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Platelet-rich Plasma (platelet-rich + plasma)
Kinds of Platelet-rich Plasma Selected AbstractsEvaluation of postoperative drainage with application of platelet-rich and platelet-poor plasma following hemithyroidectomy: A randomized controlled clinical trial,,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2008John Yoo MD Abstract Background. Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) have been used to improve hemostasis and wound healing after surgery; however, randomized controlled trials proving their efficacy are lacking. Methods. Hemithyroidectomy was performed on 52 patients. Autologous PRP and PPP were applied during wound closure in the treatment group, while saline was applied in the controls. Outcome measures were postoperative drainage, pain, analgesic use, and length of hospital stay. Results. The 24-hour cumulative drainage was reduced by 29.3% in the treatment group (44.9 mL vs 63.5 mL, p = .039). The treatment group required less analgesic medication despite similar pain scores; however, the difference was not significant. There was a trend toward decreased length of stay for thePRP/PPP group (p = .059). Conclusions. Hemithyroidectomy served as a stringent test to evaluate the wound-healing capacity of platelet-rich and platelet-poor plasma. This study provides evidence that PRP and PPP reduced postoperative drainage in soft-tissue surgery. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [source] Platelet-rich plasma may prevent titanium-mesh exposure in alveolar ridge augmentation with anorganic bovine boneJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 10 2010Jesús Torres Torres J, Tamimi F, Alkhraisat MH, Manchón Á, Linares R, Prados-Frutos JC, Hernández G, López Cabarcos E. Platelet-rich plasma may prevent titanium-mesh exposure in alveolar ridge augmentation with anorganic bovine bone. J Clin Periodontol 2010; 37: 943,951. doi: 10.1111/j.1600-051X.2010.01615.x. Abstract Objective: Bone augmentation with the titanium-mesh (Ti-mesh) technique is susceptible to a large rate of complications such as morbidity of bone graft donor site, and mesh exposure to the oral cavity. The purpose of this study was to evaluate the effectiveness of anorganic bovine bone (ABB) in alveolar bone augmentation with the Ti-mesh technique. In addition, we investigated the effect of platelet-rich plasma (PRP) in preventing mesh exposure by using it to cover the Ti-mesh. Patients and Methods: Patients included in the clinical trial were randomly allocated by a blinded assistant into two groups. The 30 patients recruited for this study underwent 43 alveolar bone augmentation with the Ti-mesh technique using ABB as graft material in all of them. In 15 patients, the Ti-meshes were covered with PRP (PRP group) whereas in the other 15 the Ti-meshes were not (control group). After 6 months, patients were called for clinical, radiographic, and histological evaluation, and implant placement surgery. A total of 97 implants were placed in the augmented bone and their evolution was followed up for a period of 24 months. Results: Significant differences were found between the two study groups in terms of complications and bone formation. In the control group, 28.5% of the cases suffered from mesh exposure, while in the PRP group, no exposures were registered. Radiographic analysis revealed that bone augmentation was higher in the PRP group than in the control group. Overall, 97.3% of implants placed in the control group and 100% of those placed in the PRP group were successful during the monitoring period. We suggest that the positive effect of PRP on the Ti-mesh technique is due to its capacity to improve soft tissue healing, thereby protecting the mesh and graft material secured beneath the gingival tissues. Conclusions: Alveolar bone augmentation using ABB alone in the Ti-mesh technique is sufficient for implant rehabilitation. Besides, covering the Ti-meshes with PRP was a determining factor in avoiding mesh exposure. Ti-mesh exposure provoked significant bone loss, but in most cases it did not affect the subsequent placement of implants. [source] Platelet-rich plasma impairs osteoclast generation from human precursors of peripheral bloodJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2010Elisabetta Cenni Abstract Platelet-rich plasma is used to accelerate bone repair for the release of osteogenic growth factors from activated platelets. To date, the effects on osteoclasts have been only scarcely investigated, even though these cells are crucial for bone remodeling. The aim of this research was the evaluation of the effects of thrombin-activated platelets (PRP) on osteoclastogenesis from human blood precursors. We evaluated both the ability to influence osteoclast differentiation induced by the receptor activator of nuclear factor-kappaB ligand (RANKL), and the ability to induce osteoclast differentiation without RANKL. In both assays, the incubation with PRP supernatant at 10% did not significantly affect the formation of tartrate-resistant acid phosphatase (TRACP)-positive multinucleated cells that were able to form the F-actin ring. However, when PRP at 25 and 50% was added to the medium without RANKL, the generation of TRACP-positive multinucleated cells was inhibited. PRP, even at 10%, reduced the osteoclast-mediated bone collagen degradation, suggesting inhibition of osteoclast activation. Similarly, after incubation with PRP supernatant, calcitonin receptor mRNA was lower than the untreated samples. In conclusion, PRP at 10% interfered with the complete differentiation process of human osteoclast precursors. At higher concentration it impaired osteoclast formation also at an early stage of differentiation. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:792,797, 2010 [source] Endothelial cells incubated with platelet-rich plasma express PDGF-B and ICAM-1 and induce bone marrow stromal cell migrationJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 11 2009Elisabetta Cenni Abstract Platelet-rich plasma (PRP) is used to accelerate bone repair through the growth factors released by platelets. The purpose of this study was to evaluate if PRP induce human umbilical vein endothelial cells (HUVEC) to express mRNA for osteogenic growth factors and stimulate the migration of bone marrow stromal cell (BMSC). The effects of PRP were compared to those induced by vascular endothelial growth factor-A (VEGF-A) or, as a negative control, by platelet poor plasma (PPP). After incubation with PRP, but not with PPP, HUVEC showed an increased expression of mRNA for platelet derived growth factor-B (PDGF-B), and this effect was not inhibited by an anti-VEGF-A antibody. The migration of BMSC was more stimulated by HUVEC incubated with PRP than by HUVEC incubated with low serum medium or PPP. Besides, PRP increased the expression of intercellular adhesion molecule-1 (ICAM-1) and osteoprotegerin, but did not affect the expression either of the receptor activator for nuclear factor ,B ligand (RANKL) or of RANK. These findings support the hypothesis that PRP contribute to bone repair by favoring the pro-osteogenic function of endothelial cells, including the recruitment of osteoblast precursors and the expression of adhesion molecules for monocyte/macrophages, while inhibiting their pro-osteolytic properties. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1493,1498, 2009 [source] Antimicrobial activity of platelet-leukocyte gel against Staphylococcus aureusJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2008Dirk Jan F. Moojen Abstract Platelet-leukocyte gel (PLG) contains high concentrations of platelets and leukocytes. As leukocytes play an important role in the innate host-defense, we hypothesized that PLG might have antimicrobial properties. This study investigated the antimicrobial activity of PLG against Staphylococcus aureus and the contribution of myeloperoxidase (MPO), present in leukocytes, in this process. Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were obtained from whole blood of six donors. PLG was prepared by mixing PRP with autologous (PLG-AT) or bovine thrombin (PLG-BT). Antimicrobial activity of PLG-AT, PLG-BT, PRP, and PPP was determined in a bacterial kill assay. MPO release was measured by ELISA and activity was measured using a MPO activity assay. Cultures showed a rapid decrease in the number of bacteria for both PLG-AT and PLG-BT, which was maximal between 4 and 8 h, to approximately 1% of the bacteria in controls. The effect of PLG-AT was largest and significantly different compared to PRP (p,=,0.004) and PPP (p,<,0.001), however not compared to PLG-BT (p,=,0.093). PLG-AT, PLG-BT, and PRP showed a comparable, gradually increasing MPO release. MPO activity was comparable for all groups and remained stable. No correlation between MPO release, activity, and bacterial kill could be found. PLG appears to have potent antimicrobial capacity, but the role of MPO in this activity is questionable. PLG might represent a useful strategy against postoperative infections. However, additional research should elucidate its exact antimicrobial activity. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:404,410, 2008 [source] Does Bipolar Pacemaker Current Activate Blood Platelets?PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2009GRUNDE GJESDAL M.D. Objective: The aim of this study was to investigate whether bipolar pacemaker current lead can activate blood platelets. The null hypothesis was that 1 minute of electrical stimulation of platelets would not influence their subsequent reactivity to adenosine diphosphate (ADP). Background: Both platelets and muscle cells contain actin and myosin filaments, and both cells are activated following calcium influx. Muscle cells open their calcium channels and contract when exposed to an electric current. Current through a bipolar pacemaker lead will expose a small volume of blood, including platelets, to the depolarizing current. Platelet activation may ensue, resulting in aggregation, release reaction, and contraction. In contrast, a unipolar pacemaker system will not depolarize blood, but transmit current directly into the myocardium, and the current afterward passes through other tissues before returning to the pacemaker can. Methods: Platelet-rich plasma was prepared from two healthy subjects. Platelet reactivity to the agonist ADP was tested in paired samples in an aggregometer in a case/control setup. Results: Eighteen of 46 tested pairs of platelet-rich plasma showed increased reactivity in the paced sample; 26 were unchanged while two showed decreased reactivity in the paced sample. Using a two-sided sign test, the null hypothesis was rejected (P = 0.0004). Conclusions: The study demonstrates increased reactivity to ADP in platelets exposed in vitro to stimulation by pacemaker current. The clinical relevance of these findings remains to be investigated. [source] Activated platelets contribute to stimulation of cardiac afferents during ischaemia in cats: role of 5-HT3 receptorsTHE JOURNAL OF PHYSIOLOGY, Issue 3 2002Liang-Wu Fu Myocardial ischaemia activates blood platelets and cardiac sympathetic afferents, which mediate chest pain and cardiovascular reflex responses. We have demonstrated that activated platelets stimulate ischaemically sensitive cardiac sympathetic afferents. Platelets absorb and release 5-hydroxytryptamine (5-HT) when they are activated. In the present study we hypothesized that, by releasing 5-HT, activated platelets stimulate cardiac afferents during ischaemia through a 5-HT3 receptor mechanism. Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were obtained from cats. Activation of platelets in PRP was induced by thrombin (5 units ml,1) or collagen (2 mg kg,1). Using high-performance liquid chromatography, we observed that the concentration of 5-HT was increased significantly in suspensions of platelets activated with thrombin (PRP+thrombin, 28 ± 1.7 ,m) or collagen (PRP+collagen, 27 ± 2.5 ,m) compared with suspensions of unactivated platelets (PRP+saline, 2.3 ± 0.8 ,m) and PPP. During myocardial ischaemia and reperfusion, tirofiban, a specific inhibitor of platelet glycoprotein (GP) IIb-IIIa receptors (100 ,g kg,1, I.V., followed by 5 ,g kg,1 min,1), significantly reduced the increase in the concentration of 5-HT in cardiac venous plasma from ischaemic region. Nerve activity of single-unit cardiac afferents was recorded from the left sympathetic chain (T2-T5) in anaesthetized cats. Eighty ischaemically sensitive and seven ischaemically insensitive cardiac afferents were identified. Tirofiban reduced the ischaemia-related increase in activity of seven cardiac sympathetic afferents by 50 %. Injection of 1.5 ml of PRP+collagen or PRP+thrombin into the left atrium (LA) increased activity of 16 cardiac afferents. Tropisetron (300 ,g kg,1, I.V.), a selective 5-HT3 receptor antagonist, eliminated the afferent's responses to platelets activated with collagen or thrombin. Moreover, LA injection of 5-HT (20-40 ,g kg,1) and PBG (100 ,g kg,1), a 5-HT3 receptor agonist, stimulated nine ischaemically sensitive cardiac sympathetic afferents, significantly increasing the activity of these afferents. However, injection of ,-M-5-HT (100 ,g kg,1, LA), a 5-HT2 receptor agonist, stimulated only two of the nine ischaemically sensitive cardiac afferents, and thus did not significantly alter impulse activity of this group of afferents. Both the 5-HT1 (5-CT, 100 ,g kg,1, LA) and 5-HT4 receptor agonists (SC53116, 100 ,g kg,1, LA) did not stimulate any of the nine afferents tested. Tropisetron (300 ,g kg,1, I.V.) also eliminated the response of seven ischaemically sensitive cardiac afferents to exogenous 5-HT and attenuated the ischaemia-related increase in activity of nine cardiac sympathetic afferents by 41 %. Conversely, LA injection of 5-HT (40 ,g kg,1) did not stimulate any of seven ischaemically insensitive cardiac afferents, although this group of afferents consistently responded to bradykinin (3 ,g, LA). These data indicate that during myocardial ischaemia the activated platelets stimulate cardiac sympathetic afferents, at least in part, through a 5-HT3 receptor mechanism. [source] Flow cytometric and morphological characterization of platelet-rich plasma gelCLINICAL ORAL IMPLANTS RESEARCH, Issue 6 2006Juan Emilio Fernández-Barbero Abstract Background of problems: Platelet-rich plasma (PRP) gel is derived from an autogenous preparation of concentrated platelets and is widely used in implant dentistry as a vector for cell growth factors. However, limited data are available on its structure and composition. The present study was aimed at providing a flow cytometric and ultrastructural characterization of PRP gel. Materials and methods: Twenty PRP gel samples were obtained from healthy volunteers. These PRP gel specimens were prepared for transmission (TEM) and scanning electron microscopy (SEM) examination of their morphological ultrastructure. Flow cytometry with CD41-PE monoclonal antibody was used to detect platelet cells, as this antibody recognizes human-platelet-specific antigen CD41. Results: Both SEM and TEM showed that PRP gel contains two components: a fibrillar material with striated band similar to fibrin filaments, and a cellular component that contains human platelet cells. Both techniques indicated that no morphological elements were bound between the cellular component and the fibrillar material. The cells were confirmed as platelet cells by flow cytometric study after incubation with specific monoclonal antibody CD41-PE. Conclusion: PRP gel contains a fibrillar and a cellular (largely human platelet cell) component. This unique structure may be capable of acting as a vehicle for carrying of cells that are essential for soft/hard tissue regeneration. [source] Chalcones as potent antiplatelet agents and calcium channel blockersDRUG DEVELOPMENT RESEARCH, Issue 1 2001Chun-Nan Lin Abstract In an effort to continually develop potent antiplatelet agents with vasorelaxing and antiinflammatory actions, a novel series of antiinflammatory chalcones was continually screened to evaluate their antiplatelet and vasorelaxing effects. Their structure,activity relationships and mode of action were discussed and characterized. A novel series of antiinflammatory chalcones was studied on antiplatelet effect in rabbit washed platelets and human platelet-rich plasma (PRP) and vasorelaxing effect in rat thoracic aorta. Arachidonic acid-induced platelet aggregation was potently inhibited by almost all the chalcone derivatives and 13,15 also had a potent inhibitory effect on cyclooxygenase. The selective chalcones 12,16 tested in human PRP significantly inhibited secondary aggregation induced by adrenaline. In rat thoracic aorta, most of chalcones at high concentration significantly depressed the contractions induced by Ca2+ (1.9 mM) in high K+ (80 mM) medium and the phasic and tonic contractions caused by norepinephrine (3 ,M). In the rat thoracic aorta, the phenylephrine- and high K+ -induced 45Ca2+ influx were both inhibited by a selective chalcone derivative, 14. These results indicate that the antiplatelet actions of chalcones are mainly mediated through the suppression of cyclooxygenase activity and reduced thromboxane formation and their inhibitory effects on the contractile response caused by high K+ and norepinephrine in rat thoracic aorta are mainly due to inhibition of Ca2+ influx through both voltage-dependent and receptor-operated Ca2+ channels. Drug Dev. Res. 53:9,14, 2001. © 2001 Wiley-Liss, Inc. [source] The PFA-100Ô system for the assessment of platelet function in normotensive and hypertensive pregnanciesINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2001Marco Marietta Platelet function was studied in 30 pregnant women: 14 normotensive (C), and 16 affected by pregnancy-induced hypertension (PIH). Platelet aggregometry (PA) on platelet-rich plasma according to Born was compared with the new PFA-100Ô System (Dade International Inc, Miami, USA). This device evaluates platelet function (expressed in seconds as closure time, CT) in anticoagulated whole blood ex vivo at high shear rates. PA (expressed as percentage of light transmission) and CT were measured at baseline and after incubation with L-Arginine (L-Arg). MANOVA for repeated measures showed that L-Arg incubation significantly decreased PA (F=7.2, P < 0.05) and increased CT (F=6.05, P < 0.05) in the whole population of pregnant women. Moreover, we analysed separately both parameters in C and in PIH subjects. No differences in PA were found in both groups, neither at baseline nor after L-Arginine incubation. In contrast, CT was significantly longer in PIH in comparison to C before (95.9 s vs. 84 s, P < 0.05) as well after (115 s vs. 92 s, P < 0.05) L-Arginine incubation. Data from PFA-100Ô confirm our previous reports that during pregnancy the L-Arginine: Nitric Oxide pathway regulates platelet function. In hypertensive patients a significant decrease in platelet function was found by using the PFA-100Ô system. [source] Platelet-rich plasma may prevent titanium-mesh exposure in alveolar ridge augmentation with anorganic bovine boneJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 10 2010Jesús Torres Torres J, Tamimi F, Alkhraisat MH, Manchón Á, Linares R, Prados-Frutos JC, Hernández G, López Cabarcos E. Platelet-rich plasma may prevent titanium-mesh exposure in alveolar ridge augmentation with anorganic bovine bone. J Clin Periodontol 2010; 37: 943,951. doi: 10.1111/j.1600-051X.2010.01615.x. Abstract Objective: Bone augmentation with the titanium-mesh (Ti-mesh) technique is susceptible to a large rate of complications such as morbidity of bone graft donor site, and mesh exposure to the oral cavity. The purpose of this study was to evaluate the effectiveness of anorganic bovine bone (ABB) in alveolar bone augmentation with the Ti-mesh technique. In addition, we investigated the effect of platelet-rich plasma (PRP) in preventing mesh exposure by using it to cover the Ti-mesh. Patients and Methods: Patients included in the clinical trial were randomly allocated by a blinded assistant into two groups. The 30 patients recruited for this study underwent 43 alveolar bone augmentation with the Ti-mesh technique using ABB as graft material in all of them. In 15 patients, the Ti-meshes were covered with PRP (PRP group) whereas in the other 15 the Ti-meshes were not (control group). After 6 months, patients were called for clinical, radiographic, and histological evaluation, and implant placement surgery. A total of 97 implants were placed in the augmented bone and their evolution was followed up for a period of 24 months. Results: Significant differences were found between the two study groups in terms of complications and bone formation. In the control group, 28.5% of the cases suffered from mesh exposure, while in the PRP group, no exposures were registered. Radiographic analysis revealed that bone augmentation was higher in the PRP group than in the control group. Overall, 97.3% of implants placed in the control group and 100% of those placed in the PRP group were successful during the monitoring period. We suggest that the positive effect of PRP on the Ti-mesh technique is due to its capacity to improve soft tissue healing, thereby protecting the mesh and graft material secured beneath the gingival tissues. Conclusions: Alveolar bone augmentation using ABB alone in the Ti-mesh technique is sufficient for implant rehabilitation. Besides, covering the Ti-meshes with PRP was a determining factor in avoiding mesh exposure. Ti-mesh exposure provoked significant bone loss, but in most cases it did not affect the subsequent placement of implants. [source] Regenerative treatment with platelet-rich plasma combined with a bovine-derived xenograft in smokers and non-smokers: 12-month clinical and radiographic resultsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 1 2010Selcuk Yilmaz Abstract Aim: The purpose of this study was to assess the healing response of intrabony defects following regenerative treatment with platelet-rich plasma (PRP) combined with a bovine-derived xenograft (BDX) in smokers and non-smokers. Materials and Methods: A total of 24 advanced chronic periodontitis patients, 12 smokers and 12 non-smokers, with 113 intrabony defects with an intrabony component of 3 mm were included in this study. Defects were surgically treated with PRP/BDX. At baseline and 12 months after surgery, the following parameters were recorded: plaque and sulcus bleeding indices, probing depth (PD), relative attachment level, marginal recession, probing and radiographic bone levels. Results: Considering the soft tissue measurements, smokers and non-smokers presented a mean PD reduction of 3.97 ± 0.76 and 4.63 ± 0.52 mm, recession of 0.76 ± 0.44 and 0.50 ± 0.12 mm and attachment gain of 3.26 ± 0.42 and 4.06 ± 0.40 mm, respectively. Evaluation of the hard tissue findings revealed that the mean clinical and radiographic bone gains in smokers and non-smokers were 2.83 ± 0.47 and 3.63 ± 0.38 mm, 2.98 ± 0.38 and 3.67 ± 0.48 mm, respectively. Inter-group differences for PD reduction (p<0.05), attachment (p<0.001), clinical (p<0.001) and radiographic bone gains (p<0.001) were found to be significant between smokers and non-smokers. Conclusions: Within the limits of this study, the results indicate that treatment outcome following PRP/BDX application in intrabony defects is impaired with smoking. [source] Mesenchymal stem cells and platelet-rich plasma enhance bone formation in sinus grafting: a histomorphometric study in minipigsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 6 2008Francesco Pieri Abstract Objectives: Autologous, allogenic, and alloplastic materials for sinus augmentation have specific drawbacks, which has stimulated an ongoing search for new materials and tissue-engineering constructs. We investigated whether mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) seeded on a fluorohydroxyapatite (FH) scaffold can improve bone formation and bone-to-implant contact (BIC) in maxillary sinus grafting. Material and Methods: Bilateral sinus augmentation procedures were performed in eight minipigs. MSCs, PRP, and FH scaffold (test site) or FH alone (control site) were grafted in each maxillary sinus. Distal to the osteotomy, one dental implant per sinus was placed in the grafting material through the facial sinus wall. The animals were killed 3 months after grafting, and block sections of the implant sites were harvested and prepared for histomorphometric analysis. Results: After 12 weeks, a significant increase in bone formation occurred in the test sites compared with the control sites (42.51%versus 18.98%; p=0.001). In addition, BIC was significantly greater in the test sites compared with the control sites in the regenerated area (23.71%versus 6.63%; p=0.028). Conclusions: These findings show that sinus augmentation with MSCs,PRP, combined with FH may enhance bone formation and osseointegration of dental implants compared with FH alone in minipigs. [source] Effectiveness of a combination of platelet-rich plasma, bovine porous bone mineral and guided tissue regeneration in the treatment of mandibular grade II molar furcations in humansJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 8 2003Vojislav Lekovic Abstract Objective: A combination of platelet-rich plasma (PRP), bovine porous bone mineral (BPBM) and guided tissue regeneration (GTR) has been shown to be effective as regenerative treatment for intrabony periodontal defects. The purpose of this study was to evaluate the effectiveness of PRP, BPBM and GTR used in combination as regenerative treatment for grade II molar furcation defects in humans. Material and methods: Using a split-mouth design, a total of 52 grade II mandibular molar furcation defects were treated either with PRP/BPBM/GTR (experimental group, n=26) or with an open flap debridement (control group, n=26). The primary outcomes evaluated in this study included changes in pocket depth, attachment level and re-entry bone levels (horizontal and vertical) between baseline and 6 months postoperatively. Results: The results showed that the experimental group presented with significantly greater pocket reduction (4.07±0.33 mm for experimental and 2.49±0.38 mm for control sites), gain in clinical attachment (3.29 ± 0.42 mm for experimental and 1.68±0.31 mm for control sites), vertical defect fill (2.56± 0.36 mm for experimental and ,0.19±0.02 for control sites) and horizontal defect fill (2.28±0.33 mm for experimental and 0.08±0.02 mm for control sites) than the control group. Conclusions: It was concluded that the PRP/BPBM/GTR combined technique is an effective modality of regenerative treatment for mandibular grade II furcation defects. Further studies are necessary to elucidate the role played by each component of the combined therapy in achieving these results. Zusammenfassung Ziel: Eine Kombination von plättchemreichen Plasma (PRP), bovinem porösem Knochenmineral (BPBM) und gesteuerter Geweberegeneration (GTR) wurde als effektiv bei der regenerativen Behandlung von intraalveolären parodontalen Knochendefekten gezeigt. Der Zweck dieser Studie war die Evaluation der Effektivität von PRP, BPBM und GTR in der Kombination als regenerative Behandlung für Grad II Furkationsdefekte bei menschlichen Molaren. Material und Methoden: Unter Nutzung eines split-mouth Design wurden 52 Grad II Unterkiefermolaren Furkationsdefekte entweder mit PRP/BPBM/GTR (experimentelle Gruppe, n=26) oder mit einer offenen Reinigung (Lappenoperation) (Kontrollgruppe, n=26) behandelt. Die primären Ergebnisse die in dieser Studie evaluiert wurden, bezogen die Veränderung der Sondierungstiefen, des Stützgewebeniveaus und des Knochenniveaus bei reentry-Operationen (horizontal und vertikal) zwischen Basis und 6 Monate post operationem ein. Ergebnisse: Die Ergebnisse zeigten, dass die experimentelle Gruppe eine höhere Reduktion der Sondierungstiefen (4.07±0.33 mm für experimentelle und 2.49±0.38 mm für Kontrollflächen), einen höheren Stützgewebegewinn (3.29±0.42 mm für experimentelle und 1.68± 0.31 mm für Kontrollflächen), eine größere vertikale Defektfüllung (2.56±0.36 mm für experimentelle und ,0.19±0.02 für Kontrollflächen) sowie horizontale Defektfüllung (2.28± 0.33 mm für experimentelle und 0.08±0.02 mm für Kontrollflächen) verglichen mit den Kontrollen zeigte. Schlussfolgerungen: Es wird gefolgert, dass die Kombination von PRB/BPBM/GTR eine effektive Modifikation der regenerativen Behandlung bei Grad II Furkationsdefekten bei unteren Molaren ist. Weitere Studien sind notwendig, um die Rolle jeder Komponente dieser kombinierten Therapie in der Erzielung dieser Ergebnisse zu erfassen. Résumé Objectif: Une combinaison de plasma riche en plaquette (PRP), de minéral d'os bovin poreux (BPBM) et de régénération tissulaire guidée (GTR) a prouvé son efficacité en tant que traitement régénératif pour les lésions intra-osseuses parodontales. Cette étude se propose d'évaluer l'intérêt de l'utilisation en combinaison de PRP, BPBM et GTR comme traitement de régénération des lésions furcatoires molaires de classe II chez l'homme. Matériels et Méthodes: Par une étude conçue en bouche croisée, 52 lésions furcatoires molaires mandibullaires ont été traitées soit avec PRP/BPBM/GTR (groupe expérimental, n=26) ou par simple lambeau d'accès (groupe contrôle, n=26). Les objectifs primaires évalués dans cette étude étaient la modification de la profondeur de poche, le niveau d'attache et les niveaux osseux lors de la réentrée (en horizontal et en vertical) mesurés six mois post-op. Résultats: les résultats montrent que le groupe expérimental présentait significativement une plus importante réduction de poche (4.07±0.33 mm contre 2.49±0.38 mm pour les sites contrôles), un gain d'attache clinique plus important (3.29± 0.42 mm contre 1.68±0.31 mm pour les sites contrôles), un comblement vertical des lésions(2.56±0.36 mm contre ,0.19±0.02 pour les sites contrôles) et un comblement horizontal des lésions (2.28±0.33 mm contre 0.08± 0.02 mm pour les sites contrôles). Conclusions: Nous en concluons que la technique combinant PRP/BPBM/GTR est un traitement régénératif efficace pour les lésions de furcation molaire mandibulaire de classe II. Des études complémentaires sont nécessaires pour élucider le rôle joué par chaque élément de cette combinaison dans l'obtention de ces résultats. [source] In vivo study on the healing of bone defects treated with bone marrow stromal cells, platelet-rich plasma, and freeze-dried bone allografts, alone and in combinationJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2006D. Dallari Abstract The repair of confined trabecular bone defects in rabbits treated by autologous bone marrow stromal cells (BMSC), platelet-rich plasma (PRP), freeze-dried bone allografts (FDBA) alone and in combination (BMSC,+,PRP; FDBA,+,BMSC; FDBA,+,PRP; FDBA,+,PRP,+,BMSC) was compared. A critical size defect was created in the distal part of the femurs of 48 adult rabbits. Histology and histomorphometry were used in the evaluation of healing at 2, 4, and 12 weeks after surgery. The healing rate (%) was calculated by measuring the residual bone defect area. Architecture of the newly formed bone was compared with that of bone at the same distal femur area of healthy rabbits. The defect healing rate was higher in PRP,+,BMSC, FDBA,+,PRP, FDBA,+,BMSC, and FDBA,+,PRP,+,BMSC treatments, while lower values were achieved with PRP treatment at all experimental times. The highest bone-healing rate at 2 weeks was achieved with FDBA,+,PRP,+,BMSC treatment, which resulted significantly different from PRP (p,<,0.05) and BMSC (p,<,0.05) treatments. At 4 weeks, the bone-healing rate increased except for PRP treatment. Finally, the bone-healing rate of FDBA,+,PRP, FDBA,+,BMSC, and FDBA,+,PRP,+,BMSC was significantly higher than that of PRP at 12 weeks (p,<,0.05). At 12 weeks, significant differences still existed between PRP, BMSC, and FDBA groups and normal bone (p,<,0.05). These results showed that the combination of FDBA, BMSC and PRP permitted an acceleration in bone healing and bone remodeling processes. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] Epidermal growth factor released from platelet-rich plasma promotes endothelial cell proliferation in vitroJOURNAL OF PERIODONTAL RESEARCH, Issue 1 2010M.-P. Bertrand-Duchesne Bertrand-Duchesne M-P, Grenier D, Gagnon G. Epidermal growth factor released from platelet-rich plasmapromotes endothelial cell proliferation in vitro. J Periodont Res 2009; doi: 10.1111/j.1600-0765.2009.01205.x. © 2009 The Authors. Journal compilation © 2009 Blackwell Munksgaard Background and Objective:, The therapeutic benefits of platelet-rich plasma (PRP) for the promotion of healing and regeneration of periodontal tissues are thought to result from enrichment in growth factors released from platelets. The aim of this study was to evaluate the effects of specific growth factors released from PRP on endothelial cell proliferation. Material and Methods:, The levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor BB (PDGF-BB), basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) in supernatants of calcium- and thrombin-activated PRP samples from five donors were quantified by enzyme-linked immunosorbent assay. Supernatants were treated with neutralizing antibodies specific to each growth factor, and the effects of these treatments on human umbilical vein endothelial cell (HUVEC) proliferation in vitro were determined. The effect of removing EGF from PRP supernatants with antibody-coated beads on HUVEC proliferation was also tested. Results:, Average concentrations of VEGF, PDGF-BB, bFGF and EGF in PRP supernatants were 189, 27,190, 39.5 and 513 pg/mL, respectively. The addition of EGF neutralizing antibodies to the PRP supernatants significantly reduced HUVEC proliferation (up to 40%), while such an inhibition was not observed following neutralization of the other growth factors. Removal of EGF from PRP supernatants by treatment with antibody-coated beads also resulted in a significant decrease in HUVEC proliferation. Recombinant EGF increased HUVEC proliferation in vitro in a dose-dependent manner. Conclusion:, This study showed that PRP supernatants are highly mitogenic for endothelial cells and provided evidence that this effect may be due, at least in part, to the presence of EGF. In vivo experiments are needed to confirm the roles of specific growth factors released from PRP in the healing of oral surgical and/or periodontal wounds. [source] Bone healing in critical-size defects treated with platelet-rich plasma: a histologic and histometric study in rat calvariaJOURNAL OF PERIODONTAL RESEARCH, Issue 2 2008M. R. Messora Background and Objective:, The purpose of this study was to analyze histologically the influence of autologous platelet-rich plasma on bone healing in surgically created critical-size defects in rat calvaria. Material and Methods:, Thirty-two rats were divided into two groups: the control group (group C) and the platelet-rich plasma group. An 8-mm-diameter critical-size defect was created in the calvarium of each animal. In group C the defect was filled by a blood clot only. In the platelet-rich plasma group, 0.35 mL of platelet-rich plasma was placed in the defect and covered by 0.35 mL of platelet-poor plasma. Both groups were divided into subgroups (n = 8) and killed at either 4 or 12 wk postoperatively. Histometric (using image-analysis software) and histologic analyses were performed. The amount of new bone formed was calculated as a percentage of the total area of the original defect. Percentage data were transformed into arccosine for statistical analysis (analysis of variance, Tukey, p < 0.05). Results:, No defect completely regenerated with bone. The platelet-rich plasma group had a statistically greater amount of bone formation than group C at both 4 wk (17.68% vs. 7.20%, respectively) and 12 wk (24.69% vs. 11.65%, respectively) postoperatively. Conclusion:, Within the limits of this study, it can be concluded that platelet-rich plasma placed in the defects and covered by platelet-poor plasma significantly enhanced bone healing in critical-size defects in rat calvaria. [source] Synthesis of (2E)-2-methyl-3-(4-{[4-(quinolin-2-ylmethoxy)phenyl]sulfanyl}phenyl)prop-2-enoic acid (VUFB 20609) and 2-methyl-3-(4-{[4-(quinolin-2-ylmethoxy)phenyl]sulfanyl}phenyl)propanoic acid (VUFB 20584) as potential antileukotrienic agentsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2004J. Jampílek The Synthesis of (2E)-2-methyl-3-(4-{[4-(quinolin-2-ylmethoxy)phenyl]sulfanyl}phenyl) prop-2-enoic acid (VUFB 20609) and racemic 2-methyl-3-(4-{[4-(quinolin-2-ylmethoxy) phenyl]sulfanyl}phenyl)propanoic acid (VUFB 20584) as new potential antileukotrienic drugs are described. Due to a low reactivity of the 4-substituted aryl bromides (coupling of the 4-substituted aryl bromides do not provide an activating functional group with 4-methoxybenzene-1-thiol), special conditions, in particular specific heterogeneous copper catalysts, were used. Catalytic hydrogenation of the conjugated double bond on Pd/C in the presence of the sulfanyl group is discussed. In-vitro cytotoxicity testing was performed using a microplate colorimetric acid phosphatase assay. Antiplatelet activity was evaluated using an in-vitro test in human platelet-rich plasma. Some substances inhibited arachidonic acid-induced platelet aggregation. [source] Severe hemophilia with mild bleeding phenotype: molecular characterization and global coagulation profileJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2010E. SANTAGOSTINO Summary.,Background: Patients with severe hemophilia may show very varied bleeding tendencies, and the reasons for this heterogeneous clinical expression are unclear. The factor VIII/FIX genotype is the main determinant of the residual factor activity; however, different bleeding phenotypes have also been reported in patients sharing the same mutation. Such global coagulation tests as thrombin generation assays are tools with which to investigate different coagulation profiles among severe hemophiliacs. Objectives, patients and methods: This case,control study was aimed at comprehensively evaluating the role of genotype and endogenous thrombin potential (ETP) as predictors of the clinical phenotype in severe hemophiliacs with an extremely mild bleeding tendency (cases, n = 22), in comparison with those showing a typical bleeding tendency (controls, n = 50). Results: Cases were more frequently affected by hemophilia B than by hemophilia A, and showed a lower incidence of severe FVIII/FIX gene defects (referred to as null mutations), higher FVIII and FIX antigen levels and higher ETP values in platelet-rich plasma than controls (P < 0.05). By multivariate logistic regression, only non-null mutations were confirmed as an independent predictor of a mild clinical phenotype. Conclusions: These results indicate that non-null mutations represent the main determinant of the bleeding tendency, and that ETP measurement in platelet-rich plasma is able to identify severe hemophiliacs with a mild clinical phenotype. [source] Diagnostic utility of light transmission platelet aggregometry: results from a prospective study of individuals referred for bleeding disorder assessmentsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2009C. P. M. HAYWARD Summary.,Background: Light transmission aggregometry (LTA) is commonly performed to assess individuals for bleeding disorders. Objectives: The goal was to evaluate the incidence and spectrum of platelet function abnormalities in a prospective cohort of individuals referred for bleeding disorder assessments after exclusion of thrombocytopenia and von Willebrand disease. Patients/methods: Subjects were healthy controls and patients from a prospective cohort of individuals referred for bleeding disorder assessments after exclusion of thrombocytopenia and von Willebrand disease. LTA was performed by standardized methods using platelet-rich plasma adjusted to 250 × 109 platelets L,1. Maximal aggregation data were analyzed to determine the likelihood of detecting a platelet function disorder by LTA, and the sensitivity and specificity of LTA for platelet disorders. Results: The incidence of false positive LTA among subjects excluded of having bleeding disorders was similar to healthy controls. Abnormal LTA was more common in subjects with bleeding disorders and the likelihood of a bleeding disorder was significantly increased (odds ratio 32) when maximal aggregation was reduced with two or more agonists. Receiver operator curve analyses indicated that LTA had high specificity and moderate sensitivity for detecting inherited defects in platelet function and that the LTA agonists 1.25 ,g mL,1 collagen, 6 ,M epinephrine, 1.6 mM arachidonic acid and 1.0 ,M thromboxane analogue U44619 detected most inherited disorders with abnormal LTA. Conclusions: LTA is valuable for detecting platelet function abnormalities among individuals referred for bleeding problems, particularly when the test indicates abnormal responses to multiple agonists. [source] Platelet hyperprocoagulant activity in Type 2 diabetes mellitus: attenuation by glycoprotein IIb/IIIa inhibitionJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2008M. RAZMARA Summary.,Background:,Platelets are hyperactive in Type 2 diabetes mellitus (T2DM), and antiplatelet treatment with glycoprotein (GP) IIb/IIIa inhibitors provides better thrombotic protection in DM than in non-diabetic subjects. Objective:,We hypothesized that diabetic platelets are hyperprocoagulant, and that this hyperactivity can be inhibited by GPIIb/IIIa blockade. Methods:,Patients with T2DM and gender/age/body mass index-matched non-diabetic controls were recruited (n = 12 for both) to study the effect of GPIIb/IIIa blockade on platelet procoagulant activity. Platelet phosphotidylserine (PS), factor (F) Va expression, and platelet-derived microparticle (PDMP) generation were measured by whole blood flow cytometry. Platelet-dependent thrombin generation and plasma clotting time were monitored in recalcified platelet-rich plasma. Results:,Compared to controls, basal platelet activation was similar, while thrombin receptor activating peptide stimulated activation was enhanced in patients with T2DM. Diabetic platelets also displayed more profound elevations of platelet PS exposure, FVa binding, and PDMP generation upon stimulation. These alterations resulted in a hyperprocoagulant state, as evidenced by a marked increase in the platelet procoagulant index, enhanced thrombin generation, and a shortened plasma clotting time. GPIIb/IIIa blockade by c7E3 or SR121566 decreased platelet PS exposure and FVa binding, and diminished platelet procoagulant activity in patients with T2DM. Conclusions:,Platelets have increased procoagulant activity in patients with T2DM. The hyperprocoagulant activity is counteracted by GPIIb/IIIa blockade. [source] Complement activation triggered by chondroitin sulfate released by thrombin receptor-activated plateletsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2008O. A. HAMAD Summary.,Background:,Chondroitin sulfate (CS) is a glycosaminoglycan released by activated platelets. Objective:,Here we test the hypothesis that CS released by activated platelets can trigger complement activation in the fluid phase. Methods and results:,Thrombin receptor-activating peptide (TRAP)-6 was used to activate platelets in platelet-rich plasma and blood, anticoagulated with the thrombin inhibitor lepirudin. TRAP activation induced fluid-phase complement activation, as reflected by the generation of C3a and sC5b-9, which could be attenuated by the C3 inhibitor compstatin. Chondroitinase ABC treatment of supernatants from activated platelets totally inhibited the activation, indicating that platelet-derived CS had initiated the complement activation. Furthermore, addition of purified CS to plasma strongly triggered complement activation. C1q was identified as the recognition molecule, as it bound directly to CS, and CS-triggered complement activation could be restored in C1q-depleted serum by adding purified C1q. TRAP activation of whole blood increased the expression of CD11b on leukocytes and generation of leukocyte,platelet complexes. It was demonstrated that these leukocyte functions were dependent on C3 activation and signaling via C5a, as this expression could be inhibited by compstatin and by a C5aR antagonist. Conclusions:,We conclude that platelets trigger complement activation in the fluid phase by releasing CS, which leads to inflammatory signals mediated by C5a. [source] Ex vivo inhibition of thrombus formation by an anti-glycoprotein VI Fab fragment in non-human primates without modification of glycoprotein VI expressionJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2008P. OHLMANN Summary.,Objectives:,Glycoprotein (GP)VI is an attractive target for the development of new antithrombotic drugs. Its deficiency protects animals in several models of thrombosis, arterial stenosis and ischemia-,reperfusion while inducing no major bleeding tendency. The Fab fragment of one anti-GPVI monoclonal antibody (9O12.2) inhibits all GPVI functions in vitro. The aim of this study was to determine the ex vivo effects of 9O12.2 Fab on hemostasis, coagulation and thrombosis in non-human primates. Methods and results:,Blood samples were collected from cynomolgus monkeys before and after (30, 90 and 150 min, 1 and 7 days) a bolus injection of 9O12.2 Fab (4 mg kg,1) or vehicle. Platelet counts and coagulation tests (prothrombin time, activated partial thromboplastin time) were not modified following Fab injection. The PFA-100 closure time increased during the first hours and returned to initial values on day + 1. Platelet-bound Fab was detected from 30 min to 24 h after Fab injection without GPVI depletion at any time. Collagen-induced platelet aggregation was selectively and fully inhibited at 30 min. Thrombus formation on collagen in flowing whole blood (1500 s,1) was delayed and decreased, and collagen-induced or tissue factor-induced thrombin generation in platelet-rich plasma was profoundly inhibited. Conclusion:,The anti-GPVI 9O12.2 Fab inhibits thrombus formation ex vivo in non-human primates with a composite effect on platelet activation and thrombin generation in the absence of GPVI depletion. [source] Heritability of platelet function in families with premature coronary artery diseaseJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2007P. F. BRAY Summary.,Background:,Variations in platelet function among individuals may be related to differences in platelet-related genes. The major goal of our study was to estimate the contribution of inheritance to the variability in platelet function in unaffected individuals from white and African American families with premature coronary artery disease.Methods:,Platelet reactivity, in the absence of antiplatelet agents, was assessed by in vitro aggregation and the platelet function analyzer closure time. Heritability was estimated using a variance components model.Results:,Both white (n = 687) and African American (n = 321) subjects exhibited moderate to strong heritability (h2) for epinephrine- and adenosine diphosphate-induced aggregation (0.36,0.42 for white and >0.71 for African American subjects), but heritability for collagen-induced platelet aggregation in platelet-rich plasma was prominent only in African American subjects. Platelet lag phase after collagen stimulation was heritable in both groups (0.47,0.50). A limited genotype analysis demonstrated that the C825T polymorphism of GNB3 was associated with the platelet aggregation response to 2 ,M epinephrine, but the effect differed by race.Conclusions:,Considering the few and modest genetic effects reported to affect platelet function, our findings suggest the likely existence of undiscovered important genes that modify platelet reactivity, some of which affect multiple aspects of platelet biology. [source] Platelet function in sepsisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2004A. YAGUCHI Summary.,Background: Coagulation abnormalities and thrombocytopenia are common in severe sepsis, but sepsis-related alterations in platelet function are ill-defined. Objectives: The purpose of this study was to elucidate the effect of sepsis on platelet aggregation, adhesiveness, and growth factor release. Patients and methods: Agonist-induced platelet aggregation was measured in platelet-rich plasma separated from blood samples collected from 47 critically ill patients with sepsis of recent onset. Expression of platelet adhesion molecules was measured by flow cytometry and the release of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) was measured by ELISA in the supernatant of platelet aggregation. Results: Septic patients had consistently decreased platelet aggregation compared with controls, regardless of the platelet count, thrombin generation, or overt disseminated intravascular coagulation (DIC) status. The severity of sepsis correlated to the platelet aggregation defect. Adhesion molecules, receptor expression (CD42a, CD42b, CD36, CD29, PAR-1), and ,-granule secretion detected by P-selectin expression remained unchanged but the release of growth factors was differentially regulated with increased VEGF and unchanged PDGF after agonist activation even in uncomplicated sepsis. Conclusions: Sepsis decreases circulating platelets' hemostatic function, maintains adhesion molecule expression and secretion capability, and modulates growth factor production. These results suggest that sepsis alters the hemostatic function of the platelets and increases VEGF release in a thrombin-independent manner. [source] Factor VIIa-mediated tenase function on activated platelets under flowJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2004M. S. Goel Summary.,Background: Tissue factor (TF) and/or active factor (F)VIIa may be stored inside resting platelets. Objectives: The objective of this study was to examine if platelets, following activation of GPVI, could support tenase and prothrombinase activity without any exogenously added tissue factor. Methods: Thrombin (IIa) formation on gel-filtered platelets with added factors or the clotting of platelet-free plasma (PFP) or platelet-rich plasma (PRP) supplemented with corn trypsin inhibitor (CTI) (to inhibit factor XIIa) was studied in well plate assays with a fluorogenic thrombin substrate or in flow assays by fibrin visualization. Results: Pretreatment of convulxin (CVX)-stimulated, fibrinogen-adherent, gel-filtered platelets with anti-TF, anti-FVII/VIIa, or 1 nm PPACK [inhibitor of FVIIa, factor XIa and factor (F)IIa] delayed fibrin deposition on platelets perfused with PFP/CTI at 62.5 s,1. Anti-TF or anti-FVII/VIIa also attenuated thrombin generation in plate assays using recalcified PRP/CTI treated with CVX. Anti-TF or anti-FVII/VIIa (but not inhibited factor IXa) delayed the burst in thrombin production by gel-filtered platelets suspended in prothrombin and CVX by 14 min and 40 min, respectively. Anti-FVII/VIIa completely eliminated thrombin generation on fibrinogen-adherent, gel-filtered platelets pretreated with 10 µm PPACK and 10 µm EGR-CK [inhibitor of factor (F)Xa], rinsed, and then supplemented with CVX, prothrombin, and FX. Addition of anionic phospholipid to PFP/CTI or to a mixture of prothrombin, FX, and recVIIa was not sufficient to generate detectable tenase activity. Lastly, isolated, unactivated neutrophils suspended in FX, FII and recVIIa supported a very low level of thrombin generation sensitive to antagonism of P-selectin, CD18, and TF. Conclusions: Activated platelets supported tenase and prothrombinase activity by elevating the function or level of FVIIa and exposing active FVIIa or FVIIa-cofactor(s), distinct from anionic lipid, that may be, in part, TF. [source] Initiating and potentiating role of platelets in tissue factor-induced thrombin generation in the presence of plasma: subject-dependent variation in thrombogram characteristicsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 3 2004K. Vanschoonbeek Summary., The hemostatic activity of plasma is determined by platelet activation and coagulation, which processes are mutually stimulatory. We studied this interaction by measuring the cleavage of fluorescent thrombin substrate in platelet-rich plasma (PRP), using the calibrated thrombogram method. In freshly isolated human plasma, thrombin formation triggered by tissue factor was fully dependent on the presence of platelets. It was abolished by annexin A5, indicating dependence on phosphatidylserine (PS) exposure at activated platelets. Comparison of plasmas from various subjects showed considerable interindividual variation in total amount of thrombin generation, regardless of whether platelets or PS-containing phospholipids were present. Integrin ,IIb,3 antagonists and ADP receptor blockage, but not aspirin, decreased the rate of thrombin generation (thrombin peak level) and extended the time of onset. Platelet inhibition with cAMP-elevating agents decreased the thrombin-forming rate, but surprisingly shortened the onset time. Stimulation of platelets with agonists of Gi/q-coupled receptors and, to a larger extent, with collagen or Ca2+ -ionophore increased the rate of thrombin generation and shortened its onset. In PRP from donors with low and high generation, platelet inhibitors and activators were similarly effective. Taken together, these results indicate that, in tissue factor-triggered PRP, PS exposure on activated platelets regulates both onset and rate of thrombin generation. However, coagulant activity rather than platelet activation determines the total amount of thrombin formed, i.e. the endogenous thrombin potential. Thus, kinetics of thrombin generation in PRP are controlled by platelet inhibitors and agonists, but the process is restricted in amount by the subject-dependent variation in coagulation. [source] Different effects of abciximab and cytochalasin D on clot strength in thrombelastographyJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2004T. Lang Summary., Maximum amplitude (MA) in thrombelastography (TEG) consists of a plasmatic and a platelet component. To assess the magnitude of the plasmatic component, pharmacological approaches have been proposed to eliminate the platelet component. We evaluated the individual and combined effects of abciximab and cytochalasin D on the MA of TEG. Whole blood, platelet-rich plasma (PRP) and homologous platelet-poor plasma (PPP) from 20 healthy volunteers were spiked with abciximab or cytochalasin D or a combination of both and TEGs performed. Abciximab and cytochalasin D decreased MA in all samples. MA of whole blood (18.6 ± 3.1 mm) and PRP (33.7 ± 3.5 mm) spiked with abciximab or cytochalasin D alone (15.0 ± 2.9 mm and 25.0 ± 4.0 mm) were significantly higher when compared with abciximab and cytochalasin D combined (10.4 ± 3.0 and 20.2 ± 3.5 mm). While MA of PRP and homologous PPP were significantly (P < 0.001) different after individual administration of abciximab and cytochalasin D, combination of both abolished this difference (20.2 ± 3.5 mm and 20.4 ± 3.7 mm, P = 0.372). In whole blood of critically ill patients or patients undergoing major surgery there was also a significant difference of MA between abciximab alone and in combination with cytochalasin D (16.5 ± 11.3 mm and 11.3 ± 7.7 mm, P < 0.001). This indicates that in contrast to individual administration of abciximab or cytochalasin D, a combination of both compounds eliminates the platelet-specific effect on MA of TEG tracings. [source] Differential response of platelets to chemokines: RANTES non-competitively inhibits stimulatory effect of SDF-1,JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2004B. Shenkman Summary.,Background:,Among the chemokines related to CXC and CC receptor groups and released from platelets, leukocytes and endothelial cells, SDF-1, TARC and MDC have been found to be platelet agonists. Platelets do not contain SDF-1,. In contrast, RANTES is constitutively present in platelet ,-granules and released upon platelet activation. Objectives:,To study a possible role of RANTES as a modulator of SDF-1, effect on platelets, in relation to CXCR4 and various CC receptors. Methods:,CXCR-4 (CXCL12) receptor expression and platelet activation were evaluated by flow cytometry, platelet deposition was studied by cone and plate(let) analyzer, and platelet aggregation by turbidometric aggregometry. Results:,Flow cytometry studies revealed similar expression of CXCR-4, the specific receptor of SDF-1, on intact, inactivated, and activated platelets. Preincubation of platelets with RANTES affected neither CXCR-4 expression, nor SDF-1, binding to the platelet membrane. In the presence of fibrinogen, SDF-1, activated gel-filtered platelets. RANTES did not activate platelets, but substantially (by 70%) inhibited SDF-1,-induced fibrinogen binding. Similarly, RANTES abrogated the promoting effect of SDF-1, on whole blood platelet adhesion to endothelial cell monolayer under venous flow conditions. In platelet-rich plasma, RANTES moderately inhibited SDF-1,-induced platelet aggregation, while it did not affect aggregation induced by thrombin-receptor activation peptide, adenosine diphosphate, or phorbol 12-myristate 13-acetate. A synergistic inhibitory effect of RANTES and prostaglandin E1 used at subthreshold concentrations, on SDF-1,-induced aggregation and SDF-1,-induced fibrinogen binding to platelets was observed, which may suggest involvement of RANTES in a cAMP-dependent signal transduction pathway. Conclusions:,RANTES non-competitively inhibits activation of platelets by SDF-1,, and thus may play a regulatory role in platelet response to inflammation. [source] von Willebrand factor stimulates thrombin-induced exposure of procoagulant phospholipids on the surface of fibrin-adherent plateletsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 3 2003J. J. Briedé Summary., Studies from our laboratory have demonstrated that von Willebrand factor (VWF) stimulates thrombin generation in platelet-rich plasma. The precise role of VWF and fibrin in this reaction, however, remained to be clarified. In the present study we utilized thrombin-free planar fibrin layers and washed platelets to examine the relationship between platelet,fibrin interaction and exposure of coagulation-stimulating phosphatidylserine (PS) under conditions of low and high shear stress. Our study confirms that platelet adhesion to fibrin at a shear rate of 1000 s,1 requires fibrin-bound VWF. The cytosolic calcium concentration ([Ca2+]i) of stationary platelets was not elevated and PS exposing platelets were virtually absent (2 ± 2%). However, thrombin activation resulted in a marked increase in the number of PS exposing platelets (up to 85 ± 14%) along with a transient elevation in [Ca2+]i from 0.05 µmol L,1 up to 1.1 ± 0.2 µmol L,1. Platelet adhesion to fibrin at a shear rate of 50 s,1 is mediated by thrombin but not by fibrin-bound VWF. The [Ca2+]i of these thrombin-activated platelets was elevated (0.2 ± 0.1 µmol L,1), but only a minority of the platelets (11 ± 8%) exposed PS. The essential role of VWF in this thrombin-induced procoagulant response became apparent from low shear rate perfusion studies over fibrin that was incubated with VWF and botrocetin. After treatment with thrombin, the majority of the adherent platelets (57 ± 23%) exposed PS and had peak values of [Ca2+]i of about 0.6 µmol L,1. Taken together, these results demonstrate that thrombin-induced exposure of PS and high calcium response on fibrin-adherent platelets depends on shear- or botrocetin-induced VWF,platelet interaction. [source] | ||||||||||||||||||||||||||||