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Thomas A. Horbett - One of the best experts on this subject based on the ideXlab platform.
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effects of adsorbed proteins and surface chemistry on foreign body giant cell formation tumor necrosis factor alpha release and Procoagulant activity of monocytes
Journal of Biomedical Materials Research Part A, 2004Co-Authors: Mingchao Shen, Iris Garcia, Ronald V Maier, Thomas A. HorbettAbstract:The adhesion and activation of monocytes and macrophages are thought to affect the foreign body response to implanted medical devices. However, these cells interact with devices indirectly, because of the prior adsorption of proteins. Therefore, we preadsorbed several “model” biomaterial surfaces with proteins and then measured foreign body giant cell (FBGC) formation, tumor necrosis factor alpha (TNFα) release, and Procoagulant activity. The model surfaces were tissue culture polystyrene (TCPS), untreated polystyrene (PS), and Primaria, whereas the proteins used were albumin, fibronectin, fibrinogen, and immunoglobulin. FBGC formation, TNFα release, and Procoagulant activity of monocytes were the highest for surfaces preadsorbed with IgG. FBGC formation was lower on surfaces with adsorbed fibrinogen and fibronectin than on uncoated surfaces. TNFα release and Procoagulant activity of monocytes were similar on surface adsorbed with fibrinogen, fibronectin, or albumin. Monocyte activation was also affected by the surface chemistry of the substrates, because FBGC formation was the highest on PS and the lowest on TCPS. Monocyte Procoagulant activity was the highest on Primaria. Adsorbed proteins and surface chemistry were found to have strong effects on FBGC formation, monocyte TNFα release, and Procoagulant activity in vitro, providing support for the idea that these same variables could affect macrophage-mediated foreign body response to biomaterials in vivo. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 70A: 533–541, 2004
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the effect of adsorbed fibrinogen fibronectin von willebrand factor and vitronectin on the Procoagulant state of adherent platelets
Biomaterials, 2000Co-Authors: J M Grunkemeier, Weibor Tsai, Clive D. Mcfarland, Thomas A. HorbettAbstract:Procoagulant (activated) platelets provide a site for assembly of the prothrombinase complex which can rapidly convert prothrombin into thrombin (a potent inducer of clot formation). Previously, we reported that adhesion of platelets to surfaces preadsorbed with blood plasma caused them to become Procoagulant. In the present study we investigated the effect of adsorbed adhesion proteins (fibrinogen (Fg), fibronectin (Fn), von Willebrand factor (vWF) and vitronectin (Vn)) on the Procoagulant activity of adherent platelets. Adsorbed Fn, vWF and Fg promoted platelet adhesion in the following order: Fn
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hemocompatibility of treated polystyrene substrates contact activation platelet adhesion and Procoagulant activity of adherent platelets
Journal of Biomedical Materials Research, 1998Co-Authors: J M Grunkemeier, Weibor Tsai, Thomas A. HorbettAbstract:Platelet adhesion to biomaterials is often used as an index of blood compatibility, but a more clinically relevant issue is whether the adherent platelets are able to promote clot formation (i.e., if they are in the Procoagulant state). Platelets rapidly generate thrombin when they are in the Procoagulant state and the Va/Xa complex is present. We found that adherent platelets are Procoagulant by three different methods: binding of FITC–Annexin V, acceleration of thrombin generation in the presence of Xa, Va, and prothrombin; and clotting of recalcified plasma. In the clotting time studies, the effect of adherent platelets on TCPS was completely eliminated by the addition of Annexin V, which is known to bind tightly to Procoagulant platelets. The degree of Procoagulant activity of adherent platelets was determined by measuring thrombin generation rates in the presence of the clotting factors Va, Xa, and prothrombin and normalizing to the number of adherent platelets. Two key observations were made in these studies. First, the Procoagulant activity of platelets adherent to untreated and to several types of treated polystyrenes, as well as to glass and PET, was much greater than the Procoagulant activity of unstimulated bulk phase platelets. Little difference in the Procoagulant activity of adherent platelets was observed among the materials tested, however. Second, the Procoagulant activity of platelets prestimulated with ionophore and subsequently allowed to adhere to Plastek® M was much greater than when adherent platelets were stimulated by the adhesion event only. Measured values for platelet adhesion, platelet activation, and contact activation of blood plasma are discussed in the context of their potential combined impact on blood clotting. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 657–670, 1998.
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hemocompatibility of treated polystyrene substrates contact activation platelet adhesion and Procoagulant activity of adherent platelets
Journal of Biomedical Materials Research, 1998Co-Authors: J M Grunkemeier, Weibor Tsai, Thomas A. HorbettAbstract:Platelet adhesion to biomaterials is often used as an index of blood compatibility, but a more clinically relevant issue is whether the adherent platelets are able to promote clot formation (i.e., if they are in the Procoagulant state). Platelets rapidly generate thrombin when they are in the Procoagulant state and the VA/Xa complex is present. We found that adherent platelets are Procoagulant by three different methods: binding of FITC-Annexin V, acceleration of thrombin generation in the presence of Xa, Va, and prothrombin; and clotting of recalcified plasma. In the clotting times studies, the effect of adherent platelets on TCPS was completely eliminated by the addition of Annexin V, which is known to bind tightly to Procoagulant platelets. The degree of Procoagulant activity of adherent platelets was determined by measuring thrombin generation rates in the presence of the clotting factors Va, Xa, and prothrombin and normalizing to the number of adherent platelets. Two key observations were made in these studies. First, the Procoagulant activity of platelets adherent to untreated and to several types of treated polystyrenes, as well as to glass and PET, was much greater than the Procoagulant activity of unstimulated bulk phase platelets. Little difference in the Procoagulant activity of adherent platelets was observed among the materials tested, however. Second, the Procoagulant activity of platelets prestimulated with ionophore and subsequently allowed to adhere to Plastek M was much greater than when adherent platelets were stimulated by the adhesion event only. Measured values for platelet adhesion, platelet activation, and contact activation of blood plasma are discussed in the context of their potential combined impact on blood clotting.
Erwin A Vogler - One of the best experts on this subject based on the ideXlab platform.
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contributions of contact activation pathways of coagulation factor xii in plasma
Journal of Biomedical Materials Research Part A, 2009Co-Authors: Kaushik Chatterjee, Erwin A Vogler, Christopher A Siedlecki, Zhe GuoAbstract:Activation of human blood plasma coagulation by contact with hydrophilic or hydrophobic surfaces (Procoagulants) is dominated by kallikrein (Kal)-mediated activation of the blood zymogen FXII (Hageman Factor). Mathematical modeling of prekallikrein (PK)-deficient platelet-poor plasma (dPKPPP) and PK-reconstituted dPKPPP (RdPKPPP) coagulation shows that autoactivation of FXII () produces no more than about 25% of the total FXIIa produced by the intrinsic pathway. Autoactivation and reciprocal-activation increase in the same proportion with Procoagulant surface energy (water-wettability), whereas total amount of FXIIa produced per-unit-area Procoagulant remains roughly constant for any particular Procoagulant. These results suggest that Procoagulant surfaces initiate the intrinsic cascade by producing a bolus of FXIIa in proportion to surface energy or surface area but play no additional role in subsequent molecular events in the cascade. Results further suggest that reciprocal-activation occurs in proportion to the amount of FXIIa produced by the initiating autoactivation step. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
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autoactivation of blood factor xii at hydrophilic and hydrophobic surfaces
Biomaterials, 2006Co-Authors: Rui Zhuo, Christopher A Siedlecki, Erwin A VoglerAbstract:Abstract Contact activation of blood factor XII (FXII, Hageman factor) in neat-buffer solution is shown not to be specific for anionic hydrophilic Procoagulants as proposed by the accepted biochemistry of surface activation. Rather, FXII activation in the presence of plasma proteins leads to an apparent specificity for hydrophilic surfaces that is actually due to a relative diminution of the FXII→FXIIa reaction at hydrophobic surfaces. FXII activation in neat-buffer solution was effectively instantaneous upon contact with either hydrophilic (fully water-wettable clean glass) or hydrophobic (poorly water-wettable silanized glass) Procoagulant particles, with greater FXIIa yield obtained by activation with hydrophobic Procoagulants. In sharp contrast, both activation rate and yield was found to be significantly attenuated at hydrophobic surfaces in the presence of plasma proteins. Putative FXIIa produced by surface activation with both hydrophilic and hydrophobic Procoagulants was shown to hydrolyze blood factor XI (FXI) to the activated form FXIa ( FXI ⟶ FXIIa FXIa ) that causes FXI-deficient plasma to rapidly coagulate.
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Procoagulant stimulus processing by the intrinsic pathway of blood plasma coagulation
Biomaterials, 2005Co-Authors: Rui Zhuo, Rachel E Miller, Karen M Bussard, Christopher A Siedlecki, Erwin A VoglerAbstract:Abstract Potentiation of the intrinsic pathway of human blood plasma coagulation in vitro by contact with a solid Procoagulant surface leads to bolus release of thrombin (FIIa) in concentration proportion to the intensity of activation as measured by Procoagulant surface area or energy (water wettability). This rather remarkable finding is confirmed using two different assays: one triggering coagulation substantially through the intrinsic pathway alone and the second triggering coagulation through the intrinsic pathway in the presence of exogenous FIIa spikes. Similarity of experimental outcomes of these assays strongly suggests that endogenous FIIa production through the intrinsic pathway is independent of the absolute amount of FIIa present in plasma. Furthermore, we corroborate previous work indicating that Procoagulant surfaces remain activating after repeated use and are not poisoned or denatured in the process of activating plasma coagulation. It is concluded that the sharp control mechanism that gives rise to bolus-production of FIIa from the intrinsic pathway must occur between surface activation of FXII and the FII→FIIa step, is not related to inhibition by FIIa, and does not involve deactivation of Procoagulant surfaces.
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Contact activation of the plasma coagulation cascade. I. Procoagulant surface chemistry and energy
Journal of Biomedical Materials Research, 1995Co-Authors: Erwin A Vogler, Jane C. Graper, Harry W. Sugg, Lorraine M. Lander, Garry R. Harper, William J. BrittainAbstract:Contact activation of the intrinsic pathway of porcine blood plasma coagulation is shown to be a steep exponential-like function of Procoagulant surface energy, with low activation observed for poorly water-wettable surfaces and very high activation for fully water-wettable surfaces. Test Procoagulants studied were a system of oxidized polystyrene films with varying wettability (surface energy) and glass discs bearing close-packed self-assembled silane monolayers (SAMs) with well-defined chemistry consisting of 12 different terminating chemical functionalities. A monotonic trend of increasing coagulation activation with increasing water wettability was observed for the oxidized polystyrene system whereas results with SAM Procoagulants suggested a level of chemical specificity over and above the surface energy trend. In particular, it was noted that coagulation activation by SAMs terminated with -CO 2 H was much higher than anticipated based on surface wettability whereas -NH 3 ? ?-terminated SAMs exhibited very low Procoagulant activity. SAMs terminated in -(CH 2 ) 2 (CF 2 ) 7 CF 3 behaved as anticipated based on surface energy with very low Procoagulant activity and did not exhibit special properties sometimes attributed to perfluorinated compounds. Quantitative ranking of the inherent coagulation activation properties of Procoagulant surfaces was obtained by application of a straightforward phenomenological model expressed in a closed-form mathematical equation relating coagulation time to Procoagulant surface area. Fit of the model with a single adjustable parameter to experimental measurements of porcine platelet-poor plasma coagulation time was very good, implying that assertions and simplifications of the model adequately simulated reality. Two important propositions of the model were that (1) the number of putative activating sites scaled linearly with Procoagulant surface area, and (2) contact activation of the plasma coagulation cascade was catalytic in the sense that these activating sites were not consumed or poisoned by irreversible or slowly reversible protein adsorption during coagulation. An extension of the coagulation model proposed that Procoagulant activation properties scale exponentially with the surface density of polar (acid-base) sites, which, in turn, was related to Procoagulant wettability. © 1995 John Wiley & Sons, Inc.
Christopher A Siedlecki - One of the best experts on this subject based on the ideXlab platform.
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contributions of contact activation pathways of coagulation factor xii in plasma
Journal of Biomedical Materials Research Part A, 2009Co-Authors: Kaushik Chatterjee, Erwin A Vogler, Christopher A Siedlecki, Zhe GuoAbstract:Activation of human blood plasma coagulation by contact with hydrophilic or hydrophobic surfaces (Procoagulants) is dominated by kallikrein (Kal)-mediated activation of the blood zymogen FXII (Hageman Factor). Mathematical modeling of prekallikrein (PK)-deficient platelet-poor plasma (dPKPPP) and PK-reconstituted dPKPPP (RdPKPPP) coagulation shows that autoactivation of FXII () produces no more than about 25% of the total FXIIa produced by the intrinsic pathway. Autoactivation and reciprocal-activation increase in the same proportion with Procoagulant surface energy (water-wettability), whereas total amount of FXIIa produced per-unit-area Procoagulant remains roughly constant for any particular Procoagulant. These results suggest that Procoagulant surfaces initiate the intrinsic cascade by producing a bolus of FXIIa in proportion to surface energy or surface area but play no additional role in subsequent molecular events in the cascade. Results further suggest that reciprocal-activation occurs in proportion to the amount of FXIIa produced by the initiating autoactivation step. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
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autoactivation of blood factor xii at hydrophilic and hydrophobic surfaces
Biomaterials, 2006Co-Authors: Rui Zhuo, Christopher A Siedlecki, Erwin A VoglerAbstract:Abstract Contact activation of blood factor XII (FXII, Hageman factor) in neat-buffer solution is shown not to be specific for anionic hydrophilic Procoagulants as proposed by the accepted biochemistry of surface activation. Rather, FXII activation in the presence of plasma proteins leads to an apparent specificity for hydrophilic surfaces that is actually due to a relative diminution of the FXII→FXIIa reaction at hydrophobic surfaces. FXII activation in neat-buffer solution was effectively instantaneous upon contact with either hydrophilic (fully water-wettable clean glass) or hydrophobic (poorly water-wettable silanized glass) Procoagulant particles, with greater FXIIa yield obtained by activation with hydrophobic Procoagulants. In sharp contrast, both activation rate and yield was found to be significantly attenuated at hydrophobic surfaces in the presence of plasma proteins. Putative FXIIa produced by surface activation with both hydrophilic and hydrophobic Procoagulants was shown to hydrolyze blood factor XI (FXI) to the activated form FXIa ( FXI ⟶ FXIIa FXIa ) that causes FXI-deficient plasma to rapidly coagulate.
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Procoagulant stimulus processing by the intrinsic pathway of blood plasma coagulation
Biomaterials, 2005Co-Authors: Rui Zhuo, Rachel E Miller, Karen M Bussard, Christopher A Siedlecki, Erwin A VoglerAbstract:Abstract Potentiation of the intrinsic pathway of human blood plasma coagulation in vitro by contact with a solid Procoagulant surface leads to bolus release of thrombin (FIIa) in concentration proportion to the intensity of activation as measured by Procoagulant surface area or energy (water wettability). This rather remarkable finding is confirmed using two different assays: one triggering coagulation substantially through the intrinsic pathway alone and the second triggering coagulation through the intrinsic pathway in the presence of exogenous FIIa spikes. Similarity of experimental outcomes of these assays strongly suggests that endogenous FIIa production through the intrinsic pathway is independent of the absolute amount of FIIa present in plasma. Furthermore, we corroborate previous work indicating that Procoagulant surfaces remain activating after repeated use and are not poisoned or denatured in the process of activating plasma coagulation. It is concluded that the sharp control mechanism that gives rise to bolus-production of FIIa from the intrinsic pathway must occur between surface activation of FXII and the FII→FIIa step, is not related to inhibition by FIIa, and does not involve deactivation of Procoagulant surfaces.
Yona Nadir - One of the best experts on this subject based on the ideXlab platform.
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heparanase Procoagulant activity factor xa and plasminogen activator inhibitor 1 are increased in shift work female nurses
Annals of Hematology, 2015Co-Authors: Yona Nadir, Ron Hoffman, Benjamin Brenner, Gleb Saharov, Anat Kerenpolitansky, Inna Tzoran, Tamar ShochatAbstract:Epidemiologic studies indicate on an increased risk of cardiovascular disease and cancer in shift workers, although the underling mechanism is obscure. Heparanase directly enhances tissue factor (TF) activity leading to increased factor Xa production and subsequent activation of the coagulation system. In the present study, a comparison of coagulation markers among healthy shift working (SW) vs. healthy daytime working (DW) female nurses was performed. Thirty SW and 30 DW female nurses were enrolled. For each of the 60 participants, blood was drawn between 7:00 and 8:00 a.m. and at least 8 h after the last work shift. Plasma was studied for coagulation marker that included TF/heparanase Procoagulant activity, TF activity, heparanase Procoagulant activity, heparanase level, factor Xa level, plasminogen activator inhibitor 1 (PAI-1), plasminogen, α2-antiplasmin, fibrinogen, global protein C, von Willebrand factor, and D-dimer by chromogenic assays and enzyme-linked immunosorbent assays (ELISAs). Sleep quality was assessed by self-report according to the Pittsburgh Sleep Quality Index. The heparanase Procoagulant activity increased by 2-fold and the TF/heparanase Procoagulant activity increased by 1.5-fold in SW nurses compared to DW nurses (P < 0.05). Factor Xa levels and PAI-1 levels were significantly higher among SW nurses compared to the DW group (22 vs. 18 ng/ml, P < 0.05, and 32 vs. 22 ng/ml, P < 0.005, respectively). No significant differences were found in the other tested coagulation markers between the study groups. Heparanase Procoagulant activity, factor Xa level, and PAI-1 level were significantly higher in SW nurses compared to the DW group. These alterations of blood coagulation activation may potentially contribute to cardiovascular and cancer morbidity.
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heparanase Procoagulant activity is elevated and predicts survival in non small cell lung cancer patients
Thrombosis Research, 2014Co-Authors: Yona Nadir, Itay Shafat, Adi Meir, Michelle Wöllner, Elena Axelman, Israel Vlodavsky, Galit Sarig, R. Hoffman, Nissim Ben-haimAbstract:Abstract Background Heparanase is implicated in angiogenesis and tumor progression. We had earlier demonstrated that heparanase may also affect the hemostatic system in a non-enzymatic manner. It forms a complex and enhances the activity of the blood coagulation initiator- tissue factor (TF). Although increased heparanase antigen level in the plasma and biopsies of cancer patients was previously demonstrated, in the present study we evaluated, for the first time, the heparanase Procoagulant activity in the plasma of patients with lung cancer. Materials and Methods Sixty five patients with non-small cell lung cancer at presentation and twenty controls were recruited. Plasma was studied for TF / heparanase Procoagulant activity, TF activity and heparanase Procoagulant activity using chromogenic assay and heparanase antigen levels by ELISA. Results Heparanase antigen levels were higher in the study group compared to control (P = 0.05). TF / heparanase activity, and even more apparent, heparanase Procoagulant activity were significantly higher in the study group compared to controls (P = 0.008, P Conclusions Elevated heparanase Procoagulant activity in patients with lung cancer reveals a new mechanism of coagulation system activation in malignancy. Heparanase Procoagulant activity can potentially be used as a predictor for survival.
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heparanase Procoagulant activity is elevated in women using oral contraceptives
Human Reproduction, 2013Co-Authors: Moshe Matan, Elena Axelman, Benjamin Brenner, Yona NadirAbstract:STUDY QUESTION: What is the effect of estrogen on heparanase procogulant activity? SUMMARY ANSWER: Estrogen increases heparanase Procoagulant activity. WHAT IS KNOWN ALREADY: Estrogen therapy increases the risk of thrombosis and was previously found to up-regulate heparanase expression. Heparanase is involved in angiogenesis and metastasis and has been shown to form a complex with tissue factor (TF) and also shown to enhance the generation of factor Xa. STUDY DESIGN SIZE DURATION: A case-control study. Thirty-four healthy women using oral contraceptives (OC) and 41 women not using hormonal therapy and not pregnant per history were enrolled over a 5-month period at the Rambam Medical Center Haifa Israel. In vitro estrogen receptor-positive (MCF-7) and -negative (MDA-231) cell lines were incubated with estrogen tamoxifen and ICI-182.780 a pure estrogen receptor antagonist. The cell medium was evaluated for TF/heparanase complex activity TF activity and heparanase Procoagulant activity by chromogenic substrate. PARTICIPANTS/MATERIALS SETTING METHODS: Exclusion criteria included age <18 years post-menopausal women concomitant medications other than supplement minerals and vitamins acute or chronic illness. MAIN RESULTS AND THE ROLE OF CHANCE: The study demonstrates increased risk of high heparanase Procoagulant activity in OC users. When a cutoff level of 0.25 (absorbance 405-490 nm) was set the odds ratio was 131 (P < 0.0001). When all results were studied by quartiles in quartiles 3 and 4 the results were almost exclusively of the OC users (P < 0.0001). In cell cultures estrogen and tamoxifen increased heparanase Procoagulant activity in the medium of estrogen receptor-positive (MCF-7) cells. LIMITATIONS REASONS FOR CAUTION: The main limitation of the current study is that the two estrogens given to the women and cell cultures ethinyl estradiol (EE) and 17-beta-estradiol (E2) respectively may have different effects on the coagulation system although an increase in heparanase Procoagulant activity was demonstrated in both of them. Although the sample size of the study group was limited significant differences in the activation of the extrinsic coagulation pathway were demonstrated. WIDER IMPLICATIONS OF THE FINDINGS: The clinical relevance of the heparanase Procoagulant activity assay as a screening tool in thrombophilia work-up should further be elucidated. STUDY FUNDING/COMPETING INTEREST(S): No external funding was sought for this study. Authors Nadir and Brenner are named in a US Provisional Patent Application No. 29509/WO/12 filed on 18.01.2012. The other authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.
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an assay to evaluate heparanase Procoagulant activity
Thrombosis Research, 2011Co-Authors: Yona Nadir, Yael Kenig, Itay Shafat, Arie Drugan, Benjamin BrennerAbstract:BACKGROUND: Heparanase that was cloned from and is abundant in the placenta is implicated in cell invasion, tumor metastasis and angiogenesis. Recently, we demonstrated that heparanase is directly involved in the regulation of the hemostatic system. Heparanase was shown to form a complex and enhance tissue factor (TF) activity, resulting in increased factor Xa production (Nadir et al. Haematologica, 2010). The present work suggests a novel assay to evaluate heparanase Procoagulant activity. METHODS: Heparanase Procoagulant activity was studied using purified proteins of heparanase, TF, factor VIIa and factor X. The assay was verified in 55 plasma samples and compared to heparanase and tissue factor pathway inhibitor (TFPI) levels by ELISA and factor Xa, thrombin levels and antithrombin activity by chromogenic substrates. Thirty five samples were of third-trimester pregnant women (weeks 36-41) who were in labor or came for appointed elective cesarean section and 20 control samples were of non-pregnant healthy women. RESULTS: Heparanase Procoagulant activity assay was shown to differentiate heparanase Procoagulant effect from TF activity, in purified proteins. Heparanase Procoagulant activity was significantly higher in the plasma of pregnant women compared to non-pregnant (p < 0.005). Heparanase relative contribution to the TF / heparanase complex activity was significantly higher in the plasma of pregnant women compared to non-pregnant (29% increase, p < 0.0001). Differences in heparanase Procoagulant activity were more prominent than changes in heparanase levels by ELISA, TF activity, factor Xa, thrombin and free TFPI levels. CONCLUSIONS: Heparanase Procoagulant activity can be determined by the suggested assay. The assay revealed a significant contribution of heparanase to the Procoagulant state in late third-trimester pregnancy and at delivery.
J M Grunkemeier - One of the best experts on this subject based on the ideXlab platform.
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the effect of adsorbed fibrinogen fibronectin von willebrand factor and vitronectin on the Procoagulant state of adherent platelets
Biomaterials, 2000Co-Authors: J M Grunkemeier, Weibor Tsai, Clive D. Mcfarland, Thomas A. HorbettAbstract:Procoagulant (activated) platelets provide a site for assembly of the prothrombinase complex which can rapidly convert prothrombin into thrombin (a potent inducer of clot formation). Previously, we reported that adhesion of platelets to surfaces preadsorbed with blood plasma caused them to become Procoagulant. In the present study we investigated the effect of adsorbed adhesion proteins (fibrinogen (Fg), fibronectin (Fn), von Willebrand factor (vWF) and vitronectin (Vn)) on the Procoagulant activity of adherent platelets. Adsorbed Fn, vWF and Fg promoted platelet adhesion in the following order: Fn
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hemocompatibility of treated polystyrene substrates contact activation platelet adhesion and Procoagulant activity of adherent platelets
Journal of Biomedical Materials Research, 1998Co-Authors: J M Grunkemeier, Weibor Tsai, Thomas A. HorbettAbstract:Platelet adhesion to biomaterials is often used as an index of blood compatibility, but a more clinically relevant issue is whether the adherent platelets are able to promote clot formation (i.e., if they are in the Procoagulant state). Platelets rapidly generate thrombin when they are in the Procoagulant state and the Va/Xa complex is present. We found that adherent platelets are Procoagulant by three different methods: binding of FITC–Annexin V, acceleration of thrombin generation in the presence of Xa, Va, and prothrombin; and clotting of recalcified plasma. In the clotting time studies, the effect of adherent platelets on TCPS was completely eliminated by the addition of Annexin V, which is known to bind tightly to Procoagulant platelets. The degree of Procoagulant activity of adherent platelets was determined by measuring thrombin generation rates in the presence of the clotting factors Va, Xa, and prothrombin and normalizing to the number of adherent platelets. Two key observations were made in these studies. First, the Procoagulant activity of platelets adherent to untreated and to several types of treated polystyrenes, as well as to glass and PET, was much greater than the Procoagulant activity of unstimulated bulk phase platelets. Little difference in the Procoagulant activity of adherent platelets was observed among the materials tested, however. Second, the Procoagulant activity of platelets prestimulated with ionophore and subsequently allowed to adhere to Plastek® M was much greater than when adherent platelets were stimulated by the adhesion event only. Measured values for platelet adhesion, platelet activation, and contact activation of blood plasma are discussed in the context of their potential combined impact on blood clotting. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 657–670, 1998.
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hemocompatibility of treated polystyrene substrates contact activation platelet adhesion and Procoagulant activity of adherent platelets
Journal of Biomedical Materials Research, 1998Co-Authors: J M Grunkemeier, Weibor Tsai, Thomas A. HorbettAbstract:Platelet adhesion to biomaterials is often used as an index of blood compatibility, but a more clinically relevant issue is whether the adherent platelets are able to promote clot formation (i.e., if they are in the Procoagulant state). Platelets rapidly generate thrombin when they are in the Procoagulant state and the VA/Xa complex is present. We found that adherent platelets are Procoagulant by three different methods: binding of FITC-Annexin V, acceleration of thrombin generation in the presence of Xa, Va, and prothrombin; and clotting of recalcified plasma. In the clotting times studies, the effect of adherent platelets on TCPS was completely eliminated by the addition of Annexin V, which is known to bind tightly to Procoagulant platelets. The degree of Procoagulant activity of adherent platelets was determined by measuring thrombin generation rates in the presence of the clotting factors Va, Xa, and prothrombin and normalizing to the number of adherent platelets. Two key observations were made in these studies. First, the Procoagulant activity of platelets adherent to untreated and to several types of treated polystyrenes, as well as to glass and PET, was much greater than the Procoagulant activity of unstimulated bulk phase platelets. Little difference in the Procoagulant activity of adherent platelets was observed among the materials tested, however. Second, the Procoagulant activity of platelets prestimulated with ionophore and subsequently allowed to adhere to Plastek M was much greater than when adherent platelets were stimulated by the adhesion event only. Measured values for platelet adhesion, platelet activation, and contact activation of blood plasma are discussed in the context of their potential combined impact on blood clotting.