereafter until 7 EU/ml. As expected based on the effect of LPS on PO activation, an increasing presence of LPS led to a general trend increase in activity of the enzyme in the plasma fraction; however, the effect was moreover inhibitory in the HLS fraction. From the results here, we conclude that protein coagulation is an important response, along with increased PO activity, that could manifest in Sudanonautes africanus after exposure to 'free' LPS or select LPS-bearing organisms in their environment.

  10. Advances of Coagulation Factor XIII

    PubMed Central

    Shi, Da-Yu; Wang, Shu-Jie

    2017-01-01

    Objective: To provide a comprehensive literature review on roles of coagulation factor XIII (FXIII) in coagulation, wound healing, neoplasm, bone metabolism, and pregnancy. Data Sources: All articles in PubMed with key words Coagulation factor XIII, wound, leukemia, tumor, bone, and pregnancy with published date from 2001 to 2016 were included in the study. Frequently cited publications before 2000 were also included. Study Selection: We reviewed the role of FXIII in biologic processes as documented in clinical, animal, and in vitro studies. Results: FXIII, a member of the transglutaminase (TG) family, plays key roles in various biological processes. Besides its well-known function in coagulation, the cross-linking of small molecules catalyzed by FXIII has been found in studies to help promote wound healing, improve bone metabolism, and prevent miscarriages. The study has also shown that FXIII concentration level differs in the blood of patients with leukemia and solid tumors and offers promises as a diagnostic indicator. Conclusions: FXIII has many more biologic functions besides being known as coagulation factor. The TG activity of FXIII contributes to several processes, including wound healing, bone extracellular matrix stabilization, and the interaction between embryo and decidua of uterus. Further research is needed to elucidate the link between FXIII and leukemia and solid tumors. PMID:28091415

  11. 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

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

    PubMed

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

    2016-04-01

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

  13. Coagulation factor V mediates inhibition of tissue factor signaling by activated protein C in mice

    PubMed Central

    Liang, Hai Po H.; Kerschen, Edward J.; Basu, Sreemanti; Hernandez, Irene; Zogg, Mark; Jia, Shuang; Hessner, Martin J.; Toso, Raffaella; Rezaie, Alireza R.; Fernández, José A.; Camire, Rodney M.; Ruf, Wolfram; Griffin, John H.

    2015-01-01

    The key effector molecule of the natural protein C pathway, activated protein C (aPC), exerts pleiotropic effects on coagulation, fibrinolysis, and inflammation. Coagulation-independent cell signaling by aPC appears to be the predominant mechanism underlying its highly reproducible therapeutic efficacy in most animal models of injury and infection. In this study, using a mouse model of Staphylococcus aureus sepsis, we demonstrate marked disease stage–specific effects of the anticoagulant and cell signaling functions of aPC. aPC resistance of factor (f)V due to the R506Q Leiden mutation protected against detrimental anticoagulant effects of aPC therapy but also abrogated the anti-inflammatory and mortality-reducing effects of the signaling-selective 5A-aPC variant that has minimal anticoagulant function. We found that procofactor V (cleaved by aPC at R506) and protein S were necessary cofactors for the aPC-mediated inhibition of inflammatory tissue-factor signaling. The anti-inflammatory cofactor function of fV involved the same structural features that govern its cofactor function for the anticoagulant effects of aPC, yet its anti-inflammatory activities did not involve proteolysis of activated coagulation factors Va and VIIIa. These findings reveal a novel biological function and mechanism of the protein C pathway in which protein S and the aPC-cleaved form of fV are cofactors for anti-inflammatory cell signaling by aPC in the context of endotoxemia and infection. PMID:26341257

  14. Repeated action of a constant magnetic field on the blood coagulation system in artificially produced anemia

    NASA Technical Reports Server (NTRS)

    Zabrodina, L. V.

    1974-01-01

    Changes are discussed in the coagulatory system of the blood in rabbits under the influence of a constant magnetic field of an intensity of 2500 oersteds against the background of artificially induced anemia. Reversibility of the changes produced and the presence of the adaptational effect are noted. Taking all this into consideration, the changes involving the coagulatory system of the blood which arise under the influence of a constant magnetic field may be considered to have a nerve-reflex nature.

  15. Activation of coagulation during alimentary lipemia under real-life conditions.

    PubMed

    Elmas, Elif; Kälsch, Thorsten; Suvajac, Nenad; Leweling, Hans; Neumaier, Michael; Dempfle, Carl-Erik; Borggrefe, Martin

    2007-01-08

    High intake of saturated fat is a predictor of coronary heart disease mortality. The phenomenon of postprandial angina pectoris has been described many years ago. Although earlier studies have demonstrated postprandial activation of coagulation factors VII and XII, platelets and monocytes, conclusive evidence for intravascular fibrin formation after a fat-rich meal has not been reported yet. The present study included 33 healthy physicians (7 females, 26 males) with a mean age of 42 years (range 27-62 years), and 27 coronary heart disease patients (8 females, 19 males) with a mean age of 63 years (range 47-81 years). Of the coronary heart disease patients, 26/27 were treated with acetylsalicylic acid and 25/27 with lipid-lowering drugs simvastatin or atorvastatin. Blood samples were drawn 30-60 min before and 30-60 min after a dinner consisting of rye bread with liversausage and black pudding as hors d'oeuvre, lettuce with smoked bacon in a lard dressing, stuffed fried goose with red cabbage, potato dumplings and sweet chestnuts, and white and brown mousse au chocolat. Average intake per person was 3760 kcal, with 125.9 g protein, 238.0 g fat and 268.9 g carbohydrate. We measured a significant postprandial increase in fibrinopeptide A (FpA) levels from 1.14+/-1.23 microg/l to 4.18+/-2.86 microg/l (p<0.0001) in healthy probands, and 4.66+/-13.61 microg/l to 12.80+/-15.04 microg/l (p<0.0001) in coronary heart disease patients. Triglycerides increased from 137.6+/-60.5 to 201.5+/-75.0 mg/dl in healthy probands and from 211.9+/-94.6 to 273.6+/-122.5 mg/dl in coronary heart disease patients. Fat-rich meals may cause procoagulant episodes, which may promote vascular complications such as myocardial infarction, transient ischemia attacks in susceptible persons.

  16. 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

  17. 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

  18. Prostate cancer: beware of disseminated intravascular coagulation

    PubMed Central

    Desai, Mihir; John, Babbin; Evans, Gillian; Eddy, Ben

    2015-01-01

    Disseminated intravascular coagulation (DIC) is a pathological systemic condition resulting from aberrant activation of the coagulation system. It is characterised by the release and activation of procoagulants into the blood, with an associated consumption coagulopathy. Its association with solid and haematological malignancies is well described in literature. This case describes an elderly man, known to have prostate cancer, who following transurethral resection of the prostate developed DIC with haematuria, spontaneous ecchymoses and mucosal bleeding. Subsequent investigations revealed a prostate-specific antigen (PSA) >1000 µg/L, and staging CT showed multiple sclerotic metastatic lesions affecting the thoracic and lumbar vertebra, as well as infiltration into his left femur. Coagulation normalised with blood products and vitamin K within 1 week, and the patient responded to antiandrogen therapy with a reduction in pain and PSA on discharge. PMID:25819815

  19. Effect of Ibuprofen Dose on Platelet Aggregation and Coagulation in Blood Samples From Pigs

    DTIC Science & Technology

    2015-03-01

    responses between human and pig blood samples in trauma situations. INTRODUCTION Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic ... analgesic , and antipyretic effects, different profiles of actions have been observed in Aspirin and ibupro- fen. At equivalent effective doses of

  20. Release of alpha 2-plasmin inhibitor from plasma fibrin clots by activated coagulation factor XIII. Its effect on fibrinolysis.

    PubMed Central

    Mimuro, J; Kimura, S; Aoki, N

    1986-01-01

    When blood coagulation takes place in the presence of calcium ions, alpha 2-plasmin inhibitor (alpha 2PI) is cross-linked to fibrin by activated coagulation Factor XIII (XIIIa) and thereby contributes to the resistance of fibrin to fibrinolysis. It was previously shown that the cross-linking reaction is a reversible one, since the alpha 2PI-fibrinogen cross-linked complex could be dissociated. In the present study we have shown that the alpha 2PI-fibrin cross-linking reaction is also a reversible reaction and alpha 2PI which had been cross-linked to fibrin can be released from fibrin by disrupting the equilibrium, resulting in a decrease of its resistance to fibrinolysis. When the fibrin clot formed from normal plasma in the presence of calcium ions was suspended in alpha 2PI-deficient plasma of buffered saline, alpha 2PI was gradually released from fibrin on incubation. When alpha 2PI was present in the suspending milieu, the release was decreased inversely to the concentrations of alpha 2PI in the suspending milieu. The release was accelerated by supplementing XIIIa or the presence of a high concentration of the NH2-terminal 12-residue peptide of alpha 2PI (N-peptide) which is cross-linked to fibrin in exchange for the release of alpha 2PI. When the release of alpha 2PI from fibrin was accelerated by XIIIa or N-peptide, the fibrin became less resistant to the fibrinolytic process, resulting in an acceleration of fibrinolysis which was proportional to the degree of the release of alpha 2PI. These results suggest the possibility that alpha 2PI could be released from fibrin in vivo by disrupting the equilibrium of the alpha 2PI-fibrin cross-linking reaction, and that the release would result in accelerated thrombolysis. Images PMID:2419360

  1. Neutralisation of the anti-coagulant effects of heparin by histones in blood plasma and purified systems.

    PubMed

    Longstaff, Colin; Hogwood, John; Gray, Elaine; Komorowicz, Erzsebet; Varjú, Imre; Varga, Zoltán; Kolev, Krasimir

    2016-03-01

    Neutrophil extracellular traps (NETs) composed primarily of DNA and histones are a link between infection, inflammation and coagulation. NETs promote coagulation and approaches to destabilise NETs have been explored to reduce thrombosis and treat sepsis. Heparinoids bind histones and we report quantitative studies in plasma and purified systems to better understand physiological consequences. Unfractionated heparin (UFH) was investigated by activated partial thromboplastin time (APTT) and alongside low-molecular-weight heparins (LMWH) in purified systems with thrombin or factor Xa (FXa) and antithrombin (AT) to measure the sensitivity of UFH or LMWH to histones. A method was developed to assess the effectiveness of DNA and non-anticoagulant heparinoids as anti-histones. Histones effectively neutralised UFH, the IC50 value for neutralisation of 0.2 IU/ml UFH was 1.8 µg/ml histones in APTT and 4.6 µg/ml against 0.6 IU/ml UFH in a purified system. Histones also inhibited the activities of LMWHs with thrombin (IC50 6.1 and 11.0 µg/ml histones, for different LMWHs) or FXa (IC50 7.8 and 7.0 µg/ml histones). Direct interactions of UFH and LMWH with DNA and histones were explored by surface plasmon resonance, while rheology studies showed complex effects of histones, UFH and LMWH on clot resilience. A conclusion from these studies is that anticoagulation by UFH and LMWH will be compromised by high affinity binding to circulating histones even in the presence of DNA. A complete understanding of the effects of histones, DNA and heparins on the haemostatic system must include an appreciation of direct effects on fibrin and clot structure.

  2. Removal of humic and tannic acids by adsorption-coagulation combined systems with activated biochar.

    PubMed

    Jung, Chanil; Phal, Narong; Oh, Jeill; Chu, Kyoung Hoon; Jang, Min; Yoon, Yeomin

    2015-12-30

    Despite recent interest in transforming biomass into bio-oil and syngas, there is inadequate information on the compatibility of byproducts (e.g., biochar) with agriculture and water purification infrastructures. A pyrolysis at 300°C yields efficient production of biochar, and its physicochemical properties can be improved by chemical activation, resulting in a suitable adsorbent for the removal of natural organic matter (NOM), including hydrophobic and hydrophilic substances, such as humic acids (HA) and tannic acids (TA), respectively. In this study, the adsorption affinities of different HA and TA combinations in NOM solutions were evaluated, and higher adsorption affinity of TA onto activated biochar (AB) produced in the laboratory was observed due to its superior chemisorption tendencies and size-exclusion effects compared with that of HA, whereas hydrophobic interactions between adsorbent and adsorbate were deficient. Assessment of the AB role in an adsorption-coagulation hybrid system as nuclei for coagulation in the presence of aluminum sulfate (alum) showed a synergistic effect in a HA-dominated NOM solution. An AB-alum hybrid system with a high proportion of HA in the NOM solution may be applicable as an end-of-pipe solution.

  3. Pharmaceutical wastewater treatment by internal micro-electrolysis--coagulation, biological treatment and activated carbon adsorption.

    PubMed

    Wang, Kangle; Liu, Suiqing; Zhang, Qiang; He, Yiliang

    2009-12-01

    Treatment of pharmaceutical wastewater by the combined process of internal micro-electrolysis and coagulation, biological treatment and activated carbon adsorption was studied. Internal micro-electrolysis and coagulation served as the pretreatment for the wastewater before biological treatment to reduce the contaminants' toxicity to microbes and improve the biodegradability of wastewater to guarantee the smooth operation of the biological process. Biological treatment was the main body of the whole process which took an unparalleled role in removing COD (chemical oxygen demand). Activated carbon adsorption was adopted as the post-treatment process to further remove the remaining non-biodegradable particles. Results showed that the removal rates of COD and S2- (sulphide ion) by pretreatment were 66.9% and 98.9%, respectively, and the biodegradability, as measured by the ratio of biodegradable COD to initial COD, of the wastewater was greatly improved from 0.16 +/- 0.02 to 0.41 +/- 0.02. The overall removal rate of COD in the wastewater achieved by this combined treatment process was up to 96%, and the effluent COD met the Chinese tertiary discharge standard (GB 8978-1996).

  4. Acetaminophen and Meloxicam Inhibit Platelet Aggregation and Coagulation in Blood Samples from Humans

    DTIC Science & Technology

    2014-01-01

    participant was sampled once with a total of 100-ml blood volume. Exclusion criteria included pregnancy, on- going therapeutic anticoagulation , and use...of thromboxane A2 (TxA2) from prostaglandin H2, which is generated from arachidonic acid by cyclo-oxygenase (COX-1). The antiplatelet effects of...is acetaminophen? Some practical cautions with this widely used agent . Clin Pediatr (Phila) 1973; 12:692– 696. 3 Whyte IM, Buckley NA, Reith DM

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

    DTIC Science & Technology

    2012-03-30

    1995;78:2025-2032. [7] Fried SJ, Satiani B, Zeeb P. Normothermic rapid volume replacement for hypovolemic shock : an in vivo and in vitro study...hemorrhagic shock to restore blood volume, cardiac output and flow to the microcirculation [11-16]. Lactated Ringer’s (LR) and Hextend (HX) are the...lyte solution with glucose, was selected for the battlefield resuscitation of casualties in shock by the Tactical Combat Casualty Care commit- tee

  6. Microfluidics and Coagulation Biology

    PubMed Central

    Colace, Thomas V.; Tormoen, Garth W.

    2014-01-01

    The study of blood ex vivo can occur in closed or open systems, with or without flow. Microfluidic devices facilitate measurements of platelet function, coagulation biology, cellular biorheology, adhesion dynamics, pharmacology, and clinical diagnostics. An experimental session can accommodate 100s to 1000s of unique clotting events. Using microfluidics, thrombotic events can be studied on defined surfaces of biopolymers, matrix proteins, and tissue factor under constant flow rate or constant pressure drop conditions. Distinct shear rates can be created on a device with a single perfusion pump. Microfluidic devices facilitated the determination of intraluminal thrombus permeability and the discovery that platelet contractility can be activated by a sudden decrease in flow. Microfluidics are ideal for multicolor imaging of platelets, fibrin, and phosphatidylserine and provide a human blood analog to the mouse injury models. Overall, microfluidic advances offer many opportunities for research, drug testing under relevant hemodynamic conditions, and clinical diagnostics. PMID:23642241

  7. In vitro/in vivo effect of Citrus limon (L. Burm. f.) juice on blood parameters, coagulation and anticoagulation factors in rabbits.

    PubMed

    Riaz, Azra; Khan, Rafeeq Alam; Mirza, Talat; Mustansir, Tazeen; Ahmed, Mansoor

    2014-07-01

    The genus Citrus of the family Rutaceae includes many species e.g. Citrus indica, Citrus aurantifolia and Citrus limon, among which Citrus limon L. Burm. f. has been reported to have highest antimicrobial activity. It is used as antidote against certain venom, due to its platelet inhibitory effect and also reported to have hypocholesterolemic effect. However its anticoagulant and thrombolytic effect were not been investigated, hence a prospective in-vitro/in-vivo study was designed to determine the effect of Citrus limon on blood parameters, coagulation and anticoagulation factors. In-vitro tests revealed highly significant increase in thrombin time and activated partial thromboplastin time by Citrus limon, whereas fibrinogen concentration was significantly reduced in comparison to control, however prothrombin time was not affected significantly. In-vivo testing of Citrus limon was done at three different doses i.e. 0.2ml/kg, 0.4ml/kg and 0.6ml/kg in healthy rabbits. Significant changes were observed in hematological parameters such as erythrocytes, hemoglobin and mean corpuscular hemoglobin concentration. Bleeding time and thrombin time was significantly prolonged and there was increase in protein C and thrombin antithrombin complex levels. These results may be due to inactivation of thrombin because it significantly decreases fibrinogen concentration and inhibit platelet aggregation. Citrus limon showed maximal anticoagulant effect at 0.4ml/kg, which suggest that Citrus limon possesses an anti-thrombin component and could prevent thrombosis playing a cardio protective role.

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

    PubMed

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

    2016-07-01

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

  9. Microrheological Coagulation Assay Exploiting Micromechanical Resonators.

    PubMed

    Padovani, Francesco; Duffy, James; Hegner, Martin

    2017-01-03

    Rheological measurements in biological liquids yield insights into homeostasis and provide information on important molecular processes that affect fluidity. We present a fully automated cantilever-based method for highly precise and sensitive measurements of microliter sample volumes of human blood plasma coagulation (0.009 cP for viscosity range 0.5-3 cP and 0.0012 g/cm(3) for density range 0.9-1.1 g/cm(3)). Microcantilever arrays are driven by a piezoelectric element, and resonance frequencies and quality factors of sensors that change over time are evaluated. A highly accurate approximation of the hydrodynamic function is introduced that correlates resonance frequency and quality factor of cantilever beams immersed in a fluid to the viscosity and density of that fluid. The theoretical model was validated using glycerol reference solutions. We present a surface functionalization protocol that allows minimization of unspecific protein adsorption onto cantilevers. Adsorption leads to measurement distortions and incorrect estimation of the fluid parameters (viscosity and density). Two hydrophilic terminated self-assembled monolayers (SAMs) sensor surfaces are compared to a hydrophobic terminated SAM coating. As expected, the hydrophobic modified surfaces induced the highest mass adsorption and could promote conformational changes of the proteins and subsequent abnormal biological activity. Finally, the activated partial thromboplastin time (aPTT) coagulation assay was performed, and the viscosity, density, and coagulation rate of human blood plasma were measured along with the standard coagulation time. The method could extend and improve current coagulation testing.

  10. CrataBL, a lectin and Factor Xa inhibitor, plays a role in blood coagulation and impairs thrombus formation.

    PubMed

    Salu, Bruno R; Ferreira, Rodrigo S; Brito, Marlon V; Ottaiano, Tatiana F; Cruz, José Walber M C; Silva, Mariana Cristina C; Correia, Maria Tereza S; Paiva, Patrícia M G; Maffei, Francisco Humberto A; Oliva, Maria Luiza Vilela

    2014-09-01

    Arterial thrombosis is an important complication of diabetes and cancer, being an important target for therapeutic intervention. Crataeva tapia bark lectin (CrataBL) has been previously shown to have hypoglycemiant effect and also to induce cancer cell apoptosis. It also showed inhibitory activity against Factor Xa (Kiapp=8.6 μm). In the present study, we evaluated the anti-thrombotic properties of CrataBL in arterial thrombosis model. CrataBL prolongs the activated partial thromboplastin time on human and mouse plasma, and it impairs the heparin-induced potentiation of antithrombin III and heparin-induced platelet activation in the presence of low-dose ADP. It is likely that the dense track of positive charge on CrataBL surface competes with the heparin ability to bind to antithrombin III and to stimulate platelets. In the photochemically induced thrombosis model in mice, in the groups treated with 1.25, 5.0, or 10 mg/kg CrataBL, prior to the thrombus induction, the time of total artery occlusion was prolonged by 33.38%, 65%, and 66.11%, respectively, relative to the time of the control group. In contrast to heparin, the bleeding time in CrataBL-treated mice was no longer than in the control. In conclusion, CrataBL was effective in blocking coagulation and arterial thrombus formation, without increasing bleeding time.

  11. Blood plasma contact activation on silicon, titanium and aluminium.

    PubMed

    Arvidsson, Sara; Askendal, Agneta; Tengvall, Pentti

    2007-03-01

    In the present work, blood plasma protein deposition to spontaneously air oxidized silicon, titanium and aluminium was re-investigated in vitro. Immunological- and null ellipsometry methods were used to detect and quantitate adsorbed proteins, RIA methods to study the retention of preadsorbed 125I-HSA upon exposure to buffer or blood plasma, and kallikrein-specific colorimetric substrate S-2302 to follow the surface generation of kallikrein. The results show that the contact activation of coagulation and complement systems are connected on Si and Ti, but not on Al, via coagulation factor XII. Preadsorbed 125I-HSA was most readily displaced on silicon, followed by titanium and aluminium. The surfaces displayed different antibody binding patterns after short and long-time exposures to plasma. Titanium and silicon bound anti-HMWK after 1 min in plasma, but aluminium did not. When the plasma incubation time was prolonged up to 2h the anti-HMWK binding disappeared totally on titanium and decreased on silicon. During the same time period, anti-C3c binding increased to the three types of surfaces. Also, the anti-C3c binding onto Si and Ti, but not Al, disappeared after incubation in Factor XII deficient plasma or when a specific coagulation factor XII (Factor XII) inhibitor, corn trypsin inhibitor (CTI) was added to normal plasma. The surface contacted plasmas cleaved the kallikrein-specific reagent S-2302 both after single surface contact, and after reincubation of surfaces in fresh plasma. The results show that C3b and Factor XIIa and their degradation products were retained at the surfaces.

  12. Immobilized transition metals stimulate contact activation and drive factor XII-mediated coagulation

    PubMed Central

    Mutch, N.J.; Waters, E.K.; Morrissey, J. H.

    2012-01-01

    Summary Background Upon contact with an appropriate surface, factor XII (FXII) undergoes autoactivation or cleavage by kallikrein. Zn2+ is known to facilitate binding of FXII and the cofactor, high molecular weight kininogen (HK), to anionic surfaces. Objectives To investigate whether transition metals immobilized on liposome surfaces can initiate coagulation via the contact pathway. Methods & Results Liposomes containing a metal ion-chelating lipid (DOGS-NTA) were prepared by membrane extrusion (20% DOGS-NTA, 40% phosphatidylcholine, 10% phosphatidylserine, and 30% phosphatidylethanolamine). Ni2+ immobilized on such liposomes accelerated clotting in normal, but not FXI- or FXII-deficient plasma. Results were comparable to a commercial aPTT reagent. Charging such liposomes with other transition metals revealed differences in their procoagulant capacity, with Ni2+> Cu2+> Co2+ and Zn2+. Plasma could be depleted of FXI, FXII and HK by adsorption with Ni2+-containing beads, resulting in delayed clot times. Consistent with this, FXI, FXII and HK bound to immobilized Ni2+ or Cu2+ with high affinity as determined by surface plasmon resonance. In the presence of Ni2+-bearing liposomes, Km and kcat values derived for autoactivation of FXII and prekallikrein, as well as for activation of FXII by kallikrein or prekallikrein by FXIIa, were similar to literature values in the presence of dextran sulfate. Conclusions Immobilized Ni2+ and Cu2+ bind FXII, FXI and HK with high affinity and stimulate activation of the contact pathway, driving FXII-mediated coagulation. Activation of the contact system by immobilized transition metals may have implications during pathogenic infection or in individuals exposed to high levels of pollution. PMID:22905925

  13. Influence of synoptic processes on fibrinolysis and fibrinogenolysis in healthy persons. [meteorological effects on blood coagulation

    NASA Technical Reports Server (NTRS)

    Marchenko, V. I.

    1974-01-01

    It is shown that on days with frontal activity in the atmosphere the levels of fibrinolysis and fibrinogenolysis are increased. The reactions of fibrinolysis and fibrinogenolysis to the passage of warm and cold fronts varies with the season of the year.

  14. CIRCULATING MICROPARTICLES, BLOOD CELLS, AND ENDOTHELIUM INDUCE PROCOAGULANT ACTIVITY IN SEPSIS THROUGH PHOSPHATIDYLSERINE EXPOSURE.

    PubMed

    Zhang, Yan; Meng, Huan; Ma, Ruishuang; He, Zhangxiu; Wu, Xiaoming; Cao, Muhua; Yao, Zhipeng; Zhao, Lu; Li, Tao; Deng, Ruijuan; Dong, Zengxiang; Tian, Ye; Bi, Yayan; Kou, Junjie; Thatte, Hemant S; Zhou, Jin; Shi, Jialan

    2016-03-01

    Sepsis is invariably accompanied by altered coagulation cascade; however, the precise role of phosphatidylserine (PS) in inflammation-associated coagulopathy in sepsis has not been well elucidated. We explored the possibility of exposed PS on microparticles (MPs), blood cells, as well as on endothelium, and defined its role in procoagulant activity (PCA) in sepsis. PS-positive MPs and cells were detected by flow cytometry, while PCA was assessed with clotting time, purified coagulation complex, and fibrin formation assays. Plasma levels of PS MPs derived from platelets, leukocytes (including neutrophils, monocytes, and lymphocytes), erythrocytes, and endothelial cells were elevated by 1.49-, 1.60-, 2.93-, and 1.53-fold, respectively, in septic patients. Meanwhile, PS exposure on blood cells was markedly higher in septic patients than in controls. Additionally, we found that the endothelial cells (ECs) treated with septic serum in vitro exposed more PS than with healthy serum. Isolated MPs/blood cells from septic patients and cultured ECs treated with septic serum in vitro demonstrated significantly shortened coagulation time, greatly enhanced intrinsic/extrinsic FXa generation, and increased thrombin formation. Importantly, confocal imaging of MPs or septic serum-treated ECs identified binding sites for FVa and FXa to form prothrombinase, and further supported fibrin formation in the area where PS exposure was abundant. Pretreatment with lactadherin blocked PS on MPs/blood cells/ECs, prolonged coagulation time by at least 25%, reduced FXa/thrombin generation, and inhibited fibrin formation by approximately 85%. Our findings suggest a key role for PS exposed on MPs, blood cells, and endothelium in augmenting coagulation in sepsis. Therefore, therapies targeting PS may be of particular importance.

  15. Is extracorporeal CO2-Removal really "safe" and "less" invasive? Observation of blood injury and coagulation impairment during ECCO2R.

    PubMed

    Kalbhenn, Johannes; Neuffer, Nadine; Zieger, Barbara; Schmutz, Axel

    2017-02-07

    Extracorporeal CO2-Removal (ECCO2R) is promoted with attributes like "safe" and "less invasive" compared to (high-flow) veno-venous ECMO-Systems. With our experience in coagulation disorders during ECMO-therapy with this observational study we for the first time prospectively evaluate hemolysis and coagulation disorders during ECCO2R. Eight consecutive patients with predominant hypercapnic respiratory failure were treated with the Hemolung® Respiratory Assist System (RAS) (Alung-Technologies, Pittsburg, USA). Bleeding as well as changes of coagulation parameters was prospectively assessed. Overall therapy was observed in seven patients with 52 treatment days. In 4 out of 7 patients (57%) relevant clinical bleeding symptoms occurred. Thrombocytopenia, hemolysis, factor XIII deficiency and acquired von Willebrand syndrome (loss of high molecular weight von Willebrand factor (VWF) multimers) were typical findings and spontaneously recovered after discontinuation of the extracorporeal system. In one patient extracorporeal system stopped because of thrombotic occlusion. 6 out of 7 patients required transfusion of red blood cells. Our observation shows that even low-flow extracorporeal lung support is associated with relevant clinical bleeding symptoms, blood-cell-injury, development of acquired von Willebrand syndrome and need for transfusion. In our opinion it therefore is too early to quote ECCO2R "safe" and "less invasive".

  16. Revisiting the mechanism of coagulation factor XIII activation and regulation from a structure/functional perspective

    PubMed Central

    Gupta, Sneha; Biswas, Arijit; Akhter, Mohammad Suhail; Krettler, Christoph; Reinhart, Christoph; Dodt, Johannes; Reuter, Andreas; Philippou, Helen; Ivaskevicius, Vytautas; Oldenburg, Johannes

    2016-01-01

    The activation and regulation of coagulation Factor XIII (FXIII) protein has been the subject of active research for the past three decades. Although discrete evidence exists on various aspects of FXIII activation and regulation a combinatorial structure/functional view in this regard is lacking. In this study, we present results of a structure/function study of the functional chain of events for FXIII. Our study shows how subtle chronological submolecular changes within calcium binding sites can bring about the detailed transformation of the zymogenic FXIII to its activated form especially in the context of FXIIIA and FXIIIB subunit interactions. We demonstrate what aspects of FXIII are important for the stabilization (first calcium binding site) of its zymogenic form and the possible modes of deactivation (thrombin mediated secondary cleavage) of the activated form. Our study for the first time provides a structural outlook of the FXIIIA2B2 heterotetramer assembly, its association and dissociation. The FXIIIB subunits regulatory role in the overall process has also been elaborated upon. In summary, this study provides detailed structural insight into the mechanisms of FXIII activation and regulation that can be used as a template for the development of future highly specific therapeutic inhibitors targeting FXIII in pathological conditions like thrombosis. PMID:27453290

  17. Antibodies against oxidized phospholipids in laboratory tests exploring lupus anti-coagulant activity

    PubMed Central

    Rolla, R; Vidali, M; Serino, R; Pergolini, P; Albano, E; Bellomo, G

    2007-01-01

    Lupus anti-coagulants (LA) are a variety of anti-phospholipid antibodies characterized by their capacity to interfere with phospholipid-dependent coagulation assays. LA are increasingly recognized as important predictors of thrombosis. However, the antigen specificity of LA is still poorly characterized. Growing evidence indicates that oxidized phospholipids are among the targets of anti-phospholipid antibodies. This prompted us to investigate the role of IgG directed against different oxidized phospholipids in 164 subjects without clotting factor defects that were tested for the presence of LA using a LA-sensitive activate partial thromboplastin time (aPTT-FSL) and a screening/confirmation assay based on diluted Russell's viper venom test (dRVVT-PL). The response to aPTT-FSL was significantly (P < 0·0005) associated with high titres of IgG against oxidized phosphatidylserine, phosphatidylethanolamine and phosphatidylinositol, whereas positivity to dRVVT-PL was associated with the elevation of IgG against oxidized phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine (P < 0·0005) and phosphatidylinositol (P < 0·01). No difference in reactivity against oxidized cardiolipin was evident between the different groups. Positivity to the dRVVT-PL test was also associated significantly (P < 0·005) with the elevation of anti-cardiolipin and anti-β2-glycoprotein-1 IgG. However, stepwise logistic regression demonstrated that IgG recognizing oxidized phosphatidylethanolamine and oxidized phosphatidylcholine were the only independent predictors of the response to dRVVT-PL assay, while IgG recognizing oxidized phosphatidylethanolamine and oxidized phosphatidylinositol were independent predictors of the response to aPTT-FSL test. In conclusion, autoantibodies against defined oxidized phospholipids are independent predictors of LA detection by aPTT-FSL or dRVVT-PL assays and might contribute to the variability often observed in the responses to the functional

  18. Sensitivity of three activated partial thromboplastin time reagents to coagulation factor deficiencies.

    PubMed

    Turi, D C; Peerschke, E I

    1986-01-01

    Three activated partial thromboplastin time (APTT) reagent test systems, General Diagnostics Automated APTT, American Dade Actin FS, and Pacific Hemostasis (Thromboscreen KAPTT) reagent, containing different activators for the APTT assay, were evaluated for their precision and sensitivity to factor deficiencies in the intrinsic coagulation system. The data suggest that micronized silica and ellagic acid reagent systems were similar in sensitivity to Factor VIII, X, and XII deficiencies, whereas, the micronized kaolin reagent was significantly less sensitive to these deficiencies. Factor XI deficiency was detected equally well with the use of all three reagent systems. The ellagic acid reagent was somewhat more sensitive to Factor IX deficiency than the micronized silica reagent, and the micronized kaolin reagent was again least sensitive. Both the micronized silica and ellagic acid based reagents were insensitive to all but severe deficiencies in prekallikrein, whereas the micronized kaolin reagent was unable to detect this deficiency. All three reagents were insensitive to all but severe deficiencies in high-molecular-weight kininogen. The authors conclude that the reagent systems tested, containing micronized silica or ellagic acid as activators, are similar in sensitivity when used in a routine activated partial thromboplastin time to screen for factor deficiencies, whereas the reagent system containing micronized kaolin as an activator is less sensitive.

  19. Dynamics of change of lipid and monoamine metabolisms and the blood coagulation system during experimental atherosclerosis caused by restriction of movement

    NASA Technical Reports Server (NTRS)

    Gvishiani, G. S.; Kobakhidze, N. G.

    1980-01-01

    Shifts in lipid, catecholamine, and blood coagulation systems following various periods (1, 2, 3, and 4 months) of experimentally induced atherosclerosis were studied. The same indices were studied in the tissues of the myocardium, liver, and brain stem-reticular formation after decapitation of the animals at the end of the experiment. Periodic motion restriction caused an increase in blood beta-lipoproteins in the rabbits at the beginning of the experiment. An increase in general cholesterol content and a decrease in the lecithincholesterol index were established at the end of the experiment. Myocardial beta-lipoprotein and brain stem reticular formation general cholesterol contents were elevated; catecholamine content was increased at the end of the experiment. In the initial months, free adrenaline basically increased, while in later months blood adrenaline decreased and blood noradrenaline increased.

  20. [Separation of coagulation factor VIII with high activity using gigaporous anion exchange chromatography].

    PubMed

    Kang, Limei; Zhang, Yan; Luo, Jian; Li, You; Zhou, Yuefang; Yu, Rong; Su, Zhiguo

    2012-06-01

    A purification process to obtain coagulation factor VIII (F VIII) with high activity from human plasma was established. Based on the analysis of the size ratio between F VIII and matrix porous medium and its effect on the protein activity, a novel purification process designed was superporous ion exchange chromatography (IEC). The operating conditions of gigaporous and traditional anion exchange chromatography were optimized separately. The chromogenic substrate, gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) were used to monitor the bioactivity and purity of the chromatographic products. The results showed that the superporous medium could not only protect structure of macro-protein but also enhance its mass transfer, finally giving FVIII product with high activity. The yield of F VIII in superporous chromatography was about five times of commercially agarose chromatography and the specific activity was up to 154 IU/mg protein. Furthermore, we studied the regeneration process of the superporous medium, washing the column with 5 column volumes of 1 mol/L NaOH at a low flow rate, to ensure the chromatographic stability. This purification process is simple, reproducible and suitable for large-scale production.

  1. Combining Coagulation/MIEX with Biological Activated Carbon Treatment to Control Organic Fouling in the Microfiltration of Secondary Effluent

    PubMed Central

    Pramanik, Biplob Kumar; Roddick, Felicity A.; Fan, Linhua

    2016-01-01

    Coagulation, magnetic ion exchange resin (MIEX) and biological activated carbon (BAC) were examined at lab scale as standalone, and sequential pre-treatments for controlling the organic fouling of a microfiltration membrane by biologically treated secondary effluent (BTSE) using a multi-cycle approach. MIEX gave slightly greater enhancement in flux than coagulation due to greater removal of high molecular weight (MW) humic substances, although it was unable to remove high MW biopolymers. BAC treatment was considerably more effective for improving the flux than coagulation or MIEX. This was due to the biodegradation of biopolymers and/or their adsorption by the biofilm, and adsorption of humic substances by the activated carbon, as indicated by size exclusion chromatography. Coagulation or MIEX followed by BAC treatment further reduced the problematic foulants and significantly improved the flux performance. The unified membrane fouling index showed that the reduction of membrane fouling by standalone BAC treatment was 42%. This improved to 65%, 70%, and 93% for alum, ferric chloride and MIEX pre-treatment, respectively, when followed by BAC treatment. This study showed the potential of sequential MIEX and BAC pre-treatment for controlling organic fouling and thus enhancing the performance of microfiltration in the reclamation of BTSE. PMID:27483327

  2. Combining Coagulation/MIEX with Biological Activated Carbon Treatment to Control Organic Fouling in the Microfiltration of Secondary Effluent.

    PubMed

    Pramanik, Biplob Kumar; Roddick, Felicity A; Fan, Linhua

    2016-07-30

    Coagulation, magnetic ion exchange resin (MIEX) and biological activated carbon (BAC) were examined at lab scale as standalone, and sequential pre-treatments for controlling the organic fouling of a microfiltration membrane by biologically treated secondary effluent (BTSE) using a multi-cycle approach. MIEX gave slightly greater enhancement in flux than coagulation due to greater removal of high molecular weight (MW) humic substances, although it was unable to remove high MW biopolymers. BAC treatment was considerably more effective for improving the flux than coagulation or MIEX. This was due to the biodegradation of biopolymers and/or their adsorption by the biofilm, and adsorption of humic substances by the activated carbon, as indicated by size exclusion chromatography. Coagulation or MIEX followed by BAC treatment further reduced the problematic foulants and significantly improved the flux performance. The unified membrane fouling index showed that the reduction of membrane fouling by standalone BAC treatment was 42%. This improved to 65%, 70%, and 93% for alum, ferric chloride and MIEX pre-treatment, respectively, when followed by BAC treatment. This study showed the potential of sequential MIEX and BAC pre-treatment for controlling organic fouling and thus enhancing the performance of microfiltration in the reclamation of BTSE.

  3. Silver nanoparticles influence on the blood activation process and their release to blood plasma from synthetic polymer scaffold

    NASA Astrophysics Data System (ADS)

    Major, R.; Lackner, J. M.; Sanak, M.; Major, B.

    2016-03-01

    In the present work, blood and blood plasma interaction to silver stabilised polyelectrolytes was investigated in vitro. The designed materials are dedicated for regeneration of the cardiovascular system. Silver nanoparticles were introduced into the polyelectrolyte structure in order to reduce the risk of bacterial biofilm formation. The introduction of Ag nanoparticles occurred by deposition at high vacuum by magnetron sputtering. The analysis of blood-materials interactions were performed by using commercially available tester, Impact-R (Diamed). The assessment of silver ion nanoparticles release into the plasma consisted in determining the Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT). Unmodified surface of polyelectrolytes is a strong activator for blood elements. The introduction of silver nanoparticles resulted in a significant reduction in the probability of clotting. The extrinsic pathway of coagulation determined on the basis of the PT and the intrinsic and common pathways of coagulation measured by the APTT did not indicate the danger out of range. Microstructure was studied using TEM on thin foils prepared from the cross-section of samples subjected to biomedical treatments. The observations revealed hetero- interface between two different crystalline solids.

  4. Influences of ABO blood group, age and gender on plasma coagulation factor VIII, fibrinogen, von Willebrand factor and ADAMTS13 levels in a Chinese population

    PubMed Central

    Wang, Zongkui; Dou, Miaomiao; Du, Xi; Ma, Li; Sun, Pan; Cao, Haijun; Ye, Shengliang; Jiang, Peng; Liu, Fengjuan; Lin, Fangzhao

    2017-01-01

    Background ABO blood group is a hereditary factor of plasma levels of coagulation factor VIII (FVIII) and von Willebrand factor (VWF). Age and gender have been shown to influence FVIII, VWF, fibrinogen (Fbg), and ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 motif, 13). We investigated the effects of ABO type, age, and gender on plasma levels of FVIII, Fbg, VWF, and ADAMTS13 in a Chinese population. Methods A total of 290 healthy volunteers were eligible for this study. ABO blood group was determined by indirect technique. FVIII:C and Fbg were measured by clotting assays. VWF antigen (VWF:Ag), collagen-binding activity (VWF:CBA), and ADAMTS13 antigen were assessed by ELISA, whereas VWF ristocetin cofactor activity (VWF:Rcof) was performed by agglutination of platelets with ristocetin. Results Mean FVIII:C and VWF levels (VWF:Ag, VWF:CBA, and VWF:Rcof) were significantly higher in non-O than in O type subjects (p < 0.05 for all comparison). ADAMTS13 antigen decreased with increasing age, whereas the other parameters increased. Other than ADAMTS13 (p < 0.01), no gender-related variations were observed in the other parameters. Moreover, FVIII:C, Fbg, VWF:Ag, VWF:CBA, and VWF:Rcof showed significant and positive relationships with age (r = 0.421, 0.445, 0.410, 0.401, and 0.589, resp.; all p < 0.001), whereas a negative relationship was observed for ADAMTS13 antigen (r = 0.306; p = 0.006). Furthermore, FVIII:C were strongly correlated with VWF:Ag, VWF:CBA, and VWF:Rcof (r = 0.746, r = 0.746, and r = 0.576, resp.; p < 0.0001). VWF parameters were also strongly correlated with each other (r = 0.0.847 for VWF:Ag and VWF:CBA; r = 0.722 for VWF:Ag and VWF:Rcof; p < 0.0001). Conclusions ABO blood group, age, and gender showed different effects on plasma levels of FVIII:C, Fbg, VWF:Ag, VWF:CBA, VWF:Rcof, and ADAMTS13 antigen. These new data on a Chinese population are quite helpful to compare with other ethnic groups. PMID

  5. The Role of Putative Phosphatidylserine-Interactive Residues of Tissue Factor on Its Coagulant Activity at the Cell Surface

    PubMed Central

    Ansari, Shabbir A.; Pendurthi, Usha R.; Sen, Prosenjit; Rao, L. Vijaya Mohan

    2016-01-01

    Exposure of phosphatidylserine (PS) on the outer leaflet of the cell membrane is thought to play a critical role in tissue factor (TF) decryption. Recent molecular dynamics simulation studies suggested that the TF ectodomain may directly interact with PS. To investigate the potential role of TF direct interaction with the cell surface phospholipids on basal TF activity and the enhanced TF activity following the decryption, one or all of the putative PS-interactive residues in the TF ectodomain were mutated and tested for their coagulant activity in cell systems. Out of the 9 selected TF mutants, five of them -TFS160A, TFS161A, TFS162A, TFK165A, and TFD180A- exhibited a similar TF coagulant activity to that of the wild-type TF. The specific activity of three mutants, TFK159A, TFS163A, and TFK166A, was reduced substantially. Mutation of the glycine residue at the position 164 markedly abrogated the TF coagulant activity, resulting in ~90% inhibition. Mutation of all nine lipid binding residues together did not further decrease the activity of TF compared to TFG164A. A similar fold increase in TF activity was observed in wild-type TF and all TF mutants following the treatment of THP-1 cells with either calcium ionomycin or HgCl2, two agents that are commonly used to decrypt TF. Overall, our data show that a few select TF residues that are implicated in interacting with PS contribute to the TF coagulant activity at the cell surface. However, our data also indicate that TF regions outside of the putative lipid binding region may also contribute to PS-dependent decryption of TF. PMID:27348126

  6. [Coagulation disorders in cirrhosis].

    PubMed

    Téllez-Avila, Felix I; Chávez-Tapia, Norberto C; Torre-Delgadillo, Aldo

    2007-01-01

    The liver plays a central role in the clotting process. In this organ are sintetizated the major part of the coagulation factors. Historically, was considered that alteration in liver function causes important bleeding disorders. However, actual evidence is not in agreement with this asseveration. Decreased synthesis of clotting and inhibitor factors, decrease clearance of activated factors, quantitative and qualitative platelet defects, hyperfibrinolysis and intravascular coagulation are some of the defects observed in liver diseases. Thrombotic events, even if rare in cirrhotic patients, occur manly in the portal and mesenteric veins. The aim of the present work is to review the present evidence in coagulation disorders and liver disease.

  7. Lower-Extremity Functional Electrical Stimulation Decreases Platelet Aggregation and Blood Coagulation in Persons With Chronic Spinal Cord Injury: A Pilot Study

    PubMed Central

    Kahn, Nighat N; Feldman, Susan P; Bauman, William A

    2010-01-01

    Background: Individuals with spinal cord injury (SCI) develop premature cardiovascular disease. Regular exercise reduces the incidence and symptoms of cardiovascular disease in able-bodied individuals; these salutary effects of exercise have not been documented in persons with SCI. Objective: To evaluate the effects of functional electrical stimulation leg cycle ergometry (FES-LCE) exercise training on platelet aggregation and blood coagulation in persons with SCI. Participants: Subjects (n  =  14) with stable chronic (>1 year) paraplegia (T1–T10) or tetraplegia (C4–C8). Methods: Blood samples were collected before and after the first and eighth sessions (2 sessions per week for 4 weeks) of FES exercise. Results: Platelet aggregation was inhibited by 20% after the first session and by 40% (P < 0.001) after the eighth session. Thrombin activity was unchanged after the first session (10.7 ± 0.85 s to 10.43 ± 0.56 s) and decreased after the eighth session (12.5 ± 1.98 s to 11.1 ± 1.7 s; P < 0.0003). Antithrombin III activity increased after the first (103.8% ± 8.9% to 110% ± 6.9%; P < 0.0008) and eighth sessions (107.8% ± 12.1% to 120.4% ± 13.1%; P < 0.0001). Cyclic adenosine monophosphate increased after the first (9.9% ± 2.5% to 15.8% ± 3%; P < 0.001) and eighth sessions (17.8% ± 4.2% to 36.5% ± 7.6%; P < 0.0001). After the eighth session, factors V and X increased significantly (88% ± 27% to 103% ± 23%, P < 0.0001; 100% ± 40% to 105% ± 7%, P < 0.01, respectively); factors VII and VIII and fibrinogen did not change significantly. A significant reduction in platelet activation/aggregation was demonstrated in response to FES-LCE. The decrease in thrombin level was caused by the simultaneous increase in antithrombin activity. Conclusion: These findings provide new insight into the potential protective effects of FES-LCE against the risk of cardiovascular disease. PMID:20486534

  8. Coagulation and sepsis.

    PubMed

    Levi, Marcel; van der Poll, Tom

    2017-01-01

    Severe sepsis is almost invariably associated with systemic activation of coagulation. There is ample evidence that demonstrates a wide-ranging cross-talk between hemostasis and inflammation, which is probably implicated in the pathogenesis of organ dysfunction in patients with sepsis. Inflammation not only leads to initiation and propagation of coagulation activity, but coagulation also markedly influences inflammation. Molecular mechanisms that play a role in inflammation-induced effects on coagulation have been recognized in much detail. Pro-inflammatory cells and cyto- and chemokines can activate the coagulation system and downregulate crucial physiological anticoagulant mechanisms. Initiation of coagulation activation and consequent thrombin generation is caused by expression of tissue factor on activated monocytes and endothelial cells and is ineffectually offset by tissue factor pathway inhibitor. At the same time, endothelial-associated anticoagulant pathways, in particular the protein C system, is impaired by pro-inflammatory cytokines. Also, fibrin removal is severely obstructed by inactivation of the endogenous fibrinolytic system, mainly as a result of upregulation of its principal inhibitor, plasminogen activator inhibitor type 1 (PAI-1). Increased fibrin generation and impaired break down lead to deposition of (micro)vascular clots, which may contribute to tissue ischemia and ensuing organ dysfunction. The foundation of the management of coagulation in sepsis is the explicit and thorough treatment of the underlying disorder by antibiotic treatment and source control measures. Adjunctive strategies focused at the impairment of coagulation, including anticoagulants and restoration of physiological anticoagulant mechanisms, may supposedly be indicated and have been found advantageous in experimental and initial clinical trials.

  9. Gas exchange and the coagulation system of the blood during the effect on the body of high concentrations of oxygen and carbon dioxide

    NASA Technical Reports Server (NTRS)

    Palosh, L.; Agadzhanyan, N. A.; Davydov, G. A.; Rybakov, B. K.; Sergiyenko, A. S.

    1974-01-01

    Maximum permissible concentrations of oxygen and carbon dioxide in a controlled atmosphere were determined by evaluating their effects on human gas exchange, blood coagulation, and tolerances to acute hypoxia, acceleration, and physical loads. It was found that functional disturbances depend on the concentration of respiratory gases and the length of stay in an altered atmosphere. By changing the atmospheric composition and by bringing the gaseous environment into accordance with the work and rest regimen and energy expenditures, the general reactivity of the body changes favorably.

  10. Markers of coagulation activation and acute kidney injury in patients after hematopoietic cell transplantation

    PubMed Central

    Hingorani, Sangeeta R; Seidel, Kristy; Pao, Emily; Lawler, Rick; McDonald, George B.

    2015-01-01

    Acute kidney injury (AKI) is common after hematopoietic cell transplant (HCT). The etiology of AKI is unknown because biopsies are rarely performed. The pathophysiology of injury is inferred from clinical data. Thrombotic microangiopathy (TMA) is often invoked as the cause of renal injury. Patients > 2 years undergoing their first HCT at Fred Hutchinson Cancer Research Center (FHCRC) participated in this study. We prospectively measured plasma markers of coagulation activation, (PAI-1 and tPA) and fibrinolyis (D-dimer) weekly in 149 patients during the first 100 days post-transplant. Cox proportional hazards modeling was used to determine associations between these markers and AKI (doubling of baseline serum creatinine). Kruskal-Wallis test was used to determine associations between day 100 urinary albumin to creatinine ratios (ACR) and these markers. Thirty one percent of patients developed AKI. Though elevations in these markers occurred frequently, neither PAI-1 nor tPA were associated with development of AKI. D-dimer was associated with a slightly increased risk of AKI (RR=1.76; p-value 0.04). None of these markers were associated with micro- or macroalbuminuria at day 100. The lack of an association with AKI suggests that endothelial injury in the form of TMA is not a common cause of AKI early after transplant. PMID:25665045

  11. A sequence variation scan of the coagulation factor VIII (FVIII) structural gene and associations with plasma FVIII activity levels.

    PubMed

    Viel, Kevin R; Machiah, Deepa K; Warren, Diane M; Khachidze, Manana; Buil, Alfonso; Fernstrom, Karl; Souto, Juan C; Peralta, Juan M; Smith, Todd; Blangero, John; Porter, Sandra; Warren, Stephen T; Fontcuberta, Jordi; Soria, Jose M; Flanders, W Dana; Almasy, Laura; Howard, Tom E

    2007-05-01

    Plasma factor VIII coagulant activity (FVIII:C) level is a highly heritable quantitative trait that is strongly correlated with thrombosis risk. Polymorphisms within only 1 gene, the ABO blood-group locus, have been unequivocally demonstrated to contribute to the broad population variability observed for this trait. Because less than 2.5% of the structural FVIII gene (F8) has been examined previously, we resequenced all known functional regions in 222 potentially distinct alleles from 137 unrelated nonhemophilic individuals representing 7 racial groups. Eighteen of the 47 variants identified, including 17 single-nucleotide polymorphisms (SNPs), were previously unknown. As the degree of linkage disequilibrium across F8 was weak overall, we used measured-genotype association analysis to evaluate the influence of each polymorphism on the FVIII:C levels in 398 subjects from 21 pedigrees known as the Genetic Analysis of Idiopathic Thrombophilia project (GAIT). Our results suggested that 92714C>G, a nonsynonymous SNP encoding the B-domain substitution D1241E, was significantly associated with FVIII:C level. After accounting for important covariates, including age and ABO genotype, the association persisted with each C-allele additively increasing the FVIII:C level by 14.3 IU dL(-1) (P = .016). Nevertheless, because the alleles of 56010G>A, a SNP within the 3' splice junction of intron 7, are strongly associated with 92714C>G in GAIT, additional studies are required to determine whether D1241E is itself a functional variant.

  12. A sequence variation scan of the coagulation factor VIII (FVIII) structural gene and associations with plasma FVIII activity levels

    PubMed Central

    Viel, Kevin R.; Machiah, Deepa K.; Warren, Diane M.; Khachidze, Manana; Buil, Alfonso; Fernstrom, Karl; Souto, Juan C.; Peralta, Juan M.; Smith, Todd; Blangero, John; Porter, Sandra; Warren, Stephen T.; Fontcuberta, Jordi; Soria, Jose M.; Dana Flanders, W.; Almasy, Laura

    2007-01-01

    Plasma factor VIII coagulant activity (FVIII:C) level is a highly heritable quantitative trait that is strongly correlated with thrombosis risk. Polymorphisms within only 1 gene, the ABO blood-group locus, have been unequivocally demonstrated to contribute to the broad population variability observed for this trait. Because less than 2.5% of the structural FVIII gene (F8) has been examined previously, we resequenced all known functional regions in 222 potentially distinct alleles from 137 unrelated nonhemophilic individuals representing 7 racial groups. Eighteen of the 47 variants identified, including 17 single-nucleotide polymorphisms (SNPs), were previously unknown. As the degree of linkage disequilibrium across F8 was weak overall, we used measured-genotype association analysis to evaluate the influence of each polymorphism on the FVIII:C levels in 398 subjects from 21 pedigrees known as the Genetic Analysis of Idiopathic Thrombophilia project (GAIT). Our results suggested that 92714C>G, a nonsynonymous SNP encoding the B-domain substitution D1241E, was significantly associated with FVIII:C level. After accounting for important covariates, including age and ABO genotype, the association persisted with each C-allele additively increasing the FVIII:C level by 14.3 IU dL−1 (P = .016). Nevertheless, because the alleles of 56010G>A, a SNP within the 3′ splice junction of intron 7, are strongly associated with 92714C>G in GAIT, additional studies are required to determine whether D1241E is itself a functional variant. PMID:17209060

  13. High Pressure Homogenization of Porcine Pepsin Protease: Effects on Enzyme Activity, Stability, Milk Coagulation Profile and Gel Development

    PubMed Central

    Leite Júnior, Bruno Ricardo de Castro; Tribst, Alline Artigiani Lima; Cristianini, Marcelo

    2015-01-01

    This study investigated the effect of high pressure homogenization (HPH) (up to 190 MPa) on porcine pepsin (proteolytic and milk-clotting activities), and the consequences of using the processed enzyme in milk coagulation and gel formation (rheological profile, proteolysis, syneresis, and microstructure). Although the proteolytic activity (PA) was not altered immediately after the HPH process, it reduced during enzyme storage, with a 5% decrease after 60 days of storage for samples obtained with the enzyme processed at 50, 100 and 150 MPa. HPH increased the milk-clotting activity (MCA) of the enzyme processed at 150 MPa, being 15% higher than the MCA of non-processed samples after 60 days of storage. The enzyme processed at 150 MPa produced faster aggregation and a more consistent milk gel (G’ value 92% higher after 90 minutes) when compared with the non-processed enzyme. In addition, the gels produced with the enzyme processed at 150 MPa showed greater syneresis after 40 minutes of coagulation (forming a more compact protein network) and lower porosity (evidenced by confocal microscopy). These effects on the milk gel can be associated with the increment in MCA and reduction in PA caused by the effects of HPH on pepsin during storage. According to the results, HPH stands out as a process capable of changing the proteolytic characteristics of porcine pepsin, with improvements on the milk coagulation step and gel characteristics. Therefore, the porcine pepsin submitted to HPH process can be a suitable alternative for the production of cheese. PMID:25938823

  14. High Pressure Homogenization of Porcine Pepsin Protease: Effects on Enzyme Activity, Stability, Milk Coagulation Profile and Gel Development.

    PubMed

    Leite Júnior, Bruno Ricardo de Castro; Tribst, Alline Artigiani Lima; Cristianini, Marcelo

    2015-01-01

    This study investigated the effect of high pressure homogenization (HPH) (up to 190 MPa) on porcine pepsin (proteolytic and milk-clotting activities), and the consequences of using the processed enzyme in milk coagulation and gel formation (rheological profile, proteolysis, syneresis, and microstructure). Although the proteolytic activity (PA) was not altered immediately after the HPH process, it reduced during enzyme storage, with a 5% decrease after 60 days of storage for samples obtained with the enzyme processed at 50, 100 and 150 MPa. HPH increased the milk-clotting activity (MCA) of the enzyme processed at 150 MPa, being 15% higher than the MCA of non-processed samples after 60 days of storage. The enzyme processed at 150 MPa produced faster aggregation and a more consistent milk gel (G' value 92% higher after 90 minutes) when compared with the non-processed enzyme. In addition, the gels produced with the enzyme processed at 150 MPa showed greater syneresis after 40 minutes of coagulation (forming a more compact protein network) and lower porosity (evidenced by confocal microscopy). These effects on the milk gel can be associated with the increment in MCA and reduction in PA caused by the effects of HPH on pepsin during storage. According to the results, HPH stands out as a process capable of changing the proteolytic characteristics of porcine pepsin, with improvements on the milk coagulation step and gel characteristics. Therefore, the porcine pepsin submitted to HPH process can be a suitable alternative for the production of cheese.

  15. Evaluation of Resuscitation Fluids on Endothelial Glycocalyx, Venular Blood Flow, and Coagulation Function After Hemorrhagic Shock in Rats

    DTIC Science & Technology

    2013-10-01

    thrombin inhibition, leading to coagulopathy. Using intravital microscopy, we have obtained direct in vivo data showing glycocalyx thickness reduction...collected in 3.2% citrate for coagulation assays (ROTEM, TEM Innovations GmbH, Munich, Germany). Intravital Microscopy The system described in detail...microscopic fields containing venules were randomly selected. The first dye (TR-Dx70) was injected 5 min before baseline. Image sequences of

  16. Monitoring the effects of fibrinogen concentration on blood coagulation using quartz crystal microbalance (QCM) and its comparison with thromboelastography

    NASA Astrophysics Data System (ADS)

    Lakshmanan, Ramji S.; Efremov, Vitaly; Cullen, Sinéad; Byrne, Barry; Killard, Anthony J.

    2013-05-01

    Fibrinogen has been identified as a major risk factor in cardiovascular disorders. Fibrinogen (340 kDa) is a soluble dimeric glycoprotein found in plasma and is a major component of the coagulation cascade. It has been identified as a major risk factor in cardiovascular disorders. The time taken for its conversion to fibrin is usually used as an "endpoint" in most clot-based assays, without any information on dynamic changes in physical properties or kinetics of a forming clot. A global coagulation profile as measured by Thromboelastography® (TEG®) provides information on both the time and kinetics of changes in physical property of the forming clot. In this work, Quartz crystal microbalance (QCM), which is a piezoelectric resonator has been used to study coagulation of plasma and compared with TEG. The changes in resonant frequency (Δf) and half width at half maximum (HWHM or ΔΓ) were used to evaluate effect of fibrinogen concentration. It has been shown that TEG is less sensitive to low concentrations of fibrinogen and dilution while QCM is able to monitor clot formation in both the circumstances.

  17. Inhibition of the activation of Hageman factor (factor XII) by peripheral blood cells.

    PubMed Central

    Ratnoff, O D; Emanuelson, M M; Ziats, N P

    1987-01-01

    Suspensions of peripheral blood mononuclear cells (PBMC), monocytes, T or B lymphocytes, platelets or granulocytes, and cell-depleted supernatant fluids of these suspensions inhibited activation of Hageman factor (HF, Factor XII) by ellagic acid, a property not shared by erythrocytes. PBMC also inhibited HF activation by glass or sulfatides. Contaminating platelets may have contributed to inhibition by PBMC. Elaboration of agents inhibiting HF activation required metabolically active cells. The inhibitor(s) in PBMC supernates were not identified with known agents, but had properties of a nonenzymatic protein. PBMC supernates did not contain fibrinogen, nor alter the thrombin, prothrombin, or partial thromboplastin times of normal plasma, amidolysis by activated plasma thromboplastin antecedent (Factor XIa) or activated Stuart factor (Factor Xa) or esterolysis by C1 (C1 esterase); they inhibited plasmin minimally. These experiments suggest that peripheral blood cells may impede intravascular coagulation. Whether this property helps maintain the fluidity of blood is unclear. PMID:3498741

  18. Rate of mixing controls rate and outcome of autocatalytic processes: theory and microfluidic experiments with chemical reactions and blood coagulation.

    PubMed

    Pompano, Rebecca R; Li, Hung-Wing; Ismagilov, Rustem F

    2008-08-01

    This article demonstrates that the rate of mixing can regulate the rate and outcome of both biological and nonbiological autocatalytic reaction systems that display a threshold response to the concentration of an activator. Plug-based microfluidics was used to control the timing of reactions, the rate of mixing, and surface chemistry in blood clotting and its chemical model. Initiation of clotting of human blood plasma required addition of a critical concentration of thrombin. Clotting could be prevented by rapid mixing when thrombin was added near the critical concentration, and mixing also affected the rate of clotting when thrombin was added at concentrations far above the critical concentration in two clinical clotting assays for human plasma. This phenomenon was modeled by a simple mechanism--local and global competition between the clotting reaction, which autocatalytically produces an activator, and mixing, which removes the activator. Numerical simulations showed that the Damköhler number, which describes this competition, predicts the effects of mixing. Many biological systems are controlled by thresholds, and these results shed light on the dynamics of these systems in the presence of spatial heterogeneities and provide simple guidelines for designing and interpreting experiments with such systems.

  19. Milestones and perspectives in coagulation and hemostasis.

    PubMed

    Lippi, Giuseppe; Favaloro, Emmanuel J; Franchini, Massimo; Guidi, Gian Cesare

    2009-02-01

    Hemostasis is traditionally defined as the physiologic process whereby bleeding is antagonized and possibly stopped to minimize blood loss. The first medical description of the clinical and inherited features of hemostasis can be dated back more than 1000 years, when Abu al-Qasim Khalaf ibn 'Abbas al-Andalusi al-Zahrawi' medical treatise provided some initial insights into this puzzling process. Since then, continuous and revolutionary scientific developments have contributed to decoding several aspects of this intricate but essential physiologic phenomenon, providing a reliable model to explain the leading mechanisms involved. Although the point at which bleeding stops is commonly referred to as "coagulation," blood coagulation is actually only one part of a two-part hemostatic process that develops through sequential steps referred to as primary and secondary hemostasis. Throughout its activation and development, the coagulation cascade is strictly regulated by a series of natural inhibitors, which prevent unnecessary and excessive clotting. The aim of this article is to provide a concise overview of the major discoveries and past and current perspectives in coagulation and hemostasis.

  20. [Acquired coagulant factor inhibitors].

    PubMed

    Nogami, Keiji

    2015-02-01

    Acquired coagulation factor inhibitors are an autoimmune disease causing bleeding symptoms due to decreases in the corresponding factor (s) which result from the appearance of autoantibodies against coagulation factors (inhibitor). This disease is quite different from congenital coagulation factor deficiencies based on genetic abnormalities. In recent years, cases with this disease have been increasing, and most have anti-factor VIII autoantibodies. The breakdown of the immune control mechanism is speculated to cause this disease since it is common in the elderly, but the pathology and pathogenesis are presently unclear. We herein describe the pathology and pathogenesis of factor VIII and factor V inhibitors. Characterization of these inhibitors leads to further analysis of the coagulation process and the activation mechanisms of clotting factors. In the future, with the development of new clotting examination method (s), we anticipate that further novel findings will be obtained in this field through inhibitor analysis. In addition, detailed elucidation of the coagulation inhibitory mechanism possibly leading to hemostatic treatment strategies for acquired coagulation factor disorders will be developed.

  1. Platelet adhesion, contact phase coagulation activation, and C5a generation of polyethylene glycol acid-grafted high flux cellulosic membrane with varieties of grafting amounts.

    PubMed

    Fushimi, F; Nakayama, M; Nishimura, K; Hiyoshi, T

    1998-10-01

    Grafting of polyethylene glycol chains onto cellulosic membrane can be expected to reduce the interaction between blood (plasma protein and cells) and the membrane surface. Alkylether carboxylic acid (PEG acid) grafted high flux cellulosic membranes for hemodialysis, in which the polyethylene glycol chain bears an alkyl group at one side and a carboxyl group at the other side, have been developed and evaluated. PEG acid-grafted high flux cellulosic membranes with various grafting amounts have been compared with respect to platelet adhesion, the contact phase of blood coagulation, and complement activation in vitro. A new method of quantitating platelet adhesion on hollow-fiber membrane surfaces has been developed, which is based on the determination of lactate dehydrogenase (LDH) activity after lysis of the adhered platelets. PEG acid-grafted high flux cellulosic membranes showed reduced platelet adhesion and complement activation effects in grafting amounts of 200 ppm or higher without detecting adverse effects up to grafting amounts of 850 ppm. The platelet adhesion of a PEG acid-grafted cellulosic membrane depends on both the flux and grafting amounts of the membrane. It is concluded that the grafting of PEG acid onto a cellulosic membrane improves its biocompatibility as evaluated in terms of platelet adhesion, complement activation, and thrombogenicity.

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

    PubMed Central

    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

    Introduction 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. Methods and Results 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. Conclusions 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. PMID:27764259

  3. [Ratio of erythrocyte and plasma in massive blood transfusion].

    PubMed

    Wen, Xian-Hui; Liu, Feng-Xia; Zhang, Jun-Hua; Gui, Rong

    2014-06-01

    This study was purposed to explore the suitable ratio between fresh frozen plasma and erythrocyte by retrospective analysis of coagulation in patients with massive blood transfusion. The clinical data of 151 cases with massive blood transfusion from January 2011 to January 2013 were analyzed retrospectively. According to coagulation, patients were divided into coagulation normal group (138 cases) and coagulation dysfunction group (13 cases). Based on the ratio of 1:1 of fresh frozen plasma and erythrocyte, the patients were divided into high plasma group(2:1), medium plasma group (1:1) and low plasma (<1:1) subgroups. Coagulation was detected before and after 24 h of massive blood transfusion. The results showed that prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) were prolonged, fibrinogen (FIB) level decreased significantly (all P < 0.05) in the low plasma subgroup of coagulation normal group after massive blood transfusion 24 h; the high plasma and the medium plasma group of coagulation normal group had no significant changes in coagulation (P > 0.05); prothrombin time, activated partial thromboplastin time, thrombin time and fibrinogen level in the medium plasma and low plasma subgroup of coagulation dysfunction group after massive transfusion was still in abnormal levels (P > 0.05), coagulation function in high plasma subgroup was improved significantly (P < 0.05). It is concluded that the ratio of plasma to erythrocyte should be adjusted according to the patient's coagulation function during massive blood transfusion, the ratio between fresh frozen plasma and erythrocyte is recommended to be 2:1 in patients of coagulation dysfunction in order to improve the patient's coagulation function and to reduce the incidence of adverse event, the ratio of fresh frozen plasma to erythrocyte is recommended to be 1:1 in patients with normal coagulation so as to reduce the dilutional coagulopathy and hypervolemia of blood.

  4. The absorbed dose to blood from blood-borne activity

    NASA Astrophysics Data System (ADS)

    Hänscheid, H.; Fernández, M.; Lassmann, M.

    2015-01-01

    The radiation absorbed dose to blood and organs from activity in the blood is relevant for nuclear medicine dosimetry and for research in biodosimetry. The present study provides coefficients for the average absorbed dose rates to the blood from blood-borne activity for radionuclides frequently used in targeted radiotherapy and in PET diagnostics. The results were deduced from published data for vessel radius-dependent dose rate coefficients and reasonable assumptions on the blood-volume distribution as a function of the vessel radius. Different parts of the circulatory system were analyzed separately. Vessel size information for heart chambers, aorta, vena cava, pulmonary artery, and capillaries was taken from published results of morphometric measurements. The remaining blood not contained in the mentioned vessels was assumed to reside in fractal-like vascular trees, the smallest branches of which are the arterioles or venules. The applied vessel size distribution is consistent with recommendations of the ICRP on the blood-volume distribution in the human. The resulting average absorbed dose rates to the blood per nuclear disintegration per milliliter (ml) of blood are (in 10-11 Gy·s-1·Bq-1·ml) Y-90: 5.58, I-131: 2.49, Lu-177: 1.72, Sm-153: 2.97, Tc-99m: 0.366, C-11: 4.56, F-18: 3.61, Ga-68: 5.94, I-124: 2.55. Photon radiation contributes 1.1-1.2·10-11 Gy·s-1·Bq-1·ml to the total dose rate for positron emitters but significantly less for the other nuclides. Blood self-absorption of the energy emitted by ß-particles in the whole blood ranges from 37% for Y-90 to 80% for Tc-99m. The correspondent values in vascular trees, which are important for the absorbed dose to organs, range from 30% for Y-90 to 82% for Tc-99m.

  5. Transfusion and coagulation management in liver transplantation.

    PubMed

    Clevenger, Ben; Mallett, Susan V

    2014-05-28

    There is wide variation in the management of coagulation and blood transfusion practice in liver transplantation. The use of blood products intraoperatively is declining and transfusion free transplantations take place ever more frequently. Allogenic blood products have been shown to increase morbidity and mortality. Primary haemostasis, coagulation and fibrinolysis are altered by liver disease. This, combined with intraoperative disturbances of coagulation, increases the risk of bleeding. Meanwhile, the rebalancing of coagulation homeostasis can put patients at risk of hypercoagulability and thrombosis. The application of the principles of patient blood management to transplantation can reduce the risk of transfusion. This includes: preoperative recognition and treatment of anaemia, reduction of perioperative blood loss and the use of restrictive haemoglobin based transfusion triggers. The use of point of care coagulation monitoring using whole blood viscoelastic testing provides a picture of the complete coagulation process by which to guide and direct coagulation management. Pharmacological methods to reduce blood loss include the use of anti-fibrinolytic drugs to reduce fibrinolysis, and rarely, the use of recombinant factor VIIa. Factor concentrates are increasingly used; fibrinogen concentrates to improve clot strength and stability, and prothrombin complex concentrates to improve thrombin generation. Non-pharmacological methods to reduce blood loss include surgical utilisation of the piggyback technique and maintenance of a low central venous pressure. The use of intraoperative cell salvage and normovolaemic haemodilution reduces allogenic blood transfusion. Further research into methods of decreasing blood loss and alternatives to blood transfusion remains necessary to continue to improve outcomes after transplantation.

  6. Transfusion and coagulation management in liver transplantation

    PubMed Central

    Clevenger, Ben; Mallett, Susan V

    2014-01-01

    There is wide variation in the management of coagulation and blood transfusion practice in liver transplantation. The use of blood products intraoperatively is declining and transfusion free transplantations take place ever more frequently. Allogenic blood products have been shown to increase morbidity and mortality. Primary haemostasis, coagulation and fibrinolysis are altered by liver disease. This, combined with intraoperative disturbances of coagulation, increases the risk of bleeding. Meanwhile, the rebalancing of coagulation homeostasis can put patients at risk of hypercoagulability and thrombosis. The application of the principles of patient blood management to transplantation can reduce the risk of transfusion. This includes: preoperative recognition and treatment of anaemia, reduction of perioperative blood loss and the use of restrictive haemoglobin based transfusion triggers. The use of point of care coagulation monitoring using whole blood viscoelastic testing provides a picture of the complete coagulation process by which to guide and direct coagulation management. Pharmacological methods to reduce blood loss include the use of anti-fibrinolytic drugs to reduce fibrinolysis, and rarely, the use of recombinant factor VIIa. Factor concentrates are increasingly used; fibrinogen concentrates to improve clot strength and stability, and prothrombin complex concentrates to improve thrombin generation. Non-pharmacological methods to reduce blood loss include surgical utilisation of the piggyback technique and maintenance of a low central venous pressure. The use of intraoperative cell salvage and normovolaemic haemodilution reduces allogenic blood transfusion. Further research into methods of decreasing blood loss and alternatives to blood transfusion remains necessary to continue to improve outcomes after transplantation. PMID:24876736

  7. [Coagulation disorders in the intensive care station].

    PubMed

    Hart, C; Spannagl, M

    2014-05-01

    Coagulation disorders are frequently encountered in the intensive care unit (ICU) and are challenging due to a variety of potential etiologies. Critically ill patients with coagulation abnormalities may present with an increased risk of bleeding, show coagulation activation resulting in thromboembolism, or have no specific symptoms. Hemostatic abnormalities observed in ICU patients range from isolated thrombocytopenia or prolonged global clotting tests to complex and life-threatening coagulation defects. Successful management of coagulation disorders requires prompt and accurate identification of the underlying cause. This review describes the most frequently occurring diagnoses found in intensive care patients with thrombocytopenia and coagulation test abnormalities and summarizes appropriate diagnostic interventions and current approaches to differential diagnosis.

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

    PubMed

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

    1991-03-01

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

  9. A comparative study of coagulation, granular- and powdered-activated carbon for the removal of perfluorooctane sulfonate and perfluorooctanoate in drinking water treatment.

    PubMed

    Pramanik, Biplob Kumar; Pramanik, Sagor Kumar; Suja, Fatihah

    2015-01-01

    Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are persistent organic pollutants in the environment and their occurrence causes toxicological effects on humans. We examined different conventional coagulant treatments such as alum, ferric chloride and polyaluminium chloride in removing these compounds. These were then compared with a natural coagulant (Moringa oleifera). We also investigated the powdered-activated carbon (PAC) and granular-activated carbon (GAC) for removing these compounds. At an initial dose of 5 mg/L, polyaluminium chloride led to a higher reduction of PFOS/PFOA compared with alum which in turn was higher than ferric. The removal efficiency increased with the increase in coagulant dose and decrease in pH. M. oleifera was very effective in reducing PFOS and PFOA than conventional coagulants, with a reduction efficiencies of 65% and 72%, respectively, at a dose of 30 mg/L. Both PAC and GAC were very effective in reducing these compounds than coagulations. PAC led to a higher reduction in PFOS and PFOA than GAC due to its greater surface area and shorter internal diffusion distances. The addition of PAC (10 min contact time) with coagulation (at 5 mg/L dosage) significantly increased the removal efficiency, and the maximum removal efficiency was for M. oleifera with 98% and 94% for PFOS and PFOA, respectively. The reduction efficiency of PFOS/PFOA was reduced with the increase in dissolved organic concentration due to the adsorption competition between organic molecules and PFOS/PFOA.

  10. Reincarnation of ancient links between coagulation and complement.

    PubMed

    Conway, E M

    2015-06-01

    Throughout evolution, organisms have developed means to contain wounds by simultaneously limiting bleeding and eliminating pathogens and damaged host cells via the recruitment of innate defense mechanisms. Disease emerges when there is unchecked activation of innate immune and/or coagulation responses. A key component of innate immunity is the complement system. Concurrent excess activation of coagulation and complement - two major blood-borne proteolytic pathways - is evident in numerous diseases, including atherosclerosis, diabetes, venous thromboembolic disease, thrombotic microangiopathies, arthritis, cancer, and infectious diseases. Delineating the cross-talk between these two cascades will uncover novel therapeutic insights.

  11. Hysteresis-like binding of coagulation factors X/Xa to procoagulant activated platelets and phospholipids results from multistep association and membrane-dependent multimerization.

    PubMed

    Podoplelova, Nadezhda A; Sveshnikova, Anastasia N; Kurasawa, James H; Sarafanov, Andrey G; Chambost, Herve; Vasil'ev, Sergey A; Demina, Irina A; Ataullakhanov, Fazly I; Alessi, Marie-Christine; Panteleev, Mikhail A

    2016-06-01

    Binding of coagulation factors X (fX) and Xa (fXa) to activated platelets is required for the formation of membrane-dependent enzymatic complexes of intrinsic tenase and prothrombinase. We carried out an in-depth characterization of fX/fXa binding to phospholipids and gel-filtered, thrombin-activated platelets. Flow cytometry, surface plasmon resonance, and computational modeling were used to investigate interactions of fX/fXa with the membranes. Confocal microscopy was employed to study fXa binding to platelet thrombi formed in flowing whole blood under arterial conditions. Binding of fX/fXa to either vesicles or procoagulant platelets did not follow a traditional one-step reversible binding model. Their dissociation was a two-step process resulting in a plateau that was up to 10-fold greater than the saturation value observed in the association experiments. Computational modeling and experimental evidence suggested that this was caused by a combination of two-step association (mainly for fX) and multimerization on the membrane (mainly for fXa). Importantly, fX formed multimers with fXa, thereby improving its retention. The same binding/dissociation hysteresis was observed for annexin V known to form trimers on the membranes. Experiments with platelets from gray syndrome patients showed that alpha-granular factor Va provided an additional high-affinity binding site for fXa that did not affect the hysteresis. Confocal microscopy observation of fXa binding to platelet thrombi in a flow chamber and its wash-out confirmed that this phenomenon persisted under physiologically relevant conditions. This suggests its possible role of "locking" coagulation factors on the membrane and preventing their inhibition in plasma and removal from thrombi by flow.

  12. The crystal structure of the active domain of Anopheles anti-platelet protein, a powerful anti-coagulant, in complex with an antibody.

    PubMed

    Sugiyama, Kanako; Iyori, Mitsuhiro; Sawaguchi, Asuka; Akashi, Satoko; Tame, Jeremy R H; Park, Sam-Yong; Yoshida, Shigeto

    2014-06-06

    Blood clotting is a vitally important process that must be carefully regulated to prevent blood loss on one hand and thrombosis on the other. Severe injury and hemophilia may be treated with pro-coagulants, whereas risk of obstructive clotting or embolism may be reduced with anti-coagulants. Anti-coagulants are an extremely important class of drug, one of the most widely used types of medication, but there remains a pressing need for novel treatments, however, as present drugs such as warfarin have significant drawbacks. Nature provides a number of examples of anti-coagulant proteins produced by blood-sucking animals, which may provide templates for the development of new small molecules with similar physiological effects. We have, therefore, studied an Anopheles anti-platelet protein from a malaria vector mosquito and report its crystal structure in complex with an antibody. Overall the protein is extremely sensitive to proteolysis, but the crystal structure reveals a stable domain built from two helices and a turn, which corresponds to the functional region. The antibody raised against Anopheles anti-platelet protein prevents it from binding collagen. Our work, therefore, opens new avenues to the development of both novel small molecule anti-clotting agents and anti-malarials.

  13. Leucaena leucocephala serine proteinase inhibitor: primary structure and action on blood coagulation, kinin release and rat paw edema.

    PubMed

    Oliva, M L; Souza-Pinto, J C; Batista, I F; Araujo, M S; Silveira, V F; Auerswald, E A; Mentele, R; Eckerskorn, C; Sampaio, M U; Sampaio, C A

    2000-03-07

    A serine proteinase inhibitor isolated from Leucaena leucocephala seeds (LlTI) was purified to homogeneity by acetone fractionation, ion exchange chromatography, gel filtration and reverse phase chromatography (HPLC). SDS-PAGE indicated a protein with M(r) 20000 and two polypeptide chains (alpha-chain, M(r) 15000, and beta-chain, M(r) 5000), the sequence being determined by automatic Edman degradation and by mass spectroscopy. LlTI is a 174 amino acid residue protein which shows high homology to plant Kunitz inhibitors, especially those double chain proteins purified from the Mimosoideae subfamily. LlTI inhibits plasmin (K(i) 3.2 x 10(-10) M), human plasma kallikrein (K(i) 6.3 x 10(-9) M), trypsin (K(i) 2.5 x 10(-8) M) and chymotrypsin (K(i) 1.4 x 10(-8) M). Factor XIIa activity is inhibited but K(i) was not determined, and factor Xa, tissue kallikrein and thrombin are not inhibited by LlTI. The action of LlTI on enzymes that participate in the blood clotting extrinsic pathway is confirmed by the prolongation of activated partial thromboplastin time, used as clotting time assay. The inhibition of the fibrinolytic activity of plasmin was confirmed on the hydrolysis of fibrin plates. LlTI inhibits kinin release from high molecular weight kininogen by human plasma kallikrein in vitro and, administered intravenously, causes a decrease in paw edema induced by carrageenin or heat in male Wistar rats. In addition, lower concentrations of bradykinin were found in limb perfusion fluids of LlTI-treated rats.

  14. Endovascular treatment of chronic cerebro spinal venous insufficiency in patients with multiple sclerosis modifies circulating markers of endothelial dysfunction and coagulation activation: a prospective study.

    PubMed

    Napolitano, Mariasanta; Bruno, Aldo; Mastrangelo, Diego; De Vizia, Marcella; Bernardo, Benedetto; Rosa, Buonagura; De Lucia, Domenico

    2014-10-01

    We performed a monocentric observational prospective study to evaluate coagulation activation and endothelial dysfunction parameters in patients with multiple sclerosis undergoing endovascular treatment for cerebro-spinal-venous insufficiency. Between February 2011 and July 2012, 144 endovascular procedures in 110 patients with multiple sclerosis and chronical cerebro-spinal venous insufficiency were performed and they were prospectively analyzed. Each patient was included in the study according to previously published criteria, assessed by the investigators before enrollment. Endothelial dysfunction and coagulation activation parameters were determined before the procedure and during follow-up at 1, 3, 6, 9, 12, 15 and 18 months after treatment, respectively. After the endovascular procedure, patients were treated with standard therapies, with the addition of mesoglycan. Fifty-five percent of patients experienced a favorable outcome of multiple sclerosis within 1 month after treatment, 25% regressed in the following 3 months, 24.9% did not experience any benefit. In only 0.1% patients, acute recurrence was observed and it was treated with high-dose immunosuppressive therapy. No major complications were observed. Coagulation activation and endothelial dysfunction parameters were shown to be reduced at 1 month and stable up to 12-month follow-up, and they were furthermore associated with a good clinical outcome. Endovascular procedures performed by a qualified staff are well tolerated; they can be associated with other currently adopted treatments. Correlations between inflammation, coagulation activation and neurodegenerative disorders are here supported by the observed variations in plasma levels of markers of coagulation activation and endothelial dysfunction.

  15. Evaluation of waste activated sludge as a coagulant aid for the treatment of industrial wastewater containing mixed surfactants.

    PubMed

    Sriwiriyarat, Tongchai; Jangkorn, Siriprapha

    2009-04-01

    Wastewater generated by the industry manufacturing detergents and various kinds of consumer products normally contains very high contents of mixed surfactants, organic matters expressed as chemical oxygen demand (COD), and phosphates that must be treated prior to discharge to the aquatic environment. In this study, jar-test experiments were conducted to evaluate the waste activated sludge (WAS) as a coagulation aid in the coagulation-flocculation process with ferric chloride or aluminum sulfate as a coagulant for the treatment of wastewater collected from the aforementioned industry. The WAS was selected because of its adsorption capability of anionic surfactants and its availability from the wastage stream of biological wastewater treatment process. The effective dosages of both coagulants with and without the WAS additions were determined in this study. Without the WAS addition, the concentrations of 800 mg/L aluminum sulfate at the optimum pH value of 8 and 2208 mg/L ferric chloride at the optimum pH value of 12 were the optimum chemical dosages. It appears that aluminum sulfate was more effective than ferric chloride based on the chemical dosage and removal efficiency. The turbidity, suspended particles, anionic surfactants, COD, and phosphates removal efficiencies of aluminum sulfate and ferric chloride under the optimum dosage were 95.6, 88.2, 78.4, 73.5, 47.3% and 98.8, 92.0, 72.7, 67.5, 53.1%, respectively. The addition of 200 mg/L WAS was sufficient to reduce the optimum dosages of both chemicals by 200 mg/L. The cationic surfactant existing in the wastewater worked as a flocculating agent leading to the flocculation of waste activated sludge resulting in the enmeshment of the suspended particles and colloids on which the COD, anionic surfactants, and phosphates were adsorbed. However, the substances removal efficiencies of ferric chloride and aluminum sulfate were slightly enhanced and reduced, respectively. It is possibly explained that the settling time

  16. Keeping the blood flowing-plasminogen activator genes and feeding behavior in vampire bats.

    PubMed

    Tellgren-Roth, Asa; Dittmar, Katharina; Massey, Steven E; Kemi, Cecilia; Tellgren-Roth, Christian; Savolainen, Peter; Lyons, Leslie A; Liberles, David A

    2009-01-01

    The blood feeding vampire bats emerged from New World leaf-nosed bats that fed on fruit and insects. Plasminogen activator, a serine protease that regulates blood coagulation, is known to be expressed in the saliva of Desmodus rotundus (common vampire bat) and is thought to be a key enzyme for the emergence of blood feeding in vampire bats. To better understand the evolution of this biological function, we studied the plasminogen activator (PA) genes from all vampire bat species in light of their feeding transition to bird and subsequently mammalian blood. We include the rare species Diphylla ecaudata and Diaemus youngi, where plasminogen activator had not previously been studied and demonstrate that PA gene duplication observed in Desmodus is not essential to the vampire phenotype, but relates to the emergence of predominant mammalian blood feeding in this species. Plasminogen activator has evolved through gene duplication, domain loss, and sequence evolution leading to change in fibrin-specificity and susceptibility to plasminogen activator inhibitor-1. Before undertaking this study, only the four plasminogen activator isoforms from Desmodus were known. The evolution of vampire bat plasminogen activators can now be linked phylogenetically to the transition in feeding behavior among vampire bat species from bird to mammalian blood.

  17. Keeping the blood flowing—plasminogen activator genes and feeding behavior in vampire bats

    NASA Astrophysics Data System (ADS)

    Tellgren-Roth, Åsa; Dittmar, Katharina; Massey, Steven E.; Kemi, Cecilia; Tellgren-Roth, Christian; Savolainen, Peter; Lyons, Leslie A.; Liberles, David A.

    2009-01-01

    The blood feeding vampire bats emerged from New World leaf-nosed bats that fed on fruit and insects. Plasminogen activator, a serine protease that regulates blood coagulation, is known to be expressed in the saliva of Desmodus rotundus (common vampire bat) and is thought to be a key enzyme for the emergence of blood feeding in vampire bats. To better understand the evolution of this biological function, we studied the plasminogen activator (PA) genes from all vampire bat species in light of their feeding transition to bird and subsequently mammalian blood. We include the rare species Diphylla ecaudata and Diaemus youngi, where plasminogen activator had not previously been studied and demonstrate that PA gene duplication observed in Desmodus is not essential to the vampire phenotype, but relates to the emergence of predominant mammalian blood feeding in this species. Plasminogen activator has evolved through gene duplication, domain loss, and sequence evolution leading to change in fibrin-specificity and susceptibility to plasminogen activator inhibitor-1. Before undertaking this study, only the four plasminogen activator isoforms from Desmodus were known. The evolution of vampire bat plasminogen activators can now be linked phylogenetically to the transition in feeding behavior among vampire bat species from bird to mammalian blood.

  18. Effects of hemolysis and lipemia interference on kaolin-activated thromboelastography, and comparison with conventional coagulation tests.

    PubMed

    Tang, Ning; Jin, Xi; Sun, Ziyong; Jian, Cui

    2017-04-01

    The effects of hemolysis and lipemia on thromboelastography (TEG) analysis have been scarcely evaluated in human samples, and neglected in clinical practice. We aimed to investigate the effects of in vitro mechanical hemolysis and lipemia on TEG analysis and conventional coagulation tests. Twenty-four healthy volunteers were enrolled in the study. Besides the controls, three groups with slight, moderate and severe mechanical hemolysis were constituted according to free hemoglobin (Hb) concentrations of 0.5-1.0, 2.0-6.0 and 7.0-13.0 g/L, respectively; and three groups with mild, moderate and high lipemia were established according to triglyceride concentrations of ∼6.0, ∼12.0, and ∼18.0 mmol/L, respectively. Four TEG parameters, reaction time (R), coagulation time (K), angle (α), and maximum amplitude (MA), were measured alongside conventional plasma tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) by mechanical method, and platelet count by optical method. Results showed that the median R and MA values at moderate and severe hemolysis and K at severe hemolysis exceeded respective reference intervals, and were considered unacceptable. Median values of TEG parameters in lipemic samples were all within reference intervals. Bias values of conventional plasma tests PT, APTT and FIB in hemolyzed or lipemic samples were all lower than the Clinical Laboratory Improvement Amendments (CLIA) allowable limits. Bias values of platelet count at moderate to severe hemolysis and lipemia exceeded the CLIA allowable limits. In conclusion, the detection of TEG was in general more affected by mechanical hemolysis than plasma coagulation tests. Pre-analytical variables should be taken into account when unexpected TEG results are obtained.

  19. A Mixture of Ethanol Extracts of Persimmon Leaf and Citrus junos Sieb Improves Blood Coagulation Parameters and Ameliorates Lipid Metabolism Disturbances Caused by Diet-Induced Obesity in C57BL/6J Mice.

    PubMed

    Kim, Ae Hyang; Kim, Hye Jin; Ryu, Ri; Han, Hye Jin; Han, Young Ji; Lee, Mi-Kyung; Choi, Myung-Sook; Park, Yong Bok

    2016-02-01

    This study investigated the effects of a flavonoid-rich ethanol extract of persimmon leaf (PL), an ethanol extract of Citrus junos Sieb (CJS), and a PL-CJS mixture (MPC) on mice fed a highfat diet (HFD). We sought to elucidate the mechanisms of biological activity of these substances using measurements of blood coagulation indices and lipid metabolism parameters. C57BL/6J mice were fed a HFD with PL (0.5% (w/w)), CJS (0.1% (w/w)), or MPC (PL 0.5%, CJS 0.1% (w/w)) for 10 weeks. In comparison with data obtained for mice in the untreated HFD group, consumption of MPC remarkably prolonged the activated partial thromboplastin time (aPTT) and prothrombin time (PT), whereas exposure to PL prolonged aPTT only. Lower levels of plasma total cholesterol, hepatic cholesterol, and erythrocyte thiobarbituric acid-reactive substances, hepatic HMG-CoA reductase, and decreased SREBP-1c gene expression were observed in mice that received PL and MPC supplements compared with the respective values detected in the untreated HFD animals. Our results indicate that PL and MPC may have beneficial effects on blood circulation and lipid metabolism in obese mice.

  20. Can activation of coagulation and impairment of fibrinolysis in patients with anxiety and depression be reversed after improvement of psychiatric symptoms? Results of a pilot study.

    PubMed

    Geiser, Franziska; Gessler, Katharina; Conrad, Rupert; Imbierowicz, Katrin; Albus, Christian; Harbrecht, Ursula

    2012-08-01

    Anxiety and depression are associated with an activation of coagulation and impairment of fibrinolysis. This study addresses the question whether these findings are reversed after psychotherapy and improvement of psychiatric symptoms. Three factors of coagulation and fibrinolysis as well as level of anxiety and depression were reassessed in 12 patients 1 to 3 years after intensive inpatient psychotherapy. The patients showed a substantial improvement of their severe anxiety disorder and comorbid depressive disorder. Simultaneously, we found a significant decrease in factor VII and plasminogen activator inhibitor. We conclude that reduction of severe anxiety and depression may be associated with a reversal of the procoagulant effect (activation of coagulation and impairment of fibrinolysis) of these psychological states. Because of the small sample size of this pilot study, further research is needed.

  1. 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.

  2. Protein-Templated Formation of an Inhibitor of the Blood Coagulation Factor Xa through a Background-Free Amidation Reaction.

    PubMed

    Jaegle, Mike; Steinmetzer, Torsten; Rademann, Jörg

    2017-03-20

    Protein-templated reactions enable the target-guided formation of protein ligands from reactive fragments, ideally with no background reaction. Herein, we investigate the templated formation of amides. A nucleophilic fragment that binds to the coagulation factor Xa was incubated with the protein and thirteen differentially activated dipeptides. The protein induced a non-catalytic templated reaction for the phenyl and trifluoroethyl esters; the latter was shown to be a completely background-free reaction. Starting from two fragments with millimolar affinity, a 29 nm superadditive inhibitor of factor Xa was obtained. The fragment ligation reaction was detected with high sensitivity by an enzyme activity assay and by mass spectrometry. The reaction progress and autoinhibition of the templated reaction by the formed ligation product were determined, and the structure of the protein-inhibitor complex was elucidated.

  3. Protein‐Templated Formation of an Inhibitor of the Blood Coagulation Factor Xa through a Background‐Free Amidation Reaction

    PubMed Central

    Jaegle, Mike; Steinmetzer, Torsten

    2017-01-01

    Abstract Protein‐templated reactions enable the target‐guided formation of protein ligands from reactive fragments, ideally with no background reaction. Herein, we investigate the templated formation of amides. A nucleophilic fragment that binds to the coagulation factor Xa was incubated with the protein and thirteen differentially activated dipeptides. The protein induced a non‐catalytic templated reaction for the phenyl and trifluoroethyl esters; the latter was shown to be a completely background‐free reaction. Starting from two fragments with millimolar affinity, a 29 nm superadditive inhibitor of factor Xa was obtained. The fragment ligation reaction was detected with high sensitivity by an enzyme activity assay and by mass spectrometry. The reaction progress and autoinhibition of the templated reaction by the formed ligation product were determined, and the structure of the protein–inhibitor complex was elucidated. PMID:28199769

  4. Activation states of blood eosinophils in asthma.

    PubMed

    Johansson, M W

    2014-04-01

    Asthma is characterized by airway inflammation rich in eosinophils. Airway eosinophilia is associated with exacerbations and has been suggested to play a role in airway remodelling. Recruitment of eosinophils from the circulation requires that blood eosinophils become activated, leading to their arrest on the endothelium and extravasation. Circulating eosinophils can be envisioned as potentially being in different activation states, including non-activated, pre-activated or 'primed', or fully activated. In addition, the circulation can potentially be deficient of pre-activated or activated eosinophils, because such cells have marginated on activated endothelium or extravasated into the tissue. A number of eosinophil surface proteins, including CD69, L-selectin, intercellular adhesion molecule-1 (ICAM-1, CD54), CD44, P-selectin glycoprotein ligand-1 (PSGL-1, CD162), cytokine receptors, Fc receptors, integrins including αM integrin (CD11b), and activated conformations of Fc receptors and integrins, have been proposed to report cell activation. Variation in eosinophil activation states may be associated with asthma activity. Eosinophil surface proteins proposed to be activation markers, with a particular focus on integrins, and evidence for associations between activation states of blood eosinophils and features of asthma are reviewed here. Partial activation of β1 and β2 integrins on blood eosinophils, reported by monoclonal antibodies (mAbs) N29 and KIM-127, is associated with impaired pulmonary function and airway eosinophilia, respectively, in non-severe asthma. The association with lung function does not occur in severe asthma, presumably due to greater eosinophil extravasation, specifically of activated or pre-activated cells, in severe disease.

  5. Impact of coagulation as a pre-treatment for UVC/H2O2-biological activated carbon treatment of a municipal wastewater reverse osmosis concentrate.

    PubMed

    Umar, Muhammad; Roddick, Felicity; Fan, Linhua

    2016-01-01

    After coagulation of high salinity reverse osmosis concentrate (ROC) with either alum or ferric chloride followed by UVC/H2O2 treatment, biological activated carbon (BAC) was investigated for the removal of DOC. BAC treatment mainly removed low molecular weight (LMW) neutral molecules indicating that biodegradation was the predominant mechanism of organic matter removal. Coagulation with ferric chloride gave greater DOC reductions than alum both as a stand-alone treatment and after the sequence of UVC/H2O2 and BAC treatment. However, overall reduction after the sequence of coagulation, UVC/H2O2 and BAC treatment was only marginally greater for ferric chloride (68%) than for alum (62%). Trihalomethane formation potential and N-Nitrosodimethylamine concentration decreased markedly after UVC/H2O2 treatment. UVC/H2O2 treatment of the ROC led to the generation of extreme toxicity according to the Microtox assay, but no toxicity was observed after BAC, demonstrating its advantage for enabling safe disposal of the treated ROC. Implementation of coagulation as a pre-treatment and BAC as a post-treatment markedly reduced (6-8 times) the electrical energy dose (EED) required for the UVC/H2O2 process. The sequence of coagulation, UVC/H2O2 and BAC treatment was demonstrated as a potential process for the removal of organic matter from high salinity municipal ROC.

  6. Effects of coagulation temperature on measurements of complement function in serum samples from patients with systemic lupus erythematosus.

    PubMed Central

    Baatrup, G; Sturfelt, G; Junker, A; Svehag, S E

    1992-01-01

    Blood samples from 15 patients with systemic lupus erythematosus (SLE) and 15 healthy blood donors were allowed to coagulate for one hour at room temperature, followed by one hour at 4 or 37 degrees C. The complement activity of the serum samples was assessed by three different functional assays. Serum samples from patients with SLE obtained by coagulation at 37 degrees C had a lower complement activity than serum samples from blood coagulated at 4 degrees C when the capacity of the serum samples to solubilise precipitable immune complexes and to support the attachment of complement factors to solid phase immune complexes was determined. Haemolytic complement activity was not affected by the coagulation temperature. The content of C1q binding immune complexes in paired serum samples obtained after coagulation at 4 and 37 degrees C was similar and the size distribution of the immune complexes, determined by high performance gel permeation chromatography, was also similar. This study shows that the results of functional complement assays, applied to serum samples from patients with SLE cannot be compared unless the conditions for blood coagulation and serum handling are defined and are the same. The data also indicate that assays measuring complement mediated solubilisation of immune complexes and the fixation of complement factors to solid phase immune complexes are more sensitive indicators of complement activity than the haemolytic assay. PMID:1632665

  7. 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

  8. The reciprocal relationship between inflammation and coagulation.

    PubMed

    O'Brien, Mauria

    2012-05-01

    Inflammation and coagulation constitute two host defense systems with complementary roles in eliminating invading pathogens, limiting tissue damage, and restoring homeostasis. Extensive cross talk exists between these 2 systems, whereby inflammation leads to activation of coagulation, and coagulation considerably affects inflammatory activity. Infection leads to the production of proinflammatory cytokines that, in turn, stimulate the production of tissue factor. Activation of the coagulation system and ensuing thrombin generation are dependent on the expression of tissue factor. Conversely, activated coagulation proteases may affect specific receptors on inflammatory cells and endothelial cells and thereby modulate the inflammatory response. Activation of coagulation with the simultaneous down-regulation of endothelial-bound anticoagulant mechanisms and endogenous fibrinolysis characterizes the pathophysiology of sepsis. The mechanisms by which these highly complex and codependent defense strategies are linked together both in health and disease is the focus of this review.

  9. Poultry blood preservation and the impact of preservation on flocculant activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chicken blood is an attractive but problematic raw material for the production of biobased flocculants. Blood begins to degrade as soon as it is collected – it rapidly coagulates, and at longer time scales, the red blood cells lyse and microbial growth results in hydrogen sulfide production. This s...

  10. 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

  11. Coagulation in patients with severe sepsis.

    PubMed

    Levi, Marcel; Poll, Tom van der

    2015-02-01

    In the majority of patients with severe sepsis, systemic activation of coagulation is present. Increasing evidence points to an extensive cross-talk between coagulation and inflammation that may play an important role in the pathogenesis of sepsis. Inflammation not only leads to activation of coagulation, but coagulation also considerably affects inflammatory activity. Molecular pathways that contribute to inflammation-induced activation of coagulation have been precisely identified. Proinflammatory cytokines and other mediators are capable of activating the coagulation system and downregulating important physiological anticoagulant pathways. Activation of the coagulation system and ensuing thrombin generation is dependent on expression of tissue factor on activated mononuclear cells and endothelial cells, and is insufficiently counteracted by TFPI. Simultaneously, endothelial-bound anticoagulant mechanism, in particular the protein C system, is shutoff by proinflammatory cytokines. In addition, fibrin removal is severely inhibited, because of inactivation of the fibrinolytic system, caused by an upregulation of its main inhibitor, plasminogen activator inhibitor type 1 (PAI-1). Increased fibrin formation and impaired removal lead to (micro)vascular thrombosis, which may result in tissue ischemia and subsequent organ damage. The cornerstone of the management of coagulation in sepsis is the specific and vigorous treatment of the underlying disorder. Strategies aimed at the inhibition of coagulation activation may theoretically be justified and have been found beneficial in experimental and initial clinical studies. Heparin may be an effective anticoagulant approach and alternative strategies comprise restoration of physiological anticoagulant pathways.

  12. Asthma and coagulation.

    PubMed

    de Boer, J Daan; Majoor, Christof J; van 't Veer, Cornelis; Bel, Elisabeth H D; van der Poll, Tom

    2012-04-05

    Asthma is a chronic airway disease characterized by paroxysmal airflow obstruction evoked by irritative stimuli on a background of allergic lung inflammation. Currently, there is no cure for asthma, only symptomatic treatment. In recent years, our understanding of the involvement of coagulation and anticoagulant pathways, the fibrinolytic system, and platelets in the pathophysiology of asthma has increased considerably. Asthma is associated with a procoagulant state in the bronchoalveolar space, further aggravated by impaired local activities of the anticoagulant protein C system and fibrinolysis. Protease-activated receptors have been implicated as the molecular link between coagulation and allergic inflammation in asthma. This review summarizes current knowledge of the impact of the disturbed hemostatic balance in the lungs on asthma severity and manifestations and identifies new possible targets for asthma treatment.

  13. Coagulation in Liver Disease.

    PubMed

    Hoffman, Maureane

    2015-07-01

    The liver plays a key role in hemostasis as the site of synthesis of many of the proteins involved in the coagulation, antithrombotic and fibrinolytic systems that interact to both establish hemostasis, and preventing thrombosis. The common laboratory tests, prothrombin time (PT) and activated partial thromboplastin time (aPTT), evolved from studies of plasma clotting in test tubes. Such studies laid the basis for the coagulation cascade model of hemostasis. However, thought has evolved to place a greater emphasis on the active roles of cells in localizing and regulating hemostasis. The PT and aPTT do not reflect the roles of cellular elements in hemostasis, nor do they reflect the crucial roles of antithrombotic and fibrinolytic systems. Thus, though the PT may indeed reflect the synthetic capacity of the liver, it does not accurately reflect the risk of bleeding or thrombosis in patients with liver failure.

  14. Hydroxyurea increases plasma concentrations of microparticles and reduces coagulation activation and fibrinolysis in patients with sickle cell anemia.

    PubMed

    Brunetta, Denise Menezes; De Santis, Gil Cunha; Silva-Pinto, Ana Cristina; Oliveira de Oliveira, Luciana Correa; Covas, Dimas Tadeu

    2015-01-01

    Microparticles (MPs) are present in healthy subjects and their concentration increases in patients at high risk of thrombosis. We evaluated 10 patients with sickle cell anemia (SCA) treated with hydroxyurea (HU) and 13 SCA patients without this treatment. MP concentrations were determined by flow cytometry. Coagulation was evaluated using the thrombin-antithrombin complex (TAT) and D-dimers. Total MP concentrations were increased in the HU-treated group (265 × 10(6)/ml vs. 67.45 × 10(6)/ml; p = 0.0026), as well as MPs derived from RBC (67.83 × 10(6)/ml vs. 26.31 × 10(6)/ml; p = 0.05), monocytes (51.31 × 10(6)/ml vs. 9.03 × 10(6)/ml; p = 0.0084), monocytes with tissue factor (TF) expression (2.27 × 10(6)/ml vs. 0.27 × 10(6)/ml; p = 0.0058), endothelium (49.42 × 10(6)/ml vs. 7.23 × 10(6)/ml; p = 0.007) and endothelium with TF (1.42 × 10(6)/ml vs. 0.26 × 10(6)/ml; p = 0.0043). Furthermore, the concentrations of TAT (7.56 vs. 10.98 µg/l; p = 0.014) and D-dimers (0.65 vs. 1.29 µg/ml; p = 0.007) were reduced with HU. The MP elevation may suggest a direct cytotoxic effect of HU. Another explanation is a cell surface increase secondary to a megaloblastic process, resulting in increased vesicle release. In our opinion, the known benefits of HU on SCA patients, along with the reduction in coagulation activation, surpass its potential detrimental effect on MPs. Future studies should elucidate the role of MPs and demonstrate their significance in different contexts.

  15. Preliminary assessment of Hedychium coronarium essential oil on fibrinogenolytic and coagulant activity induced by Bothrops and Lachesis snake venoms

    PubMed Central

    2014-01-01

    Background The search for new inhibitors of snake venom toxins is essential to complement or even replace traditional antivenom therapy, especially in relation to compounds that neutralize the local effects of envenomations. Besides their possible use as alternative to traditional antivenom therapy, some plant species possess bioactive secondary metabolites including essential oils, which can be extracted from weeds that are considered substantial problems for agriculture, such as Hedychium coronarium. Methods The essential oils of leaves and rhizomes from H. coronarium were extracted by hydrodistillation, and their potential inhibitory effects on the coagulant and fibrinogenolytic activities induced by the venoms of Lachesis muta, Bothrops atrox and Bothrops moojeni were analyzed. Citrated human plasma was used to evaluate the clotting time whereas changes in fibrinogen molecules were visualized by electrophoresis in polyacrylamide gel. The experimental design used for testing coagulation inhibition was randomized in a 3 × 2 factorial arrangement (concentration × essential oils), with three replications. The essential oils were compared since they were extracted from different organs of the same botanical species, H. coronarium. Results The results suggest that the oils interact with venom proteases and plasma constituents, since all oils evaluated, when previously incubated with venoms, were able to inhibit the clotting effect, with less inhibition when oils and plasma were preincubated prior to the addition of venoms. Conclusions Thus, after extensive characterization of their pharmacological and toxicological effects, the essential oils can be used as an alternative to complement serum therapy, especially considering that these plant metabolites generally do not require specific formulations and may be used topically immediately after extraction. PMID:26413083

  16. The Inflammatory Actions of Coagulant and Fibrinolytic Proteases in Disease

    PubMed Central

    Schuliga, Michael

    2015-01-01

    Aside from their role in hemostasis, coagulant and fibrinolytic proteases are important mediators of inflammation in diseases such as asthma, atherosclerosis, rheumatoid arthritis, and cancer. The blood circulating zymogens of these proteases enter damaged tissue as a consequence of vascular leak or rupture to become activated and contribute to extravascular coagulation or fibrinolysis. The coagulants, factor Xa (FXa), factor VIIa (FVIIa), tissue factor, and thrombin, also evoke cell-mediated actions on structural cells (e.g., fibroblasts and smooth muscle cells) or inflammatory cells (e.g., macrophages) via the proteolytic activation of protease-activated receptors (PARs). Plasmin, the principle enzymatic mediator of fibrinolysis, also forms toll-like receptor-4 (TLR-4) activating fibrin degradation products (FDPs) and can release latent-matrix bound growth factors such as transforming growth factor-β (TGF-β). Furthermore, the proteases that convert plasminogen into plasmin (e.g., urokinase plasminogen activator) evoke plasmin-independent proinflammatory actions involving coreceptor activation. Selectively targeting the receptor-mediated actions of hemostatic proteases is a strategy that may be used to treat inflammatory disease without the bleeding complications of conventional anticoagulant therapies. The mechanisms by which proteases of the coagulant and fibrinolytic systems contribute to extravascular inflammation in disease will be considered in this review. PMID:25878399

  17. Factor IX Amagasaki: A new mutation in the catalytic domain resulting in the loss of both coagulant and esterase activities

    SciTech Connect

    Miyata, Toshiyuki; Iwanaga, Sadaaki ); Sakai, Toshiyuki; Sugimoto, Mitsuhiko; Naka, Hiroyuki; Yamamoto, Kazukuni; Yoshioka, Akira; Fukui, Hiromu ); Mitsui, Kotoko; Kamiya, Kensyu; Umeyama, Hideaki )

    1991-11-26

    Factor IX Amagasaki (AMG) is a naturally occurring mutant of factor IX having essentially no coagulant activity, even though normal levels of antigen are detected in plasma. Factor IX AMG was purified from the patient's plasma by immunoaffinity chromatography with an anti-factor IX monoclonal antibody column. Factor IX AMG was cleaved normally by factor VIIa-tissue factor complex, yielding a two-chain factor IXa. Amino acid composition and sequence analysis of one of the tryptic peptides isolated from factor IX AMG revealed that Gly-311 had been replaced by Glu. The authors identified a one-base substitution of guanine to adenine in exon VIII by amplifying exon VIII using the polymerase chain reaction method and sequencing the product. This base mutation also supported the replacement of Gly-311 by Glu. In the purified system, factor IXa AMG did not activate for factor X in the presence of factor VIII, phospholipids, and Ca{sup 2+}, and no esterase activity toward Z-Arg-p-nitrobenzyl ester was observed. The model building of the serine protease domain of factor IXa suggests that the Gly-311 {yields} Glu exchange would disrupt the specific conformational state in the active site environment, resulting in the substrate binding site not forming properly. This is the first report to show the experimental evidence for importance of a highly conserved Gly-142 (chymotrypsinogen numbering) located in the catalytic site of mammalian serine proteases so far known.

  18. A case of maternal vitamin K deficiency associated with hyperemesis gravidarum: its potential impact on fetal blood coagulability.

    PubMed

    Shigemi, Daisuke; Nakanishi, Kazuho; Miyazaki, Miwa; Shibata, Yoshie; Suzuki, Shunji

    2015-01-01

    Vitamin K deficiency is associated with malnutrition in some complications, such as hyperemesis gravidarum, active gastrointestinal diseases, and psychological disorders. Maternal vitamin K deficiency can cause fetal bleeding, in particular, fetal intracranial hemorrhage. Although fetal hemorrhage is uncommon, severe damage to the fetus may be inevitable. We describe a pregnant woman with vitamin K deficiency possibly due to hyperemesis gravidarum. The patient was treated for the deficiency, and no fetal or neonatal hemorrhagic diseases were manifested.

  19. Prehospital coagulation monitoring of resuscitation with point-of-care devices.

    PubMed

    Schött, Ulf

    2014-05-01

    A variety of point-of-care monitors for the measurement of hematocrit, hemoglobin, blood gas with electrolytes, and lactate can be used also in the prehospital setting for optimizing and individualizing trauma resuscitation. Point-of-care coagulation testing with activated prothrombin test, prothrombin test, and activated coagulation/clotting time tests is available for prehospital use. Although robust, battery driven, and easy to handle, many devices lack documentation for use in prehospital care. Some of the devices correspond poorly to corresponding laboratory analyses in acute trauma coagulopathy and at lower hematocrits. In trauma, viscoelastic tests such as rotational thromboelastometry and thromboelastography can rapidly detect acute trauma coagulopathy and give an overall dynamic picture of the hemostatic system and the interaction between its different components: coagulation activation, fibrin polymerization, fibrin platelet interactions within the clot, and fibrinolysis. Rotational thromboelastometry is shock resistant and has the potential to be used outside the hospital setting to guide individualized coagulation factor and blood component therapies. Sonoclot and Rheorox are two small viscoelastic instruments with one-channel options, but with less documentation. The point-of-care market for coagulation tests is quickly expanding, and new devices are introduced all the time. Still they should be better adopted to prehospital conditions, small, robust, battery charged, and rapid and use small sample volumes and whole blood.

  20. A comparative study on the efficiency of ozonation and coagulation-flocculation as pretreatment to activated carbon adsorption of biologically stabilized landfill leachate.

    PubMed

    Oloibiri, Violet; Ufomba, Innocent; Chys, Michael; Audenaert, Wim T M; Demeestere, Kristof; Van Hulle, Stijn W H

    2015-09-01

    The present work investigates the potential of coagulation-flocculation and ozonation to pretreat biologically stabilized landfill leachate before granular activated carbon (GAC) adsorption. Both iron (III) chloride (FeCl3) and polyaluminium chloride (PACl) are investigated as coagulants. Better organic matter removal is observed when leachate was treated with FeCl3. At a dose of 1mg FeCl3/mg CODo (CODo: initial COD content), the COD and α254 removal was 66% and 88%, respectively. Dosing 1mg PACl/mg CODo resulted in 44% COD and 72% α254 removal. The settle-ability of sludge generated by PACl leveled off at 252mL/g, while a better settle-ability of 154mL/g was obtained for FeCl3 after dosing 1mg coagulant/mg CODo. For ozonation, the percentage of COD and α254 removal increased as the initial COD concentration decreased. Respectively 44% COD and 77% α254 removal was observed at 112mg COD/L compared to 5% COD and 26% α254 removal at 1846mg COD/L. Subsequent activated carbon adsorption of ozonated, coagulated and untreated leachate resulted in 77%, 53% and 8% total COD removal after treatment of 6 bed volumes. Clearly showing the benefit of treating the leachate before GAC adsorption. Mathematical modeling of the experimental GAC adsorption data with Thomas and Yoon-Nelson models show that ozonation increases the adsorption capacity and breakthrough time of GAC by a factor of 2.5 compared to coagulation-flocculation.

  1. Activation and Coagulation Biomarkers are Independent Predictors for the Development of Opportunistic Disease in Patients with HIV Infection

    PubMed Central

    Rodger, Alison J; Fox, Zoe; Lundgren, Jens D; Kuller, Lew; Boesecke, Christoph; Gey, Daniela; Skoutelis, Athanassios; Goetz, Matthew Bidwell; Phillips, Andrew N

    2010-01-01

    Background Activation and coagulation biomarkers were measured within the SMART trial. Their associations with opportunistic disease (OD) in HIV-positive patients were examined. Methods Inflammatory (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], amyloid-A, and amyloid-P) and coagulation (D-dimer and prothrombin-fragment 1+2) markers were determined. Conditional logistic regression analyses were used to assess associations between these biomarkers and risk of OD. Results The 91 patients who developed an OD were matched to 182 controls. Patients with hsCRP≥5 μg/mL at baseline had a 3.5 (95%CI: 1.5-8.1) higher odds of OD versus those with hsCRP<1 μg/ml, Ptrend=0.003, and patients with IL-6≥3 pg/mL at baseline had a 2.4 (95%CI: 1.0-5.4) higher odds of OD versus those with IL-6<1.5 pg/mL, Ptrend=0.02. No other baseline biomarkers predicted development of an OD. Latest hsCRP (OR: 7.6 (95%CI: 2.0-28.5) for those with hsCRP≥5 μg/mL versus hsCRP<1 μg/mL, Ptrend=0.002), latest amyloid-A (OR: 3.8 (95%CI: 1.1-13.4) for those with amyloid-A ≥6 mg/L versus amyloid-A <2 mg/L, Ptrend=0.03) and latest IL-6 (OR 2.4 (95%CI: 0.7-8.8) for those with IL-6≥3 pg/mL versus IL-6<1.5 pg/mL, Ptrend=0.04) were also associated with developing an OD. Conclusions Higher IL-6 and hsCRP independently predicted development of OD. These biomarkers could provide additional prognostic information for predicting risk of OD. PMID:19678756

  2. Coagulation Changes During Graded Orhostatic Stress and Recovery

    NASA Astrophysics Data System (ADS)

    Goswami, Nandu; Cvirn, Gerhard; Schlagenhauf, Aaxel; Leschnik, Bettina; Koestenberger, Martin; Roessler, Andreas; Jantscher, Andreas; Waha, James Elvis; Wolf, Sabine; Vrecko, Karoline; Juergens, Guenther; Hinghofer-Szalkay, Helmut

    2013-02-01

    Background: Orthostatic stress has been introduced as a novel paradigm for activating the coagulation system. We examined whether graded orthostatic stress (using head up tilt, HUT + lower body negative pressure, LBNP) until presyncope leads to anti / pro-coagulatory changes and how rapidly they return to baseline during recovery. Methodology: Eight male subjects were enrolled in this study. Presyncopal runs were carried out using HUT + LBNP. At minute zero, the tilt table was brought from 0° (supine) to 70 ° head-up position for 4 min, after which pressure in the LBNP chamber was reduced to -15, -30, and -45 mm Hg every 4 min. At presyncope, the subjects were returned to supine position. Coagulatory responses and plasma mass density (for volume changes) were measured before, during and 20 min after the orthostatic stress. Whole blood coagulation was examined by means of thrombelastometry. Platelet aggregation in whole blood was examined by using impedance aggregometry. Thrombin generation parameters, prothrombin levels, and markers of endothelial activation were measured in plasma samples. Results: At presyncope, plasma volume was 20 % below the initial supine value. Blood cell counts, prothrombin levels, thrombin peak, endogenous thrombin potential (ETP), and tissue factor pathway inhibitor (TFPI) levels increased during the protocol, commensurate with hemoconcentration. The markers of endothelial activation (tissue factor, TF, tissue plasminogen activator, t-PA) and the markers of thrombin generation (Prothrombin fragments 1 and 2, F1+2, and thrombin-antithrombin complex, TAT) increased significantly. During recovery, all the coagulation parameters returned to initial supine values except F1 +2 and TAT. Conclusion: Head-up tilt/LBNP leads to activation of the coagulation system. Some of the markers of thrombin formation are still at higher than supine levels during recovery.

  3. Removal of Trace Pharmaceuticals from Water using coagulation and powdered activated carbon as pretreatment to ultrafiltration membrane system.

    PubMed

    Sheng, Chenguang; Nnanna, A G Agwu; Liu, Yanghe; Vargo, John D

    2016-04-15

    In this study, the efficacy of water treatment technologies: ultra-filtration (UF), powdered activated carbon (PAC), coagulation (COA) and a combination of these technologies (PAC/UF and COA/UF) to remove target pharmaceuticals (Acetaminophen, Bezafibrate, Caffeine, Carbamazepine, Cotinine, Diclofenac, Gemfibrozil, Ibuprofen, Metoprolol, Naproxen, Sulfadimethoxine, Sulfamethazine, Sulfamethoxazole, Sulfathiazole, Triclosan and Trimethoprim) was investigated. Samples of wastewater from municipal WWTPs were analyzed using direct aqueous injection High Performance Liquid Chromatography with Tandem Quadrupole Mass Spectrometric (LC/MS/MS) detection. On concentration basis, results showed an average removal efficiency of 29%, 50%, and 7%, respectively, for the UF, PAC dosage of 50ppm, and COA dosage of 10ppm. When PAC dosage of 100ppm was used as pretreatment to the combined PAC and UF in-line membrane system, a 90.3% removal efficiency was achieved. The removal efficiency of UF in tandem with COA was 33%, an increase of 4% compared with the single UF treatment. The adsorption effect of PAC combined with the physical separation process of UF revealed the best treatment strategy for removing pharmaceutical contaminant from water.

  4. Depinning as a coagulation process

    NASA Astrophysics Data System (ADS)

    İşeri, M.; Kaspar, D.; Mungan, M.

    2016-08-01

    We consider a one-dimensional model that describes the depinning of an elastic string of particles in a strongly pinning, phase-disordered periodic environment under a slowly increasing force. The evolution towards depinning occurs by the triggering of avalanches in regions of activity which are at first isolated, but later grow and merge. For large system sizes the dynamically critical behavior is dominated by the coagulation of these active regions. Our analysis and numerical simulations show that the evolution of the sizes of active regions is well described by a Smoluchowski coagulation equation, allowing us to predict correlation lengths and avalanche sizes in terms of certain moments of the size distribution.

  5. [Blood coagulation disorders in children].

    PubMed

    Kurnik, K

    2008-12-01

    As in adults, haemorrhagic or thrombotic events may also occur in children. The underlying reasons are inborn or acquired. Inherited disorders usually present during in early infancy. In order to interpret clinical and laboratory findings in children, it is necessary to keep in mind some specific paediatric features. This knowledge also forms the basic requirement to choose the appropriate therapy.

  6. Local activation of coagulation and inhibition of fibrinolysis in the lung during ventilator associated pneumonia

    PubMed Central

    Schultz, M; Millo, J; Levi, M; Hack, C; Weverling, G; Garrard, C; van der Poll, T

    2004-01-01

    Methods: Non-directed bronchial lavage (NBL) was performed on alternate days in patients expected to require mechanical ventilation for more than 5 days. A total of 28 patients were studied, nine of whom developed VAP. Results: In patients who developed VAP a significant increase in thrombin generation was observed in the airways, as reflected by a rise in the levels of thrombin-antithrombin complexes in NBL fluid accompanied by increases in soluble tissue factor and factor VIIa concentrations. The diagnosis of VAP was preceded by a decrease in fibrinolytic activity in NBL fluid. Indeed, before VAP was diagnosed clinically, plasminogen activator activity levels in NBL fluid gradually declined, which appeared to be caused by a sharp increase in NBL fluid levels of plasminogen activator inhibitor 1. Conclusion: VAP is characterised by a shift in the local haemostatic balance to the procoagulant side, which precedes the clinical diagnosis of VAP. PMID:14760153

  7. Interactions among Hageman factor (HG, Factor XII), plasma thromboplastin antecedent (PTA, Factor XI), plasma prekallikrein (PK, Fletcher factor) and high molecular weight kininogen (HMW-K, Fitzgerald factor) in blood coagulation.

    PubMed

    Saito, H; Ratnoff, O D

    1979-01-01

    Studies of plasmas from individuals with Hageman trait (factor XII deficiency), plasma thromboplastin antecedent (PTA, factor XI) deficiency, Fletcher trait (plasma prekallikrein deficiency) and Fitzgerald trait (high molecular weight-kininogen deficiency) have revealed the importance of these proteins in blood coagulation. The interactions among them, however, are not fully elucidated. We have studied these reactions by two different approaches. (1) In a purified system, high molecular weight kininogen was absolutely required for activation of PTA by HF and ellagic acid (EA). The yield of activated PTA was proportional to the amount of HF, HMW-K, and PTA in the mixtures, suggesting that these three proteins may form a complex in the presence of EA. (2) In experiments with whole plasma, we took advantage of the adsorption of EA to Sephadex gels. When normal plasma or plasma deficient in HF, PK, HMW-K or PTA was exposed to Sephadex-EA and was separated by centrifugation, each supernatant plasma except that deficient in HF shortened the prolonged partial thromboplastin time (PTT) of HF-deficient plasma. Plasma simultaneously depleted of HMW-K, PK and PTA also shortened the PTT of HF-deficient plasma and of plasma depleted of HF and PK, but had virtually no procoagulant effect upon the PTT of plasma depleted of HF and MHW-K. Thus, exposure of HF in plasma to Sephadex-EA appeared to generate a clot-promoting form of HF in the absence of other clotting factors, but its expression required the presence of HMW-K.

  8. In vitro and in vivo anti-coagulant activity and toxicological studies of marine sulfated glycosaminoglycans.

    PubMed

    Krichen, Fatma; Ghlissi, Zohra; Amor, Ikram Ben; Sayari, Nadhem; Kallel, Rim; Gargouri, Jalel; Sahnoun, Zouheir; Boudawara, Tahia; Bougatef, Ali

    2017-01-01

    The present study aimed to characterize and evaluate the in vitro and in vivo anticoagulant activity of sulfated glycosaminoglycans from the skins of smooth hound (SHSG) and grey triggerfish (GTSG). The analysis of SHSG and GTSG with acetate cellulose electrophoresis in Zn-acetate revealed the presence of hyaluronic acid (HA), chondroitin sulfate (CS) and dermatan sulfate (DS). Both glycosaminoglycans were evaluated for their in vitro anticoagulant activities using activated partial thromboplastin time (aPTT), thrombin time (TT) and prothrombine time (PT) tests. SHSG and GTSG and calciparin were tested as in vivo anticoagulants by subcutaneous (s.c) injection to adult female Wistar rats in a concentration of 75mg/kg of body weight. The administration of SHSG, GTSG and calciparin to rats induced a significant decrease of platelet rates compared to the control. The aPTT assay of SHSG and GTSG was prolonged 1.3 and 1.23-fold respectively compared with the control. Toxicity studies were performed to investigate whether or not SHSG and GTSG can cause pathological changes in the liver, proteins and DNA. The concentration and catalytic activity of liver oxidative stress markers and enzymes, respectively, as well as the observed hepatic morphological changes indicated that calciparin induced hepatic toxicity and oxidative damage in the liver. The higher activity and lower toxicity of SHSG and GTSG recommended these compounds as a better drug candidate than calciparin.

  9. Evaluation of coagulation activation after Rhinovirus infection in patients with asthma and healthy control subjects: an observational study

    PubMed Central

    2014-01-01

    Background Asthma exacerbations are frequently triggered by rhinovirus infections. Both asthma and respiratory tract infection can activate haemostasis. Therefore we hypothesized that experimental rhinovirus-16 infection and asthmatic airway inflammation act in synergy on the haemostatic balance. Methods 28 patients (14 patients with mild allergic asthma and 14 healthy non-allergic controls) were infected with low-dose rhinovirus type 16. Venous plasma and bronchoalveolar lavage fluid (BAL fluid) were obtained before and 6 days after infection to evaluate markers of coagulation activation, thrombin-antithrombin complexes, von Willebrand factor, plasmin-antiplasmin complexes, plasminogen activator inhibitor type-1, endogenous thrombin potential and tissue factor-exposing microparticles by fibrin generation test, in plasma and/or BAL fluid. Data were analysed by nonparametric tests (Wilcoxon, Mann Whitney and Spearman correlation). Results 13 patients with mild asthma (6 females, 19-29 y) and 11 healthy controls (10 females, 19-31 y) had a documented Rhinovirus-16 infection. Rhinovirus-16 challenge resulted in a shortening of the fibrin generation test in BAL fluid of asthma patients (t = -1: 706 s vs. t = 6: 498 s; p = 0.02), but not of controls (t = -1: 693 s vs. t = 6: 636 s; p = 0.65). The fold change in tissue factor-exposing microparticles in BAL fluid inversely correlated with the fold changes in eosinophil cationic protein and myeloperoxidase in BAL fluid after virus infection (r = -0.517 and -0.528 resp., both p = 0.01). Rhinovirus-16 challenge led to increased plasminogen activator inhibitor type-1 levels in plasma in patients with asthma (26.0 ng/mL vs. 11.5 ng/mL in healthy controls, p = 0.04). Rhinovirus-16 load in BAL showed a linear correlation with the fold change in endogenous thrombin potential, plasmin-antiplasmin complexes and plasminogen activator inhibitor type-1. Conclusions Experimental rhinovirus

  10. An invertebrate coagulation system activated by endotoxin: evidence for enzymatic mediation

    PubMed Central

    Young, Neal S.; Levin, Jack; Prendergast, Robert A.

    1972-01-01

    Lysates prepared from the amebocytes of Limulus polyphemus, the horseshoe crab, are gelled by endotoxin. Studies were carried out to characterize the components of amebocyte lysate and to examine the kinetics of their reaction with endotoxin. Analysis of amebocyte lysate using sucrose density gradients showed two peaks at 46% and 86% gradient volumes. G50 and G75 Sephadex column chromatography resulted in three protein peaks. One fraction contained a clottable protein, which had a molecular weight of approximately 27,000, and was heat stable. Another fraction contained a high molecular weight, heat labile material, which was activated by endotoxin and reacted with the clottable protein to form a gel. The rate of the reaction between endotoxin and amebocyte lysate was dependent upon the concentration of endotoxin and the concentration of the fraction containing the high molecular weight material. The activity of this fraction was inhibited by diisopropyl fluorophosphate, parachloromercuribenzoate, and para-chloromercuriphenyl sulfonate, suggesting that enzymatic activity depended upon serine hydroxyl and sulfhydryl groups. The reaction between endotoxin and the fractions of lysate was temperature and pH dependent. The data suggest that endotoxin activates an enzyme which then gels the clottable protein contained in amebocyte lysate. Images PMID:4624351

  11. Coagulation testing in the perioperative period.

    PubMed

    Thiruvenkatarajan, Venkatesan; Pruett, Ashlee; Adhikary, Sanjib Das

    2014-09-01

    Perioperative coagulation management is a complex task that has a significant impact on the perioperative journey of patients. Anaesthesia providers play a critical role in the decision-making on transfusion and/or haemostatic therapy in the surgical setting. Various tests are available in identifying coagulation abnormalities in the perioperative period. While the rapidly available bedside haemoglobin measurements can guide the transfusion of red blood cells, blood product administration is guided by many in vivo and in vitro tests. The introduction of newer anticoagulant medications and the implementation of the modified in vivo coagulation cascade have given a new dimension to the field of perioperative transfusion medicine. A proper understanding of the application and interpretation of the coagulation tests is vital for a good perioperative outcome.

  12. Coagulation assays and anticoagulant monitoring.

    PubMed

    Funk, Dorothy M Adcock

    2012-01-01

    Anticoagulant therapy, including conventional agents and a variety of new oral, fast-acting drugs, is prescribed for millions of patients annually. Each anticoagulant varies in its effect on routine and specialty coagulation assays and each drug may require distinct laboratory assay(s) to measure drug concentration or activity. This review provides an overview of the assorted assays that can measure anticoagulant drug concentration or activity and includes key assay interferences. The effect of these conventional and new anticoagulant agents on specialty coagulation assays used to evaluate for bleeding or clotting disorders, and whether this impact is physiological or factitious, is included. Also provided is a short review of superwarfarin poisoning and features distinguishing this from warfarin overdose. Knowledge of clinically significant pearls and pitfalls pertinent to coagulation assays in relation to anticoagulant therapy are important to optimize patient care.

  13. Clinical and prognostic significance of coagulation assays in lung cancer.

    PubMed

    Tas, Faruk; Kilic, Leyla; Serilmez, Murat; Keskin, Serkan; Sen, Fatma; Duranyildiz, Derya

    2013-03-01

    Activation of coagulation and fibrinolysis is frequently encountered among cancer patients. Such tumors are supposed to be associated with higher risk of invasion, metastases and eventually worse outcome. The aim of this study is to explore the prognostic value of blood coagulation tests for lung cancer patients. The study comprised 110 lung cancer patients. Pretreatment blood coagulation tests including PT, aPTT, PTA, INR, D-dimer, fibrinogen levels and platelet counts were evaluated. The plasma level of all coagulation tests revealed statistically significant difference between patient and control group (p < 0.001). There was a significant association between D-Dimer levels and histological subtypes of NSCLC, pointing an elevated plasma D-dimer level in squamous cell cancer (p = 0.035). Patients with extensive stage SCLC exhibited evidently higher levels of D-Dimer, INR and PLT (p = 0.037, p = 0.042, p = 0.04, respectively). Prolongation of PT and INR had statistically significant adverse effect on survival (p = 0.05 and p = 0.014, respectively). Although prolonged aPTT and high levels of D-dimer was associated with worse survival, the difference was not statistically significant (p = 0.117, p = 0.104). Multivariate analysis revealed INR as the sole independent prognostic variable among coagulation parameters (p = 0.05). In conclusion, elevation of PT and INR are associated with decreased survival in lung cancer patients.

  14. 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).

  15. Evaluation of cytotoxicity and inflammatory activity of wastewater collected from a textile factory before and after treatment by coagulation-flocculation methods.

    PubMed

    Makene, Vedastus W; Tijani, Jimoh O; Petrik, Leslie F; Pool, Edmund J

    2016-08-01

    Effective treatment of textile effluent prior to discharge is necessary in order to avert the associated adverse health impacts on human and aquatic life. In the present investigation, coagulation/flocculation processes were evaluated for the effectiveness of the individual treatment. Effectiveness of the treatment was evaluated based on the physicochemical characteristics. The quality of the pre-treated and post-flocculation treated effluent was further evaluated by determination of cytotoxicity and inflammatory activity using RAW264.7 cell cultures. Cytotoxicity was determined using WST-1 assay. Nitric oxide (NO) and interleukin 6 (IL-6) were used as biomarkers of inflammation. NO was determined in cell culture supernatant using the Griess reaction assay. The IL-6 secretion was determined using double antibody sandwich enzyme linked immunoassay (DAS ELISA). Cytotoxicity results show that raw effluent reduced the cell viability significantly (P < 0.001) compared to the negative control. All effluent samples treated by coagulation/flocculation processes at 1 in 100 dilutions had no cytotoxic effects on RAW264.7 cells. The results on inflammatory activities show that the raw effluent and effluent treated with 1.6 g/L of Fe-Mn oxide induced significantly (P < 0.001) higher NO production than the negative control. The inflammatory results further show that the raw effluent induced significantly (P < 0.001) higher production of IL-6 than the negative control. Among the coagulants/flocculants evaluated Al2(SO4)3.14H2O at a dosage of 1.6 g/L was the most effective to remove both toxic and inflammatory pollutants. In conclusion, the inflammatory responses in RAW264.7 cells can be used as sensitive biomarkers for monitoring the effectiveness of coagulation/flocculation processes used for textile effluent treatment.

  16. Coagulation fibrinolysis in sickle-cell disease

    PubMed Central

    Gordon, P. A.; Breeze, G. R.; Mann, J. R.; Stuart, J.

    1974-01-01

    A study of fibrinolytic activity in sickle-cell patients during asymptomatic periods has shown a normal fibrinolytic response to exercise and local heat to the arm. During vasoocclusive crises there was no significant decrease in fibrinolytic activity. These results contrast with earlier reports of decreased fibrinolysis during crisis and a suggestion that fibrinolytic activators might be of value in preventing vasoocclusive episodes. Patients in painful crisis showed a significant rise in fibrinogen concentration and fall in platelet count. The former may contribute to localized vascular sludging by increasing whole-blood viscosity, while the latter probably results from local trapping of platelets in areas of sickling or from subsequent splenic sequestration of damaged platelets. There was no evidence of disseminated, as opposed to localized, intravascular coagulation during crisis. PMID:4412492

  17. Cerebral blood flow response to functional activation

    PubMed Central

    Paulson, Olaf B; Hasselbalch, Steen G; Rostrup, Egill; Knudsen, Gitte Moos; Pelligrino, Dale

    2010-01-01

    Cerebral blood flow (CBF) and cerebral metabolic rate are normally coupled, that is an increase in metabolic demand will lead to an increase in flow. However, during functional activation, CBF and glucose metabolism remain coupled as they increase in proportion, whereas oxygen metabolism only increases to a minor degree—the so-called uncoupling of CBF and oxidative metabolism. Several studies have dealt with these issues, and theories have been forwarded regarding the underlying mechanisms. Some reports have speculated about the existence of a potentially deficient oxygen supply to the tissue most distant from the capillaries, whereas other studies point to a shift toward a higher degree of non-oxidative glucose consumption during activation. In this review, we argue that the key mechanism responsible for the regional CBF (rCBF) increase during functional activation is a tight coupling between rCBF and glucose metabolism. We assert that uncoupling of rCBF and oxidative metabolism is a consequence of a less pronounced increase in oxygen consumption. On the basis of earlier studies, we take into consideration the functional recruitment of capillaries and attempt to accommodate the cerebral tissue's increased demand for glucose supply during neural activation with recent evidence supporting a key function for astrocytes in rCBF regulation. PMID:19738630

  18. Pharmacokinetics of danaparoid sodium, dalteparin sodium and heparin determined by inhibitory effect on the activated coagulation factor X activity after single intravenous administration in rabbits.

    PubMed

    Ishida, M; Nakada, Y; Horiuchi, M; Sakamoto, F

    1998-08-01

    The inhibitory effect on the activated coagulation factor X activity (anti-Xa activity) in plasma and urine of danaparoid sodium (DAS, CAS 9005-49-6) was compared with that of dalteparin sodium (DLS, CAS 9041-08-1) and heparin (CAS 9005-49-6) after single intravenous administration at a dose of 640 anti-Xa U/kg to male rabbits. The elimination of half-life of DAS was 9.90 h and was 6.0 times longer than that of DLS and 16.5 times longer than that of heparin. The area under the plasma concentration-time curve (AUC) of DAS was 47.13 +/- 14.55 anti-Xa U.h/ml and was 2.4 times larger than that of DLS and 2.9 times larger than that of heparin. The urinary cumulative excretion of anti-Xa activity of DAS and DLS was 42.6 +/- 6.4% and 16.4 +/- 0.8% of dose, respectively, in 24 h after dosing, respectively. But the anti-Xa activity in urine was not detected at any sampling points after administration of heparin. DAS has a longer elimination half-life and a higher renal excretion of anti-Xa activity than that of DLS and heparin. Therefore, in comparison to DLS and heparin, it seems that the anticoagulant activity of DAS has a long duration.

  19. Virus inactivation in aluminum and polyaluminum coagulation.

    PubMed

    Matsui, Yoshihiko; Matsushita, Taku; Sakuma, Satoru; Gojo, Takahito; Mamiya, Teppei; Suzuoki, Hiroshi; Inoue, Takanobu

    2003-11-15

    Inorganic aluminum salts, such as aluminum sulfate, are coagulants that cause small particles, such as bacteria and viruses as well as inorganic particles, to destabilize and combine into larger aggregates. In this investigation, batch coagulation treatments of water samples spiked with Qbeta, MS2, T4, and P1 viruses were conducted with four different aluminum coagulants. The total infectious virus concentration in the suspension of floc particles that eventually formed by dosing with coagulant was measured after the floc particles were dissolved by raising the pH with an alkaline beef extract solution. The virus concentrations were extremely reduced after the water samples were dosed with aluminum coagulants. Viruses mixed with and adsorbed onto preformed aluminum hydroxide floc were, however, completely recovered after the floc dissolution. These results indicated that the aluminum coagulation process inactivates viruses. Virucidal activity was most prominent with the prehydrolyzed aluminum salt coagulant, polyaluminum chloride (PACl). Virucidal activity was lower in river water than in ultrapure water--natural organic matter in the river water depressed the virucidal activity. Mechanisms and kinetics of the virus inactivation were discussed. Our results suggest that intermediate polymers formed during hydrolysis of the aluminum coagulants sorbed strongly to viruses, either rendering them inactive or preventing infectivity.

  20. MASP-3 is the exclusive pro-factor D activator in resting blood: the lectin and the alternative complement pathways are fundamentally linked

    PubMed Central

    Dobó, József; Szakács, Dávid; Oroszlán, Gábor; Kortvely, Elod; Kiss, Bence; Boros, Eszter; Szász, Róbert; Závodszky, Péter; Gál, Péter; Pál, Gábor

    2016-01-01

    MASP-3 was discovered 15 years ago as the third mannan-binding lectin (MBL)-associated serine protease of the complement lectin pathway. Lacking any verified substrate its role remained ambiguous. MASP-3 was shown to compete with a key lectin pathway enzyme MASP-2 for MBL binding, and was therefore considered to be a negative complement regulator. Later, knock-out mice experiments suggested that MASP-1 and/or MASP-3 play important roles in complement pro-factor D (pro-FD) maturation. However, studies on a MASP-1/MASP-3-deficient human patient produced contradicting results. In normal resting blood unperturbed by ongoing coagulation or complement activation, factor D is present predominantly in its active form, suggesting that resting blood contains at least one pro-FD activating proteinase that is not a direct initiator of coagulation or complement activation. We have recently showed that all three MASPs can activate pro-FD in vitro. In resting blood, however, using our previously evolved MASP-1 and MASP-2 inhibitors we proved that neither MASP-1 nor MASP-2 activates pro-FD. Other plasma proteinases, particularly MASP-3, remained candidates for that function. For this study we evolved a specific MASP-3 inhibitor and unambiguously proved that activated MASP-3 is the exclusive pro-FD activator in resting blood, which demonstrates a fundamental link between the lectin and alternative pathways. PMID:27535802

  1. Breaking boundaries—coagulation and fibrinolysis at the neurovascular interface

    PubMed Central

    Bardehle, Sophia; Rafalski, Victoria A.; Akassoglou, Katerina

    2015-01-01

    Blood proteins at the neurovascular unit (NVU) are emerging as important molecular determinants of communication between the brain and the immune system. Over the past two decades, roles for the plasminogen activation (PA)/plasmin system in fibrinolysis have been extended from peripheral dissolution of blood clots to the regulation of central nervous system (CNS) functions in physiology and disease. In this review, we discuss how fibrin and its proteolytic degradation affect neuroinflammatory, degenerative and repair processes. In particular, we focus on novel functions of fibrin—the final product of the coagulation cascade and the main substrate of plasmin—in the activation of immune responses and trafficking of immune cells into the brain. We also comment on the suitability of the coagulation and fibrinolytic systems as potential biomarkers and drug targets in diseases, such as multiple sclerosis (MS), Alzheimer’s disease (AD) and stroke. Studying coagulation and fibrinolysis as major molecular pathways that regulate cellular functions at the NVU has the potential to lead to the development of novel strategies for the detection and treatment of neurologic diseases. PMID:26441525

  2. Inhibiting the intrinsic pathway of coagulation with a FXII-targeting RNA Aptamer

    PubMed Central

    Woodruff, R. S.; Xu, Y.; Layzer, J.; Wu, W.; Ogletreee, M.L.; Sullenger, B.A.

    2013-01-01

    Background Exposure of the plasma protein factor XII to an anionic surface generates activated factor XII that not only triggers the intrinsic pathway of blood coagulation through the activatio of factor XI, but also mediates various vascular responses through activation of the plasma contact system. While deficiencies of factor XII are not associated with excessive bleeding, thrombosis models in factor deficient animals have suggested that this protein contributes to stable thrombus formation. Therefore, factor XII has emerged as an attractive therapeutic target to treat or prevent pathological thrombosis formation without increasing the risk for hemorrhage. Objectives Utilizing an in vitro directed evolution and chemical biology approach, we sought to isolate a nuclease resistant RNA aptamer that binds specifically to factor XII and directly inhibits factor XII coagulant function. Methods and Results Herein, we describe the isolation and characterization of a high affinity RNA aptamer targeting factor XII/XIIa that dose dependently prolongs fibrin clot formation and thrombin generation in clinical coagulation assays. This aptamer functions as a potent anticoagulant by inhibiting the autoactivation of factor XII, as well as inhibiting intrinsic pathway activation (factor XI activation). However, the aptamer does not affect the factor XIIa-mediated activation of the proinflammatory kallikrein-kinin system (plasma kallikrein activation). Conclusions We have generated a specific and potent factor XII/XIIa aptamer anticoagulant that offers targeted inhibition of discrete macromolecular interactions involved in the activation of the intrinsic pathway of blood coagulation. PMID:23692437

  3. Cerebral blood volume changes during brain activation

    PubMed Central

    Krieger, Steffen Norbert; Streicher, Markus Nikolar; Trampel, Robert; Turner, Robert

    2012-01-01

    Cerebral blood volume (CBV) changes significantly with brain activation, whether measured using positron emission tomography, functional magnetic resonance imaging (fMRI), or optical microscopy. If cerebral vessels are considered to be impermeable, the contents of the skull incompressible, and the skull itself inextensible, task- and hypercapnia-related changes of CBV could produce intolerable changes of intracranial pressure. Because it is becoming clear that CBV may be useful as a well-localized marker of neural activity changes, a resolution of this apparent paradox is needed. We have explored the idea that much of the change in CBV is facilitated by exchange of water between capillaries and surrounding tissue. To this end, we developed a novel hemodynamic boundary-value model and found approximate solutions using a numerical algorithm. We also constructed a macroscopic experimental model of a single capillary to provide biophysical insight. Both experiment and theory model capillary membranes as elastic and permeable. For a realistic change of input pressure, a relative pipe volume change of 21±5% was observed when using the experimental setup, compared with the value of approximately 17±1% when this quantity was calculated from the mathematical model. Volume, axial flow, and pressure changes are in the expected range. PMID:22569192

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

    SciTech Connect

    Borensztajn, Keren S. . E-mail: K.S.Borensztajn@amc.uva.nl; Bijlsma, Maarten F.; Groot, Angelique P.; Brueggemann, Lois W.; Versteeg, Henri H.; Reitsma, Pieter H.; Peppelenbosch, Maikel P.; Spek, C. Arnold

    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 with 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.

  5. Indolic uremic solutes enhance procoagulant activity of red blood cells through phosphatidylserine exposure and microparticle release.

    PubMed

    Gao, Chunyan; Ji, Shuting; Dong, Weijun; Qi, Yushan; Song, Wen; Cui, Debin; Shi, Jialan

    2015-10-28

    Increased accumulation of indolic uremic solutes in the blood of uremic patients contributes to the risk of thrombotic events. Red blood cells (RBCs), the most abundant blood cells in circulation, may be a privileged target of these solutes. However, the effect of uremic solutes indoxyl sulfate (IS) and indole-3-acetic acid (IAA) on procoagulant activity (PCA) of erythrocyte is unclear. Here, RBCs from healthy adults were treated with IS and IAA (mean and maximal concentrations reported in uremic patients). Phosphatidylserine (PS) exposure of RBCs and their microparticles (MPs) release were labeled with Alexa Fluor 488-lactadherin and detected by flow cytometer. Cytosolic Ca(2+) ([Ca(2+)]) with Fluo 3/AM was analyzed by flow cytometer. PCA was assessed by clotting time and purified coagulation complex assays. We found that PS exposure, MPs generation, and consequent PCA of RBCs at mean concentrations of IS and IAA enhanced and peaked in maximal uremic concentrations. Moreover, 128 nM lactadherin, a PS inhibitor, inhibited over 90% PCA of RBCs and RMPs. Eryptosis or damage, by indolic uremic solutes was due to, at least partially, the increase of cytosolic [Ca(2+)]. Our results suggest that RBC eryptosis in uremic solutes IS and IAA plays an important role in thrombus formation through releasing RMPs and exposing PS. Lactadherin acts as an efficient anticoagulant in this process.

  6. The susceptibility of plasma coagulation factor XI to nitration and peroxynitrite action.

    PubMed

    Ponczek, Michał Błażej

    2016-10-01

    Coagulation factor XI is present in blood plasma as the zymogen, like other serine proteases of hemostatic system, but as the only coagulation factor forms 140-160kDa homodimers. Its activation is induced by thrombin, and a positive feedback increases the generation of the extra thrombin. Experimental and clinical observations confirm protective roles of factor XI deficiencies in certain types of thromboembolic disorders. Thromboembolism still causes serious problems for modern civilization. Diseases associated with the blood coagulation system are often associated with inflammation and oxidative stress. Peroxynitrite is produced from nitric oxide and superoxide in inflammatory diseases. The aim of the current study is to evaluate effects of nitrative stress triggered by peroxynitrite on coagulation factor XI in human plasma employing biochemical and bioinformatic methods. The amidolytic assay shows increase in factor XI activity triggered by peroxynitrite. Peroxynitrite interferes factor XI by nitration and fragmentation, which is demonstrated by immunoprecipitation followed by western blotting. Nitrated factor XI is even present in control blood plasma. The results suggest possible modifications of factor XI on the molecular level. Computer simulations show tyrosine residues as targets of peroxynitrite action. The modifications induced by peroxynitrite in factor XI might be important in thrombotic disorders.

  7. Pretreatment with β-Boswellic Acid Improves Blood Stasis Induced Endothelial Dysfunction: Role of eNOS Activation

    PubMed Central

    Wang, Mingming; Chen, Minchun; Ding, Yi; Zhu, Zhihui; Zhang, Yikai; Wei, Peifeng; Wang, Jingwen; Qiao, Yi; Li, Liang; Li, Yuwen; Wen, Aidong

    2015-01-01

    Vascular endothelial cells play an important role in modulating anti-thrombus and maintaining the natural function of vascular by secreting many active substances. β-boswellic acid (β-BA) is an active triterpenoid compound from the extract of boswellia serrate. In this study, it is demonstrated that β-BA ameliorates plasma coagulation parameters, protects endothelium from blood stasis induced injury and prevents blood stasis induced impairment of endothelium-dependent vasodilatation. Moreover, it is found that β-BA significantly increases nitric oxide (NO) and cyclic guanosine 3’, 5’-monophosphate (cGMP) levels in carotid aortas of blood stasis rats. To stimulate blood stasis-like conditions in vitro, human umbilical vein endothelial cells (HUVECs) were exposed to transient oxygen and glucose deprivation (OGD). Treatment of β-BA significantly increased intracellular NO level. Western blot and immunofluorescence as well as immunohistochemistry reveal that β-BA increases phosphorylation of enzyme nitric oxide synthase (eNOS) at Ser1177. In addition, β-BA mediated endothelium-dependent vasodilatation can be markedly blocked by eNOS inhibitor L-NAME in blood stasis rats. In OGD treated HUEVCs, the protective effect of β-BA is attenuated by knockdown of eNOS. In conclusion, the above findings provide convincing evidence for the protective effects of β-BA on blood stasis induced endothelial dysfunction by eNOS signaling pathway. PMID:26482008

  8. Disruption and activation of blood platelets in contact with an antimicrobial composite coating consisting of a pyridinium polymer and AgBr nanoparticles.

    PubMed

    Stevens, Kris N; Knetsch, Menno L; Sen, Ayusman; Sambhy, Varun; Koole, Leo H

    2009-09-01

    Composite materials made up from a pyridinium polymer matrix and silver bromide nanoparticles embedded therein feature excellent antimicrobial properties. Most probably, the antimicrobial activity is related to the membrane-disrupting effect of both the polymer matrix and Ag(+) ions; both may work synergistically. One of the most important applications of antimicrobial materials would be their use as surface coatings for percutaneous (skin-penetrating) catheters, such as central venous catheters (CVCs). These are commonly used in critical care, and serious complications due to bacterial infection occur frequently. This study aimed at examining the possible effects of a highly antimicrobial pyridinium polymer/AgBr composite on the blood coagulation system, i.e., (i) on the coagulation cascade, leading to the formation of thrombin and a fibrin cross-linked network, and (ii) on blood platelets. Evidently, pyridinium/AgBr composites could not qualify as coatings for CVCs if they trigger blood coagulation. Using a highly antimicrobial composite of poly(4-vinylpyridine)-co-poly(4-vinyl-N-hexylpyridinium bromide) (NPVP) and AgBr nanoparticles as a thin adherent surface coating on Tygon elastomer tubes, it was found that contacting blood platelets rapidly acquire a highly activated state, after which they become substantially disrupted. This implies that NPVP/AgBr is by no means blood-compatible. This disqualifies the material for use as a CVC coating. This information, combined with earlier findings on the hemolytic effects (i.e., disruption of contacting red blood cells) of similar materials, implies that this class of antimicrobial materials affects not only bacteria but also mammalian cells. This would render them more useful outside the biomedical field.

  9. Change in blood coagulation indices as a function of the incubation period of plasma in a constant magnetic field. [considering heparin tolerance and recalcification

    NASA Technical Reports Server (NTRS)

    Yepishina, S. G.

    1974-01-01

    The influence of a constant magnetic field (CMF) with a strength of 250 and 2500 oersteds on the recalcification reaction and the tolerance of plasma to heparin was studied as a function of the exposure time of the plasma to the CMF. The maximum and reliable change in the activation of the coagulatory system of the blood was observed after a 20-hour incubation of the plasma in a CMF. As the exposure time increased, the recalcification reaction changed insigificantly; the difference between the mean arithmetic of the experiment and control values was not statistically reliable. The tolerance of the plasma to heparin as a function of the exposure time to the CMF of the plasma was considerably modified, an was statistically reliable.

  10. 1918 pandemic influenza virus and Streptococcus pneumoniae co-infection results in activation of coagulation and widespread pulmonary thrombosis in mice and humans.

    PubMed

    Walters, Kathie-Anne; D'Agnillo, Felice; Sheng, Zong-Mei; Kindrachuk, Jason; Schwartzman, Louis M; Kuestner, Rolf E; Chertow, Daniel S; Golding, Basil T; Taubenberger, Jeffery K; Kash, John C

    2016-01-01

    To study bacterial co-infection following 1918 H1N1 influenza virus infection, mice were inoculated with the 1918 influenza virus, followed by Streptococcus pneumoniae (SP) 72 h later. Co-infected mice exhibited markedly more severe disease, shortened survival time and more severe lung pathology, including widespread thrombi. Transcriptional profiling revealed activation of coagulation only in co-infected mice, consistent with the extensive thrombogenesis observed. Immunohistochemistry showed extensive expression of tissue factor (F3) and prominent deposition of neutrophil elastase on endothelial and epithelial cells in co-infected mice. Lung sections of SP-positive 1918 autopsy cases showed extensive thrombi and prominent staining for F3 in alveolar macrophages, monocytes, neutrophils, endothelial and epithelial cells, in contrast to co-infection-positive 2009 pandemic H1N1 autopsy cases. This study reveals that a distinctive feature of 1918 influenza virus and SP co-infection in mice and humans is extensive expression of tissue factor and activation of the extrinsic coagulation pathway leading to widespread pulmonary thrombosis.

  11. Innate immunity, coagulation and placenta-related adverse pregnancy outcomes.

    PubMed

    Li, Min; Huang, S Joseph

    2009-12-01

    Maternal immunity undergoes subtle adjustment in order to tolerate the semi-allogeneic embryo and maintain the host defense against potential pathogens. Concomitantly, coagulation systems change from an anti-coagulant state to a pro-coagulant state to meet the hemostatic challenge of placentation and delivery. Innate immunity and blood coagulation systems are the first line of defense to protect a host against exogenous challenges, including alloantigens and mechanical insults, and preserve the integrity of an organism. The interactions between coagulation and immune systems have been extensively studied. Immune cells play a pivotal role in the initiation of the coagulation cascade, whereas coagulation proteases display substantial immuno-modulatory effects. Upon exogenous challenges, the immune and coagulation systems are capable of potentiating each other leading to a vicious cycle. Natural killer (NK) cells, macrophages (Mphis) and dendritic cells (DCs) are three major innate immune cells that have been demonstrated to play essential roles in early pregnancy. However, immune maladaptation and hemostatic imbalance have been suggested to be responsible for adverse pregnant outcomes, such as preeclampsia (PE), miscarriage, recurrent spontaneous abortion (RSA) and intrauterine growth restriction (IUGR). In this review, we will summarize the mutual regulation between blood coagulation and innate immune systems as well as their roles in the maintenance of normal pregnancy and in the pathogenesis of adverse pregnancy outcomes.

  12. Whole blood tissue factor procoagulant activity is elevated in patients with sickle cell disease.

    PubMed

    Key, N S; Slungaard, A; Dandelet, L; Nelson, S C; Moertel, C; Styles, L A; Kuypers, F A; Bach, R R

    1998-06-01

    We developed a simple assay for the measurement of tissue factor procoagulant activity (TF PCA) in whole blood samples that avoids the need for mononuclear cell isolation. This method combines convenience of sample collection and processing with a high degree of sensitivity and specificity for TF. Using this method, we have determined that TF PCA is detectable in whole blood samples from normal individuals, which is itself a novel observation. Essentially all PCA could be shown to be localized in the mononuclear cell fraction of blood. Compared with controls, whole blood TF levels were significantly (P < .000001) elevated in patients with sickle cell disease (SCD), regardless of the subtype of hemoglobinopathy (SS or SC disease). No significant difference in TF PCA was observed between patients in pain crisis compared with those in steady-state disease. Because TF functions as cofactor in the proteolytic conversion of FVII to FVIIa in vitro, it was expected that an increase in circulating TF PCA would lead to an increased in vivo generation of FVIIa. On the contrary, FVIIa levels were actually decreased in the plasma of patients with SCD. Plasma TF pathway inhibitor (TFPI) antigen levels were normal in SCD patients, suggesting that accelerated clearance of FVIIa by the TFPI pathway was not responsible for the reduced FVIIa levels. We propose that elevated levels of circulating TF PCA may play an important role in triggering the activation of coagulation known to occur in patients with SCD. Because TF is the principal cellular ligand for FVIIa, it is possible that increased binding to TF accounts for the diminished plasma FVIIa levels.

  13. Effect of blood activity on dosimetric calculations for radiopharmaceuticals

    NASA Astrophysics Data System (ADS)

    Zvereva, Alexandra; Petoussi-Henss, Nina; Li, Wei Bo; Schlattl, Helmut; Oeh, Uwe; Zankl, Maria; Graner, Frank Philipp; Hoeschen, Christoph; Nekolla, Stephan G.; Parodi, Katia; Schwaiger, Markus

    2016-11-01

    The objective of this work was to investigate the influence of the definition of blood as a distinct source on organ doses, associated with the administration of a novel radiopharmaceutical for positron emission tomography-computed tomography (PET/CT) imaging—(S)-4-(3-18F-fluoropropyl)-L-glutamic acid (18F-FSPG). Personalised pharmacokinetic models were constructed based on clinical PET/CT images from five healthy volunteers and blood samples from four of them. Following an identifiability analysis of the developed compartmental models, person-specific model parameters were estimated using the commercial program SAAM II. Organ doses were calculated in accordance to the formalism promulgated by the Committee on Medical Internal Radiation Dose (MIRD) and the International Commission on Radiological Protection (ICRP) using specific absorbed fractions for photons and electrons previously derived for the ICRP reference adult computational voxel phantoms. Organ doses for two concepts were compared: source organ activities in organs parenchyma with blood as a separate source (concept-1); aggregate activities in perfused source organs without blood as a distinct source (concept-2). Aggregate activities comprise the activities of organs parenchyma and the activity in the regional blood volumes (RBV). Concept-1 resulted in notably higher absorbed doses for most organs, especially non-source organs with substantial blood contents, e.g. lungs (92% maximum difference). Consequently, effective doses increased in concept-1 compared to concept-2 by 3-10%. Not considering the blood as a distinct source region leads to an underestimation of the organ absorbed doses and effective doses. The pronounced influence of the blood even for a radiopharmaceutical with a rapid clearance from the blood, such as 18F-FSPG, suggests that blood should be introduced as a separate compartment in most compartmental pharmacokinetic models and blood should be considered as a distinct source in

  14. Viscoelasticity and Ultrastructure in Coagulation and Inflammation: Two Diverse Techniques, One Conclusion.

    PubMed

    Swanepoel, Albe C; Nielsen, Vance G; Pretorius, Etheresia

    2015-08-01

    The process of blood clotting has been studied for centuries. A synopsis of current knowledge pertaining to haemostasis and the blood components, including platelets and fibrin networks which are closely involved in coagulation, are discussed. Special emphasis is placed on tissue factor (TF), calcium and thrombin since these components have been implicated in both the coagulation process and inflammation. Analysis of platelets and fibrin morphology indicate that calcium, tissue factor and thrombin at concentrations used during viscoelastic analysis (with thromboelastography or TEG) bring about alterations in platelet and fibrin network ultrastructure, which is similar to that seen in inflammation. Scanning electron microscopy indicated that, when investigating platelet structure in disease, addition of TF, calcium or thrombin will mask disease-induced alterations associated with platelet activation. Therefore, washed platelets without any additives is preferred for morphological analysis. Furthermore, morphological and viscoelastic analysis confirmed that thrombin activation is the preferred method of fibrin activation when investigating fibrin network ultrastructure.

  15. Proteases in blood clotting.

    PubMed

    Walsh, Peter N; Ahmad, Syed S

    2002-01-01

    The serine proteases, cofactors and cell-receptor molecules that comprise the haemostatic mechanism are highly conserved modular proteins that have evolved to participate in biochemical reactions in blood coagulation, anticoagulation and fibrinolysis. Blood coagulation is initiated by exposure of tissue factor, which forms a complex with factor VIIa and factor X, which results in the generation of small quantities of thrombin and is rapidly shutdown by the tissue factor pathway inhibitor. The generation of these small quantities of thrombin then activates factor XI, resulting in a sequence of events that lead to the activation of factor IX, factor X and prothrombin. Sufficient thrombin is generated to effect normal haemostasis by converting fibrinogen into fibrin. The anticoagulant pathways that regulate blood coagulation include the protein C anticoagulant mechanism, the serine protease inhibitors in plasma, and the Kunitz-like inhibitors, tissue factor pathway inhibitor and protease nexin 2. Finally, the fibrinolytic mechanism that comprises the activation of plasminogen into plasmin prevents excessive fibrin accumulation by promoting local dissolution of thrombi and promoting wound healing by reestablishment of blood flow.

  16. Does Bicarbonate Correct Coagulation Function Impaired by Acidosis in Swine?

    DTIC Science & Technology

    2006-07-01

    L bicarbonate to a pH of 7.4 (A-Bi, n 6). Blood samples were taken at base - line, 15 minutes after acidosis induction, and 15 minutes after...Behring, Deerfield, IL). Plasma fibrinogen concentra- tion was determined by BCS Coagulation System based on fibrinogen functional activities in the...0.05). Hct decreased from 31 1% to 28 1% in A-LR and from 29 1% to 25 1% in A-Bi (p 0.05). Arterial base excess (BE) dropped from 7.1 0.7

  17. Powdered activated carbon coupled with enhanced coagulation for natural organic matter removal and disinfection by-product control: application in a Western Australian water treatment plant.

    PubMed

    Kristiana, Ina; Joll, Cynthia; Heitz, Anna

    2011-04-01

    The removal of organic precursors of disinfection by-products (DBPs), i.e. natural organic matter (NOM), prior to disinfection and distribution is considered as the most effective approach to minimise the formation of DBPs. This study investigated the impact of the addition of powdered activated carbon (PAC) to an enhanced coagulation treatment process at an existing water treatment plant on the efficiency of NOM removal, the disinfection behaviour of the treated water, and the water quality in the distribution system. This is the first comprehensive assessment of the efficacy of plant-scale application of PAC combined with enhanced coagulation on an Australian source water. As a result of the PAC addition, the removal of NOM improved by 70%, which led to a significant reduction (80-95%) in the formation of DBPs. The water quality in the distribution system also improved, indicated by lower concentrations of DBPs in the distribution system and better maintenance of disinfectant residual at the extremities of the distribution system. The efficacy of the PAC treatment for NOM removal was shown to be a function of the characteristics of the NOM and the quality of the source water, as well as the PAC dose. PAC treatment did not have the capacity to remove bromide ion, resulting in the formation of more brominated DBPs. Since brominated DBPs have been found to be more toxic than their chlorinated analogues, their preferential formation upon PAC addition must be considered, especially in source waters containing high concentrations of bromide.

  18. Blood group isoantibody stimulation in man by feeding blood group-active bacteria

    PubMed Central

    Springer, Georg F.; Horton, Richard E.

    1969-01-01

    It was investigated whether or not the human blood group isoantibodies A and B could be induced by immunogenic stimuli via natural routes with a kind of antigenic substance to which all humans are commonly exposed, or if the appearance of these antibodies is independent of antigenic stimuli as has long been believed. Escherichia coli O86, which possess high human blood group B and faint A activity in vitro, were fed to healthy humans and those with intestinal disorders. 80% of the sick individuals of blood group O and A responded with a significant rise of anti-B antibodies which was frequently de novo in infants; significant increase of anti-A isoantibodies among blood group O individuals was less frequent. Over one-third of the healthy individuals also had a significant isoantibody increase. Intestinal lesions favor isoantibody stimulation by intestinal bacteria; this view was supported by the study of control infants. Persons of blood group A responded more frequently with anti-B and anti-E. coli O86 antibody production than those of blood group O. Isoantibody increase was accompanied with antibody rise against E. coli O86. Inhalation of E. coli O86 or blood group AH(O)-specific hog mucin also evoked isoantibodies. The induced isoantibodies were specifically inhibited by small amounts of human blood group substances. E. coli O86-induced anti-blood group antibodies in germ-free chickens and preexisting blood group antibodies in ordinary chickens were neutralized by intravenous injection of E. coli O86 lipopolysaccharide. This study demonstrates that human isoantibodies A and B are readily elicited via physiological routes, by blood group-active E. coli, provided the genetically determined apparatus of the host is responsive. Antibodies against a person's own blood group were not formed. Interpretation of these results permits some careful generalizations as to the origin of so-called natural antibodies. PMID:4893685

  19. Identification of highly active flocculant proteins in bovine blood.

    PubMed

    Piazza, George J; Nuñez, Alberto; Garcia, Rafael A

    2012-03-01

    Synthetic polymeric flocculants are used extensively for wastewater remediation, soil stabilization, and reduction in water leakage from unlined canals. Sources of highly active, inexpensive, renewable flocculants are needed to replace synthetic flocculants. High kaolin flocculant activity was documented for bovine blood (BB) and blood plasma with several anticoagulant treatments. BB serum also had high flocculant activity. To address the hypothesis that some blood proteins have strong flocculating activity, the BB proteins were separated by SEC. Then, the major proteins of the flocculant-active fractions were separated by SDS-PAGE. Identity of the major protein components was determined by tryptic digestion and peptide analysis by MALDI TOF MS. The sequence of selected peptides was confirmed using TOF/TOF-MS/MS fragmentation. Hemoglobin dimer (subunits α and β) was identified as the major protein component of the active fraction in BB; its high flocculation activity was confirmed by testing a commercial sample of hemoglobin. In the same manner, three proteins from blood plasma (fibrinogen, γ-globulin, α-2-macroglobulin) were found to be highly active flocculants, but bovine serum albumin, α-globulin, and β-globulin were not flocculants. On a mass basis, hemoglobin, γ-globulin, α-2-macroglobulin were as effective as anionic polyacrylamide (PAM), a widely used synthetic flocculant. The blood proteins acted faster than PAM, and unlike PAM, the blood proteins flocculants did not require calcium salts for their activity.

  20. Coagulation sensors based on magnetostrictive delay lines for biomedical and chemical engineering applications

    NASA Astrophysics Data System (ADS)

    Maliaritsi, E.; Zoumpoulakis, L.; Simitzis, J.; Vassiliou, P.; Hristoforou, E.

    2006-04-01

    Coagulation sensors based on the magnetostrictive delay line technique are presented in this paper. They are based on magnetostrictive ribbons and are used for measuring the coagulation, curing or solidification time of different liquids. Experimental results indicate that the presented sensing elements can determine the blood coagulation with remarkable repeatability, thus allowing their use as blood coagulation sensors. Additionally, results indicate that they can also measure curing time of resins, solidification of fluids and coagulation of chemical substances, therefore allowing their implementation in chemical engineering applications.

  1. Identification of highly active flocculant proteins in bovine blood

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine blood is an excellent flocculating agent, faster acting and as effective on a mass basis as polyacrylamide, the most widely utilized polymeric flocculant. To determine the molecular basis of flocculation activity, whole bovine blood (BB) and BB plasma were fractionated by size exclusion chro...

  2. Coagulation induced by C3aR-dependent NETosis drives protumorigenic neutrophils during small intestinal tumorigenesis

    PubMed Central

    Guglietta, Silvia; Chiavelli, Andrea; Zagato, Elena; Krieg, Carsten; Gandini, Sara; Ravenda, Paola Simona; Bazolli, Barbara; Lu, Bao; Penna, Giuseppe; Rescigno, Maria

    2016-01-01

    Excessive activation of blood coagulation and neutrophil accumulation have been described in several human cancers. However, whether hypercoagulation and neutrophilia are linked and involved in cancer development is currently unknown. Here we show that spontaneous intestinal tumorigenesis correlates with the accumulation of low-density neutrophils with a pro-tumorigenic N2 phenotype and unprompted neutrophil extracellular traps (NET) formation. We find that increased circulating lipopolysaccharide induces upregulation of complement C3a receptor on neutrophils and activation of the complement cascade. This leads to NETosis, induction of coagulation and N2 polarization, which prompts tumorigenesis, showing a novel link between coagulation, neutrophilia and complement activation. Finally, in a cohort of patients with small but not large intestinal cancer, we find a correlation between neutrophilia and hypercoagulation. This study provides a mechanistic explanation for the tumour-promoting effects of hypercoagulation, which could be used as a new biomarker or as a therapeutic target. PMID:26996437

  3. Dust coagulation in ISM

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

  4. COAGULATION PARAMETERS IN THE AMERICAN FLAMINGO (PHOENICOPTERUS RUBER).

    PubMed

    Gardhouse, Sara; Eshar, David; Beaufrère, Hugues

    2016-06-01

    American flamingos ( Phoenicopterus ruber ) are commonly kept in zoologic collections. When presented to veterinarians in states of health and illness, evaluation of selected coagulation parameters can aid in assessment of various coagulopathies, as well as other disease processes such as septicemia, vasculitis, and hepatic disease. Sixteen American flamingos (eight males, eight females) were presented for annual health evaluations. A blood sample was collected from the medial metatarsal vein, and prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, and fibrin degradation products (FDPs) were evaluated using an automated hemostasis analyzer. Results were reported as median and range (minimum-maximum): PT = 72.7 (39 to >100 sec), APTT = 97.5 (6.1 to >200 sec), fibrinogen = 184 (138-364 mg/dl), and FDPs = <5 (<5 to >20 μg/ml). To the authors' knowledge, this is the first report of coagulation parameters in American flamingos. Knowledge of coagulation parameters will allow for better clinical assessment and management of American flamingos.

  5. The Interface between Inflammation and Coagulation in Cardiovascular Disease

    PubMed Central

    Demetz, Gabriele; Ott, Ilka

    2012-01-01

    The intimate connection between coagulation and inflammation in the pathogenesis of vascular disease has moved more and more into focus of clinical research. This paper focuses on the essential components of this interplay in the settings of cardiovascular disease and acute coronary syndrome. Tissue factor, the main initiator of the extrinsic coagulation pathway, plays a central role via causing a proinflammatory response through activation of coagulation factors and thereby initiating coagulation and downstream cellular signalling pathways. Regarding activated clotting factors II, X, and VII, protease-activated receptors provide the molecular link between coagulation and inflammation. Hereby, PAR-1 displays deleterious as well as beneficial properties. Unravelling these interrelations may help developing new strategies to ameliorate the detrimental reciprocal aggravation of inflammation and coagulation. PMID:22518344

  6. [Activation and inhibitory mechanisms of blood platelets].

    PubMed

    Suzuki-Inoue, Katsue

    2014-07-01

    Exposure of platelets to subendothelial matrices initiates physiological hemostasis and pathological thrombosis. Under high shear stress, von Willebrand factor bridges newly exposed collagen to glycoprotein (GP) Ib on platelets. This initial tethering facilitates association between the collagen receptor GPVI and collagen, which generates tyrosine kinase-dependent activation signals, followed by release of secondary mediators and integrin activation. Activated integrin can bind to their ligands including fibrinogen. The released secondary mediators, ADP and thromboxane A2, activate integrin of flowing platelets, which enables formation of platelet thrombi by binding of activated flowing platelets and adhered platelets to collagen via binding between activated aIIbbeta3 integrin and fibrinogen. Platelets also have inhibitory mechanisms, which help to prevent unwanted platelet activation in vivo.

  7. International reference standards in coagulation.

    PubMed

    Raut, Sanj; Hubbard, Anthony R

    2010-07-01

    Measurement of coagulation factor activity using absolute physico-chemical techniques is not possible and estimation therefore relies on comparative bioassay relative to a reference standard with a known or assigned potency. However the inherent variability of locally prepared and calibrated reference standards can give rise to poor agreement between laboratories and methods. Harmonisation of measurement between laboratories at the international level relies on the availability of a common source of calibration for local reference standards and this is provided by the World Health Organization (WHO) International Standards which define the International Unit for the analyte. This article describes the principles, practices and problems of biological standardisation and the development and use of reference standards for assays of coagulation factors, with particular emphasis on WHO International Standards for both concentrates and plasma.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26109079

  9. 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.

  10. Stability, sterility, coagulation, and immunologic studies of salmon coagulation proteins with potential use for mammalian wound healing and cell engineering.

    PubMed

    Laidmäe, Ivo; McCormick, Margaret E; Herod, Julia L; Pastore, Jennifer J; Salum, Tiit; Sawyer, Evelyn S; Janmey, Paul A; Uibo, Raivo

    2006-12-01

    Fibrin sealants made by polymerization of fibrinogen activated by the protease thrombin have many applications in hemostasis and wound healing. In treatments of acute injury or surgical wounds, concentrated fibrin preparations mimic the initial matrix that normally prevents bleeding and acts as a scaffold for cells that initiate tissue repair. However risks of infectious disease, immunogenic reaction, and the high cost of purified human or other mammalian blood proteins limit widespread use of these materials. Purified coagulation proteins from Atlantic salmon represent a potentially safer, equally effective, and less costly alternative in part because of the low ambient temperature of these farmed animals and the absence of endogenous agents known to be infectious in mammalian hosts. This study reports rheologic measurements of lyophilized salmon fibrinogen and thrombin that demonstrate stability to prolonged storage and gamma irradiation sufficient to reduce viral loads by over five orders of magnitude. Coagulation and immunologic studies in rats and rabbits treated intraperitoneally with salmon fibrin show no deleterious effects on coagulation profiles and no cross reactivity with host fibrinogen or thrombin. The results support the potential of salmon fibrin as an alternative to mammalian proteins in clinical applications.

  11. Whole Blood Cholinesterase Activity in 20 Species of Wild Birds.

    PubMed

    Horowitz, Igal H; Yanco, Esty G; Landau, Shmulik; Nadler-Valency, Rona; Anglister, Nili; Bueller-Rosenzweig, Ariela; Apelbom-Halbersberg, Tal; Cuneah, Olga; Hanji, Vera; Bellaiche, Michel

    2016-06-01

    Clinical signs of organophosphate and carbamate intoxication in wild birds can be mistaken for those of other diseases, thus potentially delaying diagnosis and implementation of life-saving treatment. The objective of this study was to determine the reference interval for blood cholinesterase activity in 20 different wild avian species from 7 different orders, thereby compiling a reference database for wildlife veterinarians. Blood was collected from birds not suspected of having organophosphate or carbamate toxicosis, and the modified Michel method, which determines the change in blood pH that directly correlates with cholinesterase activity, was used to measure blood cholinesterase levels. Results of change in blood pH values ranged from 0.11 for the white-tailed eagle ( Haliaeetus albicilla ) to 0.90 for the honey buzzard ( Pernis apivorus ). The results showed that even within the same family, interspecies differences in normal cholinesterase blood activity were not uncommon. The findings emphasized the importance of determining reference intervals for avian blood cholinesterase activity at the species level.

  12. 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

  13. Systemic platelet dysfunction is the result of local dysregulated coagulation and platelet activation in the brain in a rat model of isolated traumatic brain injury.

    PubMed

    Ploplis, Victoria A; Donahue, Deborah L; Sandoval-Cooper, Mayra J; MorenoCaffaro, Maria; Sheets, Patrick; Thomas, Scott G; Walsh, Mark; Castellino, Francis J

    2014-10-01

    Coagulopathy after severe traumatic brain injury (TBI) has been extensively reported. Clinical studies have identified a strong relationship between diminished platelet-rich thrombus formation, responsiveness to adenosine diphosphate agonism, and severity of TBI. The mechanisms that lead to platelet dysfunction in the acute response to TBI are poorly understood. The development of a rodent model of TBI that mimics the coagulopathy observed clinically has recently been reported. Using immunohistochemical techniques and thromboelastography platelet mapping, the current study demonstrated that the expression of coagulation (tissue factor and fibrin) and platelet activation (P-selectin) markers in the injured brain paralleled the alteration in systemic platelet responsiveness to the agonists, adenosine diphosphate and arachodonic acid. Results of this study demonstrate that local procoagulant changes in the injured brain have profound effects on systemic platelet function.

  14. Commonly Used Dietary Supplements on Coagulation Function during Surgery

    PubMed Central

    Wang, Chong-Zhi; Moss, Jonathan; Yuan, Chun-Su

    2015-01-01

    Background Patients who undergo surgery appear to use dietary supplements significantly more frequently than the general population. Because they contain pharmacologically active compounds, dietary supplements may affect coagulation and platelet function during the perioperative period through direct effects, pharmacodynamic interactions, and pharmacokinetic interactions. However, in this regard, limited studies have been conducted that address the pharmacological interactions of dietary supplements. To avoid possible bleeding risks during surgery, information of potential complications of dietary supplements during perioperative management is important for physicians. Methods Through a systematic database search of all available years, articles were identified in this review if they included dietary supplements and coagulation/platelet function, while special attention was paid to studies published after 1990. Results Safety concerns are reported in commercially available dietary supplements. Effects of the most commonly used natural products on blood coagulation and platelet function are systematically reviewed, including 11 herbal medicines (echinacea, ephedra, garlic, ginger, ginkgo, ginseng, green tea, kava, saw palmetto, St John’s wort, and valerian) and 4 other dietary supplements (coenzyme Q10, glucosamine and chondroitin sulfate, fish oil, and vitamins). Bleeding risks of garlic, ginkgo, ginseng, green tea, saw palmetto, St John’s wort, and fish oil are reported. Cardiovascular instability was observed with ephedra, ginseng, and kava. Pharmacodynamic and pharmacokinetic interactions between dietary supplements and drugs used in the perioperative period are discussed. Conclusions To prevent potential problems associated with the use of dietary supplements, physicians should be familiar with the perioperative effects of commonly used dietary supplements. Since the effects of dietary supplements on coagulation and platelet function are difficult to

  15. Coagulation factors bound to procoagulant platelets concentrate in cap structures to promote clotting.

    PubMed

    Podoplelova, Nadezhda A; Sveshnikova, Anastasia N; Kotova, Yana N; Eckly, Anita; Receveur, Nicolas; Nechipurenko, Dmitry Yu; Obydennyi, Sergey I; Kireev, Igor I; Gachet, Christian; Ataullakhanov, Fazly I; Mangin, Pierre H; Panteleev, Mikhail A

    2016-09-29

    Binding of coagulation factors to phosphatidylserine (PS)-exposing procoagulant-activated platelets followed by formation of the membrane-dependent enzyme complexes is critical for blood coagulation. Procoagulant platelets formed upon strong platelet stimulation, usually with thrombin plus collagen, are large "balloons" with a small (∼1 μm radius) "cap"-like convex region that is enriched with adhesive proteins. Spatial distribution of blood coagulation factors on the surface of procoagulant platelets was investigated using confocal microscopy. All of them, including factors IXa (FIXa), FXa/FX, FVa, FVIII, prothrombin, and PS-sensitive marker Annexin V were distributed nonhomogeneously: they were primarily localized in the "cap," where their mean concentration was by at least an order of magnitude, higher than on the "balloon." Assembly of intrinsic tenase on liposomes with various PS densities while keeping the PS content constant demonstrated that such enrichment can accelerate this reaction by 2 orders of magnitude. The mechanisms of such acceleration were investigated using a 3-dimensional computer simulation model of intrinsic tenase based on these data. Transmission electron microscopy and focal ion beam-scanning electron microscopy with Annexin V immunogold-labeling revealed a complex organization of the "caps." In platelet thrombi formed in whole blood on collagen under arterial shear conditions, ubiquitous "caps" with increased Annexin V, FX, and FXa binding were observed, indicating relevance of this mechanism for surface-attached platelets under physiological flow. These results reveal an essential heterogeneity in the surface distribution of major coagulation factors on the surface of procoagulant platelets and suggest its importance in promoting membrane-dependent coagulation reactions.

  16. Coagulation profile, gene expression and bioinformatics characterization of coagulation factor X of striped murrel Channa striatus.

    PubMed

    Arasu, Abirami; Kumaresan, Venkatesh; Sathyamoorthi, Akila; Arasu, Mariadhas Valan; Al-Dhabi, Naif Abdullah; Arockiaraj, Jesu

    2016-08-01

    A transcriptome wide analysis of the constructed cDNA library of snakehead murrel Channa striatus revealed a full length cDNA sequence of coagulation factor X. Sequence analysis of C. striatus coagulation factor X (CsFX) showed that the cDNA contained 1232 base pairs (bp) comprising 1209 bp open reading frame (ORF). The ORF region encodes 424 amino acids with a molecular mass of 59 kDa. The polypeptide contains γ-carboxyglutamic acid (GLA) rich domain and two epidermal growth factor (EGF) like domains including EGF-CA domain and serine proteases trypsin signature profile. CsFX exhibited the maximum similarity with fish species such as Stegastes partitus (78%), Poecilia formosa (76%) and Cynoglossus semilaevis (74%). Phylogenetically, CsFX is clustered together with the fish group belonging to Actinopterygii. Secondary structure of factor X includes alpha helix 28.54%, extended strand 20.75%, beta turn 7.78% and random coil 42.92%. A predicted 3D model of CsFX revealed a short α-helix and a Ca(2+) (Gla domain) binding site in the coil. Four disulfide bridges were found in serine protease trypsin profile. Obviously, the highest gene expression (P < 0.05) was noticed in blood. Further, the changes in expression of CsFX was observed after inducing with bacterial (Aeromonas hydrophila) and fungal (Aphanomyces invadans) infections and other synthetic immune stimulants. Variation in blood clotting time (CT), prothrombin time (PT) and activated prothromboplastin time (APTT) was analyzed and compared between healthy and bacterial infected fishes. During infection, PT and APTT showed a declined clotting time due to the raised level of thrombocytes.

  17. Extensive coagulation monitoring in patients after implantation of the MicroMed Debakey continuous flow axial pump.

    PubMed

    Bonaros, Nikolaos; Mueller, Michael-Rolf; Salat, Andreas; Schima, Heinrich; Roethy, Wilfried; Kocher, Alfred A; Roche, Alfred A; Wolner, Ernst; Wieselthaler, Georg M

    2004-01-01

    Ventricular assist device (VAD) implantation is associated with impaired primary hemostasis and thromboembolic complications. Recently, a new generation of implantable continuous flow axial pumps was introduced into clinical application. To study the potential thrombogenic properties of this type of pump, we applied extensive platelet monitoring was applied. In our institution, 13 patients received the MicroMed DeBakey VAD as a bridge to transplantation. Routine coagulation tests (platelet count, activated partial thromboplastin time, prothrombin time, antithrombin III activity) and platelet function tests (whole blood aggregometry, thrombelastography, flow cytometry) were performed. No clinically relevant thromboembolic events were detected. No correlation was found between global function tests, platelet aggregation, and thrombelastography. No correlation was detected between platelet activation and hemolysis parameters. Platelet aggregation and coagulation index were significantly suppressed early after operation. A subsequent phase of hyper-aggregability, starting around day 6, suggested the initiation of antiaggregation therapy. Platelet activation markers were upregulated in the postoperative period but were returned to preoperative levels after initiation of aspirin. In contrast to routine coagulation monitoring, platelet function tests reflect in detail the coagulation status of blood pump recipients and the efficiency of antiaggregation therapy. Aspirin and dipyridamole therapy in addition to oral anticoagulation using phenprocoumon may contribute to platelet function and clot mechanics restoration and is, therefore, recommended for patients after VAD implantation.

  18. [Investigation of coagulation time: PT and APTT].

    PubMed

    Ramakers, Christian; van der Heul, Cees; van Wijk, Eduard M

    2012-01-01

    The first case report describes an extremely prolonged activated partial thromboplastin time (APTT) in a patient with no history of increased bleeding tendency. Heparin use was excluded. The APTT mixing study combined with the medical history suggests a deficiency in one of the non-essential coagulation factors. This was confirmed by factor XII activity of <1%. The second case report describes a prolonged APTT in a patient with no history of increased bleeding tendency. The negative bleeding tendency in combination with a failure of the mixing study to correct the coagulation assay results suggests a factor inhibitor, most probably lupus anticoagulant. Indeed, the lupus anticoagulant was positive and the anti-cardiolipin antibody titre was also positive. Aberrations in the process of haemostasis can be efficiently screened using a platelet count, an APTT, a PT and a thorough physical examination combined with a thorough medical history taking. Common causes of prolonged PT and/or APTT are the use of oral anticoagulants or heparin, vitamin K deficiency and liver disease. Other causes include coagulation factor deficiencies, coagulation factor inhibitors and diffuse intravascular coagulation.

  19. Hypothesis: Disseminated Intravascular Inflammation as the Inflammatory Counterpart to Disseminated Intravascular Coagulation

    NASA Astrophysics Data System (ADS)

    Bull, Brian S.; Bull, Maureen H.

    1994-08-01

    We have identified a leukocyte activation syndrome that is occasionally associated with the transfusion of intraoperatively recovered erythrocytes. This syndrome appears to result from intravascular damage caused by leukocytes activated during the erythrocyte salvage process. We hypothesize that this syndrome is part of a larger disease grouping: disseminated intravascular inflammation (DII). DII is the analog of the coagulation disorder disseminated intravascular coagulation. In disseminated intravascular coagulation, the organ damage results from uncontrolled activation of the clotting pathway; in DII the damage is caused by leukocytes that have become activated by direct contact with bacteria or in rare instances-such as erythrocyte salvage-in the absence of bacteria and bacterial products. Recent studies of the hazards associated with intraoperative blood salvage indicate that activation of leukocytes can be achieved by exposure to activated platelets alone. If such activated leukocytes are reinfused along with the washed erythrocytes, widespread organ damage may result. The lung is the organ most severely affected by activated leukocytes. Adult respiratory distress syndrome is one outcome. It is likely that DII is a presently unrecognized pathophysiological process that complicates a variety of primary disease states and increases their lethality.

  20. Blood

    MedlinePlus

    ... The liquid part, called plasma, is made of water, salts, and protein. Over half of your blood is plasma. The solid part of your blood contains red blood cells, white blood cells, and platelets. Red ...

  1. Functional Nanoparticles Activate a Decellularized Liver Scaffold for Blood Detoxification.

    PubMed

    Xu, Fen; Kang, Tianyi; Deng, Jie; Liu, Junli; Chen, Xiaolei; Wang, Yuan; Ouyang, Liang; Du, Ting; Tang, Hong; Xu, Xiaoping; Chen, Shaochen; Du, Yanan; Shi, Yujun; Qian, Zhiyong; Wei, Yuquan; Deng, Hongxin; Gou, Maling

    2016-04-01

    Extracorporeal devices have great promise for cleansing the body of virulence factors that are caused by venomous injuries, bacterial infections, and biological weaponry. The clinically used extracorporeal devices, such as artificial liver-support systems that are mainly based on dialysis or electrostatic interaction, are limited to remove a target toxin. Here, a liver-mimetic device is shown that consists of decellularized liver scaffold (DLS) populated with polydiacetylene (PDA) nanoparticles. DLS has the gross shape and 3D architecture of a liver, and the PDA nanoparticles selectively capture and neutralize the pore-forming toxins (PFTs). This device can efficiently and target-orientedly remove PFTs in human blood ex vivo without changing blood components or activating complement factors, showing potential application in antidotal therapy. This work provides a proof-of-principle for blood detoxification by a nanoparticle-activated DLS, and can lead to the development of future medical devices for antidotal therapy.

  2. Postoperative bleeding in a patient with normal screening coagulation tests.

    PubMed

    Nourbakhsh, Eva; Anvari, Reza; D'cunha, Nicholas; Thaxton, Lauren; Malik, Asim; Nugent, Kenneth

    2011-09-01

    A 54-year-old man was brought to the emergency room after a head-on collision. He had multiple fractures in his lower extremities and required immediate surgery. After surgery, the patient had a persistent drop in hemoglobin, hematocrit and platelets despite red blood cell transfusions. Laboratory studies included normal prothrombin time, activated partial thromboplastin time, normal plasminogen functional activity, negative antiplatelet antibodies, normal platelet functional analysis and negative disseminated intravascular coagulation screen. Factor XIII antigen levels were 25% of predicted, and the diagnosis of factor XIII deficiency was made. The patient was treated with cryoprecipitate, and the bleeding stopped. Patients with factor XIII deficiency have either a rare congenital or acquired coagulation disorder. Both presentations have normal standard laboratory clotting tests, and the diagnosis requires an assay measuring factor XIII activity or antigen levels. The usual treatment includes cryoprecipitate, fresh-frozen plasma or recombinant factor XIII. This deficiency should be considered in patients with unexplained spontaneous, traumatic or postoperative bleeding.

  3. Performance of a coincidence based blood activity monitor

    SciTech Connect

    Moses, W.W.

    1989-12-01

    A new device has been constructed that measures the positron emitting radio-tracer concentration in arterial blood by extracting blood with a peristaltic pump, then measuring the activity concentration by detecting coincident pairs of 511 keV photons with a pair of heavy inorganic scintillators attached to photomultiplier tubes. The sensitivity of this device is experimentally determined to be 610 counts/second per {mu}Ci/ml, and has a paralyzing dead time of 1.2 {mu}s, so is capable of measuring blood activity concentration as high as 1 mCi/ml. Its performance is compared to two other blood monitoring methods: discrete blood samples counted with a well counter and device that uses a plastic scintillator to directly detect positrons. The positron detection efficiency of this device for {sup 18}F is greater than the plastic scintillation counter, and also eliminates the radioisotope dependent correction factors necessary to convert count rate to absolute concentration. Coincident photon detection also has the potential of reducing the background compared to direct positron detection, thereby increasing the minimum detectable isotope concentration. 10 refs., 6 figs.

  4. Genetic engineering and coagulation factors.

    PubMed

    Fass, D N; Toole, J J

    1985-06-01

    It is unfortunate that we cannot report, in the area of coagulation, advances that have been seen in related fields such as thrombolytic therapy. The reported progress (Gold et al, 1984; Van de Werf et al, 1984) with human recombinant tissue plasminogen activator (Pennica et al, 1983) augers well for the application of recombinant technology to the problems faced by patients with coagulation defects. While plasminogen activator is being assessed in an acute therapeutic setting, its use signals a beginning of the application of the technology to abnormalities of the haemostatic mechanism. Chronic administration of coagulation factors for prophylaxis and replacement therapy would appear to be just one more step down the pathway illuminated by the biochemists, microbiologists and cell biologists who have preceded the clinicians in this promising area. There is no record of the use of genetically engineered materials in the treatment of coagulation defects, primarily because the body of knowledge and refined techniques have only recently been acquired. For this reason we have had to project developments in other areas onto the problems that exist for the haemostatically compromised patient. In describing the potential usefulness of these technologies, it is difficult to ascertain where the logical projection, from a fully investigated model system, diverges from flights of imaginative fancy. Cloning projects considered overly ambitious and grandiose at the beginning of this decade are already accomplished feats. The feasibility of gene therapy in the mammalian system has been demonstrated, and trade publications now discuss governmental approval for investigative use of this procedure in 1985. Panels of physicians, scientists and even politicians now seriously contemplate and promulgate views and regulations pertaining to the efficacy and ethics of the use of genetic engineering in the treatment of human disease. The haemophilias will certainly be among the first

  5. [Effect of xuebijing oral effervescent tablet on endotoxin induced fever and disseminated intravascular coagulation rabbit model].

    PubMed

    Guo, Shan-Shan; Gao, Ying-Jie; Tian, Xue-Chuan; Jin, Ya-Hong; Liu, Fang-Zhou; Cui, Xiao-Lan

    2013-08-01

    In order to discover the mechanism of Xuebijing oral effervescent tablet (XBJOET) to treat infectious diseases, the effect of XBJOET on endotoxin induced rabbit fever and disseminated intravascular coagulation (DIC) was investigated. Auricle microcirculation in rabbit was detected by laser speckle blood perfusion imager system; coagulation function was measured by coagulation analyzer, fibrinolytic system was quantified by Elisa assay and micro thrombosis in tissues was observed with HE staining under light microscope. The results demonstrated that the body temperature of rabbit decreased significantly at 1-3 h after administration with 4.8, 2.4 and 1.2 g x kg(-1) XBJOET to endotoxin induced DIC rabbit model, the auricle microcirculation blood flow in model group (54.45 +/- 14.53) PU was lower than that in control group (77.18 +/- 12.32) PU. The auricle microcirculation blood flow increased markedly and there was significant difference between model group and 1.2 g x kg(-1) XBJOET group. There was significant difference between model group and control group in the content of PAI1 and FIB. The PAI1 levels in model and control groups were (30.48 +/- 2.46) ng x mL(-1) and (20.93 +/- 3.25) ng x mL(-1), respectively. The FIB levels in model and control group were (3.34 +/- 1.09) g x L(-1) and (4.84 +/- 1.10) g x L(-1), respectively. The content of PAI1 in rabbit plasma decreased notably, there were significant differences between model group and 4.8, 2.4 g x kg(-1) XBJOET groups. On the contrary the content of FIB increased. XBJOET possessed pharmacological activities of curing infectious fever and DIC, the mechanism of which is related to amelioration of microcirculation disturbance, inhibition of fibrinolytic system activation and coagulation and micro thrombosis elimination.

  6. A comparison of kaolin-activated versus nonkaolin-activated thromboelastography in native and citrated blood.

    PubMed

    Thalheimer, Ulrich; Triantos, Christos K; Samonakis, Dimitrios N; Zambruni, Andrea; Senzolo, Marco; Leandro, Gioacchino; Patch, David; Burroughs, Andrew K

    2008-09-01

    Thromboelastography can be performed with native or citrated blood (a surrogate to native blood in healthy controls, surgical and cirrhotic patients). Activators such as kaolin are increasingly used to reduce the time to trace generation. To compare kaolin-activated thromboelastography with nonkaolin-activated thromboelastography of native and citrated blood in patients with liver disease, patients undergoing treatment with warfarin or low-molecular weight heparin and healthy volunteers. We studied thromboelastography parameters in 21 healthy volunteers (group 1) and 50 patients, including 20 patients with liver cirrhosis with a nonbiliary aetiology (group 2), 10 patients with primary biliary cirrhosis or primary sclerosing cholangitis (group 3), 10 patients on warfarin treatment (group 4) and 10 patients with enoxaparin prophylaxis (group 5). Thromboelastography was performed using four methods: native blood (kaolin-activated and nonkaolin-activated) and citrated blood (kaolin-activated and nonkaolin-activated). For all thromboelastography parameters, correlation was poor (Spearman correlation coefficient < 0.70) between nonkaolin-activated and kaolin-activated thromboelastography, for both citrated and native blood. In healthy volunteers, in patients with liver disease and in those receiving anticoagulant treatment, there was a poor correlation between nonkaolin-activated and kaolin-activated thromboelastography. Kaolin-activated thromboelastography needs further validation before routine clinical use in these settings, and the specific methodology must be considered in comparing published studies.

  7. 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.

  8. Veno-occlusive disease in pediatric patients after hematopoietic stem cell transplantation: relevance of activated coagulation and fibrinolysis markers and natural anticoagulants.

    PubMed

    Jevtic, Dragana; Zecevic, Zeljko; Veljkovic, Dobrila; Dopsaj, Violeta; Radojicic, Zoran; Elezovic, Ivo

    2011-04-01

    Prediction of veno-occlusive disease (VOD), its precise diagnosis, and treatment have been the subject of various studies, but still remain unclear. Our goal was to investigate the levels of activated coagulation and fibrinolysis markers and natural anticoagulants in pediatric patients with VOD after hematopoietic stem cell transplantation (HSCT). We investigated 47 pediatric patients: 20 with neuroblastoma, 17 with leukemias, and 10 with lymphomas and measured the values of antithrombin (AT), protein C (PC), fibrinogen (FI), thrombin AT complex, prothrombin fragments 1+2 (F1+2), and D-dimer from day -7 to day +30 post-HSCT. Patients were monitored for the occurrence of VOD, and it occurred in 10 patients at a median post-HSCT day of 17.5 (range: 2 to 28 d). In the VOD group, at baseline the levels of FI were significantly lower, and on days +7 and +14 a relevant difference existed in F1+2 levels. The levels of PC were significantly lower on day +14. Logistic multivariate regression analysis between the groups showed significantly different D-dimer levels on day +14. On day +30, the levels of PC, AT, and F1+2 were different between these 2 groups of patients. The levels of D-dimer and F1+2 were increased, and PC and FI decreased before the clinical onset of VOD. The parameter differences may have a predictive value in VOD onset, which makes them candidates to be routinely monitored in patients after HSCT.

  9. Strongly Accelerated Margination of Active Particles in Blood Flow

    PubMed Central

    Gekle, Stephan

    2016-01-01

    Synthetic nanoparticles and other stiff objects injected into a blood vessel filled with red blood cells are known to marginate toward the vessel walls. By means of hydrodynamic lattice-Boltzmann simulations, we show that active particles can strongly accelerate their margination by moving against the flow direction: particles located initially in the channel center migrate much faster to their final position near the wall than in the nonactive case. We explain our findings by an enhanced rate of collisions between the stiff particles and the deformable red blood cells. Our results imply that a significantly faster margination can be achieved either technically by the application of an external magnetic field (if the particles are magnetic) or biologically by self-propulsion (if the particles are, e.g., swimming bacteria). PMID:26789773

  10. Advances in the treatment of inherited coagulation disorders.

    PubMed

    Escobar, M A

    2013-09-01

    Inherited coagulation disorders constitute a broad spectrum of coagulation factor deficiencies that include X-linked factor (F)VIII or FIX deficiency that causes haemophilia, and autosomal recessive disorders producing heterogeneous deficiencies in fibrinogen (FI), prothrombin (FII), FV, FVII, FX, FXI, FXIII and combined FV+FVIII. Significant advances in treatments for patients with congenital haemophilia A (FVIII deficiency) and B (FIX deficiency) over the last two decades have resulted from improvements in the production, availability and patient access to factor replacement products. Translation of advances in biotechnology, namely recombinant protein technology, targeted protein modifications to improve function and potentially reduce immunogenicity, and advanced formulations to optimize bioavailability and sustain activity offer promisingly new treatments for haemophilia as well as recessively inherited bleeding disorders in patients who otherwise have few therapeutic options. Though a theoretical risk remains for blood-borne viral infections with pooled plasma-derived products, this concern has diminished with breakthroughs in purification and viral inactivation methods. Development of inhibitory antibodies is still the most daunting problem for patients with inherited bleeding disorders, complicating treatment approaches to control and prevent bleeding, and posing risks for allergic and anaphylactic reactions in susceptible patients. The objectives of this review are to (i) highlight emerging advances in hemostatic therapies that are bioengineered to improve pharmacokinetic properties and bioavailability, sustain functional activity, and possibly eliminate immunogenicity of recombinant factor proteins; and (ii) present an overview of key clinical trials of novel factor products currently in the development pipeline.

  11. Coagulant recovery and reuse for drinking water treatment.

    PubMed

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

    2016-01-01

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

  12. Ir-CPI, a coagulation contact phase inhibitor from the tick Ixodes ricinus, inhibits thrombus formation without impairing hemostasis

    PubMed Central

    Decrem, Yves; Rath, Géraldine; Blasioli, Virginie; Cauchie, Philippe; Robert, Séverine; Beaufays, Jérôme; Frère, Jean-Marie; Feron, Olivier; Dogné, Jean-Michel; Dessy, Chantal; Vanhamme, Luc

    2009-01-01

    Blood coagulation starts immediately after damage to the vascular endothelium. This system is essential for minimizing blood loss from an injured blood vessel but also contributes to vascular thrombosis. Although it has long been thought that the intrinsic coagulation pathway is not important for clotting in vivo, recent data obtained with genetically altered mice indicate that contact phase proteins seem to be essential for thrombus formation. We show that recombinant Ixodes ricinus contact phase inhibitor (Ir-CPI), a Kunitz-type protein expressed by the salivary glands of the tick Ixodes ricinus, specifically interacts with activated human contact phase factors (FXIIa, FXIa, and kallikrein) and prolongs the activated partial thromboplastin time (aPTT) in vitro. The effects of Ir-CPI were also examined in vivo using both venous and arterial thrombosis models. Intravenous administration of Ir-CPI in rats and mice caused a dose-dependent reduction in venous thrombus formation and revealed a defect in the formation of arterial occlusive thrombi. Moreover, mice injected with Ir-CPI are protected against collagen- and epinephrine-induced thromboembolism. Remarkably, the effective antithrombotic dose of Ir-CPI did not promote bleeding or impair blood coagulation parameters. To conclude, our results show that a contact phase inhibitor is an effective and safe antithrombotic agent in vivo. PMID:19808248

  13. Cord blood banking activity in Iran National Cord Blood Bank: a two years experience.

    PubMed

    Jamali, Mostafa; Atarodi, Kamran; Nakhlestani, Mozhdeh; Abolghasemi, Hasan; Sadegh, Hosein; Faranoosh, Mohammad; Golzade, Khadije; Fadai, Razieh; Niknam, Fereshte; Zarif, Mahin Nikougoftar

    2014-02-01

    Today umbilical cord blood (UCB) has known as a commonly used source of hematopoietic stem cells for allogeneic transplantation and many cord blood banks have been established around the world for collection and cryopreservation of cord blood units. Herein, we describe our experience at Iran National Cord Blood Bank (INCBB) during 2 years of activity. From November 2010 to 2012, UCBs were collected from 5 hospitals in Tehran. All the collection, processing, testing, cryopreservation and storage procedures were done according to standard operation procedures. Total nucleated cells (TNC) count, viability test, CD34+ cell count, colony forming unit (CFU) assay, screening tests and HLA typing were done on all banked units. Within 3770 collected units, only 32.9% fulfilled banking criteria. The mean volume of units was 105.2 ml and after volume reduction the mean of TNC, viability, CD34+ cells and CFUs was 10.76×10(8), 95.2%, 2.99×10(6) and 7.1×10(5), respectively. One unit was transplanted at Dec 2012 to a 5-year old patient with five of six HLA compatibilities. In our country banking of UCB is new and high rate of hematopoietic stem cell transplants needs expanding CB banks capacity to find more matching units, optimization of methods and sharing experiences to improve biological characterization of units.

  14. Blood

    MedlinePlus

    ... that die or are lost from the body. White Blood Cells White blood cells (WBCs, and also ... of severe pain. previous continue Diseases of the White Blood Cells Neutropenia (pronounced: new-truh-PEE-nee- ...

  15. Plasminogen Activator Inhibitor-1 Deficiency Augments Visceral Mesothelial Organization, Intrapleural Coagulation, and Lung Restriction in Mice with Carbon Black/Bleomycin–Induced Pleural Injury

    PubMed Central

    Jeffers, Ann; Alvarez, Alexia; Owens, Shuzi; Koenig, Kathleen; Quaid, Brandon; Komissarov, Andrey A.; Florova, Galina; Kothari, Hema; Pendurthi, Usha; Mohan Rao, L. Vijaya; Idell, Steven

    2014-01-01

    Local derangements of fibrin turnover and plasminogen activator inhibitor (PAI)-1 have been implicated in the pathogenesis of pleural injury. However, their role in the control of pleural organization has been unclear. We found that a C57Bl/6j mouse model of carbon black/bleomycin (CBB) injury demonstrates pleural organization resulting in pleural rind formation (14 d). In transgenic mice overexpressing human PAI-1, intrapleural fibrin deposition was increased, but visceral pleural thickness, lung volumes, and compliance were comparable to wild type. CBB injury in PAI-1−/− mice significantly increased visceral pleural thickness (P < 0.001), elastance (P < 0.05), and total lung resistance (P < 0.05), while decreasing lung compliance (P < 0.01) and lung volumes (P < 0.05). Collagen, α-smooth muscle actin, and tissue factor were increased in the thickened visceral pleura of PAI-1−/− mice. Colocalization of α-smooth muscle actin and calretinin within pleural mesothelial cells was increased in CBB-injured PAI-1−/− mice. Thrombin, factor Xa, plasmin, and urokinase induced mesothelial–mesenchymal transition, tissue factor expression, and activity in primary human pleural mesothelial cells. In PAI-1−/− mice, D-dimer and thrombin–antithrombin complex concentrations were increased in pleural lavage fluids. The results demonstrate that PAI-1 regulates CBB-induced pleural injury severity via unrestricted fibrinolysis and cross-talk with coagulation proteases. Whereas overexpression of PAI-1 augments intrapleural fibrin deposition, PAI-1 deficiency promotes profibrogenic alterations of the mesothelium that exacerbate pleural organization and lung restriction. PMID:24024554

  16. Adrenergic and non-adrenergic control of active skeletal muscle blood flow: implications for blood pressure regulation during exercise.

    PubMed

    Holwerda, Seth W; Restaino, Robert M; Fadel, Paul J

    2015-03-01

    Blood flow to active skeletal muscle increases markedly during dynamic exercise. However, despite the massive capacity of skeletal muscle vasculature to dilate, arterial blood pressure is well maintained. Sympathetic nerve activity is elevated with increased intensity of dynamic exercise, and is essential for redistribution of cardiac output to active skeletal muscle and maintenance of arterial blood pressure. In addition, aside from the sympathetic nervous system, evidence from human studies is now emerging that supports roles for non-adrenergic vasoconstrictor pathways that become active during exercise and contribute to vasoconstriction in active skeletal muscle. Neuropeptide Y and adenosine triphosphate are neurotransmitters that are co-released with norepinephrine from sympathetic nerve terminals capable of producing vasoconstriction. Likewise, plasma concentrations of arginine vasopressin, angiotensin II (Ang II) and endothelin-1 (ET-1) increase during dynamic exercise, particularly at higher intensities. Ang II and ET-1 have both been shown to be important vasoconstrictor pathways for restraint of blood flow in active skeletal muscle and the maintenance of arterial blood pressure during exercise. Indeed, although both adrenergic and non-adrenergic vasoconstriction can be attenuated in exercising muscle with greater intensity of exercise, with the higher volume of blood flow, the active skeletal muscle vasculature remains capable of contributing importantly to the maintenance of blood pressure. In this brief review we provide an update on skeletal muscle blood flow regulation during exercise with an emphasis on adrenergic and non-adrenergic vasoconstrictor pathways and their potential capacity to offset vasodilation and aid in the regulation of blood pressure.

  17. A short contemporary history of disseminated intravascular coagulation.

    PubMed

    Levi, Marcel; van der Poll, Tom

    2014-11-01

    Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation, leading to a widespread deposition of fibrin in the circulation. There is ample experimental and pathological evidence that the fibrin deposition contributes to multiple organ failure. The massive and ongoing activation of coagulation may result in depletion of platelets and coagulation factors, which may cause bleeding (consumption coagulopathy). The syndrome of DIC is well known in the medical literature for centuries, although a more precise description of the underlying mechanisms had to await the 20th century. Initial ideas on a role of the contact activation system as the primary trigger for the systemic activation of coagulation as well as a presumed hyperfibrinolytic response in DIC have been found to be misconceptions. Experimental and clinical evidence now indicate that the initiation of coagulation in DIC is caused by tissue factor expression, which in combination with downregulated physiological anticoagulant pathways and impaired fibrinolysis leads to widespread fibrin deposition. In addition, an extensive bidirectional interaction between coagulation and inflammation may further contribute to the pathogenesis of DIC.

  18. Chemotactic and Phagocytic Activity of Blood Neutrophils in Allergic Asthma.

    PubMed

    Mosca, Tainá; Menezes, Maria C S; Silva, Ademir Veras; Stirbulov, Roberto; Forte, Wilma C N

    2015-01-01

    Allergic asthma is a chronic inflammatory airway disease, and has been considered a T helper-2-biased response. Studies suggest that neutrophils may be associated with exacerbation and asthma severity. We sought to evaluate the chemotactic activity and phagocytic capacity by peripheral blood neutrophils from individuals with controlled and uncontrolled allergic asthma, and compare the results with non-asthmatic controls groups. Blood neutrophils were isolated from 95 patients: 24 with controlled asthma, 24 uncontrolled asthma, 24 healthy subjects and 23 patients with IgE-mediated allergies other than asthma. The neutrophil chemotaxis, stimulated with LPS, autologous serum or homologous serum, was determined using Boyden chambers. The phagocytic capacity was assessed by ingestion of zimosan particles, and digestion phase was analyzed by NBT test. The phagocytic digestion phase and chemotaxis by neutrophils from asthmatic patients was higher than in non-asthmatic controls (p  < 0.05). Autologous serum-induced neutrophil chemotaxis in patients with uncontrolled asthma was greater (p  < 0.05) than in other study groups. The ingestion phase of phagocytosis showed similar values in asthmatics and non-asthmatics. We conclude that the blood neutrophil from controlled and uncontrolled asthmatic patients exhibit activation markers, particularly phagocytic digestion and chemotactic activities.

  19. Isolation and study of an acquired inhibitor of human coagulation factor V.

    PubMed Central

    Nesheim, M E; Nichols, W L; Cole, T L; Houston, J G; Schenk, R B; Mann, K G; Bowie, E J

    1986-01-01

    A coagulation Factor V inhibitor developed in a man 75 yr of age in association with an anaplastic malignancy and drug treatment (including the aminoglycoside antibiotic, gentamicin). The patient did not bleed abnormally, despite both surgical challenge and plasma Factor V activity of less than 1%. The inhibited plasma had grossly prolonged prothrombin and activated partial thromboplastin times, but a normal thrombin time. Mixing studies indicated progressive coagulation inhibition with normal plasma, but not with Factor V-deficient plasma, and reversal of coagulation inhibition by the addition of bovine Factor V to the patient's plasma. 1 ml of patient plasma inhibited the Factor V activity of 90 ml of normal human plasma. The inhibitor was isolated by sequential affinity chromatography on protein A-Sepharose and Factor V-Sepharose. The IgG isolate markedly inhibits the activity of prothrombinase assembled from purified Factors Xa and Va, calcium ion, and phospholipid vesicles, and partially inhibits prothrombinase assembled from purified Factor Xa, calcium ion, and normal platelets. The Factor V of platelets, however, appears relatively inaccessible to the antibody, inasmuch as platelets isolated from whole blood supplemented for 8 h with the antibody functioned normally with respect to platelet Factor V-mediated prothrombinase function. The absence of obvious hemorrhagic difficulties in the patient, the total inhibition of plasma Factor V by the inhibitor, and the apparent inaccessibility of platelet Factor V to the inhibitor specifically implicate platelet Factor V in the maintenance of hemostasis. Images PMID:3944265

  20. Cell-based laboratory evaluation of coagulation activation by antineoplastic drugs for the treatment of lymphoid tumors

    PubMed Central

    Tsunaka, Misae; Arai, Reina; Ohashi, Ayaka; Koyama, Takatoshi

    2016-01-01

    Objectives: Combining vorinostat, L-asparaginase, and doxorubicin (Dox) led to improved response rates in the treatment of lymphoid tumors. However, deep-vein thrombosis has been noted as one of the most serious side effects with these drugs, and how these regimens cause deep-vein thrombosis is unclear. Methods: We investigated the procoagulant effects of vorinostat, L-asparaginase, and doxorubicin in lymphoid tumors, focusing on tissue factor, phosphatidylserine, and antithrombin. The human vascular endothelial cell line EAhy926 as well as the lymphoid neoplastic cell lines HUT78 (cutaneous T-cell lymphoma), Molt4 (acute T-lymphoblastic leukemia), and Ramos (Burkitt lymphoma) were employed to investigate these procoagulant effects. Results: Vorinostat, L-asparaginase, and doxorubicin induced exposure of phosphatidylserine and procoagulant activity on the surface of lymphoid tumor cells. Vorinostat and doxorubicin also induced phosphatidylserine exposure and increased procoagulant activity on EAhy926 cells. Expression of tissue factor antigen was induced by doxorubicin on the surface of each type of cells, whereas expression of tissue factor mRNA was unchanged. Secretion of antithrombin from HepG2 cells was reduced only by L-asparaginase. Conclusion: These data suggest that vorinostat and doxorubicin may induce procoagulant activity in vessels through apoptosis of tumor cells and through phosphatidylserine exposure and/or tissue factor expression on vascular endothelial cells. L-asparaginase may induce a thrombophilic state by reducing the secretion of anticoagulant proteins such as antithrombin. The laboratory methods described here could be useful to evaluate the procoagulant effects of antineoplastic drugs. PMID:27504186

  1. A shear gradient-activated microfluidic device for automated monitoring of whole blood haemostasis and platelet function

    PubMed Central

    Jain, Abhishek; Graveline, Amanda; Waterhouse, Anna; Vernet, Andyna; Flaumenhaft, Robert; Ingber, Donald E.

    2016-01-01

    Accurate assessment of blood haemostasis is essential for the management of patients who use extracorporeal devices, receive anticoagulation therapy or experience coagulopathies. However, current monitoring devices do not measure effects of haemodynamic forces that contribute significantly to platelet function and thrombus formation. Here we describe a microfluidic device that mimics a network of stenosed arteriolar vessels, permitting evaluation of blood clotting within small sample volumes under pathophysiological flow. By applying a clotting time analysis based on a phenomenological mathematical model of thrombus formation, coagulation and platelet function can be accurately measured in vitro in patient blood samples. When the device is integrated into an extracorporeal circuit in pig endotoxemia or heparin therapy models, it produces real-time readouts of alterations in coagulation ex vivo that are more reliable than standard clotting assays. Thus, this disposable device may be useful for personalized diagnostics and for real-time surveillance of antithrombotic therapy in clinic. PMID:26733371

  2. A shear gradient-activated microfluidic device for automated monitoring of whole blood haemostasis and platelet function.

    PubMed

    Jain, Abhishek; Graveline, Amanda; Waterhouse, Anna; Vernet, Andyna; Flaumenhaft, Robert; Ingber, Donald E

    2016-01-06

    Accurate assessment of blood haemostasis is essential for the management of patients who use extracorporeal devices, receive anticoagulation therapy or experience coagulopathies. However, current monitoring devices do not measure effects of haemodynamic forces that contribute significantly to platelet function and thrombus formation. Here we describe a microfluidic device that mimics a network of stenosed arteriolar vessels, permitting evaluation of blood clotting within small sample volumes under pathophysiological flow. By applying a clotting time analysis based on a phenomenological mathematical model of thrombus formation, coagulation and platelet function can be accurately measured in vitro in patient blood samples. When the device is integrated into an extracorporeal circuit in pig endotoxemia or heparin therapy models, it produces real-time readouts of alterations in coagulation ex vivo that are more reliable than standard clotting assays. Thus, this disposable device may be useful for personalized diagnostics and for real-time surveillance of antithrombotic therapy in clinic.

  3. 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.

  4. 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.

  5. Human blood platelets lack nitric oxide synthase activity.

    PubMed

    Böhmer, Anke; Gambaryan, Stepan; Tsikas, Dimitrios

    2015-01-01

    Reports on expression and functionality of nitric oxide synthase (NOS) activity in human blood platelets and erythrocytes are contradictory. We used a specific gas chromatography-mass spectrometry (GC-MS) method to detect NOS activity in human platelets. The method measures simultaneously [(15)N]nitrite and [(15)N]nitrate formed from oxidized (15)N-labeled nitric oxide ((15)NO) upon its NOS-catalyzed formation from the substrate l-[guanidino-(15)N2]-arginine. Using this GC-MS assay, we did not detect functional NOS in non-stimulated platelets and in intact platelets activated by various agonists (adenosine diphosphate, collagen, thrombin, or von Willebrand factor) or lysed platelets. l-[guanidino-nitro]-Arginine-inhibitable NOS activity was measured after addition of recombinant human endothelial NOS to lysed platelets. Previous and recent studies from our group challenge expression and functionality of NOS in human platelets and erythrocytes.

  6. The effects of 7.5% NaCl/6% dextran 70 on coagulation and platelet aggregation in humans

    NASA Technical Reports Server (NTRS)

    Hess, J. R.; Dubick, M. A.; Summary, J. J.; Bangal, N. R.; Wade, C. E.

    1992-01-01

    The combination solution of 7.5% NaCl/6% dextran 70 (HSD) administered IV gives hemodynamic improvement in the treatment of hemorrhagic hypotension. Since earlier dextran solutions were reported to interfere with blood coagulation, the effects of HSD on the prothrombin time (PT), the activated partial thromboplastin time (APTT), platelet aggregation, and platelet concentration were studied. The HSD mixed with human plasma (1:5 and 1:10) slightly prolonged PT, but had no effect on the APTT, compared with saline controls. The HSD also decreased human platelet aggregation at the 1:5 dilution. In separate mixing studies, the hypertonic saline component of HSD was associated with the prolongation of PT and decreased platelet aggregation. The data from these studies indicate that at its proposed therapeutic dose, HSD is expected to have minimal effect on blood coagulation.

  7. Procoagulant activity in stored units of red blood cells.

    PubMed

    Aleshnick, Maya; Foley, Jonathan H; Keating, Friederike K; Butenas, Saulius

    2016-06-10

    The procoagulant activity (PA) of stored units of red blood cells (RBC) increases over time, which is related to the expression/exposure of tissue factor (TF). However, there is a discrepancy between the TF measured and changes in PA observed, suggesting that other blood components contribute to this activity. Our goal was to evaluate changes in PA of stored RBCs and to determine possible contributors to it. RBC units from 4 healthy donors were prepared and stored at 4 °C. On selected days, RBC aliquots were reconstituted with autologous plasma and tested in the thromboelastography assay. Corresponding supernatants were tested in a clotting assay. For all donors, the clotting time (CT) of reconstituted RBC units decreased from ∼3000-4000s on day 1 to ∼1000-1600s on day 30, with the most dramatic changes occurring between days 1 and 5. Anti-TF antibody slightly prolonged the CT. The concentration of TF did not change significantly over time and was within the range of 0.3-2.3 pM. Bovine lactadherin (LTD) prolonged the CT of the RBC (by 2.4-3.4-fold in days 3-5 and by 1.3-1.8-fold at day 30). Anti-TF antibody together with LTD had a cumulative effect on the CT prolongation. CT of supernatants responded to both anti-TF and anti-FXIa antibodies. Three contributors to the PA of stored RBC were identified, i.e. FXIa in solution and phosphatidylserine and TF exposed on blood cells and microparticles. Failure of LTD and antibodies to completely eliminate PA suggests that other components of blood could contribute to it.

  8. Current Pathological and Laboratory Considerations in the Diagnosis of Disseminated Intravascular Coagulation

    PubMed Central

    Alhamdi, Yasir; Abrams, Simon T.

    2016-01-01

    Systemically sustained thrombin generation in vivo is the hallmark of disseminated intravascular coagulation (DIC). Typically, this is in response to a progressing disease state that is associated with significant cellular injury. The etiology could be infectious or noninfectious, with the main pathophysiological mechanisms involving cross-activation among coagulation, innate immunity, and inflammatory responses. This leads to consumption of both pro- and anticoagulant factors as well as endothelial dysfunction and disrupted homeostasis at the blood vessel wall interface. In addition to the release of tissue plasminogen activator (tPA) and soluble thrombomodulin (sTM) following cellular activation and damage, respectively, there is the release of damage-associated molecular patterns (DAMPs) such as extracellular histones and cell-free DNA. Extracellular histones are increasingly recognized as significantly pathogenic in critical illnesses through direct cell toxicity, the promotion of thrombin generation, and the induction of neutrophil extracellular trap (NET) formation. Clinically, high circulating levels of histones and histone–DNA complexes are associated with multiorgan failure, DIC, and adverse patient outcomes. Their measurements as well as that of other DAMPs and molecular markers of thrombin generation are not yet applicable in the routine diagnostic laboratory. To provide a practical diagnostic tool for acute DIC, a composite scoring system using rapidly available coagulation tests is recommended by the International Society on Thrombosis and Haemostasis. Its usefulness and limitations are discussed alongside the advances and unanswered questions in DIC pathogenesis. PMID:27578502

  9. Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension.

    PubMed

    Kossmann, Sabine; Lagrange, Jeremy; Jäckel, Sven; Jurk, Kerstin; Ehlken, Moritz; Schönfelder, Tanja; Weihert, Yvonne; Knorr, Maike; Brandt, Moritz; Xia, Ning; Li, Huige; Daiber, Andreas; Oelze, Matthias; Reinhardt, Christoph; Lackner, Karl; Gruber, Andras; Monia, Brett; Karbach, Susanne H; Walter, Ulrich; Ruggeri, Zaverio M; Renné, Thomas; Ruf, Wolfram; Münzel, Thomas; Wenzel, Philip

    2017-02-01

    Multicellular interactions of platelets, leukocytes, and the blood vessel wall support coagulation and precipitate arterial and venous thrombosis. High levels of angiotensin II cause arterial hypertension by a complex vascular inflammatory pathway that requires leukocyte recruitment and reactive oxygen species production and is followed by vascular dysfunction. We delineate a previously undescribed, proinflammatory coagulation-vascular circuit that is a major regulator of vascular tone, blood pressure, and endothelial function. In mice with angiotensin II-induced hypertension, tissue factor was up-regulated, as was thrombin-dependent endothelial cell vascular cellular adhesion molecule 1 expression and integrin αMβ2- and platelet-dependent leukocyte adhesion to arterial vessels. The resulting vascular inflammation and dysfunction was mediated by activation of thrombin-driven factor XI (FXI) feedback, independent of factor XII. The FXI receptor glycoprotein Ibα on platelets was required for this thrombin feedback activation in angiotensin II-infused mice. Inhibition of FXI synthesis with an antisense oligonucleotide was sufficient to prevent thrombin propagation on platelets, vascular leukocyte infiltration, angiotensin II-induced endothelial dysfunction, and arterial hypertension in mice and rats. Antisense oligonucleotide against FXI also reduced the increased blood pressure and attenuated vascular and kidney dysfunction in rats with established arterial hypertension. Further, platelet-localized thrombin generation was amplified in an FXI-dependent manner in patients with uncontrolled arterial hypertension, suggesting that platelet-localized thrombin generation may serve as an inflammatory marker of high blood pressure. Our results outline a coagulation-inflammation circuit that promotes vascular dysfunction, and highlight the possible utility of FXI-targeted anticoagulants in treating hypertension, beyond their application as antithrombotic agents in

  10. BLOOD COAGULATION, FIBRINOLYSIS AND CELLULAR HAEMOSTASIS

    PubMed Central

    Piazza, Gregory; Fanikos, John; Zayaruzny, Maksim; Goldhaber, Samuel Z.

    2010-01-01

    SUMMARY The number of acutely ill hospitalized medical patients at risk for acute venous thromboembolism (VTE) has not been well defined. Therefore, we used the 2003 United States Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample database to estimate VTE events among hospitalized medical patients. We then modeled the potential reduction in VTE with universal utilization of appropriate pharmacological thromboprophylaxis. We calculated that 8,077,919 acutely ill hospitalized medical patients were at risk for VTE. Heart failure, respiratory failure, pneumonia, and cancer were the most common medical diagnoses. We estimated that 196,134 VTE-related events occurred in 2003, afflicting two out of every 100 acutely ill hospitalized medical patients. These VTE-related events were comprised of 122,235 symptomatic deep vein thromboses, 32,654 symptomatic episodes of pulmonary embolism, and 41,245 deaths due to VTE. In our model, rates of pharmacological thromboprophylaxis prescription were low for various acute medical illnesses, ranging from 15.3% to 49.2%. However, with universal thromboprophylaxis, 114,174 VTE-related events would have been prevented. In conclusion, acutely ill medical patients represent a large population vulnerable to the development of VTE during hospitalization. The number of VTE-related events would be halved with universal thromboprophylaxis. Further efforts focused on improving VTE prevention strategies in hospitalized medical patients are warranted. PMID:19718471

  11. Functional consequences of blood clotting in insects.

    PubMed

    Haine, Eleanor R; Rolff, Jens; Siva-Jothy, Michael T

    2007-01-01

    Recent in vitro studies have revealed several important aspects of the biochemical and cellular processes involved in insect blood clotting. However, in vivo empirical studies of the functional consequences of clotting are lacking, despite the role of coagulation in wound-healing, preventing infection, and its homology with vertebrate wound repair. Here we present results of the in vivo effects of haemolymph coagulation and its consequences on the spatial disposition of immune activity, in the American cockroach Periplaneta americana. Our results demonstrate that clotting: (1) localises immune effectors in the vicinity of a breach of the cuticle; (2) restricts the spread of invasive particles across the haemocoel, and (3) is greater when wounding is associated with non-self. Our results demonstrate that haemolymph coagulation has major functional consequences, the most important of which is the compartmentalisation of the open haemocoel.

  12. Chemical sympathectomy attenuates inflammation, glycocalyx shedding and coagulation disorders in rats with acute traumatic coagulopathy.

    PubMed

    Xu, Lin; Yu, Wen-Kui; Lin, Zhi-Liang; Tan, Shan-Jun; Bai, Xiao-Wu; Ding, Kai; Li, Ning

    2015-03-01

    Acute traumatic coagulopathy (ATC) may trigger sympathoadrenal activation associated with endothelial damage and coagulation disturbances. Overexcitation of sympathetic nerve in this state would disrupt sympathetic-vagal balance, leading to autonomic nervous system dysfunction. The aim of this study was to evaluate the autonomic function in ATC and its influence on inflammation, endothelial and coagulation activation. Male Sprague-Dawley rats were randomly assigned to sham, ATC control (ATCC) and ATC with sympathectomy by 6-hydroxydopamine (ATCS) group. Sham animals underwent the same procedure without trauma and bleeding. Following trauma and hemorrhage, rats underwent heart rate variability (HRV) test, which predicts autonomic dysfunction through the analysis of variation in individual R-R intervals. Then, rats were euthanized at baseline, and at 0, 1 and 2 h after shock and blood gas, conventional coagulation test and markers of inflammation, coagulation, fibrinolysis, endothelial damage and catecholamine were measured. HRV showed an attenuation of total power and high frequency, along with a rise of low frequency and low frequency : high frequency ratio in the ATC rats, which both were reversed by sympathectomy in the ATCS group. Additionally, sympathetic denervation significantly suppressed the increase of proinflammatory cytokines, tumor necrosis factor-α and the fibrinolysis markers including tissue-type plasminogen activator and plasmin-antiplasmin complex. Serum catecholamine, soluble thrombomodulin and syndecan-1 were also effectively inhibited by sympathectomy. These data indicated that autonomic dysfunction in ATC involves both sympathetic activation and parasympathetic inhibition. Moreover, sympathectomy yielded anti-inflammatory, antifibrinolysis and endothelial protective effects in rats with ATC. The role of autonomic neuropathy in ATC should be explored further.

  13. Enhanced Cholinergic Activity Improves Cerebral Blood Flow during Orthostatic Stress

    PubMed Central

    Serrador, Jorge M.; Freeman, Roy

    2017-01-01

    Cerebral blood flow (CBF) and consequently orthostatic tolerance when upright depends on dilation of the cerebral vasculature in the face of reduced perfusion pressure associated with the hydrostatic gradient. However, it is still unclear if cholinergic activation plays a role in this dilation. To determine if enhancing central cholinergic activity with the centrally acting acetylcholinesterase inhibitor, physostigmine would increase CBF when upright compared to the peripherally acting acetylcholinesterase inhibitor, neostigmine, or saline. We performed a randomized double-blind dose-ranging study that took place over 3 days in a hospital-based research lab. Eight healthy controls (six women and two men, mean age, 26 years; range 21–33) were given infusions of physostigmine, neostigmine, or saline on three different days. Five-minute tilts were repeated at baseline (no infusion), Dose 1 (0.2 μg/kg/min physostigmine; 0.1 μg/kg/min neostigmine) and Dose 2 (0.6 μg/kg/min physostigmine or 0.3 μg/kg/min neostigmine), and placebo (0.9% NaCl). Cerebral blood velocity, beat-to-beat blood pressure, and end-tidal CO2 were continuously measured during tilts. Physostigmine (0.6 μg/kg/min) resulted in higher cerebral blood velocity during tilt (90.5 ± 1.5%) than the equivalent neostigmine (85.5 ± 2.6%) or saline (84.8 ± 1.7%) trials (P < 0.05). This increase occurred despite a greater postural hypocapnia, suggesting physostigmine had a direct vasodilatory effect on the cerebral vasculature. Cerebral hypoperfusion induced by repeated tilts was eliminated by infusion of physostigmine not neostigmine. In conclusion, this study provides the first evidence that enhancement of central, not peripheral, cholinergic activity attenuates the physiological decrease in CBF seen during upright tilt. These data support the need for further research to determine if enhancing central cholinergic activity may improve symptoms in patients with symptomatic

  14. Implementation of a microcontroller-based semi-automatic coagulator.

    PubMed

    Chan, K; Kirumira, A; Elkateeb, A

    2001-01-01

    The coagulator is an instrument used in hospitals to detect clot formation as a function of time. Generally, these coagulators are very expensive and therefore not affordable by a doctors' office and small clinics. The objective of this project is to design and implement a low cost semi-automatic coagulator (SAC) prototype. The SAC is capable of assaying up to 12 samples and can perform the following tests: prothrombin time (PT), activated partial thromboplastin time (APTT), and PT/APTT combination. The prototype has been tested successfully.

  15. Air pollution source apportionment before, during, and after the 2008 Beijing Olympics and association of sources to aldehydes and biomarkers of blood coagulation, pulmonary and systemic inflammation, and oxidative stress in healthy young adults

    NASA Astrophysics Data System (ADS)

    Altemose, Brent A.

    Based on principal component analysis (PCA) of air pollution data collected during the Summer Olympic Games held in Beijing, China during 2008, the five source types of air pollution identified -- natural soil/road dust, vehicle and industrial combustion, vegetative burning, oil combustion, and secondary formation, were all distinctly lower during the Olympics. This was particularly true for vehicle and industrial combustion and oil combustion, and during the main games period between the opening and closing ceremonies. The reduction in secondary formation was reflective of a reduction in nitrogen oxides, but this also contributed to increased ozone concentrations during the Olympic period. Among three toxic aldehydes measured in Beijing during the same time period, only acetaldehyde had a reduction in mean concentration during the Olympic air pollution control period compared to the pre-Olympic period. Accordingly, acetaldehyde was significantly correlated with primary emission sources including vegetative burning and oil combustion, and with several pollutants emitted mainly from primary sources. In contrast, formaldehyde and acrolein increased during the Olympic air pollution control period; accordingly both were significantly correlated with ozone and with the secondary formation source type. These findings indicate primary sources may dominate for acetaldehyde while secondary sources may dominate for formaldehyde and acrolein. Biomarkers for pulmonary inflammation (exhaled breath condensate (EBC) pH, exhaled nitric oxide, and EBC nitrite) and hemostasis and blood coagulation (vWF and sCD62p) were most consistently associated with vehicle and industrial combustion, oil combustion, and vegetative burning. The systemic inflammation biomarker 8-OHdG was most consistently associated with vehicle and industrial combustion. In contrast, the associations between the biomarkers and the aldehydes were generally not significant or in the hypothesized direction, although

  16. The relationship of electronically monitored physical activity to blood pressure, heart rate, and the circadian blood pressure profile.

    PubMed

    Mansoor, G A; White, W B; McCabe, E J; Giacco, S

    2000-03-01

    We studied how closely changes in electronically monitored physical activity are reflected in changes in blood pressure and heart rate in a group of untreated hypertensive subjects. Thirty-nine hypertensive patients (office blood pressure > 140/ 90 mm Hg) of mean age 57 +/- 10 years (mean +/-SD) wore an ambulatory blood pressure monitor and a wrist actigraph simultaneously. Both average and peak activity for 5 min before each valid blood pressure reading were determined, as was average activity for awake and sleep periods, determined by patient kept diaries. For the overall group, awake and 24-h activities were inversely correlated to age (n = 39, r = -0.42; P = 0.01 and n = 39, r = -0.38; P = 0.01, respectively). No correlation was found between group awake activity and group-average blood pressure or heart rate. For individual patients, there was marked variation in the degree of correlation between awake activity measures (both peak and average) and blood pressure and heart rate. The strongest positive correlation was between activity levels and the heart rate-pressure product. Nondipper profile hypertensives had higher sleep activity than dipper hypertensives (44 +/- 28 units/min v 25 +/- 20 units/min, df = 37, t = 2.12; P = 0.04), but awake activity levels were similar. The higher sleep activity remained after adjustment for age. These findings indicate that the relationship between actigraphic activity and hemodynamic parameters is highly variable and that the rate-pressure product is the strongest correlate of short-term activity. Furthermore, hypertensives with the nondipper profile have higher sleep activity than dipper hypertensives. These findings stress the need for further study into the role of day-to-day activity in determining ambulatory blood pressure and heart rate variability.

  17. Disseminated intravascular coagulation (DIC)

    MedlinePlus

    ... serious disorder in which the proteins that control blood clotting become overactive. Causes When you are injured, proteins ... Supportive treatments may include: Plasma transfusions to replace blood clotting factors if a large amount of bleeding is ...

  18. Blood Compatibility Evaluations of Fluorescent Carbon Dots.

    PubMed

    Li, Sha; Guo, Zhong; Zhang, Yi; Xue, Wei; Liu, Zonghua

    2015-09-02

    Because of their unique advantages, fluorescent carbon dots are gaining popularity in various biomedical applications. For these applications, good biosafety is a prerequisite for their use in vivo. Studies have reported the preliminary biocompatibility evaluations of fluorescent carbon dots (mainly cytotoxicity); however, to date, little information is available about their hemocompatibility, which could impede their development from laboratory to bedside. In this work, we evaluated the hemocompatibility of fluorescent carbon dots, which we prepared by hydrothermal carbonization of α-cyclodextrin. The effects of the carbon dots on the structure and function of key blood components were investigated at cellular and molecular levels. In particular, we considered the morphology and lysis of human red blood cells, the structure and conformation of the plasma protein fibrinogen, the complement activation, platelet activation, and in vitro and in vivo blood coagulation. We found that the carbon dots have obvious concentration-dependent effects on the blood components. Overall, concentrations of the fluorescent carbon dots at ≤0.1 mg/mL had few adverse effects on the blood components, but at higher doses, the carbon dots impair the structure and function of the blood components, causing morphological disruptions and lysis of red blood cells, interference in the local microenvironments of fibrinogen, activation of the complement system, and disturbances in the plasma and whole blood coagulation function in vitro. However, the carbon dots tend to activate platelets only at low concentrations. Intravenous administration of the carbon dots at doses up to 50 mg/kg did not impair the blood coagulation function. These results provide valuable information for the clinical application of fluorescent carbon dots.

  19. How Is Disseminated Intravascular Coagulation Diagnosed?

    MedlinePlus

    ... Platelets are blood cell fragments that help with blood clotting. Abnormal platelet numbers may be a sign of ... following tests examine the proteins active in the blood clotting process and how long it takes them to ...

  20. Glycerol monooleate-blood interactions.

    PubMed

    Ericsson, Emma M; Faxälv, Lars; Weissenrieder, Anna; Askendal, Agneta; Lindahl, Tomas L; Tengvall, Pentti

    2009-01-01

    In the present study the initial blood compatibility of glycerol monooleate (GMO)-coated surfaces was evaluated after deposition to surfaces and in bulk. The model surface was silica onto which multiple layers of fibrinogen or human serum albumin (HSA) was immobilized. The protein-coated surfaces were subsequently dip-coated in GMO in ethanol and used for blood plasma and whole blood experiments. The characterization methods included null ellipsometry, scanning electron microscopy, imaging of coagulation, hemolysis test and whole blood coagulation time by free oscillation rheometry. The results showed a GMO film thickness of approximately 350 A (approximately 4 microg/cm(2)) upon dip-coating in ethanolic solution. A major part of the deposited layer detached in aqueous solutions, especially during shear conditions. The coagulation time on GMO was significantly prolonged compared to that on HSA coated silica. Whole blood tests showed that GMO is a very weak hemolytic agent. Deposited GMO detached easily from surfaces upon rinsing or shearing, although a stable layer with undefined phase structure and a thickness of 50-70 A remained on HSA and fibrinogen precoated surfaces. This indicates that GMO has stronger adhesive forces to its substrate compared to the cohesive forces acting within the bulk GMO. The ability of GMO to detach from itself and tentatively form micelles or lipid bilayers when subjected to flowing blood may be of use in extravascular applications. It is concluded that GMO results in weak blood activation, and the material may in spite of this be suitable in selected biomaterial applications, especially as a biosealant and in colloidal dispersions.

  1. Nephrotic syndrome resulting in thromboembolic disease and disseminated intravascular coagulation in a dog.

    PubMed

    Ritt, M G; Rogers, K S; Thomas, J S

    1997-01-01

    Thromboembolic disease and progression to disseminated intravascular coagulation (DIC) are potential life-threatening complications for dogs with nephrotic syndrome. Platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), plasma concentration of fibrinogen degradation products (FDPs), antithrombin III (ATIII), protein C, and plasminogen were used to identify hemostatic abnormalities in a dog with nephrotic syndrome. Pulmonary thromboembolic disease was diagnosed by thoracic radiography, arterial blood gas analysis, and pulmonary scintigraphy. Prompt recognition and treatment of hemostatic complications is necessary in dogs with nephrotic syndrome.

  2. [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.

  3. Thermophoretically modified aerosol brownian coagulation.

    PubMed

    Arias-Zugasti, Manuel; Rosner, Daniel E

    2011-08-01

    A theory of aerosol coagulation rates resulting from continuum-regime brownian coagulation in the presence of size-dependent particle thermophoresis is developed and explored here. We are motivated by a wide variety of applications in which particle brownian coagulation occurs in a nonisothermal gas where differential thermophoretic drift contributes to, but does not dominate, the encounter frequency between suspended spherical particles (e.g., mist droplets) of different sizes. We employ a Smoluchowski-like population-balance to demonstrate the relative roles of brownian diffusion and thermophoresis in shaping the short and long time (asymptotic or "coagulation-aged") mist-droplet size distribution (DSD) function. To carry out these combined-mechanism DSD-evolution calculations we developed a rational "coupled" coagulation rate constant (allowing for simultaneous brownian diffusion and relative thermophoretic drift) rather than simply adding the relevant individual coagulation "kernels." Dimensionless criteria are provided to facilitate precluding other coagulation mechanisms not considered here (such as simultaneous sedimentation or Marangoni-flow-induced mist-droplet phoresis) and potential complications not included in the present model [as finite-rate coalescence, initial departures from the continuum (Stokes drag-) limit, and even dense (nonideal) vapor effects].

  4. Thermophoretically modified aerosol Brownian coagulation

    NASA Astrophysics Data System (ADS)

    Arias-Zugasti, Manuel; Rosner, Daniel E.

    2011-08-01

    A theory of aerosol coagulation rates resulting from continuum-regime Brownian coagulation in the presence of size-dependent particle thermophoresis is developed and explored here. We are motivated by a wide variety of applications in which particle Brownian coagulation occurs in a nonisothermal gas where differential thermophoretic drift contributes to, but does not dominate, the encounter frequency between suspended spherical particles (e.g., mist droplets) of different sizes. We employ a Smoluchowski-like population-balance to demonstrate the relative roles of Brownian diffusion and thermophoresis in shaping the short and long time (asymptotic or “coagulation-aged”) mist-droplet size distribution (DSD) function. To carry out these combined-mechanism DSD-evolution calculations we developed a rational “coupled” coagulation rate constant (allowing for simultaneous Brownian diffusion and relative thermophoretic drift) rather than simply adding the relevant individual coagulation “kernels.” Dimensionless criteria are provided to facilitate precluding other coagulation mechanisms not considered here (such as simultaneous sedimentation or Marangoni-flow-induced mist-droplet phoresis) and potential complications not included in the present model [as finite-rate coalescence, initial departures from the continuum (Stokes drag-) limit, and even dense (nonideal) vapor effects].

  5. Rotavirus activates dendritic cells derived from umbilical cord blood monocytes.

    PubMed

    Rosales-Martinez, D; Gutierrez-Xicotencatl, L; Badillo-Godinez, O; Lopez-Guerrero, D; Santana-Calderon, A; Cortez-Gomez, R; Ramirez-Pliego, O; Esquivel-Guadarrama, F

    2016-10-01

    Rotavirus is the most common cause of acute infectious diarrhea in human neonates and infants. However, the studies aimed at dissecting the anti-virus immune response have been mainly performed in adults. Dendritic cells (DCs) play a crucial role in innate and acquired immune responses. Therefore, it is very important to determine the response of neonatal and infant DCs to rotavirus and to compare it to the response of adult DCs. Thus, we determined the response of monocyte-derived DCs from umbilical cord blood (UCB) and adult peripheral blood (PB) to rotavirus in vitro. It was found that the rotavirus and its genome, composed of segmented doubled stranded RNA (dsRNA), induced the activation of neonatal DCs, as these cells up-regulated the levels of CD40, CD86, MHC II, TLR-3 and TLR-4, the production of cytokines IL-6, IL-12/23p40, IL-10, TGF-β (but not of IL-12p70), and the message for TNF-α and IFN-β. This activation enabled the neonatal DCs to induce a strong proliferation of allogeneic CD4(+) T cells and the production of IFN-γ. Moreover, neonatal DCs could be infected by rotavirus and sustain its replication. Neonatal DCs had a similar response as adult DCs towards rotavirus and its genome. However, adult DCs had a biased pro-inflammatory response compared to neonatal DCs, which showed a biased regulatory profile, as they produced higher levels of IL-10 and TGF-β, and were less efficient in inducing a Th1 type response. So it can be concluded that rotavirus and its genome can induce the activation of neonatal DCs in spite of their tolerogenic bias.

  6. Pleasant Events, Activity Restriction, and Blood Pressure in Dementia Caregivers

    PubMed Central

    Chattillion, Elizabeth A.; Ceglowski, Jenni; Roepke, Susan K.; von Känel, Roland; Losada, Andres; Mills, Paul J.; Romero-Moreno, Rosa; Grant, Igor; Patterson, Thomas L.; Mausbach, Brent T.

    2012-01-01

    Objective A combination of high engagement in pleasurable activities and low perceived activity restriction is potentially protective for a number of health and quality of life outcomes. This study tests the newly proposed Pleasant Events and Activity Restriction (PEAR) model to explain level of blood pressure (BP) in a sample of elderly dementia caregivers. Methods This cross-sectional study included 66 caregivers, ≥ 55 years of age, providing in-home care to a relative with dementia. Planned comparisons were made to assess group differences in BP between caregivers reporting high engagement in pleasant events plus low perceived activity restriction (HPLR; N = 22) to those with low pleasure plus high restriction (LPHR; N = 23) or those with either high pleasure plus high restriction or low pleasure plus low restriction (HPHR/LPLR; N = 21). Results After adjustments for age, sex, body mass index, use of anti-hypertensive medication, physical activity, and number of health problems, HPLR participants (86.78 mm Hg) had significantly lower mean arterial pressure compared to LPHR participants (94.70 mm Hg) (p = .01, Cohen’s d=0.89) and HPHR/LPLR participants (94.84 mm Hg) (p = .023, d=0.91). Similar results were found in post-hoc comparisons of both systolic and diastolic BP. Conclusions This study extends support for the PEAR model to physical health outcomes. Differences in BP between the HPLR group and other groups were of large magnitude and thus clinically meaningful. The findings may inform intervention studies aimed at investigating whether increasing pleasant events and lowering perceived activity restriction may lower BP. PMID:22888824

  7. Determination of phosphodiesterase I activity in human blood serum.

    PubMed

    Hynie, I; Meuffels, M; Poznanski, W J

    1975-09-01

    Phosphodiesterase I (EC 3.1.4.1) activity was detected in normal human blood serum. The enzyme is stable at laboratory temperature for three days, but is inactivated at pH less than 7. The pH for optimum activity increases with the substrate concentration (under the conditions used, from pH 9.0 to 10.2) and, conversely, the Km increases with pH and buffer concentration. The enzyme is inhibited by ethylenediaminetetraacetate but not by phosphate (0.1 mol/liter). We developed a simple quantitative method for its determination, based on hydrolysis of the p-nitrophenyl ester of thymidine 5'-monophosphate and subsequent measurement of the liberated p-nitrophenol at 400 nm in NaOH (0.1 mol/liter). Normal values (mean +/- 2 SD) were determined to be 33 +/- 6.4 U/liter. Preliminary studies indicate that phosphodiesterase I activity is greater than normal in serum of patients with necrotic changes in the liver or kidney or in cases of breast cancer, but not in that of patients with myocardial infarction, bone cancer, lung cancer, or chronic liver cirrhosis.

  8. 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.

  9. Assessment of the effects of dalteparin on coagulation variables and determination of a treatment schedule for use in cats.

    PubMed

    Schönig, Jette C; Mischke, Reinhard H

    2016-07-01

    OBJECTIVE To determine a treatment protocol for SC administration of dalteparin to cats on the basis of currently available detailed pharmacokinetic data and to assess the effect of SC administration of dalteparin to cats on coagulation variables such as activated partial thromboplastin time (aPTT), thrombin time, and results for thromboelastometry, compared with effects on anti-activated coagulation factor X (anti-Xa) activity. ANIMALS 6 healthy domestic shorthair cats. PROCEDURES Cats received 14 injections of dalteparin (75 anti-Xa U/kg, SC) at 6-hour intervals. Blood samples were collected before and 2 hours after the first and second injections on days 1, 2, and 4. Anti-Xa activity was measured by use of a chromogenic substrate assay, aPTT and thrombin time were measured by use of an automated coagulometer, and viscoelastic measurements were obtained with thromboelastrometry. RESULTS 2 hours after the second injection, the target peak anti-Xa activity range of 0.5 to 1.0 U/mL was achieved in all cats, whereas median trough values remained below this range. Peak anti-Xa activity had only minimal effects on coagulation variables; the maximum median ratio for aPTT (in relationship to the value before the first dalteparin injection) was 1.23. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study indicated that this treatment protocol resulted in reproducible anti-Xa activity in cats that was mostly within the targeted peak range of anti-Xa activity recommended for humans. Treatment in accordance with this protocol may not require routine coagulation monitoring of cats, but this must be confirmed in feline patients.

  10. Disorders of coagulation in pregnancy.

    PubMed

    Katz, D; Beilin, Y

    2015-12-01

    The process of haemostasis is complex and is further complicated in the parturient because of the physiological changes of pregnancy. Understanding these changes and the impact that they have on the safety profile of the anaesthetic options for labour and delivery is crucial to any anaesthetist caring for the parturient. This article analyses current theories on coagulation and reviews the physiological changes to coagulation that occur during pregnancy and the best methods with which to evaluate coagulation. Finally, we examine some of the more common disorders of coagulation that occur during pregnancy, including von Willebrand disease, common factor deficiencies, platelet disorders, the parturient on anticoagulants, and the more rare acute fatty liver of pregnancy, with a focus on their implications for neuraxial anaesthesia.

  11. Sequential coagulation factor VIIa domain binding to tissue factor

    SciTech Connect

    Oesterlund, Maria; Persson, Egon; Freskgard, Per-Ola . E-mail: msv@ifm.liu.se

    2005-12-02

    Vessel wall tissue factor (TF) is exposed to blood upon vascular damage which enables association with factor VIIa (FVIIa). This leads to initiation of the blood coagulation cascade through localization and allosteric induction of FVIIa procoagulant activity. To examine the docking pathway of the FVIIa-TF complex, various residues in the extracellular part of TF (sTF) that are known to interact with FVIIa were replaced with cysteines labelled with a fluorescent probe. By using stopped-flow fluorescence kinetic measurements in combination with surface plasmon resonance analysis, we studied the association of the resulting sTF variants with FVIIa. We found the docking trajectory to be a sequence of events in which the protease domain of FVIIa initiates contact with sTF. Thereafter, the two proteins are tethered via the first epidermal growth factor-like and finally the {gamma}-carboxyglutamic acid (Gla) domain. The two labelled sTF residues interacting with the protease domain of FVIIa bind or become eventually ordered at different rates, revealing kinetic details pertinent to the allosteric activation of FVIIa by sTF. Moreover, when the Gla domain of FVIIa is removed the difference in the rate of association for the remaining domains is much more pronounced.

  12. Blood Management Issues: Getting Clots Together When You Want Them

    PubMed Central

    McMillan, Darryl; Potger, Kieron; Southwell, Joanne

    2011-01-01

    Abstract: Coagulation is a complex process that allows whole blood to form clots at tissue and vessel sites where damage has occurred. Activation of the hemostasis system causes platelets and fibrin-containing clot to stop the bleeding. Perfusionists must find ways to preserve the coagulation system if we are to avoid bleeding in the cardiopulmonary bypass patient. It is still unclear what techniques are best to continue maintaining hemostasis and avoiding transfusion in patients requiring cardiopulmonary bypass (CPB). There are numerous factors that come into play with the use of CPB including deactivating the coagulation system with anticoagulants, hemodilution of the circulating blood volume, inflammatory response, and a possible pro-coagulant response from protamine with heparin reversal once the surgical procedure has been completed and CPB terminated. All these factors make achieving hemostasis post CPB extremely difficult. This review attempts to assess what is currently being discussed in the literature, which may improve hemostasis with cardiopulmonary bypass. There is still no one technique that will improve hemostasis post CPB. Perhaps the answer may lie in a combination of reported techniques that may in some way lead to the preserving of coagulation factors during CPB. PMID:21449241

  13. [Extracorporeal shockwave lithotripsy in patients with coagulation disorders].

    PubMed

    Ruiz Marcellán, F J; Mauri Cunill, A; Cabré Fabré, P; Argentino Gancedo Rodríguez, V; Güell Oliva, J A; Ibarz Servio, L; Ramón Dalmau, M

    1992-03-01

    During treatment of renal lithiasis with extracorporeal shock wave lithotripsy (ESWL) hemorrhagic events, especially renal hematoma, may present. A coagulation study is warranted in order to institute hemotherapy for blood factor deficiencies. We reviewed the records of 4,000 patients that had undergone ESWL. Of these, 17 (12 males, 5 females) presented coagulation disorders. The bleeding diatheses were due to platelet deficiency in 6 cases, plasma defects in 5, platelet and plasma disorders in 2, and capillary wall defects in 5 cases. The underlying cause was hepatosplenic disease in 12 cases, iatrogenic in 1, connectivopathy and corticoids in 2, and capillary purpura of unknown cause in 2 cases. Due to this protocol, no patient presented hemorrhage or hematoma from shock wave-induced lesions. These results show that a complete coagulation study must be performed in order to institute the necessary measures in patients with disorders of hemostasis due to the high risk of hematoma repeatedly reported in the literature.

  14. Comparison of coagulation performance and floc properties of a novel zirconium-glycine complex coagulant with traditional coagulants.

    PubMed

    Zhang, Zhilin; Wu, Chunde; Wu, Yue; Hu, Caixia

    2014-05-01

    A new inorganic-organic hybrid material zirconium-glycine complex (ZGC) was firstly used as a coagulant in a coagulation process to treat Pearl River raw water. Its coagulation performance was compared with commonly used aluminum (Al) coagulants such as aluminum sulfate (Al2(SO4)3) and polyaluminum chloride (PAC), in terms of water quality parameters and floc properties. ZGC coagulation achieved higher removal of turbidity (93.8%) than other traditional coagulants. Charge neutralization was proven to act as a dominant mechanism during ZGC coagulation. The aggregated flocs with ZGC showed the fastest growth rate and good recovery ability compared with the other coagulants and achieved the largest floc size within 5 min. The ZGC coagulant can decrease the hydraulic retention time and increase removal efficiency.

  15. PLASMA COAGULATION BY ORGANISMS OTHER THAN STAPHYLOCOCCUS AUREUS.

    PubMed

    BAYLISS, B G; HALL, E R

    1965-01-01

    Bayliss, Berenice G. (Washington State University, Pullman), and Elizabeth R. Hall. Plasma coagulation by organisms other than Staphylococcus aureus. J. Bacteriol. 89:101-105. 1965.-Approximately 200 organisms were investigated for their ability to clot human and rabbit plasma. Various anticoagulants were used in preparing the plasma: acid-citrate-dextrose, ethylenediaminetetraacetate, balanced oxalate, potassium and sodium oxalates, and heparin. Twelve organisms were found which coagulated citrated plasma in less than 8 hr: four strains of Streptococcus faecalis; two strains of S. faecalis var. zymogenes; three strains of S. faecalis var. liquefaciens; and one strain each of S. pyogenes, Escherichia coli, and Serratia marcescens. Six strains of coagulase-positive Staphylococcus were selected for use as controls. Experiments were performed to determine the mechanism by which these microorganisms coagulated citrated plasma. As this was the only plasma clotted, it was presumed that the citrate was utilized by the microorganisms, thereby releasing the calcium which was then made available so that normal physiological clotting could occur. To test this hypothesis, a chromatographic method was employed to determine the presence or absence of citrate. Coagulation tests, by use of increasing amounts of citrate, showed a linear relationship between the amount of citrate in the plasma and the coagulation time. It was demonstrated that the organisms must be actively metabolizing to clot citrated plasma. Proof for this was obtained by using a cell-free filtrate, to which thimerosal had been added to inhibit growth, instead of whole cultures for the coagulation test. Only the coagulase-positive staphylococci coagulated the citrated plasma under these conditions. From the results obtained, it was concluded that plasma coagulation by these organisms was by citrate utilization.

  16. Autoantibodies to coagulation factors: from pathophysiology to diagnosis and therapy.

    PubMed

    Cugno, Massimo; Gualtierotti, Roberta; Tedeschi, Alberto; Meroni, Pier Luigi

    2014-01-01

    Autoantibodies may develop against coagulation factors altering their function or promoting their rapid clearance. In non-congenitally deficient patients, they are usually in association with autoimmune diseases, malignancies, pregnancy or advanced age. The possible development of coagulation factor autoantibodies should be considered when a patient presents with bleeding symptoms without any prior bleeding diathesis. The most common disorder associated with coagulation factor autoantibodies is acquired factor VIII deficiency, which is characterized by hemorrhages involving soft tissues, muscles and skin; hemarthroses are less frequent than in the inherited form. Acquired deficiencies of von Willebrand factor and factor XIII due to autoantibodies are emerging conditions. Autoantibodies to the other coagulation factors may be associated with a wide spectrum of clinical manifestations ranging from minimal or no bleeding to life-threatening conditions. The diagnostic approach begins with global coagulation tests: prothrombin time (PT) and activated partial thromboplastin time (aPTT). In case of prolonged times, mixing studies (typically using normal plasma in a 1:1 proportion) should be performed. Specific factor and inhibitor assays, assessment of lupus anticoagulant and eventually enzyme immunoassays for specific anti-factor antibodies complete the evaluation. A prompt diagnosis of specific coagulation factor inhibitors is mandatory for starting an appropriate treatment aimed at overcoming the deficient factor, in case of bleeding, and, if possible, at the suppression of the autoantibody's production.

  17. Characterization of the biological effect of fish fibrin glue in experiments on rats: Immunological and coagulation studies

    PubMed Central

    Laidmäe, Ivo; Salum, Tiit; Sawyer, Evelyn S.; Janmey, Paul A.; Uibo, Raivo

    2011-01-01

    Fibrin glues (FG) of human or bovine origin are widely used for haemostasis and wound healing. In addition FGs are studied in many biomedical areas like cell therapy or tissue engineering. As any mammalian plasma products FG-s pose risk of transmission of bacteria, viruses, or prions and may compromise patient homeostasis. In this study, we examined coagulation parameters and immunological status of rats treated with salmon-derived FG. We evaluated the changes in thrombin time, prothrombin activity, and presence of antibodies on 46 Wistar rats. This study shows that salmon-derived FG, injected intraperitoneally, does not cause coagulation disturbances in the peripheral blood. After a first challenge with salmon-derived FG there were low but detectable amounts of antibodies revealed by ELISA and immunoblot. After a second administration there was substantial elevation of antibodies to FG components and other copurifying plasma proteins. Antibody reactivity to human Factor Va, revealed in three animals, was not associated with FG application. Taken together, blood immunological and coagulation parameters support the suitability of salmon-derived FG in the development of fibrin sealants for medical use. PMID:19484773

  18. Voltage-activated proton current in eosinophils from human blood.

    PubMed Central

    Gordienko, D V; Tare, M; Parveen, S; Fenech, C J; Robinson, C; Bolton, T B

    1996-01-01

    negative potentials and enhancement of maximum conductance (gH,max). The proton current recorded in eosinophils was significantly augmented under conditions of elevated cytosolic free calcium concentration ([Ca2+]i). The threshold level of [Ca2+]i associated with this effect lay between 0.1 and 1 microM and was not measurably affected by cytosolic acidification. 7. Eosinophils from human blood possess a voltage-dependent H+ conductance (gH) which normally allows protons to move outwards only; raising [Ca2+]i was associated with augmentation of gH and intracellular acidification or arachidonate shifted its activation range negatively towards physiological potentials. PMID:8910217

  19. ABO/Rh Blood-Typing Model: A Problem-Solving Activity

    ERIC Educational Resources Information Center

    Wake, Carol

    2005-01-01

    An ARO/Rh Blood-Typing kit useful for students to visualize blood-typing activities and practice problem-solving skills with transfusion reactions is presented. The model also enables students to identify relationships between A, B, and Rh antigens and antibodies in blood and to understand molecular mechanisms involved in transfusion agglutination…

  20. [Age-related changes in blood plasma antioxidant activity in population of the southern Altai].

    PubMed

    Chanchaev, E A; Aĭzman, R I

    2012-01-01

    The blood plasma antioxidant activity was studied in the Russian and Kazakh aborigines of the southern Altai low and high mountains. There was established a decrease of the