Sample records for prt treated platelets

  1. Mirasol PRT system inactivation efficacy evaluated in platelet concentrates by bacteria-contamination model

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    Jocić Miodrag


    Full Text Available Background/Aim. Bacterial contamination of blood components, primarily platelet concentrates (PCs, has been identified as one of the most frequent infectious complications in transfusion practice. PC units have a high risk for bacterial growth/multiplication due to their storage at ambient temperature (20 ± 2°C. Consequences of blood contamination could be effectively prevented or reduced by pathogen inactivation systems. The aim of this study was to determine the Mirasol pathogen reduction technology (PRT system efficacy in PCs using an artificial bacteria-contamination model. Methods. According to the ABO blood groups, PC units (n = 216 were pooled into 54 pools (PC-Ps. PC-Ps were divided into three equal groups, with 18 units in each, designed for an artificial bacteria-contamination. Briefly, PC-Ps were contaminated by Staphylococcus epidermidis, Staphylococcus aureus or Escherichia coli in concentrations 102 to 107 colony forming units (CFU per unit. Afterward, PC-Ps were underwent to inactivation by Mirasol PRT system, using UV (l = 265-370 nm activated riboflavin (RB. All PC-Ps were assayed by BacT/Alert Microbial Detection System for CFU quantification before and after the Mirasol treatment. Samples from non-inactivated PC-P units were tested after preparation and immediately following bacterial contamination. Samples from Mirasol treated units were quantified for CFUs one hour, 3 days and 5 days after inactivation. Results. A complete inactivation of all bacteria species was obtained at CFU concentrations of 102 and 103 per PC-P unit through storage/ investigation period. The most effective inactivation (105 CFU per PC-P unit was obtained in Escherichia coli setting. Contrary, inactivation of all the three tested bacteria species was unworkable in concentrations of ≥ 106 CFU per PC-P unit. Conclusion. Efficient inactivation of investigated bacteria types with a significant CFU depletion in PC-P units was obtained - 3 Log for all

  2. The effect of pathogen reduction technology (Mirasol) on platelet quality when treated in additive solution with low plasma carryover. (United States)

    Johnson, L; Winter, K M; Reid, S; Hartkopf-Theis, T; Marschner, S; Goodrich, R P; Marks, D C


    Pathogen reduction technologies (PRT) for platelets are now compatible with both plasma and platelet additive solutions (PAS). The aim of this study was to examine the effect of PRT on the platelet storage lesion, in the presence of PAS with low plasma carryover. PRT-treated (Mirasol) and untreated buffy coat-derived platelet concentrates prepared in 28% plasma/PAS-IIIM were evaluated using in vitro cell quality parameters on days 1, 2, 5, and 7 post-collection. At day 5, there were no significant differences between control and PRT treated platelets for swirl, viability, pO(2) , pCO(2) , mean platelet volume and adenosine diphosphate-induced aggregation. PRT treatment did not affect the functional integrity of the mitochondria. However, PRT resulted in a decrease in pH and enhancement of platelet glycolysis and activation, evidenced by increased glucose consumption and lactate production rates, increased expression of CD62P, CD63, annexin V staining and increased secretion of cytokines (P < 0.05). Hypotonic shock response and aggregation in response to collagen were also significantly reduced in PRT treated platelets (P < 0.05). Despite the observed differences in platelet metabolism and activation observed following PRT treatment in PAS and low plasma carryover, the results suggest that treatment and storage of platelets in PAS is no more detrimental to platelets than treatment and storage in plasma. © 2011 The Author(s). Vox Sanguinis © 2011 International Society of Blood Transfusion.

  3. Hemostatic function of buffy coat platelets in additive solution treated with pathogen reduction technology

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    Ostrowski, Sisse R; Bochsen, Louise; Windeløv, Nis Agerlin


    BACKGROUND: Pathogen reduction technologies (PRTs) may influence the hemostatic potential of stored platelet (PLT) concentrates. To investigate this, buffy coat PLTs (BCPs) stored in PLT additive solution (SSP+) with or without Mirasol PRT treatment (CaridianBCT Biotechnologies) were compared...... by functional hemostatic assays. STUDY DESIGN AND METHODS: We performed in vitro comparison of PRT (PRT-BCP) and control pooled-and-split BCPs (CON-BCP) after 2, 3, 6, 7, and 8 days' storage. Hemostatic function was evaluated with thrombelastography (TEG) and impedance aggregometry (Multiplate), the latter also...... in a sample matrix (Day 2) with or without addition of red blood cells (RBCs), control plasma, and/or PRT-treated plasma. RESULTS: PRT treatment of 8-day-stored BCPs influenced clot formation (TEG) minimally, with reductions in maximum clot strength (maximum amplitude, p = 0.014) but unchanged initial fibrin...

  4. Hemostatic function of buffy coat platelets in additive solution treated with pathogen reduction technology. (United States)

    Ostrowski, Sisse R; Bochsen, Louise; Windeløv, Nis A; Salado-Jimena, José A; Reynaerts, Inge; Goodrich, Raymond P; Johansson, Pär I


    Pathogen reduction technologies (PRTs) may influence the hemostatic potential of stored platelet (PLT) concentrates. To investigate this, buffy coat PLTs (BCPs) stored in PLT additive solution (SSP+) with or without Mirasol PRT treatment (CaridianBCT Biotechnologies) were compared by functional hemostatic assays. We performed in vitro comparison of PRT (PRT-BCP) and control pooled-and-split BCPs (CON-BCP) after 2, 3, 6, 7, and 8 days' storage. Hemostatic function was evaluated with thrombelastography (TEG) and impedance aggregometry (Multiplate), the latter also in a sample matrix (Day 2) with or without addition of red blood cells (RBCs), control plasma, and/or PRT-treated plasma. PRT treatment of 8-day-stored BCPs influenced clot formation (TEG) minimally, with reductions in maximum clot strength (maximum amplitude, p = 0.014) but unchanged initial fibrin formation (R), clot growth rate (α), and fibrinolysis resistance. In the absence of RBCs and plasma, PRT impaired aggregation (Multiplate) in stored BCPs, with reduced aggregation against thrombin receptor activating peptide-6 (p Addition of RBCs and PRT-treated or untreated plasma to PRT-BCP and CON-BCP, respectively, enhanced aggregation in both groups. Mirasol PRT treatment of BCPs had a minimal influence on clot formation, whereas aggregation in the absence of RBCs and plasma was significantly reduced. Addition of RBCs and plasma increased agonist-induced responses resulting in comparable aggregation between PRT-BCP and CON-BCP. The clinical relevance for PLT function in vivo of these findings will be investigated in a clinical trial. © 2010 American Association of Blood Banks.

  5. In vitro cell quality of buffy coat platelets in additive solution treated with pathogen reduction technology. (United States)

    Ostrowski, Sisse R; Bochsen, Louise; Salado-Jimena, José A; Ullum, Henrik; Reynaerts, Inge; Goodrich, Raymond P; Johansson, Pär I


    Pathogen reduction technologies (PRTs) may induce storage lesion in platelet (PLT) concentrates. To investigate this, buffy coat PLTs (BCPs) in PLT additive solution (AS; SSP+) with or without Mirasol PRT (CaridianBCT Biotechnologies) were assessed by quality control tests and four-color flow cytometry. In vitro comparison of PRT and control pooled-and-split BCPs after 2, 3, 6, 7, and 8 days of storage was made. PLT concentration, count per unit, swirl, metabolism, activation (CD62P, PAC1, CD42b/GPIb, CD63, CD40L/CD154, CD40, annexin V), and microparticle, sCD40L, and sCD62P release were evaluated. PRT induced a minor initial PLT loss (Day 2 [mean±SD], 302×10(9) ±44×10(9) PLTs/unit vs. 325× 10(9) ±46×10(9) PLTs/unit; pcontrol BCP. Swirling was comparable and declined with similar rates in PRT-treated and control BCPs during storage. PRT enhanced PLT metabolism and activation, evidenced by lower pH(22) ; increased glucose consumption and lactate production rates (p<0.01); early increases in CD62P-, PAC1-, CD63-, CD40L-, CD40-, and annexin V-positive PLTs; reduced GPIb expression; and enhanced release of PLT-derived MPs and sCD40L (all p<0.05). CD62P and PAC1 expression changed with different kinetics during storage and varying GPIb expression was displayed within the CD62P/PAC1-positive PLT subsets. PRT treatment of BCP in AS induced a minor initial PLT loss and enhanced metabolism and PLT activation. The clinical relevance for PLT function in vivo of these findings will be investigated in a clinical trial. © 2010 American Association of Blood Banks.

  6. Pathogen reduction treatment using riboflavin and ultraviolet light impairs platelet reactivity toward specific agonists in vitro

    NARCIS (Netherlands)

    Zeddies, Sabrina; de Cuyper, Iris M.; van der Meer, Pieter F.; Daal, Brunette B.; de Korte, Dirk; Gutiérrez, Laura; Thijssen-Timmer, Daphne C.


    Recent studies showed that Mirasol pathogen reduction treatment (PRT) leads to increased P-selectin expression and increased oxygen and glucose consumption in resting platelets (PLTs). This study investigates the effect of PRT on PLT activation. Untreated or Mirasol-treated PLTs were analyzed at

  7. In vitro cell quality of buffy coat platelets in additive solution treated with pathogen reduction technology

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Bochsen, Louise; Salado-Jimena, José A


    Pathogen reduction technologies (PRTs) may induce storage lesion in platelet (PLT) concentrates. To investigate this, buffy coat PLTs (BCPs) in PLT additive solution (AS; SSP+) with or without Mirasol PRT (CaridianBCT Biotechnologies) were assessed by quality control tests and four-color flow...

  8. Reactivity of mouse antibodies against bromelain-treated mouse erythrocytes with thrombin-treated mouse platelets. (United States)

    Kawaguchi, S


    The reactivity of mouse antibodies against bromelain-treated mouse erythrocytes (BrMRBC) with mouse platelets before and after thrombin treatment was assessed by flow cytometry. Anti-BrMRBC antibodies could bind to thrombin-treated platelets, although normal platelets were also weakly reactive with the antibodies. The binding of anti-BrMRBC antibodies to platelets was confirmed by complement-dependent lysis. It is suggested that thrombin-activated platelets may be a real target for anti-BrMRBC antibodies. PMID:2467876

  9. Effects of altered platelet number on pulmonary hypertension and platelet sequestration in monocrotaline pyrrole-treated rats

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    White, S.M.; Wagner, J.G.; Roth, R.A.


    To study the role of platelets in monocrotaline pyrrole (MCTP)-induced pulmonary hypertension, pulmonary sequestration of 111In-labeled platelets in rats treated with MCTP and anti-rat platelet serum (PAS) was examined. Lung injury from a single, intravenous injection of MCTP (3.5 mg/kg) at Day 8 was evident as elevated lung weight and lavage fluid protein and lactate dehydrogenase activity. Additionally, right ventricular hypertrophy and elevated pulmonary arterial pressures (PAP) occurred. Treatment with PAS on Days 6-8 did not affect the lung injury but resulted in an attenuation of the pulmonary hypertensive response. Pulmonary platelet sequestration was also decreased in PAS-treated rats, yet the sequestration in the lungs of MCTP-treated rats that received PAS was significantly higher than that in the lungs of N,N-dimethylformamide (DMF) controls. MCTP-treated rats receiving control serum (CS) tended to sequester more 111In-labeled platelets than respective DMF controls, but this was not statistically significant. Blood platelet half-life was unaltered in rats receiving CS. When rats were treated similarly with MCTP and PAS and were killed at 18 days, the attenuation of the pulmonary hypertensive response previously described was not observed, and lung injury was more extensive than when CS was given. Apparently, platelet depletion delayed the development of the pulmonary hypertensive response. Supranormal platelet numbers produced by splenectomy did not affect MCTP-induced lung injury or the elevation in PAP. These results support the hypothesis that the development of MCTP-induced pulmonary hypertension is mediated in part by platelets.

  10. Pathogen reduction treatment of buffy coat platelet concentrates in additive solution induces proapoptotic signaling. (United States)

    Reid, Samantha; Johnson, Lacey; Woodland, Narelle; Marks, Denese C


    Pathogen reduction technology (PRT) can potentially reduce the risk of transfusion-transmitted infections. However, PRT treatment of platelet (PLT) concentrates also results in reduced PLT quality and increased markers of apoptosis during storage. The aim of this study was to investigate changes to the expression and activation of proteins involved in apoptosis signaling. Samples from riboflavin and ultraviolet light PRT-treated and untreated (control) buffy coat-derived PCs in 70% SSP+ and 30% plasma were taken on Days 1, 5, and 7 of storage. Phosphatidylserine (PS) exposure, expression of Bcl-2 family proteins, cytochrome c release, and cleavage of caspase-3 and caspase-3 substrates were analyzed using flow cytometry and Western blotting. Compared to untreated controls, markers of apoptosis signaling were increased after PRT and subsequent storage. PS exposure on the PLT outer membrane was significantly higher after PRT on Days 5 and 7 of storage (p controls. This study demonstrated an increase in proapoptotic signaling during PLT storage, which was exacerbated by PRT. Many of these differences emerged outside the current 5-day storage period. These changes may not currently influence PLT transfusion quality, but will need to be carefully evaluated when considering extending PLT storage beyond 5 days. © 2012 American Association of Blood Banks.

  11. Effects of autologous platelet transfusion on platelet inhibition in ticagrelor-treated and clopidogrel-treated subjects. (United States)

    Teng, R; Carlson, G F; Nylander, S; Andersson, T L G


    Essentials Limited data on hemostatic benefits of platelet transfusion (PT) exist. 44 healthy subjects had a single dose of ticagrelor or clopidogrel ± autologous PT post-dosing. PT did not reverse ticagrelor's antiplatelet effects and had minimal impact post clopidogrel. Post-ticagrelor, PT is unlikely to be beneficial, and the benefits post-clopidogrel are unknown. Background Antiplatelet agents increase bleeding risk. Few data on hemostatic benefits of platelet transfusion exist. Objective To assess the effect of autologous platelet transfusion on ticagrelor-mediated and clopidogrel-mediated platelet inhibition in a single-center, open-label, randomized, cross-over study (NCT01744288). Methods Forty-four healthy subjects received ticagrelor (180 mg) or clopidogrel (600 mg; two functional CYP2C19 alleles [*1 or *17] required) with or without platelet transfusion (14-day washout). Subjects received one autologous platelet apheresis unit (approximately six pooled donor platelet units) 24 h (n = 15) or 48 h (n = 13) after ticagrelor or 48 h after clopidogrel (n = 16). Platelet apheresis was conducted 72 h before transfusion. Aspirin (81 mg per day) was taken from after apheresis until 24 h before transfusion. P2Y12 reaction units (PRUs) and inhibition of platelet aggregation (IPA) induced by ADP were measured. Results Mean age and body mass index were 30 years (standard deviation [SD] 6 years) and 26.9 kg m(-2) (SD 4.0 kg m(-2) ), respectively; 98% of subjects were men, and 39 of 44 completed treatment. Platelet transfusion 24 h after ticagrelor had minimal effects on IPA or PRU values within 48 h after transfusion. Platelet transfusion 48 h after ticagrelor also had minimal effects on IPA or PRU values at most post-transfusion times. Platelet transfusion 48 h after clopidogrel, versus no transfusion, had a small reversing effect on IPA (24 h, 36 h, and 48 h) and PRU values (12 h, 24 h, and 36 h) after transfusion. Conclusions Autologous platelet transfusion is

  12. Chemotherapy induced thrombocytopenia treated by four types of platelets concentrates

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    Nikolić Ljubinka I.


    Full Text Available Introduction: Serious adverse event of anticancer chemotherapy is glanulocytopenia and thrombocytopenia which can decrease efficiency of final therapy results. After many years, platelet concentrates transfusion (PCT is still researching problem without sure standpoint. The aim: To determine whether there is a difference in the clinical efficiency in the use of 4 types of platelet applied for transfusion; - to ascertain whether platelet count increase expressed as corrected count increment (CCI, is a better parameter for the evaluation of platelet transfusion efficiency than the bleeding time (Bt, as the only readily assessable in vivo platelet function related parameter. Subjects and methods: This paper is a part of academic (noncommercial IV phase observational nointervetion study. Investigation included 78 patients diagnosed with malignant lymphoma and metastatic solid tumors, transfused by platelet concentrates. Patients were devided into 4 groups, based on the type of platelet concentrates used for transfusion. Results: Patients, were transfused with total number of 647 PC units (235 units were non-leukodepleted and 412 units were leukodepleted. Mean number of PC transfusions per patient was 8.3 PC units, and 4.8 PC unit per one transfusion episode. Before PCT: platelets values were: 18.1 x109/L ±13.1, Bt 8.4±6.1min, and after PCT were 28.2 x109/L ±22.1, 4.7±4.4 min respectively ((p<0.01. Mean CCI value was 13.8±30.4. CCI was corrected in 196/129 PCT and Bt in 122/129 PCT. After supportive therapy using PCs Bt was corrected and became similar in all 4 groups. Discussion: Clinical output is the most important parameter for treatment decision because many patients can tolerate prolonged periods of profound thrombocytopenia without serious bleeding problems. Conclusion: In all 4 investigated groups of patients bleeding time was a far better parameter compared with CCI for the PC therapy efficiency. Authors suggest to be careful and follow

  13. Platelet count in healthy subjects treated with antiplatelet drugs

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    Maczy González-Rincón


    Full Text Available Platelet count in peripheral blood of healthy subjects with antiplatelet drugs. 20 subjects were analized. They were distributed in two groups: subject A: 10 who received aspirin (100 mg and B:10 with Clopidogrel (75 mg for 7 days. In all subjects studied platelet count in peripheral blood and PRP. It found a platelet count before treatment with antiplatelet agents in peripheral blood of 258,6 ± 54,46 x 109 l and 7 days after 254 ± 41,86 x 109 l (aspirin and 285,4 ± 70, 196,5 ± 37,90 x 109 l (Clopidogrel respectively. In the PRP of subjects before receiving aspirin was 486,5 ± 129,54 x 109 l and after 449,2 ± 85,51 x 109 l; prior to Clopidogrel ingestion was 565,2 ± 150,41 and 592,9 ± 203,46 x 109 l after treatment. Significant differences were found only for the platelet count in the Clopidogrel Group (p < 0.05. A significant decrease in platelet count was observed in peripheral blood after administration of Clopidogrel, possibly as a result of its pharmacological mechanism. More studies are needed to assess a greater number of individuals and better measure the effect of antiplatelet agents.

  14. platelets

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    Joanna Saluk


    Full Text Available Platelets are the smallest, depleted of nucleus blood cells which contain a typical cellular organelles including the mitochondria, so that have active metabolism. Platelets possess the highly organized cytoskeleton, specific secretory granules and unique membrane receptors system responsible for their high reactivity. The key role of blood platelets is to maintain normal hemostasis, but they also play important roles in inflammation, immune processes and the cancer progression. The anucleated, small platelets occur in representatives of all clusters of mammals, so it seems to be an adaptation feature. In other vertebrates similar hemostatic functions are played by large nucleated platelets, which are much more weakly reactive. Small, reactive platelets, appearing in the evolution of mammals, allowed the formation of clots faster and slower blood loss in case of injury, but also increased the risk of thromboembolic and cardiovascular diseases. Daily the human body forms about 1x1011 platelets, which are produced by a process of differentiation, maturation and fragmentation of the cytoplasm of mature megakaryocytes. The emergence of platelets is the final stage of megakaryocyte differentiation and is followed by formation of the direct precursors called proplatelets. The anucleated platelets are regarded as terminally differentiated cells, which are not capable of further cell division. However, despite the absence of a nucleus, in blood platelets the synthesis and transcription of mitochondrial DNA and protein synthesis occurring on the basis of mRNA from megakaryocytes has been confirmed. However, recent studies published in 2012 show that the platelets are capable not only of the process of protein synthesis, but also of generation of new cells, which are functionally and structurally similar to the parent platelets.

  15. Platelet-rich therapies for musculoskeletal soft tissue injuries. (United States)

    Moraes, Vinícius Y; Lenza, Mário; Tamaoki, Marcel Jun; Faloppa, Flávio; Belloti, João Carlos


    Platelet-rich therapies are being used increasingly in the treatment of musculoskeletal soft tissue injuries such as ligament, muscle and tendon tears and tendinopathies. These therapies can be used as the principal treatment or as an augmentation procedure (application after surgical repair or reconstruction). Platelet-rich therapies are produced by centrifuging a quantity of the patient's own blood and extracting the active, platelet-rich, fraction. The platelet-rich fraction is applied to the injured tissue; for example, by injection. Platelets have the ability to produce several growth factors, so these therapies should enhance tissue healing. There is a need to assess whether this translates into clinical benefit. To assess the effects (benefits and harms) of platelet-rich therapies for treating musculoskeletal soft tissue injuries. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (25 March 2013), the Cochrane Central Register of Controlled Trials (CENTRAL 2013 Issue 2), MEDLINE (1946 to March 2013), EMBASE (1980 to 2013 Week 12) and LILACS (1982 to March 2012). We also searched trial registers (to Week 2 2013) and conference abstracts (2005 to March 2012). No language or publication restrictions were applied. We included randomised and quasi-randomised controlled trials that compared platelet-rich therapy with either placebo, autologous whole blood, dry needling or no platelet-rich therapy for people with acute or chronic musculoskeletal soft tissue injuries. Primary outcomes were functional status, pain and adverse effects. Two review authors independently extracted data and assessed each study's risk of bias. Disagreement was resolved by discussion or by arbitration by a third author. We contacted trial authors for clarification of methods or missing data. Treatment effects were assessed using risk ratios for dichotomous data and mean differences (MD) or standardised mean differences (SMD) for continuous data, together with

  16. Differential proteomic analysis of platelets suggested target-related proteins in rabbit platelets treated with Rhizoma Corydalis. (United States)

    Li, Chun-Hong; Chen, Cen; Zhang, Qian; Tan, Chen-Ning; Hu, Yuan-Jia; Li, Peng; Wan, Jian-Bo; Feng, Gang; Xia, Zhi-Ning; Yang, Feng-Qing


    Corydalis yanhusuo W.T. Wang (Papaveraceae) (Rhizoma Corydalis) showed inhibitory effects on rabbit platelet aggregation induced by ADP, thrombin (THR) or arachidonic acid (AA). This study separates and identifies the possible target-related platelet proteins and suggests possible signal cascades of RC antiplatelet aggregation. Based on comparative proteomics, the differentially expressed platelet proteins treated before and after with 50 mg/mL RC 90% ethanol extract (for 15 min at 37 °C) were analyzed and identified by two dimensional gel electrophoresis (2-DE) and MALDI-TOF-MS/MS. To further verify the possible signalling pathways of RC antiplatelet aggregation function, the concentration of calcium (Ca2+) was measured by Fura-2/AM fluorescence (Ex 340/380 nm, Em 500 nm) (RC final concentrations of 0.0156-0.1563 mg/mL), the levels of P-selectin and cyclic guanosine monophosphate (cGMP) were quantified by ELISA (OD. 450 nm) (RC final concentrations of 0.0156-1.5625 mg/mL), and the 5-hydroxytryptamine (5-HT) level was measured using ortho-phthalaldehyde (OPT) fluorescence (Ex 340 nm, Em 470 nm) (RC final concentrations of 0.3125-1.5625 mg/mL). The expression of 52 proteins were altered in rabbit platelets after the treatment and the MALDI-TOF-MS analysis indicated that those proteins include 12 cytoskeleton proteins, 7 cell signalling proteins, 3 molecular chaperone proteins, 6 proteins related to platelet function, 16 enzymes and 7 other related proteins. Furthermore, RC extract could decrease the levels of 5-HT [inhibition rate of 96.80% (p rabbit platelets. The present study indicated that P2Y12 receptor might be one of the direct target proteins of RC in platelets. The signal cascades network of RC after binding with P2Y12 receptor is mediating Gαi proteins to activate downstream signalling pathways (AC and/or PI3K signalling pathways) for the inhibition of platelet aggregation.

  17. Inter-patient variability of platelet reactivity in patients treated with prasugrel and ticagrelor. (United States)

    Siller-Matula, Jolanta M; Akca, Betül; Neunteufl, Thomas; Maurer, Gerald; Lang, Irene M; Kreiner, Gerhard; Berger, Rudolf; Delle-Karth, Georg


    The aim of this study was to evaluate the distribution of platelet reactivity values in patients treated with prasugrel and ticagrelor. This prospective observational study enrolled 200 patients treated with prasugrel or ticagrelor. Platelet aggregation was determined by multiple electrode aggregometry after stimulation with adenosine diphosphate (ADP) in the maintenance phase of treatment with prasugrel or ticagrelor. Only 3% of patients in the prasugrel group and 2% of study participants in the ticagrelor group had high on treatment platelet reactivity (HTPR). The majority of patients displayed low on treatment platelet reactivity (LTPR; prasugrel: 69%; ticagrelor: 64%). The pharmacodynamic effect was similar in patients treated with prasugrel and ticagrelor: the median level of ADP-induced platelet aggregation was 15U (interquartile range IQR 9-21U) under prasugrel treatment and 17U (IQR 8-24U) under ticagrelor treatment (p=0.370). In conclusion, our study suggests that there is some degree of variability in ADP-induced platelet aggregation under treatment with prasugrel and ticagrelor.

  18. Circulating reticulated platelets over time in patients with myocardial infarction treated with prasugrel or ticagrelor. (United States)

    Eisen, Alon; Lerman-Shivek, Hila; Perl, Leor; Rechavia, Eldad; Leshem-Lev, Dorit; Zemer-Wassercug, Noa; Dadush, Oshrat; Kazum, Shirit; Codner, Pablo; Kornowski, Ran; Lev, Eli I


    Reticulated platelets (RP) are young, hyperactive platelets that are increased during situations of enhanced platelet turnover such as acute myocardial infarction (AMI). The dynamics of RP levels after AMI is not established. We aimed to characterize the levels of circulating RP over time in patients with AMI. Patients with AMI treated with ticagrelor or prasugrel who underwent percutaneous coronary intervention (PCI) were tested for circulating RP using flow cytometry with Thiazole orange staining at 3 time points at 2-4 days, 30-60 days and 1 year post PCI. Platelet reactivity was assessed using the VerifyNow P2Y12 assay at these time points (results in platelet reactivity units-PRU). Thirty-five patients were included in the study (mean age 62.6 ± 9.1 years, 82.9 % males). Median RP levels were similar at the first and second time points (17.5 %, IQR 25-75: 10.8-22.4 % and 14.9 %, IQR 25-75: 9.7-26.8 %, respectively; p = 0.75). However, RP levels after 1 year were significantly lower as compared to the first and second time points (10.5 % (IQR 25-75: 5.3-18.1 %), p = 0.005 and p = 0.01, respectively). Residual platelet reactivity was very low at all 3 time points (median PRU 25, IQR 25-75: 7-53) and did not change significantly between them (p = 0.66). No significant correlation was found between levels of RP and PRU at any given time point. RP levels of patients with AMI treated with prasugrel or ticagrelor decrease over time after the acute event. However, RP levels over time do not correlate well with residual platelet reactivity.

  19. Prognostic value of pre-therapy platelet elevation in oropharyngeal cancer patients treated with chemoradiation (United States)

    Shoultz-Henley, Sara; Garden, Adam S.; Mohamed, Abdallah S. R.; Sheu, Tommy; Kroll, Michael H.; Rosenthal, David I.; Gunn, G. Brandon; Hayes, Amos J.; French, Chloe; Eichelberger, Hillary; Kalpathy-Cramer, Jayashree; Smith, Blaine D.; Phan, Jack; Ayoub, Zeina; Lai, Stephen Y.; Pham, Brian; Kies, Merrill; Gold, Kathryn A.; Sturgis, Erich; Fuller, Clifton D.


    The purpose of this study is to evaluate potential associations between increased platelets and oncologic outcomes in oropharyngeal cancer patients receiving concurrent chemoradiation. 433 oropharyngeal cancer patients (OPC) treated with intensity modulated radiation therapy (IMRT) with concurrent chemotherapy between 2002 and 2012 were included under an approved IRB protocol. Complete blood count (CBC) data was extracted. Platelet and hemoglobin from the last phlebotomy (PLTpre-chemoRT, Hgbpre-chemoRT) before start of treatment were identified. Patients were risk-stratified using Dahlstrom-Sturgis criteria and were tested for association with survival and disease-control outcomes. Locoregional control (LRC), freedom from distant metastasis (FDM) and overall survival (OS) were decreased (ptherapy platelet indices. On Bayesian information criteria analysis, the optimal prognostic model was then used to develop nomograms predicting 3-, 5-, and 10-year OS. In conclusion, pre-treatment platelet elevation is a promising predictor of prognosis, and further work should be done to elucidate the utility of anti-platelets in modifying risk in OPC patients. PMID:26414107

  20. Pathogen reduction technologies: The pros and cons for platelet transfusion. (United States)

    Magron, Audrey; Laugier, Jonathan; Provost, Patrick; Boilard, Eric


    The transfusion of platelets is essential for diverse pathological conditions associated with thrombocytopenia or platelet disorders. To maintain optimal platelet quality and functions, platelets are stored as platelet concentrates (PCs) at room temperature under continuous agitation-conditions that are permissive for microbial proliferation. In order to reduce these contaminants, pathogen reduction technologies (PRTs) were developed by the pharmaceutical industry and subsequently implemented by blood banks. PRTs rely on chemically induced cross-linking and inactivation of nucleic acids. These technologies were initially introduced for the treatment of plasma and, more recently, for PCs given the absence of a nucleus in platelets. Several studies verified the effectiveness of PRTs to inactivate a broad array of bacteria, viruses, and parasites. However, the safety of PRT-treated platelets has been questioned in other studies, which focused on the impact of PRTs on platelet quality and functions. In this article, we review the literature regarding PRTs, and present the advantages and disadvantages related to their application in platelet transfusion medicine.

  1. Treatment of buffy coat platelets in platelet additive solution with the mirasol(®) pathogen reduction technology system. (United States)

    Castrillo, Azucena; Cardoso, Marcia; Rouse, Lindsay


    The Mirasol pathogen reduction technology (PRT) system uses riboflavin and ultraviolet light and is currently approved and used in Europe for the treatment of platelets and plasma. Mirasol treatment is intended to reduce the infectious pathogen load and to inactivate leukocytes in blood products. Our objective was to evaluate buffy coat platelet concentrates (BCPCs) prepared with platelet additive solution (PAS) and treated with the Mirasol system and to examine the effects on platelet cell quality during storage. 26 BCPCs were prepared and split, creating 13 paired control and test units. The test units were treated with the Mirasol system and the platelet quality was assessed in all units over 7 days of storage. All products met the incoming specifications for Mirasol treatment, and the pH of all Mirasol-treated BCPCs in PAS met the requirements of the Council of Europe guidelines throughout storage. Analysis of lactate production and glucose consumption rates, CD62p expression and cytokines indicates enhanced cellular metabolism in treated platelets, but the levels were within previously published ranges. While Mirasol-treated BCPCs in PAS had increased metabolism and activation compared to controls, the results indicate that these units can be stored for 7 days with acceptable cell quality.

  2. Effect of atorvastatin on platelet thromboxane A(2) synthesis in aspirin-treated patients with acute myocardial infarction. (United States)

    Santos, M Teresa; Fuset, M Paz; Ruano, Miguel; Moscardó, Antonio; Valles, Juana


    Inhibition of platelet thromboxane A(2) (TXA(2)) by aspirin is critical in patients with acute myocardial infarction (AMI), but some patients have persistent platelet TXA(2) production within 48 hours of the onset of AMI. Statins are known to reduce TXA(2) in aspirin-free patients with hypercholesterolemia. We hypothesized that treatment with aspirin plus atorvastatin could reduce persistent TXA(2) synthesis and aspirin resistance in patients with AMI. We evaluated platelet function in 184 aspirin-treated patients within 48 hours of the onset of AMI. Patients were divided into group A (treated with aspirin alone, n = 139) and group B (treated with aspirin plus atorvastatin, n = 45). We studied collagen-induced platelet TXA(2) synthesis, serotonin ((14)C-5HT) release and recruitment, and adenosine diphosphate-, arachidonic acid-, and collagen-induced platelet aggregation. Persistent TXA(2) synthesis was detected in 25% and 9% of groups A and B, respectively (p = 0.03). TXA(2), arachidonic acid-aggregation, and collagen-induced responses were significantly reduced in patients receiving dual treatment compared to those receiving aspirin monotherapy. Atorvastatin did not modify platelet reactivity in patients with efficiently blocked TXA(2) synthesis. These results strongly suggest a direct effect of the statin on platelet eicosanoid synthesis. This was confirmed in vitro by incubating washed aspirin-free and aspirin (1 muM)-treated platelets from normal subjects with 1 to 20 microM atorvastatin. Atorvastatin in vitro significantly reduced platelet TXA(2) synthesis and collagen-induced aggregation. In conclusion, atorvastatin combined with aspirin early in the onset of the acute event significantly reduced persistent TXA(2) and TXA(2)-dependent aspirin resistance. This could contribute to the clinical benefit of atorvastatin in patients with AMI.

  3. Relationship of cytokine levels and clinical effect on platelet-rich plasma-treated lateral epicondylitis. (United States)

    Lim, Wonbong; Park, Sang H; Kim, Bora; Kang, Sin W; Lee, Jung W; Moon, Young L


    Lateral epicondylitis (LE) is difficult to manage and can result in significant patient morbidity. Currently, the clinical use of platelet-rich plasma (PRP) for painful tendons has received attention, but its efficacy remains controversial. This study aimed to investigate the clinical effects of PRP and its biological components. A total of 156 patients with LE were randomly divided into group 1, treated with a single injection of 2-ml autologous PRP, and group 2, treated with a control received only physical therapy without injection. Both groups used a tennis elbow strap and performed stretching and strengthening exercises during 24 weeks' follow-up. Pain and functional improvements were assessed using the visual analog scale (VAS), Modified Mayo Clinic Performance Index for the elbow, and magnetic resonance imaging (MRI). White blood cell count, platelet count, and levels of platelet-derived growth factor-AB (PDGF-AB), PDGF-BB, transforming growth factor-β (TGF-β), vascular endothelial growth factor, epithelial growth factor, and interleukin-1 β in PRP were measured and investigated for statistical correlation with the clinical score. At 24 weeks, all pain and functional variables, including VAS score, Mayo Clinic performance scores, and MRI grade, improved significantly in group 1 (p PRP than in whole blood. TGF-β level significantly correlated with Mayo Clinic performance score and MRI grade improvement. Thus, TGF-β level in PRP is considered to play a pivotal role in tendon healing. These results may contribute to identifying the best protocol for PRP application in tendinopathies. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  4. Assessment of the healing of standardized wounds in rabbits treated serially with autologous platelet-rich plasma gel

    Directory of Open Access Journals (Sweden)

    Eliane Szücs dos Santos


    Full Text Available Recent studies have been carried out to evaluate the role of platelet-rich plasma (PRP in the cicatrization of wounds; however, the protocols for treatment have been based on a single application of PRP.To evaluate the effect of autologous platelet-rich plasma in gel form on the cicatrization of cutaneous wounds in vivo experimental model, wounds were induced in the dorsal areas of six New Zealand white rabbits with the aid of an 8-mm punch. The right side was used as a control (A and treated with 0.9% NaCl, whereas the left side (B was treated serially with the autologous platelet-rich plasma gel. Lesions were assessed over a 17-day period. At days 0, 10 and 17, the animals were evaluated and morphological and morphometric analyses of the wounds were performed. At day 17, a biopsy was performed for histopathological evaluation. Macroscopically, wounds treated with PRP showed better cicatrization and higher contraction percentages than the control wounds. Regarding the percentage of wound contraction, it was found that the average treated wound with autologous platelet-rich plasma gelwas 95% while withthecontrolwas88%. We concluded that autologous platelet-rich plasma gel is effective and accelerates cicatrization when used serially in short intervals, thus confirming its therapeutic potential in cutaneous lesions and potential as an alternative wound treatment option.

  5. Inhibition of ovine in vitro fertilization by anti-Prt antibody: hypothetical model for Prt/ZP interaction. (United States)

    Pimenta, Jorge; Sardinha, João; Marques, Carla C; Domingos, Ana; Baptista, Maria C; Barbas, João P; Martins, Ivo C; Mesquita, Patrícia; Pessa, Pedro; Soares, Rui; Viegas, Aldino; Cabrita, Eurico; Horta, E M António; Fontes, Carlos A; Prates, A M José; Pereira, M L N Rosa


    The impact of prion proteins in the rules that dictate biological reproduction is still poorly understood. Likewise, the role of prnt gene, encoding the prion-like protein testis specific (Prt), in ram reproductive physiology remains largely unknown. In this study, we assessed the effect of Prt in ovine fertilization by using an anti-Prt antibody (APPA) in fertilization medium incubated with spermatozoa and oocytes. Moreover, a computational model was constructed to infer how the results obtained could be related to a hypothetical role for Prt in sperm-zona pellucida (ZP) binding. Mature ovine oocytes were transferred to fertilization medium alone (control) or supplemented with APPA, or pre-immune serum (CSerum). Oocytes were inseminated with ovine spermatozoa and after 18 h, presumptive zygotes (n=142) were fixed to evaluate fertilization rates or transferred (n=374) for embryo culture until D6-7. Predicted ovine Prt tertiary structure was compared with data obtained by circular dichroism spectroscopy (CD) and a protein-protein computational docking model was estimated for a hypothetical Prt/ZP interaction. The fertilizing rate was lower (P=0.006) in APPA group (46.0+/-6.79%) when compared to control (78.5+/-7.47%) and CSerum (64.5+/-6.65%) groups. In addition, the cleavage rate was higher (PZP docking. Computational analyses predicted a favorable Prt-binding activity towards ZP domains. Our data indicates that the presence of APPA reduces the number of fertilized oocytes and of cleaved embryos. Moreover, the CD analysis data reinforces the predicted ovine Prt trend towards an alpha-helical structure. Predicted protein-protein docking suggests a possible interaction between Prt and ZP, thus supporting an important role for Prt in ovine fertilization.

  6. Use of platelet growth factors in treating wounds and soft-tissue injuries:


    Bolta, Zoran; Rožman, Primož


    Tissue repair begins with clot formation and platelet degranulation, which release the growth factors (GFs) necessary for wound repair. Platelet-derived GFs are biologically active substances that enhance tissue repair mechanisms such as chemotaxis, cell proliferation, angiogenesis, extracellular matrix deposition, and remodeling. This review describes the biological background ofthe topical therapy of wounds and soft-tissue injuries with platelet gel (PG) and PG-derived GFs as well as the su...

  7. Advantages of Pure Platelet-Rich Plasma Compared with Leukocyte- and Platelet-Rich Plasma in Treating Rabbit Knee Osteoarthritis (United States)

    Yin, Wen-Jing; Xu, Hai-Tao; Sheng, Jia-Gen; An, Zhi-Quan; Guo, Shang-Chun; Xie, Xue-Tao; Zhang, Chang-Qing


    Background Concentrated leukocytes in leukocyte- and platelet-rich plasma (L-PRP) may deliver increased levels of pro-inflammatory cytokines to activate the NF-κB signaling pathway, to counter the beneficial effects of growth factors on osteoarthritic cartilage. However, to date no relevant studies have substantiated that in vivo. Material/Methods Autologous L-PRP and pure platelet-rich plasma (P-PRP) were prepared, measured for componential composition, and injected intra-articularly after 4, 5, and 6 weeks post-anterior cruciate ligament transection. Caffeic acid phenethyl ester (CAPE) was injected intraperitoneally to inhibit NF-κB activation. All rabbits were sacrificed after 8 weeks postoperative. Enzyme-linked immunosorbent assays were performed to determine interleukin 1β (IL-1β) and prostaglandin E2 (PGE2) concentrations in the synovial fluid, Indian ink staining was performed for gross morphological assessment, and hematoxylin and eosin staining and toluidine blue staining were performed for histological assessment. Results Compared with L-PRP, P-PRP injections achieved better outcomes regarding the prevention of cartilage destruction, preservation of cartilaginous matrix, and reduction of IL-1β and PGE2 concentrations. CAPE injections reversed the increased IL-1β and PGE2 concentrations in the synovial fluid after L-PRP injections and improved the outcome of L-PRP injections to a level similar to P-PRP injections, while they had no influence on the therapeutic efficacy of P-PRP injections. Conclusions Concentrated leukocytes in L-PRP may release increased levels of pro-inflammatory cytokines to activate the NF-κB signaling pathway, to counter the beneficial effects of growth factors on osteoarthritic cartilage, and finally, result in a inferior efficacy of L-PRP to P-PRP for the treatment of osteoarthritis. PMID:27086145

  8. Uric acid and high-residual platelet reactivity in patients treated with clopidogrel or ticagrelor

    NARCIS (Netherlands)

    Barbieri, L.; Verdoia, M.; Pergolini, P.; Nardin, M.; Rolla, R.; Marino, P.; Bellomo, G.; Suryapranata, H.; Luca, G. De


    BACKGROUND AND AIM: High residual platelet reactivity (HRPR) is still an important challenge, despite the advent of new potent ADP-antagonists. Therefore it is of extreme importance to identify factors that can influence platelet activation. Serum uric acid (SUA) has been largely addressed in the

  9. Collagen quantification in rabbit dermal wounds treated with heterologous platelet-rich plasma gel

    Directory of Open Access Journals (Sweden)

    Maria Elisa Marin Marques


    Full Text Available Platelet-rich plasma (PRP has been extensively studied as a biomaterial for wound treatment, and the heterologous PRP is usefulin the event that obtaining the patient’s own blood is impossible. This study aimed to evaluate and compare wound healing in rabbits and quantify the collagen in experimentally induced wounds in a control group and in a group treated with heterologous PRP gel. We hypothesize that this gelis capable of promoting proper healing with no adverse reactions, increased collagen content. The clinical aspects of coloring, edema, hyperemia, exudation, crust, granulation, pain sensitivity, and retraction index of the wounds were measuredon days 7, 14, and 17 after the injury. Collagen quantification by Picrosirius staining and evaluation under polarized light was performed on the 17th day. Crust was present in both groups at all evaluated time points, with the absence of other clinical signs. The wound contraction rate and collagen quantity did not differ between groups. In conclusion, the suggested hypothesis was partially confirmed; the heterologous PRP gel was unable to increase the amount of collagen and accelerate the wound healing process, however, wound healing was efficient and similar in both groups and there was no local adverse reaction. Thus, despite the scarcity of studies in the literature, the heterologous PRP gel is an effective alternative treatment for wounds in the absence of other sources of PRP.

  10. Acute thrombocytopenia in patients treated with amiodarone is caused by antibodies specific for platelet membrane glycoproteins (United States)

    Sahud, Mervyn A.; Caulfield, Michael; Clarke, Nigel; Koch, Robert; Bougie, Daniel; Aster, Richard


    Summary Amiodarone has been implicated as a cause of thrombocytopenia but the responsible mechanism is unknown. We performed studies in three patients to characterize the pathogenesis of this complication. No amiodarone-dependent, platelet-reactive antibodies were identified using conventional serological techniques. However, water-insoluble amiodarone solubilized in methanol and diluted to 1·0 mg/ml in aqueous buffer reproducibly promoted binding of IgG antibodies in patient serum to platelets. Solid phase assays identified drug-dependent antibodies specific for platelet gly coproteins (GP)Ia/IIa (integrin α2β1) in each patient and a second antibody specific for GPIIb/IIIa (αIIbβ3 integrin) in one patient. When studied by ion mobility analysis and transmission electron microscopy, the serologically active amiodarone preparation, a milky suspension, was found to consist of particles 2–30 nm in diameter, typical of a coacervate, a state characteristic of amiodarone in aqueous medium. The findings provide evidence that thrombocytopenia in the three patients studied was caused by drug-dependent antibodies specific for platelet glycoproteins GPIa/IIa and/or GPIIb/IIIa. We postulate that, in vivo, amiodarone may become incorporated into occult lipophilic domains in platelet glycoproteins, producing structural modifications that are immunogenic in some individuals, and that the resulting antibodies can cause platelet destruction in a person taking this drug. PMID:23952260

  11. TXA2 synthesis and COX1-independent platelet reactivity in aspirin-treated patients soon after acute cerebral stroke or transient ischaemic attack. (United States)

    Valles, Juana; Lago, Aida; Moscardo, Antonio; Tembl, Jose; Parkhutik, Vera; Santos, Maria T


    The pharmacological target of aspirin is the inhibition of cyclooxygenase-1 (COX1) and thromboxane-A2 (TX) synthesis. Very few data are available on TX assessment in patients with stroke. We studied platelet TX synthesis, COX1-independent platelet reactivity, the influence of platelet-erythrocyte interactions and the potential association between platelet responses and the severity of stroke, evaluated with a clinical score (NIHSS). We examined 157 aspirin-treated patients with acute stroke or TIA, 128 aspirin-free and 15 aspirin-treated healthy subjects (HS). Collagen-induced TX, platelet recruitment in whole blood and platelets ± erythrocytes (haematocrit 40%) were assessed in patients on daily-aspirin within three days from onset. Arachidonic-acid-, ADP-, thrombin-receptor activating peptide TRAP-, and collagen-induced aggregation were also evaluated. Partial TX inhibition (aspirin-free controls) was observed in 13% of patients. This was associated with marked increases in COX1-dependent responses (arachidonic-acid- and collagen-induced aggregation and platelet recruitment; Paspirin-treated HS) were most likely to suffer severe stroke (Paspirin varied across patients. Partial TX inhibition and COX1-independent platelet hyperfunction were associated with more-severe stroke. Copyright © 2013. Published by Elsevier Ltd.

  12. Inflammatory response in chronic degenerative endometritis mares treated with platelet-rich plasma. (United States)

    Reghini, Maria Fernanda S; Ramires Neto, Carlos; Segabinazzi, Lorenzo G; Castro Chaves, Maria Manoela B; Dell'Aqua, Camila de Paula F; Bussiere, Maria Clara C; Dell'Aqua, José Antonio; Papa, Frederico O; Alvarenga, Marco Antonio


    Degenerative changes of the endometrium are directly related to age and fertility in mares. Chronic degenerative endometritis (CDE) is correlated with uterine fluid retention and reduced ability to clear uterine inflammation. Recent research in the areas of equine surgery and sports medicine has shown that platelet-rich plasma (PRP) treatment acts as an immunomodulator of the inflammatory response. Therefore, the aim of this study was to determine if the uterine infusion of PRP could modulate the local inflammatory response and modify the intrauterine NO concentrations after artificial insemination (AI) in both normal mares and those with CDE. Thirteen mares with endometrium classified as grade III on the histology (mares with CDE) and eight mares with endometrial histological classification I or II-a normal mares were selected to investigate the effect of PRP therapy. The mares were inseminated with fresh semen in two consecutive cycles in a crossover study design. Thereby, each mare served as its own control and the treatment was performed with intrauterine PRP infusion four hours after AI. The percentage of neutrophils in uterine cytology (CIT, %), uterine fluid accumulation observed on ultrasonography (FLU, mm) and nitric oxide concentration of uterine fluid (NO, μM) were analyzed before and 24 hours after AI. The results reported that mares with CDE (CIT, 68.3 ± 3.27, FLU, 10.7 ± 1.61) have a higher (P  0.05) between categories of mares. In treated cycles with PRP, the intrauterine inflammatory response decrease (P PRP was effective in modulating the exacerbated uterine inflammatory response to semen in mares with CDE but did not reduce NO concentrations in intrauterine fluid. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. The distinctive regulatory roles of PrtT in the cell metabolism of Penicillium oxalicum

    NARCIS (Netherlands)

    Chen, Ling; Zou, Gen; Zhang, Lei; de Vries, Ronald P; Yan, Xing; Zhang, Jun; Liu, Rui; Wang, Chengshu; Qu, Yinbo; Zhou, Zhihua; van den Brink, J.

    PrtT is a fungal-specific transcription activator of extracellular proteases in Aspergilli. In this study, the roles of the PrtT homolog from Penicillum oxalicum was investigated by transcription profiling in combination with electrophoretic mobility shift assay (EMSA). The prtT deletion

  14. Platelet-Rich-Plasma Injections in Treating Lateral Epicondylosis: a Review of the Recent Evidence. (United States)

    Murray, D J; Javed, S; Jain, N; Kemp, S; Watts, A C


    Lateral epicondylosis is common, with various treatment modalities. Platelet-rich-plasma injections from autologous blood have recently been used in centres worldwide for the treatment of tennis elbow. We review and present the recent published evidence on the effectiveness of PRP injections for lateral epicondylosis. Nine studies met our inclusion criteria including 6 RCT's for the purpose of analysis. PRP injections have an important and effective role in the treatment of this debilitating pathology, in cases where physiotherapy has been unsuccessful.

  15. Increased platelet aggregation and serum thromboxane levels in aspirin-treated patients with prior myocardial infarction. (United States)

    Larsen, Sanne Bøjet; Neergaard-Petersen, Søs; Grove, Erik Lerkevang; Kristensen, Steen Dalby; Hvas, Anne-Mette


    The antiplatelet effect of aspirin displays considerable inter-individual variability. We investigated the antiplatelet effect of aspirin in patients with coronary artery disease on aspirin mono-therapy with and without prior myocardial infarction (MI). Further, we investigated whether the effect of aspirin differed between patients with and without aspirin use at the time of MI onset. We performed a study on 231 patients, including 171 with prior MI. Among patients with only one prior MI (116 patients), 59 patients were on aspirin at the time of MI onset. All patients received 75 mg aspirin as mono-therapy. Platelet aggregation was assessed by multiple electrode aggregometry (Multiplate) and VerifyNow, and platelet activation was evaluated by soluble P-selectin. Furthermore, we measured serum thromboxane B2. MI patients had higher median platelet aggregation levels than patients without prior MI when evaluated by Multiplate (parachidonic acidaspirin before MI onset had significantly higher median aggregation levels compared with MI patients not on aspirin when evaluated by Multiplate (pcollagen=0.02) and VerifyNow (paspirin dose and optimal compliance. Serum thromboxane B2 levels were higher in MI patients than in patients without prior MI. Finally, patients on aspirin before MI onset had higher aggregation levels compared with patients not on aspirin.

  16. Improved platelet compatiblity of water vapour glow discharge treated non-woven poly(ethylene terephthalate) leukocyte-reduction filters for different types of platelet concentrates

    NARCIS (Netherlands)

    Kostelijk, E. H.; Klomp, A. J.; Engbers, G. H.; Gouwerok, C. W.; Verhoeven, A. J.; van Aken, W. G.; Feijen, J.; de Korte, D.


    Non-woven poly[ethylene terephthalate] (NW-PET) filter fabric, usually used for leucocyte removal of red cells, was modified by water vapour glow discharge (WVGD) treatment to improve platelet compatibility. Modified filter material was evaluated with different kinds of platelet concentrates (PCs).

  17. Improved platelet compatibility of water vapour glow discharge treated non-woven poly(ethylene therephthalate) leukocyte-reduction filters of different types of platelet concentrates

    NARCIS (Netherlands)

    Kostelijk, E.H.; Klomp, A.J.A.; Klomp, A.J.A.; Engbers, G.H.M.; Gouwerok, C.W.N.; van Aken, W.G.; Verhoeven, A.J.; Feijen, Jan; de Korte, D.


    Non-woven poly[ethylene terephthalate] (NW-PET) filter fabric, usually used for leucocyte removal of red cells, was modified by water vapour glow discharge (WVGD) treatment to improve platelet compatibility. Modified filter material was evaluated with different kinds of platelet concentrates (PCs).


    Directory of Open Access Journals (Sweden)

    Tsvetan Sokolov


    Full Text Available OBJECTIVE: To study the effect of platelet-rich plasma (PRP on contaminated problematic skin ulcers in patients with diabetes. MATERIAL AND METHODS: A total of 6 patients had been treated within the period from 2012 to 2014; they had various types of problematic wounds and diabetes type 2. Patients’ distribution by sex was as follows: 1 man and 5 women; mean age- 68 years. Ulcer types: acute (2 patients, hard-to-heal (2 patients and chronic (2 patients ulcers. The mean size of the skin and soft tissue defect was 9,5 cm2. Pathogenic microflora was isolated in 4 patients - S. aureus in three and Е. Coli in one. Based on a scheme developed by us, all cases were treated by administering platelet-rich plasma, derived by PRGF Endoret system. Follow-up period was within 4 – 6 months (4,5 on average. We used platelet rich plasma derived by PRGF Endoret system, applied on the wound bed on a weekly basis. RESULTS: Application of PRP allowed successful closure of all wounds. There were no complications associated with treatment of PRP. Epithelialization of the wound took 15 weeks on average for all patients. One patient presented with hyperkeratosis. Initial score of followed wounds, based on the scales are as follows: Total wound score – 10 p. Total anatomic score – 8 p. Total score – 15 p. at the initial stage. At the end of the treatment period scores were as follows - 0 p., which means excellent results CONCLUSION: We believe that the application of PRP may become optimal therapy in the treatment of contaminated problematic wounds in diabetic patients. PRP not only stimulates wound healing, but also has antimicrobial properties, which may contribute to the prevention of infections.

  19. Effects of ticagrelor versus clopidogrel on platelet function in fibrinolytic-treated STEMI patients undergoing early PCI. (United States)

    Dehghani, Payam; Lavoie, Andrea; Lavi, Shahar; Crawford, Jennifer J; Harenberg, Sebastian; Zimmermann, Rodney H; Booker, Jeff; Kelly, Sheila; Cantor, Warren J; Mehta, Shamir R; Bagai, Akshay; Goodman, Shaun G; Cheema, Asim N


    Patients undergoing PCI early after fibrinolytic therapy are at high risk for both thrombotic and bleeding complications. We sought to assess the pharmacodynamic effects of ticagrelor versus clopidogrel in the fibrinolytic-treated STEMI patients undergoing early PCI. Patients undergoing PCI within 24 hours of tenecteplase (TNK), aspirin, and clopidogrel for STEMI were randomized to receive additional clopidogrel 300 mg followed by 75 mg daily or ticagrelor 180 mg followed by 90 mg twice daily. The platelet reactivity units (PRU) were measured with the VerifyNow Assay before study drug administration (baseline) at 4 and 24 hours post-PCI. The primary end point was PRU ≤208 at 4 hours. A total of 140 patients (74 in ticagrelor and 66 in clopidogrel group) were enrolled. The mean PRU values at baseline were similar for the 2 groups (257.8±52.9 vs 259.5±56.7, P=.85, respectively). Post-PCI, patients on ticagrelor, compared to those on clopidogrel, had significantly lower PRU at 4 hours (78.7±88 vs 193.6±86.5, respectively, Pclopidogrel-treated patients, Pclopidogrel and aspirin at the time of fibrinolysis and were undergoing early PCI frequently had PRU >208. In this high-risk population, ticagrelor provides more prompt and potent platelet inhibition compared with clopidogrel (Funded by Astra Zeneca; NCT01930591, Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Effects of Ramadan fasting on platelet reactivity in diabetic patients treated with clopidogrel. (United States)

    Bouida, W; Baccouche, H; Sassi, M; Dridi, Z; Chakroun, T; Hellara, I; Boukef, R; Hassine, M; Added, F; Razgallah, R; Khochtali, I; Nouira, S


    The effects of Ramadan fasting (RF) on clopidogrel antiplatelet inhibition were not previously investigated. The present study evaluated the influence of RF on platelet reactivity in patients with high cardiovascular risk (CVR) in particular those with type 2 diabetes mellitus (DM). A total of 98 stable patients with ≥2 CVR factors were recruited. All patients observed RF and were taking clopidogrel at a maintenance dose of 75 mg. Clinical findings and serum lipids data were recorded before Ramadan (Pre-R), at the last week of Ramadan (R) and 4 weeks after the end of Ramadan (Post-R). During each patient visit, nutrients intakes were calculated and platelet reactivity assessment using Verify Now P2Y12 assay was performed. In DM patients, the absolute PRU changes from baseline were +27 (p = 0.01) and +16 (p = 0.02) respectively at R and Post-R. In addition, there was a significant increase of glycemia and triglycerides levels with a significant decrease of high-density lipoprotein. In non DM patients there was no significant change in absolute PRU values and metabolic parameters. Clopidogrel resistance rate using 2 cut-off PRU values (235 and 208) did not change significantly in DM and non DM patients. RF significantly decreased platelet sensitivity to clopidogrel in DM patients during and after Ramadan. This effect is possibly related to an increase of glycemia and serum lipids levels induced by fasting. Clinical NCT02720133. Registered 24 July 2014.Retrospectively registered.

  1. Assessment of platelet function in acute ischemic stroke patients previously treated with aspirin. (United States)

    Lago, Aida; Parkhutik, Vera; Tembl, Jose Ignacio; Vallés, Juana; Santos, Maria Teresa; Moscardó, Antonio


    Platelet inhibition measured by platelet function tests could be critical to understand the reasons for early recurrence and to guide therapeutic recommendations. We assess the platelet function during the acute phase of ischemic stroke in patients pretreated with aspirin who continue their treatment with aspirin only, are started on clopidogrel only, or add clopidogrel to aspirin. Sixty-four patients were taking aspirin before the stroke. Depending on the administered antiplatelet, 3 groups were defined: ASA: patients who continued on aspirin orally or intravenous acetylsalicylate of lysine, n = 30; CLO: patients who discontinued aspirin and were started on clopidogrel, n = 16; and ASA + CLO: patients who were prescribed both aspirin and clopidogrel, n = 10. Collagen-induced thromboxane A2 (TXA2) synthesis, ADP (adenosine diphosphate)-induced aggregation, and occlusion time (PF-100) were measured. CLO group only had a marked elevation of TXA2 (17.44 ± 15.62 ng/mL, P = .000) and a shortening of the platelet function analyzer (PFA)-100 closure time (157.13 ± 88 seconds, P = .047) compared with the other 2 groups (ASA: TXA2, .62 ± 1.59 ng/mL; ASA + CLO: TXA2 1.79 ± 4.59 ng/mL). They achieved a small (13%) but significant reduction of ADP-induced aggregation (87.00 ± 23.06 mm, P = .008) compared with the ASA group (102.82 ± 22.38 seconds). Stopping aspirin intake within the first 72 hours of the acute stroke drastically increases TXA2 synthesis. During the same time window, the freshly prescribed clopidogrel manages to reduce the ADP-induced aggregation only slightly (13%). This study offers analytic proof that the common practice of replacing aspirin with clopidogrel does not leave stroke patients fully protected during the first days after an ischemic stroke. Possible solutions could be to preserve aspirin during a few days or to use loading doses of clopidogrel at hospital admission. Copyright © 2014 National Stroke Association. Published by Elsevier Inc

  2. Efficacy of intra-tendinous injection of platelet-rich plasma in treating tendinosis: comprehensive assessment of a rat model. (United States)

    Dallaudière, Benjamin; Lempicki, Marta; Pesquer, Lionel; Louedec, Liliane; Preux, Pierre Marie; Meyer, Philippe; Hummel, Vincent; Larbi, Ahmed; Deschamps, Lydia; Journe, Clement; Hess, Agathe; Silvestre, Alain; Sargos, Paul; Loriaut, Philippe; Boyer, Patrick; Schouman-Claeys, Elisabeth; Michel, Jean Baptiste; Serfaty, Jean Michel


    To assess the potential of intra-tendinous injection of platelet rich plasma (PRP) to treat tendinosis (T+) in a rat model of patellar and Achilles T+, and evaluate its local toxicity. Thirty rats (120 patellar and Achilles tendons) were used. We induced T+ into 80 tendons (patellar = 40, Achilles = 40) by injecting collagenase at day 0 under ultrasound (US) guidance. Clinical examination and US at day 3, followed by US-guided intra-tendinous injection of either PRP (PRPT+, n = 40) or physiological serum (ST+, n = 40, control). Follow-up was at days 6, 13, 18 and 25 using clinical, US and histological evaluation. To study PRP toxicity, we injected PRP into 40 normal tendons (PRPT-) and compared with 40 untreated normal tendons (T-). All PRPT+ showed better joint mobilisation compared with ST+ at day 6 (P = 0.005), day 13 (P = 0.02), day 18 (P = 0.003) and day 25 (P = 0.01). Similar results were found regarding US and histology, with smaller collagen fibre diameters (day 6, P = 0.003, day 25, P ≤ 0.004), less disorganisation and fewer neovessels (day 6, P = 0.003, day 25, P = 0.0003) in PRPT+ compared with ST+. Comparison between PRPT- and T- showed no PRP toxicity (P = 0.18). Our study suggests that mono-injection of PRP in T+ improves tendon healing, with no local toxicity. • We assessed the potential of platelet rich plasma (PRP) to treat tendinosis. • We treated patellar and Achilles tendinosis in a rat model. • We evaluated clinical, imaging and histological data. • Intra-tendinous PRP injection could be useful in the treatment of tendinosis.

  3. Effects of platelet-rich fibrin on healing of intra-bony defects treated with anorganic bovine bone mineral

    Directory of Open Access Journals (Sweden)

    Yasemin SEZGIN

    Full Text Available Abstract Anorganic bovine bone mineral (ABBM is extensively used in the treatment of intra-bony defects. Platelet-rich fibrin (PRF is a new-generation platelet concentrate with a simplified technique. Although certain studies have reported the use of PRF in the treatment of intra-bony defects, to date, none of them have evaluated its additive effects with ABBM. Therefore, a randomised, split-mouth clinical trial was conducted to compare healing of intra-bony defects treated with an ABBM-PRF combination with healing of those treated with ABBM alone. By using a split-mouth design, 15 paired intra-bony defects were randomly treated with either ABBM alone (control group or ABBM-PRF combination (test group. Following clinical parameters and radiographical measurements were recorded at baseline and 6 months after treatment: plaque index (PI, gingival index (GI, probing depth (PD, gingival recession (GR, clinical attachment level (CAL, vertical bone loss, depth of defect and defect angle. Preoperative clinical and radiographical measurements were similar for the test and control groups. Statistically significant reductions in GI, PD, CAL, vertical bone loss, depth of intra-bony defect and widening of defect angle were detected after treatment in both groups. With respect to inter-group analysis, gain in CAL was significantly greater in the test group than in the control group, whereas no inter-group differences were observed in any other parameter. The results of this study indicate that both therapies are effective in the treatment of intra-bony defects.

  4. Evaluation of amotosalem treated platelets over 7 days of storage with an automated cytometry assay panel. (United States)

    Diquattro, M; De Francisci, G; Bonaccorso, R; Tagliavia, A M; Marcatti, M; Palma, B; Agliastro, R


    Pathogen Inactivation allows to overcome microbial contamination and growth related to storage of platelets concentrates (PC) at room temperature. The aim of our study was to evaluate the platelet storage lesion extending the storage period of pathogen inactivated platelet concentrates over 7 days using an automated cytometry assay panel. We analyzed 43 concentrates subjected to pathogen inactivation (CPPI) at 3, 5 and 7 days evaluating: platelet count, mean platelet volume, platelets at low optical density, platelets at high density, GPIIb-IIIa glycoprotein, platelet microparticles, lactate dehydrogenase. The collection bags (Fenwal) and the IBS kit made in PL2410/PL2411 are approved for the conservation of PC up to 7 days. Data analysis was performed with anova test. All the parameters except small platelets and PMP were statistically different among day 7 vs. 3 and day 7 vs. 5. Our study showed a progressive modification of pathogen inactivated platelet concentrates observed up to 7 days. The persistence of the secretory pool and the presence of the platelet membrane fibrinogen receptor suggest the persistence of a potential hemostatic efficacy. Clinical studies are necessary to directly correlate this type of analysis to 24 h recovery or survival of transfused platelets in humans. © 2013 John Wiley & Sons Ltd.

  5. The ATP-gated P2X1 receptor plays a pivotal role in activation of aspirin-treated platelets by thrombin and epinephrine. (United States)

    Grenegård, Magnus; Vretenbrant-Oberg, Karin; Nylander, Martina; Désilets, Stéphanie; Lindström, Eva G; Larsson, Anders; Ramström, Ida; Ramström, Sofia; Lindahl, Tomas L


    Human platelets express protease-activated receptor 1 (PAR1) and PAR4 but limited data indicate for differences in signal transduction. We studied the involvement of PAR1 and PAR4 in the cross-talk between thrombin and epinephrine. The results show that epinephrine acted via alpha(2A)-adrenergic receptors to provoke aggregation, secretion, and Ca(2+) mobilization in aspirin-treated platelets pre-stimulated with subthreshold concentrations of thrombin. Incubating platelets with antibodies against PAR4 or the PAR4-specific inhibitor pepducin P4pal-i1 abolished the aggregation. Furthermore, platelets pre-exposed to the PAR4-activating peptide AYPGKF, but not to the PAR1-activating peptide SFLLRN, were aggregated by epinephrine, whereas both AYPGKF and SFLLRN synergized with epinephrine in the absence of aspirin. The roles of released ATP and ADP were elucidated by using antagonists of the purinergic receptors P2X(1), P2Y(1), and P2Y(12) (i.e. NF449, MRS2159, MRS2179, and cangrelor). Intriguingly, ATP, but not ADP, was required for the epinephrine/thrombin-induced aggregation. In Western blot analysis, a low concentration of AYPGKF, but not SFLLRN, stimulated phosphorylation of Akt on serine 473. Moreover, the phosphatidyl inositide 3-kinase inhibitor LY294002 antagonized the effect of epinephrine combined with thrombin or AYPGKF. Thus, in aspirin-treated platelets, PAR4, but not PAR1, interacts synergistically with alpha(2A)-adrenergic receptors, and the PI3-kinase/Akt pathway is involved in this cross-talk. Furthermore, in PAR4-pretreated platelets, epinephrine caused dense granule secretion, and subsequent signaling from the ATP-gated P2X(1)-receptor and the alpha(2A)-adrenergic receptor induced aggregation. These results suggest a new mechanism that has ATP as a key element and circumvents the action of aspirin on epinephrine-facilitated PAR4-mediated platelet activation.

  6. Uncommon Odontogenic Orocutaneous Fistula of the Jaw Treated with Platelet-Rich Fibrin

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    Kani Bilginaylar


    Full Text Available Orocutaneous fistula (OCF of dental origin is a relatively rare condition and continues to be a challenging diagnosis. Misdiagnosis of OCF usually leads to unnecessary and noneffective treatment. A 21-year-old male referred with a complaint of a lesion on the chin which was misdiagnosed as a carbuncle (lesion of nonodontogenic origin by a physician. After radiological examination, there was a lesion around the apical region of right central incisor. These findings indicated a sinus tract associated with dental origin. After root canal treatment, apical surgery was performed and platelet-rich fibrin (PRF was administered to the cavity of the lesion as a gel form to improve healing and also used as a membrane form to cut off the relation between infected area and the skin. All procedures were performed intraorally; no extraoral intervention was performed. Three months later, clinical and radiological examination showed total healing without scar formation. The key to successful treatment of OCF is accurate diagnosis. Additionally, the use of PRF after surgical interventions is an effective and innovative therapy to improve healing.

  7. Is prnt a pseudogene? Identification of ram Prt in testis and ejaculated spermatozoa.

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    Jorge Pimenta

    Full Text Available A hallmark of prion diseases or transmissible spongiform encephalopaties is the conversion of the cellular prion protein (PrP(C, expressed by the prion gene (prnp, into an abnormally folded isoform (PrP(Sc with amyloid-like features that causes scrapie in sheep among other diseases. prnp together with prnd (which encodes a prion-like protein designated as Doppel, and prnt (that encodes the prion protein testis specific--Prt with sprn (shadow of prion protein gene, that encodes Shadoo or Sho genes, constitute the "prion gene complex". Whereas a role for prnd in the proper functioning of male reproductive system has been confirmed, the function of prnt, a recently discovered prion family gene, comprises a conundrum leading to the assumption that ruminant prnt is a pseudogene with no protein expression. The main objective of the present study was to identify Prt localization in the ram reproductive system and simultaneously to elucidate if ovine prnt gene is transcribed into protein-coding RNA. Moreover, as Prt is a prnp-related protein, the amyloid propensity was also tested for ovine and caprine Prt. Recombinant Prt was used to immunize BALB/c mice, and the anti-Prt polyclonal antibody (APPA immune response was evaluated by ELISA and Western Blot. When tested by indirect immunofluorescence, APPA showed high avidity to the ram sperm head apical ridge subdomain, before and after induced capacitation, but did not show the same behavior against goat spermatozoa, suggesting high antibody specificity against ovine-Prt. Prt was also found in the testis when assayed by immunohistochemistry during ram spermatogenesis, where spermatogonia, spermatocytes, spermatids and spermatozoa, stained positive. These observations strongly suggest ovine prnt to be a translated protein-coding gene, pointing to a role for Prt protein in the ram reproductive physiology. Besides, caprine Prt appears to exhibit a higher amyloid propensity than ovine Prt, mostly associated

  8. Identification of developmentally regulated PCP-responsive non-coding RNA, prt6, in the rat thalamus.

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    Hironao Takebayashi

    Full Text Available Schizophrenia and similar psychoses induced by NMDA-type glutamate receptor antagonists, such as phencyclidine (PCP and ketamine, usually develop after adolescence. Moreover, adult-type behavioral disturbance following NMDA receptor antagonist application in rodents is observed after a critical period at around 3 postnatal weeks. These observations suggest that the schizophrenic symptoms caused by and psychotomimetic effects of NMDA antagonists require the maturation of certain brain neuron circuits and molecular networks, which differentially respond to NMDA receptor antagonists across adolescence and the critical period. From this viewpoint, we have identified a novel developmentally regulated phencyclidine-responsive transcript from the rat thalamus, designated as prt6, as a candidate molecule involved in the above schizophrenia-related systems using a DNA microarray technique. The transcript is a non-coding RNA that includes sequences of at least two microRNAs, miR132 and miR212, and is expressed strongly in the brain and testis, with trace or non-detectable levels in the spleen, heart, liver, kidney, lung and skeletal muscle, as revealed by Northern blot analysis. The systemic administration of PCP (7.5 mg/kg, subcutaneously (s.c. significantly elevated the expression of prt6 mRNA in the thalamus at postnatal days (PD 32 and 50, but not at PD 8, 13, 20, or 24 as compared to saline-treated controls. At PD 50, another NMDA receptor antagonist, dizocilpine (0.5 mg/kg, s.c., and a schizophrenomimetic dopamine agonist, methamphetamine (4.8 mg/kg, s.c., mimicked a significant increase in the levels of thalamic prt6 mRNAs, while a D2 dopmamine receptor antagonist, haloperidol, partly inhibited the increasing influence of PCP on thalamic prt6 expression without its own effects. These data indicate that prt6 may be involved in the pathophysiology of the onset of drug-induced schizophrenia-like symptoms and schizophrenia through the possible

  9. Immunohistochemical Expression of Collagens in the Skin of Horses Treated with Leukocyte-Poor Platelet-Rich Plasma (United States)

    Silva, Mariana Brettas; Pinto, José de Oliveira; Lima, Marianna Barros de Souza; Crepaldi, Júlio; Lopes, Gabriela Francine Martins; dos Santos, Hélio Batista; Ribeiro, Rosy Iara Maciel de Azambuja; Thomé, Ralph Gruppi


    This study evaluated the immunohistochemical expression of type I (COL I) and III (COL III) collagens during the healing process of skin treated with leukocyte-poor platelet-rich plasma (LP-PRP). Seven healthy gelding crossbred horses aged 16 to 17 years were used. Two rectangle-shaped wounds were created surgically in the right and left gluteal regions. Twelve hours after wound induction, 0.5 mL of the LP-PRP was administered in each edge of the wounds of one of the gluteal regions. The contralateral region was used as control (CG). Three samples were obtained: after wound induction (T0), 14 days (T1) of healing process, and after complete closure of the skin (T2). The normal skin (T0) showed strong staining for type III and I collagen in papillary and reticular dermis, respectively. In the scar of the treated group, COL III showed important (p < 0.05) increase in immunoreaction in T2 compared with T1. The administration of a single dose of LP-PRP 12 h after induction of wound in horses does not influence formation of collagens I and III. However, the intense labeling for COL III suggests that the tissue was still weak during the macroscopic closure of the wound, demonstrating that healing was not completely finished. PMID:26236743

  10. Eptifibatide provides additional platelet inhibition in non-ST-elevation myocardial infarction patients already treated with aspirin and clopidogrel. Results of the platelet activity extinction in non-Q-wave myocardial infarction with aspirin, clopidogrel, and eptifibatide (PEACE) study. (United States)

    Dalby, Miles; Montalescot, Gilles; Bal dit Sollier, Claire; Vicaut, Eric; Soulat, Thierry; Collet, Jean Philippe; Choussat, Rémi; Gallois, Vanessa; Drobinski, Gérard; Drouet, Ludovic; Thomas, Daniel


    The present study hypothesis was that eptifibatide offered further antiplatelet efficacy above clopidogrel in non-ST-elevation myocardial infarction (NSTEMI) patients before an expeditive coronary intervention. Although thienopyridines and glycoprotein (GP) IIb/IIIa antagonists are often co-prescribed in the context of NSTEMI, the antiplatelet interaction of these agents is poorly described and the superiority of GP IIb/IIIa antagonists above thienopyridine treatment alone is not clear. Thirty-two NSTEMI patients treated with aspirin and enoxaparin were studied using flow cytometry to define parameters of platelet activation with a panel of agonists before clopidogrel, after clopidogrel, and during an eptifibatide infusion following the clopidogrel load. After platelet activation with adenosine diphosphate, thrombin receptor-activating peptide, or U46-619, relative reductions in conformationally activated GP IIb/IIIa receptor expression (evaluated with PAC-1) of 48%, 43%, and 33%, respectively (all p pro-inflammatory effect.

  11. Use of platelet rich plasma to treat plantar fasciitis: design of a multi centre randomized controlled trial

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    Peerbooms Joost C


    Full Text Available Abstract Background If conservative treatment for chronic plantar fasciitis fails, often a corticosteroid injection is given. Corticosteroid injection gives temporarily pain reduction, but no healing. Blood platelets initiate the natural healing rate. GPS® gives an eightfold concentrate platelets of patients own blood. Injection of these platelets in the attachment of the fascia to the os calcis might induce a healing rate. Methods and design A randomized controlled multi centre trial will be performed. The study population consists of 120 patients of 18 years and older. Patients with chronic plantar fasciitis will be allocated randomly to have a steroid injection or an autologous platelet concentrate injections. Data will be collected before the procedure, 4,8,12,26 weeks and 1 year after the procedure. The main outcome measures of this study are pain and function measured with questionnaires. Conclusion Recent literature show positive effects for the treatment of tendinosis with autologous platelet injections. The forthcoming trial will compare treatment for chronic plantar fasciitis with a steroid injection versus an autologous platelet injection. Our results will be published as soon as they become available. Trial Registration Trial registration number: NCT00758641.

  12. The combination use of platelet-rich fibrin and treated dentin matrix for tooth root regeneration by cell homing. (United States)

    Ji, Baohui; Sheng, Lei; Chen, Gang; Guo, Shujuan; Xie, Li; Yang, Bo; Guo, Weihua; Tian, Weidong


    Endogenous regeneration through cell homing provides an alternative approach for tissue regeneration, except cell transplantation, especially considering clinical translation. However, tooth root regeneration through cell homing remains a provocative approach in need of intensive study. Both platelet-rich fibrin (PRF) and treated dentin matrix (TDM) are warehouses of various growth factors, which can promote cell homing. We hypothesized that endogenous stem cells are able to sense biological cues from PRF membrane and TDM, and contribute to the regeneration of tooth root, including soft and hard periodontal tissues. Therefore, the biological effects of canine PRF and TDM on periodontal ligament stem cells (PDLSCs) and bone marrow mesenchymal stem cells (BMSCs) were evaluated respectively in vitro. Beagle dogs were used as orthotopic transplantation model. It was found that PRF significantly recruited and stimulated the proliferation of PDLSCs and BMSCs in vitro. Together, PRF and TDM induced cell differentiation by upregulating the mineralization-related gene expression of bone sialoprotein (BSP) and osteopotin (OPN) after 7 days coculture. In vivo, transplantation of autologous PRF and allogeneic TDM into fresh tooth extraction socket achieved successful root regeneration 3 months postsurgery, characterized by the regeneration of cementum and periodontal ligament (PDL)-like tissues with orientated fibers, indicative of functional restoration. The results suggest that tooth root connected to the alveolar bone by cementum-PDL complex can be regenerated through the implantation of PRF and TDM in a tooth socket microenvironment, probably by homing of BMSCs and PDLSCs. Furthermore, bioactive cues and inductive microenvironment are key factors for endogenous regeneration. This approach provides a tangible pathway toward clinical translation.

  13. The distinctive regulatory roles of PrtT in the cell metabolism of Penicillium oxalicum. (United States)

    Chen, Ling; Zou, Gen; Zhang, Lei; de Vries, Ronald P; Yan, Xing; Zhang, Jun; Liu, Rui; Wang, Chengshu; Qu, Yinbo; Zhou, Zhihua


    PrtT is a fungal-specific transcription activator of extracellular proteases in Aspergilli. In this study, the roles of the PrtT homolog from Penicillum oxalicum was investigated by transcription profiling in combination with electrophoretic mobility shift assay (EMSA). The prtT deletion dramatically reduced extracellular protease activities and caused intracellular nutrient limitation when cultured on casein as the sole carbon source. PrtT was found to directly regulate the expression of an intracellular peptidase encoding gene (tripeptidyl-peptidase) and the gene encoding the extracellular dipeptidyl-aminopeptidase V, in addition to the expected extracellular peptidase genes (carboxypeptidase and aspergillopepsin). Five amylase genes (α-amylase, glucoamylase, α-glucosidase) and three major facilitator superfamily transporter genes related to maltose, monosaccharide and peptide transporting were also confirmed as putative targets of PrtT by EMSA. In contrast, the transcription levels of other genes encoding polysaccharide degrading enzymes (e.g. cellulases) and most iron or multidrug transporter encoding genes were up- or down-regulated in the ΔprtT mutant due to nutrient limitation resulting from the reduced usage of the sole carbon source, casein. These results deepen the understanding of the interaction of regulation systems for nitrogen and carbon catabolism, which benefit strain improvement of P. oxalicum for industrial enzyme production. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Platelet activation by riboflavin and UV light: is it really the other side of the coin? (United States)

    Del Proposto, Gianpaolo; Lanti, Alessandro; Fiorelli, Eleonora; Palazzo, Gloria; Guiducci, Giorgia; Messina, Francesca; De Masi, Alessandra; Ferraro, Angelo Salvatore; Chiru, Oana Marilena; Cerrone, Paola; Antonelli, Maddalena; Adorno, Gaspare


    Nowadays transfusion safety is still put at risk by contamination of pathogens. The Mirasol PRT System blocks the replication of pathogens and white blood cells. Our goal was to quantify the activation of platelets after treatment with the Mirasol device. From September to December 2013, 131 platelet collections were studied using a simple flow cytometric strategy. There was a significant correlation between the percentage of platelet activated before and after the treatment. Our results induced us to think that the activation of platelets after treatment was acceptable. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Real-time monitoring of the functional status of platelets treated by Infukoll using a computer-aided laser phase microscope (United States)

    Vasilenko, Irina A.; Babakova, Svetlana; Kiseleva, Elena; Dyugeev, Adyan; Konradov, Alexander A.; Shabalin, Vladimir


    Combined analysis of optic-geometrical characteristics makes it possible to comprehensively evaluate the morphological and functional state of the cytological object, which can not be done during visual observation. The technique is discussed for real-time monitoring of the functional status of platelets using computer-aided phase microscope (CPM) 'Cytoscan'. High accuracy and sensitivity of CPM with respect to determination of local temporal phase make it possible to register the dynamic processes in the voluntarily chosen points and sections of micro-objects, to obtain the Fourier's spectra and other characteristics suitable for statistical analysis. Human platelets were prepared from venous blood of healthy donors and pregnant women by standard methods, suspended in culture medium 199 and treated by different doses of 6% Infukoll HES. Nonfixating and nonstaining cells were studied with CPM: height accuracy 0.5 nm, magnification 1000, acquisition time 4 - 30 s. In our experiments we used time resolution about 0.03 s and 30 x lens with numerical aperture 0.65. During investigations of temporal processes a certain section was chosen in the topogram of cell image and local values for the phase of scattered wave in each of the points of the chosen cell's profile were measured. On the basis of the results of automated phase image analysis of optic-geometrical characteristics of living cells, the new quantitative express-method for evaluating of the functional status of human platelets was developed and tested. The structural changes of cells were visualized in alteration of 3-D images, phase profiles, in the decrease of mean cell phase diameters, heights, volumes, in disturbance of histograms of phase heights distribution by cell image points. New data on the behavior of platelets treated by Infukoll in vitro and in vivo were obtained. Analysis of intracellular dynamics was allowed to characterize the cell's regions of maximal activity, but the intensity of processes

  16. [Relevance of CYP2C19 2 regarding platelet reactivity in patients with acute coronary syndrome treated with clopidogrel]. (United States)

    Cano, Pedro; Consuegra-Sánchez, Luciano; Conesa, Pablo; Torres-Moreno, Daniel; Jaulent, Leticia; Dau, Derek; Picó, Francisco; Villegas, Manuel


    Previous studies have shown that the metabolism of P2Y12 receptor blockers is influenced not only by CYP2C19 2 but also by PON1-Q192R alelles. We aimed to evaluate the impact of CYP2C19 2 and PON1-Q192R polymorphisms carriage in platelet reactivity and clinical outcome in patients with ischemic heart disease undergoing cardiac catheterization. We recruited prospectively patients with acute coronary syndrome undergoing cardiac catheterization (n=247). We evaluated the genotype (CYP2C19 2, CYP2C19 17, PON1-Q192R) with TaqMan(®) assay and platelet aggregometry in all patients. We assessed both in and out-of-hospital events (unstable angina, periprocedural and spontaneous myocardial infarction, myocardial infarction, all-cause death, stent thrombosis and stroke) during follow-up. Carriers of CYP2C19 2 alleles showed a significant higher residual platelet reactivity (PRU, mean [SD], 252 [76] vs. 287 [74], P=.002). Carriers of PON1-Q192R CT(RQ) and TT(QQ) alleles and CYP2C19 17 did not present a different response to clopidogrel. In a multivariable setting for the prediction of platelet reactivity, the contribution of CYP2C19 2 was modest (Wald=7.5; odds ratio [OR] for ≥ 1 alelle 2=2,786, 95% confidence interval [95% CI] 1,337-5,808). Independent predictors were baseline hemoglobin levels (g/dL, OR .666, 95% CI .555-.801) and the use of statins (OR .376, 95% CI .162-.873). Body mass index was a risk factor (OR 1,074, CI 95% 1,005-1,148). Studied polymorphisms did not predict an adverse outcome. CYP2C19 2 polymorphism influenced moderately platelet reactivity but did not show an impact on clinical outcome in patients with acute coronary syndrome. Neither CYP2C19 17 nor PON1-Q192R polymorphisms showed an impact upon platelet reactivity or outcome. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  17. Immunohistological Evaluation of Revascularized Immature Permanent Necrotic Teeth Treated by Platelet-Rich Plasma: An Animal Investigation


    Saeed Moradi; Ali Talati; Maryam Forghani; Amir Hossein Jafarian; Mandana Naseri; Shiva Shojaeian


    Objective: Pulp regeneration within the root canal of necrotic teeth is considered an ideal treatment to allow for continued root development and recover teeth vitality. This study aims to evaluate the inductive effect of platelet-rich plasma (PRP) on expression of angiogenesis factors and pulpal revascularization of immature necrotic teeth. Materials and Methods: In this experimental animal study, we randomly divided 28 immature premolars from two mixed breed dogs into four gr...

  18. A comparative study to evaluate the efficacy of platelet-rich plasma and triamcinolone to treat tennis elbow


    Vanamali B Seetharamaiah; Amrit Gantaguru; Sunil Basavarajanna


    Background: Lateral elbow pain is common with a population prevalence of 1%?3%. The study was a comparative trial to validate the efficacy of single injection of platelet-rich plasma (PRP) for tennis elbow as compared with single injections of triamcinolone and placebo (normal saline) over a short term period. Materials and Methods: Comparative trial with 3- and 6-month followup evaluated with visual analog scale (VAS) and facial pain scale (FPS). Our study included a total of eighty patients...

  19. Predictors of high on-aspirin platelet reactivity in high-risk vascular patients treated with single or dual antiplatelet therapy. (United States)

    Amsallem, Myriam; Manzo-Silberman, Stephane; Dillinger, Jean-Guillaume; Sideris, Georgios; Voicu, Sebastian; Bal dit Sollier, Claire; Drouet, Ludovic; Henry, Patrick


    Aspirin is the key treatment in the secondary prevention of atherothrombosis. Interindividual variability of response has been linked to a higher risk for ischemic events. The aim of this study was to identify clinical and biologic factors predicting high on-aspirin platelet reactivity (HPR) in a high-risk, "real-world" population of vascular patients. All platelet testing performed from 2011 to 2013 in consecutive patients receiving long-term treatment with aspirin for coronary or cerebrovascular disease was retrospectively analyzed. Indications for platelet testing were recurrent ischemic events or high-risk angioplasty. HPR was defined as aggregation intensity≥20% using light-transmission aggregometry with arachidonic acid 0.5 mg/ml. Collagen-epinephrine platelet function analysis was also performed (thresholdantiplatelet treatment were recorded. A total of 1,508 patients were included (mean age 63 years, 71% men, 23% with diabetes). Antiplatelet treatment was aspirin alone in 333 patients and dual-antiplatelet therapy in 1,175 patients. HPR was found in 11.1% of patients. In multivariate analysis, independent predictive factors of HPR on light-transmission aggregometry with arachidonic acid were diabetes mellitus (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.39 to 3.16), age (OR 1.25, 95% CI 1.06 to 1.47), fibrinogen level (OR 1.20, 95% CI 1.02 to 1.42), and von Willebrand factor level (OR 1.06, 95% CI 1.03 to 1.09). On light-transmission aggregometry with arachidonic acid and collagen-epinephrine platelet function analysis, fibrinogen remained the main factor associated with HPR (OR 1.33, 95% CI 1.19 to 1.61). Similar results were found in patients treated with aspirin alone or dual-antiplatelet therapy. A fibrinogen level>4.0 g/L was associated with a 3.9-fold increased risk for HPR in patients aged aspirin in this large population of high-risk vascular patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Evaluation of pain regression in patients with temporomandibular dysfunction treated by intra-articular platelet-rich plasma injections: a preliminary report. (United States)

    Pihut, M; Szuta, M; Ferendiuk, E; Zeńczak-Więckiewicz, D


    The objective of this study was to evaluate the regression of temporomandibular pain as a result of intra-articular injections of platelet-rich plasma (PRP) to patients with temporomandibular joint dysfunction previously subjected to prosthetic treatment. The baseline study material consisted of 10 patients, both males and females, aged 28 to 53 years, previously treated due to painful temporomandibular joint dysfunction using occlusal splints. All patients were carried out to a specialist functional assessment of the dysfunction using the Polish version of the RDC/TMD questionnaire axis I and II. Intra-articular injections were preceded by a preparation of PRP. The injection sites were determined by the method used during arthroscopic surgical procedures. Following aspiration, 0.5 mL of plasma was injected into each temporomandibular joint. The comparison of the intensity of pain during all examinations suggests a beneficial effect of the procedure being performed as the mean VAS score was 6.5 at examination I, 2.8 at examination II, and 0.6 at examination III. Application of the intra-articular injections of platelet-rich plasma into the temporomandibular joints has a positive impact on the reduction of the intensity of pain experienced by patients treated for temporomandibular joint dysfunction.

  1. Validity and reliability of pre-class reading tasks for waves and optics (PRT-WO

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    Asrab Ali Nur Faralina


    Full Text Available This study aims to produce a valid and reliable instrument in preparing students prior to class at university level of introductory Waves and Optics course. The instrument so called Pre-class Reading Task for Waves and Optics (PRT-WO was used to probe students’ knowledge acquired through targeted reading activities. In practice, PRT-WO was given in a series before actual face-to-face class as a reading assignment. PRT-WO was content validated through expert review which was analyzed using the interrater reliability Cohen’s kappa. An item analysis was done to identify inappropriate items further evaluated using the reliability test of Kuder-Richardson 20 (KR20. The finding reveals that the value of kappa is 0.66 and the value of KR20 is 0.68, indicating that the developed instrument is valid and reliable.

  2. Clinical outcomes in patients treated for coronary in-stent restenosis with drug-eluting balloons: Impact of high platelet reactivity.

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    Adrienn Tornyos

    Full Text Available The impact of high platelet reactivity (HPR on clinical outcomes after elective percutaneous coronary interventions (PCI with drug-eluting balloons (DEB due to in-stent restenosis (ISR is unknown.We sought to evaluate the prognostic importance of HPR together with conventional risk factors in patients treated with DEB.Patients treated with DEB due to ISR were enrolled in a single-centre, prospective registry between October 2009 and March 2015. Only patients with recent myocardial infarction (MI received prasugrel, others were treated with clopidogrel. HPR was defined as an ADP-test >46U with the Multiplate assay and no adjustments were done based on results. The primary endpoint of the study was a composite of cardiovascular mortality, MI, any revascularization or stroke during one-year follow-up.194 stable angina patients were recruited of whom 90% were treated with clopidogrel. Clinical characteristics and procedural data were available for all patients; while platelet function testing was performed in 152 subjects of whom 32 (21% had HPR. Patients with HPR had a higher risk for the primary endpoint (HR: 2.45; CI: 1.01-5.92; p = 0.03. The difference was primarily driven by a higher risk for revascularization and MI. According to the multivariate analysis, HPR remained a significant, independent predictor of the primary endpoint (HR: 2.88; CI: 1.02-8.14; p = 0.04, while total DEB length and statin treatment were other independent correlates of the primary outcome.HPR was found to be an independent predictor of repeat revascularization and MI among elective patients with ISR undergoing PCI with DEB.

  3. Platelet mimicry

    DEFF Research Database (Denmark)

    Moghimi, Seyed Moein; Hunter, Alan Christy; Peer, Dan


    Here we critically examine whether coating of nanoparticles with platelet membranes can truly disguise them against recognition by elements of the innate immune system. We further assess whether the "cloaking technology" can sufficiently equip nanoparticles with platelet-mimicking functionalities...

  4. The PRT Pocket Guide: Pivotal Response Treatment for Autism Spectrum Disorders (United States)

    Koegel, Robert L.; Koegel, Lynn Kern


    What is Pivotal Response Treatment? What's the research behind it, what does it look like in practice, and what are some good examples of how to use it? Now one concise book gives professionals and parents all the basics of the widely used PRT--one of a select group of highly effective, evidence-based treatments for autism. great resource for…

  5. Demand modeling of innovative transport system PRT at the Rotterdam port area

    NARCIS (Netherlands)

    Li, H.; Chen, Y.; Li, J.; Zuylen, H.J. van; Arem, B. van


    Demand modeling for a newly built transit system is a major issue for the feasibility study. The complexity for such demand modeling stems from the complicated multi-modal trip making by travelers. This paper proposes to build an innovative transit system PRT in the east port area of Rotterdam to

  6. [Investigation of mechanisms of action of growth factors of autologous platelet-rich plasma used to treat erectile dysfunction]. (United States)

    Epifanova, M V; Chalyi, M E; Krasnov, A O


    To determine the quantitative and qualitative composition of growth factors (PDGF-AA, PDGF-BB, VEGF, VEGF-D, FGF-acid, FGF-basic) and platelets in various modifications of APRP. Blood of 12 male volunteers (control group) and 12 patients with ED was used to prepare APRP and the subsequently determine the concentration of growth factors. The growth factor concentrations (FGF acid, FGF basic, PDGF-AA, PDGF-BB, VEGF, VEGF-D) was determined using a flow cytometry-based xMAP Luminex (Gen-Probe) system. Concentration of platelets in APRP obtained by two stage centrifugation, reached 1480 (1120-1644) in the control group and 1232 (956-1502) in patients with ED. The concentration of growth factors in the samples prepared without preliminary freezing was: PDGF-AA 842 (22-3700), PDGF-BB 2837 (1460-4100), FGF-basic 7.9 (0.28-127), FGF-acid 3, 4 (0.14-11), VEGF 19 (4.6-46), VEGF-D 21 (14-38). After thawing, the concentration of all growth factors in the samples increased. The study findings suggest that the mechanism of erectile function recovery following the use of APRP is through the active substances detected in APRP, i.e. FGF-basic, PDGF-AA, PDGF-BB, VEGF, VEGF-D and FGF-acid. Also, the study showed that the content of growth factors in APRP after of freezing/thawing is higher than in APRP that has not been frozen. This is due to the cell membrane destruction at extremely low temperatures during freezing.

  7. Inhibition of platelet-derived growth factor (PDGF) receptor affects follicular development and ovarian proliferation, apoptosis and angiogenesis in prepubertal eCG-treated rats. (United States)

    Pascuali, Natalia; Scotti, Leopoldina; Abramovich, Dalhia; Irusta, Griselda; Di Pietro, Mariana; Bas, Diana; Tesone, Marta; Parborell, Fernanda


    The platelet-derived growth factor (PDGF) system is crucial for blood vessel stability. In the present study, we evaluated whether PDGFs play a critical intraovarian survival role in gonadotropin-dependent folliculogenesis. We examined the effect of intrabursal administration of a selective platelet-derived growth factor receptor (PDGFR) inhibitor (AG1295) on follicular development, proliferation, apoptosis and blood vessel formation and stability in ovaries from rats treated with equine chorionic gonadotropin (eCG). The percentages of preantral follicles (PAFs) and early antral follicles (EAFs) were lower in AG1295-treated ovaries than in control ovaries (p < 0.01-0.05). The percentage of atretic follicles (AtrFs) increased in AG1295-treated ovaries compared to control (p < 0.05). The ovarian weight and estradiol concentrations were lower in AG1295-treated ovaries than in the control group (p < 0.01 and p < 0.05, respectively), whereas progesterone concentrations did not change. AG1295 decreased the proliferation index in EAFs (p < 0.05) and increased the percentage of nuclei positive for cleaved caspase-3 and apoptotic DNA fragmentation (p < 0.01-0.05). AG1295 increased the expression of Bax (p < 0.05) without changes in the expression of Bcl-2 protein. AG1295-treated ovaries increased the cleavage of caspase-8 (p < 0.05) and decreased AKT and BAD phosphorylation compared with control ovaries (p < 0.05). AG1295 caused a decrease not only in the endothelial cell area but also in the area of pericytes and vascular smooth muscle cells (VSMCs) in the ovary (p < 0.05). Our findings suggest that the local inhibition of PDGFs causes an increase in ovarian apoptosis through an imbalance in the ratio of antiapoptotic to proapoptotic proteins, thus leading a larger number of follicles to atresia. PDGFs could exert their mechanism of action through an autocrine/paracrine effect on granulosa and theca cells mediated by PDGFRs. In

  8. An innovative approach to treating vaginal mesh exposure after abdominal sacral colpopexy: endoscopic resection of mesh and platelet-rich plasma; initial experience in three women. (United States)

    Castellani, Daniele; Valloni, Alessandra; Piccirilli, Angela; Paradiso Galatioto, Giuseppe; Vicentini, Carlo


    Polypropylene mesh exposure is uncommon after abdominal sacral colpopexy (ASC), but in case of symptomatic vaginal mesh exposure, surgery is needed. When treating it, care must be taken to completely remove the exposed mesh (EM), saving as much vaginal tissue as possible to avoid a subsequent shortened and narrowed vagina. In this video, we present a minimally invasive technique for treating EM after ASC using endoscopic mesh resection and autologous platelet-rich plasma (PRP) technology. Three women were referred to our outpatient clinic for vaginal vault mesh exposure after laparoscopic ASC with concomitant hysterectomy. All women underwent endoscopic bipolar PlasmaKinetic resection (BPR) of EM, and PRP gel was delivered in the surgical site to cover the gap left by the resection. Mean operative time was 39.6 min. Surgery was uneventful in all cases. All women recovered sexual function, and nobody experienced relapsed pelvic organ prolapse at 1-year follow-up. Our preliminary results show that BPR and PRP are safe, effective, and feasible for treating vaginal mesh exposure with conservation of anatomy and sexual function.

  9. Partial cranial cruciate ligament tears treated with stem cell and platelet rich plasma combination therapy in 36 dogs: a retrospective study

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    Sherman Canapp


    Full Text Available Objective: To evaluate outcomes in 36 dogs with a partial CCL tear treated with autologous bone marrow aspirate concentrate (BMAC or adipose derived progenitor cells (ADPC with platelet rich plasma (PRP combination.Materials and Methods: Medical records of client-owned dogs diagnosed with an early partial (≤50% tear of the craniomedial band of the CCL that were treated with BMAC-PRP or ADPC-PRP were reviewed from 2010-2015. Signalment, medical history, physical and orthopedic examination, objective temporospatial gait analyses, radiographs, day 0 and day 90 diagnostic arthroscopy findings, treatment, and outcome were among the data collected. A functional owner questionnaire, including the validated Helsinki chronic pain index (HCPI, was sent to owners whose dog was known to not have had a TPLO. Statistical analysis was performed on data, where significance was established at p50% CCL tear and a TPLO was performed. Four additional dogs were known to have had a TPLO performed elsewhere. Baseline and day 90 post treatment objective gait analyses were available on 11 of the 36 dogs. A significant difference was found between the treated limb TPI% at day 0 and day 90 (p=0.0124, and between the treated limb and contralateral limb TPI% at day 0 (p=0.0003. No significant difference was found between the treated limb and contralateral limb TPI% at day 90 (p=0.7466. Twelve questionnaires were returned, of which 8 were performance/sporting dogs. Seven of the 8 had returned to sport; the remaining dog had just begun a return to sport conditioning program 6 months post treatment. All 12 respondents believed their dog had an excellent or very good quality of life, and rated their dog’s procedural outcome as excellent or good.Conclusion: The use of BMAC-PRP and ADPC-PRP shows promise for the treatment of early partial CCL tears in dogs.

  10. High leukocyte count and interleukin-10 predict high on-treatment-platelet-reactivity in patients treated with clopidogrel. (United States)

    Osmancik, Pavel; Paulu, Petra; Tousek, Petr; Kocka, Viktor; Widimsky, Petr


    According to recent trials, a significant number of patients do not have a completely effective response to clopidogrel. The aim of the study was to evaluate the rate of clopidogrel resistance in the context of important clinical characteristics and to specifically determine the relation between clopidogrel efficacy and biomarkers of inflammation. Consecutive non-selected patients following PCI were enrolled into the study. All patients received a loading dose of 600 mg of clopidogrel. The effect of clopidogrel was assessed using the VerifyNow assay 24 h after clopidogrel administration, clopidogrel resistance was defined as PRU ≥ 240. At the same time, standard parameters of biochemistry and hematology, the concentration of anti-inflammatory cytokine interleukin-10 and of soluble CD40 ligand, were measured. 378 patients were enrolled. 243 (64.3%) patients were responders (R) and 135 patients (35.7%) were non-responders (NR). Non-responders were older (R 65.7 ± 13.3, NR 69.8 ± 11.5, P leukocyte count (R 9.8 ± 3.5, NR 11.7 ± 12.8, P leukocytes and IL-10 were associated with an increased risk for being a non-responder. Older, obese patients, especially women had a higher risk of high on-treatment-platelet-reactivity. Higher concentrations of leukocytes and interleukin-10 were also an important factor associated with the risk of low clopidogrel responsiveness.

  11. A comparative study to evaluate the efficacy of platelet-rich plasma and triamcinolone to treat tennis elbow. (United States)

    Seetharamaiah, Vanamali B; Gantaguru, Amrit; Basavarajanna, Sunil


    Lateral elbow pain is common with a population prevalence of 1%-3%. The study was a comparative trial to validate the efficacy of single injection of platelet-rich plasma (PRP) for tennis elbow as compared with single injections of triamcinolone and placebo (normal saline) over a short term period. Comparative trial with 3- and 6-month followup evaluated with visual analog scale (VAS) and facial pain scale (FPS). Our study included a total of eighty patients with unilateral or bilateral tennis elbows. The study population included patients between 20 and 40 years age group belonging to either sex with seventy unilateral and ten bilateral affections for more than 3-month duration. Patients suffering from elbow pain due to other problems or those who have received any form of injection were excluded from the study. One milliliter of 2% Xylocaine injection was given before injecting the proposed formulation under trial. VAS and FPS were used for scoring pain. Kruskal-Wallis test and Mann-Whitney U-tests were used for statistical analyses at 12 and 24 weeks. Overall, 49 females and 31 males were included with thirty elbows in each group. Both the PRP and triamcinolone groups had better pain relief at 3 and 6 months as compared to normal saline group ( P PRP group had statistically significant better pain relief than triamcinolone group. In the triamcinolone group, 13 patients had injection site hypopigmentation and 3 patients had subdermal atrophy. Over a short term period, PRP gives better pain relief than triamcinolone or normal saline in tennis elbow which needs to be validated over long term period by further studies.

  12. A Pilot Study Evaluating the Effectiveness of Platelet-Rich Plasma Therapy for Treating Degenerative Tendinopathies: A Randomized Control Trial with Synchronous Observational Cohort.

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    Marni Wesner

    Full Text Available This pilot study aimed to inform future research evaluating the effectiveness of Platelet Rich Plasma (PRP injection for tendinopathy.Randomized control trial (RCT and synchronous observational cohort studies. For the RCT, consecutive consenting patients treated at an academic sports medicine clinic were randomly assigned to either a PRP or placebo control group.The Glen Sather Sport Medicine Clinic, Edmonton, Canada.The RCT included 9 participants with rotator cuff tendinopathy. The cohort study included 178 participants with a variety of tendinopathies.Patients receiving PRP were injected with 4 ml of platelets into the supraspinatus and/or infraspinatus, while patients in the placebo group were injected with 4 ml of saline. All participants undertook a 3-month standardized, home-based, daily exercise program.Participants in the RCT were re-evaluated 3, and 6 months post-injection. Change scores before and after injection on pain, disability and MRI-documented pathology outcomes were compared. In the cohort study, pain and disability were measured at 1, 2 and 3 months post-injection.For the RCT, 7 participants received PRP and 2 received placebo injections. Patients receiving PRP reported clinically important improvements in pain (>1.5/10 on VAS, disability (>15 point DASH change, and tendon pathology while those receiving placebo injections did not. In the observational cohort, statistically and clinically significant improvements in pain and disability were observed.This pilot study provides information for planning future studies of PRP effectiveness. Preliminary results indicate intratendinous, ultrasound-guided PRP injection may lead to improvements in pain, function, and MRI-documented tendon ISRCTN68341698.

  13. [Effects of use of riboflavin and ultraviolet light for pathogen inactivation on quality of platelet concentrates]. (United States)

    Stanojković, Zoran; Antić, Ana; Stojanović, Miodrag


    the mentioned difference in the measured parameters between K4 and I4 (the end of storage--the fifth day). All the platelet units were sterile till the seventh day, when the investigation ended. Platelet concentrates inactivated by riboflavin and UV rays (Mirasol PRT sistem, Caridian BCT, USA) keep all the characteristics assessed by the Guide to the preparation, use and quality assurance of blood components (Council of Europe), during the whole storage period (five days). The obtained data were correlated with existing up to date literature and demonstrated that Mirasol treated platelets were safe and could be incorporated effectively in the routine blood bank and transfusion setting.

  14. Effect of platelet-rich plasma on the healing of intrabony defects treated with an anorganic bovine bone mineral: a pilot study. (United States)

    Döri, Ferenc; Kovács, Viola; Arweiler, Nicole B; Huszár, Tamás; Gera, István; Nikolidakis, Dimitris; Sculean, Anton


    Periodontal therapy using the combination of platelet-rich plasma (PRP) and different grafting materials has been suggested as a modality to enhance the outcome of regenerative surgery. In most clinical studies, a barrier membrane was used to cover the defects, and thus, the effects of PRP may have been masked by the effects of the barrier. The data from controlled clinical studies evaluating the effect of regenerative therapy using various grafting materials with or without PRP are still limited. The purpose of this study was to clinically compare the healing of intrabony defects treated with either a combination of an anorganic bovine bone mineral (ABBM) and PRP to those obtained with ABBM alone. Thirty patients with advanced chronic periodontal disease and displaying one intrabony defect were randomly treated with PRP + ABBM or ABBM alone. The following clinical parameters were evaluated at baseline and 1 year after treatment: plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), gingival recession (GR), and clinical attachment level (CAL). The primary outcome variable was CAL. No statistical significant differences in any of the investigated parameters between the two groups were observed at baseline. Healing was uneventful in all patients. In the PRP + ABBM group, mean PD decreased from 8.6 +/- 1.8 mm to 3.4 +/- 1.4 mm (P or=3 mm were measured in 80% (12 of 15 defects) of cases treated with PRP + ABBM and in 87% (13 of 15 defects) of cases treated with ABBM alone. No statistically significant differences in any of the investigated parameters were observed between the two groups at the 1-year reevaluation. Within the limits of the present study, it can be concluded that 1) at 1 year after regenerative surgery with PRP + ABBM and ABBM alone, significant PD reductions and CAL gains were found, and 2) the use of PRP failed to improve the results obtained with ABBM alone.

  15. Immunohistological Evaluation of Revascularized Immature Permanent Necrotic Teeth Treated by Platelet-Rich Plasma: An Animal Investigation. (United States)

    Moradi, Saeed; Talati, Ali; Forghani, Maryam; Jafarian, Amir Hossein; Naseri, Mandana; Shojaeian, Shiva


    Pulp regeneration within the root canal of necrotic teeth is considered an ideal treatment to allow for continued root development and recover teeth vitality. This study aims to evaluate the inductive effect of platelet-rich plasma (PRP) on expression of angiogenesis factors and pulpal revascularization of immature necrotic teeth. In this experimental animal study, we randomly divided 28 immature premolars from two mixed breed dogs into four groups, two experimental, negative and a positive control. Premolars in negative control group were left intact to develop normally. In the positive control and experimental groups, we removed the pulps and induced pulp necrosis, after which the chambers were sealed. Then, we applied the revascularization protocol in the experimental teeth located in the right quadrant. Two months later, the same protocol was applied to the left quadrant. The root canals were disinfected by irrigation with sodium hypochlorite (NaOCl) solution and application a triple antibiotic past. Following the induction of a blood clot (BC) inside the canal space, the coronal portion of the canals was assigned to either of two experimental groups: group 1 [BC+PRP+ mineral trioxide aggregate (MTA)], group 2 (BC+MTA). Access cavities were sealed with a Glass Ionomer. The jaws that held the teeth were processed for histologic analysis of newly formed tissue and immunohistochemical evaluation according to vascular endothelial growth factor (VEGF) and factor VIII expressions in the canals. Histological analysis demonstrated no significant difference in the formation of new vital tissue inside the root canals between groups1 (42.8%) and 2 (43.5%, P>0.05). Based on immunohistochemical evaluation, micro-vessel density (MVD) of the granulation tissues in both groups were similar and were higher compared with the normal pulp. We observed strongly positive expressions of VEGF and factor VIII in the stromal and endothelial cells, with severe intensity after one month

  16. Analysis of experimental tendinitis in rats treated with laser and platelet-rich plasma therapies by Raman spectroscopy and histometry. (United States)

    de Carvalho, Paula Kariluce; Silveira, Landulfo; Barbosa, Danillo; Munin, Egberto; Salgado, Miguel Angel Castillo; Villaverde, Antonio Balbin


    The objective of this controlled experimental study was to analyze the changes in the Achilles tendons of rats with experimentally induced tendinitis after treatment with platelet-rich plasma (PRP) and/or laser therapies by histometry to quantify fibroblasts and by Raman spectroscopy to determine the biochemical concentration of collagen types I and III. Fifty-four male Wistar rats were divided into six treatment groups: control (G1); PRP only (G2); irradiation with 660 nm laser (G3); irradiation with 830 nm laser (G4); PRP plus 660 nm laser irradiation (G5); and PRP plus 830 nm laser irradiation (G6). Injuries (partial tenotomy) were inflicted in the middle third of the Achilles tendon, with PRP added prior to suture in the appropriate experimental groups. A diode laser (model Laser Flash® III, DMC Equipamentos Ltda, São Carlos, SP, Brazil) that can be operated in two wavelengths 660 and 830 nm was used for irradiation treatments. The irradiation protocol was energy density of 70 J/cm², 20 s irradiation time, and 0.028 cm² spot area, per point in three points in the injured. The histometry was made in micrographical images of the H&E stained sections and evaluated by ImageJ (version 1.46r)®. Raman spectra were collected using a dispersive spectrometer at 830 nm excitation, 200 mW power, and 10 s integration time (P-1 Raman system, Lambda Solutions, Inc. MA, USA). The relative amount of type I collagen was significantly greater in the PRP plus 830 nm laser irradiation group (468 ± 188) than in the control (147 ± 137), 630 nm laser only (191 ± 117), and 830 nm laser only (196 ± 106) groups (p < 0.01), while the quantity of type III collagen was significantly greater in the PRP-only group compared to both irradiated groups without PRP (p < 0.05). Treatment with PRP combined with irradiation at 830 nm resulted in a larger number of fibroblasts and increased concentration of type I collagen, thus accelerating the healing of the injured

  17. Immunohistological Evaluation of Revascularized Immature Permanent Necrotic Teeth Treated by Platelet-Rich Plasma: An Animal Investigation (United States)

    Moradi, Saeed; Talati, Ali; Forghani, Maryam; Jafarian, Amir Hossein; Naseri, Mandana; Shojaeian, Shiva


    Objective Pulp regeneration within the root canal of necrotic teeth is considered an ideal treatment to allow for continued root development and recover teeth vitality. This study aims to evaluate the inductive effect of platelet-rich plasma (PRP) on expression of angiogenesis factors and pulpal revascularization of immature necrotic teeth. Materials and Methods In this experimental animal study, we randomly divided 28 immature premolars from two mixed breed dogs into four groups, two experimental, negative and a positive control. Premolars in negative control group were left intact to develop normally. In the positive control and experimental groups, we removed the pulps and induced pulp necrosis, after which the chambers were sealed. Then, we applied the revascularization protocol in the experimental teeth located in the right quadrant. Two months later, the same protocol was applied to the left quadrant. The root canals were disinfected by irrigation with sodium hypochlorite (NaOCl) solution and application a triple antibiotic past. Following the induction of a blood clot (BC) inside the canal space, the coronal portion of the canals was assigned to either of two experimental groups: group 1 [BC+PRP+ mineral trioxide aggregate (MTA)], group 2 (BC+MTA). Access cavities were sealed with a Glass Ionomer. The jaws that held the teeth were processed for histologic analysis of newly formed tissue and immunohistochemical evaluation according to vascular endothelial growth factor (VEGF) and factor VIII expressions in the canals. Results Histological analysis demonstrated no significant difference in the formation of new vital tissue inside the root canals between groups1 (42.8%) and 2 (43.5%, P>0.05). Based on immunohistochemical evaluation, micro-vessel density (MVD) of the granulation tissues in both groups were similar and were higher compared with the normal pulp. We observed strongly positive expressions of VEGF and factor VIII in the stromal and endothelial cells

  18. Evaluation of Mirasol pathogen reduction system by artificially contaminating platelet concentrates with Staphylococcus epidermidis: A pilot study from India

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    Kabita Chatterjee


    Full Text Available Background and Objectives: This study was conducted to assess the efficacy of Mirasol pathogen reduction system for platelets aimed at preventing bacterial regrowth by spiking buffy coat pooled platelets (BCPP with clinically relevant load of Staphylococous epidermidis. Materials and Methods: BCPP units were prepared using Teruflex BP-kit with Imugard III-S-PL (Terumo BCT, Tokyo, Japan. Two BCPP units were pooled, of which 40 ml of negative control (NC was removed. The remaining volume of the platelet unit was inoculated with clinically relevant load of bacteria (total of 30 CFU of S. epidermidis in 1 ml; following this the platelet unit was split into two parts. One part served as positive control (PC and the other part was subjected to pathogen reduction technique (Mirasol PRT, CaridianBCT Biotechnologies, Lakewood, CO, USA. Bacterial detection was performed using BacT/ALERT system, controls after day 1 and day 7 following inoculation of bacteria and on day 7 for Mirasol-treated unit. Results: Of the 32 treatment cycles, 28 were valid and 4 were invalid. No regrowth was observed in 96.4% (27 of 28 after treatment with Mirasol pathogen reduction system. Of four invalid tests, on two instances the NC showed growth, whereas in other 2 no regrowth was detected in 7th day PC. Bacterial screening of PCs by BacT/ALERT after 24 h of incubation was 28.6%, whereas the effectiveness increased to 100% when incubated for 7 days. Conclusions: Mirasol system was effective in inactivating S.epidermidis when it was deliberately inoculated into BCPP at clinically relevant concentrations. Such systems may significantly improve blood safety by inactivating traditional and emerging transfusion-transmitted pathogens.

  19. Mean Platelet Volume and Platelet Immunofluorescence as Indicators of Platelet Compatibility. (United States)


    2.5 ml of 1.2% EDTA in 0.9% NaCl. The platelet- rich plasm (PRP) was isolated by centrifugation at 280 X g for 5 mimmter. The PRP from all the blood...samples was pooled, and the platelets were concentrated by cpntrifugation at 1000 X g for 10 minutes. The platelet- poor plasma (PPP) was removed and -6.4% 2 shrinking 18. TABLE 2 .60A PLATLET _RLUME OF A+ OR 0+ DONOR PLATELETS TREATED WITH EITHER &U,&06OS S O SRUMNFRN AN AOIMMUNIZED TR

  20. The Secreted Protease PrtA Controls Cell Growth, Biofilm Formation and Pathogenicity in Xylella fastidiosa (United States)

    Gouran, Hossein; Gillespie, Hyrum; Nascimento, Rafael; Chakraborty, Sandeep; Zaini, Paulo A.; Jacobson, Aaron; Phinney, Brett S.; Dolan, David; Durbin-Johnson, Blythe P.; Antonova, Elena S.; Lindow, Steven E.; Mellema, Matthew S.; Goulart, Luiz R.; Dandekar, Abhaya M.


    Pierce’s disease (PD) is a deadly disease of grapevines caused by the Gram-negative bacterium Xylella fastidiosa. Though disease symptoms were formerly attributed to bacteria blocking the plant xylem, this hypothesis is at best overly simplistic. Recently, we used a proteomic approach to characterize the secretome of X. fastidiosa, both in vitro and in planta, and identified LesA as one of the pathogenicity factors of X. fastidiosa in grapevines that leads to leaf scorching and chlorosis. Herein, we characterize another such factor encoded by PD0956, designated as an antivirulence secreted protease “PrtA” that displays a central role in controlling in vitro cell proliferation, length, motility, biofilm formation, and in planta virulence. The mutant in X. fastidiosa exhibited reduced cell length, hypermotility (and subsequent lack of biofilm formation) and hypervirulence in grapevines. These findings are supported by transcriptomic and proteomic analyses with corresponding plant infection data. Of particular interest, is the hypervirulent response in grapevines observed when X. fastidiosa is disrupted for production of PrtA, and that PD-model tobacco plants transformed to express PrtA exhibited decreased symptoms after infection by X. fastidiosa. PMID:27492542

  1. Multiple gingival recession coverage treated with vestibular incision subperiosteal tunnel access approach with or without platelet-rich fibrin - A case series

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    Surbhi Garg


    Full Text Available Background: Gingival recession involves both soft tissue and hard tissue loss. In this evolutionary era of dentistry, newer techniques have evolved for complete coverage of isolated recession defects. Since 2012, vestibular incision subperiosteal tunnel access (VISTA technique was used with various regenerative membranes to treat multiple recession defects (MRDs. Platelet-rich fibrin (PRF membrane, a pool of growth factors but have any added advantage to recession coverage techniques is controversial. Thus, in this case series, we compare the effect of VISTA with or without PRF-membrane for the treatment of Classes I and III MRDs. Subjects and Methods: Four patients between of age 30 and 40 years (two patients having bilateral Class I and another two having bilateral Class III MRDs were selected from the Department of Periodontics, ITS Dental College, Greater Noida and designated as Case I–IV simultaneously. Recession defects at antagonist sites in each patient were corrected by VISTA approach with or without PRF-membrane. Recorded clinical parameters included recession depth, recession width, pocket probing depth, and clinical attachment level (CAL at baseline and 6 months postoperatively. Results: Patients having Class I recession defects showed almost complete root coverage with VISTA technique alone and reflected no added advantage of PRF-membrane. However, patients with Class III recession defects treated with VISTA + PRF-membrane showed more reduction in recession depth and gain in CAL as compared to sites treated with VISTA only. Conclusion: VISTA alone is a convenient technique for treatment of Class I MRDs. Addition of PRF-membrane for Class III recession defects give better outcome in term of reduction of recession depth and gain in CAL 6 month postoperatively.

  2. The paraoxonase 1 (PON1), platelet-activating factor acetylohydrolase (PAF-AH) and dimethylarginine dimethylaminohydrolase (DDAH) activity in the metformin treated normal and diabetic rats. (United States)

    Wójcicka, Grażyna; Jamroz-Wiśniewska, Anna; Czechowska, Grażyna; Korolczuk, Agnieszka; Marciniak, Sebastian; Bełtowski, Jerzy


    Antidiabetic agents per se, apart from their glucose-lowering effect, can have an important impact on modifying the cardiovascular risk. The present study was undertaken to determine whether the known cardio-protective effects of metformin are linked to its potential ability to affect activities of HDL's paraoxonase (PON1) and platelet activating factor acetylohydrolase (PAF-AH) or via its interaction with the asymmetric dimethylarginine (ADMA)- dimethylarginine dimethylaminohydrolase (DDAH) axis. Normal and streptozotocin (STZ)-induced diabetic rats were treated with metformin (300mg/kg; 4 weeks). The activity of PON1, PAF-AH and DDAH were measured spectrophotometrically. The plasma ADMA level was determined by ELISA method. In STZ-induced diabetic rats the long-term administration of metformin normalized reduced PON1 activity assayed toward paraoxon (+42.5%, PPAF-AH activity in the plasma. Moreover, metformin increased DDAH activity in the renal cortex (+38.24%, P<0.01). Additionally metformin administration caused the increase in PON1 activity in the liver (+29.2%, P<0.01) accompanied by the reduction in the lipid peroxidation (-59.8%, P<0.001). Similarly, in non-diabetic treated rats the increase in liver PON1 activity was observed toward both paraoxon (+80.19%, P<0.001) and phenyl acetate (+29.3%, P<0.05), respectively. The present study has demonstrated that insulin-sensitizer metformin is important for preserving antioxidant HDL function in diabetes. Metformin might also exert its effect against diabetic complications by improving DDAH activity in the kidney and increasing PON1 activity in the liver. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Platelet Donation (United States)

    ... body. I imagined the faces of many different strangers, taking time out of their day… their jobs… ... thing to do for another human being. A stranger. Someone’s platelets made their way to Phil that ...

  4. Evidence that platelet buoyant density, but not size, correlates with platelet age in man

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    Mezzano, D.; Hwang, K.; Catalano, P.; Aster, R.H.


    Following infusion of 51Cr-labeled autologous platelets into normal subjects, high-density (HD) and low-density (LD) platelet cohorts were isolated by prolonged centrifugation in isosmotic arabino-galactan (Stractan). Specific radio-activity of LD platelets declined rapidly post-infusion (T1/2 . 1.5 days), but specific radioactivity of HD platelets remained constant or increased over a 3--4-day period and gradually declined for 6--7 days thereafter. These differences were exaggerated when platelet cohorts enriched in LD or HD cells by slow centrifugation in high-density albumin were labeled and transfused. Mean survival of a platelet cohort enriched with HD cells was significantly (P less than 0.02) shorter (7.73 days) than that of a cohort enriched with LD cells (9.33) days). In normal subjects treated with aspirin, capacity for thromboxane synthesis was regained more rapidly (P less than 0.05) in LD than in HD platelets. HD and LD platelets differed only slightly in mean volume (HD platelets . 7.57 mu3, LD platelets . 6.87 mu3, 0.05 less than P less than 0.01). We believe the most logical interpretation of these findings is that under normal conditions in man, newly formed platelets are less dense on the average than total platelets and become more dense as they age in the circulation. Thus, specific radioactivity of LD platelets declines rapidly as these platelets move into a more dense compartment and are replaced by newly formed, unlabelled cells; specific radioactivity of HD platelets remains constant or increases as labelled platelets enter this compartment in numbers equal to or greater than the number leaving it at the end of their life span. The similarity in mean volumes of LD and HD platelets suggests that platelet size is unrelated to platelet age under normal conditions.

  5. Magnetic Nanoparticle Labeling of Human Platelets from Platelet Concentrates for Recovery and Survival Studies. (United States)

    Aurich, Konstanze; Wesche, Jan; Palankar, Raghavendra; Schlüter, Rabea; Bakchoul, Tamam; Greinacher, Andreas


    Platelets are the smallest blood cells and important for hemostasis. Platelet concentrates (PC) are medicinal products transfused to prevent or treat bleeding. Typically, platelets in PCs are assessed by in vitro tests for their function. However, in vivo testing of these platelets is highly desirable. To distinguish transfused platelets from patients or probands own cells after PC transfusions within the scope of clinical studies, platelets need to be efficiently labeled with minimal preactivation prior to transfusion. Here we report on a method for improved cell uptake of ferucarbotran magnetic nanoparticles contained in Resovist, an FDA-approved MRI contrast agent, by modifying the nanoparticle shell with human serum albumin (HSA). Both HSA-ferucarbotran nanoparticles and magnetically labeled platelets were produced according to EU-GMP guidelines. Platelet function after labeling was evaluated by light transmission aggregometry and by determination of expression of CD62P as platelet activation marker. Magnetic labeling does not impair platelet function and platelets showed reasonable activation response to agonists. Platelet survival studies in NOD/SCID-mice resulted in comparable survival behavior of magnetically labeled and nonlabeled platelets. Additionally, labeled platelets can be recovered from whole blood by magnetic separation.

  6. Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios as independent predictors of cervical stromal involvement in surgically treated endometrioid adenocarcinoma

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    Wang D


    Full Text Available Dan Wang, Jia-Xin Yang, Dong-Yan Cao, Xi-Run Wan, Feng-Zhi Feng, Hui-Fang Huang, Keng Shen, Yang Xiang Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China Background: The purpose of this study was to evaluate the relationship between preoperative inflammatory markers (neutrophil-lymphocyte ratio and platelet-lymphocyte ratio and cervical stromal involvement in patients with endometrioid adenocarcinoma. Methods: We studied 318 patients with endometrioid adenocarcinoma who underwent comprehensive surgical staging. We used univariate and multivariate analyses of cervical stromal involvement and receiver-operating curves to calculate optimal cutoff values for neutrophil-lymphocyte and platelet-lymphocyte ratios to predict cervical stromal involvement. Results: The presence of cervical stromal involvement was associated with neutrophil-lymphocyte ratio and platelet-lymphocyte ratio (P = 0.009 and P = 0.031, respectively. Multivariate analysis showed that higher neutrophil-lymphocyte and platelet-lymphocyte ratios independently predicted cervical stromal involvement (odds ratio 3.10, 95% confidence interval 1.10–8.76, P = 0.032, and odds ratio 5.27, 95% confidence interval 1.94–14.35, P = 0.001, respectively. At a threshold of 2.01, the neutrophil-lymphocyte ratio was 71.0% sensitive and 63.8% specific for stromal involvement; at a 172.24 threshold, the platelet-lymphocyte ratio was 48.4% sensitive and 88.9% specific. Conclusion: Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios can help identify the risk of cervical stromal involvement in patients with endometrial cancer. Evaluating these ratios may help select patients who should be particularly watched and tested for cervical stromal involvement. Keywords: neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, endometrioid adenocarcinoma

  7. Platelet Function Tests (United States)

    ... Patient Resources For Health Professionals Subscribe Search Platelet Function Tests Send Us Your Feedback Choose Topic At ... Also Known As Platelet Aggregation Studies PFT Platelet Function Assay PFA Formal Name Platelet Function Tests This ...

  8. Platelet antibodies blood test (United States)

    This blood test shows if you have antibodies against platelets in your blood. Platelets are a part of the blood ... Chernecky CC, Berger BJ. Platelet antibody - blood. In: Chernecky ... caused by platelet destruction, hypersplenism, or hemodilution. ...

  9. Ativação de plaquetas de eqüinos com laminite induzida e tratados com ketoprofeno, fenilbutazona e flunixin meglumina Platelets activation in equine with induced laminitis and treated with ketoprophen, phenylbutazone and flunixin meglumin

    Directory of Open Access Journals (Sweden)

    F.O. Paes Leme


    Full Text Available Avaliou-se a ativação de plaquetas em 20 eqüinos com laminite induzida, tratados com ketoprofeno, fenilbutazona e flunixin meglumina. As alterações de plaquetas incluíram mudança de forma, alteração da relação entre os eixos maior e menor, aumento de perímetro, emissão de pseudópodes, aumento no número dealfa-grânulos e de grânulos de glicogênio e redução no número degama-grânulos. As plaquetas de eqüinos, quando ativadas, apresentaram perfil de organela diferente de plaquetas normais, e as drogas antiinflamatórias, não-esteroidais, demonstraram atividade na ativação plaquetária de eqüinos in vivo. O flunixin meglumina apresentou melhor atividade em modular a ativação plaquetária de eqüinos in vivo do que a fenilbutazona e o ketoprofeno.The platelets activation from 20 equines submitted to laminitis induction and treated with ketoprophen, phenylbutazone and flunixin meglumin, was evaluated. The platelets changes included shape change, altered relations between axis, increased perimeter, pseudopodia, increased alpha-granules and glycogen-granules, and decreased in gamma-granules. Platelets when activated present a different organelle profile than normal ones. Equine activated platelets had different organelles profile than normal ones, and anti-inflammatory drugs can modulate the platelet activation, being the flunixin meglumin better than phenylbutazone and ketoprophen.

  10. New single-nucleotide polymorphisms associated with differences in platelet reactivity and their influence on survival in patients with type 2 diabetes treated with acetylsalicylic acid: an observational study. (United States)

    Milanowski, Lukasz; Pordzik, Justyna; Janicki, Piotr K; Kaplon-Cieslicka, Agnieszka; Rosiak, Marek; Peller, Michal; Tyminska, Agata; Ozieranski, Krzysztof; Filipiak, Krzysztof J; Opolski, Grzegorz; Mirowska-Guzel, Dagmara; Postula, Marek


    Genetic polymorphisms may contribute to platelet reactivity in diabetic patients; however, the information on their influence on long-term antiplatelet therapy is lacking. Our aim was to evaluate the role of previously described genetic variants and platelet reactivity on risk of all-cause mortality and cardiovascular events. Blood samples were obtained from 303 Caucasian patients. Genome-wide genotyping was performed using Illumina Human Omni 2.5-Quad microarrays, and individual genotyping of selected SNPs was performed using a custom Sequenom iPLEX assay in conjunction with the Mass ARRAY platform. Platelet reactivity was measured with VerifyNow Aspirin Assay and PFA-100 Assay. Univariate and multivariate Cox regression analyses were performed to determine the impact of genetic variants and platelets reactivity on risk of all-cause mortality and cardiovascular events. Among the 237 patients included in the follow-up, death from any cause occurred in 34 (14.3%) patients and cardiovascular events occurred in 51 (21.5%) patients within a median observation time of 71 months (5.9 years). In univariate analyses, significant association in the presence of minor alleles in TXBA2R (rs1131882) with primary (HR 2.54, 95% CI 1.15-5.60, p = 0.021) and secondary endpoint (HR 2.06, 95% CI 1.06-4.04, p = 0.034) was observed. In addition, multivariate analyses revealed the impact of this polymorphism on primary (HR 2.34, 95% CI 1.09-5.00, p = 0.029) and secondary endpoint (HR 1.89, 95% CI 1.00-3.57, p = 0.048). Results of the study demonstrate for the first time an association between genetic polymorphism within TXBA2R gene encoding platelet's surface receptor and long-term survival of diabetic patients treated with ASA.

  11. Calpain Activator Dibucaine Induces Platelet Apoptosis

    Directory of Open Access Journals (Sweden)

    Jun Liu


    Full Text Available Calcium-dependent calpains are a family of cysteine proteases that have been demonstrated to play key roles in both platelet glycoprotein Ibα shedding and platelet activation and altered calpain activity is associated with thrombotic thrombocytopenic purpura. Calpain activators induce apoptosis in several types of nucleated cells. However, it is not clear whether calpain activators induce platelet apoptosis. Here we show that the calpain activator dibucaine induced several platelet apoptotic events including depolarization of the mitochondrial inner transmembrane potential, up-regulation of Bax and Bak, down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation and phosphatidylserine exposure. Platelet apoptosis elicited by dibucaine was not affected by the broad spectrum metalloproteinase inhibitor GM6001. Furthermore, dibucaine did not induce platelet activation as detected by P-selectin expression and PAC-1 binding. However, platelet aggregation induced by ristocetin or α-thrombin, platelet adhesion and spreading on von Willebrand factor were significantly inhibited in platelets treated with dibucaine. Taken together, these data indicate that dibucaine induces platelet apoptosis and platelet dysfunction.

  12. Analysis of the rate of maturogenesis of a traumatized Cvek′s stage 3 anterior tooth treated with platelet-rich fibrin as a regenerative tool using three-dimensional cone-beam computed tomography: An original case report

    Directory of Open Access Journals (Sweden)

    Raji Viola Solomon


    Full Text Available Regenerative endodontic procedures are biologically based procedures which deal with the regeneration of pulp-like tissue, more idealistically the pulp-dentin complex. The regeneration of this pulp-dentin complex in an infected necrotic tooth with an open apex is possible only when the canal is effectively disinfected. Though there are various procedures for treating open apex ranging from Ca(OH 2 apexification, mineral trioxide aggregate apexification and surgical approach, regeneration of tissues has always taken superior hand over the repair of tissues. The mechanics behind the regenerative endodontic procedures is that despite the tooth being necrotic, some pulp tissue can survive apically which under favorable conditions proliferate to aid in the process of regeneration. In the past 2 decades, an increased understanding of the physiological roles of platelets in wound healing and after tissue injury has led to the idea of using platelets as therapeutic tools in the field regenerative endodontics. In the present case report with an open apex, high sterilization protocol is followed using triple antibiotic paste as intra-canal medicament, followed which platelet rich fibrin is used as the regenerative material of choice. Over an 18-month follow-up period, clinically patient is asymptomatic and radiographically there is complete regression of the periapical lesion and initiation of the root end closure.

  13. LDL oxidation by platelets propagates platelet activation via an oxidative stress-mediated mechanism. (United States)

    Carnevale, Roberto; Bartimoccia, Simona; Nocella, Cristina; Di Santo, Serena; Loffredo, Lorenzo; Illuminati, Giulio; Lombardi, Elisabetta; Boz, Valentina; Del Ben, Maria; De Marco, Luigi; Pignatelli, Pasquale; Violi, Francesco


    Platelets generate oxidized LDL (ox-LDL) via NOX2-derived oxidative stress. We investigated if once generated by activated platelets ox-LDL can propagate platelet activation. Experiments were performed in platelets from healthy subjects (HS), hyper-cholesterolemic patients and patients with NOX2 hereditary deficiency. Agonist-stimulated platelets from HS added with LDL were associated with a dose-dependent increase of reactive oxidant species and ox-LDL. Agonist-stimulated platelets from HS added with a fixed dose of LDL (57.14 μmol/L) or added with homogenized human atherosclerotic plaque showed enhanced ox-LDL formation (approximately +50% and +30% respectively), which was lowered by a NOX2 inhibitor (approximately -35% and -25% respectively). Compared to HS, ox-LDL production was more pronounced in agonist-stimulated platelet rich plasma (PRP) from hyper-cholesterolemic patients but was almost absent in PRP from NOX2-deficient patients. Platelet aggregation and 8-iso-PGF2α-ΙΙΙ formation increased in LDL-treated washed platelets (+42% and +53% respectively) and PRP (+31% and +53% respectively). Also, LDL enhanced platelet-dependent thrombosis at arterial shear rate (+33%) but did not affect platelet activation in NOX2-deficient patients. Platelet activation by LDL was significantly inhibited by CD36 or LOX1 blocking peptides, two ox-LDL receptor antagonists, or by a NOX2 inhibitor. LDL-added platelets showed increased p38MAPK (+59%) and PKC (+51%) phosphorylation, p47(phox) translocation to platelet membrane (+34%) and NOX2 activation (+30%), which were inhibited by ox-LDL receptor antagonists. Platelets oxidize LDL, which in turn amplify platelet activation via specific ox-LDL receptors; both effects are mediated by NOX2 activation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Platelet transfusion. (United States)


    The statement printed below was agreed at a consensus conference on platelet transfusion organised by the Royal College of Physicians of Edinburgh and held in Edinburgh in November 1997. We publish this statement at the request of the organising committee to bring it to the attention of physicians who do not read the haematological literature. The statement will also appear in the British Journal of Haematology in 1998 with the scientific evidence upon which it is based.

  15. A megakaryocyte with no platelets: anti-platelet antibodies, apoptosis, and platelet production. (United States)

    Perdomo, José; Yan, Feng; Chong, Beng H


    Primary immune thrombocytopenia (ITP) and drug-induced thrombocytopenia (DITP) are disorders caused primarily by the presence of anti-platelet auto-antibodies (Abs). Hematologists have traditionally seen thrombocytopenia as the result of increased destruction of Ab-coated platelets by the reticuloendothelial system. While accurate, this approach does not fully account for other laboratory observations. There is increasing evidence suggesting a significant cellular component in the etiology of both ITP and DITP. In ITP, megakaryocytes (Mks) show characteristics consistent with increased apoptosis, which correlates with a reduction in platelet production capacity. Platelet production by Mks is impaired in both the bone marrow of ITP patients and in Mks produced in vitro when treated with ITP or DITP auto-Abs. Recently, it was shown that anti GPIb/IX DITP Abs act directly on Mks and induce apoptosis, hinder differentiation, and prevent platelet production. The origin of pathological megakaryocytic apoptosis is yet to be explored in more detail but current observations imply that there is a direct contribution by anti-platelet Abs. Here we review the evidence for Ab-mediated megakaryocytic damage in ITP and DITP, examine possible molecular mechanisms and consider potential clinical implications.

  16. A Study of a Merging Section of PRT System with Bulk Arrival and its Control Strategy (United States)

    Hoshino, Takahiro; Inoue, Kousuke; Tsuboi, Kazuhiro; Hamamatsu, Yoshio

    This paper deals with a merging section of Personal Rapid Transit system with bulk arrival. Vehicles arrive at a merging section from a main line and a sub line. In most of the previous studies on PRT system, vehicles on the main line have priority. Then, a queue is formed only on the sub line. In this situation, the queuing delay on the sub line may become extremely long. We propose a control strategy whereby vehicles on the main line are not stopped in normal situation; vehicles on the main line are only stopped when the number of waiting vehicles on the sub line exceeds some specific number. This specific number is a sort of threshold. Thus, queues are formed on the main line and the sub line, respectively. Both of the queuing delays are controlled with the threshold. The optimal value of the threshold can be obtained by analyzing the stochastic model. By the optimal value, we can set the rate of queuing delay between the main and sub lines to an arbitrary rate.

  17. Characterization of an extensin-modifying metalloprotease: N-terminal processing and substrate cleavage pattern of Pectobacterium carotovorum Prt1

    DEFF Research Database (Denmark)

    Feng, Tao; Nyffenegger, Christian; Højrup, Peter


    Compared to other plant cell wall-degrading enzymes, proteases are less well understood. In this study, the extracellular metalloprotease Prt1 from Pectobacterium carotovorum (formerly Erwinia carotovora) was expressed in Escherichia coli and characterized with respect to N-terminal processing......, thermal stability, substrate targets, and cleavage patterns. Prt1 is an autoprocessing protease with an N-terminal signal pre-peptide and a pro-peptide which has to be removed in order to activate the protease. The sequential cleavage of the N-terminus was confirmed by mass spectrometry (MS......) fingerprinting and N-terminus analysis. The optimal reaction conditions for the activity of Prt1 on azocasein were at pH 6.0, 50 °C. At these reaction conditions, KM was 1.81 mg/mL and kcat was 1.82 × 107 U M-1. The enzyme was relatively stable at 50 °C with a half-life of 20 min. Ethylenediaminetetraacetic acid...

  18. The S-layer Associated Serine Protease Homolog PrtX Impacts Cell Surface-Mediated Microbe-Host Interactions of Lactobacillus acidophilus NCFM

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    Brant R. Johnson


    Full Text Available Health-promoting aspects attributed to probiotic microorganisms, including adhesion to intestinal epithelia and modulation of the host mucosal immune system, are mediated by proteins found on the bacterial cell surface. Notably, certain probiotic and commensal bacteria contain a surface (S- layer as the outermost stratum of the cell wall. S-layers are non-covalently bound semi-porous, crystalline arrays of self-assembling, proteinaceous subunits called S-layer proteins (SLPs. Recent evidence has shown that multiple proteins are non-covalently co-localized within the S-layer, designated S-layer associated proteins (SLAPs. In Lactobacillus acidophilus NCFM, SLP and SLAPs have been implicated in both mucosal immunomodulation and adhesion to the host intestinal epithelium. In this study, a S-layer associated serine protease homolog, PrtX (prtX, lba1578, was deleted from the chromosome of L. acidophilus NCFM. Compared to the parent strain, the PrtX-deficient strain (ΔprtX demonstrated increased autoaggregation, an altered cellular morphology, and pleiotropic increases in adhesion to mucin and fibronectin, in vitro. Furthermore, ΔprtX demonstrated increased in vitro immune stimulation of IL-6, IL-12, and IL-10 compared to wild-type, when exposed to mouse dendritic cells. Finally, in vivo colonization of germ-free mice with ΔprtX led to an increase in epithelial barrier integrity. The absence of PrtX within the exoproteome of a ΔprtX strain caused morphological changes, resulting in a pleiotropic increase of the organisms’ immunomodulatory properties and interactions with some intestinal epithelial cell components.

  19. Multidisciplinary approach to non-surgical management of inguinal disruption in a professional hockey player treated with platelet-rich plasma, manual therapy and exercise: a case report. (United States)

    St-Onge, Eric; MacIntyre, Ian G; Galea, Anthony M


    To present the clinical management of inguinal disruption in a professional hockey player and highlight the importance of a multidisciplinary approach to diagnosis and management. A professional hockey player with recurrent groin pain presented to the clinic after an acute exacerbation of pain while playing hockey. The patient received a clinical diagnosis of inguinal disruption. Imaging revealed a tear in the rectus abdominis. Management included two platelet-rich plasma (PRP) injections to the injured tissue, and subsequent manual therapy and exercise. The patient returned to his prior level of performance in 3.5 weeks. This case demonstrated the importance of a multidisciplinary team and the need for advanced imaging in athletes with groin pain. Research quality concerning the non-surgical management of inguinal disruption remains low. This case adds evidence that PRP, with the addition of manual therapy and exercise may serve as a relatively quick and effective non-surgical management strategy.

  20. Prevalência de alta reatividade plaquetária em pacientes tratados com aspirina encaminhados para angiografia coronária Prevalence of high platelet reactivity in aspirin-treated patients referred for coronary angiography

    Directory of Open Access Journals (Sweden)

    André Manica


    Full Text Available FUNDAMENTO: A aspirina (Ácido Acetilsalicílico - AAS é capaz de reduzir eventos adversos cardiovasculares em pacientes portadores de Doença Arterial Coronariana (DAC através da inibição da atividade plaquetária. Alguns pacientes com DAC, apesar da terapia com AAS, apresentam Alta Reatividade Plaquetária (ARP, o que determina um maior risco para o desenvolvimento de eventos cardiovasculares. OBJETIVO: O objetivo deste estudo foi determinar a prevalência de ARP em pacientes tratados com AAS e encaminhados para cinecoronariografia, além de avaliar se existe uma possível correlação entre a gravidade da DAC e o desenvolvimento de ARP. MÉTODOS: Estudo de centro único onde foram incluídos 115 pacientes consecutivos, tratados com AAS e portadores de DAC estável. A reatividade plaquetária induzida pelo ADP e colágeno foram avaliadas através da Agregometria de Transmitância Luminosa (ATL. Pacientes com agregação plaquetária maior que 70%, induzida por ambos os reagentes, foram classificados como tendo ARP e, neste grupo, a adesão ao tratamento com AAS foi avaliada através da dosagem dos níveis séricos de salicilato. RESULTADOS: A média de idade foi de 60,9 anos e a dose média de AAS foi de 164,2 mg. Tabagismo e diabetes melito estavam presentes em 28,7% e 31,5% dos pacientes, respectivamente. Foi encontrada ARP em 14 pacientes (13%, entretanto, em sete indivíduos (50% com ARP observaram-se baixos níveis séricos de salicilato (BACKGROUND: Aspirin (ASA reduces adverse events in coronary artery disease (CAD patients by inhibiting platelets. Some CAD patients have high platelet reactivity (HPR despite ASA therapy and these individuals have increased risk of adverse events. OBJECTIVE: The purpose of this study was to determine the prevalence of HPR in ASA-treated patients referred for coronary angiography and to assess whether the HPR correlates with the severity of CAD. METHODS: This single center investigation enrolled 115

  1. Drug-Free Platelets Can Act as Seeds for Aggregate Formation During Antiplatelet Therapy (United States)

    Hoefer, Thomas; Armstrong, Paul C.; Finsterbusch, Michaela; Chan, Melissa V.; Kirkby, Nicholas S.


    Objective— Reduced antiplatelet drug efficacy occurs in conditions of increased platelet turnover, associated with increased proportions of drug-free, that is, uninhibited, platelets. Here, we detail mechanisms by which drug-free platelets promote platelet aggregation in the face of standard antiplatelet therapy. Approach and Results— To model standard antiplatelet therapy, platelets were treated in vitro with aspirin, the P2Y12 receptor blocker prasugrel active metabolite, or aspirin plus prasugrel active metabolite. Different proportions of uninhibited platelets were then introduced. Light transmission aggregometry analysis demonstrated clear positive associations between proportions of drug-free platelets and percentage platelet aggregation in response to a range of platelet agonists. Using differential platelet labeling coupled with advanced flow cytometry and confocal imaging we found aggregates formed in mixtures of aspirin-inhibited platelets together with drug-free platelets were characterized by intermingled platelet populations. This distribution is in accordance with the ability of drug-free platelets to generate thromboxane A2 and so drive secondary platelet activation. Conversely, aggregates formed in mixtures of prasugrel active metabolite–inhibited or aspirin plus prasugrel active metabolite–inhibited platelets together with drug-free platelets were characterized by distinct cores of drug-free platelets. This distribution is consistent with the ability of drug-free platelets to respond to the secondary activator ADP. Conclusions— These experiments are the first to image the interactions of inhibited and uninhibited platelets in the formation of platelet aggregates. They demonstrate that a general population of platelets can contain subpopulations that respond strikingly differently to overall stimulation of the population and so act as the seed for platelet aggregation. PMID:26272940

  2. Platelet concentration in platelet concentrates and periodontal regeneration-unscrambling the ambiguity. (United States)

    Suchetha, A; Lakshmi, P; Bhat, Divya; Mundinamane, Darshan B; Soorya, K V; Bharwani, G Ashit


    Platelet-rich-plasma (PRP) and Platelet-rich-fibrin (PRF) are extensively used autologous platelet concentrates in periodontal regeneration, and PRF has a better efficacy as compared to PRP. The rationale for this difference has often been attributed to the difference in the structure of the fibrin matrix. However, the effect of concentration of platelets on the regenerative potential of these concentrates is obscure. The study was conducted to evaluate and compare, clinically and radiographically, the efficacy of PRF and PRP in the treatment of periodontal endosseous defects and to assess the effect of platelet concentration on periodontal regeneration. Twenty intrabony defects were selected and divided into two groups randomly by the coin toss method. Group I received PRP and Group II subjects were treated with PRF. The platelet counts in PRP and PRF were analyzed. Clinical and radiological parameters were assessed at baseline and 3, 6, and 9 months postoperatively. Kruskal-Wallis Chi-square test, Wilcoxon signed rank test, t-test, and Spearman's rank correlation were used for statistical analysis of data. There was statistically significant improvement in all the parameters in the two groups except in relation to gingival recession. There was a statistically significant difference between the platelet count in Group I and Group II (P = 0.002). PRP and PRF appear to have nearly comparable effects in terms of periodontal regeneration. The concentration of platelets appears to play a paradoxical role in regeneration. The regenerative potential of platelets appears to be optimal within a limited range.

  3. Pulmonary function in patients with acute coronary syndrome treated with ticagrelor or clopidogrel (from the Platelet Inhibition and Patient Outcomes [PLATO] pulmonary function substudy). (United States)

    Storey, Robert F; Becker, Richard C; Harrington, Robert A; Husted, Steen; James, Stefan K; Cools, Frank; Steg, Philippe Gabriel; Khurmi, Nardev S; Emanuelsson, Hakan; Lim, Soo Teik; Cannon, Christopher P; Katus, Hugo A; Wallentin, Lars


    The Platelet Inhibition and Patient Outcomes (PLATO) trial showed that ticagrelor reduced the risk for cardiovascular events in patients with acute coronary syndromes compared to clopidogrel but was associated with increased incidence of dyspnea. This substudy assessed whether ticagrelor affects pulmonary function in patients with acute coronary syndromes: 199 patients enrolled in the PLATO trial and receiving randomized treatment with ticagrelor 90 mg twice daily (n = 101) or clopidogrel 75 mg/day (n = 98) took part in the pulmonary function substudy. Patients with advanced lung disease, congestive heart failure, or coronary artery bypass graft surgery after the index event were excluded. Pulse oximetry (blood oxygen saturation), spirometry (forced expiratory volume in 1 second, forced vital capacity, and forced expiratory flow between 25% and 75% of forced vital capacity before and 20 minutes after inhalation of a β(2) agonist), lung volumes (total lung capacity, functional residual capacity, residual volume), and diffusion capacity were performed after patients received study medication for 30 to 40 days. Tests were then repeated <10 days before and approximately 30 days after the discontinuation of study medication. After a mean treatment duration of 31 days, there were no differences between the groups for any of the pulmonary function parameters. At the end of treatment (mean 211 days) and after the discontinuation of study medication (mean 32 days after the last dose), there was also no evidence of a change in pulmonary function in either group. For example, forced expiratory volume in 1 second values before β(2) agonist inhalation in the ticagrelor and clopidogrel groups were 2.81 ± 0.73 and 2.70 ± 0.84 L, respectively, at the first visit and did not change significantly at subsequent visits. In conclusion, no effect of ticagrelor on pulmonary function was seen in this cohort of patients with acute coronary syndromes compared to clopidogrel. Copyright

  4. Tamoxifen Directly Inhibits Platelet Angiogenic Potential and Platelet-Mediated Metastasis. (United States)

    Johnson, Kelly E; Forward, Jodi A; Tippy, Mason D; Ceglowski, Julia R; El-Husayni, Saleh; Kulenthirarajan, Rajesh; Machlus, Kellie R; Mayer, Erica L; Italiano, Joseph E; Battinelli, Elisabeth M


    Platelets, which are mainly known for their role in hemostasis, are now known to play a crucial role in metastasis. Tamoxifen is a selective estrogen receptor modulator that is widely used for the treatment of breast cancer. Tamoxifen and its metabolites have been shown to directly impact platelet function, suggesting that this drug has additional mechanisms of action. The purpose of this study was to determine whether tamoxifen exerts antitumor effects through direct platelet inhibition. This study found that pretreatment with tamoxifen leads to a significant inhibition of platelet activation. Platelets exposed to tamoxifen released significantly lower amounts of proangiogenic regulator vascular endothelial growth factor. In vitro angiogenesis assays confirmed that tamoxifen pretreatment led to diminished capillary tube formation and decreased endothelial migration. Tamoxifen and its metabolite, 4-hydroxytamoxifen, also significantly inhibited the ability of platelets to promote metastasis in vitro. Using a membrane-based array, we identified several proteins associated with angiogenesis metastasis that were lower in activated releasate from tamoxifen-treated platelets, including angiogenin, chemokine (C-X-C motif) ligand 1, chemokine (C-C motif) ligand 5, epidermal growth factor, chemokine (C-X-C motif) ligand 5, platelet-derived growth factor dimeric isoform BB, whereas antiangiogenic angiopoietin-1 was elevated. Platelets isolated from patients on tamoxifen maintenance therapy were also found to have decreased activation responses, diminished vascular endothelial growth factor release, and lower angiogenic and metastatic potential. We demonstrate that tamoxifen and its metabolite 4-hydroxytamoxifen directly alter platelet function leading to decreased angiogenic and metastatic potential. Furthermore, this study supports the idea of utilizing targeted platelet therapies to inhibit the platelet's role in angiogenesis and malignancy. © 2017 American Heart

  5. Interaction of the RNP1 motif in PRT1 with HCR1 promotes 40S binding of eukaryotic initiation factor 3 in yeast

    DEFF Research Database (Denmark)

    Nielsen, Klaus H; Valásek, Leos; Sykes, Caroah


    We found that mutating the RNP1 motif in the predicted RRM domain in yeast eukaryotic initiation factor 3 (eIF3) subunit b/PRT1 (prt1-rnp1) impairs its direct interactions in vitro with both eIF3a/TIF32 and eIF3j/HCR1. The rnp1 mutation in PRT1 confers temperature-sensitive translation initiation...... in vivo and reduces 40S-binding of eIF3 to native preinitiation complexes. Several findings indicate that the rnp1 lesion decreases recruitment of eIF3 to the 40S subunit by HCR1: (i) rnp1 strongly impairs the association of HCR1 with PRT1 without substantially disrupting the eIF3 complex; (ii) rnp1......) hcr1Delta impairs 40S binding of eIF3 in otherwise wild-type cells. Interestingly, rnp1 also reduces the levels of 40S-bound eIF5 and eIF1 and increases leaky scanning at the GCN4 uORF1. Thus, the PRT1 RNP1 motif coordinates the functions of HCR1 and TIF32 in 40S binding of eIF3 and is needed...

  6. Platelet Count and Plateletcrit

    African Journals Online (AJOL)

    Aim: To determine whether platelet count, plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width. (PDW) and their ratios can predict mortality in hospitalised children. Methods: Children who died during hospital stay were the cases. Controls were age matched children admitted contempora- neously.

  7. Prophylactic platelets in dengue

    DEFF Research Database (Denmark)

    Whitehorn, James; Rodriguez Roche, Rosmari; Guzman, Maria G


    Dengue is the most important arboviral infection of humans. Thrombocytopenia is frequently observed in the course of infection and haemorrhage may occur in severe disease. The degree of thrombocytopenia correlates with the severity of infection, and may contribute to the risk of haemorrhage...... of platelets in dengue. Respondents were all physicians involved with the treatment of patients with dengue. Respondents were asked that their answers reflected what they would do if they were the treating physician. We received responses from 306 physicians from 20 different countries. The heterogeneity...... of the responses highlights the variation in clinical practice and lack of an evidence base in this area and underscores the importance of prospective clinical trials to address this key question in the clinical management of patients with dengue....

  8. Rhesus monkey platelets

    Energy Technology Data Exchange (ETDEWEB)

    Harbury, C.B.


    The purpose of this abstract is to describe the adenine nucleotide metabolism of Rhesus monkey platelets. Nucleotides are labelled with /sup 14/C-adenine and extracted with EDTA-ethanol (EE) and perchlorate (P). Total platelet ATP and ADP (TATP, TADP) is measured in the Holmsen Luciferase assay, and expressed in nanomoles/10/sup 8/ platelets. TR=TATP/TADP. Human platelets release 70% of their TADP, with a ratio of released ATP/ADP of 0.7. Rhesus platelets release 82% of their TADP, with a ratio of released ATP/ADP of 0.33. Thus, monkey platelets contain more ADP than human platelets. Thin layer chromatography of EE gives a metabolic ratio of 11 in human platelets and 10.5 in monkey platelets. Perchlorate extracts metabolic and actin bound ADP. The human and monkey platelets ratios were 5, indicating they contain the same proportion of actin. Thus, the extra ADP contained in monkey platelets is located in the secretory granules.

  9. Vibrio cholerae cytolysin causes an inflammatory response in human intestinal epithelial cells that is modulated by the PrtV protease.

    Directory of Open Access Journals (Sweden)

    Gangwei Ou

    Full Text Available BACKGROUND: Vibrio cholerae is the causal intestinal pathogen of the diarrheal disease cholera. It secretes the protease PrtV, which protects the bacterium from invertebrate predators but reduces the ability of Vibrio-secreted factor(s to induce interleukin-8 (IL-8 production by human intestinal epithelial cells. The aim was to identify the secreted component(s of V. cholerae that induces an epithelial inflammatory response and to define whether it is a substrate for PrtV. METHODOLOGY/PRINCIPAL FINDINGS: Culture supernatants of wild type V. cholerae O1 strain C6706, its derivatives and pure V. cholerae cytolysin (VCC were analyzed for the capacity to induce changes in cytokine mRNA expression levels, IL-8 and tumor necrosis factor-alpha (TNF-alpha secretion, permeability and cell viability when added to the apical side of polarized tight monolayer T84 cells used as an in vitro model for human intestinal epithelium. Culture supernatants were also analyzed for hemolytic activity and for the presence of PrtV and VCC by immunoblot analysis. CONCLUSIONS/SIGNIFICANCE: We suggest that VCC is capable of causing an inflammatory response characterized by increased permeability and production of IL-8 and TNF-alpha in tight monolayers. Pure VCC at a concentration of 160 ng/ml caused an inflammatory response that reached the magnitude of that caused by Vibrio-secreted factors, while higher concentrations caused epithelial cell death. The inflammatory response was totally abolished by treatment with PrtV. The findings suggest that low doses of VCC initiate a local immune defense reaction while high doses lead to intestinal epithelial lesions. Furthermore, VCC is indeed a substrate for PrtV and PrtV seems to execute an environment-dependent modulation of the activity of VCC that may be the cause of V. cholerae reactogenicity.

  10. Platelet antibody detection by flow cytometry: an effective method to evaluate and give transfusional support in platelet refractoriness

    Directory of Open Access Journals (Sweden)

    Carolina Bonet Bub


    Full Text Available BACKGROUND: Immune platelet refractoriness is mainly caused by human leukocyte antigen antibodies (80-90% of cases and, to a lesser extent, by human platelet antigen antibodies. Refractoriness can be diagnosed by laboratory tests and patients should receive compatible platelet transfusions. A fast, effective and low cost antibody-screening method which detects platelet human leukocyte/platelet antigen antibodies is essential in the management of immune platelet refractoriness. OBJECTIVE: The aim of this study was to evaluate the efficiency of the flow cytometry platelet immunofluorescence test to screen for immune platelet refractoriness. METHODS: A group of prospective hematologic patients with clinically suspected platelet refractoriness treated in a referral center in Campinas, SP during July 2006 and July 2011 was enrolled in this study. Platelet antibodies were screened using the flow cytometry platelet immunofluorescence test. Anti-human leukocyte antigen antibodies were detected by commercially available methods. The sensitivity, specificity and predictive values of the immunofluorescence test were determined taking into account that the majority of antiplatelet antibodies presented human leukocyte antigen specificity. RESULTS: Seventy-six samples from 32 female and 38 male patients with a median age of 43.5 years (range: 5-84 years were analyzed. The sensitivity of the test was 86.11% and specificity 75.00% with a positive predictive value of 75.61% and a negative predictive value of 85.71%. The accuracy of the method was 80.26%. CONCLUSION: This study shows that the flow cytometry platelet immunofluorescence test has a high correlation with the anti-human leukocyte antigen antibodies. Despite a few limitations, the method seems to be efficient, fast and feasible as the initial screening for platelet antibody detection and a useful tool to crossmatch platelets for the transfusional support of patients with immune platelet refractoriness.

  11. Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

    Directory of Open Access Journals (Sweden)

    Mărginean Alina


    Full Text Available It is well known that critically ill patients require special attention and additional consideration during their treatment and management. The multiple systems and organ dysfunctions, typical of the critical patient, often results in different patterns of enteral absorption in these patients. Anti-platelet drugs are the cornerstone in treating patients with coronary and cerebrovascular disease. Dual anti-platelet therapy with aspirin and clopidogrel is the treatment of choice in patients undergoing elective percutaneous coronary interventions and is still widely used in patients with acute coronary syndromes. However, despite the use of dual anti-platelet therapy, some patients continue to experience cardiovascular ischemic events. Recurrence of ischemic events is partly attributed to the fact that some patients have poor inhibition of platelet reactivity despite treatment. These patients are considered low- or nonresponders to therapy. The underlying mechanisms leading to resistance are not yet fully elucidated and are probably multifactorial, cellular, genetic and clinical factors being implicated. Several methods have been developed to asses platelet function and can be used to identify patients with persistent platelet reactivity, which have an increased risk of thrombosis. In this paper, the concept of anti-platelet therapy resistance, the underlying mechanisms and the methods used to identify patients with low responsiveness to anti-platelet therapy will be highlighted with a focus on aspirin and clopidogrel therapy and addressing especially critically ill patients.

  12. Genetic determinants of on-aspirin platelet reactivity: focus on the influence of PEAR1.

    Directory of Open Access Journals (Sweden)

    Morten Würtz

    Full Text Available Platelet aggregation during aspirin treatment displays considerable inter-individual variability. A genetic etiology likely exists, but it remains unclear to what extent genetic polymorphisms determine platelet aggregation in aspirin-treated individuals.To identify platelet-related single nucleotide polymorphisms (SNPs influencing platelet aggregation during aspirin treatment. Furthermore, we explored to what extent changes in cyclooxygenase-1 activity and platelet activation may explain such influence.We included 985 Danish patients with stable coronary artery disease treated with aspirin 75 mg/day mono antiplatelet therapy. Patients were genotyped for 16 common SNPs in platelet-related genes using standard PCR-based methods (TaqMan. Platelet aggregation was evaluated by whole blood platelet aggregometry employing Multiplate Analyzer (agonists: arachidonic acid and collagen and VerifyNow Aspirin. Serum thromboxane B2 was measured to confirm aspirin adherence and was used as a marker of cyclooxygenase-1 activity. Soluble P-selectin was used as marker of platelet activation. Platelet aggregation, cyclooxygenase-1 activity, and platelet activation were compared across genotypes in adjusted analyses.The A-allele of the rs12041331 SNP in the platelet endothelial aggregation receptor-1 (PEAR1 gene was associated with reduced platelet aggregation and increased platelet activation, but not with cyclooxygenase-1 activity. Platelet aggregation was unaffected by the other SNPs analyzed.A common genetic variant in PEAR1 (rs12041331 reproducibly influenced platelet aggregation in aspirin-treated patients with coronary artery disease. The exact biological mechanism remains elusive, but the effect of this polymorphism may be related to changes in platelet activation. Furthermore, 14 SNPs previously suggested to influence aspirin efficacy were not associated with on-aspirin platelet NCT01383304.

  13. The incidence of bradyarrhythmias and clinical bradyarrhythmic events in patients with acute coronary syndromes treated with ticagrelor or clopidogrel in the PLATO (Platelet Inhibition and Patient Outcomes) trial: results of the continuous electrocardiographic assessment substudy. (United States)

    Scirica, Benjamin M; Cannon, Christopher P; Emanuelsson, Håkan; Michelson, Eric L; Harrington, Robert A; Husted, Steen; James, Stefan; Katus, Hugo; Pais, Prem; Raev, Dimitar; Spinar, Jindrich; Steg, Ph Gabriel; Storey, Robert F; Wallentin, Lars


    The aim of this study was to determine whether ticagrelor increased the risk of ventricular pauses compared with clopidogrel and whether these pauses were associated with any clinical bradycardic events in patients presenting with acute coronary syndromes. Ticagrelor, an oral reversibly binding P2Y(12) inhibitor, provides more potent and consistent inhibition of platelet aggregation than clopidogrel but in a phase II study was associated with increased risk for ventricular pauses. A prospective continuous electrocardiographic (cECG) assessment was therefore performed within the PLATO (Platelet Inhibition and Patient Outcomes) study comparing ticagrelor and clopidogrel in patients hospitalized with acute coronary syndromes. Patients in the cECG assessment had planned 7-day cECG recording initiated at the time of randomization (week 1), which was within 24 h of symptom onset, and then repeated at 1 month after randomization during the convalescent phase. The principal safety endpoint was the incidence of ventricular pauses lasting at least 3 s. Investigators also reported symptomatic bradycardic adverse events during the entire study duration (median 277 days). A total of 2,908 patients were included in the cECG assessment, of whom 2,866 (98.5%) had week 1 recordings, 1,991 (68.4%) had 1-month recordings, and 1,949 (67.0%) had both. During the first week after randomization, ventricular pauses ≥3 s occurred more frequently in patients receiving ticagrelor than clopidogrel (84 [5.8%] vs. 51 [3.6%]; relative risk: 1.61; p = 0.006). At 1 month, pauses ≥3 s occurred overall less frequently and were similar between treatments (2.1% vs. 1.7%). Most were ventricular pauses, and the greatest excess associated with ticagrelor were asymptomatic, sinoatrial nodal in origin (66%), and nocturnal. There were no differences between ticagrelor and clopidogrel in the incidence of clinically reported bradycardic adverse events, including syncope, pacemaker placement, and cardiac

  14. Platelet extracellular vesicles induce a pro-inflammatory smooth muscle cell phenotype. (United States)

    Vajen, Tanja; Benedikter, Birke J; Heinzmann, Alexandra C A; Vasina, Elena M; Henskens, Yvonne; Parsons, Martin; Maguire, Patricia B; Stassen, Frank R; Heemskerk, Johan W M; Schurgers, Leon J; Koenen, Rory R


    Extracellular vesicles (EVs) are mediators of cell communication during health and disease, and abundantly released by platelets upon activation or during ageing. Platelet EVs exert modulatory effects on immune and vascular cells. Platelet EVs may modulate the function of vascular smooth muscle cells (SMC). Platelet EVs were isolated from platelet-rich plasma and incubated with SMC in order to assess binding, proliferation, migration and pro-inflammatory phenotype of the cells. Platelet EVs firmly bound to resting SMC through the platelet integrin αIIbβ3, while binding also occurred in a CX3CL1-CX3CR1-dependent manner after cytokine stimulation. Platelet EVs increased SMC migration comparable to platelet derived growth factor or platelet factor 4 and induced SMC proliferation, which relied on CD40- and P-selectin interactions. Flow-resistant monocyte adhesion to platelet EV-treated SMC was increased compared with resting SMC. Again, this adhesion depended on integrin αIIbβ3 and P-selectin, and to a lesser extent on CD40 and CX3CR1. Treatment of SMC with platelet EVs induced interleukin 6 secretion. Finally, platelet EVs induced a synthetic SMC morphology and decreased calponin expression. Collectively, these data indicate that platelet EVs exert a strong immunomodulatory activity on SMC. In particular, platelet EVs induce a switch towards a pro-inflammatory phenotype, stimulating vascular remodelling.

  15. Platelet alloimmunization after transfusion

    DEFF Research Database (Denmark)

    Taaning, E; Simonsen, A C; Hjelms, E


    BACKGROUND AND OBJECTIVES: The frequency of platelet-specific antibodies after one series of blood transfusions has not been reported, and in multiply transfused patients is controversial. MATERIALS AND METHODS: We studied the frequency of alloimmunization against platelet antigens in 117 patients...... who received a single series of blood transfusions. They received mostly saline-adenine-glucose+mannitol red blood cell components (poor in leukocytes and platelets) in connection with cardiac surgery. Platelet-specific antibodies were detected with the platelet ELISA and the monoclonal...... immunization. CONCLUSION: There was a low incidence of platelet-specific antibodies after one series of blood transfusions in this group of patients. This is similar to the results of some previous studies in multiply transfused patients, but not with those of others who found a higher incidence....

  16. Mechanism of platelet functional changes and effects of anti-platelet agents on in vivo hemostasis under different gravity conditions. (United States)

    Li, Suping; Shi, Quanwei; Liu, Guanglei; Zhang, Weilin; Wang, Zhicheng; Wang, Yuedan; Dai, Kesheng


    Serious thrombotic and hemorrhagic problems or even fatalities evoked by either microgravity or hypergravity occur commonly in the world. We recently reported that platelet functions are inhibited in microgravity environments and activated under high-G conditions, which reveals the pathogenesis for gravity change-related hemorrhagic and thrombotic diseases. However, the mechanisms of platelet functional variations under different gravity conditions remain unclear. In this study we show that the amount of filamin A coimmunoprecipitated with GPIbalpha was enhanced in platelets exposed to modeled microgravity and, in contrast, was reduced in 8 G-exposed platelets. Hypergravity induced actin filament formation and redistribution, whereas actin filaments were reduced in platelets treated with modeled microgravity. Furthermore, intracellular Ca2+ levels were elevated by hypergravity. Pretreatment of platelets with the cell-permeable Ca2+ chelator BAPTA-AM had no effect on cytoskeleton reorganization induced by hypergravity but significantly reduced platelet aggregation induced by ristocetin/hypergravity. Two anti-platelet agents, aspirin and tirofiban, effectively reversed the shortened tail bleeding time and reduced the death rate of mice exposed to hypergravity. Furthermore, the increased P-selectin surface expression was obviously reduced in platelets from mice treated with aspirin/hypergravity compared with those from mice treated with hypergravity alone. These data suggest that the actin cytoskeleton reorganization and intracellular Ca2+ level play key roles in the regulation of platelet functions in different gravitational environments. The results with anti-platelet agents not only further confirm the activation of platelets in vivo but also suggest a therapeutic potential for hypergravity-induced thrombotic diseases.

  17. Mean platelet volume and mean platelet volume/platelet count ratio ...

    African Journals Online (AJOL)

    Mean platelet volume and mean platelet volume/platelet count ratio as a risk stratification tool in the assessment of severity of acute ischemic stroke. ... The mean platelet volume (MPV) is a laboratory marker associated with platelet function and activity. Increased MPV in thromboembolic disease is reflected as an important ...

  18. Streptococcus pneumoniae serine protease HtrA, but not SFP or PrtA, is a major virulence factor in pneumonia

    NARCIS (Netherlands)

    de Stoppelaar, Sacha F.; Bootsma, Hester J.; Zomer, Aldert; Roelofs, Joris J. T. H.; Hermans, Peter W. M.; van 't Veer, Cornelis; van der Poll, Tom


    Streptococcus (S.) pneumoniae is a common causative pathogen in pneumonia. Serine protease orthologs expressed by a variety of bacteria have been found of importance for virulence. Previous studies have identified two serine proteases in S. pneumoniae, HtrA (high-temperature requirement A) and PrtA

  19. Serine protease PrtA from Streptococcus pneumoniae plays a role in the killing of S. pneumoniae by apolactoferrin. (United States)

    Mirza, Shaper; Wilson, Landon; Benjamin, William H; Novak, Jan; Barnes, Stephen; Hollingshead, Susan K; Briles, David E


    It is known that apolactoferrin, the iron-free form of human lactoferrin, can kill many species of bacteria, including Streptococcus pneumoniae. Lactoferricin, an N-terminal peptide of apolactoferrin, and fragments of it are even more bactericidal than apolactoferrin. In this study we found that apolactoferrin must be cleaved by a serine protease in order for it to kill pneumococci. The serine protease inhibitors were able to block killing by apolactoferrin but did not block killing by a lactoferrin-derived peptide. Thus, the killing of pneumococci by apolactoferrin appears to require a protease to release a lactoferricin-like peptide(s). Incubation of apolactoferrin with growing pneumococci resulted in a 12-kDa reduction in its molecular mass, of which about 7 to 8 kDa of the reduction was protease dependent. Capsular type 2 and 19F strains with mutations in the gene encoding the major cell wall-associated serine protease, prtA, lost much of their ability to degrade apolactoferrin and were relatively resistant to killing by apolactoferrin (P mass by about 8 kDa, and greatly enhance the killing activity of the solution containing the apolactoferrin and its cleavage products. Mass spectroscopy revealed that PrtA makes a major cut between amino acids 78 and 79 of human lactoferrin, removing the N-terminal end of the molecule (about 8.6 kDa). The simplest interpretation of these data is that the mechanism by which apolactoferrin kills Streptococcus pneumoniae requires the release of a lactoferricin-like peptide(s) and that it is this peptide(s), and not the intact apolactoferrin, which kills pneumococci.

  20. Measurement of platelet aggregation, independently of patient platelet count

    DEFF Research Database (Denmark)

    Vinholt, P J; Frederiksen, H; Hvas, A-M


    Essentials •Platelet function may influence bleeding risk in thrombocytopenia, but useful tests are needed. •A flow cytometric platelet aggregation test independent of the patient platelet count was made. •Platelet aggregation was reduced in thrombocytopenic patients with hematological cancer....... •High platelet aggregation ruled out bleeding tendency in thrombocytopenic patients. Summary Background Methods for testing platelet aggregation in thrombocytopenia are lacking. Objective To establish a flow-cytometric test of in vitro platelet aggregation independently of the patient's platelet count...

  1. Surfactants reduce platelet-bubble and platelet-platelet binding induced by in vitro air embolism. (United States)

    Eckmann, David M; Armstead, Stephen C; Mardini, Feras


    The effect of gas bubbles on platelet behavior is poorly characterized. The authors assessed platelet-bubble and platelet-platelet binding in platelet-rich plasma in the presence and absence of bubbles and three surface-active compounds. Platelet-rich plasma was prepared from blood drawn from 16 volunteers. Experimental groups were surfactant alone, sparging (microbubble embolization) alone, sparging with surfactant, and neither sparging nor surfactant. The surfactants were Pluronic F-127 (Molecular Probes, Eugene, OR), Perftoran (OJSC SPC Perftoran, Moscow, Russia), and Dow Corning Antifoam 1510US (Dow Corning, Midland, MI). Videomicroscopy images of specimens drawn through rectangular glass microcapillaries on an inverted microscope and Coulter counter measurements were used to assess platelet-bubble and platelet-platelet binding, respectively, in calcium-free and recalcified samples. Histamine-induced and adenosine diphosphate-induced platelet-platelet binding were measured in unsparged samples. Differences between groups were considered significant for P bubbles in sparged, surfactant-free samples. With sparging and surfactant, few platelets adhered to bubbles. Numbers of platelet singlets and multimers not adherent to bubbles were different (P surfactant. No significant platelet-platelet binding occurred in uncalcified, sparged samples, although 20-30 platelets adhered to bubbles. Without sparging, histamine and adenosine diphosphate provoked platelet-platelet binding with and without surfactants present. Sparging causes platelets to bind to air bubbles and each other. Surfactants added before sparging attenuate platelet-bubble and platelet-platelet binding. Surfactants may have a clinical role in attenuating gas embolism-induced platelet-bubble and platelet-platelet binding.

  2. Flavanols and Platelet Reactivity

    Directory of Open Access Journals (Sweden)

    Debra A. Pearson


    Full Text Available Platelet activity and platelet-endothelial cell interactions are important in the acute development of thrombosis, as well as in the pathogenesis of cardiovascular disease. An increasing number of foods have been reported to have platelet-inhibitory actions, and research with a number of flavanol-rich foods, including, grape juice, cocoa and chocolate, suggests that these foods may provide some protection against thrombosis. In the present report, we review a series of in vivo studies on the effects of flavanol-rich cocoa and chocolate on platelet activation and platelet-dependent primary hemostasis. Consumption of flavanol-rich cocoa inhibited several measures of platelet activity including, epinephrine- and ADP-induced glycoprotein (GP IIb/IIIa and P-Selectin expression, platelet microparticle formation, and epinephrine-collagen and ADP-collagen induced primary hemostasis. The epinephrine-induced inhibitory effects on GP IIb/IIIa and primary hemostasis were similar to, though less robust than those associated with the use of low dose (81 mg aspirin. These data, coupled with information from other studies, support the concept that flavanols present in cocoa and chocolate can modulate platelet function through a multitude of pathways.

  3. Platelet activation and aggregation

    DEFF Research Database (Denmark)

    Jensen, Maria Sander; Larsen, O H; Christiansen, Kirsten


    This study introduces a new laboratory model of whole blood platelet aggregation stimulated by endogenously generated thrombin, and explores this aspect in haemophilia A in which impaired thrombin generation is a major hallmark. The method was established to measure platelet aggregation initiated...

  4. Achieved platelet aggregation inhibition after different antiplatelet regimens during percutaneous coronary intervention for ST-segment elevation myocardial infarction

    NARCIS (Netherlands)

    Ernst, N.M.S.K.; Suryapranata, H.; Miedema, Kor; Slingerland, R.J.; Ottervanger, J.P.; Hoornije, J.C.A.; Gosselink, A.T.M.; Dambrink, J.H.E.; de Boer, M.J.; Zijlstra, F.; van't Hof, A.W.J.


    Objectives To evaluate the extent of platelet aggregation inhibition in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), treated with different antiplatelet agents and dosages. Background The extent of platelet aggregation

  5. Platelet function in dogs

    DEFF Research Database (Denmark)

    Nielsen, Line A.; Zois, Nora Elisabeth; Pedersen, Henrik D.


    Background: Clinical studies investigating platelet function in dogs have had conflicting results that may be caused by normal physiologic variation in platelet response to agonists. Objectives: The objective of this study was to investigate platelet function in clinically healthy dogs of 4...... different breeds by whole-blood aggregometry and with a point-of-care platelet function analyzer (PFA-100), and to evaluate the effect of acetylsalicylic acid (ASA) administration on the results from both methods. Methods: Forty-five clinically healthy dogs (12 Cavalier King Charles Spaniels [CKCS], 12...... applied. However, the importance of these breed differences remains to be investigated. The PFA-100 method with Col + Epi as agonists, and ADP-induced platelet aggregation appear to be sensitive to ASA in dogs....

  6. Platelet counts and mean platelet volume amongst elderly Nigerians ...

    African Journals Online (AJOL)

    determining reference values of Platelet Counts, Mean Platelet Volume and the relationship between the Platelet Count and Mean Platelet Volume. These parameters were determined from 400 healthy elderly subjects comprising 210 males and 190 females. with a mean age of 69.4±7.9 years . 400 young adults were used ...

  7. Platelet concentration in platelet concentrates and periodontal regeneration-unscrambling the ambiguity

    Directory of Open Access Journals (Sweden)

    A Suchetha


    Full Text Available Context: Platelet-rich-plasma (PRP and Platelet-rich-fibrin (PRF are extensively used autologous platelet concentrates in periodontal regeneration, and PRF has a better efficacy as compared to PRP. The rationale for this difference has often been attributed to the difference in the structure of the fibrin matrix. However, the effect of concentration of platelets on the regenerative potential of these concentrates is obscure. Aims: The study was conducted to evaluate and compare, clinically and radiographically, the efficacy of PRF and PRP in the treatment of periodontal endosseous defects and to assess the effect of platelet concentration on periodontal regeneration. Materials and Methods: Twenty intrabony defects were selected and divided into two groups randomly by the coin toss method. Group I received PRP and Group II subjects were treated with PRF. The platelet counts in PRP and PRF were analyzed. Clinical and radiological parameters were assessed at baseline and 3, 6, and 9 months postoperatively. Statistical Analysis: Kruskal–Wallis Chi-square test, Wilcoxon signed rank test, t-test, and Spearman's rank correlation were used for statistical analysis of data. Results: There was statistically significant improvement in all the parameters in the two groups except in relation to gingival recession. There was a statistically significant difference between the platelet count in Group I and Group II (P = 0.002. Conclusion: PRP and PRF appear to have nearly comparable effects in terms of periodontal regeneration. The concentration of platelets appears to play a paradoxical role in regeneration. The regenerative potential of platelets appears to be optimal within a limited range.

  8. Down-regulation of platelet surface CD47 expression in Escherichia coli O157:H7 infection-induced thrombocytopenia.

    Directory of Open Access Journals (Sweden)

    Ya-Lan Guo

    Full Text Available BACKGROUND: Platelet depletion is a key feature of hemolytic uremic syndrome (HUS caused by Shiga toxin-producing Escherichia coli (STEC infection. The mechanism underlying STEC-induced platelet depletion, however, is not completely understood. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrated for the first time that platelet surface expression of CD47 was significantly decreased in C57BL6 mice treated with concentrated culture filtrates (CCF from STEC O157:H7. STEC O157:H7 CCF treatment also led to a sharp drop of platelet counts. The reduction of cell surface CD47 was specific for platelets but not for neutrophil, monocytes and red blood cells. Down-regulation of platelet surface CD47 was also observed in isolated human platelets treated with O157:H7 CCF. Platelet surface CD47 reduction by O157:H7 CCF could be blocked by anti-TLR4 antibody but not anti-CD62 antibody. Down-regulation of platelet surface CD47 was positively correlated with platelet activation and phagocytosis by human monocyte-derived macrophages. Furthermore, the enhanced phagocytosis process of O157:H7 CCF-treated platelets was abolished by addition of soluble CD47 recombinants. CONCLUSIONS/SIGNIFICANCE: Our results suggest that platelet CD47 down-regulation may be a novel mechanism underneath STEC-induced platelet depletion, and that the interactions between CD47 and its receptor, signal regulatory protein alpha (SIRPalpha, play an essential role in modulating platelet homeostasis.

  9. Platelet-collagen adhesion enhances platelet aggregation induced by binding of VWF to platelets

    Energy Technology Data Exchange (ETDEWEB)

    Laduca, F.M.; Bell, W.R.; Bettigole, R.E. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA) State Univ. of New York, Buffalo (USA))


    Ristocetin-induced platelet aggregation (RIPA) was evaluated in the presence of platelet-collagen adhesion. RIPA of normal donor platelet-rich plasma (PRP) demonstrated a primary wave of aggregation mediated by the binding of von Willebrand factor (VWF) to platelets and a secondary aggregation wave, due to a platelet-release reaction, initiated by VWF-platelet binding and inhibitable by acetylsalicylic acid (ASA). An enhanced RIPA was observed in PRP samples to which collagen had been previously added. These subthreshold concentrations of collagen, which by themselves were insufficient to induce aggregation, caused measurable platelet-collagen adhesion. Subthreshold collagen did not cause microplatelet aggregation, platelet release of ({sup 3}H)serotonin, or alter the dose-responsive binding of {sup 125}I-labeled VWF to platelets, which occurred with increasing ristocetin concentrations. However, ASA inhibition of the platelet release reaction prevented collagen-enhanced RIPA. These results demonstrate that platelet-collagen adhesion altered the platelet-release reaction induced by the binding of VWF to platelets causing a platelet-release reaction at a level of VWF-platelet binding not normally initiating a secondary aggregation. These findings suggest that platelet-collagen adhesion enhances platelet function mediated by VWF.

  10. Biofilm Formation on Stainless Steel by Streptococcus thermophilus UC8547 in Milk Environments Is Mediated by the Proteinase PrtS. (United States)

    Bassi, D; Cappa, F; Gazzola, S; Orrù, L; Cocconcelli, P S


    In Streptococcus thermophilus , gene transfer events and loss of ancestral traits over the years contribute to its high level of adaptation to milk environments. Biofilm formation capacity, a phenotype that is lost in the majority of strains, plays a role in persistence in dairy environments, such as milk pasteurization and cheese manufacturing plants. To investigate this property, we have studied S. thermophilus UC8547, a fast-acidifying dairy starter culture selected for its high capacity to form biofilm on stainless steel under environmental conditions resembling the dairy environment. Using a dynamic flow cell apparatus, it was shown that S. thermophilus UC8547 biofilm formation on stainless steel depends on the presence of milk proteins. From this strain, which harbors the prtS gene for the cell wall protease and shows an aggregative phenotype, spontaneous mutants with impaired biofilm capacity can be isolated at high frequency. These mutants lack the PrtS expendable island, as confirmed by comparison of the genome sequence of UC8547Δ3 with that of the parent strain. The prtS island excision occurs between two 26-bp direct repeats located in the two copies of the IS Sth1 flanking this genomic island. The central role of PrtS was confirmed by analyzing the derivative strain UC8547Δ16, whose prtS gene was interrupted by an insertional mutation, thereby making it incapable of biofilm formation. PrtS, acting as a binding substance between the milk proteins adhered to stainless steel and S. thermophilus cell envelopes, mediates biofilm formation in dairy environments. This feature provides S. thermophilus with an ecological benefit for its survival and persistence in this environment. IMPORTANCE The increased persistence of S. thermophilus biofilm has consequences in the dairy environment: if, on the one hand, the release of this microorganism from biofilm can promote the fermentation of artisanal cheeses, under industrial conditions it may lead to undesirable

  11. A Randomized Clinical Trial Comparison Between Pivotal Response Treatment (PRT) and Adult-Driven Applied Behavior Analysis (ABA) Intervention on Disruptive Behaviors in Public School Children with Autism. (United States)

    Mohammadzaheri, Fereshteh; Koegel, Lynn Kern; Rezaei, Mohammad; Bakhshi, Enayatolah


    Children with autism often demonstrate disruptive behaviors during demanding teaching tasks. Language intervention can be particularly difficult as it involves social and communicative areas, which are challenging for this population. The purpose of this study was to compare two intervention conditions, a naturalistic approach, Pivotal Response Treatment (PRT) with an adult-directed ABA approach on disruptive behavior during language intervention in the public schools. A randomized clinical trial design was used with two groups of children, matched according to age, sex and mean length of utterance. The data showed that the children demonstrated significantly lower levels of disruptive behavior during the PRT condition. The results are discussed with respect to antecedent manipulations that may be helpful in reducing disruptive behavior.

  12. Congenital platelet function defects (United States)

    Arnold DM, Patriquin C, Toltl LJ, Nazi I, Smith J, Kelton J. Diseases of platelet number: immune thrombocytopenia, neonatal alloimmune thrombocytopenia, and posttransfusion purpura. In: Hoffman R, Benz EJ ...

  13. El PRT-ERP y la lucha por la libertad de los presos políticos, 1971-1973

    Directory of Open Access Journals (Sweden)

    Ariel Eidelman


    Full Text Available Este trabajo aborda la represión política de la militancia revolucionaria por parte del régimen militar y la problemática de los presos políticos en la etapa 1971-1973 en Argentina. Se realiza un análisis de las principales características de la legislación represiva. Centralmente refiere a las diferentes iniciativas desarrolladas por el PRT-ERP en relación con sus militantes presos y en particular a la constitución de una Comisión de familiares de presos políticos, estudiantiles y gremiales para la organización de la solidaridad y defensa de los mismos. Apuntamos a destacar la amplia actividad de defensa y solidaridad con los presos políticos desarrollada por un conjunto de organizaciones como un antecedente importante, pero no reconocido, para la constitución del movimiento de derechos humanos de la Argentina en 1975-1976

  14. A Randomized Clinical Trial Comparison Between Pivotal Response Treatment (PRT) and Structured Applied Behavior Analysis (ABA) Intervention for Children with Autism


    Mohammadzaheri, Fereshteh; Koegel, Lynn Kern; Rezaee,Mohammad; Rafiee, Seyed Majid


    Accumulating studies are documenting specific motivational variables that, when combined into a naturalistic teaching paradigm, can positively influence the effectiveness of interventions for children with autism spectrum disorder (ASD). The purpose of this study was to compare two ABA intervention procedures, a naturalistic approach, Pivotal Response Treatment (PRT) with a structured ABA approach in a school setting. A Randomized Clinical Trial design using two groups of children, matched ac...

  15. Monitoring aspirin therapy with the Platelet Function Analyzer-100

    DEFF Research Database (Denmark)

    Mortensen, Jette; Poulsen, Tina Svenstrup; Grove, Erik Lerkevang


    . The Platelet Function Analyzer-100 (PFA-100) is a commonly used platelet function test. We aimed to assess the reproducibility of the PFA-100 and the agreement with optical platelet aggregometry (OPA) in healthy volunteers and in patients with coronary artery disease (CAD) treated with low-dose aspirin....... MATERIAL AND METHODS: Twenty-one healthy volunteers and 43 patients with CAD took part in the study. During treatment with aspirin 75 mg daily, all participants had platelet function assessed in duplicate with the PFA-100 and OPA on 4 consecutive days. Additionally, platelet function was assessed before...... aspirin treatment in healthy subjects. Serum-thromboxane B(2) (S-TxB(2)) was measured to assess compliance. RESULTS: In healthy volunteers not receiving aspirin, duplicate measurements resulted in coefficients of variation (CV) of 7.9 % for the PFA-100 and 5.2 % for OPA. During aspirin treatment, CVs were...

  16. Effective ultraviolet irradiation of platelet concentrates in teflon bags

    Energy Technology Data Exchange (ETDEWEB)

    Capon, S.M.; Sacher, R.A.; Deeg, H.J. (Georgetown Univ., Washington, DC (USA))


    Several plastic materials used in blood storage were evaluated for their ability to transmit ultraviolet B (UVB) light. A plastic bag manufactured from sheets of transparent Teflon efficiently (78-86%) transmitted UVB light and was employed in subsequent functional studies of lymphocytes and platelets exposed to UVB light while contained in these bags. In vitro experiments showed a UVB dose-dependent abrogation of lymphocyte responder and stimulator functions, with concurrent preservation of platelet aggregation responses. In a phase I pilot study, UVB-treated platelet concentrates were administered to four bone marrow transplant recipients. Adverse effects attributable to the transfusions were not observed, and patients showed clinically effective transfusion responses. No patient developed lymphocytotoxic HLA or platelet antibodies. These studies suggest that platelets can be effectively irradiated with UVB light in a closed system. However, numerous variables, including container material, volume and composition of contents, steady exposure versus agitation, and exact UV wavelength, must be considered.

  17. Preaggregation reactions of platelets. (United States)

    Gear, A R


    Whether platelet volume increases during the morphological changes preceding aggregation has been investigated. Previous research is controversial; resistive-counting techniques reveal an increase, centrifugal methods do not. Platelets were sized with a computerized, resistive-particle counter before and after incubation with adenosine diphosphate (ADP). Resistive volume increased by 14% (p less than 0.001) in the absence of EDTA, and only 7% in its presence (ADP, 10 micro M). EDTA inhibited platelet volume changes, whether these were shrinking induced by warming or swelling by ADP. Handling of platelets, such as during centrifugation, also caused particle swelling. Particle density decreased after ADP exposure, without release of serotonin, suggesting uptake of water. Platelet shape was experimentally manipulated to test the hypothesis that resistive volume changes stem from artifacts of particle shape. Scanning electron microscopy confirmed that colchicine, chlorpromazine, and a temperature cycle of 0 degrees to 37 degrees all caused extensive alteration from the disc shape. Subsequent exposure to ADP increased resistive volume, and in the case of chlorpromazine, no long pseudopodia were extruded. It is concluded that preaggregation reactions of platelets can be associated with an increase in particle volume, and that earlier research based on centrifugation and the presence of ETA failed to reveal the increase because of inhibitory and apparent swelling effects.

  18. Intracellular origin and ultrastructure of platelet-derived microparticles. (United States)

    Ponomareva, A A; Nevzorova, T A; Mordakhanova, E R; Andrianova, I A; Rauova, L; Litvinov, R I; Weisel, J W


    Essentials Platelet microparticles play a major role in pathologies, including hemostasis and thrombosis. Platelet microparticles have been analyzed and classified based on their ultrastructure. The structure and intracellular origin of microparticles depend on the cell-activating stimulus. Thrombin-treated platelets fall apart and form microparticles that contain cellular organelles. Background Platelet-derived microparticles comprise the major population of circulating blood microparticles that play an important role in hemostasis and thrombosis. Despite numerous studies on the (patho)physiological roles of platelet-derived microparticles, mechanisms of their formation and structural details remain largely unknown. Objectives Here we studied the formation, ultrastructure and composition of platelet-derived microparticles from isolated human platelets, either quiescent or stimulated with one of the following activators: arachidonic acid, ADP, collagen, thrombin or calcium ionophore A23187. Methods Using flow cytometry, transmission and scanning electron microscopy, we analyzed the intracellular origin, structural diversity and size distributions of the subcellular particles released from platelets. Results The structure, dimensions and intracellular origin of microparticles depend on the cell-activating stimulus. The main structural groups include a vesicle surrounded by one thin membrane or multivesicular structures. Thrombin, unlike other stimuli, induced formation of microparticles not only from the platelet plasma membrane and cytoplasm but also from intracellular structures. A fraction of these vesicular particles having an intracellular origin contained organelles, such as mitochondria, glycogen granules and vacuoles. The size of platelet-derived microparticles depended on the nature of the cell-activating stimulus. Conclusion The results obtained provide a structural basis for the qualitative differences of various platelet activators, for specific

  19. How Is Immune Thrombocytopenia Treated? (United States)

    ... information about platelet transfusions, go to the Health Topics Blood Transfusion article. Treating Infections Some infections can briefly lower ... experiences with clinical research. More Information Related Health Topics Blood ... Tests Thrombocytopenia Thrombotic Thrombocytopenic Purpura Other ...

  20. Clinical uses of radiolabeled platelets

    Energy Technology Data Exchange (ETDEWEB)

    Datz, F.L.; Christian, P.E.; Baker, W.J.


    Platelets were first successfully radiolabeled in 1953. At that time, investigators were primarily interested in developing a technique to accurately measure platelet life span in both normal and thrombocytopenic patients. Studies using platelets labeled with /sup 51/Cr have shown shortened platelet survival times in a number of diseases including idiopathic thrombocytopenic purpura, coronary artery disease, and diabetes mellitus. More recently, labels such as /sup 111/In have been developed that allow in vivo imaging of platelets. Indium-111 platelets are being used to better understand the pathophysiology of atherosclerosis, thrombophlebitis, pulmonary embolism and clotting disorders, and to improve the clinical diagnosis of these diseases.

  1. Antipsychotic Drugs Inhibit Platelet Aggregation via P2Y1 and P2Y12 Receptors

    Directory of Open Access Journals (Sweden)

    Chang-Chieh Wu


    Full Text Available Antipsychotic drugs (APDs used to treat clinical psychotic syndromes cause a variety of blood dyscrasias. APDs suppress the aggregation of platelets; however, the underlying mechanism remains unknown. We first analyzed platelet aggregation and clot formation in platelets treated with APDs, risperidone, clozapine, or haloperidol, using an aggregometer and rotational thromboelastometry (ROTEM. Our data indicated that platelet aggregation was inhibited, that clot formation time was increased, and that clot firmness was decreased in platelets pretreated with APDs. We also examined the role two major adenosine diphosphate (ADP receptors, P2Y1 and P2Y12, play in ADP-mediated platelet activation and APD-mediated suppression of platelet aggregation. Our results show that P2Y1 receptor stimulation with ADP-induced calcium influx was inhibited by APDs in human and rats’ platelets, as assessed by in vitro or ex vivo approach, respectively. In contrast, APDs, risperidone and clozapine, alleviated P2Y12-mediated cAMP suppression, and the release of thromboxane A2 and arachidonic acid by activated platelets decreased after APD treatment in human and rats’ platelets. Our data demonstrate that each APD tested significantly suppressed platelet aggregation via different mechanisms.

  2. Using the Platelet Function Analyzer-100 for monitoring aspirin therapy

    DEFF Research Database (Denmark)

    Poulsen, Tina Svenstrup; Mickley, Hans; Korsholm, Lars


    INTRODUCTION: The aim of the study was to evaluate the test characteristics of the Platelet Function Analyzer-100 (PFA-100) in patients treated with aspirin. METHODS AND RESULTS: The study consisted of two sub-studies. In study 1, 10 patients with ischemic heart disease (IHD) and 10 controls had...... platelet function assessed by optical platelet aggregation and the PFA-100 method in two 5-week periods. Patients with IHD were treated with aspirin 150 mg/day (first 5-week period), and 300 mg/day (second 5-week period), whereas the controls only received aspirin (150 mg/day) during the second 5-week...... period. From the results of study 1, we found that a cut-off value for the PFA-100 collagen/epinephrine cartridge aspirin (sensitivity 0.91, specificity 1.00). A good agreement between the PFA-100 method and optical platelet aggregation was found. Within...

  3. The Platelet and Platelet Function Testing in Liver Disease

    NARCIS (Netherlands)

    Hugenholtz, Greg G. C.; Porte, Robert J.; Lisman, Ton

    Patients who have liver disease commonly present with alterations in platelet number and function. Recent data have questioned the contribution of these changes to bleeding complications in these patients. Modern tests of platelet function revealed compensatory mechanisms for the decreased platelet

  4. Mean Platelet Volume (MPV), Platelet Distribution Width (PDW ...

    African Journals Online (AJOL)

    Background: Thrombocytopenia has been shown to predict mortality. We hypothesize that platelet indices may be more useful prognostic indicators. Our study subjects were children one month to 14 years old admitted to our hospital. Aim: To determine whether platelet count, plateletcrit (PCT), mean platelet volume (MPV) ...

  5. Reproducibility of Manual Platelet Estimation Following Automated Low Platelet Counts

    Directory of Open Access Journals (Sweden)

    Zainab S Al-Hosni


    Full Text Available Objectives: Manual platelet estimation is one of the methods used when automated platelet estimates are very low. However, the reproducibility of manual platelet estimation has not been adequately studied. We sought to assess the reproducibility of manual platelet estimation following automated low platelet counts and to evaluate the impact of the level of experience of the person counting on the reproducibility of manual platelet estimates. Methods: In this cross-sectional study, peripheral blood films of patients with platelet counts less than 100 × 109/L were retrieved and given to four raters to perform manual platelet estimation independently using a predefined method (average of platelet counts in 10 fields using 100× objective multiplied by 20. Data were analyzed using intraclass correlation coefficient (ICC as a method of reproducibility assessment. Results: The ICC across the four raters was 0.840, indicating excellent agreement. The median difference of the two most experienced raters was 0 (range: -64 to 78. The level of platelet estimate by the least-experienced rater predicted the disagreement (p = 0.037. When assessing the difference between pairs of raters, there was no significant difference in the ICC (p = 0.420. Conclusions: The agreement between different raters using manual platelet estimation was excellent. Further confirmation is necessary, with a prospective study using a gold standard method of platelet counts.

  6. SIRT1 prevents pulmonary thrombus formation induced by arachidonic acid via downregulation of PAF receptor expression in platelets. (United States)

    Kim, Yun Hak; Bae, Jin Ung; Kim, In Suk; Chang, Chulhun L; Oh, Sae Ock; Kim, Chi Dae


    SIRT1, a class III histone deacetylase, is critically involved in cellular response to stress and modulates cardiovascular risk factors. However, its role in thrombus formation is largely unknown. Thus, this study investigated the effect of SIRT1 on pulmonary thrombus formation, and then identified its role in the modulation of platelet aggregation. In isolated human platelets, cell aggregation was increased by various platelet activators, such as platelet activating factor (PAF), arachidonic acid (AA), ADP, and thrombin. AA- and PAF-mediated platelet aggregations were suppressed by WEB2086, a PAF receptor (PAFR) antagonist. Pulmonary thrombus formation induced by PAF or AA was also attenuated by WEB2086, suggesting that PAFR plays a key role in AA-induced platelet aggregation. In platelets isolated from SIRT1-TG mice as well as in platelets treated with resveratrol or reSIRT1, PAFR expression was decreased, whereas this expressional downregulation by SIRT1 activators was inhibited in platelets treated with MG132 (a proteasome inhibitor) or NH 4 Cl (a lysosome inhibitor). Furthermore, platelet aggregation induced by AA was markedly attenuated by resveratrol and reSIRT1. Likewise, the increased pulmonary thrombus formation in mice treated with AA was also attenuated by SIRT1 activators. In line with these results, pulmonary thrombus formation was markedly attenuated in SIRT1-TG mice. Taken together, this study showed that SIRT1 downregulates PAFR expression on platelets via proteasomal and lysosomal pathways, and that this downregulation inhibits platelet aggregation in vitro and pulmonary thrombus formation in vivo.

  7. Assessment of platelet function in healthy cats in response to commonly prescribed antiplatelet drugs using three point-of-care platelet function tests. (United States)

    Ho, Kimberly K; Abrams-Ogg, Anthony Cg; Wood, R Darren; O'Sullivan, M Lynne; Kirby, Gordon M; Blois, Shauna L


    Objectives The objective was to determine if decreased platelet function could be detected after treatment with aspirin and/or clopidogrel in healthy cats using three point-of-care platelet function tests that evaluate platelet function by different methods: Multiplate (by impedance), Platelet Function Analyzer 100 (by mechanical aperture closure) and Plateletworks (by platelet counting). Methods Thirty-six healthy cats were randomly assigned to receive one of three oral treatments over an 8 day period: (1) aspirin 5 mg q72h; (2) aspirin 20.25 mg q72h; or (3) clopidogrel 18.75 mg q24h. Cats treated with 5 and 20.25 mg aspirin also received clopidogrel on days 4-8. Platelet aggregation in response to adenosine diphosphate and collagen ± arachidonic acid was assessed on days 1 (baseline), 4 and 8. Aspirin and clopidogrel metabolites were measured by high-performance liquid chromatography. Platelet function in response to treatment was analyzed by ANCOVA, linear regression and Spearman correlation. Results The only solitary aspirin effect was detected using Plateletworks with collagen in cats treated with 20.25 mg. The only effect detected by Multiplate was using arachidonic acid in cats treated with both aspirin 20.25 mg and clopidogrel. All clopidogrel treatment effects were detected by Platelet Function Analyzer 100, Plateletworks (adenosine diphosphate) and Plateletworks (collagen). Drug metabolites were present in all cats, but concentrations were minimally correlated to platelet function test results. Conclusions and relevance Platelet Function Analyzer 100 and Plateletworks using adenosine diphosphate ± collagen agonists may be used to detect decreased platelet function in response to clopidogrel treatment. Either aspirin is not as effective an antiplatelet drug as clopidogrel, or the tests used were not optimal to measure aspirin effect. Cats with heart disease are commonly prescribed antiplatelet drugs to decrease the risk of aortic thromboembolism

  8. Biology of Platelet Purinergic Receptors and Implications for Platelet Heterogeneity

    Directory of Open Access Journals (Sweden)

    Milka Koupenova


    Full Text Available Platelets are small anucleated cells present only in mammals. Platelets mediate intravascular hemostatic balance, prevent interstitial bleeding, and have a major role in thrombosis. Activation of platelet purinergic receptors is instrumental in initiation of hemostasis and formation of the hemostatic plug, although this activation process becomes problematic in pathological settings of thrombosis. This review briefly outlines the roles and function of currently known platelet purinergic receptors (P1 and P2 in the setting of hemostasis and thrombosis. Additionally, we discuss recent novel studies on purinergic receptor distribution according to heterogeneous platelet size, and the possible implication of this distribution on hemostatic function.

  9. Mean Platelet Volume

    African Journals Online (AJOL)

    Department of Chest Disease, Bolu, Turkey. E-mail: Telephone number: +903742534618. Fax number: +903742534615 effective and should have wide spread acceptance. At present, none of the available diagnostic tests meets all these criteria. The mean platelet volume (MPV) is potentially one of.

  10. In vitro effects of ethanol on the pathways of platelet aggregation

    Energy Technology Data Exchange (ETDEWEB)

    Rand, M.L.; Kinlough-Rathbone, R.L.; Packham, M.A.; Mustard, J.F.


    Ethanol is reported to inhibit platelet aggregation in vivo and in vitro, but the mechanisms of its action on stimulus-response coupling in platelets is unknown. Platelet aggregation to thrombin occurs through at least three pathways: released ADP; thromboxane A/sub 2/ (TXA/sub 2/); and a third pathway(s). Aggregation of rabbit platelets in citrated platelet-rich plasma (PRP) or washed suspensions to ADP (0.5-10 was not affected by ethanol, at concentrations up to 5 mg/ml (lethal). Primary ADP-induced (5 aggregation of human platelets in PRP was also unaffected by ethanol, but secondary aggregation and release of /sup 14/C-serotonin, due to TXA/sub 2/ formation, was inhibited by ethanol (2 and 4 mg/ml). Since arachidonate (AA)-induced (25-250 aggregation and release by washed rabbit platelets was unaltered by ethanol, it may inhibit mobilization of AA from platelet membrane phospholipids. Ethanol (2-4 mg/ml) inhibited rabbit platelet aggregation and release to low concentrations of thrombin (< 10 mU/ml) or collagen, and also inhibited aggregation and release of aspirin-treated (500 M) rabbit platelets (that cannot form TXA/sub 2/) to low concentrations of thrombin (< 10 mU/ml). Thus, ethanol does not inhibit the mobilization of AA, and partially inhibits the third pathway(s) of platelet aggregation.

  11. Reversal of shortened platelet survival in rats by the antifibrinolytic agent, epsilon aminocaproic acid. (United States)

    Winocour, P D; Kinlough-Rathbone, R L; Richardson, M; Mustard, J F


    Platelet survival in rabbits and rats is shortened by placing indwelling catheters in the aorta; this shortening appears to be at least partly related to the extent of vessel wall injury and platelet interaction with the repeatedly damaged wall. Treatment of rabbit platelets with plasmin and other proteolytic enzymes in vitro shortens their survival when they are returned to the circulation. Because platelets may be exposed to plasmin and other proteolytic enzymes in rabbits and rats with indwelling aortic catheters, we examined the effect of epsilon-aminocaproic acid (EACA) on platelet survival in rats. At a dose of 1 g/kg every 4 h, EACA significantly reduced whole blood fibrinolytic activity and prolonged the shortened platelet survival in rats with indwelling aortic catheters. Mean platelet survival for untreated rats with indwelling aortic catheters was 38.6 +/- 1.9 h, and for rats treated with EACA, 53.8 +/- 3.8 h. Scanning electron microscopy showed that the injured vessel wall of these animals was mainly covered with platelets and fibrin, whereas in control animals that did not receive EACA, the injured surface was mainly covered with platelets and little fibrin was observed. Thus shortened platelet survival during continuous vessel wall injury may result from the local generation of plasmin or the release of proteolytic enzymes at sites where platelets (and possibly leukocytes) interact with the vessel wall. Images PMID:6848557

  12. Studies on a novel serine protease of a ΔhapAΔprtV Vibrio cholerae O1 strain and its role in hemorrhagic response in the rabbit ileal loop model.

    Directory of Open Access Journals (Sweden)

    Aurelia Syngkon

    Full Text Available BACKGROUND: Two well-characterized proteases secreted by Vibrio cholerae O1 strains are hemagglutinin protease (HAP and V. cholerae protease (PrtV. The hapA and prtV knock out mutant, V. cholerae O1 strain CHA6.8ΔprtV, still retains residual protease activity. We initiated this study to characterize the protease present in CHA6.8ΔprtV strain and study its role in pathogenesis in rabbit ileal loop model (RIL. METHODOLOGY/PRINCIPAL FINDINGS: We partially purified the residual protease secreted by strain CHA6.8ΔprtV from culture supernatant by anion-exchange chromatography. The major protein band in native PAGE was identified by MS peptide mapping and sequence analysis showed homology with a 59-kDa trypsin-like serine protease encoded by VC1649. The protease activity was partially inhibited by 25 mM PMSF and 10 mM EDTA and completely inhibited by EDTA and PMSF together. RIL assay with culture supernatants of strains C6709 (FA ratio 1.1+/-0.3 n = 3, CHA6.8 (FA ratio 1.08+/-0.2 n = 3, CHA6.8ΔprtV (FA ratio 1.02+/-0.2 n = 3 and partially purified serine protease from CHA6.8ΔprtV (FA ratio 1.2+/-0.3 n = 3 induced fluid accumulation and histopathological studies on rabbit ileum showed destruction of the villus structure with hemorrhage in all layers of the mucosa. RIL assay with culture supernatant of CHA6.8ΔprtVΔVC1649 strain (FA ratio 0.11+/-0.005 n = 3 and with protease incubated with PMSF and EDTA (FA ratio 0.3+/-0.05 n = 3 induced a significantly reduced FA ratio with almost complete normal villus structure. CONCLUSION: Our results show the presence of a novel 59-kDa serine protease in a ΔhapAΔprtV V. cholerae O1 strain and its role in hemorrhagic response in RIL model.

  13. Comparison of platelet counting technologies in equine platelet concentrates. (United States)

    O'Shea, Caitlin M; Werre, Stephen R; Dahlgren, Linda A


    (1) To compare the performance of 4 platelet counting technologies in equine platelet concentrates and (2) to evaluate the ability of the Magellan platelet rich plasma (PRP) system to concentrate equine platelets. Experimental study to assess method agreement. Adult mixed breed horses (n = 32). Acid citrate dextrose-A anti-coagulated whole blood was collected and PRP produced using the Magellan system according to the manufacturer's instructions. Platelets were quantified using 4 counting methods: optical scatter (Advia 2120), impedance (CellDyn 3700), hand counting, and fluorescent antibody flow cytometry. Platelet concentrations were compared using Passing and Bablok regression analyses and mixed model ANOVA. Significance was set at P CellDyn 3700. Systematic and proportional biases were observed between these 2 automated methods when analyzed by regression analysis of the larger sample size. No bias (systematic or proportional) was observed among any of the other counting methods. Despite the bias detected between the 2 automated systems, there were no significant differences on average among the 4 counting methods evaluated, based on the ANOVA. The Magellan system consistently generated high platelet concentrations as well as higher than expected WBC concentrations. The Magellan system delivered desirably high platelet concentrations; however, WBC concentrations may be unacceptably high for some orthopedic applications. All 4 platelet counting methods tested were equivalent on average and therefore suitable for quantifying platelets in equine PRP used for clinical applications. © Copyright 2014 by The American College of Veterinary Surgeons.

  14. Storage of platelets: effects associated with high platelet content in platelet storage containers. (United States)

    Gulliksson, Hans; Sandgren, Per; Sjödin, Agneta; Hultenby, Kjell


    A major problem associated with platelet storage containers is that some platelet units show a dramatic fall in pH, especially above certain platelet contents. The aim of this study was a detailed investigation of the different in vitro effects occurring when the maximum storage capacity of a platelet container is exceeded as compared to normal storage. Buffy coats were combined in large-volume containers to create primary pools to be split into two equal aliquots for the preparation of platelets (450-520×10(9) platelets/unit) in SSP+ for 7-day storage in two containers (test and reference) with different platelet storage capacity (n=8). Exceeding the maximum storage capacity of the test platelet storage container resulted in immediate negative effects on platelet metabolism and energy supply, but also delayed effects on platelet function, activation and disintegration. Our study gives a very clear indication of the effects in different phases associated with exceeding the maximum storage capacity of platelet containers but throw little additional light on the mechanism initiating those negative effects. The problem appears to be complex and further studies in different media using different storage containers will be needed to understand the mechanisms involved.

  15. Thrombocytopenia in leptospirosis and role of platelet transfusion

    Directory of Open Access Journals (Sweden)

    Sharma Jayashree


    recognize thrombocytopenia early in the course of leptospirosis so that appropriate steps can be taken to prevent it and to treat it with platelet transfusion when it develops

  16. Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue.

    Directory of Open Access Journals (Sweden)

    Monique Ramos de Oliveira Trugilho


    Full Text Available Dengue is the most prevalent human arbovirus disease worldwide. Dengue virus (DENV infection causes syndromes varying from self-limiting febrile illness to severe dengue. Although dengue pathophysiology is not completely understood, it is widely accepted that increased inflammation plays important roles in dengue pathogenesis. Platelets are blood cells classically known as effectors of hemostasis which have been increasingly recognized to have major immune and inflammatory activities. Nevertheless, the phenotype and effector functions of platelets in dengue pathogenesis are not completely understood. Here we used quantitative proteomics to investigate the protein content of platelets in clinical samples from patients with dengue compared to platelets from healthy donors. Our assays revealed a set of 252 differentially abundant proteins. In silico analyses associated these proteins with key molecular events including platelet activation and inflammatory responses, and with events not previously attributed to platelets during dengue infection including antigen processing and presentation, proteasome activity, and expression of histones. From these results, we conducted functional assays using samples from a larger cohort of patients and demonstrated evidence for platelet activation indicated by P-selectin (CD62P translocation and secretion of granule-stored chemokines by platelets. In addition, we found evidence that DENV infection triggers HLA class I synthesis and surface expression by a mechanism depending on functional proteasome activity. Furthermore, we demonstrate that cell-free histone H2A released during dengue infection binds to platelets, increasing platelet activation. These findings are consistent with functional importance of HLA class I, proteasome subunits, and histones that we found exclusively in proteome analysis of platelets in samples from dengue patients. Our study provides the first in-depth characterization of the platelet

  17. Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue. (United States)

    Trugilho, Monique Ramos de Oliveira; Hottz, Eugenio Damaceno; Brunoro, Giselle Villa Flor; Teixeira-Ferreira, André; Carvalho, Paulo Costa; Salazar, Gustavo Adolfo; Zimmerman, Guy A; Bozza, Fernando A; Bozza, Patrícia T; Perales, Jonas


    Dengue is the most prevalent human arbovirus disease worldwide. Dengue virus (DENV) infection causes syndromes varying from self-limiting febrile illness to severe dengue. Although dengue pathophysiology is not completely understood, it is widely accepted that increased inflammation plays important roles in dengue pathogenesis. Platelets are blood cells classically known as effectors of hemostasis which have been increasingly recognized to have major immune and inflammatory activities. Nevertheless, the phenotype and effector functions of platelets in dengue pathogenesis are not completely understood. Here we used quantitative proteomics to investigate the protein content of platelets in clinical samples from patients with dengue compared to platelets from healthy donors. Our assays revealed a set of 252 differentially abundant proteins. In silico analyses associated these proteins with key molecular events including platelet activation and inflammatory responses, and with events not previously attributed to platelets during dengue infection including antigen processing and presentation, proteasome activity, and expression of histones. From these results, we conducted functional assays using samples from a larger cohort of patients and demonstrated evidence for platelet activation indicated by P-selectin (CD62P) translocation and secretion of granule-stored chemokines by platelets. In addition, we found evidence that DENV infection triggers HLA class I synthesis and surface expression by a mechanism depending on functional proteasome activity. Furthermore, we demonstrate that cell-free histone H2A released during dengue infection binds to platelets, increasing platelet activation. These findings are consistent with functional importance of HLA class I, proteasome subunits, and histones that we found exclusively in proteome analysis of platelets in samples from dengue patients. Our study provides the first in-depth characterization of the platelet proteome in dengue

  18. Effects of hormones on platelet aggregation. (United States)

    Farré, Antonio López; Modrego, Javier; Zamorano-León, José J


    Platelets and their activation/inhibition mechanisms play a central role in haemostasis. It is well known agonists and antagonists of platelet activation; however, during the last years novel evidences of hormone effects on platelet activation have been reported. Platelet functionality may be modulated by the interaction between different hormones and their platelet receptors, contributing to sex differences in platelet function and even in platelet-mediated vascular damage. It has suggested aspects that apparently are well established should be reviewed. Hormones effects on platelet activity are included among them. This article tries to review knowledge about the involvement of hormones in platelet biology and activity.

  19. Extension of platelet concentrate storage. (United States)

    Simon, T L; Nelson, E J; Carmen, R; Murphy, S


    Extension of the storage time of platelet concentrates in a satellite bag which is part of a new blood bag system was studied by reinfusing autologous 51Cr-labeled platelets into normal volunteers, and measuring postinfusion platelet counts and bleeding times in patients requiring platelet transfusions. This satellite bag, made of polyvinylchloride plasticized with a new agent, was found to protect platelet concentrates against fall of pH better than other containers studied. This protection was felt to be due to the greater gas permeability of the new plastic. Mean in vivo recovery and half-life (greater than 31% and 3.3 days, respectively) of autologous reinfused platelets were satisfactory following 5 days of storage. Following 7 days of storage, mean recovery was 41 percent and half-life was 2.8 days. Peripheral platelet count increments in patients following platelet transfusions with concentrates stored 4 to 7 days in the new plastic were comparable to increments following transfusion of platelets stored 2 to 3 days in the other plastics studied. Bleeding times shortened in three of four patients receiving platelet concentrates stored from 4 to 6 days in the new plastic. Platelet concentrates stored in the new bag at 20 to 24 degrees C with flat-bed or elliptical agitation could be transfused for up to 5 days following phlebotomy with acceptable clinical results. The new plastic container is promising for storage of platelet concentrates for up to 7 days. Due to the higher pH of 50-ml platelet concentrates stored in bags made with the new plastic, the concentrates were superior at any storage interval to those stored in bags made of the other plastics studied.

  20. Las mujeres en la política revolucionaria. el caso del PRT-ERP en la Argentina de los años 70

    Directory of Open Access Journals (Sweden)

    Alejandra Oberti


    Full Text Available La izquierda revolucionaria argentina de los años 60 y 70 contó entre sus filas con una gran cantidad de mujeres. Muchas de ellas eran jóvenes que nacían a la vida política al mismo tiempo que surgían las organizaciones en las que militaban. Este texto explora la prensa y los documentos del PRT-ERP en un análisis que conjuga dos dimensiones. Por un lado, la  participación de las mujeres en la guerrilla, tanto en relación a su incorporación real en número y calidad de la militancia, como en la interpelación de la organización hacia ellas a través de la formación de espacios y la producción de materiales destinados específicamente a las mujeres. La otra dimensión refiere a la preocupación del PRT-ERP por pensar la subjetividad revolucionaria entrecruzando la vida cotidiana con la política, en un contexto de construcción de un modelo de militancia en la cual todos los aspectos de la vida quedaban implicados.

  1. Platelet aggregation following trauma

    DEFF Research Database (Denmark)

    Windeløv, Nis A; Sørensen, Anne M; Perner, Anders


    We aimed to elucidate platelet function in trauma patients, as it is pivotal for hemostasis yet remains scarcely investigated in this population. We conducted a prospective observational study of platelet aggregation capacity in 213 adult trauma patients on admission to an emergency department (ED......). Inclusion criteria were trauma team activation and arterial cannula insertion on arrival. Blood samples were analyzed by multiple electrode aggregometry initiated by thrombin receptor agonist peptide 6 (TRAP) or collagen using a Multiplate device. Blood was sampled median 65 min after injury; median injury...... severity score (ISS) was 17; 14 (7%) patients received 10 or more units of red blood cells in the ED (massive transfusion); 24 (11%) patients died within 28 days of trauma: 17 due to cerebral injuries, four due to exsanguination, and three from other causes. No significant association was found between...

  2. Platelet-rich plasma stimulated by pulse electric fields: Platelet activation, procoagulant markers, growth factor release and cell proliferation. (United States)

    Frelinger, A L; Torres, A S; Caiafa, A; Morton, C A; Berny-Lang, M A; Gerrits, A J; Carmichael, S L; Neculaes, V B; Michelson, A D


    Therapeutic use of activated platelet-rich plasma (PRP) has been explored for wound healing, hemostasis and antimicrobial wound applications. Pulse electric field (PEF) stimulation may provide more consistent platelet activation and avoid complications associated with the addition of bovine thrombin, the current state of the art ex vivo activator of therapeutic PRP. The aim of this study was to compare the ability of PEF, bovine thrombin and thrombin receptor activating peptide (TRAP) to activate human PRP, release growth factors and induce cell proliferation in vitro. Human PRP was prepared in the Harvest SmartPreP2 System and treated with vehicle, PEF, bovine thrombin, TRAP or Triton X-100. Platelet activation and procoagulant markers and microparticle generation were measured by flow cytometry. Released growth factors were measured by ELISA. The releasates were tested for their ability to stimulate proliferation of human epithelial cells in culture. PEF produced more platelet-derived microparticles, P-selectin-positive particles and procoagulant annexin V-positive particles than bovine thrombin or TRAP. These differences were associated with higher levels of released epidermal growth factor after PEF than after bovine thrombin or TRAP but similar levels of platelet-derived, vascular-endothelial, and basic fibroblast growth factors, and platelet factor 4. Supernatant from PEF-treated platelets significantly increased cell proliferation compared to plasma. In conclusion, PEF treatment of fresh PRP results in generation of microparticles, exposure of prothrombotic platelet surfaces, differential release of growth factors compared to bovine thrombin and TRAP and significant cell proliferation. These results, together with PEF's inherent advantages, suggest that PEF may be a superior alternative to bovine thrombin activation of PRP for therapeutic applications.

  3. Effect of Cold Storage on Shear-induced Platelet Aggregation and Clot Strength (United States)


    components after open heart surgery in children . Blood. 1991; 77:930 936. 15. Holme S, Heaton A. In vitro platelet aging at 22-C is reduced compared to in...Circulation and hemostatic effectiveness of platelets stored at 4 C or 22 C: studies in aspirin -treated normal volunteers. Transfusion. 1976;16:20 23. J

  4. Platelet immunology in fungal infections. (United States)

    Speth, Cornelia; Rambach, Günter; Lass-Flörl, Cornelia


    Up to date, perception of platelets has changed from key players in coagulation to multitaskers within the immune network, connecting its most diverse elements and crucially shaping their interplay with invading pathogens such as fungi. In addition, antimicrobial effector molecules and mechanisms in platelets enable a direct inhibitory effect on fungi, thus completing their immune capacity. To precisely assess the impact of platelets on the course of invasive fungal infections is complicated by some critical parameters. First, there is a fragile balance between protective antimicrobial effects and detrimental reactions that aggravate the fungal pathogenesis. Second, some platelet effects are exerted indirectly by other immune mediators and are thus difficult to quantify. Third, drugs such as antimycotics, antibiotics, or cytostatics, are commonly administered to the patients and might modulate the interplay between platelets and fungi. Our article highlights selected aspects of the complex interactions between platelets and fungi and the relevance of these processes for the pathogenesis of fungal infections.

  5. Effect of CYP2C19*2 and *3 loss-of-function alleles on platelet reactivity and adverse clinical events in East Asian acute myocardial infarction survivors treated with clopidogrel and aspirin. (United States)

    Jeong, Young-Hoon; Tantry, Udaya S; Kim, In-Suk; Koh, Jin-Sin; Kwon, Tae Jung; Park, Yongwhi; Hwang, Seok-Jae; Bliden, Kevin P; Kwak, Choong Hwan; Hwang, Jin-Yong; Gurbel, Paul A


    As compared with whites, East Asians more often carry the cytochrome P450 (CYP) 2C19 loss-of-function (LOF) allele with the CYP2C19*3 variant. The influence of the CYP2C19 LOF alleles (*2 and *3) on clopidogrel response and clinical outcomes in East Asians with acute myocardial infarction (AMI) has not been reported. We sought to evaluate the effect of the CYP2C19 variants on clopidogrel pharmacodynamics and long-term prognosis in these patients. Patients who survived an AMI (n=266) were enrolled in a single-center registry. Predischarge platelet reactivity was assessed with light transmittance aggregometry and the VerifyNow P2Y12 assay; the CYP2C19*2, *3, *17 and ABCB1 3435C>T variants were determined. The primary clinical end point was the composite of cardiovascular death, nonfatal MI, and ischemic stroke. The median exposure to clopidogrel was 21 months (interquartile range, 13-29). The ABCB1 3435C>T was not related to clopidogrel response or cardiovascular events. Carriage of the CYP2C19 LOF variant allele was relatively high (60.9%, n=162; *2/*17=2, *3/*17=1, *1/*2=96, *1/*3=29, *2/*2=20, and *2/*3=14). Platelet reactivity increased proportionally according to the number of the CYP2C19 LOF alleles. In a multivariate regression analysis, the risk of high on-treatment platelet reactivity (HPR) increased depending on the number of CYP2C19 LOF allele [1 LOF allele; odds ratio (OR), 1.8; 95% confidence interval (CI), 0.8 to 4.2, P=0.152; and 2 LOF alleles; OR, 2.8; 95% CI, 1.2 to 6.5; P=0.016]; platelet reactivity and the rate of HPR did not differ between the CYP2C19*2 versus *3 allele carriage. In addition, cardiovascular event occurrence increased according to the number of the CYP2C19 LOF allele; compared with noncarriers, carriers of 1 [hazard ratio (HR), 3.1; 95% CI, 0.8 to 11.6; P=0.089] and 2 CYP2C19 LOF allele(s) (HR, 10.1; 95% CI, 1.8-58.8; P=0.008) were associated with clinical end point. The clinical impact of the CYP2C19*2 versus *3 allele carriage

  6. Standard versus low-dose weight-adjusted heparin in patients treated with the platelet glycoprotein IIb/IIIa receptor antibody fragment abciximab (c7E3 Fab) during percutaneous coronary revascularization. PROLOG Investigators. (United States)

    Lincoff, A M; Tcheng, J E; Califf, R M; Bass, T; Popma, J J; Teirstein, P S; Kleiman, N S; Hattel, L J; Anderson, H V; Ferguson, J J; Cabot, C F; Anderson, K M; Berdan, L G; Musco, M H; Weisman, H F; Topol, E J


    Blockade of the platelet glycoprotein IIb/IIIa receptor by abciximab (c7E3 Fab) during coronary intervention reduces the incidence of ischemic complications, but has been associated with a doubling of the risk for bleeding complications. The present pilot study investigated whether modification of heparin dosing and/or early sheath removal would reduce the hemorrhagic complications associated with abciximab. One hundred three patients undergoing coronary intervention received abciximab (0.25 mg/kg bolus, 10 microg/min infusion for 12 hours) and aspirin and were randomized by a 2 x 2 factorial design to 1 of 2 weight-adjusted heparin doses and to 1 of 2 strategies for heparin discontinuation and vascular sheath removal. In the "standard-dose heparin" group, an initial bolus of 100 U/kg was administered to achieve a procedural activated clotting time (ACT) > or = 300 seconds; in the "low-dose heparin" group, an initial bolus of 70 U/kg was administered without adjustment for ACT. In the "late sheath removal" arm, heparin infusion was continued for the 12-hour duration of abciximab infusion, followed by sheath removal; in the "early sheath removal" group, heparin was stopped after the interventional procedure and sheaths were removed during the abciximab infusion. There were no apparent differences between patients randomized to the different treatment groups with regard to the occurrence of ischemic end points. Rates of bleeding and blood transfusion were reduced by low-dose heparin and early sheath removal and were lowest when both strategies were combined. Reduction and weight adjustment of heparin dose and early sheath removal in the setting of platelet inhibition with abciximab during coronary intervention may be useful in diminishing the incidence of hemorrhagic complications without loss of clinical efficacy.

  7. Autologous periodontal stem cell assistance in periodontal regeneration technique (SAI-PRT) in the treatment of periodontal intrabony defects: A case report with one-year follow-up. (United States)

    Kl, Vandana; Ryana, Haneet; Dalvi, Priyanka Jairaj


    Numerous animal and human studies have provided evidence supporting the belief that periodontal ligament stem cells (PDLSCs) can be harnessed for regeneration of periodontal tissues. Based on current literature on the use of ex vivo stem culture and associated problems, this case report describes a novel approach of direct application PDLSCs using stem cell assistance in periodontal regeneration technique (SAI-PRT) for the regeneration of intrabony periodontal defects bypassing ex vivo cultures. SAI-PRT has emerged as a constructive avenue in the treatment of periodontal osseous defects. Moreover, the current technique is less technique-sensitive, cost-effective and yields promising results.

  8. Orthobiologics and platelet rich plasma

    National Research Council Canada - National Science Library

    Dhillon, Mandeep S; Behera, Prateek; Patel, Sandeep; Shetty, Vijay


    ... in many chronic musculoskeletal ailments. Investigators have published results of laboratory as well as clinical studies, using orthobiologics like platelet rich plasma, stem cells, autologous conditioned serum etc...

  9. Novel aspects of platelet aggregation

    Directory of Open Access Journals (Sweden)

    Roka-Moya Y. M.


    Full Text Available The platelet aggregation is an important process, which is critical for the hemostatic plug formation and thrombosis. Recent studies have shown that the platelet aggregation is more complex and dynamic than it was previously thought. There are several mechanisms that can initiate the platelet aggregation and each of them operates under specific conditions in vivo. At the same time, the influence of certain plasma proteins on this process should be considered. This review intends to summarize the recent data concerning the adhesive molecules and their receptors, which provide the platelet aggregation under different conditions.

  10. Isolation of Platelet-Derived Extracellular Vesicles

    NARCIS (Netherlands)

    Aatonen, Maria; Valkonen, Sami; Böing, Anita; Yuana, Yuana; Nieuwland, Rienk; Siljander, Pia


    Platelets participate in several physiological functions, including hemostasis, immunity, and development. Additionally, platelets play key roles in arterial thrombosis and cancer progression. Given this plethora of functions, there is a strong interest of the role of platelet-derived

  11. Exosomes: novel effectors of human platelet lysate activity. (United States)

    Torreggiani, E; Perut, F; Roncuzzi, L; Zini, N; Baglìo, S R; Baldini, N


    Despite the popularity of platelet-rich plasma (PRP) and platelet lysate (PL) in orthopaedic practice, the mechanism of action and the effectiveness of these therapeutic tools are still controversial. So far, the activity of PRP and PL has been associated with different growth factors (GF) released during platelet degranulation. This study, for the first time, identifies exosomes, nanosized vesicles released in the extracellular compartment by a number of elements, including platelets, as one of the effectors of PL activity. Exosomes were isolated from human PL by differential ultracentrifugation, and analysed by electron microscopy and Western blotting. Bone marrow stromal cells (MSC) treated with three different exosome concentrations (0.6 μg, 5 μg and 50 μg) showed a significant, dose-dependent increase in cell proliferation and migration compared to the control. In addition, osteogenic differentiation assays demonstrated that exosome concentration differently affected the ability of MSC to deposit mineralised matrix. Finally, the analysis of exosome protein content revealed a higher amount of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-BB) and transforming growth factor beta 1 (TGF-β1) as compared to PL. In regards to RNA content, an enrichment of small RNAs in exosomes as compared to donor platelets has been found. These results suggest that exosomes consistently contribute to PL activity and could represent an advantageous nanodelivery system for cell-free regeneration therapies.

  12. Identification of the platelet ADP receptor targeted by antithrombotic drugs. (United States)

    Hollopeter, G; Jantzen, H M; Vincent, D; Li, G; England, L; Ramakrishnan, V; Yang, R B; Nurden, P; Nurden, A; Julius, D; Conley, P B


    Platelets have a crucial role in the maintenance of normal haemostasis, and perturbations of this system can lead to pathological thrombus formation and vascular occlusion, resulting in stroke, myocardial infarction and unstable angina. ADP released from damaged vessels and red blood cells induces platelet aggregation through activation of the integrin GPIIb-IIIa and subsequent binding of fibrinogen. ADP is also secreted from platelets on activation, providing positive feedback that potentiates the actions of many platelet activators. ADP mediates platelet aggregation through its action on two G-protein-coupled receptor subtypes. The P2Y1 receptor couples to Gq and mobilizes intracellular calcium ions to mediate platelet shape change and aggregation. The second ADP receptor required for aggregation (variously called P2Y(ADP), P2Y(AC), P2Ycyc or P2T(AC)) is coupled to the inhibition of adenylyl cyclase through Gi. The molecular identity of the Gi-linked receptor is still elusive, even though it is the target of efficacious antithrombotic agents, such as ticlopidine and clopidogrel and AR-C66096 (ref. 9). Here we describe the cloning of this receptor, designated P2Y12, and provide evidence that a patient with a bleeding disorder has a defect in this gene. Cloning of the P2Y12 receptor should facilitate the development of better antiplatelet agents to treat cardiovascular diseases.

  13. Newly Formed Reticulated Platelets Undermine Pharmacokinetically Short-Lived Antiplatelet Therapies. (United States)

    Armstrong, Paul C; Hoefer, Thomas; Knowles, Rebecca B; Tucker, Arthur T; Hayman, Melissa A; Ferreira, Plinio M; Chan, Melissa V; Warner, Timothy D


    Aspirin together with thienopyridine P2Y12 inhibitors, commonly clopidogrel, is a cornerstone of antiplatelet therapy. However, many patients receiving this therapy display high on-treatment platelet reactivity, which is a major therapeutic hurdle to the prevention of recurrent thrombotic events. The emergence of uninhibited platelets after thrombopoiesis has been proposed as a contributing factor to high on-treatment platelet reactivity. Here, we investigate the influences of platelet turnover on platelet aggregation in the face of different dual-antiplatelet therapy strategies. Traditional light transmission aggregometry, cytometry, advanced flow cytometric imaging, and confocal microscopy were used to follow the interactions of populations of platelets from healthy volunteers and patients with stable cardiovascular disease. Newly formed, reticulated platelets overproportionately contributed to, and clustered at, the core of forming aggregates. This phenomenon was particularly observed in samples from patients treated with aspirin plus a thienopyridine, but was absent in samples taken from patients treated with aspirin plus ticagrelor. Reticulated platelets are more reactive than older platelets and act as seeds for the formation of platelet aggregates even in the presence of antiplatelet therapy. This is coherent with the emergence of an uninhibited subpopulation of reticulated platelets during treatment with aspirin plus thienopyridine, explained by the short pharmacokinetic half-lives of these drugs. This phenomenon is absent during treatment with ticagrelor, because of its longer half-life and ability to act as a circulating inhibitor. These data highlight the important influences of pharmacokinetics on antiplatelet drug efficacies, especially in diseases associated with increased platelet turnover. © 2017 The Authors.

  14. The influence of environmental variables on platelet concentration in horse platelet-rich plasma. (United States)

    Rinnovati, Riccardo; Romagnoli, Noemi; Gentilini, Fabio; Lambertini, Carlotta; Spadari, Alessandro


    Platelet-rich plasma (PRP) commonly refers to blood products which contain a higher platelet (PLT) concentration as compared to normal plasma. Autologous PRP has been shown to be safe and effective in promoting the natural processes of soft tissue healing or reconstruction in humans and horses. Variability in PLT concentration has been observed in practice between PRP preparations from different patients or from the same individual under different conditions. A change in PLT concentration could modify PRP efficacy in routine applications. The aim of this study was to test the influence of environmental, individual and agonistic variables on the PLT concentration of PRP in horses. Six healthy Standardbred mares were exposed to six different variables with a one-week washout period between variables, and PRP was subsequently obtained from each horse. The variables were time of withdrawal during the day (morning/evening), hydration status (overhydration/dehydration) treatment with anti-inflammatory drugs and training periods on a treadmill. The platelet concentration was significantly higher in horses treated with a non-steroidal anti-inflammatory drug (P = 0.03). The leukocyte concentration increased 2-9 fold with respect to whole blood in the PRP which was obtained after exposure to all the variable considered. Environmental variation in platelet concentration should be taken into consideration during PRP preparation.

  15. Circulating primers enhance platelet function and induce resistance to antiplatelet therapy (United States)

    Blair, T A; Moore, S F; Hers, I


    Background Aspirin and P2Y12 antagonists are antiplatelet compounds that are used clinically in patients with thrombosis. However, some patients are ‘resistant’ to antiplatelet therapy, which increases their risk of developing acute coronary syndromes. These patients often present with an underlying condition that is associated with altered levels of circulating platelet primers and platelet hyperactivity. Platelet primers cannot stimulate platelet activation, but, in combination with physiologic stimuli, significantly enhance platelet function. Objectives To explore the role of platelet primers in resistance to antiplatelet therapy, and to evaluate whether phosphoinositide 3-kinase (PI3K) contributes to this process. Methods and Results We used platelet aggregation, thromboxane A2 production and ex vivo thrombus formation as functional readouts of platelet activity. Platelets were treated with the potent P2Y12 inhibitor AR-C66096, aspirin, or a combination of both, in the presence or absence of the platelet primers insulin-like growth factor-1 (IGF-1) and thrombopoietin (TPO), or the Gz-coupled receptor ligand epinephrine. We found that platelet primers largely overcame the inhibitory effects of antiplatelet compounds on platelet functional responses. IGF-1-mediated and TPO-mediated, but not epinephrine-mediated, enhancements in the presence of antiplatelet drugs were blocked by the PI3K inhibitors wortmannin and LY294002. Conclusions These results demonstrate that platelet primers can contribute to antiplatelet resistance. Furthermore, our data demonstrate that there are PI3K-dependent and PI3K-independent mechanisms driving primer-mediated resistance to antiplatelet therapy. PMID:26039631

  16. Effects of cancer on platelets. (United States)

    van Es, Nick; Sturk, Auguste; Middeldorp, Saskia; Nieuwland, Rienk


    The main function of circulating platelets is to stop bleeding upon vascular injury by the formation of a hemostatic plug. The presence of cancer results in numerical and functional abnormalities of platelets. Thrombocytosis is commonly observed in cancer patients and is associated with decreased survival. Conversely, thrombocytopenia has been shown to have antimetastatic effects in experimental models. Tumor cells also can induce changes in the platelet activation status, both in direct and indirect manners. Direct tumor cell-induced platelet aggregation enables the formation of a cloak of aggregated platelets around circulating tumor cells (CTCs) that shields them from attacks by the immune system and facilitates metastasis to distant sites. Cancer also can induce platelet activation in various indirect ways. Tumor cells shed small extracellular vesicles that expose the transmembrane protein tissue factor (TF)--the initiator of the extrinsic coagulation cascade. The abundant presence of TF in the circulation of cancer patients can result in local generation of thrombin, the most potent platelet activator. Another pathway of indirect platelet activation is by increased formation of neutrophil extracellular traps in the presence of tumor-secreted granulocyte colony-stimulating factor (G-CSF). Last, tumor cells may regulate the selective secretion of angiogenic proteins from platelet granules, which enables the tumor to stimulate and stabilize the immature neovasculature in the tumor environment. Since there is little doubt that the cancer-induced platelet alterations are beneficial to tumor growth and dissemination, it could be worthwhile to intervene in the underlying mechanisms for anticancer purposes. Antiplatelet and anticoagulant agents that inhibit platelet activation and thrombin generation can potentially slow cancer progression, although the clinical evidence thus far is not unequivocal. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Platelet Rich Plasma in Periodontal Therapy

    National Research Council Canada - National Science Library

    S Sathya Priya Eshwar; Dhayanand John Victor; S Sangeetha; PSG Prakash


    Keywords: Growth factors, Platelet concentrates, Platelet Rich Plasma, Regenerative medicine, Tissue engineering Introduction The goal of periodontal therapy is to improve periodontal health and thereby...

  18. Therapeutic angiogenesis for the critical limb ischemia decreases platelet activation. (United States)

    Chudý, Peter; Chudá, Daniela; Hudeček, Jan; Fedorová, Jana; Sinák, Igor; Hlinka, Luboš; Talapková, Renáta; Laca, Ludovít; Kubisz, Peter


    Platelets are required for the recruitment of bone marrow-derived mononuclear cells (BMMNC) into ischemia-induced vasculature, which underlines their key role in angiogenesis. The difference in platelet immunophenotype between healthy controls and patients with critical limb ischemia (CLI) treated with therapeutic angiogenesis (TA) using BMMNC was assessed. The impact of TA on the expression of platelet membrane markers was studied as well. CLI patients (N = 26) and blood donors as controls (N = 21) were enrolled. Bone marrow (600 ± 50 ml) was centrifuged (3200 g, 20 min, 22 °C). BMMNC (100-120 ml) were separated by Optipress I and implanted to the ischemic limb using deep intramuscular injections. Flow cytometry was employed for the peripheral blood platelets immunophenotyping. CD41FITC, CD62PE, CD36FITC, CD29FITC antibodies were used. Patients were followed up prior to the procedure and at months 1, 3 and 6. The expression of CD41 was lower in CLI patients than in the controls. P-selectin (CD62P) was higher in CLI patients than in controls at the baseline and at month 6. It was significantly down-regulated at month 3, however not at months 1 and 6 compared to baseline. Platelet GPIV (CD36) was higher at the baseline, but not during the follow-up compared to the controls. β1-integrin (CD29) progressively decreased during the follow-up as compared to the baseline value. Platelets in CLI express P-selectin, GPIV and β1-integrin more abundantly than platelets of healthy subjects. TA down-regulates the expression of the respective markers. Possible mechanism could be higher clearance of the activated platelets in the ischemic tissues during angiogenesis.

  19. Treatment of diabetic foot ulcers using a blood bank platelet concentrate. (United States)

    Jeong, Seong-Ho; Han, Seung-Kyu; Kim, Woo-Kyung


    Many clinical trials have shown the effectiveness of platelet releasate on chronic wound healing, but large volumes of blood must be aspirated from patients and a platelet separator is required. Moreover, in the case of using homologous platelets, time and effort are needed to locate a suitable donor, and the donor's blood sample must be tested for a history of infectious disease. The current study was undertaken to evaluate the effect of a straightforward method using a blood bank platelet concentrate in treating diabetic foot ulcers. Fifty-two patients with diabetic foot ulcers were treated using a blood bank platelet concentrate. A control treatment (i.e., treatment with topical fibrinogen and thrombin) was performed on 48 patients. Twelve weeks after treatment, the percentage of complete healing, mean healing time, percentage of wound shrinkage, and patient satisfaction were compared. Complete wound healing was achieved in 79 percent of the blood bank platelet concentrate-treated group and 46 percent of the control group (p treatment yielded better results than the control method (mean score, 7.6 +/- 1.6 and 5.3 +/- 1.4, respectively; p treatment occurred. Treatment of diabetic foot ulcers using a blood bank platelet concentrate showed results superior to control treatment. A blood bank platelet concentrate offers a simple and effective treatment for diabetic foot ulcers.

  20. Role of newly formed platelets in thrombus formation in rat after clopidogrel treatment

    DEFF Research Database (Denmark)

    Kuijpers, Marijke J E; Megens, Remco T A; Nikookhesal, Elham


    Platelet P2Y₁₂ receptors play an important role in arterial thrombosis by stimulating thrombus growth. Both irreversibly (clopidogrel) and reversibly binding (ticagrelor, AZD6140) P2Y₁₂ antagonists are clinically used for restricted periods, but possible differences in platelet function recovery...... after drug cessation have not been investigated. We treated WKY rats with a single, high dose of 200 mg/kg clopidogrel or 40 mg/kg ticagrelor. Blood was collected at different time points after treatment. Flow cytometry confirmed full platelet protection against ADP-induced αIIbβ₃ activation shortly...... after clopidogrel or ticagrelor treatment. At later time points after clopidogrel treatment, a subpopulation of juvenile platelets appeared that was fully responsive to ADP. Addition of ticagrelor to clopidogrel-treated blood reduced αIIbβ₃ activation of the unprotected platelets. In contrast, at later...

  1. The diversity of platelet microparticles. (United States)

    Boilard, Eric; Duchez, Anne-Claire; Brisson, Alain


    Platelet microparticles are small extracellular vesicles abundant in blood. The present review will introduce the mechanisms underlying the generation of microparticles, and will describe the diverse microparticle subtypes identified to date. The most appropriate methodologies used to distinguish microparticle subtypes will be also presented. Both the megakaryocytes and platelets can generate microparticles. Circulating microparticles originating from megakaryocytes are distinguished from those derived from activated platelets by the presence of CD62P, LAMP-1, and immunoreceptor-based activation motif receptors. Close examination of platelet activation has shed light on a novel mechanism leading to microparticle production. Under physiologic flow, microparticles bud off from long membrane strands formed by activated platelets. Furthermore, mounting evidence supports the notion of microparticle heterogeneity. Platelet microparticles are commonly characterized by the expression of surface platelet antigens and phosphatidylserine. In fact, only a fraction of platelet microparticles harbor phosphatidylserine, and a distinct subset contains respiratory-competent mitochondria. During disease, the microparticle surface may undergo posttranslational modifications such as citrullination, further supporting the concept of microparticle diversity. An appreciation of the microparticle heterogeneity will support their development as potential biomarkers and may reveal functions unique to each microparticle subtype in health and disease.

  2. Effects of cancer on platelets

    NARCIS (Netherlands)

    van Es, Nick; Sturk, Auguste; Middeldorp, Saskia; Nieuwland, Rienk


    The main function of circulating platelets is to stop bleeding upon vascular injury by the formation of a hemostatic plug. The presence of cancer results in numerical and functional abnormalities of platelets. Thrombocytosis is commonly observed in cancer patients and is associated with decreased

  3. Role of platelets in inflammation

    Directory of Open Access Journals (Sweden)

    Kadir Serkan Yalçın


    Full Text Available Inflammation, which is extremely useful process for humanbody is the response of living vascular tissues topathological phenomena that removes the pathogens andinitiates the healing procedure. Microorganisms, physicaltrauma, chemical, mechanical, irradiation, or thermal injury,ischemia and immune reactions are most commoncauses of this exceptionally important event for humanbody. Platelets are non-nucleated cells in blood that producedin bone marrow as derived from megakaryocytes.Apart from stop bleeding and achieving hemostasis thereare incredibly important roles of platelets in inflammation.Platelets contain important mediators for inflammationlike neutrophils or macrophages and can alter the courseof mechanism. In this article changing platelet function ininflammation and the effect of these functions to the processof inflammation will be discussed.Key words: Platelet, inflammation, cytokines

  4. Qualification Testing of Engineering Camera and Platinum Resistance Thermometer (PRT) Sensors for Mars Science Laboratory (MSL) Project under Extreme Temperatures to Assess Reliability and to Enhance Mission Assurance (United States)

    Ramesham, Rajeshuni; Maki, Justin N.; Cucullu, Gordon C.


    Package Qualification and Verification (PQV) of advanced electronic packaging and interconnect technologies and various other types of qualification hardware for the Mars Exploration Rover/Mars Science Laboratory flight projects has been performed to enhance the mission assurance. The qualification of hardware (Engineering Camera and Platinum Resistance Thermometer, PRT) under extreme cold temperatures has been performed with reference to various project requirements. The flight-like packages, sensors, and subassemblies have been selected for the study to survive three times (3x) the total number of expected temperature cycles resulting from all environmental and operational exposures occurring over the life of the flight hardware including all relevant manufacturing, ground operations and mission phases. Qualification has been performed by subjecting above flight-like qual hardware to the environmental temperature extremes and assessing any structural failures or degradation in electrical performance due to either overstress or thermal cycle fatigue. Experiments of flight like hardware qualification test results have been described in this paper.

  5. Platelet indices in SGA newborns. (United States)

    Wasiluk, A; Dabrowska, M; Osada, J; Jasinska, E; Laudanski, T; Redzko, S


    The current study objective was to compare blood platelet indices in full-term small-for-gestational-age newborns (SGA) and full-term appropriate-for-gestational-age newborns (AGA). We introduced to our study 61 SGA newborns (31 females and 30 males) and 70 eutrophic infants (32 females and 38 males). The SGA newborns were divided into two groups: those weighing less than the 5th centile: 35 infants (16 females and 19 males) and those between the 5th and 10th centiles: 26 infants (15 females and 11 males). Platelet indices were estimated in blood samples collected from the umbilical artery. SGA demonstrated a decreased count of blood platelets (238×103/μ) as compared with AGA (286×103/μL), p=0.0001. Platelet hematocrit (PTC) also showed differences in both groups (SGA=0.19% vs. AGA=0.22%; p=0.0005). Mean platelet volume (MPV) was higher in SGA (8.25fl) as compared with AGA (7.84fl); p=0.008. Large platelet count (LPLT) was higher in AGA 6.26% vs. SGA=4.75%; p=0.01. Platelet distribution width (PDW) was found to be nearly the same (SGA=47%, AGA=46%). PDW was higher in SGA newborns SGA infants between the 5th and 10th centiles (52%); p=0.008. A decreased blood platelet count, platelet hematocrit and large metabolically active platelet count, which in addition to reduced synthesis and excessive consumption of coagulation factors in states of hiperclotting is characteristic of IUGR, enhances the possibility of bleeding complications and increases the risk of infections. From a clinical point of view, it is important to take into consideration the degree of intrauterine hypotrophy during the evaluation of hemostatic disorders.

  6. FcgammaRII mediates platelet aggregation caused by disintegrins and GPIIb/IIIa monoclonal antibody, AP2. (United States)

    Huang, Tur-Fu; Chang, Chien-Hsin; Ho, Pei-Ling; Chung, Ching-Hu


    Disintegrins, snake venom-derived Arg-Gly-Asp (RGD)-containing polypeptides, and GPIIb/IIIa antagonist (AP2) block fibrinogen binding to GPIIb/IIIa of activated platelets, however, the combination of these two agents caused platelet aggregation. We hypothesize that disintegrin initially binds to specific epitope of GPIIb/IIIa, causing conformational change, and the recruitment of FcgammaRII, which can be bound by AP2, and finally triggering platelet aggregation. We prepared human platelet suspensions and measured platelet aggregation, Ca2+ mobilization, thromboxane B2 formation, and signal transduction. Disintegrin (e.g., accutin) and AP2 (a monoclonal antibody [mAb]-raised against GPIIb/IIIa) individually inhibited human platelet aggregation caused by collagen. However, as both accutin and AP2 were sequentially added into platelet suspension, platelet aggregation occurred. Accutin/AP2 caused shape change, cytosolic Ca2+ mobilization, P-selectin expression, and thromboxane A2 formation. Tirofiban, FcgammaRII mAb, or indomethacin completely inhibited platelet aggregation caused by accutin/AP2. Accutin/AP2 also caused tyrosine phosphorylation of signal molecules. Disintegrins enhanced AP2 binding to platelets, and AP2 also promoted disintegrin binding to platelets. FcgammaRII mAb inhibited the enhanced fluorescein isothiocyanate-disintegrin binding to platelet caused by AP2. Immunoprecipitation of the lysates of disintegrin/AP2-treated platelets using FcgammaRII Ab showed complex formation of GPIIb/IIIa and FcgammaRII. FcgammaRII mediates platelet aggregation caused by disintegrin and AP2, triggering a phospholipase C, phospholipase A2, Src-, Syk kinases, and Ca2+-dependent activation process. AP2 triggers platelet aggregation via binding to accessible FcgammaRII and the conformation-altered GPIIb/IIIa caused by disintegrin.

  7. Variação circadiana dos leucócitos, fibrinogênio e plaquetas no sangue de cães submetidos a processo inflamatório, tratados com escina Leucocytes, fibrinogen and platelets circadian variation in dogs exposed to an inflamatory process and treated with aescin

    Directory of Open Access Journals (Sweden)

    Maria Vargas dos Santos


    Full Text Available Foram utilizados 20 cães machos, sem raça definida, divididos em dois grupos de 10 para análise da variação circadiana dos leucócitos, fibrinogênio e plaquetas. Todos os cães foram submetidos a um processo inflamatório subcutâneo induzido pela administração de Terebentina. Após 24 horas os animais do grupo 1 foram tratados com duas doses de 1,3mg/kg de escina com intervalos de 12 horas e os cães do grupo II mantidos como testemunha. Coletas de sangue foram feitas em todos os animais às 0, 4, 8, 12, 16, 20 e 24 horas do dia para determinação dos leucócitos, fibrinogênio e plaquetas. A escina determinou nos animais do grupo I monocitose às 0, 8, 12, 16 e 24 horas, linfopenia às 12, 16 e 24 horas, leucocitose às 0, 20 e 24 horas, aumento da taxa de fibrinogênio às 16 e 24 horas e uma diminuição das plaquetas durante todo o dia. Conclui-se que a escina determina variações circadiana instáveis do número de leucócitos, plaquetas e quantidade de fibrinogênio em cães com processo inflamatório.To analyse the circadian variations of the leucocyte, fibrinogen and platelet 20 mongrel male dogs were used divided into two groups of ten animals. The first group was exposed to an inflamatory process induced by the administration of turpentine and after 24 hours the animals were treated with Aesein 1.3mg/kg from 12 to 12 hours. The second group was only exposed to the inflamatory process. Blood samples were performed in all the animals at 0,4am, 8am, 12am, 4pm, 8pm and 12pm hours of the day to examine the parameters. Aescin has determined monocytose at 0,8am, 12am, 4pm and 12pm; linfopenia at 4pm and 12pm; leucocitosis at 0,8pm and 12 pm, as well as an increase in the amount of fibrinogen at 4pm and 12pm; and a decrease in the platelets during all day. Aescin determines unstable circadian variations in the number of leucocyte, platelet and in the amount of fibrinogen in dogs with inflamatory process.

  8. Uterine clinical findings, fertility rate, leucocyte migration, and COX-2 protein levels in the endometrial tissue of susceptible mares treated with platelet-rich plasma before and after AI. (United States)

    Segabinazzi, Lorenzo G; Friso, Aime M; Correal, Sebastian B; Crespilho, André M; Dell'Aqua, José Antonio; Miró, Jordi; Papa, Frederico O; Alvarenga, Marco Antonio


    Persistent mating-induced endometritis (PMIE) results in decreased fertility in horses, thereby causing a significant impact in the horse market. Platelet-rich plasma (PRP), a modulator of the inflammatory response, has been largely used in veterinary medicine. Here, we investigated the effects of PRP on uterine inflammation, conception rate, endometrial polymorphonuclear neutrophil (PMN) migration, and COX-2 protein levels in the endometrial tissue. Thirteen PMIE-susceptible mares were used for artificial insemination (AI). The mares were inseminated with fresh semen in three consecutive cycles in a cross-over study design. The following cycle classifications were used: control cycle, no pharmacological interference; pre-AI, 20 mL of PRP was infused 24 h before AI; and post-AI, 20 mL of PRP was infused four h after AI. Follicular dynamics were monitored daily by transrectal ultrasound. When a follicle larger than 35 mm was detected, ovulation was induced with deslorelin acetate (1 mg, im). AI was performed 24 h after ovulation induction. Intrauterine fluid (FLU) was evaluated by ultrasonography before and 24 h after AI. PMNs in uterine cytology (CYT) and biopsy (HIS) were also observed before and 24 h after AI. Pregnancy was determined within 14 days after ovulation. Number of COX-2 positive cells was evaluated by immunohistochemistry. Both PRP treatments resulted in a decrease of PMNs in the CYT after breeding when compared to controls. FLU did not differ between cycles; however, the conception rates were significantly higher in the PRP mares. Mares positive for endometritis decreased in both treatment groups, and a more intense positive COX-2 labeling was observed in the control group when compared to the two treatment groups. In conclusion, PRP beneficially reduces inflammatory response in PMIE mares independent of when treatments were administered, thus increasing chances of successful pregnancy. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Sonorheometry assessment of platelet function in cardiopulmonary bypass patients: Correlation of blood clot stiffness with platelet integrin αIIbβ3 activity, aspirin usage, and transfusion risk. (United States)

    Viola, Francesco; Lin-Schmidt, Xiefan; Bhamidipati, Castigliano; Haverstick, Doris M; Walker, William F; Ailawadi, Gorav; Lawrence, Michael B


    Impaired platelet function may underlie bleeding associated with cardiopulmonary bypass (CPB) and at present is incompletely evaluated with existing diagnostic technologies. Sonorheometry (SR) is a recently developed ultrasound-based technology that quantifies hemostasis and platelet activity from a blood sample by measuring ex vivo clot stiffness (S). We hypothesized that impaired platelet-fibrin interactions as assessed by SR would correlate with transfusion during CPB and history of prior aspirin therapy. Thirty-nine patients undergoing elective cardiopulmonary bypass (CPB) were enrolled following informed consent (University of Virginia IRB#14050) in a prospective observational pilot study to assess pre-operative platelet function and transfusion frequency. To assess platelet activity, abciximab was added to blood prior to SR and native S versus abciximab treated S created a differential test for platelet activity. Patient blood samples were activated with kaolin and SR was then used to measure clot stiffness. Patients were transfused with blood products as directed by clinical practice, with the surgical team blinded to SR results. Blood clot stiffness with and without abciximab, was compared in a ratio test (S/Sabciximab) named the Platelet Function Index (PFI). PFI was hypothesized to be positively correlated with platelet contributions through integrin αIIbβ3 to clot stiffness. PFI for CPB subjects was lower for those receiving transfusions than those not receiving transfusions (paspirin therapy was lower than for those not on aspirin therapy (paspirin effects on risk of surgical bleeding. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Macrophage pro-inflammatory cytokine secretion is enhanced following interaction with autologous platelets

    Directory of Open Access Journals (Sweden)

    Fischer Thomas H


    Full Text Available Abstract Background Macrophages are the dominant phagocyte at sites of wound healing and inflammation, and the cellular and acellular debris encountered by macrophages can have profound effects on their inflammatory profile. Following interaction with apoptotic cells, macrophages are known to switch to an anti-inflammatory phenotype. Activated platelets, however, are also a major component of inflammatory lesions and have been proposed to be pro-inflammatory mediators. In the present study, we tested the hypothesis that macrophage interaction with activated platelets results in an inflammatory response that differs from the response following phagocytosis of apoptotic cells. Methods Human monocyte-derived macrophages (hMDMs were co-incubated with autologous activated platelets (AAPs and the platelet-macrophage interaction was examined by electron microscopy and flow cytometry. The cytokines TNF-α, IL-6, and IL-23 were also measured during LPS-activated hMDM co-incubation with AAPs, which was compared to co-incubation with apoptotic lymphocytes. Cytokine secretion was also compared to platelets pre-treated with the gluococorticoid dexamethasone. Results Macrophages trapped and phagocytized AAPs utilizing a mechanism that was significantly inhibited by the scavenger receptor ligand fucoidan. LPS-induced macrophage secretion of TNF-α, IL-6, and IL-23 was inhibited by co-incubation with apoptotic cells, but enhanced by co-incubation with AAPs. The platelet-dependent enhancement of LPS-induced cytokines could be reversed by pre-loading the platelets with the glucocorticoid dexamethasone. Conclusions The interaction of human macrophages with autologous platelets results in scavenger-receptor-mediated platelet uptake and enhancement of LPS-induced cytokines. Therefore, the presence of activated platelets at sites of inflammation may exacerbate pro-inflammatory macrophage activation. The possibility of reversing macrophage activation with

  11. Maresin 1 induces a novel pro-resolving phenotype in human platelets. (United States)

    Lannan, K L; Spinelli, S L; Blumberg, N; Phipps, R P


    Essentials Specialized proresolving mediators (SPMs) promote the resolution of inflammation. This study sought to investigate the effects of SPMs on human platelet function. The SPM, Maresin 1, enhanced hemostatic, but suppressed inflammatory functions of platelets. SPMs uniquely regulate platelet function and may represent a new class of antiplatelet agents. Background Antiplatelet therapy is a cornerstone of modern medical practice and is routinely employed to reduce the likelihood of myocardial infarction, thrombosis and stroke. However, current antiplatelet therapies, such as aspirin, often have adverse side-effects, including increased risk of bleeding, and some patients are relatively 'aspirin-resistant'. Platelets are intimately involved in hemostasis and inflammation, and clinical consequences are associated with excessive or insufficient platelet activation. Objectives A major unmet need in the field of hematology is the development of new agents that safely prevent unwanted platelet activation in patients with underlying cardiovascular disease, while minimizing the risk of bleeding. Here, we investigate the potential of endogenously produced, specialized pro-resolving mediators (SPMs) as novel antiplatelet agents. SPMs are a recently discovered class of lipid-derived molecules that drive the resolution of inflammation without being overtly immunosuppressive. Methods Human platelets were treated with lipoxin A4, resolvin D1, resolvin D2, 17-HDHA or maresin 1 for 15 min, then were subjected to platelet function tests, including spreading, aggregation and inflammatory mediator release. Results We show for the first time that human platelets express the SPM receptors, GPR32 and ALX. Furthermore, our data demonstrate that maresin 1 differentially regulates platelet hemostatic function by enhancing platelet aggregation and spreading, while suppressing release of proinflammatory and prothrombotic mediators. Conclusions These data support the concept that SPMs

  12. Immunochemical characterization of platelet-specific alloantigens

    NARCIS (Netherlands)

    Mulder, A.; van Leeuwen, E. F.; Veenboer, G. J.; Tetteroo, P. A.; von dem Borne, A. E.


    Immunoprecipitation was performed with platelet-specific alloantisera (anti-Zwa, -Zwb, -Baka and antiserum Luc) and 125I-labelled platelets of a panel of donors typed for these platelet-specific alloantigens. This was done by sensitization of intact, radiolabelled platelets with the antisera,

  13. Adhesion and activation of platelets from subjects with coronary artery disease and apparently healthy individuals on biomaterials. (United States)

    Braune, S; Groß, M; Walter, M; Zhou, S; Dietze, S; Rutschow, S; Lendlein, A; Tschöpe, C; Jung, F


    On the basis of the clinical studies in patients with coronary artery disease (CAD) presenting an increased percentage of activated platelets, we hypothesized that hemocompatibility testing utilizing platelets from healthy individuals may result in an underestimation of the materials' thrombogenicity. Therefore, we investigated the interaction of polymer-based biomaterials with platelets from CAD patients in comparison to platelets from apparently healthy individuals. In vitro static thrombogenicity tests revealed that adherent platelet densities and total platelet covered areas were significantly increased for the low (polydimethylsiloxane, PDMS) and medium (Collagen) thrombogenic surfaces in the CAD group compared to the healthy subjects group. The area per single platelet-indicating the spreading and activation of the platelets-was markedly increased on PDMS treated with PRP from CAD subjects. This could not be observed for collagen or polytetrafluoroethylene (PTFE). For the latter material, platelet adhesion and surface coverage did not differ between the two groups. Irrespective of the substrate, the variability of these parameters was increased for CAD patients compared to healthy subjects. This indicates a higher reactivity of platelets from CAD patients compared to the healthy individuals. Our results revealed, for the first time, that utilizing platelets from apparently healthy donors bears the risk of underestimating the thrombogenicity of polymer-based biomaterials. © 2015 Wiley Periodicals, Inc.

  14. Neonatal thrombocytopenia and platelets transfusion

    Directory of Open Access Journals (Sweden)

    Anil K Gupta


    Full Text Available Background: Neonates often develop thrombocytopenia at some time during hospital stay. Platelet transfusion are frequently given to them and are likely to result in unnecessary transfusion. Material and Methods: Thus, we analyzed thrombocytopenia in neonates, its prevalence, and relationship if any, between clinical condition and platelet transfusion in neonates, which would have been helpful in developing guidelines and/or protocols for platelet transfusion (and reducing the donor exposure in neonates. Results: A total of 870 neonates who were admitted in Neonatal Intensive Care Unit (NICU with various morbidities had platelets count done; of these, 146 (16.7% neonate revealed thrombocytopenia. Discussion: Low birth weight babies (P 0.009 and babies born with mother having hypertension (P 0.04 showed significant thrombocytopenia. Neonates with intrauterine growth retardation (IUGR diagnosed during antenatal screening showed lower platelet count (P 0.022. Neonates having associated illness, such as sepsis, gastrointestinal, and respiratory problems, and on vasopressor drugs were found to be associated with low platelet count. Conclusion: In our study, 16.40% of thrombocytopenic neonates required platelet transfusion either alone or with other blood component during their stay in NICU.

  15. Evaluation of the TEG® platelet mapping™ assay in blood donors

    Directory of Open Access Journals (Sweden)

    Steinbrüchel Daniel A


    Full Text Available Abstract Background Monitoring of antiplatelet therapy in patients at cardiovascular risk is difficult because existing platelet function tests are too sophisticated for clinical routine. The whole blood TEG® Platelet Mapping™ assay measures clot strength as maximal amplitude (MA and enables for quantification of platelet function, including the contribution of the adenosine diphosphate (ADP and thromboxane A2 (TxA2 receptors to clot formation. Methods In 43 healthy blood donors, the analytical (CVa and inter-individual variability (CVg of the TEG® Platelet Mapping™ assay were determined together with platelet receptor inhibition in response to arachidonic acid (AA and ADP. Results The CVa of the assay for maximal platelet contribution to clot strength (MAThrombin was 3.5%, for the fibrin contribution to clot strength (MAFibrin 5.2%, for MAAA 4.5% and for MAADP it was 6.6%. The MAThrombin CVg was 2.8%, MAFibrin 4.7%, MAAA 6.6% and for MAADP it was 26.2%. Females had a higher MAThrombin compared to males (62.8 vs. 58.4 mm, p = 0.005. The platelet TxA2 receptor inhibition was 1.2% (range 0–10% and lower than for the ADP receptor (18.6% (0–58%; p Conclusion The high variability in ADP receptor inhibition may explain both the differences in response to ADP receptor inhibitor therapy and why major bleeding sometimes develops during surgery in patients not treated with ADP receptor inhibitors. An analytical variation of ~5 % for the TEG® enables, however, for routine monitoring of the variability in ADP receptor inhibition and of antiplatelet therapy.

  16. The origin and function of platelet glycosyltransferases

    DEFF Research Database (Denmark)

    Wandall, Hans H; Rumjantseva, Viktoria; Sørensen, Anne Louise Tølbøll


    that megakaryocytes package these Golgi-derived glycosyltransferases into vesicles that are sent via proplatelets to nascent platelets, where they accumulate. These glycosyltransferases are active, and intact platelets glycosylate large exogenous substrates. Furthermore, we show that activation of platelets results...... to function in the extracellular space. This platelet glycosylation machinery offers a pathway to a simple glycoengineering strategy improving storage of platelets and may serve hitherto unknown biological functions....

  17. Page 1 72 Chandra P Sharma These grafts are treated with acetone ...

    Indian Academy of Sciences (India)

    are treated with distilled ethanol for 48 hr to remove all ungrafted HEMA monomer from the samples (Jansen and Ellinghorst 1979). 3. Platelet adhesion. Washed calf platelets are prepared and suspended in tyrode solution (Sharma and Lissy. 1982) for adhesion studies. The polymers under study are exposed to platelet.

  18. Clinical Applications of Platelet-Rich Plasma in Patellar Tendinopathy

    Directory of Open Access Journals (Sweden)

    D. U. Jeong


    Full Text Available Platelet-rich plasma (PRP, a blood derivative with high concentrations of platelets, has been found to have high levels of autologous growth factors (GFs, such as transforming growth factor-β (TGF-β, platelet-derived growth factor (PDGF, fibroblastic growth factor (FGF, vascular endothelial growth factor (VEGF, and epidermal growth factor (EGF. These GFs and other biological active proteins of PRP can promote tissue healing through the regulation of fibrosis and angiogenesis. Moreover, PRP is considered to be safe due to its autologous nature and long-term usage without any reported major complications. Therefore, PRP therapy could be an option in treating overused tendon damage such as chronic tendinopathy. Here, we present a systematic review highlighting the clinical effectiveness of PRP injection therapy in patellar tendinopathy, which is a major cause of athletes to retire from their respective careers.

  19. Statin-induced changes in mitochondrial respiration in blood platelets in rats and human with dyslipidemia. (United States)

    Vevera, J; Fišar, Z; Nekovářová, T; Vrablík, M; Zlatohlávek, L; Hroudová, J; Singh, N; Raboch, J; Valeš, K


    3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used drugs for lowering blood lipid levels and preventing cardiovascular diseases. However, statins can have serious adverse effects, which may be related to development of mitochondrial dysfunctions. The aim of study was to demonstrate the in vivo effect of high and therapeutic doses of statins on mitochondrial respiration in blood platelets. Model approach was used in the study. Simvastatin was administered to rats at a high dose for 4 weeks. Humans were treated with therapeutic doses of rosuvastatin or atorvastatin for 6 weeks. Platelet mitochondrial respiration was measured using high-resolution respirometry. In rats, a significantly lower physiological respiratory rate was found in intact platelets of simvastatin-treated rats compared to controls. In humans, no significant changes in mitochondrial respiration were detected in intact platelets; however, decreased complex I-linked respiration was observed after statin treatment in permeabilized platelets. We propose that the small in vivo effect of statins on platelet energy metabolism can be attributed to drug effects on complex I of the electron transport system. Both intact and permeabilized platelets can be used as a readily available biological model to study changes in cellular energy metabolism in patients treated with statins.

  20. Ultraviolet irradiation of platelet concentrates: Feasibility in transfusion practice

    Energy Technology Data Exchange (ETDEWEB)

    Andreu, G.; Boccaccio, C.; Lecrubier, C.; Fretault, J.; Coursaget, J.; LeGuen, J.P.; Oleggini, M.; Fournel, J.J.; Samama, M. (Secteur d' Hemobiologie Transfusion, Paris (France))


    Ultraviolet (UV)-B irradiation abolishes lymphocyte functions (the ability to respond and to stimulate) in mixed lymphocyte culture (MLC). This effect may have practical application in the prevention or reduction of transfusion-induced alloimmunization against HLA class I antigens. To study this, platelet concentrates (PCs) were obtained with a cell separator, suspended in autologous plasma in a final volume of 400 mL, and transferred into a large (22 X 30 cm) cell culture bag. This plastic showed a good transmittance of UV-B rays at 310 nm (54%). PCs were placed between two quartz plates (surface of irradiation = 25 X 37 cm), and the two sides were irradiated simultaneously. Energy delivered to the surface of the plastic bag was automatically monitored. The ability to respond (in MLC and to phytohemagglutinin) and to stimulate allogeneic lymphocytes was completely abolished with energy of 0.75 J per cm2 (irradiation time less than 3 min). The temperature increase during irradiation was negligible. Platelet aggregation (collagen, adrenalin, ADP, arachidonic acid, ristocetin) was not impaired if UV-B energy was below 3 J per cm2. Recovery and survival of autologous 111In-labeled platelets were studied in four volunteers; no differences were found between UV-B-treated (1.5 J/cm2) platelets and untreated platelets. These results show that a large-scale clinical trial using UV-B-irradiated PCs to prevent HLA alloimmunization is feasible.


    Directory of Open Access Journals (Sweden)

    Uroš Mlakar


    Full Text Available Background. Laboratory evaluation is indicated when a disorder of primary haemostasis is suspected by a personal or family history of easy bruising, nose bleeds, menorrhagia or postoperative bleeding, especially following dental extraction or tonsillectomy. The traditional procedures to diagnose defect in primary haemostasis are bleeding time, measurement of von Willebrand factor and platelet aggregometry. The most widely used screening test is bleeding time. Despite attempts at standardisation, the bleeding time remains poorly reproducible and is relatively insensitive to platelet function defects. Recently, a new test method, the platelet function analyser (PFA-100 has been introduced for the investigation of primary haemostasis. PFA-100 measures the ability of platelets activated in a high-shear environment to occlude an aperture in membrane treated with collagen and epinephrine and/or collagen and ADP. The time taken for flow across the membrane to stop (closure time is recorded.Conclusions. This article highlights the benefits and limitations of the clinical utility of the PFA-100. Because of its simplicity and excellent sensitivity the PFA-100 is useful mainly as a screening test for von Willebrand disease, hereditary and acquired platelet-dysfunctions including acetylsalicylic acidinduced abnormalities. Recently the PFA-100 has been shown to be of value in monitoring antiplatelet therapy and in monitoring desmopressin treatment in von Willebrand disease.

  2. Sustained increase in platelet aggregation after the cessation of clopidogrel. (United States)

    Djukanovic, Nina; Todorovic, Zoran; Zamaklar-Trifunovic, Danijela; Protic, Dragana; Dzudovic, Boris; Ostojic, Miodrag; Obradovic, Slobodan


    This study shows that the abrupt cessation of one-year clopidogrel treatment was not associated with thrombotic events in a prospective, multicentre study that enrolled 200 patients subjected to coronary stent implantation and treated with aspirin + clopidogrel 1 year after the stent placement. The aim of the study was to investigate the causes of a sustained increase of platelet aggregability, considering that the values of platelet aggregation stimulated with ADP + PGE1 (ADPHS values) significantly increased 10-90 days after the cessation of clopidogrel. Values of platelet aggregation induced by thrombin receptor activating peptide (TRAP values) and arachidonic acid (ASPI values) were divided into quartiles on the basis of ADPHS values 10 days after stopping clopidogrel (ADPHS10 ). There was a significant difference between TRAP values divided into quartiles according to ADPHS10 , 10, 45 and 90 days after stopping clopidogrel (P clopidogrel (P = 0.028 and 0.003). The results of the study indicate that patients with early pronounced rebound phenomena to clopidogrel termination have a long-term (at least 90 days) increased platelet aggregation to other agonists such as thrombin-related activated protein and arachidonic acid, suggesting the complex mutual relationship of various factors/agonists influencing the function of platelets. © 2016 John Wiley & Sons Australia, Ltd.

  3. Platelet-rich plasma and plantar fasciitis. (United States)

    Monto, Raymond R


    Plantar fasciitis is the most common cause of heel pain and can prove difficult to treat in its most chronic and severe forms. Advanced cases of plantar fasciitis are often associated with ankle stiffness, heel spurs, and other conditions and can lead to extensive physical disability and financial loss. Most available traditional treatments, including orthoses, nonsteroidal anti-inflammatory drugs, and steroid injections have a paucity of supportive clinical evidence. More invasive treatments, ranging from corticosteroid and botulinum-A toxin injections to shockwave therapy and plantar fasciotomy, have demonstrated varying clinical success in severe cases but carry the potential for serious complication and permanent disability. Platelet-rich plasma has recently been demonstrated to be helpful in managing chronic severe tendinopathies when other techniques have failed. This review examines the pathophysiology, diagnostic options, nonoperative treatment modalities, and surgical options currently used for plantar fasciitis. It also focuses on the clinical rationale and available evidence for using autologous platelet-rich plasma to treat severe refractory chronic plantar fasciitis.

  4. Peroxynitrite may affect fibrinolysis via the reduction of platelet-related fibrinolysis resistance and alteration of clot structure. (United States)

    Misztal, Tomasz; Rusak, Tomasz; Brańska-Januszewska, Justyna; Ostrowska, Halina; Tomasiak, Marian


    We tested the hypothesis that in vitro peroxynitrite (ONOO(-), a product of activated inflammatory cells) may affect fibrinolysis in human blood through the reduction of platelet-related fibrinolysis resistance. It was found that ONOO(-) (25-300 µM) accelerated lysis of platelet-fibrin clots (in PRP) dose-dependently, whereas fibrinolysis of platelet-free clots was slightly inhibited by ≥ 1000 µM stressor. Concentrations of ONOO(-) affecting the lysis of platelet-rich clots, inhibited clot retraction (CR) in a dose-dependent manner. Thromboelastometry (ROTEM) measurements performed in PRP showed that treatment with ONOO(-) (threshold conc. 100 µM) prolongs clotting time, and reduces alpha angle, and clot formation velocity parameters indicating for reduced thrombin formation rate. In PRP, ONOO(-) (threshold conc. 100 µM) reduced the collagen-evoked exposure of phosphatidylserine (PS) on platelets' plasma membrane, the shedding of platelet-derived microparticles (PMP), and inhibited platelet-dependent thrombin generation (measured in artificial system), dose-dependently. As judged by confocal microscopy, similar ONOO(-) concentrations altered the architecture of clots formed in collagen-treated PRP. Clots formed in the presence of ONOO(-) were less dense and were composed of thicker fibers, which make them more susceptible to lysis. In platelet-depleted plasma, ONOO(-) (up to milimolar concentration) did not alter clot structure. Blockage of PS exposed on platelets resulted in an alteration of clot architecture toward more prone to lysis. ONOO(-), at lysis-affecting concentrations, inhibited the collagen-evoked secretion of fibrinolytic inhibitors from platelets. We conclude that physiologically relevant ONOO(-) concentrations may accelerate the lysis of platelet-fibrin clots predominantly via downregulation of platelet-related mechanisms including: platelet secretion, clot retraction, platelet procoagulant response, and the alteration in clot architecture

  5. Complement Activation Alters Platelet Function (United States)


    been shown to participate directly in the immune response through interaction with vascular endothelium , with antigen presenting cells (APC) and...Syk inhibition decreases platelet lodging in the lungs indicating Syk is integral in platelet sequestration and organ damage. Crossing B6.lpr...adhesive phenotype: role of PAF in spatially regulating neutrophil adhesion and spreading. Blood 110:1879-1886. 7. Lapchak, P.H., A. Ioannou, P. Rani

  6. Studies on the biological effects of ozone: 10. Release of factors from ozonated human platelets. (United States)

    Valacchi, G; Bocci, V


    In a previous work we have shown that heparin, in the presence of ozone (O3), promotes a dose-dependent platelet aggregation, while after Ca2+ chelation with citrate, platelet aggregation is almost negligible. These results led us to think that aggregation may enhance the release of platelet components. We have here shown that indeed significantly higher amount of platelet-derived growth factor (PDGF), transforming growth factor beta1 (TGF-beta1) and interleukin-8 (IL-8) are released in a dose-dependent manner after ozonation of heparinised platelet-rich plasma samples. These findings may explain the enhanced healing of torpid ulcers in patients with chronic limb ischemia treated with O3 autohaemoteraphy (O3-AHT).

  7. Studies on the Biological Effects of Ozone: 10. Release of Factors from Ozonated Human Platelets

    Directory of Open Access Journals (Sweden)

    G. Valacchi


    Full Text Available In a previous work we have shown that heparin, in the presence of ozone (O3, promotes a dose-dependent platelet aggregation, while after Ca2+ chelation with citrate, platelet aggregation is almost negligible. These results led us to think that aggregation may enhance the release of platelet components. We have here shown that indeed significantly higher amount of platelet-derived growth factor (PDGF, transforming growth factor β1 (TGF-β1 and interleukin-8(IL-8 are released in a dose-dependent manner after ozonation of heparinised platelet-rich plasma samples. These findings may explain the enhanced healing of torpid ulcers in patients with chronic limbischemia treated with O3 autohaemoteraphy (O3-AHT.

  8. Platelet-rich plasma: a biomimetic approach to enhancement of surgical wound healing. (United States)

    Fernandez-Moure, Joseph S; Van Eps, Jeffrey L; Cabrera, Fernando J; Barbosa, Zonia; Medrano Del Rosal, Guillermo; Weiner, Bradley K; Ellsworth, Warren A; Tasciotti, Ennio


    Platelets are small anucleate cytoplasmic cell bodies released by megakaryocytes in response to various physiologic triggers. Traditionally thought to be solely involved in the mechanisms of hemostasis, platelets have gained much attention due to their involvement wound healing, immunomodulation, and antiseptic properties. As the field of surgery continues to evolve so does the need for therapies to aid in treating the increasingly complex patients seen. With over 14 million obstetric, musculoskeletal, and urological and gastrointestinal surgeries performed annually, the healing of surgical wounds continues to be of upmost importance to the surgeon and patient. Platelet-rich plasma, or platelet concentrate, has emerged as a possible adjuvant therapy to aid in the healing of surgical wounds and injuries. In this review, we will discuss the wound healing properties of platelet-rich plasma and various surgical applications. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Platelet function disorders and menorrhagia in adolescents: a review of laboratory diagnosis. (United States)

    Sokkary, Nancy A; Venkateswaran, Lakshmi; Dietrich, Jennifer E; Teruya, Jun


    This article provides an overview of the prevalence and pathophysiology of platelet function disorders (PFDs) in adolescents with menorrhagia. In addition, this article reviews the various testing modalities employed for diagnosing PFDs including platelet aggregometry, platelet function analyzer (PFA-100), platelet electron microscopy (EM), flow cytometry, and thromboelastography (TEG), discuss their utility and drawbacks, and allude to the recent recommendations and consensus statements about some of these modalities. Finally, the authors have sketched out a diagnostic algorithm for platelet function testing, which will guide treating physicians to a step-wise approach while evaluating adolescents with menorrhagia for PFDs. Copyright © 2012 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  10. Genetic determinants of platelet large-cell ratio, immature platelet fraction, and other platelet-related phenotypes. (United States)

    Pujol-Moix, Núria; Vázquez-Santiago, Miquel; Morera, Agnès; Ziyatdinov, Andrey; Remacha, Angel; Nomdedeu, Josep F; Fontcuberta, Jordi; Soria, José Manuel; Souto, Juan Carlos


    Platelets play a significant role in arterial thrombosis and are involved also in venous thrombosis. The genetic determinants of several platelet-related phenotypes have been studied previously. However, to the best of our knowledge, the genetic determinants of other platelet phenotypes have not been reported such as platelet-large-cell ratio (P-LCR) index, immature platelet fraction (IPF) parameters and overall platelet function measured through the PFA-100 system. As part of the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia 2) Project, 935 individuals from 35 large Spanish families, ascertained through a proband with thrombophilia, were studied. Using variance component methods, implemented in the SOLAR package, the heritability of the following sets of platelet-related phenotypes was determined: platelet count and indices, IPF, and platelet function. High heritabilities of the platelet count and index phenotypes (from 0.41 to 0.64) were found, especially for those related to platelet volume. The heritabilities of the IPF phenotypes, as a measure of platelet turnover, were the highest (from 0.65 to 0.69). The heritabilities of the platelet function phenotypes were high also (0.45 and 0.62). The covariate age influenced all of the platelet phenotypes. Smoking influenced the platelet indices related to platelet volume and all the IPF phenotypes. Venous thrombosis showed a heritability of 0.67. We did not find a genetic correlation between any of the platelet-related phenotypes and venous thrombosis. The high heritabilities found for all of the platelet phenotypes provid promising data for the identification of new genes that underly these phenotypes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Platelet signaling-a primer. (United States)

    Goggs, Robert; Poole, Alastair W


    To review the receptors and signal transduction pathways involved in platelet plug formation and to highlight links between platelets, leukocytes, endothelium, and the coagulation system. Original studies, review articles, and book chapters in the human and veterinary medical fields. Platelets express numerous surface receptors. Critical among these are glycoprotein VI, the glycoprotein Ib-IX-V complex, integrin α(IIb) β(3) , and the G-protein-coupled receptors for thrombin, ADP, and thromboxane. Activation of these receptors leads to various important functional events, in particular activation of the principal adhesion receptor α(IIb) β(3) . Integrin activation allows binding of ligands such as fibrinogen, mediating platelet-platelet interaction in the process of aggregation. Signals activated by these receptors also couple to 3 other important functional events, secretion of granule contents, change in cell shape through cytoskeletal rearrangement, and procoagulant membrane expression. These processes generate a stable thrombus to limit blood loss and promote restoration of endothelial integrity. Improvements in our understanding of how platelets operate through their signaling networks are critical for diagnosis of unusual primary hemostatic disorders and for rational antithrombotic drug design. © Veterinary Emergency and Critical Care Society 2012.

  12. Time-dependent inhibitory effects of cGMP-analogues on thrombin-induced platelet-derived microparticles formation, platelet aggregation, and P-selectin expression

    Energy Technology Data Exchange (ETDEWEB)

    Nygaard, Gyrid [Proteomic Unit at University of Bergen (PROBE), University of Bergen, Bergen (Norway); Department of Biomedicine, University of Bergen, Bergen (Norway); Herfindal, Lars; Kopperud, Reidun [Department of Biomedicine, University of Bergen, Bergen (Norway); Aragay, Anna M. [Department of Biomedicine, University of Bergen, Bergen (Norway); Molecular Biology Institute of Barcelona (IBMB, CSIC), Barcelona (Spain); Holmsen, Holm; Døskeland, Stein Ove; Kleppe, Rune [Department of Biomedicine, University of Bergen, Bergen (Norway); Selheim, Frode, E-mail: [Proteomic Unit at University of Bergen (PROBE), University of Bergen, Bergen (Norway); Department of Biomedicine, University of Bergen, Bergen (Norway)


    Highlights: • We investigated the impact of cyclic nucleotide analogues on platelet activation. • Different time dependence were found for inhibition of platelet activation. • Additive effect was found using PKA- and PKG-activating analogues. • Our results may explain some of the discrepancies reported for cNMP signalling. - Abstract: In platelets, nitric oxide (NO) activates cGMP/PKG signalling, whereas prostaglandins and adenosine signal through cAMP/PKA. Cyclic nucleotide signalling has been considered to play an inhibitory role in platelets. However, an early stimulatory effect of NO and cGMP-PKG signalling in low dose agonist-induced platelet activation have recently been suggested. Here, we investigated whether different experimental conditions could explain some of the discrepancy reported for platelet cGMP-PKG-signalling. We treated gel-filtered human platelets with cGMP and cAMP analogues, and used flow cytometric assays to detect low dose thrombin-induced formation of small platelet aggregates, single platelet disappearance (SPD), platelet-derived microparticles (PMP) and thrombin receptor agonist peptide (TRAP)-induced P-selectin expression. All four agonist-induced platelet activation phases were blocked when platelets were costimulated with the PKG activators 8-Br-PET-cGMP or 8-pCPT-cGMP and low-doses of thrombin or TRAP. However, extended incubation with 8-Br-PET-cGMP decreased its inhibition of TRAP-induced P-selectin expression in a time-dependent manner. This effect did not involve desensitisation of PKG or PKA activity, measured as site-specific VASP phosphorylation. Moreover, PKG activators in combination with the PKA activator Sp-5,6-DCL-cBIMPS revealed additive inhibitory effect on TRAP-induced P-selectin expression. Taken together, we found no evidence for a stimulatory role of cGMP/PKG in platelets activation and conclude rather that cGMP/PKG signalling has an important inhibitory function in human platelet activation.

  13. The effects of ropivacaine hydrochloride on platelet function: an assessment using the platelet function analyser (PFA-100).

    LENUS (Irish Health Repository)

    Porter, J


    Amide local anaesthetics impair blood clotting in a concentration-dependent manner by inhibition of platelet function and enhanced fibrinolysis. We hypothesised that the presence of ropivacaine in the epidural space could decrease the efficacy of an epidural blood patch, as this technique requires that the injected blood can clot in order to be effective. Ropivacaine is an aminoamide local anaesthetic used increasingly for epidural analgesia during labour. The concentration of local anaesthetic in blood achieved in the epidural space during the performance of an epidural blood patch is likely to be the greatest which occurs (intentionally) in any clinical setting. This study was undertaken to investigate whether concentrations of ropivacaine in blood, which could occur: (i) clinically in the epidural space and (ii) in plasma during an epidural infusion of ropivacaine, alter platelet function. A platelet function analyser (Dade PFA-100, Miami) was employed to assess the effects of ropivacaine-treated blood on platelet function. The greater concentrations of ropivacaine studied (3.75 and 1.88 mg x ml(-1)), which correspond to those which could occur in the epidural space, produced significant inhibition of platelet aggregation. We conclude that the presence of ropivacaine in the epidural space may decrease the efficacy of an early or prophylactic epidural blood patch.

  14. Lipopolysaccharide-stimulated Leukocytes Contribute to Platelet Aggregative Dysfunction, Which is Attenuated by Catalase in Rats

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    Huei-Ping Dong


    Full Text Available Endotoxemia causes several hematological dysfunctions, including platelet degranulation or disseminated intravascular coagulation, which lead to thrombotic and hemorrhagic events. Here, we tested the hypothesis that bacterial lipopolysaccharide (LPS-stimulated leukocytes contribute to platelet aggregative dysfunction, and this function is attenuated by antioxidants. Plateletrich plasma (PRP was prepared from whole blood of normal and endotoxemic rats. The ability of platelet aggregation was measured by an aggregometer. LPS (50–100 μg/mL was incubated with PRP, whole blood and PRP with polymorphonuclear leukocytes (PMNs for 30 minutes, 60 minutes and 90 minutes, and platelet aggregation was detected. LPS-induced platelet aggregative dysfunction was undetectable in intact PRP which was isolated from normal whole blood, whereas it was detected in PRP isolated from endotoxemic rats and LPS-treated whole blood. Moreover, the effect of LPS-induced platelet aggregative dysfunction on intact PRP was observed when the PMNs were added. LPS-induced platelet aggregative dysfunction was significantly attenuated by catalase alone and in combination with NG-nitro-L-arginine methyl ester, but not by NG-nitro-L-arginine methyl ester alone. These results indicate that LPS-stimulated PMNs modulate platelet aggregation during LPS treatment and the effects are reversed by antioxidants. PMNs serve as an approach to understand LPS-induced platelet aggregative dysfunction during endotoxemia. During this process, the generation of reactive oxygen species, hydrogen peroxide especially, from LPS-stimulated PMNs could be an important potential factor in LPS-induced platelet aggregative dysfunction. Catalase contributes to the prevention of platelet dysfunction during LPS-induced sepsis.

  15. Inositol cyclic triphosphate [inositol 1,2-(cyclic)-4,5-triphosphate] is formed upon thrombin stimulation of human platelets.


    Ishii, H; Connolly, T M; Bross, T E; Majerus, P W


    Cleavage of polyphosphoinositides in vitro by phospholipase C results in formation of both cyclic and noncyclic inositol phosphates. We have now isolated the cyclic product of phosphatidylinositol 4,5-bisphosphate cleavage, inositol 1,2(cyclic)-4,5-triphosphate [cIns(1:2,4,5)P3], from thrombin-treated platelets. We found 0.2-0.4 nmol of cIns-(1:2,4,5)P3 per 10(9) platelets at 10 sec after thrombin; none was found in unstimulated platelets or in platelets 10 min after thrombin addition. We con...

  16. Incomplete reversibility of platelet inhibition following prolonged exposure to ticagrelor. (United States)

    Gerrits, A J; Jakubowski, J A; Sugidachi, A; Michelson, A D; Frelinger, A L


    Essentials Irreversible platelet inhibition persists after reversibly-binding ticagrelor is discontinued. Reversibility of platelet inhibition by ticagrelor and its active metabolite was assessed. Incomplete recovery was observed after prolonged exposure to ticagrelor. Activated GPIIb-IIIa and P-selectin, not platelet reactivity index, showed irreversibility. Introduction Ticagrelor is described as a reversible P2Y12 antagonist. However, residual platelet inhibition persists after discontinuation of ticagrelor when plasma levels are undetectable. We assessed the reversibility of platelet inhibition by ticagrelor and its active metabolite (T-AM) in comparison with cangrelor and prasugrel's active metabolite (P-AM). Methods Whole blood was treated in vitro with ~ 50% inhibitory concentrations of ticagrelor, T-AM, cangrelor, P-AM and assessed for ADP-stimulated activated GPIIb-IIIa and P-selectin and vasodilator-stimulated phosphoprotein (VASP) platelet reactivity index (PRI) before and after 100-fold dilution. Results Platelets exposed for 30 min to ticagrelor, T-AM or cangrelor showed full recovery of activated GPIIb-IIIa but only partial recovery of P-selectin. Longer exposure (24 h) to the drug decreased reversibility of activated GPIIb-IIIa by ticagrelor (65.1% [49.5-80.6], % of vehicle with 95% confidence interval [CI]) and T-AM (88.8% [79.2-98.3]), but not by cangrelor (101.4% [96.4-106.4]). Compared with 30 min exposure, the reversibility of P-selectin further decreased after 24 h exposure to ticagrelor (from 91.8% [82.1-101.5] to 51.8% [45.5-85.0]), but not T-AM (from 79.0% [67.8-90.3] to 77.4% [61.8-93.1]) or cangrelor (from 76.0% [67.6-84.4] to 76.2% [70.6-81.8]). In contrast, 24 h exposure to ticagrelor, T-AM and cangrelor resulted in full recovery of platelet reactivity as measured by PRI. Platelets exposed to P-AM showed no recovery of ADP reactivity. Conclusions Incomplete recovery after prolonged exposure to ticagrelor, observed by activated GPIIb

  17. Sgk1 Sensitive Pendrin Expression in Murine Platelets

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    Lisann Pelzl


    Full Text Available Background: The anion exchanger pendrin (SLC26A4 is required for proper development of the inner ear, and contributes to iodide organification in thyroid glands as well as anion transport in various epithelia, such as airways and renal tubules. SLC26A4 deficiency leads to Pendred syndrome, which is characterized by hearing loss with enlarged vestibular aqueducts and variable hypothyroidism and goiter. Pendrin expression in kidney, heart, lung and thyroid is up-regulated by the mineralocorticoid deoxycorticosterone (DOCA. Platelets express anion exchangers but virtually nothing is known about the molecular identity and regulation of those carriers. Other carriers such as the Na+/H+ exchanger are regulated by the mineralocorticoid-sensitive serum and glucocorticoid inducible kinase SGK1. Methods: The present study utilized i quantitative reverse transcription polymerase chain reaction (RT-qPCR to quantify the transcript levels of Slc26a4 as compared to Gapdh and ii western blotting to assess Slc26a4 protein abundance in murine platelets from gene-targeted mice lacking Sgk1 (sgk1-/- and respective wild type animals (sgk1+/+ treated without or with a subcutaneous injection of 2.5 mg DOCA for 3 h, or in sgk1+/+ platelets with or without in vitro treatment for 1 h with 10 µg/ml DOCA. Results: Slc26a4 was expressed in platelets, and in vitro DOCA treatment increased Slc26a4 mRNA levels in platelets isolated from sgk1+/+ mice. Moreover, in vivo DOCA treatment significantly up-regulated Slc26a4 mRNA levels in platelets isolated from sgk1+/+ but not sgk1-/- mice. An increase in Sgk1 mRNA levels paralleled that of Slc26a4 mRNA levels in platelets of sgk1+/+ mice. In addition, DOCA treatment further increased Slc26a4 protein abundance in platelets isolated from sgk1+/+ mice. Conclusions: Pendrin is expressed in platelets and is presumably regulated by SGK1 and mineralocorticoids.

  18. Availability of /sup 111/In-labeled platelet scintigraphy in patients with postinfarction left ventricular aneurysm

    Energy Technology Data Exchange (ETDEWEB)

    Tsuda, Takatoshi; Kubota, Masahiro; Iwakubo, Akifumi and others


    Eighteen patients with postinfarction left ventricular aneurysm (LVA) were examined with indium-111-labeled autologous platelet scintigraphy to identify intracardiac thrombi and to investigate the effect of antithrombotic agents on thrombogenesitiy within the LVA. Indium-111-platelet scintigraphy had a sensitivity of 60% and a specificity of 100% in detecting LVA mural thrombi. Among 6 patients showing false-negative scintigraphic studies, 4 was managed on antiplatelet therapy. Of 9 patients showing active platelet deposition on initial study, including 8 not receiving antiplatelet therapy, 5 were treated with tichlopidine (300 mg/day) for 29.8+-5.0 days. For the 5 patients, 2 had resolution and the 3 others had interruption of intraaneurysmal deposition in the second platelet study. For one patient receiving the third platelet study after warfarin therapy, it took two weeks to completely interrupt platelet deposition within the LVA. ECG gated radionuclide ventriculography and thallium-201 myocardial SPECT were also performed to assess left ventricular wall motion of left ventricular ejection fraction (LVEF) and myocardial blood perfusion. Thallium-201 SPECT showed apical or anteroapical perfusion defects. Radionuclide ventriculography pinpointed all 18 apical and anteroseptal aneurysms. A comparison between the thrombus positive group and the thrombus negative group revealed no statistical differences in LVEF and the period from the last myocardial infarction to the initial platelet scanning. These results suggest that indium-111 labeled platelet scintigraphy may be useful for identifying active left ventricular mural thrombi and for judging antiplatelet and anticoagulant therapy. (Namekawa, K).

  19. Sports medicine and platelet-rich plasma: nonsurgical therapy. (United States)

    Grambart, Sean T


    A Cochrane Review was performed to assess the effects of platelet-rich therapies for treating musculoskeletal soft tissue injuries. Selection criteria were randomized and quasirandomized controlled trials (RCTs) that compared platelet-rich therapy with either placebo, autologous whole blood, dry needling, or no platelet-rich therapy for people with acute or chronic musculoskeletal soft tissue injuries. Primary outcomes were functional status, pain, and adverse effects. The investigators found 19 studies that compared platelet-rich therapy with placebo, autologous whole blood, dry needling, or no platelet-rich therapy. Disorders included rotator cuff tears (arthroscopic repair; 6 trials); shoulder impingement syndrome surgery (1 trial); elbow epicondylitis (3 trials); anterior cruciate ligament (ACL) reconstruction (4 trials), ACL reconstruction (donor graft site application; 2 trials), patellar tendinopathy (1 trial), Achilles tendinopathy (1 trial), and acute Achilles rupture surgical repair (1 trial). They further subdivided the studies based on type of treatment, including tendinopathies in which platelet-rich therapy injections were the main treatment (5 trials), and surgical augmentation procedures in which platelet-rich therapy was applied during surgery (14 trials). The conclusion was that there is currently insufficient evidence to support the use of platelet-rich therapy for treating musculoskeletal soft tissue injuries. Researchers contemplating RCTs should consider the coverage of currently ongoing trials when assessing the need for future RCTs on specific conditions. There is a need for standardization of PRP preparation methods. At this time, the use of PRP in foot and ankle surgery as an orthobiologic does not have an absolute indication. Many of the studies are lower evidence-based from surgical techniques. Several in vitro studies have shown that growth factors promote the regeneration of bone, cartilage, and tendons. More clinical studies are

  20. Platelets and infection — an emerging role of platelets in viral infection

    Directory of Open Access Journals (Sweden)

    Alice eAssinger


    Full Text Available Platelets are anucleate blood cells that play a crucial role in the maintenance of hemostasis. While platelet activation and elevated platelet counts (thrombocytosis are associated with increased risk of thrombotic complications, low platelet counts (thrombocytopenia and several platelet function disorders increase the risk of bleeding. Over the last years more and more evidence has emerged that platelets and their activation state can also modulate innate and adaptive immune responses and low platelet counts have been identified as a surrogate marker for poor prognosis in septic patients.Viral infections often coincide with platelet activation. Host inflammatory responses result in the release of platelet activating mediators and a pro-oxidative and pro-coagulant environment, which favours platelet activation. However, viruses can also directly interact with platelets and megakaryocytes and modulate their function. Furthermore, platelets can be activated by viral antigen-antibody complexes and in response to some viruses B-lymphocytes also generate anti-platelet antibodies.All these processes contributing to platelet activation result in increased platelet consumption and removal and often lead to thrombocytopenia, which is frequently observed during viral infection. However, virus-induced platelet activation does not only modulate platelet count, but also shapes immune responses. Platelets and their released products have been reported to directly and indirectly suppress infection and to support virus persistence in response to certain viruses, making platelets a double-edged sword during viral infections. This review aims to summarize the current knowledge on platelet interaction with different types of viruses, the viral impact on platelet activation and platelet-mediated modulations of innate and adaptive immune responses.

  1. Effects of platelet-rich plasma gel on skin healing in surgical wound in horses. (United States)

    DeRossi, Rafael; Coelho, Anna Carolina Anciliero de Oliveira; Mello, Gisele Silveira de; Frazílio, Fabrício Oliveira; Leal, Cássia Rejane Brito; Facco, Gilberto Gonçalves; Brum, Karine Bonucielli


    To establish a low-cost method to prepare platelet-rich plasma (PRP) and evaluates the potential of platelet derived factors to enhance wound healing in the surgical wounds in equine. To obtain a PRP gel, calcium gluconate and autologous thrombin were added to platelet-rich plasma. For the tests six saddle horses were used and two surgical incisions were made in each animal. Wounds were treated with PRP gel or untreated. Sequential wound biopsies collected at Treatment 1: at days 5 and 30 and Treatment 2: at days 15 and 45 post wounding permitted comparison of differentiation markers and wound repair. The optimal platelets enrichment over 4.0 time's baseline values was obtained using 300 g for 10 min on the first centrifugation and 640 g for 10 min on the second centrifugation. Wounds treated with PRP gel exhibit more rapid epithelial differentiation and enhanced organization of dermal collagen compared to controls in equine.

  2. Phorbol ester stimulates calcium sequestration in saponized human platelets

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, K.; Nachmias, V.T.


    When platelets are activated by agonists, calcium (Ca2+) is released from an intracellular storage site. Recent studies using fura-2 show that, after thrombin stimulation, the rise in free calcium is transient and returns to base-line levels in 2-3 min, while the transient following ADP stimulation lasts only 15-20 s. We reported previously that the phorbol ester 12,13-phorbol myristate acetate (PMA), added at nanomolar levels after thrombin, immediately accelerated the rate of return of calcium to the base line severalfold. In the present study, we used both intact and saponized platelets to determine whether this is due to stimulation of calcium sequestration. Using fura-2 and intact platelets, we found 1) that PMA stimulated the restoration of free Ca2+ levels after ADP as well as after thrombin, and 2) that H-7, an inhibitor of protein kinase C (Ca2+/phospholipid-dependent enzyme), slowed the return of Ca2+ to baseline levels. Using saponized platelets, we also found 3) that pretreatment of platelets with PMA before saponin treatment increased the ATP-dependent /sup 45/Ca2+ uptake 2-fold, with a half-maximal effect at 5 nm; 4) that most of the Ca2+ released by ionomycin or by myoinositol 1,4,5-trisphosphate; and 5) that a GTP-binding protein inhibitor, guanosine 5'-O-(2-thiodiphosphate), decreased basal or PMA-stimulated /sup 45/Ca2+ uptake in saponin-treated platelets. Our data suggest that activation of protein kinase C stimulates the sequestration of Ca2+ independently of cAMP or myoinositol 1,4,5-trisphosphate.

  3. Platelet reactivity in patients undergoing transcatheter aortic valve implantation. (United States)

    Orvin, Katia; Eisen, Alon; Perl, Leor; Zemer-Wassercug, Noa; Codner, Pablo; Assali, Abid; Vaknin-Assa, Hana; Lev, Eli I; Kornowski, Ran


    Thromboembolic events, primarily stroke, might complicate transcatheter aortic-valve implantation (TAVI) procedures in 3-5 % of cases. Thus, it is common to administer aspirin and clopidogrel pharmacotherapy for 3-6 months following TAVI in order to prevent those events. The biologic response to the dual anti platelet treatment (DAPT) is heterogeneous, e.g. low response, known as high on treatment platelet reactivity (HTPR) may be associated with adverse thromboembolic events. Little is known about the prevalence of HTPR among patients undergoing TAVI. To assess the variability in response and rates of residual platelet reactivity in patients undergoing TAVI. We examined platelet reactivity in response to clopidogrel and aspirin in 40 consecutive patients (mean age 81.7 ± 6.5 years, 66.7 % women) who underwent successful TAVI using the VerifyNow P2Y12 assay and the multiple electrode aggregometry assay (Multiplate analyzer) in response to adenosine diphosphate and arachidonic acid respectively, at different time points before and following TAVI. Before TAVI, the majority of patients were on antiplatelet therapy (68.5 % aspirin, 12.5 % clopidogrel, 12.5 % DAPT). Following the procedure all patients were on DAPT or clopidogrel and warfarin. Among analyzed patients, 41 % had HTPR for clopidogrel and 12.5 % for aspirin at baseline, which did not significantly change 1-month following the procedure (p = 0.81 and p  = 0.33, respectively). In conclusion, patients undergoing TAVI for severe aortic stenosis and treated with DAPT have high rates of residual platelet reactivity during the peri-procedural period and up to 1-month thereafter. These findings may have clinical implications for the anti-platelet management of TAVI patients.

  4. Ex vivo recapitulation of trauma-induced coagulopathy and assessment of trauma patient platelet function under flow using microfluidic technology (United States)

    Li, Ruizhi; Elmongy, Hanna; Sims, Carrie; Diamond, Scott L.


    Background Relevant to trauma induced coagulopathy (TIC) diagnostics, microfluidic assays allow controlled hemodynamics for testing of platelet and coagulation function using whole blood. Methods Hemodilution or hyperfibrinolysis was studied under flow with modified healthy whole blood. Furthermore, platelet function was also measured using whole blood from trauma patients admitted to a Level 1 Trauma center. Platelet deposition was measured with PPACK-inhibited blood perfused over collagen surfaces at a wall shear rate of 200 s−1, while platelet/fibrin deposition was measured with corn trypsin inhibitor (CTI)-treated blood perfused over TF/collagen. Results In hemodilution studies, PPACK-treated blood displayed almost no platelet deposition when diluted to 10% Hct with saline, platelet poor plasma (PPP), or platelet rich plasma (PRP). Using similar dilutions, platelet/fibrin deposition was essentially absent for CTI-treated blood perfused over TF/collagen. To mimic hyperfibrinolysis during trauma, exogenous tPA (50 nM) was added to blood prior to perfusion over TF/collagen. At both venous and arterial flows, the generation and subsequent lysis of fibrin was detectable within 6 min, with lysis blocked by addition of the plasmin inhibitor, ε-aminocaproic acid. Microfluidic assay of PPACK-inhibited whole blood from trauma patients revealed striking defects in collagen response and secondary platelet aggregation in 14 of 21 patients, while platelet hyperfunction was detected in 3 of 20 patients. Conclusions Rapid microfluidic detection of (i) hemodilution-dependent impairment of clotting, (ii) clot instability due to lysis, (iii) blockade of fibrinolysis, or (iv) platelet dysfunction during trauma may provide novel diagnostic opportunities to predict TIC risk. Level of Evidence Level IV Study type Diagnostic Test PMID:27082706

  5. Isolation of Platelet-Derived Extracellular Vesicles. (United States)

    Aatonen, Maria; Valkonen, Sami; Böing, Anita; Yuana, Yuana; Nieuwland, Rienk; Siljander, Pia


    Platelets participate in several physiological functions, including hemostasis, immunity, and development. Additionally, platelets play key roles in arterial thrombosis and cancer progression. Given this plethora of functions, there is a strong interest of the role of platelet-derived (extracellular) vesicles (PDEVs) as functional mediators and biomarkers. Moreover, the majority of the blood-borne EVs are thought to originate from either platelets or directly from the platelet precursor cells, the megakaryocytes, which reside in the bone marrow. To circumvent confusion, we use the term PDEVs for both platelet-derived and/or megakaryocyte-derived EVs. PDEVs can be isolated from blood or from isolated platelets after activation. In this chapter, we describe all commonly used PDEV isolation methods from blood and prepurified platelets.

  6. Effect of platelet age on adhesiveness to collagen and platelet surface charge

    Energy Technology Data Exchange (ETDEWEB)

    Castellan, R.M.; Steiner, M.


    Adhesion to collagen was investigated as a function of platelet age in rat platelets. Platelet adherence was measured using EDTA-containing platelet- rich plasma which was added to preparations of collagen fibers clamped between magnetic stirrers by recording changes in light transmission. The plot of light transmission versus logarithm of time was linear and allowed calculation of a slope factor which related to the rate of adherence. Neither the amount of collagen nor the platelet count were limiting in the test. Young platelet populations (less than or equal to 1 day old) were obtained during the recovery phase from immune induced thrombocytopenia. Old platelet populations were prepared by blocking thrombopoiesis with cyclophosphamide. Young platelets did not differ significantly from randomly aged platelets in this function. The electrophoretic mobility of platelets was not affected by their age.

  7. Platelet-rich plasma releasate differently stimulates cellular commitment toward the chondrogenic lineage according to concentration (United States)

    Matsiko, Amos; Tomazette, Marcel RP; Rocha, Wanessa KR; Cordeiro-Spinetti, Eric; Levingstone, Tanya J; Farina, Marcos; O’Brien, Fergal J; El-Cheikh, Marcia C; Balduino, Alex


    Platelet-rich plasma has been used to treat articular cartilage defects, with the expectations of anabolic and anti-inflammatory effects. However, its role on cellular chondrogenic or fibrogenic commitment is still a controversy. Herein, the role of platelet-rich plasma releasate, the product obtained following platelet-rich plasma activation, on cellular commitment toward the chondrogenic lineage was evaluated in vitro. Human nasoseptal chondrogenic cells and human bone marrow mesenchymal stromal cells were used as cell types already committed to the chondrogenic lineage and undifferentiated cells, respectively, as different concentrations of platelet-rich plasma releasate were tested in comparison to commonly used fetal bovine serum. Low concentration of platelet-rich plasma releasate (2.5%) presented similar effects on cellular growth compared to 10% fetal bovine serum, for both cell types. In a three-dimensional culture system, platelet-rich plasma releasate alone did not induce full nasoseptal chondrogenic cells cartilage-like pellet formation. Nonetheless, platelet-rich plasma releasate played a significant role on cell commitment as high-passage nasoseptal chondrogenic cells only originated cartilage-like pellets when expanded in the presence of platelet-rich plasma releasate rather than fetal bovine serum. Histological analyses and measurements of pellet area demonstrated that even low concentrations of platelet-rich plasma releasate were enough to prevent nasoseptal chondrogenic cells from losing their chondrogenic potential due to in vitro expansion thereby promoting their recommitment. Low concentration of platelet-rich plasma releasate supplemented in chondrogenic medium also increased the chondrogenic potential of mesenchymal stromal cells seeded on collagen-hyaluronic acid scaffolds, as observed by an increase in chondrogenic-related gene expression, sulfated glycosaminoglycan production, and compressive modulus following in vitro culture. On the

  8. Protein degradation systems in platelets. (United States)

    Kraemer, B F; Weyrich, A S; Lindemann, S


    Protein synthesis and degradation are essential processes that allow cells to survive and adapt to their surrounding milieu. In nucleated cells, the degradation and/or cleavage of proteins is required to eliminate aberrant proteins. Cells also degrade proteins as a mechanism for cell signalling and complex cellular functions. Although the last decade has convincingly shown that platelets synthesise proteins, the roles of protein degradation in these anucleate cytoplasts are less clear. Here we review what is known about protein degradation in platelets placing particular emphasis on the proteasome and the cysteine protease calpain.

  9. Genetics Home Reference: gray platelet syndrome (United States)

    ... with the autosomal dominant form of gray platelet syndrome . Related Information What does it mean if a disorder seems to run in my ... Hemophilia Federation of America Platelet Disorder Support Association World Federation of Hemophilia ... GRAY PLATELET SYNDROME Sources for This Page Albers CA, Cvejic A, ...

  10. Platelet function testing in pediatric patients

    DEFF Research Database (Denmark)

    Hvas, Anne-Mette; Favaloro, Emmanuel J


    Introduction: Platelets play a key role in primary hemostasis and are also intricately linked to secondary hemostasis. Investigation of platelet function in children, especially in neonates, is seriously challenged by the volumes required to perform the majority of platelet function tests and due...

  11. Platelet-rich plasma combined with intralesional triamcinolone acetonide for the treatment of alopecia areata: A case report

    Directory of Open Access Journals (Sweden)

    Thamer Mubki


    Full Text Available Treatment of long standing alopecia areata can be extremely difficult. Combining more than one treatment modality may be needed. Promising results have been previously reported using platelet-rich plasma. However, combining this treatment modality with other therapies has never been evaluated. We report a patient with long standing alopecia areata treated with a combination of triamcinolone acetonide and platelet-rich plasma intradermal injections. The trial was performed in a half-head design. One half of the scalp was treated with both platelet-rich plasma and intralesional triamcinolone acetonide. The other half received intralesional triamcinolone acetonide only. The half head treated with the combined therapy showed more regrowing hairs and larger hair fiber diameter. Our limited findings suggest that combining platelet-rich plasma with intradermal triamcinolone acetonide may have a positive synergistic effect for treating alopecia areata. Controlled studies with a large number of patients are needed.

  12. Platelet aggregates and ADP-induced platelet aggregation in ...

    African Journals Online (AJOL)

    Hypertension is a condition characterized by haemodynamic vascular stress and abnormal blood flow under high pressure and it is associated with complications that are, paradoxically, thrombotic rather than haemorrhagic. Spontaneous platelet aggregation has been known to be present in hypertension which predicts ...

  13. Temel Tepki Öğretimi-TTÖ (Pivotal Response Treatment-PRT İle Gerçekleştirilen Etkililik Araştırmalarının Betimsel Analizi

    Directory of Open Access Journals (Sweden)



    Full Text Available Temel Tepki Öğretimi (TTÖ Amerika Ulusal Otizm Merkezi (NAC, 2009 tarafından yayınlanmış olan Ulusal Standartlar Raporun’da otizmli çocukların eğitimde kullanılan bilimsel dayanaklı uygulamalardan bir tanesi olarak kabul edilmektedir. TTÖ hem uygulamalı davranış analizi ilkelerine dayanan hem de doğal bir öğretim yöntemidir. Yöntem öğrenci merkezli ve aile eğitimi esaslı olup çocuklara belli temel davranışları kazandırmayı ve buna bağlı olarakta hedeflenmeyen başka alanlarda da ilerlemeler sağlanacağını savunur. Bu çalışmada TTÖ’ne yönelik bir alan yazın çalışması amaçlanmış ve bu amaçla 1995 ile 2011 yılları arasında TTÖ ile gerçekleştirilmiş olan 16 etkililik araştırmasına ulaşılarak bu araştımalar betimsel olarak analiz edilmiştir. Elde edilen bulgular TTÖ’nün okul öncesi ve ilköğretim dönemindeki otizm spektrum bozukluğu gösteren çocuklara ifade edici dil becerilerinin kazandırılmasında, sosyal becerilerin ve oyun becerilerinin öğretiminde etkili olduğunu göstermektedir Pivotal Response Treatment (PRT is one of evidence based treatments identified in the US National Autism Center's National Standards Report published in 2009. PRT is a comprehensive instructional model based on developmental approach and applied behavior analysis principles to provide learning opportunities for supporting children in their natural environments. PRT is a student-centered and parent-training based procedure and advocates that if children achieve some pivotal behaviors, it provides positive effects on untargeted behaviors and also if these pivotal behaviors are achieved once, results will be common and generalizable. The purpose of this study is, by using descriptive analysis, to review the sixteen effectiveness studies of PRT published in 1995-2011. Results of review showed that PRT is an effective procedure on language skills, social skills and play skills of preschool and

  14. Platelet count and platelet indices in women with preeclampsia

    Directory of Open Access Journals (Sweden)

    AlSheeha MA


    Full Text Available Muneera A AlSheeha,1 Rafi S Alaboudi,1 Mohammad A Alghasham,1 Javed Iqbal,2 Ishag Adam1 1Department of Obstetrics and Gynaecology, College of Medicine, Qassim University, Buriadah, 2Department of Obstetrics and Gynecology, Maternity and Children’s Hospital, Qassim, Kingdom of Saudi Arabia Background: Although the exact pathophysiology of preeclampsia is not completely understood, the utility of different platelets indices can be utilized to predict preeclampsia.Objective: To compare platelet indices, namely platelet count (PC, mean platelet volume (MPV, platelet distribution width (PDW, and PC to MPV ratio in women with preeclampsia compared with healthy controls.Setting: Qassim Hospital, Kingdom of Saudi Arabia.Design: A case–control study. Sixty preeclamptic women were the cases and an equal number of healthy pregnant women were the controls.Results: There was no significant difference in age, parity, and body mass index between the study groups. Sixteen and 44 of the cases were severe and mild preeclampsia, respectively. There was no significant difference in PDW and MPV between the preeclamptic and control women. Both PC and PC to MPV ratios were significantly lower in the women with preeclampsia compared with the controls. There was no significant difference in the PC, PDW, MPV, and PC to MPV ratio when women with mild and severe preeclampsia were compared. Using receiver operating characteristic (ROC curves, the PC cutoff was 248.0×103/µL for diagnosis of preeclampsia (P=0.019; the area under the ROC curve was 62.4%. Binary regression suggests that women with PC <248.010×103/µL were at higher risk of preeclampsia (odds ratio =2.2, 95% confidence interval =1.08–4.6, P=0.03. The PC/MPV cutoff was 31.2 for diagnosis of preeclampsia (P=0.035, the area under the ROC curve was 62.2%.Conclusion: PC <248.010×103/µL and PC to MPV ratio 31.2 are valid predictors of preeclampsia. Keywords: preeclampsia, platelets, PDW, mean platelet

  15. Effect of ionizing radiation on platelet function in vitro

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    Kalovidouris, A.E.; Papayannis, A.G. (Evangelismos Hospital, Athens (Greece))


    The effect of ionizing radiation on platelet function was investigated in vitro. Platelet-rich plasma (300x10/sup 9//l) was irradiated with doses of 1, 4, 10, 20 and 50 Gy. Platelet function tests were performed on both irradiated and control (non-irradiated) platelet samples. The platelet function tests were (1) platelet aggregation by ADP (1, 2, 4 final concentration), adrenaline and collagen, (2) ADP-release from platelets, (3) clot retraction and (4) platelet factor-3 availability. It was found that roentgen irradiation of platelets in vitro did not affect these platelet function tests.

  16. Platelet count and platelet indices in women with preeclampsia. (United States)

    AlSheeha, Muneera A; Alaboudi, Rafi S; Alghasham, Mohammad A; Iqbal, Javed; Adam, Ishag


    Although the exact pathophysiology of preeclampsia is not completely understood, the utility of different platelets indices can be utilized to predict preeclampsia. To compare platelet indices, namely platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), and PC to MPV ratio in women with preeclampsia compared with healthy controls. Qassim Hospital, Kingdom of Saudi Arabia. A case-control study. Sixty preeclamptic women were the cases and an equal number of healthy pregnant women were the controls. There was no significant difference in age, parity, and body mass index between the study groups. Sixteen and 44 of the cases were severe and mild preeclampsia, respectively. There was no significant difference in PDW and MPV between the preeclamptic and control women. Both PC and PC to MPV ratios were significantly lower in the women with preeclampsia compared with the controls. There was no significant difference in the PC, PDW, MPV, and PC to MPV ratio when women with mild and severe preeclampsia were compared. Using receiver operating characteristic (ROC) curves, the PC cutoff was 248.0×10 3 /µL for diagnosis of pre-eclampsia ( P =0.019; the area under the ROC curve was 62.4%). Binary regression suggests that women with PC preeclampsia (odds ratio =2.2, 95% confidence interval =1.08-4.6, P =0.03). The PC/MPV cutoff was 31.2 for diagnosis of preeclampsia ( P =0.035, the area under the ROC curve was 62.2%). PC preeclampsia.

  17. Platelets (thrombocytes: The other recognized functions

    Directory of Open Access Journals (Sweden)

    Nikolić Ljubinka I.


    Full Text Available Introduction: Platelets are smallest blood cells of discoid or round shape and are cytoplasmic fragments of megakaryocytes. Platelets consist of 3 types of granules: alpha granules, dense granules and lysosomes. Granule secretion releases coagulation factors, growth factors, cytokines, and a number of proteolytic enzymes. Platelets contain a number of receptors known as platelet agonists. Basic and most studied role of platelets is in hemostasis process. The aim of this paper is to point on platelet function unrelated to hemostasis. Matherials and methods: Papers on other recognized functions of platelets were searched for in biomedical journals idexed in MEDLINE form 2004 to 2016. Topic: This paper studies less known platelet functions becoming subject of interest with the development of applied science. Platelets participate in inflammation by releasing proinflammatory mediators (CD154, CD40L. Complement activation via Pselectin, platelet-generates immunomodulatory effect. CD40L accelerates releasing RANTES protein leading to intensified activation of T-lymphocytes. During embryonic development, platelets allow blood and lymph vessels separation by activating CLE-2 receptor and ligand PDPN. Platelets alleviate migration and invasiveness of tumor cells, contribute to disease progression and development of metastases. Platelets affect maturation of follicles and oocytes and have important role in embryo implantation process and placentation. Conclusion: Based on these findings, conclusion imposes platelets as not only active participants in the hemostasis process but as having significant role in inflammation, unspecified and specified body defending, tumor biology, embryonic development and in female reproductive system regulation. Numerous roles of platelets open wide range for the new drugs' operation. Their specific characteristic is the basis for the personalized Clinical pharmacology development and possibility of applying specific drug as

  18. Prognostic significance of platelet count in SLE patients. (United States)

    Abdel Galil, Sahar Mahfouz; Edrees, Azzahra Mohammed; Ajeeb, Afnan Khaled; Aldoobi, Ghadeer Sameer; El-Boshy, Mohamed; Hussain, Waleed


    Hematological abnormalities, especially thrombocytopenia (TCP), are highly prevalent among patients with systemic lupus erythematosus (SLE) and at the same time it has been reported as a significant prognostic factor of SLE course. We further investigate the correlation between platelet count and the clinical manifestations and disease activity of SLE, in a cohort of Saudi Arabian female patients. A retrospective analysis was done for the medical records of 100 SLE female patients, selected from all patients diagnosed and treated for SLE at the Rheumatology outpatient clinics in Hera'a General Hospital, Holly Makkah, Saudi Arabia. The data collected from every patient's file included laboratory investigations (complete blood count, platelet parameters, ESR, anti-double-stranded DNA antibody, ANA), clinical manifestations, as well as SLE disease activity index (SLEDAI-2k) scores throughout a period of six sequential follow-up visits. Patients were divided into three groups according to the SLEDAI-2k: mild, moderate, and high-activity group. We found that, out of 100 patients, TCP was the most prevalent hematological abnormality evident in 15%, more than leucopenia (14%) and anemia (2%). TCP was acute in onset and associated with arthritis, neurologic manifestations, and nephritis. Platelet count showed a significant negative correlation with disease activity, in all of the three groups of patients. We concluded that platelet count has a negative correlation with disease activity in SLE patients, whatever the associated manifestations, and it should be considered as a prognostic factor, identifying patients with aggressive disease course.

  19. Platelet reactivity and cardiovascular events

    NARCIS (Netherlands)

    Snoep, Jacob Daniël


    Cardiovascular disease are a leading cause of mortality and morbidity in the Western world. Platelets play an important role in the development of cardiovascular disease, not only in the acute onset of thrombosis after atherosclerotic plaque rupture but also in the initiation and progression of

  20. Inhibition of Platelet Aggregation by the Leaf Extract of Carica papaya During Dengue Infection: An In Vitro Study. (United States)

    Chinnappan, Shobia; Ramachandrappa, Vijayakumar Shettikothanuru; Tamilarasu, Kadhiravan; Krishnan, Uma Maheswari; Pillai, Agiesh Kumar Balakrishna; Rajendiran, Soundravally


    Dengue cases were reported to undergo platelet activation and thrombocytopenia by a poorly understood mechanism. Recent studies suggested that Carica papaya leaf extract could recover the platelet count in dengue cases. However, no studies have attempted to unravel the mechanism of the plant extract in platelet recovery. Since there are no available drugs to treat dengue and considering the significance of C. papaya in dengue treatment, the current study aimed to evaluate two research questions: First one is to study if the C. papaya leaf extract exerts its action directly on platelets and second one is to understand if the extract can specifically inhibit the platelet aggregation during dengue viral infection. Sixty subjects with dengue positive and 60 healthy subjects were recruited in the study. Platelet-rich plasma (PRP) and platelet-poor plasma were prepared from both the dengue-infected and healthy control blood samples. Effect of the leaf extract obtained from C. papaya leaves was assessed on plasma obtained as well as platelets collected from both healthy and dengue-infected individuals. Platelet aggregation was significantly reduced when leaf extract preincubated with dengue plasma was added into control PRP, whereas no change in aggregation when leaf extract incubated-control plasma was added into control PRP. Upon direct addition of C. papaya leaf extract, both dengue PRP and control PRP showed a significant reduction in platelet aggregation. Within the dengue group, PRP from severe and nonsevere cases showed a significant decrease in aggregation without any difference between them. From the study, it is evident that C. papaya leaf extract can directly act on platelet. The present study, the first of its kind, found that the leaf extract possesses a dengue-specific neutralizing effect on dengue viral-infected plasma that may exert a protective role on platelets.

  1. Effects of isotretinoin on the inflammatory markers and the platelet counts in patients with acne vulgaris. (United States)

    Seçkin, Havva Yıldız; Baş, Yalçın; Takçı, Zennure; Kalkan, Göknur


    Oral isotretinoin is an efficient treatment used commonly in treating the moderate and severe acne. It has various side effects that affect many systems in the body. In this study, we are planning to examine the possible effects of the oral isotretinoin on platelet density, mean platelet volume, neutrophil lymphocyte rate, platelet lymphocyte rate, and red-blood-cell distribution width level. Twenty-eight males and 84 females, 112 patients in total, diagnosed with acne vulgaris and receiving oral isotretinoin treatment were examined retrospectively. The full blood parameters of the patients before the treatment and in the third month of the treatment were recorded. A statistically meaningful increase was observed in the platelet density, hemoglobin levels. And a statistically significant decrease has been determined in the red-blood-cell distribution width level while no meaningful differences were detected in the mean platelet volume, neutrophil lymphocyte rate, platelet lymphocyte rate, and white blood cell count. The oral isotretinoin treatment has been demonstrated as having increased the platelet density, hemoglobin levels and having decreased red-blood-cell distribution width level significantly.

  2. Nanoparticles camouflaged in platelet membrane coating as an antibody decoy for the treatment of immune thrombocytopenia. (United States)

    Wei, Xiaoli; Gao, Jie; Fang, Ronnie H; Luk, Brian T; Kroll, Ashley V; Dehaini, Diana; Zhou, Jiarong; Kim, Hyeon Woo; Gao, Weiwei; Lu, Weiyue; Zhang, Liangfang


    Immune thrombocytopenia purpura (ITP) is characterized by the production of pathological autoantibodies that cause reduction in platelet counts. The disease can have serious medical consequences, leading to uncontrolled bleeding that can be fatal. Current widely used therapies for the treatment of ITP are non-specific and can, at times, result in complications that are more burdensome than the disease itself. In the present study, the use of platelet membrane-coated nanoparticles (PNPs) as a platform for the specific clearance of anti-platelet antibodies is explored. The nanoparticles, whose outer layer displays the full complement of native platelet surface proteins, act as decoys that strongly bind pathological anti-platelet antibodies in order to minimize disease burden. Here, we study the antibody binding properties of PNPs and assess the ability of the nanoparticles to neutralize antibody activity both in vitro and in vivo. Ultimately, we leverage the neutralization capacity of PNPs to therapeutically treat a murine model of antibody-induced thrombocytopenia and demonstrate considerable efficacy as shown in a bleeding time assay. PNPs represent a promising platform for the specific treatment of antibody-mediated immune thrombocytopenia by acting as an alternative target for anti-platelet antibodies, thus preserving circulating platelets with the potential of leaving broader immune function intact. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Non-enzymatic quantification of polyphosphate levels in platelet lysates and releasates. (United States)

    Schlagenhauf, Axel; Pohl, Sina; Haidl, Harald; Leschnik, Bettina; Gallistl, Siegfried; Muntean, Wolfgang


    Inorganic polyphosphate has been shown to be shed upon platelet activation inducing prothrombotic stimuli on the coagulation system. Several methods have been published to detect and quantify polyphosphate in various cells and tissues, but evaluation of platelet content has only been achieved by indirect detection of orthophosphate after enzymatic digestion, thus, relying heavily on specificity of an exopolyphosphatase that is not commercially available. We present a non-enzymatic method for quantification of platelet-derived polyphosphate featuring optimized extraction on silica spin-columns, followed by specific fluorescence detection using DAPI. This allowed us to quantify polyphosphate in platelet lysates, but also in releasates of TRAP-activated platelets for the first time. Extraction of exogenous polyphosphate from buffer and sample matrices resulted in quantitative yields while removing matrix effects observed with direct fluorescence detection. Treatment of eluted fractions with phosphatase completely abrogated polyphosphate-specific fluorescence arguing for no additional compounds influencing the fluorescence detection. This was confirmed by no change in fluorescence intensity in samples previously treated with DNase and RNase. Taken together, we developed a robust and easily standardizable method to quantify polyphosphate in platelet lysates and releasates that will facilitate polyphosphate related investigations of platelet physiology and coagulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Novel direct factor Xa inhibitory compounds from Tenebrio molitor with anti-platelet aggregation activity. (United States)

    Lee, Wonhwa; Kim, Mi-Ae; Park, InWha; Hwang, Jae Sam; Na, MinKyun; Bae, Jong-Sup


    Tenebrio molitor is an edible insect that has antimicrobial, anticancer, and antihypertensive effects. The aim of this study was to identify the unreported bioactive compounds from T. molitor larvae with inhibitory activities against factor Xa (FXa) and platelet aggregation. Isolated compounds were evaluated for their anti-FXa and anti-platelet aggregation properties by monitoring clotting time, platelet aggregation, FXa activity, and thrombus formation. A diketopiperazine (1, cyclo(L-Pro-L-Tyr)) and a phenylethanoid (2, N-acetyltyramine) were isolated and inhibited the catalytic activity of FXa in a mixed inhibition model and inhibited platelet aggregation induced by adenosine diphosphate (ADP) and U46619. They inhibited ADP- and U46619-induced phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) and the expression of P-selectin and PAC-1 in platelets. They also improved the production of nitric oxide and inhibited the oversecretion of endothelin-1 compared to that of the ADP- or U46619-treated group. In an animal model of arterial and pulmonary thrombosis, the isolated compounds showed enhanced antithrombotic effects. They also elicited anticoagulant effects in mice. Compounds 1-2 inhibited ADP-, collagen-, or U46619-induced platelet aggregation and showed similar anti-thrombotic efficacy to rivaroxaban, a positive control. Therefore, 1-2 could serve as candidates and provide scaffolds for the development of new anti-FXa and anti-platelet drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Modulation of platelet membrane function via exogenous lipid moiety exposure alters platelet responsiveness to shear. (United States)

    Leung, S L; Dimasi, A; Heiser, S; Dunn, A; Bluestein, D; Slepian, M


    Shear-induced platelet activation may cause life-threatening thrombosis, particularly in patients with mechanical support devices or coronary atherosclerosis. The majority of present anti-platelet agents target or interfere with biochemical, rather than physical mechanisms of platelet activation. Less data and understanding exists with regard to pharmacologic modulation of shear-mediated platelet activation. In this work, we hypothesized that modulating cell membrane properties, via alteration of membrane composition through addition of exogenous lipid moieties, would alter platelet responsiveness to shear. Here we tested fatty acids, lecithin and cholesterol as additive lipid compounds. We demonstrated that incorporation of fatty acids (DHA/EPA) or lecithin into the platelet membrane triggered enhanced sensitivity of platelets to shear-mediated activation. On the other hand, cholesterol incorporation provides significant protection, limiting the effect of shear on platelet activation. These findings provide valuable insight for the development of therapeutic strategies that can modulate shear-mediated platelet activation.

  6. Platelet dysfunction and inhibition of multiple electrode platelet aggregometry caused by penicillin

    Directory of Open Access Journals (Sweden)

    von Beckerath Nicolas


    Full Text Available Abstract Beta-lactam antibiotics, e.g. penicillin, may inhibit platelet function and lead to reduced response in light transmission aggregometry and adhesion. However, influence on platelet function tests more commonly used in clinical practice, such as multiple electrode platelet aggregometry (MEA, have not been described so far. We report a case of a patient with local streptococcus infection. Treatment with penicillin resulted in mild bleeding tendency after 3 days. While coagulation parameters were normal, assessment of platelet function by MEA revealed strong platelet inhibition of both ADP and arachidonic acid induced platelet aggregation comparable to normal responders to antiplatelet therapy. Change of antibiotic regime resulted in recovery of platelet function. Thus, penicillin therapy may impact on platelet function and consecutively commonly used platelet function assays, e.g. MEA.

  7. Role of platelet transfusion in children with bleeding in dengue fever. (United States)

    Pothapregada, Sriram; Kamalakannan, Banupriya; Thulasingam, Mahalakshmy


    in children with severe dengue infection in the form of significant spontaneous bleed, shock and severe thrombocytopenia. Bleeding should not be considered only indicator to transfuse platelets as it occurred in children even with normal platelet counts. The community and treating physicians should be educated regarding the judicious transfusion of platelets. Unnecessary and empirical use of platelets should be completely avoided especially during an epidemic when there is scarcity in its availability.

  8. Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury

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    Giantsoudi, Drosoula; Sethi, Roshan V. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Yeap, Beow Y. [Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts (United States); Eaton, Bree R. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Ebb, David H. [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); Caruso, Paul A.; Rapalino, Otto [Department of Radiology (O.R.) at the Massachusetts General Hospital, Boston, Massachusetts (United States); Chen, Yen-Lin E.; Adams, Judith A.; Yock, Torunn I.; Tarbell, Nancy J.; Paganetti, Harald [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); MacDonald, Shannon M., E-mail: [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)


    Background: Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. Methods and Materials: We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. Results: At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). Conclusions: Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET.

  9. Organization of the actin cytoskeleton of resting and activated platelets in suspension. (United States)

    Escolar, G; Krumwiede, M; White, J G


    The present study has employed lysine, phalloidin, and a low concentration of osmic acid to protect the actin cytoskeleton of resting and thrombin-activated platelets during detergent extraction and fixation in suspension. Thin sections of resting platelets revealed a fine amorphous layer containing a few short actin filaments mimicking discoid shape and a randomly dispersed network of actin polymers in the cytoplasm. Following thrombin activation, the cytoskeleton consisted of a peripheral layer of submembrane actin filaments following the contour of shape change, a variable number of filaments in peripheral cytoplasm and extending into pseudopods, and a concentric mass of actin filaments with constricted microtubule rings in cell centers. Prior treatment with cytochalasin B (CB) appeared to reduce the number of actin filaments in resting platelets. Thrombin activation of CB-treated cells resulted in separation of actin filaments, which became concentrated in cell centers, from microtubule coils remaining at the cell periphery. The appearance of detergent-extracted cytoskeletons of platelet actin protected during fixation in suspension by lysine and phalloidin was remarkably similar to that of resting or CB-treated platelets before and after thrombin activation when viewed in conventionally prepared thin sections without exposure to detergent during fixation. The advantage of the new procedure is revelation of the actin filament organization in suspended platelets, which is obscured by the usual glutaraldehyde-osmic acid fixation technique.

  10. Platelet-rich plasma as treatment for persistent ocular epithelial defects. (United States)

    Ronci, Corrado; Ferraro, Angelo Salvatore; Lanti, Alessandro; Missiroli, Filippo; Sinopoli, Silvia; Del Proposto, Gianpaolo; Cipriani, Chiara; De Felici, Cecilia; Ricci, Federico; Ciotti, Marco; Cudillo, Laura; Arcese, William; Adorno, Gaspare


    Platelet- rich plasma (PRP) exhibits regenerative proprieties in wound healing but the biochemical mechanisms are unclear. In this study, autologous PRP with a mean value of 338 × 10(3) platelets/µL was used to treat corneal lesions of different aetiology, while homologous PRP with 1 × 10(6) platelets/µL was used to treat cornel lesions induced by a graft versus host disease. The impact of platelet count on the levels of PDGF AA and BB, VEGF, and EGF in the two PRPs was evaluated after a cycle of freezing/thawing. Treated corneal lesions healed or improved. The levels of PDGF AA and BB, VEGF, and EGF in the autologous PRP raised from 296 ± 61; 201.8 ± 24; 53 ± 14 and 8.9 ± 2 to 1017 ± 253; 924.7 ± 222; 101 ± 46.5 and 174 ± 15.5 pg/mL, while in the homologous PRP were 3.4, 4.5, 3.2 and 2 folds higher, respectively. High level of platelet counts seems not required to treat corneal lesions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Leukocyte and platelet changes following low-dose lipopolysaccharide administration in five dogs. (United States)

    Flatland, B; Fry, M M; LeBlanc, C J; Rohrbach, B W


    Effects of low-dose LPS (0.1 μg/kg i.v.) on leukocyte and platelet parameters measured using an Advia 120 hematology analyzer were investigated. Five dogs received a saline sham treatment prior to LPS, and blood was collected before and 3, 6, and 24 h post-treatment. LPS-treated dogs had mild neutrophil toxic change and increased neutrophil bands at 3 and 6 h. Compared to saline-treated controls, total leukocyte, neutrophil, and monocyte counts of LPS-treated dogs were significantly decreased at 3 h and increased at 24 h. Compared to baseline, total leukocyte counts of LPS-treated dogs were significantly decreased at 3 h and increased at 24 h. Mean platelet volume was significantly increased and mean platelet component concentration was decreased at 3 h compared to baseline. Platelet count was significantly decreased at 3 and 6 h; plateletcrit did not change significantly. High dosage is not required in order to detect LPS-mediated hematologic effects in dogs. Low-dose LPS administration causes significant changes in leukocyte and platelet indices in dogs without causing severe clinical signs or death. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Platelets rich plasma versus minoxidil 5% in treatment of alopecia areata: A trichoscopic evaluation. (United States)

    El Taieb, Moustafa A; Ibrahim, Hassan; Nada, Essam A; Seif Al-Din, Mai


    Alopecia areata is a common cause of nonscarring alopecia that occurs in a patchy, confluent, or diffuse pattern. Dermoscopy is a noninvasive technique for the clinical diagnosis of many skin diseases. Topical minoxidil solution 5% and platelet rich plasma are important modalities used in treatment of alopecia areata. We aimed to evaluate the efficacy of PRP versus topical minoxidil 5% in the treatment of AA by clinical evaluation and trichoscopic examination. Ninety patients were allocated into three groups; the first was treated with topical minoxidil 5% solution, the second with platelets rich plasma injections, and the third with placebo. Diagnosis and follow up were done by serial digital camera photography of lesions and dermoscopic scan before and every 1 month after treatment for 3 months. Patients treated with minoxidil 5% and platelets rich plasma both have significant hair growth than placebo (p < .05). Patients treated with platelets rich plasma had an earlier response in the form of hair regrowth, reduction in short vellus hair and dystrophic hair unlike patients treated with minoxidil and control (p < .05). In conclusion, platelets rich plasma is more effective in the treatment of alopecia areata than topical minoxidil 5% as evaluated by clinical and trichoscopic examination. © 2016 Wiley Periodicals, Inc.

  13. Platelet indices and platelet-to-lymphocyte ratio predict coronary chronic total occlusion in patients with acute ST-elevation myocardial infarction

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    Hadadi Laszlo


    Full Text Available Coronary chronic total occlusion (CTO is caused by organized thrombi or atherosclerotic plaque progression. The presence of a CTO is an independent predictor of mortality in patients presenting with ST-segment elevation myocardial infarction (STEMI. Platelets have a crucial role in the pathophysiology of atherosclerosis. The aim of this retrospective study was to investigate platelet indices as predictors of CTO in patients with STEMI treated with primary percutaneous coronary intervention (pPCI. A total number of 334 patients admitted for STEMI between January 2011 and December 2013 were included and divided in two groups based on the presence of CTO (48 patients in CTO+ group, 286 patients in CTO-group. Platelet count, mean platelet volume (MPV, platelet distribution width (PDW, platelet-large cell ratio (P-LCR, lymphocyte and neutrophil count determined on admission were analyzed. MPV was larger in patients with CTO compared with patients without CTO (p=0.02, as were PDW (p=0.03 and P-LCR (p=0.01. Platelet-to-lymphocyte ratio (PLT/LYM was lower in patients with CTO: 105.2 (75.86-159.1 compared to 137 (97-188.1, p<0.01. Receiver-operator characteristic curve analysis identified an area under the curve of 0.61 (95%CI=0.57-0.67, p< 0.01 for PLT/LYM in predicting the presence of a CTO, with a cut-off value at 97.73. Lower values than this were independent predictors of a CTO in multivariate logistic regression analysis, with an Odds Ratio of 2.2 (95%CI=1.15-4.20, p=0.02. Our results support the use of platelet indices and PLT/LYM as predictors of CTO in patients presenting with STEMI.

  14. Reversal of thienopyridine-induced platelet dysfunction following desmopressin administration. (United States)

    Levine, Michael; Swenson, Steve; McCormick, Taylor; Henderson, Sean O; Thomas, Stephen H; Markland, Francis S


    Adenosine diphosphate (ADP)-receptor antagonists are widely used for thrombus prevention, although reversing their platelet dysfunction is difficult. This study evaluated the ability of desmopressin to reverse clopidogrel-induced platelet dysfunction. Sprague-Dawley rats received either clopidogrel (30 mg/kg) or placebo, followed 4 h later by saline or desmopressin (0.15, 0.3, or 0.6 μg/kg). Bleeding times and platelet aggregation studies were subsequently performed. A bleeding time >25 min was considered "prolonged." The median bleeding time for clopidogrel-exposed rats was 21 min, vs. 6 min for controls (p < 0.01). Progressively higher doses of 1-deamino-8-D-arginine vasopressin (DDAVP) were associated with a reduced number of rats with prolonged bleeding time (p = 0.001). Higher doses of DDAVP were also associated with a reduction in the median (IQR) bleeding time; 29 (13.5-30) min in rats receiving clopidogrel without DDAVP vs. 19 (12-28) min in rats receiving clopidogrel and 0.6 μg/kg DDAVP. The step-wise dosing of DDAVP resulted in a 54 % reduction in meeting the endpoint of prolonged bleeding time (OR 0.46; p = 0.025; 95 % CI 0.23-0.91). Platelet aggregation was observed in all control rats, but only some of those clopidogrel-treated rats who received 0.6 μg/kg DDAVP. In this model of an ADP-receptor antagonist, DDAVP results in partial reversal of clopidogrel-induced platelet dysfunction.

  15. Anticoagulants and inhibitors of platelet aggregation derived from leeches. (United States)

    Salzet, M


    Increased life expectancy is associated with aging populations in the developed countries, and we can expect an increased incidence of cardiovascular and inflammatory diseases and cancers. A priority for medical research is to reduce such morbidity. Leeches have been demonstrated to be a useful source of drugs to treat cardiovascular diseases, as they have evolved highly specific mechanisms to feed on their hosts by blocking blood coagulation. Powerful molecules acting at different points in the coagulation cascade or in the inhibition of platelet aggregation have been purified from these animals. Moreover, clinical trials confirm their potential to treat cardiovascular diseases.

  16. The origin and function of platelet glycosyltransferases. (United States)

    Wandall, Hans H; Rumjantseva, Viktoria; Sørensen, Anne Louise Tølbøll; Patel-Hett, Sunita; Josefsson, Emma C; Bennett, Eric P; Italiano, Joseph E; Clausen, Henrik; Hartwig, John H; Hoffmeister, Karin M


    Platelets are megakaryocyte subfragments that participate in hemostatic and host defense reactions and deliver pro- and antiangiogenic factors throughout the vascular system. Although they are anucleated cells that lack a complex secretory apparatus with distinct Golgi/endoplasmic reticulum compartments, past studies have shown that platelets have glycosyltransferase activities. In the present study, we show that members of 3 distinct glycosyltransferase families are found within and on the surface of platelets. Immunocytology and flow cytometry results indicated that megakaryocytes package these Golgi-derived glycosyltransferases into vesicles that are sent via proplatelets to nascent platelets, where they accumulate. These glycosyltransferases are active, and intact platelets glycosylate large exogenous substrates. Furthermore, we show that activation of platelets results in the release of soluble glycosyltransferase activities and that platelets contain sufficient levels of sugar nucleotides for detection of glycosylation of exogenously added substrates. Therefore, the results of the present study show that blood platelets are a rich source of both glycosyltransferases and donor sugar substrates that can be released to function in the extracellular space. This platelet-glycosylation machinery offers a pathway to a simple glycoengineering strategy improving storage of platelets and may serve hitherto unknown biologic functions.

  17. Effects of Physical (Inactivity on Platelet Function

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    Stefan Heber


    Full Text Available As platelet activation is closely related to the liberation of growth factors and inflammatory mediators, platelets play a central role in the development of CVD. Virtually all cardiovascular risk factors favor platelet hyperreactivity and, accordingly, also physical (inactivity affects platelet function. Within this paper, we will summarize and discuss the current knowledge on the impact of acute and habitual exercise on platelet function. Although there are apparent discrepancies regarding the reported effects of acute, strenuous exercise on platelet activation, a deeper analysis of the available literature reveals that the applied exercise intensity and the subjects’ cardiorespiratory fitness represent critical determinants for the observed effects. Consideration of these factors leads to the summary that (i acute, strenuous exercise can lead to platelet activation, (ii regular physical activity and/or physical fitness diminish or prevent platelet activation in response to acute exercise, and (iii habitual physical activity and/or physical fitness also favorably modulate platelet function at physical rest. Notably, these effects of exercise on platelet function show obvious similarities to the well-recognized relation between exercise and the risk for cardiovascular events where vigorous exercise transiently increases the risk for myocardial infarction and a physically active lifestyle dramatically reduces cardiovascular mortality.

  18. Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. (United States)

    Mishra, Allan; Pavelko, Terri


    Elbow epicondylar tendinosis is a common problem that usually resolves with nonoperative treatments. When these measures fail, however, patients are interested in an alternative to surgical intervention. Treatment of chronic severe elbow tendinosis with buffered platelet-rich plasma will reduce pain and increase function in patients considering surgery for their problem. Cohort study; Level of evidence, 2. One hundred forty patients with elbow epicondylar pain were evaluated in this study. All these patients were initially given a standardized physical therapy protocol and a variety of other nonoperative treatments. Twenty of these patients had significant persistent pain for a mean of 15 months (mean, 82 of 100; range, 60-100 of 100 on a visual analog pain scale), despite these interventions. All patients were considering surgery. This cohort of patients who had failed nonoperative treatment was then given either a single percutaneous injection of platelet-rich plasma (active group, n = 15) or bupivacaine (control group, n = 5). Eight weeks after the treatment, the platelet-rich plasma patients noted 60% improvement in their visual analog pain scores versus 16% improvement in control patients (P =.001). Sixty percent (3 of 5) of the control subjects withdrew or sought other treatments after the 8-week period, preventing further direct analysis. Therefore, only the patients treated with platelet-rich plasma were available for continued evaluation. At 6 months, the patients treated with platelet-rich plasma noted 81% improvement in their visual analog pain scores (P =.0001). At final follow-up (mean, 25.6 months; range, 12-38 months), the platelet-rich plasma patients reported 93% reduction in pain compared with before the treatment (P platelet-rich plasma reduced pain significantly in this pilot investigation. Further evaluation of this novel treatment is warranted. Finally, platelet-rich plasma should be considered before surgical intervention.

  19. Allicin and disulfiram enhance platelet integrin alphaIIbbeta3-fibrinogen binding. (United States)

    Manaster, Yoav; Shenkman, Boris; Rosenberg, Nurit; Savion, Naphtali


    Activation of the platelet receptor alphaIIbbeta3 (glycoprotein IIbIIIa) involves a change in the disulfide bonds pattern in the extra-cellular domain of the receptor. The disulfide-bond reducing agent, dithiothreitol (DTT), can increase integrin activity, and point mutations of specific cysteine residues of the integrin can cause its lockage at the high affinity state. The present study is aimed to support the hypothesis that prevention of specific alphaIIbbeta3 intra-molecular disulfide bond formation increases receptor-ligand binding activity. Platelet aggregation was induced by collagen or ADP and epinephrine. Integrin alphaIIbbeta3-fibrinogen binding was evaluated on prostaglandins E(1) (PGE(1))-treated washed platelets or baby hamster kidney (BHK) cells expressing human alphaIIbbeta3. Integrin was directly activated by an anti-ligand induced binding site (LIBS) PT25-2 antibody. The effect of sulfhydryl-reactive agents, such as allicin, glutathione, dithiobis nitrobenzoic acid (DTNB) and disulfiram, was tested on alphaIIbbeta3 activity. Allicin (40 microM) completely inhibited washed platelets agonist-induced aggregation. Both allicin and disulfiram (40 microM) inhibited alphaIIbbeta3-fibrinogen binding and P-selectin expression in washed platelets. However, there was an increase in alphaIIbbeta3-fibrinogen binding but not P-selectin expression in PGE(1)-treated washed platelets activated by PT25-2 antibody. At a high concentration (400 microM) both inhibited alphaIIbbeta3-fibrinogen binding. Similarly, in BHK cells expressing alphaIIbbeta3 activated by PT25-2 antibody, allicin at a low concentration increased alphaIIbbeta3 activity. Allicin and disulfiram inhibit agonist-induced washed platelet activation probably via inhibition of platelet signaling, but enhance PT25-2 antibody-induced alphaIIbbeta3 integrin activity most likely by preventing reformation of disulfide bridges thereby stabilizing the active conformation of the integrin.

  20. Platelet activation patterns in platelet size sub-populations: differential responses to aspirin in vitro. (United States)

    Mangalpally, Kiran Kumar R; Siqueiros-Garcia, Alan; Vaduganathan, Muthiah; Dong, Jing-Fei; Kleiman, Neal S; Guthikonda, Sasidhar


    Circulating platelets are heterogeneous in size and structure. Whether this translates into differences in platelet function and efficacy of antiplatelet therapy is unclear. Hence, we decided to investigate the activation patterns among different platelet populations differentiated by size, and to compare the inhibitory effects of aspirin in these populations. Circulating platelets from 9 healthy volunteers were separated by size and stratified into the largest and smallest quintiles. Platelets were stimulated with 75 μM arachidonic acid (AA), 10 μM ADP or 25 μM TRAP. Alpha-granule protein secretion and expression (P-selectin, VWF, fibrinogen), surface-protein activation (activated integrin αIIbβ3) were assessed. Platelet thromboxane B(2) (TxB(2)) synthesis following AA stimulation was measured in vitro before and after incubation with 265 μM aspirin. Reticulated (juvenile) platelets were assessed using thiazole orange staining. A greater number of large platelets in the largest quintile were reticulated compared with the smallest quintile (6.1 ± 2.8% vs. 1.2 ± 1.5% respectively, p aspirin (1029 ± 190 pg/mL vs. 851 ± 159 pg/mL, respectively, p = 0.03). After stimulation with each agonist, a greater proportion of large platelets bound fibrinogen, VWF, P-selectin and activated integrin αIIbβ3 than small platelets both in the presence and in the absence of in vitro aspirin. In an in vitro setting, large platelets appear to be more active than small platelets and continue to be more active even after in vitro aspirin. Platelets exhibit heterogeneity in size and structure. Whether this translates into platelet function and efficacy of antiplatelet therapy is unclear. We evaluated platelet functional properties and the effects of aspirin on separated platelet subpopulations in an in vitro setting. Platelets were sorted into the largest and smallest size quintiles using flow cytometry forward scatter. Alpha-granule protein release, dense granule content

  1. Defining Platelet Function During Polytrauma (United States)


    by the VCU Reanimation Engineering Shock Center (VCURES) and will be coordinated by the departments of Emergency Medicine, Pharmacy , and Surgery... terminology used, platelets appear to play a critical role in the development of coagulopathy during early trauma and the later syndrome of... history will be used as criteria for initial study inclusion. ISS will not be used as entry criteria because knowledge of all injuries is required in

  2. Complement Activation Alters Platelet Function (United States)


    SUPPLEMENTARY NOTES 14. ABSTRACT We have established base line criteria that will allow us to evaluate the role of platelets during trauma. These studies...following IRI in a similar time frame. Further studies will evaluate if these factors co-localize in tissue. We have developed B6.lprPF4-/- mice which...vascular endothelium , with antigen presenting cells (APC) and with lymphocytes, or through the release of soluble mediators that include pro-inflammatory

  3. Importance of Endogenous Fibrinolysis in Platelet Thrombus Formation (United States)

    Gorog, Diana A.


    The processes of thrombosis and coagulation are finely regulated by endogenous fibrinolysis maintaining healthy equilibrium. When the balance is altered in favour of platelet activation and/or coagulation, or if endogenous fibrinolysis becomes less efficient, pathological thrombosis can occur. Arterial thrombosis remains a major cause of morbidity and mortality in the world despite advances in medical therapies. The role endogenous fibrinolysis in the pathogenesis of arterial thrombosis has gained increasing attention in recent years as it presents novel ways to prevent and treat existing diseases. In this review article, we discuss the role of endogenous fibrinolysis in platelet thrombus formation, methods of measurement of fibrinolytic activity, its role in predicting cardiovascular diseases and clinical outcomes and future directions. PMID:28841147

  4. Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets

    DEFF Research Database (Denmark)

    Pleines, Irina; Eckly, Anita; Elvers, Margitta


    Platelet activation at sites of vascular injury is crucial for hemostasis, but it may also cause myocardial infarction or stroke. Cytoskeletal reorganization is essential for platelet activation and secretion. The small GTPase Cdc42 has been implicated as an important mediator of filopodia...... formation and exocytosis in various cell types, but its exact function in platelets is not established. Here, we show that the megakaryocyte/platelet-specific loss of Cdc42 leads to mild thrombocytopenia and a small increase in platelet size in mice. Unexpectedly, Cdc42-deficient platelets were able to form...... normally shaped filopodia and spread fully on fibrinogen upon activation, whereas filopodia formation upon selective induction of GPIb signaling was reduced compared with wild-type platelets. Furthermore, Cdc42-deficient platelets showed enhanced secretion of alpha granules, a higher adenosine diphosphate...

  5. Does bipolar pacemaker current activate blood platelets?

    DEFF Research Database (Denmark)

    Gjesdal, Grunde; Hansen, Annebirthe Bo; Brandes, Axel


    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...... 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...

  6. Platelet activation and platelet-leukocyte interaction in generalized aggressive periodontitis. (United States)

    Zhan, Yalin; Lu, Ruifang; Meng, Huanxin; Wang, Xian'e; Hou, Jianxia


    Generalized aggressive periodontitis (GAgP) is an inflammatory disease of host response to bacterial challenge. To explore the role of platelets in host-microbial interactions in patients with periodontitis, 124 patients with GAgP and 57 healthy subjects were enrolled. Reliable indicators of subclinical platelet functional status, platelet count (PLT), platelet large cell ratio (PLCR), and mean platelet volume (MPV), were significantly lower in the GAgP group than in the control group and were negatively correlated with clinical periodontal parameters. The levels of important cytosolic protein in neutrophils, calprotectin (S100A8/A9) in plasma, and gingival crevicular fluid (GCF) were significantly higher in patients with GAgP compared with healthy subjects. Moreover, the GCF calprotectin level was negatively correlated with PLCR and MPV values. To explore the possible mechanisms of changes in platelet indices in periodontitis, flow cytometry analysis was performed, and patients with GAgP were found to have a higher status of platelet activation compared with healthy controls. Porphyromonas gingivalis (P. gingivalis) and recombinant human S100A8/A9 (rhS100A8/A9) induced platelet activation and facilitated platelet-leukocyte aggregate formation in whole blood of healthy subjects. In response to P. gingivalis and rhS100A8/A9, platelets from patients with GAgP increased activation and increased formation of platelet-leukocyte aggregates compared with those from healthy subjects. Platelet aggregates and platelets attached to leukocytes were found on gingival tissues from patients with GAgP, suggesting that decreased platelet size and count in the circulation might be related to consumption of large, activated platelets at inflamed gingiva. Platelets may have a previously unrecognized role in host response to periodontal infection. © Society for Leukocyte Biology.

  7. Cancer and Thrombotic Risk: The Platelet Paradigm


    Lee, Elizabeth C.; Cameron, Scott J.


    Hematologic malignancies and solid tumors increase the risk of venous and arterial thrombosis and contribute greatly to patient morbidity and mortality. Thrombosis occurs when the intricate balance of circulating antithrombotic and prothrombotic blood elements are disrupted. In recent years, the interplay between paraneoplastic cells and platelets has become apparent, with a change in platelet phenotype causing dysregulated platelet activity. This review discusses mechanism of thrombosis in c...


    Directory of Open Access Journals (Sweden)

    K. B. Mirzaev


    Full Text Available Evaluation of platelet function with subsequent modification of antiplatelet therapy regimen is one of the areas of personalized medicine. Analysis of the causes of inadequate antiplatelet action of clopidogrel, the association of residual platelet reactivity with clinical outcomes and a review of the research on the change of antiplatelet therapy in patients with ischemic heart disease after percutaneous interventions based on the results of platelet function testing, were the aim of this review.

  9. Blood platelet serotonin following enterectomy in rats. (United States)

    Osim, E E; Wyllie, J H


    The role of the intestine as a source of platelet serotonin was investigated. Radioactive serotonin precursor. 5-Hydroxytryptophan was injected into enterectomised and sham-operated rats. Blood samples were taken at time intervals and serotonin uptake was estimated by radioactive counting. Soon (1-2 hrs) after surgery and under sodium pentobarbital anaesthesia, platelet 5HT activity was higher in enterectomised rats than in controls. The intestine may not be the major source of platelet serotonin.

  10. Platelet aggregation and quality control of platelet concentrates produced in the Amazon Blood Bank

    Directory of Open Access Journals (Sweden)

    Maria José Dantas Coêlho


    Full Text Available BACKGROUND: The study of platelet aggregation is essential to assess in vitro platelet function by different platelet activation pathways. OBJECTIVE: To assess aggregation and biochemical parameters of random platelet concentrates produced at the Fundação HEMOAM using the quality control tests defined by law. METHODS: Whole blood samples from 80 donors and the respective platelet concentrate units were tested. Platelet concentrates were tested (platelet count, aggregation and pH on days 1, 3 and 5 of storage. Additionally a leukocyte count was done only on day 1 and microbiological tests on day 5 of storage. Collagen and adenosine diphosphate were used as inducing agonists for platelet aggregation testing. RESULTS: Donor whole blood had normal aggregation (aggregation with adenosine diphosphate = 67% and with collagen = 78%. The median aggregation in platelet concentrates with adenosine diphosphate was low throughout storage (18% on day 1, 7% on day 3 and 6% on day 5 and the median aggregation with collagen was normal only on day 1 and low thereafter (54.4% on day 1, 20.5% on day 3 and 9% on day 5. CONCLUSION: Although the results were within the norms required by law, platelet concentrates had low aggregation rates. We suggest the inclusion of a functional assessment test for the quality control of platelet concentrates for a more effective response to platelet replacement therapy.

  11. Platelet activation in type 2 diabetes mellitus

    National Research Council Canada - National Science Library

    Ferroni, P; Basili, S; Falco, A; Davì, G


    The abnormal metabolic state that accompanies diabetes renders arteries susceptible to atherosclerosis, being capable of altering the functional properties of multiple cell types, including endothelium and platelets...

  12. Platelets: pleiotropic roles in atherogenesis and atherothrombosis. (United States)

    Linden, Matthew D; Jackson, Denise E


    Platelets are small, anucleate blood elements of critical importance in cardiovascular disease. The ability of platelets to activate and aggregate to form blood clots in response to endothelial injury, such as plaque rupture, is well established. These cells are therefore important contributors to ischaemia in atherothrombosis, and antiplatelet therapy is effective for this reason. However, growing evidence suggests that platelets are also important mediators of inflammation and play a central role in atherogenesis itself. Interactions between activated platelets, leukocytes and endothelial cells trigger autocrine and paracrine activation signals, resulting in leukocyte recruitment at and into the vascular wall. Direct physical interaction may contribute also, through platelet adhesion molecules assisting localization of monocytes to the site of atherogenesis and platelet granule release contributing to the chronic inflammatory milieu which leads to foam cell development and accelerated atherogenesis. Recent studies have shown that antiplatelet therapy in animal models of accelerated atherogenesis can lead to decreased plaque size and improve plaque stability. This review examines the complexity of platelet function and the nature of interactions between activated platelets, leukocytes and endothelial cells. We focus on the growing body of evidence that platelets play a critical role in atherogenesis and contribute to progression of atherosclerosis. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Platelet transfusion for patients with cancer. (United States)

    Fletcher, Craig H; DomBourian, Melkon G; Millward, Peter A


    Platelet transfusion is a critical and often necessary aspect of managing cancer. Low platelet counts frequently lead to bleeding complications; however, the drugs used to combat malignancy commonly lead to decreased production and destruction of the very cell whose function is essential to stop bleeding. The transfusion of allogeneic platelet products helps to promote hemostasis, but alloimmunization may make it difficult to manage other complications associated with cancer. The literature relating to platelet transfusion in patients with cancer was reviewed. Platelet storage, dosing, transfusion indications, and transfusion response are essential topics for health care professionals to understand because many patients with cancer will require platelet transfusions during the course of treatment. The workup and differentiation of non-immune-mediated compared with immune-mediated platelet refractoriness are vital because platelet management is different between types of refractoriness. A combination of appropriate utilization of platelet inventory and laboratory testing coupled with communication between those caring for patients with cancer and those providing blood products is essential for effective patient care.

  14. Soluble fibrin causes an acquired platelet glycoprotein VI signaling defect: implications for coagulopathy. (United States)

    Lee, M Y; Verni, C C; Herbig, B A; Diamond, S L


    Essentials Collagen and thrombin when used simultaneously generate highly activated platelets. The effect of thrombin stimulation on subsequent glycoprotein VI (GPVI) function was observed. Soluble fibrin, but not protease activated receptor (PAR) activation, prevented GPVI activation. Circulating soluble fibrin in coagulopathic blood may cause an acquired GPVI signaling defect. Background In coagulopathic blood, circulating thrombin may drive platelet dysfunction. Methods/Results Using calcium dye-loaded platelets, the effect of thrombin exposure and soluble fibrin generation on subsequent platelet GPVI function was investigated. Exposure of apixaban-treated platelet-rich plasma (12% PRP) to thrombin (1-10 nm), but not ADP or thromboxane mimetic U46619 exposure, dramatically blocked subsequent GPVI activation by convulxin, collagen-related peptide or fibrillar collagen. Consistent with soluble fibrin multimerizing and binding GPVI, the onset of convulxin insensitivity required 200-500 s of thrombin exposure, was not mimicked by exposure to PAR-1/4 activating peptides, was not observed with washed platelets, and was blocked by fibrin polymerization inhibitor (GPRP) or factor XIIIa inhibitor (T101). PAR-1 signaling through Gαq was not required because vorapaxar blocked thrombin-induced calcium mobilization but had no effect on the ability of thrombin to impair GPVI-signaling. Convulxin insensitivity was unaffected by the metalloprotease inhibitor GM6001 or the αIIb β3 antagonist GR144053, indicating negligible roles for GPVI shedding or αIIb β3 binding of fibrin. Thrombin treatment of washed platelets resuspended in purified fibrinogen also produced convulxin insensitivity that was prevented by GPRP. Exposure of apixaban/PPACK-treated whole blood to thrombin-treated fibrinogen resulted in > 50% decrease in platelet deposition in a collagen microfluidic assay that required soluble fibrin assembly. Conclusions Conversion of only 1% plasma fibrinogen in

  15. A comparison of the pharmacological profiles of prasugrel and ticagrelor assessed by platelet aggregation, thrombus formation and haemostasis in rats (United States)

    Sugidachi, A; Ohno, K; Ogawa, T; Jakubowski, JA; Hashimoto, M; Tomizawa, A


    Background and Purpose Prasugrel is a third-generation thienopyridine prodrug and ticagrelor is a non-competitive P2Y12 receptor antagonist. In their phase 3 studies, both agents reduced rates of ischemic events relative to treatment with clopidogrel. Experimental Approach The pharmacodynamic profile of anti-platelet effects of prasugrel was compared with that of ticagrelor in rats. Key Results The active metabolite of prasugrel was less potent than ticagrelor and its active metabolite on platelet aggregation in vitro. In contrast, prasugrel was a more potent antiplatelet agent than ticagrelor on ex vivo platelet aggregation: their ED50 values at peak for ADP 20 μmol·L−1 were 1.9 and 8.0 mg·kg−1, respectively. Prasugrel's inhibition of platelet aggregation was maintained for up to 24 h after administration, but ticagrelor's duration of action was substantially shorter. Prasugrel and ticagrelor significantly inhibited thrombus formation with ED50 values of 1.8 and 7.7 mg·kg−1, respectively. Both agents also prolonged bleeding times (ED200 values of 3.0 and 13 mg·kg−1 respectively) suggesting that at equivalent levels of inhibition of platelet aggregation, the agents would show comparable antithrombotic activity with similar bleeding risk. Platelet transfusion significantly increased blood platelet numbers similarly in prasugrel- and ticagrelor-treated rats. In the prasugrel-treated group, platelet transfusion caused significant shortening of bleeding time, while in the ticagrelor-treated group, platelet transfusion showed no influence on bleeding time under the experimental conditions employed. Conclusions and Implications Prasugrel and ticagrelor showed several differences in their pharmacological profiles and these disparities may reflect their differing reversibility and/or pharmacokinetic profiles. PMID:23347039

  16. A comparison of the pharmacological profiles of prasugrel and ticagrelor assessed by platelet aggregation, thrombus formation and haemostasis in rats. (United States)

    Sugidachi, A; Ohno, K; Ogawa, T; Jakubowski, Ja; Hashimoto, M; Tomizawa, A


    Prasugrel is a third-generation thienopyridine prodrug and ticagrelor is a non-competitive P2Y12 receptor antagonist. In their phase 3 studies, both agents reduced rates of ischemic events relative to treatment with clopidogrel. The pharmacodynamic profile of anti-platelet effects of prasugrel was compared with that of ticagrelor in rats. The active metabolite of prasugrel was less potent than ticagrelor and its active metabolite on platelet aggregation in vitro. In contrast, prasugrel was a more potent antiplatelet agent than ticagrelor on ex vivo platelet aggregation: their ED50 values at peak for ADP 20 μmol·L(-1) were 1.9 and 8.0 mg·kg(-1) , respectively. Prasugrel's inhibition of platelet aggregation was maintained for up to 24 h after administration, but ticagrelor's duration of action was substantially shorter. Prasugrel and ticagrelor significantly inhibited thrombus formation with ED50 values of 1.8 and 7.7 mg·kg(-1) , respectively. Both agents also prolonged bleeding times (ED200 values of 3.0 and 13 mg·kg(-1) respectively) suggesting that at equivalent levels of inhibition of platelet aggregation, the agents would show comparable antithrombotic activity with similar bleeding risk. Platelet transfusion significantly increased blood platelet numbers similarly in prasugrel- and ticagrelor-treated rats. In the prasugrel-treated group, platelet transfusion caused significant shortening of bleeding time, while in the ticagrelor-treated group, platelet transfusion showed no influence on bleeding time under the experimental conditions employed. Prasugrel and ticagrelor showed several differences in their pharmacological profiles and these disparities may reflect their differing reversibility and/or pharmacokinetic profiles. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

  17. Relation between ticagrelor response and levels of circulating reticulated platelets in patients with non-ST elevation acute coronary syndromes. (United States)

    Vaduganathan, Muthiah; Zemer-Wassercug, Noa; Rechavia, Eldad; Lerman-Shivek, Hila; Perl, Leor; Leshem-Lev, Dorit; Orvin, Katia; Kornowski, Ran; Lev, Eli I


    Antiplatelet responses to clopidogrel and prasugrel are highly variable and subject to significant rates of high on-treatment platelet reactivity (HTPR) after percutaneous coronary intervention (PCI). The proportion of circulating young reticulated platelets (RPs) inversely correlates with responsiveness to both agents. We aimed to determine the relationship between RPs and on-treatment platelet reactivity in ticagrelor-treated patients. Patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) treated with PCI and ticagrelor were tested for platelet reactivity using the VerifyNow P2Y12 assay and multiplate aggregometry. RPs levels were determined using flow cytometry with thiazole orange staining. Tests were performed at 2-4 and 30 days post-PCI. Fifty three patients were included (mean age 62.6 ± 9.8 years, 18.9 % women, 35.8 % diabetes), of which 41 patients (77 %) completed follow-up. Variability in response to ticagrelor was very low according to both assays with no identified cases of HTPR at either time-point. In addition, there were no differences in platelet reactivity, as analyzed by the VerifyNow P2Y12 assay, or in the proportion of RPs between the two time points (p > 0.5). With the multiplate assay, platelet reactivity increased between the two time-points (8.6 ± 6.0 vs. 15.5 ± 11 AU*min; p = 0.0007). There was no significant correlation between RPs and platelet reactivity at both time-points and using both assays (p > 0.5). There were no cases of HTPR up to 30-days post-PCI in patients with NSTE-ACS treated with ticagrelor. In this cohort, no correlation between % RPs and platelet reactivity was observed. Attenuation of RP-induced platelet reactivity as a novel mechanism for ticagrelor's benefit requires further investigation.

  18. Platelet genomics and proteomics in human health and disease (United States)

    Macaulay, Iain C.; Carr, Philippa; Gusnanto, Arief; Ouwehand, Willem H.; Fitzgerald, Des; Watkins, Nicholas A.


    Proteomic and genomic technologies provide powerful tools for characterizing the multitude of events that occur in the anucleate platelet. These technologies are beginning to define the complete platelet transcriptome and proteome as well as the protein-protein interactions critical for platelet function. The integration of these results provides the opportunity to identify those proteins involved in discrete facets of platelet function. Here we summarize the findings of platelet proteome and transcriptome studies and their application to diseases of platelet function. PMID:16322782

  19. Localization of GPIb/IX and GPIIb/IIIa on Discoid Platelets. (United States)

    White, J G; Krumwiede, M D; Johnson, D K; Escolar, G


    The organization and reorganization of mobile receptors, GPIIb/IIIa and GPIb/IX, on surface- and suspension-activated platelets have been studied in detail, but their distribution on resting, discoid platelets is uncertain. The present study has treated platelets in suspension with cytochalasin E before mounting on formvar grids or glass slide fragments in order to preserve their discoid appearance, then probed the organization of GPIIb/IIIa with fibrinogen coupled to gold particles (Fgn/Au) and GPIb/IX with bovine or ristocetin-activated human plasma detected by combined anti-vWF antibody and protein A coupled to gold particles. Multimers of vWF had the same tortuous, linear distribution from edge to edge observed previously on surface-activated platelets. However, the gold particles marking the complex of vWF-anti-vWF bound to GPIb/M were closer together on the discoid cells. Fgn/Au particles bound to GPIIb/IIIa receptors were uniformly distributed from edge to edge on many discoid platelets. On others they tended to clump or cluster in strips or patches. The latter organization of Fgn/Au-GPIIb/IIIa receptors may be due to the rugose nature of the discoid platelet surface or an influence of cytochalasin E. Definition of mobile receptor organization on discoid cells provides a useful baseline for determining their fate following surface or suspension activation.

  20. pH-controlled delivery of luminescent europium coated nanoparticles into platelets (United States)

    Davies, Amy; Lewis, David J.; Watson, Stephen P.; Thomas, Steven G.; Pikramenou, Zoe


    Water soluble, luminescent gold nanoparticles are delivered into human platelets via a rapid, pH-controlled mechanism using a pH low insertion peptide, pHLIP. The approach introduces cocoating of gold nanoparticles with a europium luminescent complex, EuL and the pHLIP peptide to give pHLIP•EuL•Au. The 13-nm diameter gold nanoparticles act as a scaffold for the attachment of both the luminescent probe and the peptide to target delivery. Their size allows delivery of approximately 640 lanthanide probes per nanoparticle to be internalized in human platelets, which are not susceptible to transfection or microinjection. The internalization of pHLIP•EuL•Au in platelets, which takes just minutes, was studied with a variety of imaging modalities including luminescence, confocal reflection, and transmission electron microscopy. The results show that pHLIP•EuL•Au only enters the platelets in low pH conditions, pH 6.5, mediated by the pHLIP translocation across the membrane, and not at pH 7.4. Luminescence microscopy images of the treated platelets show clearly the red luminescence signal from the europium probe and confocal reflection microscopy confirms the presence of the gold particles. Furthermore, transmission electron microscopy gives a detailed insight of the internalization and spatial localization of the gold nanoparticles in the platelets. Thus, we demonstrate the potential of the design to translocate multimodal nanoparticle probes into cells in a pH dependent manner. PMID:22308346

  1. Platelet rich plasma treatment for chronic Achilles tendinosis. (United States)

    Monto, Raymond Rocco


    Chronic Achilles tendinosis is a relatively common but difficult orthopedic condition to treat. In this study, autologous platelet rich plasma (PRP), a concentrated bioactive blood component rich in cytokines and growth factors, was evaluated to determine its potential long-term efficacy in treating chronic cases of Achilles tendinosis resistant to traditional nonoperative management. Thirty patients with chronic Achilles tendinosis who did not respond to a minimum of 6 months of traditional nonoperative treatment modalities were treated with a single ultrasound guided injection of PRP. AOFAS scoring was completed for all patients pretreatment and at 0, 1, 2, 3, 6, 12, and 24 months post-treatment. MRI and/or ultrasound studies were completed for all patients pre-treatment and at 6 months post-treatment. Prior to the PRP treatment all of the patients in this study were considering surgical Achilles repair for their severe symptoms. The average AOFAS score increased from 34 (range, 20 to 60) to 92 (range, 87 to 100) by 3 months after PRP treatment and remained elevated at 88 (range, 76 to 100) at 24 months post-treatment. Pretreatment imaging abnormalities present in the Achilles tendon on MRI and ultrasound studies resolved in 27 of 29 patients at 6 months post-treatment. Clinical success was achieved in 28 of 30 patients. Platelet-rich plasma was used effectively to treat chronic recalcitrant cases of Achilles tendinosis.


    Directory of Open Access Journals (Sweden)

    Shumez H, Prasad PVS, Kaviarasan PK, Deepika R


    Full Text Available Background: Alopecia areata (AA is a chronic non-scarring alopecia that involves the scalp and/or body, and is characterized by patchy areas of hair loss without any signs of clinical inflammation. Various therapies have been proposed for their treatment.But none have been shown to alter the course of the disease. Platelet Rich Plasma (PRP is a volume of autologous plasma that has a high platelet concentration. Growth factors released from platelets may act on stem cells in the bulge area of the follicles, stimulating the development of new follicles and promoting neovascularization. Aim: To evaluate and compare the efficacy of intralesional injection of autologous platelet rich plasma with intralesional injection of triamcinolone acetonide (10mg/ml in the treatment of alopecia areata. Methodology: 74 patients with alopecia areata were allocated into 2 groups and treated with triamcinolone and PRP injections. Treatment outcome was measured by taking into account extent and density of regrowth of hair and was expressed as a percentage of overall growth. Results: Forty eight patients were treated with triamcinolone injections and 26 patients were treated with PRP injections. Patients treated with PRP had an earlier response at the end of 6weeks than patients treated with triamcinolone. However, this difference was statistically insignificant. The overall improvement at the end of 9 weeks was 100% for all patients in both groups. Conclusion: PRP is a safe, simple, biocompatible and effective procedure for the treatment of alopecia areata with efficacy comparable with triamcinolone.

  3. In Vivo Tracking of Platelets: Circulating Degranulated Platelets Rapidly Lose Surface P-Selectin but Continue to Circulate and Function

    National Research Council Canada - National Science Library

    Michelson, A


    To examine the hypothesis that surface P-selectin-positive (degranulated) platelets are rapidly cleared from the circulation, we developed novel methods for tracking of platelets and measurement of platelet function in vivo...

  4. A Study of Platelet Inhibition, Using a 'Point of Care' Platelet Function Test, following Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction [PINPOINT-PPCI].

    Directory of Open Access Journals (Sweden)

    Thomas W Johnson

    Full Text Available Rapid coronary recanalization following ST-elevation myocardial infarction (STEMI requires effective anti-platelet and anti-thrombotic therapies. This study tested the impact of door to end of procedure ('door-to-end' time and baseline platelet activity on platelet inhibition within 24hours post-STEMI.108 patients, treated with prasugrel and procedural bivalirudin, underwent Multiplate® platelet function testing at baseline, 0, 1, 2 and 24hours post-procedure. Major adverse cardiac events (MACE, bleeding and stent thrombosis (ST were recorded. Baseline ADP activity was high (88.3U [71.8-109.0], procedural time and consequently bivalirudin infusion duration were short (median door-to-end time 55minutes [40-70] and infusion duration 30minutes [20-42]. Baseline ADP was observed to influence all subsequent measurements of ADP activity, whereas door-to-end time only influenced ADP immediately post-procedure. High residual platelet reactivity (HRPR ADP>46.8U was observed in 75% of patients immediately post-procedure and persisted in 24% of patients at 2hours. Five patients suffered in-hospital MACE (4.6%. Acute ST occurred in 4 patients, all were <120mins post-procedure and had HRPR. No significant bleeding was observed. In a post-hoc analysis, pre-procedural morphine use was associated with significantly higher ADP activity following intervention.Baseline platelet function, time to STEMI treatment and opiate use all significantly influence immediate post-procedural platelet activity.

  5. Platelet-rich fibrin: Evolution of a second-generation platelet concentrate

    Directory of Open Access Journals (Sweden)

    Sunitha Raja V


    Full Text Available Platelet-rich plasma (PRP is a platelet concentrate that has been used widely to accelerate soft-tissue and hard-tissue healing. The preparation of PRP has been described by several authors. Platelet-rich fibrin (PRF was first described by Choukroun et al. in France. It has been referred to as a second-generation platelet concentrate, which has been shown to have several advantages over traditionally prepared PRP. Its chief advantages include ease of preparation and lack of biochemical handling of blood, which makes this preparation strictly autologous. This article describes the evolution of this novel platelet concentrate, referred to as PRF.

  6. Transplantation of platelet gel spiked with cardiosphere-derived cells boosts structural and functional benefits relative to gel transplantation alone in rats with myocardial infarction (United States)

    Cheng, Ke; Shen, Deliang; Smith, Jeremy; Galang, Giselle; Sun, Baiming; Zhang, Jinying; Marbán, Eduardo


    The emerging field of stem cell therapy and biomaterials has begun to provide promising strategies for the treatment of ischemic cardiomyopathy. Platelet gel and cardiosphere-derived cells (CDCs) are known to be beneficial when transplanted separately post-myocardial infarction (MI). We hypothesize that pre-seeding platelet gel with CDCs can enhance therapeutic efficacy. Platelet gel and CDCs were derived from venous blood and heart biopsies of syngeneic rats, respectively. In vitro, the viability, growth, and morphology of CDCs cultured in platelet gel were characterized. When delivered into infarcted rat hearts, platelet gel pre-seeded with CDCs was more efficiently populated with endogenous cardiomyocytes and endothelial cells than platelet gel alone. Recruitment of endogeous c-kit positive cells was enhanced in the hearts treated with gel with CDC. At 3 weeks, the hearts treated with CDC-seeded platelet gel exhibited the greatest attenuation of adverse left ventricular (LV) remodeling and the highest cardiac function (i.e., LV ejection fraction) as compared to hearts transplanted with gel only or vehicle controls. Histological analysis revealed that, though some transplanted CDCs differentiated into cardiomyocytes and endothelial cells in the recipients’ hearts, most of the incremental benefit arose from CDC-mediated endogenous repair. Pre-seeding platelet gel with CDCs enhanced the functional benefit of biomaterial therapy for treating myocardial infarction. PMID:22243801

  7. Ex vivo recapitulation of trauma-induced coagulopathy and preliminary assessment of trauma patient platelet function under flow using microfluidic technology. (United States)

    Li, Ruizhi; Elmongy, Hanna; Sims, Carrie; Diamond, Scott L


    Relevant to trauma-induced coagulopathy diagnostics, microfluidic assays allow controlled hemodynamics for testing of platelet and coagulation function using whole blood. Hemodilution or hyperfibrinolysis was studied under flow with modified healthy whole blood. Furthermore, platelet function was also measured using whole blood from trauma patients admitted to a Level I trauma center. Platelet deposition was measured with PPACK-inhibited blood perfused over collagen surfaces at a wall shear rate of 200 s, whereas platelet/fibrin deposition was measured with corn trypsin inhibitor-treated blood perfused over tissue factor (TF)/collagen. In hemodilution studies, PPACK-treated blood displayed almost no platelet deposition when diluted to 10% hematocrit with saline, platelet-poor plasma, or platelet-rich plasma. Using similar dilutions, platelet/fibrin deposition was essentially absent for corn trypsin inhibitor-treated blood perfused over TF/collagen. To mimic hyperfibrinolysis during trauma, exogenous tissue plasminogen activator (50 nM) was added to blood before perfusion over TF/collagen. At both venous and arterial flows, the generation and subsequent lysis of fibrin were detectable within 6 minutes, with lysis blocked by addition of the plasmin inhibitor, ε-aminocaproic acid. Microfluidic assay of PPACK-inhibited whole blood from trauma patients revealed striking defects in collagen response and secondary platelet aggregation in 14 of 21 patients, whereas platelet hyperfunction was detected in three of 20 patients. Rapid microfluidic detection of (1) hemodilution-dependent impairment of clotting, (2) clot instability because of lysis, (3) blockade of fibrinolysis, or (4) platelet dysfunction during trauma may provide novel diagnostic opportunities to predict trauma-induced coagulopathy risk.

  8. Tailor-made purified human platelet lysate concentrated in neurotrophins for treatment of Parkinson's disease. (United States)

    Chou, Ming-Li; Wu, Joe-Wei; Gouel, Flore; Jonneaux, Aurélie; Timmerman, Kelly; Renn, Ting-Yi; Laloux, Charlotte; Chang, Hung-Ming; Lin, Liang-Tzung; Devedjian, Jean-Christophe; Devos, David; Burnouf, Thierry


    Human platelet lysates (PLs), which contain multiple neurotrophins, have been proposed for treating neurodegenerative disorders, including Parkinson's disease (PD). However, current PLs suspended in plasma have high protein content and contain fibrinogen/fibrin and, following activation, also proteolytic and thrombogenic enzymes. Upon brain administration, such PLs may saturate the cerebrospinal fluid and exert neurotoxicity. We assessed whether purified PLs, concentrated in neurotrophins, protected dopaminergic neurons in PD models. Platelet concentrates were collected by apheresis and centrifuged to eliminate plasma and recover the platelets. Platelets were lysed by freeze-thaw cycles, and the 10-fold concentrated platelet pellet lysates (PPLs) were heat-treated (at 56 °C for 30 min). The heat-treated PPLs were low in total proteins, depleted in both plasma and platelet fibrinogen, and devoid of thrombogenic and proteolytic activities. They exerted very high neuroprotective activity when non-oncogenic, Lund human mesencephalic (LUHMES) cells that had differentiated into dopaminergic neurons were exposed to the MPP(+) neurotoxin. Heat treatment improved the neuroprotection and inactivated the neurotoxic blood-borne hepatitis C virus. PPL did not induce inflammation in BV2 microglial cells and inhibited COX-2 expression upon lipopolysaccharide exposure. Intranasal administration in mice revealed (a) diffusion of neurotrophins in the striatum and cortex, and (b) MPTP intoxication neuroprotection in the substantia nigra and striatum and the absence of neuroinflammation. These dedicated heat-treated PPLs can be a safe and valuable candidate for a therapeutic strategy for PD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Alzheimer and platelets: low-density platelet populations reveal increased serotonin content in Alzheimer type dementia. (United States)

    Milovanovic, Micha; Eriksson, Kristoffer; Winblad, Bengt; Nilsson, Staffan; Lindahl, Tomas L; Post, Claes; Järemo, Petter


    Alzheimer's disease (AD) is a progressive form of dementia characterized by an increase in the toxic substance β-amyloid in the brain. Platelets display a substantial heterogeneity with respect to density. They further contain a substantial amount of β-amyloid precursor protein. Platelets take up and store serotonin (5-HT) that plays an important role in the pathogenesis of severe depression. The current study aims to investigate platelet serotonin content in different platelet density populations. The study involved 8 patients (age 70±8 (SD) years) (3 females/5 males) with moderate AD. 6 healthy elderly subjects (age 66±9 (SD) years) (3 females/3 males) served as controls. The platelet population was divided into 17 subpopulations according to density, using a linear Percoll™ gradient. Platelets were counted in all fractions. After cell lysis an ELISA technique was employed to determine the 5-HT content in each platelet subfraction. The two study groups did not differ significantly regarding platelet distribution in the gradients, but AD sufferers have a significantly higher 5-HT content (ptype dementia proved to be associated with lighter platelets containing more 5-HT. It is possible that platelets from AD patients release less 5-HT. It is speculated that AD synapses are affected in a manner comparable to platelets, which could explain why 5-HT reuptake inhibitors are less effective in AD dementia. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  10. Refrigerated Platelets for the Treatment of Acute Bleeding: A Review of the Literature and Reexamination of Current Standards (United States)


    circulation (10). Platelets participate in immunomodulation, maintenance and repair of vessel structures , and, their best-known function, clot forma...adults taking aspirin demonstrated that 4C-PLTs had significantly improved bleeding times in contrast to those at RT, which had little or delayed effects...1974. 20. Valeri CR: Circulation and hemostatic effectiveness of platelets stored at 4 C or 22 C: studies in aspirin -treated normal volunteers

  11. Effects of marathon running on platelet activation markers : direct evidence for in vivo platelet activation. (United States)

    Kratz, Alexander; Wood, Malissa J; Siegel, Arthur J; Hiers, Jennifer R; Van Cott, Elizabeth M


    We used the ADVIA 2120 Hematology System (Bayer HealthCare, Diagnostics Division, Tarrytown, NY) to study the effects of vigorous exercise on CBC count, WBC differential, RBC fragmentation, and platelet activation parameters in 32 healthy participants in a 26.2-mile (42.2-km) marathon. The runners demonstrated increases in hematocrit and platelet count consistent with dehydration and leukocytosis indicative of demargination of neutrophils or inflammation secondary to tissue destruction (eg, rhabdomyolysis). The number of RBC fragments was increased after the race (P = .008), consistent with exercise-induced hemolysis. The mean platelet component, a measure of platelet granularity, was decreased (P marathon. By using direct measurement of platelet granularity, our study confirms the in vivo activation of platelets by vigorous exercise and establishes the usefulness of automated cell counters for the assessment of platelet activation and of RBC fragmentation in this setting.

  12. Platelet Activation by Streptococcus pyogenes Leads to Entrapment in Platelet Aggregates, from Which Bacteria Subsequently Escape (United States)

    Svensson, Lisbeth; Baumgarten, Maria; Mörgelin, Matthias


    Platelet activation and aggregation have been reported to occur in response to a number of Gram-positive pathogens. Here, we show that platelet aggregates induced by Streptococcus pyogenes were unstable and that viable bacteria escaped from the aggregates over time. This was not due to differential activation in response to the bacteria compared with physiological activators. All the bacterial isolates induced significant platelet activation, including integrin activation and alpha and dense-granule release, at levels equivalent to those induced by potent physiological platelet activators that induced stable aggregates. The ability to escape the aggregates and to resist the antibacterial effects of platelets was dependent on active protein synthesis by the bacteria within the aggregate. We conclude that S. pyogenes bacteria can temporarily cover themselves with activated platelets, and we propose that this may facilitate survival of the bacteria in the presence of platelets. PMID:25069984

  13. Impact of dabigatran on platelet function and fibrinolysis. (United States)

    Tsantes, Argirios E; Kyriakou, Elias; Bonovas, Stefanos; Chondrogianni, Maria; Zompola, Christina; Liantinioti, Chrissoula; Simitsi, Athina; Katsanos, Aristeidis H; Atta, Maria; Ikonomidis, Ignatios; Kapsimali, Violetta; Kopterides, Petros; Tsivgoulis, Georgios


    We sought to evaluate the potential enhanced fibrinolytic and antiplatelet activity of dabigatran etexilate (DE) due to decreased thrombin levels in patients with stroke or transient ischemic attack and non-valvular atrial fibrillation (NVAF). Consecutive patients with cerebrovascular diseases and NVAF that were treated with DE in a tertiary university hospital. Fibrinolysis and platelet function were assessed by thromboelastometry (ROTEM) and platelet function analyzer (PFA)-100, respectively, before and after treatment with DE. Conventional coagulation tests, endogenous thrombin potential (ETP) and hemoclot thrombin inhibitors (HTI), were also performed in order to detect any possible correlation between dabigatran plasma levels, its anticoagulant activity and the intensity of platelet dysfunction or fibrinolysis. A total of nineteen patients fulfilled our inclusion criteria (mean age 62.3±7.2years; 47% males; median CHADS2-score: 3; interquartile range: 2-4). DE treatment was associated with a significant reduction of the lysis index (LI60) at 60min (p=0.036), and prolongation of the PFA-100 CEPI closure time (p=0.024). After dabigatran treatment, abnormal PFA-100 results were obtained in two patients (11%, 95% CI: 2%-33%). DE levels (determined by HTI) were strongly inversely correlated (rho=-0.85; pfibrinolysis and highlight the potential role of ETP as an alternative option in DE monitoring. The intensity and clinical relevance of DE antiplatelet and fibrinolytic effects require further investigation. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. In vitro platelet antiaggregatory properties of 4-methylcoumarins. (United States)

    Macáková, Kateřina; Řeháková, Zuzana; Mladěnka, Přemysl; Karlíčková, Jana; Filipský, Tomáš; Říha, Michal; Prasad, Ashok K; Parmar, Virinder S; Jahodář, Luděk; Pávek, Petr; Hrdina, Radomír; Saso, Luciano


    Platelets play a crucial role in physiological haemostasis. However, in coronary arteries damaged by atherosclerosis, enhanced platelet aggregation, with subsequent thrombus formation, is a precipitating factor in acute myocardial infarction. Current therapeutic approaches are able to reduce approximately one quarter of cardiovascular events, but they are associated with an increased risk of bleeding and in some resistant patients are not efficient. Some coumarins possess antiplatelet activity and, due to their additional antioxidant effects, may be promising drugs for use in combination with the present therapeutic agents. The aim of this study was to analyse a series of simple 4-methylcoumarins for their antiplatelet activity. Human plasma platelet suspensions were treated with different aggregation inducers [arachidonic acid (AA), collagen and ADP] in the presence of the 4-methylcoumarins. Complementary experiments were performed to explain the mechanism of action. 5,7-Dihydroxy-4-methylcoumarins, in particular those containing a lipophilic side chain at C-3, reached the activity of acetylsalicylic acid on AA-induced aggregation. Other tested coumarins were less active. Some of the tested compounds mildly inhibited either collagen- or ADP-induced aggregation. 5,7-Dihydroxy-4-methylcoumarins did not interfere with the function of thromboxane synthase, but were competitive antagonists of thromboxane A(2) receptors and inhibited cyclooxygenase-1 as well. 5,7-Dihydroxy-4-methylcoumarins appear to be promising candidates for the extension of the current spectrum of antiplatelet drugs. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  15. The effect of dabigatran and rivaroxaban on platelet reactivity and inflammatory markers. (United States)

    Zemer-Wassercug, Noa; Haim, Moti; Leshem-Lev, Dorit; Orvin, Katia L; Vaduganathan, Muthiah; Gutstein, Ariel; Kadmon, Ehud; Mager, Aviv; Kornowski, Ran; Lev, Eli I; Lev, Eli L


    The new oral anticoagulants (NOACs) reduce stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF), but dabigatran may increase risk of coronary ischemic events for unclear reasons. Thus, this study assessed the effects of dabigatran and rivaroxaban on platelet reactivity and inflammatory markers in patients with non-valvular AF. Patients with non-valvular AF planned to begin treatment with NOACs were included. Seventeen patients were prescribed dabigatran and ten rivaroxaban. Platelet function (as assessed by multiple-electrode aggregometry, Impact-R shear-induced platelet deposition, P-selectin expression and plasma RANTES levels) and high-sensitivity C-reactive protein (hs-CRP) were measured at enrollment (prior to initiation of NOAC treatment) and at least 7 days into treatment with either dabigratran or rivaroxaban. Seventeen patients treated with dabigatran (mean age 69 ± 7 years, 35 % women, mean CHADS2 score 2.6 ± 1.2), and ten patients treated with rivaroxaban (mean age 73 ± 9 years, 20 % women, mean CHADS2 score 2.7 ± 1.6) completed the study. In both groups, there were no significant differences in platelet reactivity between the baseline and on-anticoagulant treatment time-points, as measured by each of the platelet-specific assays. There was a trend towards increased platelet reactivity in response to arachidonic acid from baseline to on-treatment in both groups, probably as a result of aspirin discontinuation in 33 % of patients. No significant differences were noted between baseline and on-treatment in hs-CRP in both anticoagulant groups. Treatment with dabigatran and rivaroxaban does not appear to be associated with changes in markers of platelet reactivity or systemic inflammation.

  16. Chewing versus Swallowing Ticagrelor to Accelerate Platelet Inhibition in Acute Coronary Syndrome - the CHEERS study. For The PLATIS (Platelets and Thrombosis in Sheba) Study Group. (United States)

    Asher, Elad; Frydman, Shir; Katz, Moshe; Regev, Ehud; Sabbag, Avi; Mazin, Israel; Abu-Much, Arsalan; Kukuy, Andrew; Mazo, Anna; Erez, Aharon; Berkovitch, Anat; Narodistky, Michael; Barbash, Israel; Segev, Amit; Beigel, Roy; Matetzky, Shlomi


    It was the study objective to evaluate whether chewing a 180 mg loading dose of ticagrelor versus an equal dose of traditional oral administration, enhances inhibition of platelet aggregation 1 hour (h) after administering a ticagrelor loading dose in non-ST elevation myocardial infarction (NSTEMI) patients. Dual anti-platelet therapy represents standard care for treating NSTEMI patients. Ticagrelor is a direct acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not require metabolic activation. Fifty NSTEMI patients were randomised to receive either a chewing loading dose of 180 mg ticagrelor or an equal standard oral dose of ticagrelor. Platelet reactivity was evaluated by VerifyNow at baseline, 1 and 4 h post-loading dose. Results are reported in P2Y12 reaction units. Patients then continued to receive standard 90 mg oral ticagrelor twice daily. Baseline characteristics did not differ between the two groups. P2Y12 reaction units in the chewing group compared with the standard group at 0, 1 and 4 h after ticagrelor loading dose were: 245 vs 239 (p=0.59), 45 vs 130 (p=0.001) and 39 vs 60 (p=0.12), respectively, corresponding to a relative inhibition of platelet aggregation of 83 % vs only 47 % at 1 h (pticagrelor loading dose is feasible and facilitates both faster and improved early inhibition of platelet aggregation in NSTEMI patients, compared with a standard oral-loading dose.

  17. Freezing of Apheresis Platelet Concentrates in 6% Dimethyl Sulfoxide: The First Preliminary Study in Turkey

    Directory of Open Access Journals (Sweden)

    Soner Yılmaz


    Full Text Available Objective: Transfusion of platelet suspensions is an essential part of patient care for certain clinical indications. In this pioneering study in Turkey, we aimed to assess the in vitro hemostatic functions of platelets after cryopreservation. Materials and Methods: Seven units of platelet concentrates were obtained by apheresis. Each apheresis platelet concentrate (APC was divided into 2 equal volumes and frozen with 6% dimethyl sulfoxide (DMSO. The 14 frozen units of APCs were kept at -80 °C for 1 day. APCs were thawed at 37 °C and diluted either with autologous plasma or 0.9% NaCl. The volume and residual numbers of leukocytes and platelets were tested in both before-freezing and post-thawing periods. Aggregation and thrombin generation tests were used to analyze the in vitro hemostatic functions of platelets. Flow-cytometric analysis was used to assess the presence of frozen treated platelets and their viability. Results: The residual number of leukocytes in both dilution groups was <1x106. The mean platelet recovery rate in the plasma-diluted group (88.1±9.5% was higher than that in the 0.9% NaCl-diluted group (63±10%. These results were compatible with the European Directorate for the Quality of Medicines quality criteria. Expectedly, there was no aggregation response to platelet aggregation test. The mean thrombin generation potential of postthaw APCs was higher in the plasma-diluted group (2411 nmol/L per minute when compared to both the 0.9% NaCl-diluted group (1913 nmol/L per minute and the before-freezing period (1681 nmol/L per minute. The flowcytometric analysis results for the viability of APCs after cryopreservation were 94.9% and 96.6% in the plasma and 0.9% NaCl groups, respectively. Conclusion: Cryopreservation of platelets with 6% DMSO and storage at -80 °C increases their shelf life from 7 days to 2 years. Besides the increase in hemostatic functions of platelets, the cryopreservation process also does not affect their

  18. Novel agents for anti-platelet therapy

    Directory of Open Access Journals (Sweden)

    Ji Xuebin


    Full Text Available Abstract Anti-platelet therapy plays an important role in the treatment of patients with thrombotic diseases. The most commonly used anti-platelet drugs, namely, aspirin, ticlopidine, and clopidogrel, are effective in the prevention and treatment of cardio-cerebrovascular diseases. Glycoprotein IIb/IIIa antagonists (e.g., abciximab, eptifibatide and tirofiban have demonstrated good clinical benefits and safety profiles in decreasing ischemic events in acute coronary syndrome. However, adverse events related to thrombosis or bleeding have been reported in cases of therapy with glycoprotein IIb/IIIa antagonists. Cilostazol is an anti-platelet agent used in the treatment of patients with peripheral ischemia, such as intermittent claudication. Presently, platelet adenosine diphosphate P2Y(12 receptor antagonists (e.g., clopidogrel, prasugrel, cangrelor, and ticagrelor are being used in clinical settings for their pronounced protective effects. The new protease-activated receptor antagonists, vorapaxar and atopaxar, potentially decrease the risk of ischemic events without significantly increasing the rate of bleeding. Some other new anti-platelet drugs undergoing clinical trials have also been introduced. Indeed, the number of new anti-platelet drugs is increasing. Consequently, the efficacy of these anti-platelet agents in actual patients warrants scrutiny, especially in terms of the hemorrhagic risks. Hopefully, new selective platelet inhibitors with high anti-thrombotic efficiencies and low hemorrhagic side effects can be developed.

  19. Clinica use of platelet additive solutions. (United States)

    van Rhenen, Dick J


    Randomised clinical trial (RCT) to study the clinical efficacy and safety of new platelet products using platelet additive solutions are scarce. In this paper a number of recent RCT's is discussed. It can be the start of a development where new transfusion products enter a RCT before the product is applied in clinical practice.

  20. Platelet affinity for burro aorta collagen

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, M.D.


    Despite ingenious concepts, there are no unequivocal clues as to what, when, and how some undefined biochemical factor(s) or constituent(s) that localizes in the arterial wall can precipitate a thromboatheromatous lesion or arterial disease. The present study focused on the extraction, partial purification, and characterization of a collagen-active platelet stimulator from the aortas of aged burros. The aggregator moiety in the aorta extracts invariably had a higher affinity for platelets in citrated platelet-rich plasma of human beings than for platelets of homologous burros. The platelet-aggregating factor(s) in the aorta extract was retained by incubation with ..cap alpha..-chymotrypsin. Platelet-aggregating activity was rapidly abolished after incubation with collagenase, as determined by platelet-aggregometry tests. Evidence based on light microscope and polysaccharide histochemical reactions indicates a probability that the intracellular amorphous matrix (PAS-positive) and filamentous components (PTAH-positive) expelled from smooth muscle cells disrupted during homogenization of the aorta may be a principal source of a precursor collagen species which is a potent inducer of platelet aggregation.

  1. Depletion interactions caused by polydisperse, hard platelets

    NARCIS (Netherlands)

    July, C.; Kleshchanok, D.|info:eu-repo/dai/nl/323052517; Lang, P.R.


    We investigate depletion interactions near a wall caused by polydisperse silica-coated gibbsite platelets, using total internal reflection fluorescence microscopy (TIRF) to characterize the sphere–wall interaction potential. As no theoretical model for polydisperse platelets exists, we extend a

  2. The Platelet Function Defect of Cardiopulmonary Bypass. (United States)


    role of platelets, in Hetzer R (ed): Blood use in cardiac surgery, Darmstadt, Steinkopff, 1990, * 4. Harker LA, Malpass TW, Branson HE, Hessel EA...L, Sandesara J, Vagher JP, Alexander JC, Caprini JA: Decreased platelet number and function and increased fibrinolysis contribute to postoperative

  3. Vesiculation of platelets during in vitro aging. (United States)

    Bode, A P; Orton, S M; Frye, M J; Udis, B J


    Membranous microparticles (MP) appearing in the supernatant plasma of stored platelet concentrates (PC) were analyzed by flow cytometry. Two populations of MP were arbitrarily delineated by light scatter as larger or smaller than 0.5 micron fluorescent beads. An estimate of MP concentration was obtained by adding a known amount of fluorescent beads to each sample before analysis of a set number of counts on the flow cytometer. The addition of platelet activation inhibitors (prostaglandin E-1, theophylline, and aprotinin) to the anticoagulant during preparation of PC combined with a reduction in surface area of the storage container caused approximately a 40% reduction in the number of MP appearing during storage relative to donor-matched controls. In addition, the inhibited concentrates had 84% less platelet factor 3 (PF3) activity in the supernatant and 61% less released lactic dehydrogenase. A reduction in surface area of the container in the controls partially offset these differences. A significant correlation was found (rs = .748) between PF3 levels and the concentration of larger MP. The inhibitors did not reduce the small number of MP found in stored platelet-poor plasma. Surface antigen analysis showed that the majority of MP in PC were platelet-derived; most were positive for glycoprotein (GP) IIbIIIa (73%) and/or for GPIb (43% to 46%). We conclude that procoagulant MP are released from platelets during storage as a result of platelet activation augmented by interaction of platelets with the bag wall.

  4. Enhanced platelet MRP4 expression and correlation with platelet function in patients under chronic aspirin treatment. (United States)

    Massimi, Isabella; Lotti, Lavinia Vittoria; Temperilli, Flavia; Mancone, Massimo; Sardella, Gennaro; Calcagno, Simone; Turriziani, Ombretta; Frati, Luigi; Pulcinelli, Fabio M


    Platelet multidrug resistance protein4 (MRP4)-overexpression has a role in reducing aspirin action. Aspirin in vivo treatment enhances platelet MRP4 expression and MRP4 mediated transport inhibition reduces platelet function and delays thrombus formation. The aim of our work was to verify whether MRP4 expression is enhanced in platelets obtained from patients under chronic aspirin treatment and whether it correlates with residual platelet reactivity. We evaluated changes on mRNA and protein-MRP4 expression and platelet aggregation in four populations: healthy volunteers (HV), aspirin-free control population (CTR), patients who started the treatment less than one month ago (ASAaspirinated patients who started the treatment more than two months ago (ASA>2 months patients). In platelets obtained from ASA>2 months patients, it was found a statistically significant MRP4 enhancement of both mRNA and protein expression compared to HV, CTR and ASA2 months patients that present high levels of platelet MRP4, have higher serum TxB2 levels and collagen-induced platelet aggregation compared to patient with low levels of MRP4 in platelets. In addition collagen induced platelet aggregation is higher in in vitro aspirinated platelets obtained from patients with high levels of MRP4 patients compared to those obtained from patients with low MRP4 levels. We can assert that, in patients under chronic aspirin treatment, platelets that present high MRP4 levels have an increase of residual platelet reactivity, which is due in part to incomplete COX-1 inhibition, and in part to COX-1-independent mechanism.

  5. Platelet-rich plasma in otolaryngology. (United States)

    Stavrakas, M; Karkos, P D; Markou, K; Grigoriadis, N


    Platelet-rich plasma is a novel material that is being used more frequently in many surgical specialties. A literature review on the current and potential uses of platelet-rich plasma in otolaryngology was performed. There is limited evidence on the use of platelet-rich plasma in otolaryngology compared with other specialties: only 11 studies on various subspecialties (otology, rhinology and laryngology) were included in the final review. Based on the limited number of studies, we cannot draw safe conclusions about the value of platelet-rich plasma in otolaryngology. Nevertheless, the available literature suggests that platelet-rich plasma holds promise for future research and may have a number of clinical applications.

  6. Platelet mitochondrial function and dysfunction: physiological consequences

    Energy Technology Data Exchange (ETDEWEB)

    Popov, D.


    There is a general trend in revisiting mitochondria using the up-to-date technologies that uncovered novel attributes of this organelle, such as the intracellular displacement to locations where an energy supply is needed, the dynamic shape changes and turnover, the initiation of signaling to the rest of the cell, and the ability to crosstalk with other cellular organelles. The in-depth scrutiny of platelet mitochondria role in health and pathology is included within this ongoing revisiting trend. The current article puts into a nutshell the most recent data on platelet mitochondria function and disease-related ion, focusing on generation of stress- and apoptosis-related signaling molecules, overproduction of reactive oxygen species during activation and disease, on the biomarker potential of platelets mitochondria, and their prospective exploitation in translational applications. These novel findings complete the physiological profile of platelets and could have potential therapeutic effectiveness in platelet-associated disorders.

  7. Platelet bioreactor-on-a-chip (United States)

    Mazutis, Linas; Wu, Stephen; Sylman, Joanna L.; Ehrlicher, Allen; Machlus, Kellie R.; Feng, Qiang; Lu, Shijiang; Lanza, Robert; Neeves, Keith B.; Weitz, David A.; Italiano, Joseph E.


    Platelet transfusions total >2.17 million apheresis-equivalent units per year in the United States and are derived entirely from human donors, despite clinically significant immunogenicity, associated risk of sepsis, and inventory shortages due to high demand and 5-day shelf life. To take advantage of known physiological drivers of thrombopoiesis, we have developed a microfluidic human platelet bioreactor that recapitulates bone marrow stiffness, extracellular matrix composition, micro-channel size, hemodynamic vascular shear stress, and endothelial cell contacts, and it supports high-resolution live-cell microscopy and quantification of platelet production. Physiological shear stresses triggered proplatelet initiation, reproduced ex vivo bone marrow proplatelet production, and generated functional platelets. Modeling human bone marrow composition and hemodynamics in vitro obviates risks associated with platelet procurement and storage to help meet growing transfusion needs. PMID:25606631

  8. Platelet storage pool deficiency in Jacobsen syndrome. (United States)

    White, James G


    Jacobsen syndrome and Paris-Trousseau Syndrome share similar congenital anomalies, thrombocytopenia, giant platelet alpha granules resulting from fusion of smaller organelles, and an 11q terminal deletion at 11q23.3. Similarities in the two cohorts have suggested that the Paris-Trousseau Syndrome is a variant of Jacobsen syndrome, or the same disorder. The present study has pointed out a significant difference between the two syndromes. Platelets from six patients with Jacobsen syndrome were markedly diminished in serotonin adenine nucleotide rich dense bodies, indicating the presence of platelet storage pool deficiency. Since platelet dense bodies are reported to be normal in size, number and distribution in the Paris-Trousseau Syndrome, the presence of platelet storage pool deficiency in six patients evaluated in the present study may distinguish the two disorders.

  9. Effect of temperature on platelet adherence. (United States)

    Braune, S; Fröhlich, G M; Lendlein, A; Jung, F


    Thrombogenicity is one of the main parameters tested in vitro to evaluate the hemocompatibility of artificial surfaces. While the influence of the temperature on platelet aggregation has been addressed by several studies, the temperature influence on the adherence of platelets to body foreign surfaces as an important aspect of biomedical device handling has not yet been explored. Therefore, we analyzed the influence of two typically applied incubation-temperatures (22°C and 37°C) on the adhesion of platelets to biomaterials. Thrombogenicity of three different polymers - medical grade poly(dimethyl siloxane) (PDMS), polytetrafluoroethylene (PTFE) and polyethylene terephthalate (PET) - were studied in an in vitro static test. Platelet adhesion was studied with stringently characterized blood from apparently healthy subjects. Collection of whole blood and preparation of platelet rich plasma (PRP) was carried out at room temperature (22°C). PRP was incubated with the polymers either at 22°C or 37°C. Surface adherent platelets were fixed, fluorescently labelled and assessed by an image-based approach. Differences in the density of adherent platelets after incubation at 22°C and 37°C occurred on PDMS and PET. Similar levels of adherent platelets were observed on the very thrombogenic PTFE. The covered surface areas per single platelet were analyzed to measure the state of platelet activation and revealed no differences between the two incubation temperatures for any of the analyzed polymers. Irrespective of the observed differences between the low and medium thrombogenic PDMS and PET and the higher variability at 22°C, the thrombogenicity of the three investigated polymers was evaluated being comparable at both incubation temperatures.

  10. The effect of epoprostenol on platelet activation and consumption during experimental extracorporeal perfusion

    DEFF Research Database (Denmark)

    Skogby, M; Adrian, K; Friberg, L


    Hemorrhages are major complications experienced in 10-35% of neonates treated with extracorporeal life support (ECLS). The increased bleeding tendency is partly due to an ECLS induced thrombocytopenia and impaired platelet function. In the present study, we evaluated the effect of epoprostenol...

  11. Effects of Low Temperature on Shear-Induced Platelet Aggregation and Activation (United States)


    strategies to treat hypo- thermic coagulopathy and other complications. REFERENCES 1. Hanes SD, Quarles DA, Boucher BA. Incidence and risk factors of...609. 32. Tsvetkova NM, Crowe JH, Walker NJ, et al. Physical properties of membrane fractions isolated from human platelets: implications for chilling

  12. Platelet rich fibrin in jaw defects (United States)

    Nica, Diana; Ianes, Emilia; Pricop, Marius


    Platelet rich fibrin (PRF) is a tissue product of autologous origin abundant in growth factors, widely used in regenerative procedures. Aim of the study: Evaluation of the regenerative effect of PRF added in the bony defects (after tooth removal or after cystectomy) Material and methods: The comparative nonrandomized study included 22 patients divided into 2 groups. The first group (the test group) included 10 patients where the bony defects were treated without any harvesting material. The second group included 12 patients where the bony defects were filled with PRF. The bony defect design was not critical, with one to two walls missing. After the surgeries, a close clinically monitoring was carried out. The selected cases were investigated using both cone beam computer tomography (CBCT) and radiographic techniques after 10 weeks postoperatively. Results: Faster bone regeneration was observed in the bony defects filled with PRF comparing with the not grafted bony defects. Conclusions: PRF added in the bony defects accelerates the bone regeneration. This simplifies the surgical procedures and decreases the economic costs.

  13. Treating Infertility (United States)

    ... Education & Events Advocacy For Patients About ACOG Treating Infertility Home For Patients Search FAQs Treating Infertility Page ... Treating Infertility FAQ137, October 2017 PDF Format Treating Infertility Gynecologic Problems What is infertility? What causes infertility ...

  14. Application of an optimized flow cytometry-based quantification of Platelet Activation (PACT): Monitoring platelet activation in platelet concentrates. (United States)

    Kicken, Cécile H; Roest, Mark; Henskens, Yvonne M C; de Laat, Bas; Huskens, Dana


    Previous studies have shown that flow cytometry is a reliable test to quantify platelet function in stored platelet concentrates (PC). It is thought that flow cytometry is laborious and hence expensive. We have optimized the flow cytometry-based quantification of agonist induced platelet activation (PACT) to a labor, time and more cost-efficient test. Currently the quality of PCs is only monitored by visual inspection, because available assays are unreliable or too laborious for use in a clinical transfusion laboratory. Therefore, the PACT was applied to monitor PC activation during storage. The optimized PACT was used to monitor 5 PCs during 10 days of storage. In brief, optimized PACT uses a ready-to-use reaction mix, which is stable at -20°C. When needed, a test strip is thawed and platelet activation is initiated by mixing PC with PACT. PACT was based on the following agonists: adenosine diphosphate (ADP), collagen-related peptide (CRP) and thrombin receptor-activating peptide (TRAP-6). Platelet activation was measured as P-selectin expression. Light transmission aggregometry (LTA) was performed as a reference. Both PACT and LTA showed platelet function decline during 10-day storage after stimulation with ADP and collagen/CRP; furthermore, PACT showed decreasing TRAP-induced activation. Major differences between the two tests are that PACT is able to measure the status of platelets in the absence of agonists, and it can differentiate between the number of activated platelets and the amount of activation, whereas LTA only measures aggregation in response to an agonist. Also, PACT is more time-efficient compared to LTA and allows high-throughput analysis. PACT is an optimized platelet function test that can be used to monitor the activation of PCs. PACT has the same accuracy as LTA with regard to monitoring PCs, but it is superior to both LTA and conventional flow cytometry based tests with regard to labor-, time- and cost efficiency.

  15. Platelet utilization in the developing world: strategies to optimize platelet transfusion practices. (United States)

    Verma, Anupam; Agarwal, Prashant


    There is perennial shortage of blood and blood components in most of the developing world. The resources are inadequate in terms of meeting the ever growing demand of blood components especially platelets. A poor health care system has led to underdevelopment of blood transfusion services which ultimately affect the transfusion practices. There is a paucity of comprehensive data on the platelet usage from the developing countries which is reflective of their modest development in blood component therapy. This is in sharp contrast to the fast pace of development in platelet transfusion practice in developed world where platelet substitutes are to become a reality for clinical use in near future. In developing world a considerable heterogeneity exists for platelet transfusion practices between countries, and even within countries in hospitals where this precious resource is available. This variation in existing practices can partly be explained by factors like individual preferences, lack of any hospital transfusion policy with regard to platelet transfusion, problems of platelet availability, etc. There is a need to implement best platelet transfusion practices as platelet products are scarcely available and expensive. Few interventions are emphasized in this article in the context of improving the status of platelet utilization in developing countries.

  16. Involvement of platelets in experimental mouse trypanosomiasis: evidence of mouse platelet cytotoxicity against Trypanosoma equiperdum. (United States)

    Momi, S; Perito, S; Mezzasoma, A M; Bistoni, F; Gresele, P


    Platelets play an important role in the human response to parasites. Trypanosoma equiperdum, a parasite that has the horse as its natural host, is able to induce infection in mice and thus it may represent a simple model for studying the role of platelets in the development of a parasitosis. Although several aspects of the murine response to T. equiperdum infection have been clarified, the precise mechanism of killing of the parasite is still unclear. We have studied the involvement of blood platelets in experimental murine infection with T. equiperdum. Infected mice show a progressive decrease of the number of circulating platelets. The production of thromboxane A2 (TxA2) by platelets stimulated with collagen decreases progressively with the progression of T. equiperdum infection, compatible with in vivo platelet activation or with a possible antagonistic effect by trypanosomes on the production of TxA2. Finally, mouse platelets exert in vitro a direct parasitocidal activity on T. equiperdum at ratios >/=20:1. Complement fractions do not enhance platelet trypanocidal activity, whereas IgM fractions do, at least in short-term coincubation experiments. Our data show that platelets are involved in experimental murine T. equiperdum infection and confirm that platelet parasitocidal activity is a generalized phenomenon in mammals. Copyright 2000 Academic Press.

  17. Breaking the mold: transcription factors in the anucleate platelet and platelet-derived microparticles

    Directory of Open Access Journals (Sweden)

    Katie L Lannan


    Full Text Available Platelets are small anucleate blood cells derived from megakaryocytes. In addition to their pivotal roles in hemostasis, platelets are the smallest, yet most abundant, immune cell and regulate inflammation, immunity, and disease progression. Although platelets lack DNA, and thus no functional transcriptional activities, they are nonetheless rich sources of RNAs, possess an intact spliceosome, and are thus capable of synthesizing proteins. Previously, it was thought that platelet RNAs and translational machinery were remnants from the megakaryocyte. We now know that the initial description of platelets as cellular fragments is an antiquated notion, as mounting evidence suggests otherwise. Therefore, it is reasonable to hypothesize that platelet transcription factors are not vestigial remnants from megakaryoctes, but have important, if only partly understood functions. Proteins play multiple cellular roles to minimize energy expenditure for maximum cellular function; thus, the same can be expected for transcription factors. In fact, numerous transcription factors have non-genomic roles, both in platelets and in nucleated cells. Our lab and others have discovered the presence and nongenomic roles of transcription factors in platelets, such as the nuclear factor kappa β (NFκB family of proteins and peroxisome proliferator activated receptor gamma (PPARγ. In addition to numerous roles in regulating platelet activation, functional transcription factors can be transferred to vascular and immune cells through platelet microparticles. This method of transcellular delivery of key immune molecules may be a vital mechanism by which platelet transcription factors regulate inflammation and immunity. At the very least, platelets are an ideal model cell to dissect out the nongenomic roles of transcription factors in nucleated cells. There is abundant evidence to suggest that transcription factors in platelets play key roles in regulating inflammatory and

  18. TRA-418, a novel compound having both thromboxane A(2) receptor antagonistic and prostaglandin I(2) receptor agonistic activities: its antiplatelet effects in human and animal platelets. (United States)

    Yamada, N; Miyamoto, M; Isogaya, M; Suzuki, M; Ikezawa, S; Ohno, M; Otake, A; Umemura, K


    TRA-418 is a novel compound that has been found in our screening for compounds having both thromboxane A2 (TP) receptor antagonistic and prostaglandin I2 (IP) receptor agonistic activities. In the binding assays, TRA-418 showed a 10-fold higher affinity to TP-receptors than IP-receptors. TRA-418 inhibited platelet aggregation induced by the TP-receptor agonist, U-46619 and by arachidonic acid at concentrations lower than those required for inhibition of ADP-induced aggregations. Furthermore, TRA-418 inhibited not only platelet aggregation induced by ADP alone, but also that induced by ADP in the presence of the TP-receptor antagonist, SQ-29548. When the IC50 values of TRA-418 for platelet aggregation were estimated in platelet preparations from monkeys, dogs, cats, and rats using ADP and arachidonic acid as the platelet stimulating agents, it was found that the values estimated in monkey platelets were quite similar to those estimated in human platelets. In ex vivo platelet aggregation in monkeys, TRA-418 exhibited significant inhibitory effects on arachidonic acid-induced aggregation in platelet preparations from monkeys treated at 3 micro g kg min-1 or higher doses, where neither a significant decrease in blood pressure nor a significant increase in heart rate was observed. These results are consistent with the fact that TRA-418 has a relatively potent TP-receptor antagonistic activity together with a relatively weak IP-receptor agonistic activity.

  19. Platelets (United States)

    ... mutation that causes an abnormality of the immune (complement) system. The complement proteins are normal blood proteins ... damaged cells or destroy foreign cells. If the complement system becomes overactive because of an inherited gene mutation ...

  20. Aspirin 'resistance': impact on no-reflow, platelet and inflammatory biomarkers in diabetics after ST-segment elevation myocardial infarction. (United States)

    Kuliczkowski, Wiktor; Gasior, Mariusz; Pres, Damian; Kaczmarski, Jacek; Laszowska, Anna; Szewczyk, Marta; Hawranek, Michal; Tajstra, Mateusz; Zeglen, Slawomir; Polonski, Lech; Serebruany, Victor L


    The no-reflow (NR) phenomenon exists despite percutaneous coronary intervention (PCI), and is especially prevalent in diabetics. The causes(s) of NR are not fully elucidated, but may be associated with impaired residual platelet and inflammatory reactivity during dual-antiplatelet therapy. To assess the relationship between dual-antiplatelet therapy, NR and conventional biomarkers suggestive of platelet and inflammatory response in diabetics following ST-segment elevation myocardial infarction (STEMI) treated with PCI. Sixty diabetics with (n = 27) and without NR (n = 33) were prospectively enrolled. All patients were treated with clopidogrel and aspirin. Platelet and inflammatory biomarkers were assessed serially in the peripheral blood and right atrium before and after PCI and then at 24 h, 7 days and 30 days. Arachidonic acid (AA)-induced platelet aggregation and the serum thromboxane B2 level before and after PCI (in the peripheral and right atrium blood) were significantly higher in the NR patients than in those with no NR. AA-induced aggregation >100 (AUC*min) before PCI predicted NR in diabetic patients with 96.2% sensitivity and 38.5% specificity (AUC 0.66; 95% CI 0.52-0.71; p = 0.029). There were no other correlations between NR and platelet reactivity (collagen, adenosine diphosphate, thrombin receptor agonist peptide-induced aggregation, vasodilator-stimulated phosphoprotein platelet reactivity index, soluble P-selectin, soluble CD40 ligand, platelet-derived growth factor AB and the level of platelet-monocyte aggregates) or between NR and inflammatory indices (i.e. high-sensitivity C-reactive protein, interleukin 6 and interleukin 10). An inadequate response to aspirin, but not to clopidogrel, may be associated with the occurrence of the NR phenomenon in diabetics with STEMI who have been treated with primary PCI. © 2015 S. Karger AG, Basel.

  1. Platelet-Rich Plasma with Basic Fibroblast Growth Factor for Treatment of Wrinkles and Depressed Areas of the Skin. (United States)

    Kamakura, Tatsuro; Kataoka, Jiro; Maeda, Kazuhiko; Teramachi, Hideaki; Mihara, Hisayuki; Miyata, Kazuhiro; Ooi, Kouichi; Sasaki, Naomi; Kobayashi, Miyuki; Ito, Kouhei


    There are several treatments for wrinkles and depressed areas of the face, hands, and body. Hyaluronic acid is effective, but only for 6 months to 1 year. Autologous fat grafting may cause damage during tissue harvest. In this study, patients were injected with platelet-rich plasma plus basic fibroblast growth factor (bFGF). Platelet-rich plasma was prepared by collecting blood and extracting platelets using double centrifugation. Basic fibroblast growth factor diluted with normal saline was added to platelet-rich plasma. There were 2005 patients who received platelet-rich plasma plus bFGF therapy. Of the 2005 patients treated, 1889 were female and 116 were male patients; patients had a mean age of 48.2 years. Treated areas inlcuded 1461 nasolabial folds, 437 marionette lines, 1413 nasojugal grooves, 148 supraorbital grooves, 253 midcheek grooves, 304 foreheads, 49 temples, and 282 glabellae. Results on the Global Aesthetic Improvement Scale indicated that the level of patient satisfaction was 97.3 percent and the level of investigator satisfaction was 98.4 percent. The period for the therapy's effectiveness to become apparent was an average of 65.4 days. Platelet-rich plasma plus bFGF therapy resulted in an improved grade on the Wrinkle Severity Rating Scale. Improvement was 0.55 for a Wrinkle Severity Rating Scale grade of 2, 1.13 for a Wrinkle Severity Rating Scale grade of 3, 1.82 for a Wrinkle Severity Rating Scale grade of 4, and 2.23 for a Wrinkle Severity Rating Scale grade of 5. Platelet-rich plasma plus bFGF is effective in treating wrinkles and depressed areas of the skin of the face and body. The study revealed that platelet-rich plasma plus bFGF is an innovative therapy that causes minimal complications. Therapeutic, IV.

  2. Bivalirudin and clopidogrel with and without eptifibatide for elective stenting: effects on platelet function, thrombelastographic indexes, and their relation to periprocedural infarction results of the CLEAR PLATELETS-2 (Clopidogrel with Eptifibatide to Arrest the Reactivity of Platelets) study. (United States)

    Gurbel, Paul A; Bliden, Kevin P; Saucedo, Jorge F; Suarez, Thomas A; DiChiara, Joseph; Antonino, Mark J; Mahla, Elisabeth; Singla, Anand; Herzog, William R; Bassi, Ashwani K; Hennebry, Thomas A; Gesheff, Tania B; Tantry, Udaya S


    The primary objective of this study was to compare the effect of therapy with bivalirudin alone versus bivalirudin plus eptifibatide on platelet reactivity measured by turbidometric aggregometry and thrombin-induced platelet-fibrin clot strength (TIP-FCS) measured by thrombelastography in percutaneous coronary intervention (PCI) patients. The secondary aim was to study the relation of platelet aggregation and TIP-FCS to the occurrence of periprocedural infarction. Bivalirudin is commonly administered alone to clopidogrel naïve (CN) patients and to patients on maintenance clopidogrel therapy (MT) undergoing elective stenting. The effect of adding eptifibatide to bivalirudin on platelet reactivity (PR) and TIP-FCS, and their relation to periprocedural infarction in these patients are unknown. Patients (n = 200) stratified to clopidogrel treatment status were randomly treated with bivalirudin (n = 102) or bivalirudin plus eptifibatide (n = 98). One hundred twenty-eight CN patients were loaded with 600 mg clopidogrel immediately after stenting, and 72 MT patients were not loaded. The PR, TIP-FCS, and myonecrosis markers were serially determined. In CN and MT patients, bivalirudin plus eptifibatide was associated with markedly lower PR at all times (5- and 20-microM adenosine diphosphate-induced, and 15- and 25-microM thrombin receptor activator peptide-induced aggregation; p eptifibatide to bivalirudin lowered PR to multiple agonists and the tensile strength of the TIP-FCS, 2 measurements strongly associated with periprocedural myonecrosis. Future studies of PR and TIP-FCS for elective stenting may facilitate personalized antiplatelet therapy and enhance the selection of patients for glycoprotein IIb/IIIa blockade. (Peri-Procedural Myocardial Infarction, Platelet Reactivity, Thrombin Generation, and Clot Strength: Differential Effects of Eptifibatide + Bivalirudin Versus Bivalirudin [CLEAR PLATELETS-2]; NCT00370045.

  3. Association of PEAR1 genetic variants with platelet reactivity in response to dual antiplatelet therapy with aspirin and clopidogrel in the Chinese patient population after percutaneous coronary intervention. (United States)

    Yao, Yi; Tang, Xiao-Fang; Zhang, Jia-Hui; He, Chen; Ma, Yuan-Liang; Xu, Jing-Jing; Song, Ying; Liu, Ru; Meng, Xian-Min; Song, Lei; Chen, Jue; Wang, Miao; Xu, Bo; Gao, Run-Lin; Yuan, Jin-Qing


    Platelet Endothelial Aggregation Receptor-1 (PEAR1) is a recently reported platelet transmembrane protein which plays an important role in platelet aggregation. The aim of this study was to investigate whether PEAR1 genetic variations were associated with platelet reactivity as assessed by adenosine diphosphate(ADP)-induced platelet aggregation in Chinese patients treated with aspirin and clopidogrel. Patients with coronary heart disease (CHD) who underwent percutaneous coronary intervention (PCI) were enrolled in the study. All patients were on dual antiplatelet therapy with aspirin and clopidogrel. ADP-induced platelet aggregation was measured by thromboelastography and defined as percent inhibition of platelet aggregation (IPA). Patients (n=204) with IPA 70% were identified as low on-treatment platelet reactivity (LPR). Sixteen single nucleotide polymorphisms (SNPs) of PEAR1 were determined by a method of improved multiple ligase detection reaction. Among the 16 SNPs examined by univariate analysis, 5 SNPs were significantly associated with ADP-induced platelet aggregation. Minor allele C at rs11264580 (p=0.033), minor allele G at rs2644592 (p=0.048), minor allele T at rs3737224 (p=0.033) and minor allele T at rs41273215 (p=0.025) were strongly associated with HPR, whereas homozygous TT genotype at rs57731889 (p=0.009) was associated with LPR. Multivariate logistic regression analysis further revealed that the minor allele T at rs41273215 (p=0.038) was an independent predictor of HPR and the homozygous TT genotype at rs57731889 (p=0.003) was an independent predictor of LPR. PEAR1 genetic variations were strongly associated with ADP-induced platelet aggregation in Chinese patients with CHD treated with aspirin and clopidogrel. These genetic variations may contribute to the variability in platelet function. The utility of PEAR1 genetic variants in the assessment and prediction of cardiovascular risk warrants further investigation. Copyright © 2016 Elsevier Ltd

  4. Blood platelets in the progression of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Nina S Gowert

    Full Text Available Alzheimer's disease (AD is characterized by neurotoxic amyloid-ß plaque formation in brain parenchyma and cerebral blood vessels known as cerebral amyloid angiopathy (CAA. Besides CAA, AD is strongly related to vascular diseases such as stroke and atherosclerosis. Cerebrovascular dysfunction occurs in AD patients leading to alterations in blood flow that might play an important role in AD pathology with neuronal loss and memory deficits. Platelets are the major players in hemostasis and thrombosis, but are also involved in neuroinflammatory diseases like AD. For many years, platelets were accepted as peripheral model to study the pathophysiology of AD because platelets display the enzymatic activities to generate amyloid-ß (Aß peptides. In addition, platelets are considered to be a biomarker for early diagnosis of AD. Effects of Aß peptides on platelets and the impact of platelets in the progression of AD remained, however, ill-defined. The present study explored the cellular mechanisms triggered by Aß in platelets. Treatment of platelets with Aß led to platelet activation and enhanced generation of reactive oxygen species (ROS and membrane scrambling, suggesting enhanced platelet apoptosis. More important, platelets modulate soluble Aß into fibrillar structures that were absorbed by apoptotic but not vital platelets. This together with enhanced platelet adhesion under flow ex vivo and in vivo and platelet accumulation at amyloid deposits of cerebral vessels of AD transgenic mice suggested that platelets are major contributors of CAA inducing platelet thrombus formation at vascular amyloid plaques leading to vessel occlusion critical for cerebrovascular events like stroke.

  5. Assessment of platelet profile of healthy volunteers in the trimesters ...

    African Journals Online (AJOL)

    Assessment of platelet profile of healthy volunteers in the trimesters of pregnancy in Benin City, Nigeria. ... Thus PDW compensates for these reductions and a lack of this compensatory increase may aggravate the effect of thrombocytopenia in pregnancy. Platelet Count, Plateletcrit, Mean Platelet Volume, Platelet ...

  6. Brief Report: Platelet-Poor Plasma Serotonin in Autism (United States)

    Anderson, George M.; Hertzig, Margaret E.; McBride, P. A.


    Possible explanations for the well-replicated platelet hyperserotonemia of autism include an alteration in the platelet's handling of serotonin (5-hydroxyserotonin, 5-HT) or an increased exposure of the platelet to 5-HT. Measurement of platelet-poor plasma (PPP) levels of 5-HT appears to provide the best available index of in vivo exposure of the…

  7. 21 CFR 864.6650 - Platelet adhesion test. (United States)


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Platelet adhesion test. 864.6650 Section 864.6650...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6650 Platelet adhesion test. (a) Identification. A platelet adhesion test is a device used to determine in vitro platelet...

  8. Quality assessment of platelet concentrates prepared by platelet rich plasma-platelet concentrate, buffy coat poor-platelet concentrate (BC-PC and apheresis-PC methods

    Directory of Open Access Journals (Sweden)

    Singh Ravindra


    Full Text Available Background: Platelet rich plasma-platelet concentrate (PRP-PC, buffy coat poor-platelet concentrate (BC-PC, and apheresis-PC were prepared and their quality parameters were assessed. Study Design: In this study, the following platelet products were prepared: from random donor platelets (i platelet rich plasma - platelet concentrate (PRP-PC, and (ii buffy coat poor- platelet concentrate (BC-PC and (iii single donor platelets (apheresis-PC by different methods. Their quality was assessed using the following parameters: swirling, volume of the platelet concentrate, platelet count, WBC count and pH. Results: A total of 146 platelet concentrates (64 of PRP-PC, 62 of BC-PC and 20 of apheresis-PC were enrolled in this study. The mean volume of PRP-PC, BC-PC and apheresis-PC was 62.30±22.68 ml, 68.81±22.95 ml and 214.05±9.91 ml and ranged from 22-135 ml, 32-133 ml and 200-251 ml respectively. The mean platelet count of PRP-PC, BC-PC and apheresis-PC was 7.6±2.97 x 1010/unit, 7.3±2.98 x 1010/unit and 4.13±1.32 x 1011/unit and ranged from 3.2-16.2 x 1010/unit, 0.6-16.4 x 1010/unit and 1.22-8.9 x 1011/unit respectively. The mean WBC count in PRP-PC (n = 10, BC-PC (n = 10 and apheresis-PC (n = 6 units was 4.05±0.48 x 107/unit, 2.08±0.39 x 107/unit and 4.8±0.8 x 106/unit and ranged from 3.4 -4.77 x 107/unit, 1.6-2.7 x 107/unit and 3.2 - 5.2 x 106/unit respectively. A total of 26 units were analyzed for pH changes. Out of these units, 10 each were PRP-PC and BC-PC and 6 units were apheresis-PC. Their mean pH was 6.7±0.26 (mean±SD and ranged from 6.5 - 7.0 and no difference was observed among all three types of platelet concentrate. Conclusion: PRP-PC and BC-PC units were comparable in terms of swirling, platelet count per unit and pH. As expected, we found WBC contamination to be less in BC-PC than PRP-PC units. Variation in volume was more in BC-PC than PRP-PC units and this suggests that further standardization is required for preparation of BC

  9. Platelet thrombosis in cardiac-valve prostheses

    Energy Technology Data Exchange (ETDEWEB)

    Dewanjee, M.K.


    The contribution of platelets and clotting factors in thrombosis on cardiovascular prostheses had been quantified with several tracers. Thrombus formation in vivo could be measured semiquantitatively in animal models and patients with indium-111, Technetium-99m labeled platelets, iodine-123, iodine-131 labeled fibrinogen, and In-111 and Tc-99m labeled antibody to the fibrinogen-receptor on the platelet- membrane, or fibrin. The early studies demonstrated that certain platelet-inhibitors, e.g. sulfinpyrazone, aspirin or aspirin- persantine increased platelet survival time with mechanical valves implanted in the baboon model and patients. Thrombus localization by imaging is possible for large thrombus on thrombogenic surface of prosthesis in the acute phase. The majority of thrombus was found in the sewing ring (Dacron) in the acute phase in both the mechanical and tissue valves. The amount of retained thrombus in both mechanical and tissue valves in our one-day study in the dog model was similar (< 1% if injected In-111 platelets = 5 billion platelets). As the fibrous ingrowth covered the sewing ring, the thrombus formation decreased significantly. Only a small amount of thrombus was found on the leaflets at one month in both the dog and calf models. 38 refs., 9 figs., 5 tabs.

  10. Aspirin treatment reduces platelet resistance to deformation. (United States)

    Burris, S M; Smith, C M; Rao, G H; White, J G


    The present investigation has evaluated the influence of aspirin, its constituents, and other nonsteroidal anti-inflammatory agents on the resistance of human platelets to aspiration into micropipettes. Aspirin increased the length of platelet extensions into the micropipette over the entire negative tension range of 0.04 to 0.40 dynes/cm after exposure to the drug in vitro or after ingestion of the agent. Other cyclooxygenase inhibitors, ibuprofen and indomethacin, did not increase platelet deformability. The influence of aspirin was mimicked to some degree by high concentrations of salicylic acid, but acetylation of platelets with acetic anhydride had little influence on platelet deformability. Incubation of platelets with both salicylic acid and acetic anhydride had no more effect than salicylic acid alone. Benzoic acid, chemically similar to salicylic acid, had a minimal effect. The studies demonstrate that aspirin makes platelets more deformable, while components of the drug or other nonsteroidal antiinflammatory agents and cyclooxygenase inhibitors do not have the same influence on resistance to deformation.

  11. Use of platelet rich fibrin in a fenestration defect around an implant

    Directory of Open Access Journals (Sweden)

    R Vijayalakshmi


    Full Text Available Guided bone regeneration (GBR in implant therapy is especially useful for implant placement with dehiscence defects or fenestration defects. In alveolar ridges with marked facial/buccal depressions or in knifeedge alveolar crests, the position and direction of fixture placement is restricted. Improvement of alveolar ridge morphology becomes possible with GBR. This article describes a case in which the fenestration defect around an implant was treated by the application of platelet rich fibrin, a second generation platelet concentrate along with bone graft, and guided tissue regeneration membrane.

  12. Autologous Blood and Platelet-Rich Plasma Injections for Treatment of Lateral Epicondylitis. (United States)

    Calandruccio, James H; Steiner, Murphy M


    Lateral epicondylitis (tennis elbow) is a frequent cause of elbow pain; most patients (80%-90%) are successfully treated with standard nonoperative methods (rest, nonsteroidal anti-inflammatory drugs, bracing, and physical therapy). Autologous blood injections and platelet-rich plasma injections are the two most frequently used orthobiologic techniques in the treatment of lateral epicondylitis. Studies of the effectiveness of autologous blood injections and platelet-rich plasma report varying outcomes, some citing significant clinical relief and others reporting no beneficial effect. More research is needed to determine how to best use orthobiologics in the treatment of lateral epicondylitis. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Viability and functional integrity of washed platelets

    Energy Technology Data Exchange (ETDEWEB)

    Pineda, A.A.; Zylstra, V.W.; Clare, D.E.; Dewanjee, M.K.; Forstrom, L.A.


    The viability and functional integrity of saline- and ACD-saline-washed platelets were compared with those of unwashed platelets. After template bleeding time (TBT) was measured, 15 healthy volunteers underwent plateletpheresis and ingested 600 mg of aspirin. Autologous /sup 111/In-labeled platelets were transfused: unwashed (n = 5), washed with 0.9 percent saline solution (SS) (n = 5), and washed with a buffered 12.6 percent solution of ACD-A in 0.9 percent saline solution (n = 5). After transfusion, we measured TBT at 1, 4, and 24 hours; platelet survival at 10 minutes and 1, 4, and 24 hours and daily for 6 days; and the percentage of uptake in liver and spleen by quantitative whole-body radionuclide scintigraphy at 24 and 190 hours. We found that saline washing affected platelet recovery, 23.47 +/- 12 percent (p less than 0.001) as compared to 52.43 +/- 17 percent (p less than 0.002) for ACD-saline and 73.17 +/- 8 percent for control; that saline washing resulted in a greater liver uptake than control and ACD-saline-washed platelets (31.9 +/- 8% (p less than 0.001) vs 17.7 +/- 4.1 and 19.3 +/- 2.1% (p greater than 0.1), respectively); that, unlike control and ACD-saline-washed platelets, saline-washed platelets did not shorten bleeding time; and that neither type of washing affected survival. Although ACD-saline washing affects recovery, it also results in intact function, normal survival, higher recovery than SS platelets, and no significant liver uptake.

  14. Decrease in platelet activating factor stimulated phosphoinositide turnover during storage of human platelets in plasma

    Energy Technology Data Exchange (ETDEWEB)

    Carter, M.G.; Shukla, S.D. (Univ. of Missouri School of Medicine, Columbia (USA))


    Human platelet concentrate from the American Red Cross Blood Center was stored at 24{degree}C in a shaker and aliquots were taken out at time intervals aseptically. Platelet activating factor (PAF) stimulated turnover of phosphoinositide (PPI) was monitored by assaying {sup 32}P incorporation into phosphoinositides using platelet rich plasma (PRP). Platelets in PRP were incubated with 1 {times} 10{sup {minus}7} M PAF at 37{degree}C with gentle shaking and after 5 min their lipids were extracted and analysed by TLC for {sup 32}P-phosphoinositides. The percent stimulation of {sup 32}P incorporation by PAF (over control) into PPI was approximately 250, 100, 60, 25 and 20 on days 1, 2, 3, 5 and 6, respectively. This indicated a dramatic decrease in PAF responsive turnover of platelet PPI during storage. These findings have important implications in relation to PAF receptor activity and viability of platelets at different periods of storage.

  15. Cancer and Thrombotic Risk: The Platelet Paradigm

    Directory of Open Access Journals (Sweden)

    Elizabeth C. Lee


    Full Text Available Hematologic malignancies and solid tumors increase the risk of venous and arterial thrombosis and contribute greatly to patient morbidity and mortality. Thrombosis occurs when the intricate balance of circulating antithrombotic and prothrombotic blood elements are disrupted. In recent years, the interplay between paraneoplastic cells and platelets has become apparent, with a change in platelet phenotype causing dysregulated platelet activity. This review discusses mechanism of thrombosis in cancer, evidence for using drug therapy, and exciting research efforts to understand and hopefully control aberrant thrombotic events in patients with cancer.

  16. Haemocompatibility testing of biomaterials using human platelets. (United States)

    Jung, F; Braune, S; Lendlein, A


    Cardiovascular implants are increasingly important in regenerative medicine. To improve the safety and function of blood-contacting implants a major need exists for new polymer-based biomaterials that avoid adverse reactions, particularly thrombotic events. This review is aimed to summarize the multi-stepped and interlinked processes leading to a thrombus growth on body foreign surfaces: protein adsorption, platelet adhesion accompanied by activation and spreading and the release of substances of various organelles activating other neighboured platelets (and the plasmatic coagulation) leading to the formation of a plug of platelets and, finally, to a thrombus.

  17. Transcellular lipoxygenase metabolism between monocytes and platelets

    Energy Technology Data Exchange (ETDEWEB)

    Bigby, T.D.; Meslier, N. (Univ. of California, San Francisco (USA))


    We have examined the effects of co-culture and in vitro co-stimulation on lipoxygenase metabolism in monocytes and platelets. Monocytes were obtained from the peripheral blood of normal volunteers by discontinuous gradient centrifugation and adherence to tissue culture plastic. Platelets were obtained from the platelet-rich plasma of the same donor. When 10(9) platelets and 2.5 x 10(6) monocytes were co-stimulated with 1 microM A23187, these preparations released greater quantities of 12(S)-hydroxy-10-trans-5,8,14-cis-eicosatetraenoic acid, 5(S),12-(S)dihydroxy-6,10-trans-8,14-cis-eicosatetraenoic acid, and leukotriene C4, 5(S)-hydroxy-6(R)-S-glutathionyl-7,9-trans-11,14-cis-eicosatetraenoic (LTC4) when compared with monocytes alone. Release of arachidonic acid, 5-HETE, delta 6-trans-LTB4, and delta 6-trans-12-epi-LTB4 from monocytes was decreased in the presence of platelets. A dose-response curve was constructed and revealed that the above changes became evident when the platelet number exceeded 10(7). Dual radiolabeling experiments with 3H- and 14C-arachidonic acid revealed that monocytes provided arachidonic acid, 5-HETE, and LTA4 for further metabolism by the platelet. Monocytes did not metabolize platelet intermediates detectably. In addition, as much as 1.2 microM 12(S)-hydroxy-10-trans-5,8,14-cis-eicosatetraenoic acid and 12(S)-hydroperoxy-10-trans-5,8,14-cis-eicosatetraenoic acid had no effect on monocyte lipoxygenase metabolism. Platelets were capable of converting LTA4 to LTC4, but conversion of LTA4 to LTB4 was not detected. We conclude that the monocyte and platelet lipoxygenase pathways undergo a transcellular lipoxygenase interaction that differs from the interaction of the neutrophil and platelet lipoxygenase pathways. In this interaction monocytes provide intermediate substrates for further metabolic conversion by platelets in an unidirectional manner.

  18. Platelet Function Analyzed by Light Transmission Aggregometry

    DEFF Research Database (Denmark)

    Hvas, Anne-Mette; Favaloro, Emmanuel J


    function can also be assessed for hyper-aggregability, but this is less often evaluated. Light transmission aggregometry (LTA) was introduced in the early 1960s and has since been considered the gold standard. This optical detection system is based on changes in turbidity measured as a change in light......Analysis of platelet function is widely used for diagnostic work-up in patients with increased bleeding tendency. During the last decades, platelet function testing has also been introduced for evaluation of antiplatelet therapy, but this is still recommended for research purposes only. Platelet...

  19. Flow cytometric assessment of activation of peripheral blood platelets in dogs with normal platelet count and asymptomatic thrombocytopenia. (United States)

    Żmigrodzka, M; Guzera, M; Winnicka, A


    Platelets play a crucial role in hemostasis. Their activation has not yet been evaluated in healthy dogs with a normal and low platelet count. The aim of this study was to determine the influence of activators on platelet activation in dogs with a normal platelet count and asymptomatic thrombocytopenia. 72 clinically healthy dogs were enrolled. Patients were allocated into three groups. Group 1 consisted of 30 dogs with a normal platelet count, group 2 included 22 dogs with a platelet count between 100 and 200×109/l and group 3 consisted of 20 dogs with a platelet count lower than 100×109/l. Platelet rich-plasma (PRP) was obtained from peripheral blood samples using tripotassium ethylenediaminetetraacetic acid (K3-EDTA) as anticoagulant. Next, platelets were stimulated using phorbol-12-myristate-13-acetate or thrombin, stabilized using procaine or left unstimulated. The expression of CD51 and CD41/CD61 was evaluated. Co-expression of CD41/CD61 and Annexin V served as a marker of platelet activation. The expression of CD41/CD61 and CD51 did not differ between the 3 groups. Thrombin-stimulated platelets had a significantly higher activity in dogs with a normal platelet count than in dogs with asymptomatic thrombocytopenia. Procaine inhibited platelet activity in all groups. In conclusion, activation of platelets of healthy dogs in vitro varied depending on the platelet count and platelet activator.

  20. Platelet function analyzer (PFA)‐100® closure time in the evaluation of platelet disorders and platelet function

    National Research Council Canada - National Science Library



    Background:  Closure time (CT), measured by platelet function analyzer (PFA‐100 ® ) device, is now available to the clinical laboratory as a possible alternative or supplement to the bleeding time test. Aim...

  1. Platelet function recovery after ticagrelor withdrawal in patients awaiting urgent coronary surgery. (United States)

    Hansson, Emma C; Malm, Carl Johan; Hesse, Camilla; Hornestam, Björn; Dellborg, Mikael; Rexius, Helena; Jeppsson, Anders


    Dual antiplatelet therapy with ticagrelor and aspirin is associated with an increased risk of perioperative bleeding complications. Current guidelines recommend therefore discontinuation of ticagrelor 5 days before surgery to allow sufficient recovery of platelet function. It is not known how the time to recovery varies between individual patients after discontinuation of ticagrelor. Twenty-five patients accepted for urgent coronary artery bypass surgery and treated with ticagrelor and aspirin were included in a prospective observational study. Platelet aggregation was evaluated with impedance aggregometry at five timepoints 12-96 h after discontinuation of ticagrelor. In a subset of patients ( n  = 15), we also tested the ex vivo efficacy of platelet concentrate supplementation on platelet aggregation. There was a gradual increase in mean adenosine diphosphate-induced platelet aggregation after discontinuation of ticagrelor. After 72 h, mean aggregation was 38 ±23 aggregation units (U), which is above a previously suggested cut-off of 22 U, when patients can be operated without increased bleeding risk. However, there was a large interindividual variability (range 4‒88 U at 72 h) and 6/24 patients (25%) had ticagrelor discontinuation. Adenosine diphosphate-induced aggregation was acceptable after 72 h in the majority of patients but with a large interindividual variability. Due to the large variability, platelet function testing may prove to be a valuable tool in timing of surgery in patients with ongoing or recently stopped ticagrelor treatment. Adenosine diphosphate-induced aggregation was not improved by addition of platelet concentrate.

  2. Chronic Plantar Fasciitis: Effect of Platelet-Rich Plasma, Corticosteroid, and Placebo. (United States)

    Mahindra, Pankaj; Yamin, Mohammad; Selhi, Harpal S; Singla, Sonia; Soni, Ashwani


    Plantar fasciitis is a common cause of heel pain. It is a disabling disease in its chronic form. It is a degenerative tissue condition of the plantar fascia rather than an inflammation. Various treatment options are available, including nonsteroidal anti-inflammatory drugs, corticosteroid injections, orthosis, and physiotherapy. This study compared the effects of local platelet-rich plasma, corticosteroid, and placebo injections in the treatment of chronic plantar fasciitis. In this double-blind study, patients were divided randomly into 3 groups. Local injections of platelet-rich plasma, corticosteroid, or normal saline were given. Patients were assessed with the visual analog scale for pain and with the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle and Hindfoot score before injection, at 3 weeks, and at 3-month follow-up. Mean visual analog scale score in the platelet-rich plasma and corticosteroid groups decreased from 7.44 and 7.72 preinjection to 2.52 and 3.64 at final follow-up, respectively. Mean AOFAS score in the platelet-rich plasma and corticosteroid groups improved from 51.56 and 55.72 preinjection to 88.24 and 81.32 at final follow-up, respectively. There was a significant improvement in visual analog scale score and AOFAS score in the platelet-rich plasma and corticosteroid groups at 3 weeks and at 3-month follow-up. There was no significant improvement in visual analog scale score or AOFAS score in the placebo group at any stage of the study. The authors concluded that local injection of platelet-rich plasma or corticosteroid is an effective treatment option for chronic plantar fasciitis. Platelet-rich plasma injection is as effective as or more effective than corticosteroid injection in treating chronic plantar fasciitis. Copyright 2016, SLACK Incorporated.

  3. Collagen and Fractionated Platelet-Rich Plasma Scaffold for Dermal Regeneration. (United States)

    Houdek, Matthew T; Wyles, Cody C; Stalboerger, Paul G; Terzic, Andre; Behfar, Atta; Moran, Steven L


    Current options for in vivo regeneration of dermal tissue remain limited. The purpose of this study was to engineer a unique scaffold capable of recruiting dermal stem cells from adjacent tissue, thus circumventing the need to seed the scaffolds with stem cells before implantation, leading to skin regeneration. A hydrogel scaffold was created through combination of type I collagen along with fractionated platelet-rich plasma. This was compared to a control hydrogel consisting of type I collagen and fetal bovine serum. Hydrogels were cultured with fresh human skin tissue and incubated with supplemental media. Gels were digested weekly for cellular content as examined by flow cytometry at the 4- and 8-week time points. The fractionated platelet-rich plasma and collagen gels were then implanted onto full-thickness skin defects on the backs of rats and compared to wounds healing by secondary intention. Wound area was evaluated for epithelialization and neovascularization. Platelet-rich plasma fractionation increased platelet-derived growth factors. In contrast to collagen scaffolds, fractionated platelet-rich plasma-supplemented scaffolds recruited more dermal-derived stem cells from fresh skin tissue compared with collagen hydrogels at the 4- and 8-week time points. Furthermore, fractionated platelet-rich plasma-supplemented hydrogels accelerated wound healing, angiogenesis, and hair and sweat gland formation, ultimately regenerating a dermis-like tissue. Generation of hydrogels with fractionated platelet-rich plasma was able to improve cellular recruitment and growth and differentiation of dermal-derived stem cells, leading to hair growth and sweat gland formation. This provides a novel approach to regenerate skin for treating large defects.

  4. Evidence for the involvement of complement proteins in platelet aggregation by Streptococcus sanguis NCTC 7863. (United States)

    Ford, I; Douglas, C W; Heath, J; Rees, C; Preston, F E


    We investigated the mechanisms of platelet aggregation by the type strain of Streptococcus sanguis (NCTC 7863). This species is one of the major aetiological agents of infective endocarditis. S. sanguis NCTC 7863 caused aggregation of normal human platelets in vitro following a lag period that varied between donors (7-19 min). Platelet aggregation was dependent on one or more plasma constituents and all the necessary factors gradually became bound to the bacterial surface during the lag period. The length of the lag period was determined by the plasma of the donor and not by a feature of their platelets. Platelet aggregation by S. sanguis NCTC 7863 could be inhibited by heating plasma at 56 degrees C, by treating plasma with cobra venom factor, or by incubating with soluble Complement Receptor 1, all of which inhibit or deplete complement. Complement activation required Mg2+, but not Ca2+ ions and the the cleavage fragment, Ba, of factor B was produced, indicating that the alternative pathway was operative. Zymosan- and S. sanguis-induced aggregation showed similarities, including the same variability in lag times among donors, and absorption of plasma with zymosan prevented the plasma from supporting platelet aggregation by S. sanguis, C3, C9 and vitronectin were found to bind to S. sanguis NCTC 7863, but the latter two were present at very low levels on a non-aggregating strain of S. sanguis, SK96. The rate of assembly of the C5b-9 complex on the NCTC 7863 bacterial surface correlated with the lag time. These data suggest a role for the complement pathway in platelet aggregation by the type strain of S. sanguis.

  5. Revascularization of Immature Necrotic Teeth: Platelet rich Fibrin an Edge over Platelet rich Plasma


    Neelam Mittal; Isha Narang


    Introduction: Revascularization is one such entity that has found its clinical application in the field of endodontics for the manage-ment of immature permanent necrotic teeth. The protocols for revascularization of such teeth focus especially on delivery of stem cells and scaffolds in a nonsurgical manner rather than concentrated growth micro molecules.The hypothesis: This article proposes the role of platelet concentrates such as platelet rich fibrin (PRF) and platelet rich plasma (PRP) in ...


    Midura, Emily F.; Kuethe, Joshua W.; Rice, Teresa C.; Veile, Rosalie; England, Lisa G.; Friend, Lou Ann; Caldwell, Charles C.; Goodman, Michael D.


    An acute burn induced coagulopathy develops after scald injury, which evolves into a subacute, hypercoagulable state. Microparticles, specifically platelet-derived MPs (PMPs), have been suggested as possible contributors. We first developed a model of burn-induced coagulopathy and then sought to investigate the role of platelets and PMPs in coagulation after burn. We hypothesized that changes in circulating platelet and PMP populations after injury would contribute to the post-burn, hypercoagulable state. A murine scald model with 28% TBSA full thickness burn injury was utilized and blood samples were collected at intervals after injury. Circulating MP populations, platelet counts, overall coagulation, and platelet function were determined. Burn injury led to hypercoagulability on post-burn day one (PBD1), which persisted 6 days after injury (PBD6). On PBD1, there was a significant decrease in platelet numbers and a decline in platelet contribution to clot formation with a concomitant increase in circulating procoagulant PMPs. On PBD6, there was a significant increase in platelet numbers and in platelet activation with no change in PMPs compared with sham. Further, on PBD1 decreased ADP-induced platelet activation was observed with a contrasting increase in ADP-induced platelet activation on PBD6. We therefore concluded that there was a temporal change in the mechanisms leading to a hypercoagulable state after scald injury, that PMPs are responsible for changes seen on PBD1, and finally that ADP-induced platelet activation was key to the augmented clotting mechanisms 6 days after burn. PMID:26529651

  7. Pathogen-Reduced, Extended Platelet Storage in Platelet Additive Solution (PAS) (United States)


    evaluated, as a potentially preferred product for battlefield polytrauma. This was once standard-of-care in transfusion medicine , but was abandoned...Sound Blood Center, led by Dr. Sherrill J. Slichter, have extensive experience in studying platelet biology and transfusion medicine . Dr. Slichter’s...unit Platelet Concentration   Volume   Platelet yield   Blood Gases (pH and pCO2, PO2, HC03)   Glucose and Lactate   P-selectin

  8. Antioxidants change platelet responses to various stimulating events


    Sobotková, Alžběta; Mášová-Chrastinová, Leona; Suttnar, Jiří; Štikarová, Jana; Májek, Pavel; Reicheltová, Zuzana; Kotlín, Roman; Weisel, John W.; Malý, Martin; Jan E. Dyr


    The role of platelets in hemostasis may be influenced by alteration of the platelet redox state—the presence of antioxidants and the formation of reactive oxygen and nitrogen species. We investigated the effects of two antioxidants, resveratrol and trolox, on platelet activation. Trolox and resveratrol inhibited aggregation of washed platelets and platelet-rich plasma activated by ADP, collagen, and thrombin receptor-activating peptide. Resveratrol was a more effective agent in reducing plate...

  9. Platelet genomics and proteomics in human health and disease


    Macaulay, Iain C.; Carr, Philippa; Gusnanto, Arief; Ouwehand, Willem H.; Fitzgerald, Des; Watkins, Nicholas A.


    Proteomic and genomic technologies provide powerful tools for characterizing the multitude of events that occur in the anucleate platelet. These technologies are beginning to define the complete platelet transcriptome and proteome as well as the protein-protein interactions critical for platelet function. The integration of these results provides the opportunity to identify those proteins involved in discrete facets of platelet function. Here we summarize the findings of platelet proteome and...

  10. Plasma platelet-rich autogenous healing tendon of the gastrocnemius muscle in rabbits

    Directory of Open Access Journals (Sweden)

    Duvaldo Eurides


    Full Text Available Tendon lesions may involve the partial or total section of the common calcaneal tendon and cause postural changes of the member. This study evaluated, after 45 and 90 postoperative days (PO, the repair of the tendon of gastrocnemius muscle of rabbits with topical application of autologous platelet concentrate. Twelve adult rabbits were divided into two groups (n = 6 undergoing cardiac puncture and collection of 10 ml of blood to obtain platelet rich-plasma (PRP. Animals of both groups had a transverse tenotomy in the middle third of the lateral belly of the gastrocnemius tendon and muscle that was approximated with modified Kessler suture and nylon thread. In the animals of the treated group it was applied the average of 490.644 platelets / uL of PRP, per animal over the tendon synthesis. The treated group showed a higher amount of collagen fibers than the control one, and at 90 PO days the intensity of collagen was higher than at 45 days with more fibroblasts in the control than in treated one. The administration of plasma autogenous platelet concentrate in the repair of the gastrocnemius tendon of rabbits stimulates and organizes the repair process and causes early production of collagen fibers.

  11. Single-step separation of platelets from whole blood coupled with digital quantification by interfacial platelet cytometry (iPC). (United States)

    Basabe-Desmonts, L; Ramstrom, S; Meade, G; O'Neill, S; Riaz, A; Lee, L P; Ricco, A J; Kenny, D


    We report the efficient single-step separation of individual platelets from unprocessed whole blood, enabling digital quantification of platelet function using interfacial platelet cytometry (iPC) on a chip. iPC is accomplished by the precision micropatterning of platelet-specific protein surfaces on solid substrates. By separating platelets from whole blood using specific binding to protein spots of a defined size, iPC implements a simple incubate-and-rinse approach, without sample preparation, that enables (1) the study of platelets in the physiological situation of interaction with a protein surface, (2) the choice of the number of platelets bound on each protein spot, from one to many, (3) control of the platelet-platelet distance, including the possibility to study noninteracting single platelets, (4) digital quantification (counting) of platelet adhesion to selected protein matrices, enabling statistical characterization of platelet subpopulations from meaningfully large numbers of single platelets, (5) the study of platelet receptor expression and spatial distribution, and (6) a detailed study of the morphology of isolated single platelets at activation levels that can be manipulated. To date, we have demonstrated 1-4 of the above list. Platelets were separated from whole blood using iPC with fibrinogen, von Willebrand factor (VWF), and anti-CD42b antibody printed "spots" ranging from a fraction of one to several platelet diameters (2-24 μm). The number of platelets captured per spot depends strongly on the protein matrix and the surface area of the spot, together with the platelet volume, morphology, and activation state. Blood samples from healthy donors, a May-Hegglin-anomaly patient, and a Glanzmann's Thrombasthenia patient were analyzed via iPC to confirm the specificity of the interaction between protein matrices and platelets. For example, the results indicate that platelets interact with fibrinogen spots only through the fibrinogen receptor (

  12. Role of platelet-rich-fibrin in enhancing palatal wound healing after free graft

    Directory of Open Access Journals (Sweden)

    Vinita Jain


    Full Text Available Platelet-rich fibrin has long been used as a wound healing therapy in skin wounds and recently evidence has suggested its usage in oral cavity for different treatment procedures. This article proposes an overview of use of platelet-rich fibrin in management of complicated oral wounds. Excessive hemorrhage of the donor area, necrosis of epithelium, and morbidity associated with donor site have been described as the possible complications after harvesting subepithelial connective tissue graft, but little has been mentioned about their management. The article includes a case report of a 45-year-old male patient who showed a delayed wound healing after subepithelial connective tissue graft harvestation, which was treated with platelet-rich fibrin.

  13. The Role of Platelets and ε-Aminocaproic Acid in Arthrogryposis, Renal Dysfunction, and Cholestasis (ARC) Syndrome Associated Hemorrhage. (United States)

    Weyand, Angela C; Lombel, Rebecca M; Pipe, Steven W; Shavit, Jordan A


    Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is a rare disorder associated with platelet abnormalities resembling gray platelet syndrome. Affected patients have normal platelet numbers but abnormal morphology and function. Bleeding symptomatology ranges from postprocedural to spontaneous life-threatening hemorrhage. We report a patient with ARC syndrome and compound heterozygous mutations in VPS33B (vacuolar protein sorting 33B) who presented with significant bleeding requiring numerous admissions and transfusions. She was treated with prophylactic platelet transfusions and ε-aminocaproic acid. This was well-tolerated and significantly decreased transfusion requirements and admissions for bleeding. Our experience provides support for consideration of prophylactic measures in these patients as well as the possibility of using prophylaxis in related disorders. © 2015 Wiley Periodicals, Inc.

  14. Aspirin inhibition of platelet deposition at angioplasty sites: demonstration by platelet scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Cuningham, D.A.; Kumar, B.; Siegel, B.A.; Gilula, L.A.; Totty, W.G.; Welch, M.J.


    In-111 platelet scintigraphy was used to evaluate the effects of prior aspirin administration on the accumulation of In-111-labeled autologous platelets at sites of arterial injury resulting from iliac, femoral, or popliteal transluminal angioplasty in a nonrandomized study of 17 men. The degree of platelet localization at angioplasty sites was significantly less in nine men who had received aspirin in varying doses within the 4 days before angioplasty than in eight men who had not received aspirin for at least two weeks. The results suggest that aspirin treatment before angioplasty limits the early platelet deposition at the angioplasty site in men.

  15. Giant platelet disorder in the Cavalier King Charles Spaniel. (United States)

    Cowan, Sara M; Bartges, Joseph W; Gompf, Rebecca E; Hayes, Jimmy R; Moyers, Tamberlyn D; Snider, Carolyn C; Gerard, David A; Craft, Robert M; Muenchen, Robert A; Carroll, Roger C


    The aim of this study was to describe the clinical, functional, and morphologic characteristics of platelets in Cavalier King Charles Spaniel dogs (Cavaliers). Blood from 69 clinically normal Cavaliers was collected and anticoagulated with ethylenediamine-tetraacetic acid (EDTA) and citrate. Automated and manual platelet counts were obtained. Percent platelet aggregation in response to ADP (2, 4, 8, 16, and 32 microM) was determined. Electron microscopy was performed to examine platelet internal morphology and dense granule distribution. A cardiologist recorded the quality of murmurs. Thrombocytopenia (3 microm) were present in 33.33% (22/69). Mean manual platelet count was 118,770/microL. Manual (EDTA blood) and automated (EDTA and citrated blood) methods of platelet counting were correlated. Prevalence of cardiac murmurs was 38% (26/69). There was no association between affected dogs and murmur, signalment, or coat color. Mean percent platelet aggregation was significantly higher in controls than in Cavaliers (79% vs 38%, p=0.001). Response to ADP was unaffected by thrombocytopenia, macrothrombocytes, murmur, or any combination thereof. Platelet electron microscopy showed normal and giant sized platelets with normal internal morphology. A benign inherited giant platelet disorder affects approximately 50% of Cavalier King Charles Spaniels. It is characterized by thrombocytopenia, macrothrombocytes, or decreased platelet aggregation in response to ADP. Platelet ultrastructure is normal. Citrated or EDTA blood provides accurate platelet counts. Further studies are indicated to determine platelet glycoprotein structure and any association with mitral endocardiosis. Cavaliers may be useful models of inherited giant platelet disorders.

  16. Platelets induce apoptosis during sepsis in a contact-dependent manner that is inhibited by GPIIb/IIIa blockade.

    Directory of Open Access Journals (Sweden)

    Matthew Sharron

    Full Text Available PURPOSE: End-organ apoptosis is well-described in progressive sepsis and Multiple Organ Dysfunction Syndrome (MODS, especially where platelets accumulate (e.g. spleen and lung. We previously reported an acute sepsis-induced cytotoxic platelet phenotype expressing serine protease granzyme B. We now aim to define the site(s of and mechanism(s by which platelet granzyme B induces end-organ apoptosis in sepsis. METHODS: End-organ apoptosis in murine sepsis (i.e. polymicrobial peritonitis was analyzed by immunohistochemistry. Platelet cytotoxicity was measured by flow cytometry following 90 minute ex vivo co-incubation with healthy murine splenocytes. Sepsis progression was measured via validated preclinical murine sepsis score. MEASUREMENTS AND MAIN RESULTS: There was evident apoptosis in spleen, lung, and kidney sections from septic wild type mice. In contrast, there was a lack of TUNEL staining in spleens and lungs from septic granzyme B null mice and these mice survived longer following induction of sepsis than wild type mice. In co-incubation experiments, physical separation of septic platelets from splenocytes by a semi-permeable membrane reduced splenocyte apoptosis to a rate indistinguishable from negative controls. Chemical separation by the platelet GPIIb/IIIa receptor inhibitor eptifibatide decreased apoptosis by 66.6±10.6% (p = 0.008. Mice treated with eptifibatide in vivo survived longer following induction of sepsis than vehicle control mice. CONCLUSIONS: In sepsis, platelet granzyme B-mediated apoptosis occurs in spleen and lung, and absence of granzyme B slows sepsis progression. This process proceeds in a contact-dependent manner that is inhibited ex vivo and in vivo by the platelet GPIIb/IIIa receptor inhibitor eptifibatide. The GPIIb/IIIa inhibitors and other classes of anti-platelet drugs may be protective in sepsis.

  17. Platelets Induce Apoptosis during Sepsis in a Contact-Dependent Manner That Is Inhibited by GPIIb/IIIa Blockade (United States)

    Sharron, Matthew; Hoptay, Claire E.; Wiles, Andrew A.; Garvin, Lindsay M.; Geha, Mayya; Benton, Angela S.; Nagaraju, Kanneboyina; Freishtat, Robert J.


    Purpose End-organ apoptosis is well-described in progressive sepsis and Multiple Organ Dysfunction Syndrome (MODS), especially where platelets accumulate (e.g. spleen and lung). We previously reported an acute sepsis-induced cytotoxic platelet phenotype expressing serine protease granzyme B. We now aim to define the site(s) of and mechanism(s) by which platelet granzyme B induces end-organ apoptosis in sepsis. Methods End-organ apoptosis in murine sepsis (i.e. polymicrobial peritonitis) was analyzed by immunohistochemistry. Platelet cytotoxicity was measured by flow cytometry following 90 minute ex vivo co-incubation with healthy murine splenocytes. Sepsis progression was measured via validated preclinical murine sepsis score. Measurements and Main Results There was evident apoptosis in spleen, lung, and kidney sections from septic wild type mice. In contrast, there was a lack of TUNEL staining in spleens and lungs from septic granzyme B null mice and these mice survived longer following induction of sepsis than wild type mice. In co-incubation experiments, physical separation of septic platelets from splenocytes by a semi-permeable membrane reduced splenocyte apoptosis to a rate indistinguishable from negative controls. Chemical separation by the platelet GPIIb/IIIa receptor inhibitor eptifibatide decreased apoptosis by 66.6±10.6% (p = 0.008). Mice treated with eptifibatide in vivo survived longer following induction of sepsis than vehicle control mice. Conclusions In sepsis, platelet granzyme B-mediated apoptosis occurs in spleen and lung, and absence of granzyme B slows sepsis progression. This process proceeds in a contact-dependent manner that is inhibited ex vivo and in vivo by the platelet GPIIb/IIIa receptor inhibitor eptifibatide. The GPIIb/IIIa inhibitors and other classes of anti-platelet drugs may be protective in sepsis. PMID:22844498

  18. Efficacy and safety profile of a compound composed of platelet-rich plasma and hyaluronic acid in the treatment for knee osteoarthritis (preliminary results). (United States)

    Abate, Michele; Verna, Sandra; Schiavone, Cosima; Di Gregorio, Patrizia; Salini, Vincenzo


    The combined use of hyaluronic acid and platelet-rich plasma has never been reported in the treatment for osteoarthritis. Aim of this paper was to evaluate the efficacy of this association and to compare retrospectively these results with those of a cohort of patients treated with platelet-rich plasma only. Subjects with mild-to-moderate knee osteoarthritis were enrolled. After clinical and ultrasound evaluation, patients received a weekly intra-articular injection of 2 ml of hyaluronic acid added with 2 ml of platelet-rich plasma for 3 weeks. Follow-up was performed at 1, 3, and 6 months. The same clinical parameters were retrospectively collected from a cohort of patients treated with 4-5 ml of platelet-rich plasma only. Forty knees were treated in both groups. The intra-group comparison showed a significant improvement in clinical and functional outcomes at 1, 3, and 6 months, while the infra-group comparison did not show any significant difference. The association of platelet-rich plasma + hyaluronic acid has the same efficacy of platelet-rich plasma only, administered in higher volume. We may infer that hyaluronic acid works synergically and improves the activity of several molecules contained in platelet-rich plasma.

  19. A New Platelet-Aggregation-Inhibiting Factor Isolated from Bothrops moojeni Snake Venom

    Directory of Open Access Journals (Sweden)

    Bruna Barbosa de Sousa


    Full Text Available This work reports the purification and functional characterization of BmooPAi, a platelet-aggregation-inhibiting factor from Bothrops moojeni snake venom. The toxin was purified by a combination of three chromatographic steps (ion-exchange on DEAE-Sephacel, molecular exclusion on Sephadex G-75, and affinity chromatography on HiTrap™ Heparin HP. BmooPAi was found to be a single-chain protein with an apparent molecular mass of 32 kDa on 14% SDS-PAGE, under reducing conditions. Sequencing of BmooPAi by Edman degradation revealed the amino acid sequence LGPDIVPPNELLEVM. The toxin was devoid of proteolytic, haemorrhagic, defibrinating, or coagulant activities and induced no significant oedema or hyperalgesia. BmooPAi showed a rather specific inhibitory effect on ristocetin-induced platelet aggregation in human platelet-rich plasma, whereas it had little or no effect on platelet aggregation induced by collagen and adenosine diphosphate. The results presented in this work suggest that BmooPAi is a toxin comprised of disintegrin-like and cysteine-rich domains, originating from autolysis/proteolysis of PIII SVMPs from B. moojeni snake venom. This toxin may be of medical interest because it is a platelet aggregation inhibitor, which could potentially be developed as a novel therapeutic agent to prevent and/or treat patients with thrombotic disorders.

  20. Platelet-derived S100 family member myeloid-related protein-14 regulates thrombosis (United States)

    Wang, Yunmei; Fang, Chao; Gao, Huiyun; Bilodeau, Matthew L.; Zhang, Zijie; Croce, Kevin; Liu, Shijian; Morooka, Toshifumi; Sakuma, Masashi; Nakajima, Kohsuke; Yoneda, Shuichi; Shi, Can; Zidar, David; Andre, Patrick; Stephens, Gillian; Silverstein, Roy L.; Hogg, Nancy; Schmaier, Alvin H.; Simon, Daniel I.


    Expression of the gene encoding the S100 calcium–modulated protein family member MRP-14 (also known as S100A9) is elevated in platelets from patients presenting with acute myocardial infarction (MI) compared with those from patients with stable coronary artery disease; however, a causal role for MRP-14 in acute coronary syndromes has not been established. Here, using multiple models of vascular injury, we found that time to arterial thrombotic occlusion was markedly prolonged in Mrp14–/– mice. We observed that MRP-14 and MRP-8/MRP-14 heterodimers (S100A8/A9) are expressed in and secreted by platelets from WT mice and that thrombus formation was reduced in whole blood from Mrp14–/– mice. Infusion of WT platelets, purified MRP-14, or purified MRP-8/MRP-14 heterodimers into Mrp14–/– mice decreased the time to carotid artery occlusion after injury, indicating that platelet-derived MRP-14 directly regulates thrombosis. In contrast, infusion of purified MRP-14 into mice deficient for both MRP-14 and CD36 failed to reduce carotid occlusion times, indicating that CD36 is required for MRP-14–dependent thrombosis. Our data identify a molecular pathway of thrombosis that involves platelet MRP-14 and CD36 and suggest that targeting MRP-14 has potential for treating atherothrombotic disorders, including MI and stroke. PMID:24691441

  1. Physiopathology of blood platelets and development of platelet substitutes. Progress report, August 1, 1975--July 31, 1976

    Energy Technology Data Exchange (ETDEWEB)

    Baldini, M G


    Progress is reported on studies on the physiology of blood platelets in thrombocytopenic patients and rabbits. Methods for the detection of platelet antibodies and the preservation of platelets in vitro were investigated. Studies on the effect of low doses of x irradiation (up to 1000 R) on platelet function indicate that platelets exposed to ionizing radiation have increased functional activity. A list is included of publications that report the results of the studies in detail.

  2. Transcriptomic profiling of platelet senescence and platelet extracellular vesicles. (United States)

    Pienimaeki-Roemer, Annika; Konovalova, Tatiana; Musri, Melina M; Sigruener, Alexander; Boettcher, Alfred; Meister, Gunter; Schmitz, Gerd


    Platelets (PLTs) are derived from megakaryocytes during PLT shedding. Senescent or activated PLTs are expanded in vascular and neurological diseases and release PLT extracellular vesicles (PL-EVs). A systematic analysis of regular messenger RNA (mRNA) and small RNA composition in PLTs and PL-EVs during in vitro PLT senescence has not yet been published. We isolated PLTs, total PL-EVs, and PL-EV subsets on Days 0 and 5 from human stored donor platelet concentrates. Isolated mRNA species and microRNA (miRNA) species were analyzed by microarrays and deep sequencing. Correlation of mRNA and miRNA species (miR) and miRNA target analyses were performed using bioinformatics. During in vitro PLT senescence, residual PLT mRNA species were decreased and partially converted to miRNA species. Residual mRNAs included encoded genes relevant for atherosclerosis, inflammation (matrix metallopeptidase 14 [MMP-14], granulin [GRN], angiopoietin like 2 [ANGPTL2]), and neurotransmission (dopamine receptor 2 [DRD2], γ-aminobutyric acid type A receptor ρ3 [GABRR3]). Compared with senescent PLTs, PL-EVs have up-regulated their miRNA species involved in "diabesity" and in vascular and metabolic disease (miR-144-3p, miR-486-5p, miR-142-5p, miR-451a, miR-25-3p, miR-145-5p, and let-7f-5p). The 100 highest expressed PL-EV miRNA species determined by microarrays were compared with the 100 highest expressed PL-EV miRNA species detected by deep sequencing. This approach resulted in 66 overlaps. The regulated miRNAs (assessed by both methods) were related to neurological disorders, including targets for Alzheimer's disease (e.g., β-site amyloid precursor protein APP-cleaving enzyme 1 [BACE1], translocase of outer mitochondrial membrane 40 homolog [TOMM40], neuron navigator 3 [NAV3]). During in vitro senescence, PLTs degrade large RNA species. Concomitantly, they up-regulate a distinct set of known small RNA species involved in atherosclerosis, inflammation, and neurodegeneration. PL-EVs enrich

  3. Sodium Bicarbonate Facilitates Hemostasis in the Presence of Cerebrospinal Fluid Through Amplification of Platelet Aggregation. (United States)

    Kozuma, Yukinori; Yamamoto, Tetsuya; Ishikawa, Eiichi; Yoshida, Fumiyo; Akutsu, Hiroyoshi; Matsuda, Masahide; Nakai, Kei; Tsuruta, Wataro; Takano, Shingo; Matsumura, Akira; Ninomiya, Haruhiko


    Appropriate hemostasis is essential for clear visualization of the neural structures and cleavage planes. It is also essential for avoiding heat-induced injury, minimizing blood loss, and reducing operative time. To determine the role of cerebrospinal fluid (CSF) in platelet-dependent hemostasis during neurosurgery. The amplification of aggregation, activation of integrin αIIbβ3, intrinsic and extrinsic coagulation pathways, and activation of signaling cascades in platelets were evaluated. For comparison, various concentrations of a commercially available artificial CSF solution (aCSF), an artificial CSF solution prepared by the authors, and normal saline (NS) were used. Differences between aCSF and NS in obtaining in vivo hemostasis were assessed by measuring the tail vein bleeding time in C57BL/6N mice. Platelet aggregation was directly amplified by the addition of aCSF through increased activation of integrin αIIbβ3, phosphatidylserine exposure, and P-selectin expression. However, the prothrombin time and activated partial thromboplastin time were not primarily related to coagulation activity with the addition of aCSF. Activation of Src kinase was related to platelet activation by aCSF. The elimination of sodium bicarbonate from aCSF and the addition of the selective inhibitor of the HCO3/Cl exchanger, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt, significantly inhibited platelet aggregation. The bleeding time in aCSF-treated mice was significantly shorter than that in NS-treated mice. Sodium bicarbonate facilitates hemostasis through the amplification of platelet aggregation function. The existence of CSF and irrigation with aCSF provide better conditions for physiological hemostasis and they have the potential of improving hemostasis by bipolar coagulation or with irrigation during neuroendoscopic procedures.

  4. A Novel Model of Intravital Platelet Imaging Using CD41-ZsGreen1 Transgenic Rats.

    Directory of Open Access Journals (Sweden)

    Makoto Mizuno

    Full Text Available Platelets play pivotal roles in both hemostasis and thrombosis. Although models of intravital platelet imaging are available for thrombosis studies in mice, few are available for rat studies. The present effort aimed to generate fluorescent platelets in rats and assess their dynamics in a rat model of arterial injury. We generated CD41-ZsGreen1 transgenic rats, in which green fluorescence protein ZsGreen1 was expressed specifically in megakaryocytes and thus platelets. The transgenic rats exhibited normal hematological and biochemical values with the exception of body weight and erythroid parameters, which were slightly lower than those of wild-type rats. Platelet aggregation, induced by 20 μM ADP and 10 μg/ml collagen, and blood clotting times were not significantly different between transgenic and wild-type rats. Saphenous arteries of transgenic rats were injured with 10% FeCl3, and the formation of fluorescent thrombi was evaluated using confocal microscopy. FeCl3 caused time-dependent increases in the mean fluorescence intensity of injured arteries of vehicle-treated rats. Prasugrel (3 mg/kg, p.o., administered 2 h before FeCl3, significantly inhibited fluorescence compared with vehicle-treated rats (4.5 ± 0.4 vs. 14.9 ± 2.4 arbitrary fluorescence units at 30 min, respectively, n = 8, P = 0.0037. These data indicate that CD41-ZsGreen1 transgenic rats represent a useful model for intravital imaging of platelet-mediated thrombus formation and the evaluation of antithrombotic agents.

  5. [Platelet rich plasma versus oral paracetamol for the treatment of early knee osteoarthritis. Preliminary study]. (United States)

    Acosta-Olivo, Carlos; Esponda-Colmenares, Francisco; Vilchez-Cavazos, Félix; Lara-Arias, Jorge; Mendoza-Lemus, Oscar; Ramos-Morales, Tomas


    in the treatment of early osteoartrosis, analgesics and non-steroidal anti-inflammatory drugs are frequently used to relieve pain. Currently, platelet rich plasma is used as an alternative in the treatment of osteoartrosis. The aim of this study was to evaluate the effect of platelet rich plasma compared to paracetamol as a treatment for patients with knee osteoartrosis grade I. we evaluated 42 patients who were randomized into two groups. Group one was treated with 5 mL of platelet rich plasma in two applications, while group two was treated with 1 gr of oral paracetamol every 8 hours for 30 days. Both patient groups received supervised physical rehabilitation during the 6 month observation period. Peripheral blood samples were taken to measure plasma IL-1β, TNF-a and TGF-β1 levels at day 0 and at 6 months post-treatment. Clinical evaluation was conducted using the KOOS at the start of the study and for every subsequent month during the study period. the Knee injury and Osteoarthritis Outcome Score (KOOS) for group one at the start of the treatment was measured at 30.1 points, whereas at the end, it was measured at 48.2 points, showing a clinical improvement of 60%. There were no statistically significant differences in IL-1β and TNF-a levels between groups treated either with platelet rich plasma or paracetamol. Our patients treated with platelet rich plasma showed a statistically significant increase in the serum levels of TGF-β1, which was associated with an improvement in the clinical evaluation used (KOOS).

  6. Mildly oxidized HDL decrease agonist-induced platelet aggregation and release of pro-coagulant platelet extracellular vesicles. (United States)

    Tafelmeier, M; Fischer, A; Orsó, E; Konovalova, T; Böttcher, A; Liebisch, G; Matysik, S; Schmitz, G


    Stored platelet concentrates (PLCs) for therapeutic purpose, develop a platelet storage lesion (PSL), characterized by impaired platelet (PLT) viability and function, platelet extracellular vesicle (PL-EV) release and profound lipidomic changes. Whereas oxidized low-density lipoprotein (oxLDL) activates PLTs and promotes atherosclerosis, effects linked to oxidized high-density lipoprotein (oxHDL) are poorly characterized. PLCs from blood donors were treated with native (nHDL) or mildly oxidized HDL (moxHDL) for 5days under blood banking conditions. Flow cytometry, nanoparticle tracking analysis (NTA), aggregometry, immunoblot analysis and mass spectrometry were carried out to analyze PL-EV and platelet exosomes (PL-EX) release, PLT aggregation, protein expression, and PLT and plasma lipid composition. In comparison to total nHDL, moxHDL significantly decreased PL-EV release by -36% after 5days of PLT storage and partially reversed agonist-induced PLT aggregation. PL-EV release positively correlated with PLT aggregation. MoxHDL improved PLT membrane lipid homeostasis through enhanced uptake of lysophospholipids and their remodeling to corresponding phospholipid species. This also appeared for sphingomyelin (SM) and d18:0/d18:1 sphingosine-1-phosphate (S1P) at the expense of ceramide (Cer) and hexosylceramide (HexCer) leading to reduced Cer/S1P ratio as PLT-viability indicator. This membrane remodeling was associated with increased content of CD36 and maturation of scavenger receptor-B1 (SR-B1) protein in secreted PL-EVs. MoxHDL, more potently than nHDL, improves PLT-membrane lipid homeostasis, partially antagonizes PL-EV release and agonist-induced PLT aggregation. Altogether, this may be the result of more efficient phospho- and sphingolipid remodeling mediated by CD36 and SR-B1 in the absence of ABCA1 on PLTs. As in vitro supplement in PLCs, moxHDL has the potential to improve PLC quality and to prolong storage. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Comparison of Platelet Reactivity in Black Versus White Patients With Acute Coronary Syndromes After Treatment With Ticagrelor. (United States)

    Gaglia, Michael A; Lipinski, Michael J; Lhermusier, Thibault; Steinvil, Arie; Kiramijyan, Sarkis; Pokharel, Shreejana; Torguson, Rebecca; Angiolillo, Dominick J; Wallentin, Lars; Storey, Robert F; Waksman, Ron


    Ticagrelor, a potent platelet inhibitor, has primarily been studied in white patients. Platelet reactivity among black patients with acute coronary syndrome (ACS) on ticagrelor, however, is unknown. Our objective was to compare platelet reactivity in black versus white patients with ACS treated with ticagrelor. We conducted a prospective, pharmacodynamic study of 29 black patients with ACS treated with ticagrelor. Platelet reactivity was assessed at 1, 4, and 8 hours after a loading dose of ticagrelor 180 mg and at 30 days on a maintenance dose of ticagrelor 90 mg twice daily. Assays included light transmission aggregometry, VerifyNow P2Y12, and vasodilator-stimulated phosphoprotein. We provided comparison with a historical white cohort. Platelet reactivity among blacks with ACS on ticagrelor was similar to that in whites, except that blacks had lower values at 4 hours, 8 hours, and on maintenance therapy for light transmission aggregometry with 20 μmol/L adenosine diphosphate. Among blacks, high-on-treatment platelet reactivity for all 3 assays was uncommon at 1 hour and nonexistent at 4 hours, 8 hours, and while on maintenance therapy. Blacks preloaded with clopidogrel (n = 17) had significantly lower results of VerifyNow (64 ± 65 vs 198 ± 86, p ticagrelor, levels of platelet reactivity in blacks are similar to that in whites. This suggests that the cardiovascular benefits of ticagrelor observed in the platelet inhibition and patient outcomes (PLATO) trial are likely to be observed in blacks and whites. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. P2Y12 Receptor Blockade Augments Glycoprotein IIb‐IIIa Antagonist Inhibition of Platelet Activation, Aggregation, and Procoagulant Activity (United States)

    Berny‐Lang, Michelle A.; Jakubowski, Joseph A.; Sugidachi, Atsuhiro; Barnard, Marc R.; Michelson, Alan D.; Frelinger, Andrew L.


    Background New antiplatelet agents that provide greater, more consistent inhibition of the platelet ADP receptor P2Y12 may be used in combination with glycoprotein (GP) IIb‐IIIa antagonists, but their combined effect on platelet function and procoagulant activity is not well studied. Therefore, the objective of this study was to evaluate the independent and complementary effects of P2Y12 and GPIIb‐IIIa inhibition on platelet function and procoagulant activity. Methods and Results Healthy donor blood was treated with the active metabolite of prasugrel (R‐138727 5 μmol/L), GPIIb‐IIIa antagonists (abciximab 3 μg/mL or eptifibatide 0.9 μg/mL), and combinations thereof, exposed to physiologically relevant agonists (collagen and ADP) and then evaluated for markers of platelet activation and procoagulant activity. Significant interactions between R‐138727 and GPIIb‐IIIa antagonists were observed. R‐138727 and the GPIIb‐IIIa antagonists had additive inhibitory effects on collagen‐stimulated platelet aggregation and on the collagen plus ADP–stimulated level of activated platelet surface GPIIb‐IIIa. R‐138727 and abciximab each inhibited collagen plus ADP–stimulated platelet phosphatidylserine expression and prothrombin cleavage, and the combination produced greater inhibition than achieved with abciximab alone. In contrast, eptifibatide did not inhibit, but instead enhanced, collagen plus ADP–stimulated prothrombin cleavage. Addition of R‐138727 reduced prothrombin cleavage in eptifibatide‐treated samples, suggesting a novel mechanism for potential benefit from combined prasugrel and eptifibatide treatment. Conclusions The complementary effects of abciximab and R‐138727 on platelet activation, aggregation, and procoagulant activity suggest their combined use may, to a greater degree than with either agent alone, reduce thrombus formation in vivo. PMID:23676293

  9. A unique elastase in human blood platelets.


    James, H L; Wachtfogel, Y T; James, P L; Zimmerman, M; Colman, R W; Cohen, A. B.


    Previous investigations suggested that elastolytic activity found in platelets could be due to contamination by neutrophil elastase. In the present study, the lysate of blood platelets free of detectable neutrophils was examined for elastase-like activity using tertiary-butyloxycarbonyl (tBOC)-ala-ala-pro-ala-aminomethyl coumarin (I), tBOC-ala-ala-pro-val-aminomethyl coumarin (II), and succinyl-tri-ala-rho-nitroanilide (SAPNA), and for elastolytic activity using 3H-labeled dog and human lung ...

  10. ESPRE: Expert System for Platelet Request Evaluation


    Sielaff, B H; Scott, E.; Connelly, D. P.


    ESPRE, a knowledge-based system designed to facilitate good platelet transfusion practices, is under development at the University of Minnesota Hospital and Clinic. This microcomputer based decision support system aids Blood Bank personnel in evaluating requests for platelet transfusions. Because of a direct link with the laboratory computers, most patient data need not be entered manually, but rather can be accessed directly. ESPRE uses a combination of frames and rules during its inference ...

  11. Five-day storage of platelet concentrates. (United States)

    Rock, G; Sherring, V A; Tittley, P


    The short 72-hour shelf-life of platelet concentrates stored in standard PL146 (Fenwal) plastic bags often results in shortages of platelets. This 3-day limitation is based on the biochemical and physiological changes that occur during storage and that result in decreased viability and survival after transfusion. We assessed both in vitro and in vivo function of platelet concentrates stored for 3 and 5 days in two new plastic packs: PL732 (Fenwal) and CLX (Cutter). The concentrate pH was maintained above 7.0 in both bags and there was little change in platelet count or size following 5 days of storage. Aggregation response to adenosine diphosphate, epinephrine, and collagen was maintained well. The PCO2 values indicated good gas escape with lower values after 5 days of storage than at 0 time. Lactate accumulation and glucose utilization were also lower in these new bags. Autologous survivals of chromium-labeled platelets stored for 5 days were 6.0 days (PL732) and 5.1 days (CLX), which are equal to or better than those found for platelets stored for 3 days in PL146. Posttransfusion increments in thrombocytopenic patients were acceptable; 49 percent after 1 hour and 31 percent after 24 hours for concentrates stored in CLX and 44 percent after 1 hour and 28 percent after 24 hours for concentrates stored in PL732. Both of these new bags, which contain different types of plasticizers, provide an environment that results in an improved product and will permit 5-day storage of platelet concentrates; these two benefits will help to alleviate the difficulties in supply of platelet concentrates.

  12. Serotonergic mechanisms enhance platelet-mediated thrombogenicity. (United States)

    Galan, Ana M; Lopez-Vilchez, Irene; Diaz-Ricart, Maribel; Navalon, Fulgencio; Gomez, Esther; Gasto, Cristobal; Escolar, Gines


    Although it is generally acknowledged that serotonin (5-HT) is a weak agonist for human platelets, recent information suggests an association between serotonergic mechanisms and cardiovascular risk. We investigated the action of 5-HT on adhesive, cohesive and procoagulant properties of human platelets. Impact of 5-HT on whole blood coagulation and thrombin generation was measured by modified thromboelastometry (TEM) and specific fluorogenic assays. We evaluated the effects of 5-HT on thrombus formation in an in-vitro model of thrombosis using human flowing blood. In platelet-rich plasma (PRP), 5-HT favoured the expression of CD62-P, and procoagulant molecules on platelet membranes. These effects were potentiated in the presence of Ca(++) and/or ADP. Incubation with 5-HT accelerated clotting times and augmented clot strength in whole blood TEM, and enhanced thrombin generation in PRP. In perfusion studies, 5-HT significantly increased fibrin deposition at low shear (300s(-1)) and enhanced platelet thrombus formation on the damaged vascular surface at high shear (1,200s(-1)). Selective inhibition of serotonin reuptake (SSRI) attenuated effects of 5-HT on platelet activation and downregulated the prothrombotic tendencies observed in the previous experimental conditions. In general, reductions of thrombogenic patterns observed with SSRI were more evident under shear conditions (aggregation and perfusion systems) and less evident under steady conditions (TEM and thrombin generation assays). In conclusion, 5-HT is not a weak agonist for human platelets; instead it accentuates platelet activation, potentiates procoagulant responses on human blood and increases thrombogenesis on damaged vascular surfaces. The remarkable antithrombotic actions achieved through SSRI deserve further mechanistic and clinical investigations.

  13. Lack of effect of bioactive-rich extracts of pomegranate, persimmon, nettle, dill, kale and Sideritis and isolated bioactives on platelet function. (United States)

    Hollands, Wendy J; Saha, Shikha; Hayran, Osman; Boyko, Nadiya; Glibetic, Maria; Konic-Ristic, Aleksandra; Jorjadze, Mariam; Kroon, Paul A


    The health benefits of fruit and vegetable-rich diets may be partly due to modulation of platelet activity by bioactive phytochemicals. The aim of this study was to investigate the effects of bioactive-rich plant extracts and isolated bioactive metabolites on platelet function. Blood samples (n =15 subjects) were treated with extracts of bioactive-rich plants consumed as traditional foods in the Black Sea region, or with human metabolites of the bioactives quercetin and sulforaphane. Platelet function was assessed using the PFA-100. None of the extracts containing various flavonoids, glucosinolates and other bioactives, or isolated bioactive metabolites of quercetin or sulforaphane, caused significant changes in PFA-100 closure time (CT). In contrast, the positive controls (aspirin and Abciximab) consistently caused significant increases in CT for the platelet agonists epinephrine and ADP, respectively. These data do not support the notion that these plant bioactives can improve human platelet function. © 2013 Society of Chemical Industry.

  14. Cationic PAMAM dendrimers disrupt key platelet functions (United States)

    Jones, Clinton F.; Campbell, Robert A.; Franks, Zechariah; Gibson, Christopher C.; Thiagarajan, Giridhar; Vieira-de-Abreu, Adriana; Sukavaneshvar, Sivaprasad; Mohammad, S. Fazal; Li, Dean Y.; Ghandehari, Hamidreza; Weyrich, Andrew S.; Brooks, Benjamin D.; Grainger, David W.


    Poly(amidoamine) (PAMAM) dendrimers have been proposed for a variety of biomedical applications and are increasingly studied as model nanomaterials for such use. The dendritic structure features both modular synthetic control of molecular size and shape and presentation of multiple equivalent terminal groups. These properties make PAMAM dendrimers highly functionalizable, versatile single-molecule nanoparticles with a high degree of consistency and low polydispersity. Recent nanotoxicological studies showed that intravenous administration of amine-terminated PAMAM dendrimers to mice was lethal, causing a disseminated intravascular coagulation-like condition. To elucidate the mechanisms underlying this coagulopathy, in vitro assessments of platelet functions in contact with PAMAM dendrimers were undertaken. This study demonstrates that cationic G7 PAMAM dendrimers activate platelets and dramatically alter their morphology. These changes to platelet morphology and activation state substantially altered platelet function, including increased aggregation and adherence to surfaces. Surprisingly, dendrimer exposure also attenuated platelet-dependent thrombin generation, indicating that not all platelet functions remained intact. These findings provide additional insight into PAMAM dendrimer effects on blood components and underscore the necessity for further research on the effects and mechanisms of PAMAM-specific and general nanoparticle toxicity in blood. PMID:22497592

  15. Platelet recruitment to venous stent thrombi. (United States)

    McBane, Robert D; Karnicki, Krzysztof; Wysokinski, Waldemar E


    Thrombosis following venous stent placement is a morbid clinical outcome. Whether to target platelets or coagulation factors for venous stent thromboprophylaxis remains unclear. We sought to determine whether integrin α(IIb)β3 antagonism with lamifiban would inhibit platelet recruitment to venous stent thrombosis. Anti-thrombotic efficacy was compared between venous and arterial circulations. Pigs received either lamifiban (0.2 mg/kg bolus plus 0.2 mg/kg/h infusion; n = 6) or saline (n = 12). Carotid arteries were crush injured and then harvested 30 min later to provide an assessment of antithrombotic efficacy in the arterial circulation. Iliac venous stents were then deployed and thrombi allowed to propagate for 2 h before harvesting. Platelet deposition was measured by scintillation detection of autologous (111)In-platelets. Venous thrombi were quantified by weight and compared to platelet, Von Willebrand factor (VWF) and fibrinogen content. Arterial platelet deposition (×10(6)/cm(2)) was reduced >80% by lamifiban (398 ± 437) compared to controls (1,540 ± 883; p thrombi occurs in part through the integrin α(IIb)β3 receptor. Unlike arterial thrombosis, inhibition of this receptor is insufficient to prevent venous stent thrombosis.

  16. Platelet-Mediated Modulation of Fibrinolysis. (United States)

    Whyte, Claire S; Mitchell, Joanne L; Mutch, Nicola J


    Platelets are crucial to the hemostatic response. Their role in coagulation is well documented and they have been considered for some time to promote resistance of thrombi to fibrinolysis. Platelets confer resistance to lysis by promoting clot retraction of the immediate fibrin network and through release of plasminogen activator inhibitor-1 from their α-granules. However, recent developments in the field indicate that the role of platelets in fibrinolysis is much more diverse. Indeed, novel studies suggest that platelets form different subpopulations upon activation that play varied roles in regulating hemostasis. Likewise the developments in our understanding of thrombus formation, architecture, and changes in fibrin deposition and composition suggest that these different subpopulations of platelets may populate distinct areas within thrombi and potentially dictate the local hemostatic balance in these areas. This review will discuss the diverse roles of platelets in fibrinolysis and highlight the recent developments in the field and the contribution of both the intracellular pool of modulators as well as the membrane surface in regulating these processes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. Platelet function changes as monitored by cone and plate(let) analyzer during beating heart surgery. (United States)

    Gerrah, Rabin; Snir, Eitan; Brill, Alex; Varon, David


    Off-pump coronary artery bypass (OPCAB) is believed to reduce cardiopulmonary bypass (CPB)-related complications, including platelet damage. A hypercoagulable state instead of coagulopathy has been reported following OPCAB surgeries due to CPB. Whether platelet function is changed when the injurious effect of CPB is eliminated was investigated. Platelet function was determined with the cone and plate(let) analyzer (CPA) method. The 2 parameters, average size (AS) and surface coverage (SC) of platelet aggregates, were measured with the CPA method to assess platelet aggregation and adhesion. These parameters were evaluated, and their values were compared at several stages of OPCAB surgery. The correlations of postoperative bleeding with platelet function at different stages of the surgery and with other factors, such as platelet count, hematocrit, and transfusions, were studied. Both AS and SC increased during several stages of the operation, and postoperative values (mean +/- SD) were significantly higher than preoperative values (30.4 +/- 8.1 microm 2 versus 23.3 +/- 6.9 microm 2 for AS [ P =.02] and 7.6% +/- 3.6% versus 5.2% +/- 1.8% for SC [ P =.04]). The mean total bleeding volume was 875 micro 415 mL. Preoperative AS and SC were the only parameters significantly ( P =.01) and linearly ( r = 0.7) related to postoperative bleeding. An increased platelet function, as determined by the CPA method, is found following OPCAB surgery. This phenomenon is probably at least partially responsible for the thrombogenic state after OPCAB surgery. Lack of platelet injury attributed to CPB may divert the system toward a more thrombogenic state. Preoperative platelet function, as evaluated by the CPA method, is an independent risk factor determining postoperative bleeding.

  18. Relationship between changes in platelet reactivity and changes in platelet receptor expression induced by physical exercise. (United States)

    Aurigemma, Cristina; Fattorossi, Andrea; Sestito, Alfonso; Sgueglia, Gregory A; Farnetti, Sara; Buzzonetti, Alexia; Infusino, Fabio; Landolfi, Raffaele; Scambia, Giovanni; Crea, Filippo; Lanza, Gaetano A


    In previous studies we have consistently shown a significant increase of platelet reactivity after exercise in patients with obstructive coronary artery disease (CAD). We also observed a significant individual variability in the response to exercise of platelet reactivity in these patients. Whether exercise-induced changes in platelet reactivity correlate with changes in platelet membrane receptors in patients with CAD is unknown. We studied 26 patients with stable CAD and 10 matched healthy controls who underwent a symptom-limited treadmill exercise stress test. Venous blood samples were collected at rest and within 5 min of peak exercise. Platelet reactivity was measured by the PFA-100 method as time to occlude (closure time, CT) a ring coated with collagen/adenosine diphosphate (C/ADP). Platelet expression of glycoprotein (GP) IIb/IIIa, in both global (CD41) and active form (PAC-1), and P-selectin (CD62P) and formation of leukocyte-platelet aggregates were assessed by flow cytometry. After exercise CT did not change in controls (85.4+/-12 to 84.0+/-9 s, p=0.37), whereas it decreased in CAD patients (98.8+/-24 to 91.4+/-25 s, p5 s after exercise) and CAD group 2 (10 patients no increase in platelet reactivity after exercise). CD41 and PAC-1 expression increased in CAD group 1 (p=0.008 and p=0.026, respectively) but not in CAD group 2 (p=0.39 and p=0.50, respectively). No significant differences were observed between the 2 groups for changes in CD62P and leukocyte-platelet aggregates. Our data show that, in patients with stable CAD, an increased platelet reactivity to C/ADP stimulation after exercise, as assessed by the PFA-100 method, is specifically associated with an increased expression of platelet GP IIb/IIIa receptor.

  19. A new ibuprofen derivative inhibits platelet aggregation and ROS mediated platelet apoptosis.

    Directory of Open Access Journals (Sweden)

    Kodagahalli S Rakesh

    Full Text Available Thrombocytopenia is a serious issue connected with the pathogenesis of several human diseases including chronic inflammation, arthritis, Alzheimer's disease, cardiovascular diseases (CVDs and other oxidative stress-associated pathologies. The indiscriminate use of antibiotics and other biological drugs are reported to result in thrombocytopenia, which is often neglected during the treatment regime. In addition, augmented oxidative stress induced by drugs and pathological conditions has also been shown to induce thrombocytopenia, which seems to be the most obvious consequence of elevated rate of platelet apoptosis. Thus, blocking oxidative stress-induced platelet apoptosis would be of prime importance in order to negotiate thrombocytopenia and associated human pathologies. The current study presents the synthesis and platelet protective nature of novel ibuprofen derivatives. The potent anti-oxidant ibuprofen derivative 4f was selected for the study and the platelet protective efficacy and platelet aggregation inhibitory property has been demonstrated. The compound 4f dose dependently mitigates the oxidative stress-induced platelet apoptosis in both platelet rich plasma and washed platelets. The platelet protective nature of compound 4f was determined by assessing various apoptotic markers such as ROS generation, cytosolic Ca2+ levels, PS externalization, cytochrome C translocation, Caspase activation, mitochondrial membrane depolarization, cytotoxicity, LDH leakage and tyrosine phosphorylation of cytosolic proteins. Furthermore, compound 4f dose dependently ameliorated agonist induced platelet aggregation. Therefore, compound 4f can be estimated as a potential candidate in the treatment regime of pathological disorders associated with platelet activation and apoptosis. In addition, compound 4f can be used as an auxiliary therapeutic agent in pathologies associated with thrombocytopenia.

  20. Using six-colour flow cytometry to analyse the activation and interaction of platelets and leukocytes--A new assay suitable for bench and bedside conditions. (United States)

    Granja, Tiago; Schad, Jessica; Schüssel, Patricia; Fischer, Claudius; Häberle, Helene; Rosenberger, Peter; Straub, Andreas


    Platelets are main effector cells in haemostasis and also promote inflammation. Platelet-leukocyte complexes are key mediators in a variety of thromboinflammatory disorders and consecutive organ failure. Cell-specific epitopes and activation markers on platelets and leukocytes can be measured using flow cytometry. However, until recently a major restriction has been a paucity in antibody combinations and lack of detection strategies. We aimed to develop a six-colour flow cytometry method which depicts multiple aspects of platelet and leukocyte interactions in human whole blood. Platelets, including microparticles and aggregates, were detected in flow cytometry using a platelet-specific anti-CD41-FITC antibody and size-defined regions. The morphology of platelet-leukocyte complexes (including granulocyte and monocyte content) were depicted using anti-CD45-PerCP, anti-CD66b-PE-Cy7, and anti-CD14-APC antibodies in a single sample. Expression of platelet and leukocyte activation markers P-selectin and CD11b were detected using anti-CD62P-PE and anti-CD11b-BV421 antibodies, respectively. The sensitivity of this assay to detect the effects of various agonists (TRAP-6, ADP, collagen, epinephrine, TNF-α and LPS) is demonstrated. Furthermore, the assay is shown to detect platelet and leukocyte activation induced by extracorporeal circulation in vitro. The suitability of this assay for bedside analysis is demonstrated exemplarily in a patient treated with mechanical circulatory life support. Using the concurrent assessment of multiple parameters, this method gives detailed insights into the complexity and dynamics of platelet-leukocyte interactions. This assay carries the potential to increase our understanding of the mechanisms and pathophysiology of platelet-leukocyte interaction in the research laboratory and clinical setting. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Superoxide Dismutase 2 is dispensable for platelet function. (United States)

    Fidler, Trevor P; Rowley, Jesse W; Araujo, Claudia; Boudreau, Luc H; Marti, Alex; Souvenir, Rhonda; Dale, Kali; Boilard, Eric; Weyrich, Andrew S; Abel, E Dale


    Increased intracellular reactive oxygen species (ROS) promote platelet activation. The sources of platelet-derived ROS are diverse and whether or not mitochondrial derived ROS, modulates platelet function is incompletely understood. Studies of platelets from patients with sickle cell disease, and diabetes suggest a correlation between mitochondrial ROS and platelet dysfunction. Therefore, we generated mice with a platelet specific knockout of superoxide dismutase 2 (SOD2-KO) to determine if increased mitochondrial ROS increases platelet activation. SOD2-KO platelets demonstrated decreased SOD2 activity and increased mitochondrial ROS, however total platelet ROS was unchanged. Mitochondrial function and content were maintained in non-stimulated platelets. However SOD2-KO platelets demonstrated decreased mitochondrial function following thrombin stimulation. In vitro platelet activation and spreading was normal and in vivo, deletion of SOD2 did not change tail-bleeding or arterial thrombosis indices. In pathophysiological models mediated by platelet-dependent immune mechanisms such as sepsis and autoimmune inflammatory arthritis, SOD2-KO mice were phenotypically identical to wildtype controls. These data demonstrate that increased mitochondrial ROS does not result in platelet dysfunction.

  2. Platelet inhibition by nitrite is dependent on erythrocytes and deoxygenation.

    Directory of Open Access Journals (Sweden)

    Sirada Srihirun

    Full Text Available Nitrite is a nitric oxide (NO metabolite in tissues and blood, which can be converted to NO under hypoxia to facilitate tissue perfusion. Although nitrite is known to cause vasodilation following its reduction to NO, the effect of nitrite on platelet activity remains unclear. In this study, the effect of nitrite and nitrite+erythrocytes, with and without deoxygenation, on platelet activity was investigated.Platelet aggregation was studied in platelet-rich plasma (PRP and PRP+erythrocytes by turbidimetric and impedance aggregometry, respectively. In PRP, DEANONOate inhibited platelet aggregation induced by ADP while nitrite had no effect on platelets. In PRP+erythrocytes, the inhibitory effect of DEANONOate on platelets decreased whereas nitrite at physiologic concentration (0.1 µM inhibited platelet aggregation and ATP release. The effect of nitrite+erythrocytes on platelets was abrogated by C-PTIO (a membrane-impermeable NO scavenger, suggesting an NO-mediated action. Furthermore, deoxygenation enhanced the effect of nitrite as observed from a decrease of P-selectin expression and increase of the cGMP levels in platelets. The ADP-induced platelet aggregation in whole blood showed inverse correlations with the nitrite levels in whole blood and erythrocytes.Nitrite alone at physiological levels has no effect on platelets in plasma. Nitrite in the presence of erythrocytes inhibits platelets through its reduction to NO, which is promoted by deoxygenation. Nitrite may have role in modulating platelet activity in the circulation, especially during hypoxia.

  3. Platelet Larger Cell Ratio and High-on Treatment Platelet Reactivity During Dual Antiplatelet Therapy

    NARCIS (Netherlands)

    Verdoia, M.; Pergolini, P.; Rolla, R.; Nardin, M.; Barbieri, L.; Schaffer, A.; Bellomo, G.; Marino, P.; Suryapranata, H.; Luca, G. De


    BACKGROUND: Low response to antiplatelet agents has been associated to an increased risk of thrombotic complications and recurrent ischemic events. Platelet size has been proposed as a potential marker of platelet reactivity. Therefore, the aim of the present study was to evaluate the impact of

  4. Consistent platelet inhibition with ticagrelor 60 mg twice-daily following myocardial infarction regardless of diabetes status. (United States)

    Thomas, Mark R; Angiolillo, Dominick J; Bonaca, Marc P; Ajjan, Ramzi A; Judge, Heather M; Rollini, Fabiana; Franchi, Francesco; Ahsan, Arif J; Bhatt, Deepak L; Kuder, Julia F; Steg, Philippe Gabriel; Cohen, Marc; Muthusamy, Rangasamy; Sabatine, Marc S; Storey, Robert F


    Diabetes increases cardiovascular risk and reduces pharmacodynamic response to some oral antiplatelet drugs. This study aimed to determine whether ticagrelor 60 mg twice daily (bid) provided potent and consistent platelet inhibition in patients with vs without diabetes in the PEGASUS-TIMI 54 platelet function substudy. Out of 180 patients studied, 58 patients were randomised to and had received at least four weeks of ticagrelor 60 mg bid, with 20 (34 %) having diabetes, 58 patients received ticagrelor 90 mg bid, with 12 (21 %) having diabetes, and 64 patients received placebo, with 18 (28 %) having diabetes. Blood was sampled pre- and 2 hours post-maintenance dose. In patients treated with ticagrelor 60 mg bid, on-treatment platelet reactivity to ADP, as determined by light transmission aggregometry (LTA), VerifyNow and VASP, was similar in patients with vs without diabetes (LTA post-dose, ADP 20 µM: 29 ± 14 vs 34 ± 10 %, respectively; p = 0.19). A consistent inhibitory effect of ticagrelor 60 mg bid was observed pre- and post-dose regardless of diabetes status, even in insulin-treated patients. Patients with diabetes did not have an increased incidence of high platelet reactivity in either ticagrelor group. Platelet reactivity was similar in patients with diabetes treated with ticagrelor 60 mg vs 90 mg bid. Pharmacokinetics of ticagrelor were not affected by diabetes status. In conclusion, ticagrelor 60 mg bid is equally effective at reducing platelet reactivity in patients with and without diabetes, yielding a consistently high level of platelet inhibition regardless of diabetes status.

  5. Biomechanical study of the effect of platelet rich plasma on the treatment of medial collateral ligament lesion in rabbits. (United States)

    Costa, Eduardo Louzada da; Teixeira, Luiz Eduardo Moreira; Pádua, Bruno Jannotti; Araújo, Ivana Duval de; Vasconcellos, Leonardo de Souza; Dias, Luide Scalioni Borges


    To evaluate the use of platelet-rich plasma in the early stages of healing of traumatic injury of the medial collateral ligament in the knee of rabbits. Thirty rabbits were subjected to surgical lesion of the medial collateral ligament. Of these, 16 were treated with platelet-rich plasma and 14 with saline (control). After 3 and 6 weeks of treatment, 50% of the animals from each group were sacrificed, and biomechanical tests were performed on the injured ligament to compare the tensile strength between the two groups. Platelet-rich plasma significantly increased the tensile strength of the ligament in the groups treated after3 and 6 weeks. In the group treated with platelet-rich plasma vs. saline, the tensile strength values were 3192.5 ± 189.7 g/f vs. 2851.1 ± 193.1 g/f at3 weeks (p = 0.005) and 5915.6 ± 832.0 g/f vs. 4187.6 ± 512.9 g/f at 6 weeks (p = 0.0001). The use of platelet-rich plasma at the injury site accelerated ligament healing in an animal model, demonstrated by an increase in the tensile strength of the medial collateral ligament.

  6. Effects of different concentrations of Platelet-rich Plasma and Platelet-Poor Plasma on vitality and differentiation of autologous Adipose tissue-derived stem cells. (United States)

    Felthaus, Oliver; Prantl, Lukas; Skaff-Schwarze, Mona; Klein, Silvan; Anker, Alexandra; Ranieri, Marco; Kuehlmann, Britta


    Autologous fat grafts and adipose-derived stem cells (ASCs) can be used to treat soft tissue defects. However, the results are inconsistent and sometimes comprise tissue resorption and necrosis. This might be due to insufficient vascularization. Platelet-rich plasma (PRP) is a source of concentrated autologous platelets. The growth factors and cytokines released by platelets can facilitate angiogenesis. The simultaneous use of PRP might improve the regeneration potential of fat grafts. The optimal ratio has yet to be elucidated. A byproduct of PRP preparation is platelet-poor plasma (PPP). In this study we investigated the influence of different concentrations of PRP on the vitality and differentiation of ASCs. We processed whole blood with the Arthrex Angel centrifuge and isolated ASCs from the same donor. We tested the effects of different PRP and PPP concentrations on the vitality using resazurin assays and the differentiation of ASCs using oil-red staining. Both cell vitality and adipogenic differentiation increase to a concentration of 10% to 20% PRP. With a PRP concentration of 30% cell vitality and differentiation decrease. Both PRP and PPP can be used to expand ASCs without xenogeneic additives in cell culture. A PRP concentration above 20% has inhibitory effects.

  7. Effects of antithrombotic drugs in patients with left ventricular thrombi: assessment with indium-111 platelet imaging and two-dimensional echocardiography

    Energy Technology Data Exchange (ETDEWEB)

    Stratton, J.R.; Ritchie, J.L.


    Patients with left ventricular thrombi not caused by recent myocardial infarction were prospectively studied by indium-111 platelet imaging and two-dimensional echocardiography to determine the reproducibility of these techniques and the short-term effects of sulfinpyrazone (200 mg four times daily), aspirin (325 mg three times daily) plus dipyridamole (75 mg three times daily), and full-dose warfarin. At baseline, all patients underwent indium-111 platelet imaging and echocardiography, and the results were positive for thrombus. In six patients on no antithrombotic drug therapy, repeat platelet scans and echocardiographic studies at 6.0 +/- 3.3 weeks remained positive and were unchanged. In seven patients studied on sulfinpyrazone, three platelet scans became negative, two became equivocal, and two were unchanged; the presence and size of thrombus was constant by echocardiography in all seven patients. Of the six patients studied on aspirin plus dipyridamole, one platelet scan became negative, those of three became equivocal, and two were unchanged; all echocardiographic findings remained positive, but one patient had decreased thrombus size. Among four warfarin-treated patients, three had resolution of platelet deposition and one was unchanged; by echocardiography, thrombus resolved in one patient, was decreased in size in one, and was unchanged in two. We conclude that, in the absence of antithrombotic drug therapy, platelet imaging and echocardiographic findings are stable in patients with left ventricular thrombi not caused by recent myocardial infarction. Sulfinpyrazone, aspirin plus dipyridamole, and warfarin all interrupt platelet deposition in some patients with chronic left ventricular thrombi.

  8. Inactivation of viruses in platelet suspensions that retain their in vitro characteristics: Comparison of psoralen-ultraviolet A and merocyanine 540-visible light methods

    Energy Technology Data Exchange (ETDEWEB)

    Dodd, R.Y.; Moroff, G.; Wagner, S.; Dabay, M.H.; Dorfman, E.; George, V.; Ribeiro, A.; Shumaker, J.; Benade, L.E. (Jerome H. Holland Laboratory, American Red Cross, Rockville, MD (USA))


    The ability of two fundamentally different photochemical procedures to inactivate model viruses in platelet suspensions was compared. Merocyanine 540 (MC 540) with visible light was used as an example of an oxygen-dependent chemical-directed at the viral membrane, and aminomethyl trimethyl psoralen (AMT) with ultraviolet A light (UVA) was used as an example of a nucleic acid-directed system. Antiviral conditions in petri dishes were identified and the effects of these procedures on platelet suspensions in plastic storage containers were studied. Concentrations of photochemicals in the 10 to 150 mumol range with 30 to 60 minutes of visible light (MC 540) or 1 to 2 minutes of UVA (AMT) readily inactivated 5 to 6 log10 of vesicular stomatitis virus (VSV) and other model viruses in platelet suspensions, provided the plasma concentration was reduced to about 15 percent by the use of a synthetic platelet storage medium. Extracellular pH, morphology scores, and aggregation response dropped markedly when platelets were treated with MC 540 and visible light. However, treatment with 136 mumol per L of AMT and 1 to 3 minutes of UVA could inactivate 5 log10 of VSV in platelet suspensions with retention of platelet characteristics for 4 days, particularly if oxygen levels were reduced during treatment. These studies demonstrate that AMT-UVA treatment meets the initial requirements for virus inactivation in platelet suspensions.

  9. Platelet Factor 4 Binds to Vascular Proteoglycans and Controls Both Growth Factor Activities and Platelet Activation. (United States)

    Lord, Megan S; Cheng, Bill; Farrugia, Brooke L; McCarthy, Simon; Whitelock, John M


    Platelet factor 4 (PF4) is produced by platelets with roles in both inflammation and wound healing. PF4 is stored in platelet α-granules bound to the glycosaminoglycan (GAG) chains of serglycin. This study revealed that platelet serglycin is decorated with chondroitin/dermatan sulfate and that PF4 binds to these GAG chains. Additionally, PF4 had a higher affinity for endothelial-derived perlecan heparan sulfate chains than serglycin GAG chains. The binding of PF4 to perlecan was found to inhibit both FGF2 signaling and platelet activation. This study revealed additional insight into the ways in which PF4 interacts with components of the vasculature to modulate cellular events. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Platelet activation and platelet-leukocyte interaction in dogs naturally infected with Babesia rossi

    DEFF Research Database (Denmark)

    Goddard, Amelia; Leisewitz, Andrew L; Kristensen, Annemarie Thuri


    for regulating innate immunity and systemic inflammation. The objective of this study was to investigate PLA formation in canine babesiosis and to determine whether it was associated with outcome. Blood was collected from 36 client-owned dogs diagnosed with Babesia rossi infection and 15 healthy controls using......Using flow cytometry, platelet-leukocyte aggregate (PLA) formation has previously been documented in dogs with a variety of systemic inflammatory disorders and immune-mediated haemolytic anaemia. Platelet activation and subsequent interaction between platelets and leukocytes are important...... EDTA as anticoagulant. Activated platelets and PLA formation were detected by measuring surface expression of P-selectin (CD62P) on platelets, monocytes and neutrophils. Of the Babesia-infected dogs, 29 survived and seven died. The percentage of CD62P-positive monocytes was significantly higher (P = 0...

  11. An overview of platelet indices and methods for evaluating platelet function in thrombocytopenic patients

    DEFF Research Database (Denmark)

    Vinholt, Pernille Just; Hvas, Anne-Mette; Nybo, Mads


    Thrombocytopenia is associated with bleeding risk. However, in thrombocytopenic patients platelet count does not correlate with bleeding risk and other factors are thus likely to contribute to this risk. The present review presents currently available platelet-related markers available on automated...... haematology analysers and commonly used methods for testing platelet function. The test principles, advantages and disadvantages of each test are described. We also evaluate the current literature regarding the clinical utility of the test for prediction of bleeding in thrombocytopenia in haematological...... and oncological diseases. We find that several platelet-related markers are available but information about the clinical utility in thrombocytopenia is limited. Studies support that mean platelet volume (MPV) can aid diagnosing the cause of thrombocytopenia and low MPV may be associated with bleeding...

  12. Platelet-rich fibrin or platelet-rich plasma – which one is better? an opinion

    Directory of Open Access Journals (Sweden)

    Shweta Bansal


    Full Text Available The healing of hard and soft tissue in mediated by a wide range of intracellular and extracellular events that are regulated by signaling proteins. Platelets can play a crucial role in periodontal regeneration as they are the reservoirs of growth factors and cytokines which are the key factors for regeneration of bone and maturation of soft tissue. Platelet-rich plasma (PRP is first generation platelet concentrate. However, the short duration of cytokine release and its poor mechanical properties have resulted in search of new material. Platelet-rich fibrin (PRF is a natural fibrin-based biomaterial prepared from an anticoagulant-free blood harvest without any artificial biochemical modification (no bovine thrombin is required that allows obtaining fibrin membranes enriched with platelets and growth factors. The slow polymerization during centrifugation, fibrin-based structure, ease of preparation, minimal expense makes PRF somewhat superior in some aspect to PRP.

  13. Reduced platelet activation and platelet aggregation in patients with alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Vinholt, Pernille Just; Hvas, Anne-Mette; Nielsen, Christian


    Results from previous studies regarding platelet function in liver cirrhosis are discordant. The aim was to investigate platelet activation and platelet aggregation in patients with alcoholic liver cirrhosis. We included 27 patients with alcoholic liver cirrhosis and 22 healthy individuals...... adenosine diphosphate, thrombin receptor-activating peptide, arachidonic acid, collagen, and collagen-related peptide. Patients had lower median platelet count than healthy individuals, 125 × 10(9)/L (interquartile range [IQR] 90-185) versus 240 × 10(9) (IQR 204-285), p ... in stimulated samples were lower in patients versus healthy individuals, e.g., after collagen-related peptide stimulation, the median percentage of platelets positive for activated glycoprotein IIb/IIIa was 85% (IQR 70-94) in patients versus 97% (IQR 94-99) in healthy individuals, p

  14. [Subconjunctival application of plasma platelet concentrate in the treatment of ocular burns. Preliminary results]. (United States)

    Márquez-de-Aracena, R; Montero-de-Espinosa, I; Muñoz, M; Pereira, G


    The efficiency of the subconjunctival application of autologous platelet concentrate in patients with ocular burns was assessed. This was carried out by analysing the effect of treatment in the eyes of 10 patients suffering from ocular burns as a result of work-related accidents. Two types of treatment were evaluated: the first group only received conventional topical medical treatment; and the second group, in addition, had subconjunctival injection of plasma platelet concentrate. The clinical condition of the patient and the period in which the disease prevented the patient from working were studied; monitoring was carried out until the burns had fully healed. Statistically significant differences were found between the group treated with subconjunctival autologous platelet concentrate and the group treated with conventional topical medications, with a shorter period of time in corneal and conjunctival healing, time on sick leave and time needed for full healing. Subconjunctival infiltration of autologous platelet concentrate should be considered as a straightforward, economical and possibly effective form of treatment for traumatic accidents (burns) of the ocular surface.

  15. Effect of transdermal hormone therapy on platelet haemostasis in menopausal women. (United States)

    Stachowiak, Grzegorz; Pertyński, Tomasz; Pertyńska-Marczewska, Magdalena


    Despite the undeniably positive effect on the quality of life of menopausal women, menopausal hormone therapy (HT) also has negative side-effects, which include, among others, thromboembolic complications. To assess the effect of a popular type of this therapy - transdermal HT on platelet hemostasis, which plays a significant role in intravascular coagulation. The study group consisted of 92 postmenopausal women: 1) group G1 (n=30), treated with transdermal HT (17β-estradiol 50 μg/day plus NETA 170 μg/day); 2) group G2 (n=31), treated with the above transdermal HT and low dosage of acetylsalicylic acid (ASA); 3) control group P (n=31). All the women qualified for the study had two or more risk factors for arterial thrombosis, such as: smoking, hypertension, visceral obesity, hypercholesterolaemia, hypertriglyceridaemia, elevated levels of PAI-1, and increased fibrinogen, increased activity of coagulation factor VII. After three months of therapy, in the G1 group there was a decrease in platelet count (p = 0.004) and a decrease in GP IIb/IIIa - a platelet receptor for fibrinogen (p = 0.022). In the G2 group, no changes in the tested parameters were observed. 1) Transdermal HT in the form of combined, estrogen-progestogen patches favourably modifies platelets haemostasis, reversing the adverse effects that occur after menopause. 2) The use of low ASA doses as a thromboprophylaxis in short-term transdermal HT is not necessary.

  16. Platelet Activation Test in Unprocessed Blood (Pac-t-UB) to Monitor Platelet Concentrates and Whole Blood of Thrombocytopenic Patients. (United States)

    Roest, Mark; van Holten, Thijs C; Fleurke, Ger-Jan; Remijn, Jasper A


    Platelet concentrate transfusion is the standard treatment for hemato-oncology patients to compensate for thrombocytopenia. We have developed a novel platelet activation test in anticoagulated unprocessed blood (pac-t-UB) to determine platelet function in platelet concentrates and in blood of thrombocytopenic patients. We have measured platelet activity in a platelet concentrate and in anticoagulated unprocessed blood of a post-transfusion thrombocytopenic patient. Our data show time-dependent platelet activation by GPVI agonist (collagen related peptide; CRP), PAR-1 agonist (SFLLRN), P2Y12 agonist (ADP), and thromboxane receptor agonist (U46619) in a platelet concentrate. Furthermore, pac-t-UB showed time-dependent platelet activation in unprocessed blood of a post-transfusion patient with thrombocytopenia. Testing platelet function by different agonists in relation to storage show that 3-day-old platelet concentrates are still reactive to the studied agonists. This reactivity rapidly drops for each agonists during longer storage. Pac-t-UB is a novel tool to estimate platelet function by different agonists in platelet concentrates and in unprocessed blood of thrombocytopenic patients. In the near future, we will validate whether pac-t-UB is an adequate test to monitor the quality of platelet concentrates and whether pac-t-UB predicts the bleeding risk of transfused thrombocytopenic patients.

  17. Essential thrombocythemia treated with oral sup(32)P

    Energy Technology Data Exchange (ETDEWEB)

    Yu, H.D.; Oh, B.S.; Jang, W.S.; Roh, K.H.; Park, B.I.; Cho, M.K. (National Police Hospital, Seoul (Republic of Korea))


    A 65-year old man was admitted due to protracted gum bleeding after dental surgery. The peripheral blood smear showed thrombocytosis(1,160,000/mm/sup 3/) with bizarre, giant platelets. The paltelet adhesiveness revealed 28% (normal control 31-85%) by Salzman method and the platelet aggregation revealed moderately delayed response to collagen, but normal responsiveness to A.D,P, and no responsiveness to epinephrine, the spleen scan(sup(99m)Tc-NaTcO/sub 4/) showed the finding of splenic infraction. The gum bleeding ceased after transfusion of 8 units of platelet rich plasma, and he was treated with oral sup(32)P(2.5mCi/m/sub 2/) under the diagnosis of essential thrombocythemia. The platelet count returned toward normal 2 months after treatment, and he was in good healthy condition.

  18. A General Aspect of Platelet Rich Plasma

    Directory of Open Access Journals (Sweden)

    Onur ORAL


    Full Text Available The aim of this scientific paper is to introduce Platelet Rich Plasma (PRP cure method by people who never heard about it. People can hurt their selves, thus they can have damaged tissue; for instance broken bone, a scar or a wounded area. Furthe rmore damaged tissue can be a cartilage tissue, which takes very long time to heal. Platelets, those exist in the veins as thrombus, come up to repair those damaged tissues. However, platelets would be insufficient to cure damaged area in a short time. At this point PRP cure method give a hand to the healing process. By centrifuging people’s own blood via special kits, platelets can be separated from blood cells as plasma. That plasma’s platelet density is 3 - 5 times greater than that blood’s platelet densit y. Afterwards PRP method is implemented by injection of plasma to the damaged area or tissue. After implementation of 2 - 4 sessions per week, damaged tissue can be regenerated. It is fast healing method because densified platelet plasma is used; and it is s afe because that plasma is obtained from people’s own blood. PRP can be implemented on many areas; for instance on dentistry, sports medicine, different kind of surgeries such as plastic, vascular or orthopedic and so on. When soccer players brake their le gs, their sports life come to the end, but what if their broken legs was healed better and faster than general healing process? To sum up, PRP is very safe and the future of healing process.

  19. Relationship between platelet count and hemodialysis membranes

    Directory of Open Access Journals (Sweden)

    Nasr R


    Full Text Available Rabih Nasr,1 Chadi Saifan,1 Iskandar Barakat,2 Yorg Al Azzi,2 Ali Naboush,2 Marc Saad,2 Suzanne El Sayegh1 1Department of Nephrology, Staten Island University Hospital, Staten Island, NY, USA; 2Department of Medicine, Staten Island University Hospital, Staten Island, NY, USA Background: One factor associated with poor outcomes in hemodialysis patients is exposure to a foreign membrane. Older membranes are very bioincompatible and increase complement activation, cause leukocytosis by activating circulating factors, which sequesters leukocytes in the lungs, and activates platelets. Recently, newer membranes have been developed that were designed to be more biocompatible. We tested if the different “optiflux” hemodialysis membranes had different effects on platelet levels. Methods: Ninety-nine maintenance hemodialysis patients with no known systemic or hematologic diseases affecting their platelets had blood drawn immediately prior to, 90 minutes into, and immediately following their first hemodialysis session of the week. All patients were dialyzed using a Fresenius Medical Care Optiflux polysulfone membrane F160, F180, or F200 (polysulfone synthetic dialyzer membranes, 1.6 m2, 1.8 m2, and 2.0 m2 surface area, respectively, electron beam sterilized. Platelet counts were measured from each sample by analysis using a CBC analyzer. Results: The average age of the patients was 62.7 years; 36 were female and 63 were male. The mean platelet count pre, mid, and post dialysis was 193 (standard deviation ±74.86, 191 (standard deviation ±74.67, and 197 (standard deviation ±79.34 thousand/mm3, respectively, with no statistical differences. Conclusion: Newer membranes have no significant effect on platelet count. This suggests that they are, in fact, more biocompatible than their predecessors and may explain their association with increased survival. Keywords: platelet count, polysulfone membranes, complement activation, electron beam sterilized

  20. Calcium-binding proteins from human platelets

    Energy Technology Data Exchange (ETDEWEB)

    Gogstad, G.O.; Krutnes, M.B.; Solum, N.O.


    Calcium-binding platelet proteins were examined by crossed immunoelectrophoresis of solubilized platelets against antibodies to whole platelets followed by incubation of the immunoplates with /sup 45/Ca/sup 2 +/ and autoradiography. When the immunoplates had been pretreated with EDTA at pH 9.0 in order to remove divalent cations, three immunoprecipitates were markedly labelled with /sup 45/Ca/sup 2 +/. These corresponded to the glycoprotein IIb-IIIa complex, glycoprotein Ia and a presently unidentified antigen termed G18. These antigens were membrane-bound and surface-oriented. When an excess of EDTA was introduced in the incubation media the results revealed that the glycoprotein IIb-IIIa complex and antigen G18, but not glycoprotein Ia, contained sites with a stronger affinity for calcium than has EDTA at pH 7.4. Immunoprecipitates of the separate glycoproteins IIb and IIIa both bound calcium in the same manner as the glycoprotein IIb-IIIa complex. As another approach, platelet-rich plasma was incubated with /sup 45/Ca/sup 2 +/ prior to crossed immunoelectrophoresis of the solubilized platelets. A single immunoprecipitate was weakly labelled. This did not correspond to any of the immunoprecipitates which were visible after staining with Coomassie blue. The labelling of this antigen was markedly increased when the platelet-rich plasma had been preincubated with EDTA and in this case a weak labelling of the glycoprotein IIB-IIIa precipitate also became apparent. No increased incorporation of calcium occured in any of these immunoprecipitates when the platelets were aggregated with ADP in the presence of /sup 45/Ca/sup 2 +/.

  1. Impact of ticagrelor on P2Y1 and P2Y12 localization and on cholesterol levels in platelet plasma membrane. (United States)

    Rabani, Vahideh; Montange, Damien; Meneveau, Nicolas; Davani, Siamak


    Ticagrelor is an antiplatelet agent that inhibits platelet activation via P2Y12 antagonism. There are several studies showing that P2Y12 needs lipid rafts to be activated, but there are few data about how ticagrelor impacts lipid raft organization. Therefore, we aimed to investigate how ticagrelor could impact the distribution of cholesterol and consequently alter the organization of lipid rafts on platelet plasma membranes. We identified cholesterol-enriched raft fractions in platelet membranes by quantification of their cholesterol levels. Modifications in cholesterol and protein profiles (Flotillin 1, Flotillin 2, CD36, P2Y1, and P2Y12) were studied in platelets stimulated by ADP, treated by ticagrelor, or both. In ADP-stimulated and ticagrelor-treated groups, we found a decreased level of cholesterol in raft fractions of platelet plasma membrane compared to the control group. In addition, the peak of cholesterol in different experimental groups changed its localization on membrane fractions. In the control group, it was situated on fraction 2, while in ADP-stimulated platelets, it was located in fractions 3 to 5, and in fraction 4 in ticagrelor-treated group. The proteins studied also showed changes in their level of expression and localization in fractions of plasma membrane. Cholesterol levels of plasma membranes have a direct role in the organization of platelet membranes and could be modified by stimulation or drug treatment. Since ticagrelor and ADP both changed lipid composition and protein profile, investigating the lipid and protein composition of platelet membranes is of considerable importance as a focus for further research in anti-platelet management.

  2. Inhibition of Glycoprotein VI Clustering by Collagen as a Mechanism of Inhibiting Collagen-Induced Platelet Responses: The Example of Losartan.

    Directory of Open Access Journals (Sweden)

    Peng Jiang

    Full Text Available Exposure of platelets to collagen triggers the formation of a platelet clot. Pharmacological agents capable of inhibiting platelet activation by collagen are thus of potential therapeutic interest. Thrombus formation is initiated by the interaction of the GPIb-V-IX complex with collagen-bound vWF, while GPVI interaction with collagen triggers platelet activation that is reinforced by ADP and thromboxane A2. Losartan is an angiotensin II (Ang II type I receptor (AT1R antagonist proposed to have an antiplatelet activity via the inhibition of both the thromboxane A2 (TXA2 receptor (TP and the glycoprotein VI (GPVI. Here, we characterized in vitro the effects of losartan at different doses on platelet responses: losartan inhibited platelet aggregation and secretion induced by 1 μg . mL(-1 and 10 μg . mL(-1 of collagen with an IC50 of ~ 6 μM. Losartan inhibited platelet responses induced by the GPVI specific collagen related peptide but not by the α2β1 specific peptide. However, losartan did not inhibit the binding of recombinant GPVI to collagen, which is not in favor of a simple competition. Indeed, the clustering of GPVI observed in flow cytometry and using the Duolink methodology, was inhibited by losartan. The impact of a therapeutic dose of losartan (100 mg/day on platelet responses was analyzed ex vivo in a double blind study. No statistically significant differences were observed between losartan-treated (n=25 and non-treated (n=30 patients in terms of collagen and U46619-induced platelet activation. These data indicate that in treated patients, losartan does not achieve a measurable antiplatelet effect but provide the proof of concept that inhibiting collagen-induced GPVI clustering is of pharmacological interest to obtain an antithrombotic NCT00763893.

  3. Inhibition of Glycoprotein VI Clustering by Collagen as a Mechanism of Inhibiting Collagen-Induced Platelet Responses: The Example of Losartan (United States)

    Jiang, Peng; Loyau, Stéphane; Tchitchinadze, Maria; Ropers, Jacques; Jondeau, Guillaume; Jandrot-Perrus, Martine


    Exposure of platelets to collagen triggers the formation of a platelet clot. Pharmacological agents capable of inhibiting platelet activation by collagen are thus of potential therapeutic interest. Thrombus formation is initiated by the interaction of the GPIb-V-IX complex with collagen-bound vWF, while GPVI interaction with collagen triggers platelet activation that is reinforced by ADP and thromboxane A2. Losartan is an angiotensin II (Ang II) type I receptor (AT1R) antagonist proposed to have an antiplatelet activity via the inhibition of both the thromboxane A2 (TXA2) receptor (TP) and the glycoprotein VI (GPVI). Here, we characterized in vitro the effects of losartan at different doses on platelet responses: losartan inhibited platelet aggregation and secretion induced by 1 μg.mL-1 and 10 μg.mL-1 of collagen with an IC50 of ~ 6 μM. Losartan inhibited platelet responses induced by the GPVI specific collagen related peptide but not by the α2β1 specific peptide. However, losartan did not inhibit the binding of recombinant GPVI to collagen, which is not in favor of a simple competition. Indeed, the clustering of GPVI observed in flow cytometry and using the Duolink methodology, was inhibited by losartan. The impact of a therapeutic dose of losartan (100 mg/day) on platelet responses was analyzed ex vivo in a double blind study. No statistically significant differences were observed between losartan-treated (n=25) and non-treated (n=30) patients in terms of collagen and U46619-induced platelet activation. These data indicate that in treated patients, losartan does not achieve a measurable antiplatelet effect but provide the proof of concept that inhibiting collagen-induced GPVI clustering is of pharmacological interest to obtain an antithrombotic efficacy. Trial Registration NCT00763893 PMID:26052700

  4. Surgical management of macular holes: results using gas tamponade alone, or in combination with autologous platelet concentrate, or transforming growth factor beta 2.

    LENUS (Irish Health Repository)

    Minihan, M


    BACKGROUND: Vitrectomy and gas tamponade has become a recognised technique for the treatment of macular holes. In an attempt to improve the anatomic and visual success of the procedure, various adjunctive therapies--cytokines, serum, and platelets--have been employed. A consecutive series of 85 eyes which underwent macular hole surgery using gas tamponade alone, or gas tamponade with either the cytokine transforming growth factor beta 2 (TGF-beta 2) or autologous platelet concentrate is reported. METHODS: Twenty eyes had vitrectomy and 20% SF6 gas tamponade; 15 had vitrectomy, 20% SF6 gas, and TGF-beta 2; 50 had vitrectomy, 16% C3F8 gas tamponade, and 0.1 ml of autologous platelet concentrate prepared during the procedure. RESULTS: Anatomic success occurred in 86% of eyes, with 96% of the platelet treated group achieving closure of the macular hole. Visual acuity improved by two lines or more in 65% of the SF6 only group, 33% of those treated with TGF-beta 2 and in 74% of the platelet treated group. In the platelet treated group 40% achieved 6\\/12 or better and 62% achieved 6\\/18 or better. The best visual results were obtained in stage 2 holes. CONCLUSION: Vitrectomy for macular holes is often of benefit and patients may recover good visual acuity, especially early in the disease process. The procedure has a number of serious complications, and the postoperative posturing requirement is difficult. Patients need to be informed of such concerns before surgery.

  5. Platelet receptor polymorphisms do not influence Staphylococcus aureus–platelet interactions or infective endocarditis (United States)

    Daga, Shruti; Shepherd, James G.; Callaghan, J. Garreth S.; Hung, Rachel K.Y.; Dawson, Dana K.; Padfield, Gareth J.; Hey, Shi Y.; Cartwright, Robyn A.; Newby, David E.; Fitzgerald, J. Ross


    Cardiac vegetations result from bacterium–platelet adherence, activation and aggregation, and are associated with increased morbidity and mortality in infective endocarditis. The GPIIb/IIIa and FcγRIIa platelet receptors play a central role in platelet adhesion, activation and aggregation induced by endocarditis pathogens such as Staphylococcus aureus, but the influence of known polymorphisms of these receptors on the pathogenesis of infective endocarditis is unknown. We determined the GPIIIa platelet antigen PlA1/A2 and FcγRIIa H131R genotype of healthy volunteers (n = 160) and patients with infective endocarditis (n = 40), and investigated the influence of these polymorphisms on clinical outcome in infective endocarditis and S. aureus–platelet interactions in vitro. Platelet receptor genotype did not correlate with development of infective endocarditis, vegetation characteristics on echocardiogram or the composite clinical end-point of embolism, heart failure, need for surgery or mortality (P > 0.05 for all), even though patients with the GPIIIa PlA1/A1 genotype had increased in vivo platelet activation (P = 0.001). Furthermore, neither GPIIIa PlA1/A2 nor FcγRIIa H131R genotype influenced S. aureus-induced platelet adhesion, activation or aggregation in vitro (P > 0.05). Taken together, our data suggest that the GPIIIa and FcγRIIa platelet receptor polymorphisms do not influence S. aureus–platelet interactions in vitro or the clinical course of infective endocarditis. PMID:21044892

  6. Autologous Platelet-Rich Plasma Preparations: Influence of Nonsteroidal Anti-inflammatory Drugs on Platelet Function. (United States)

    Schippinger, Gert; Prüller, Florian; Divjak, Manuela; Mahla, Elisabeth; Fankhauser, Florian; Rackemann, Steve; Raggam, Reinhard Bernd


    Autologous platelet-rich plasma (PRP) has been widely used for the treatment of sports injuries. It has been associated with improved healing and regeneration of soft tissues in elite athletes. Athletes are commonly receiving nonsteroidal anti-inflammatory drugs (NSAIDs). As yet, the effect of these drugs on platelet function in PRP formulations has not been taken into consideration. The function of platelets in PRP produced under the influence of NSAIDs is inhibited and may lessen a possible healing effect on the site of injury. Controlled laboratory study. PRP was collected from patients receiving NSAIDs after elective orthopaedic surgery, and platelet function was evaluated using light transmission aggregometry (LTA). Results were compared with those obtained from healthy volunteers without a history of NSAID intake during the previous 2 weeks. Two different systems for blood collection and PRP production (Arthrex ACP double-syringe system and standard 4.5-mL sodium citrate blood collection tubes) were used and compared regarding the quality of PRP that was produced. For both groups, the baseline platelet counts of whole blood and the platelet counts of PRP formulations were found to be in the normal range. Both collection systems for PRP produced comparable results without significant differences between the groups. Platelet function testing with LTA revealed significantly impaired platelet aggregation in both PRP preparations, obtained from patients taking NSAIDs, irrespective of the type of NSAID (P < .001). All subjects from the control group showed normal platelet aggregation patterns when tested with LTA. Autologous PRP produced from subjects after NSAID medication shows significantly impaired platelet function and may result in lower quality regarding the content of bioactive compounds. If required, the administration of NSAIDs should be performed after blood collection for preparation of autologous PRP; otherwise, the therapeutic effect may be limited.

  7. Platelets of patients with chronic kidney disease demonstrate deficient platelet reactivity in vitro

    Directory of Open Access Journals (Sweden)

    van Bladel Esther R


    Full Text Available Abstract Background In patients with chronic kidney disease studies focusing on platelet function and properties often are non-conclusive whereas only few studies use functional platelet tests. In this study we evaluated a recently developed functional flow cytometry based assay for the analysis of platelet function in chronic kidney disease. Methods Platelet reactivity was measured using flow cytometric analysis. Platelets in whole blood were triggered with different concentrations of agonists (TRAP, ADP, CRP. Platelet activation was quantified with staining for P-selectin, measuring the mean fluorescence intensity. Area under the curve and the concentration of half-maximal response were determined. Results We studied 23 patients with chronic kidney disease (9 patients with cardiorenal failure and 14 patients with end stage renal disease and 19 healthy controls. Expression of P-selectin on the platelet surface measured as mean fluorescence intensity was significantly less in chronic kidney disease patients compared to controls after maximal stimulation with TRAP (9.7 (7.9-10.8 vs. 11.4 (9.2-12.2, P = 0.032, ADP (1.6 (1.2-2.1 vs. 2.6 (1.9-3.5, P = 0.002 and CRP (9.2 (8.5-10.8 vs. 11.5 (9.5-12.9, P = 0.004. Also the area under the curve was significantly different. There was no significant difference in half-maximal response between both groups. Conclusion In this study we found that patients with chronic kidney disease show reduced platelet reactivity in response of ADP, TRAP and CRP compared to controls. These results contribute to our understanding of the aberrant platelet function observed in patients with chronic kidney disease and emphasize the significance of using functional whole blood platelet activation assays.

  8. A Two-phase mixture model of platelet aggregation. (United States)

    Du, Jian; Fogelson, Aaron L


    We present a two-phase model of platelet aggregation in coronary-artery-sized blood vessels. The model tracks the number densities of three platelet populations as well as the concentration of a platelet activating chemical. Through the formation of elastic bonds, activated platelets can cohere with one another to form a platelet thrombus. Bound platelets in a thrombus move in a velocity field different from that of the bulk fluid. Stresses produced by the elastic bonds act on the bound platelet material. Movement of the bound platelet material and that of the background fluid are coupled through an interphase drag and an incompressibility constraint. The relative motion between bound platelets and the background fluid permits intraclot transport of individual platelets and activating chemical, allows the bound platelet density to reach levels much higher than the platelet density in the bulk blood, and allows thrombus formation to occur on a physiological timescale, all of which were precluded by our earlier single phase model. Computational results from the two-phase model indicate that through complicated fluid-structure interactions, the platelet thrombus can develop significant spatial inhomogeneities and that the amount of intraclot flow may greatly affect the growth, density, and stability of a thrombus. © The authors 2017. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  9. [Study on platelet-associated tissue factor and its significance]. (United States)

    Huang, Xi-lian; Chen, Fang-ping; Du, Jian-wei; Peng, Min-yuan; Fu, Bin; Xie, Qin-zhi; He, Shi-lin


    To explore whether normal platelet contains tissue factor (TF), and the significance of platelet-associated TF (PATF). Platelets were isolated by Sepharose 2B gel column. ELISA was used to detect the TF content in the lysates of washed platelets. Procoagulant activity of PATF was measured by one stage clotting time assay. The mRNA of TF was detected by reverse transcription polymerase chain reaction (RT-PCR). A certain amount of TF antigen (16.37 +/- 6.39) ng/L was detected in the washed-platelet lysates. Upon activation by collagen, platelets released TF and caused a marked increase in TF level in plasma (P collagen increased significantly, which could be blocked by TF McAb and poor VII plasma. TF mRNA could not be detected in washed platelets. TF content in platelets from patients with coronary heart disease was significantly higher than that from normal controls (P < 0.05). Resting platelets from the patients showed a higher procoagulant activity, which could be inhibited by TF McAb. Platelets contain TF and the latter released by activated platelet was functionally active. Platelet itself might not synthesize TF. Protein content and procoagulant activity of PATF in patients with coronary heart disease were higher than that in controls. All these indicate that platelet may be involved in coagulation and thrombosis by releasing TF.

  10. Equid herpesvirus type 1 activates platelets.

    Directory of Open Access Journals (Sweden)

    Tracy Stokol

    Full Text Available Equid herpesvirus type 1 (EHV-1 causes outbreaks of abortion and neurological disease in horses. One of the main causes of these clinical syndromes is thrombosis in placental and spinal cord vessels, however the mechanism for thrombus formation is unknown. Platelets form part of the thrombus and amplify and propagate thrombin generation. Here, we tested the hypothesis that EHV-1 activates platelets. We found that two EHV-1 strains, RacL11 and Ab4 at 0.5 or higher plaque forming unit/cell, activate platelets within 10 minutes, causing α-granule secretion (surface P-selectin expression and platelet microvesiculation (increased small events double positive for CD41 and Annexin V. Microvesiculation was more pronounced with the RacL11 strain. Virus-induced P-selectin expression required plasma and 1.0 mM exogenous calcium. P-selectin expression was abolished and microvesiculation was significantly reduced in factor VII- or X-deficient human plasma. Both P-selectin expression and microvesiculation were re-established in factor VII-deficient human plasma with added purified human factor VIIa (1 nM. A glycoprotein C-deficient mutant of the Ab4 strain activated platelets as effectively as non-mutated Ab4. P-selectin expression was abolished and microvesiculation was significantly reduced by preincubation of virus with a goat polyclonal anti-rabbit tissue factor antibody. Infectious virus could be retrieved from washed EHV-1-exposed platelets, suggesting a direct platelet-virus interaction. Our results indicate that EHV-1 activates equine platelets and that α-granule secretion is a consequence of virus-associated tissue factor triggering factor X activation and thrombin generation. Microvesiculation was only partly tissue factor and thrombin-dependent, suggesting the virus causes microvesiculation through other mechanisms, potentially through direct binding. These findings suggest that EHV-1-induced platelet activation could contribute to the thrombosis

  11. Decreased mean platelet volume in panic disorder

    Directory of Open Access Journals (Sweden)

    Göğçegöz Gül I


    Full Text Available Işil Göğçegöz Gül, Gül Eryilmaz, Eylem Özten, Gökben Hizli Sayar Neuropsychiatry Health, Practice, and Research Center, Uskudar University, Istanbul, Turkey Aim: The relationship between psychological stress and platelet activation has been widely studied. It is well known that platelets may reflect certain biochemical changes that occur in the brain when different mental conditions occur. Platelet 5-hydroxytryptamine (5-HT is also extensively studied in psychiatry. The mean platelet volume (MPV, the accurate measure of platelet size, has been considered a marker and determinant of platelet function. The aim of the present study was to search for any probable difference in the MPV of subjects with panic disorder (PD.Methods: A total of 37 drug-free subjects, aged 18 to 65 years, diagnosed with PD, with or without agoraphobia, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition (DSM-IV criteria and 45 healthy control subjects were included in the study. Platelet count and MPV were measured and recorded for each subject.Results: There were no statistically significant differences between groups in terms of female/male ratio, age, or body mass index between the PD group and control group (P=0.91, P=0.82, and P=0.93, respectively. The MPV was found to be significantly lower in the PD group compared with the control group (8.8±0.9 fL vs 9.2±0.8 fL; P=0.02. All the participants had MPV values in the standard range of 6.9–10.8 fL.Conclusion: We concluded that abnormalities of the 5-HT1A receptor function in the central nervous system of subjects with a diagnosis of PD are also mirrored in as an alteration in platelet activity. Measurements of platelet activity may be used as a tool for neuropsychiatric and psychopharmacological research and for studying how certain mental diseases and medications affect the central nervous system. Keywords: 5-HT, thrombocyte, anxiety 

  12. Mean platelet volume in hepatitis A. (United States)

    Almiş, H; Bucak, I H; Çelik, V; Tekin, M; Karakoç, F; Konca, Ç; Turgut, M


    Hepatitis A virus (HAV) still continues to be a serious public health problem worldwide. Mean platelet volume (MPV) is a marker of platelet function and activation. This study aimed to evaluate the relationship between MPV in acute hepatitis A patients as compared to the control group and to assess MPV as an acute phase reactant in acute hepatitis A. Seventy-six patients were enrolled in this study. The control group consisted of 41 healthy age- and sex-matched individuals. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, prothrombin time (PT), platelet count (PC), serum albumin (ALB), and mean platelet volume (MPV) levels were recorded. The diagnosis of HAV infection was based on anti-HAV Ig M positivity. The mean levels of MPV in the study group were significantly statistically lower than in the control group (p 0.05), but the MPV levels correlated with the platelet counts (p children with acute hepatitis A. MPV levels were significantly lower in the patients with acute hepatitis A as compared to the healthy control group. This study demonstrated that MPV may be a negative acute phase reactant for acute hepatitis A. Further studies will explain the role that MPV plays in inflammation and other viral infections.

  13. Lea blood group antigen on human platelets

    Energy Technology Data Exchange (ETDEWEB)

    Dunstan, R.A.; Simpson, M.B.; Rosse, W.F.


    One- and two-stage radioligand assays were used to determine if human platelets possess the Lea antigen. Goat IgG anti-Lea antibody was purified by multiple adsorptions with Le(a-b-) human red blood cells, followed by affinity chromatography with synthetic Lea substance and labeling with /sup 125/I. Human IgG anti-Lea antibody was used either in a two stage radioassay with /sup 125/I-labeled mouse monoclonal IgG anti-human IgG as the second antibody or, alternatively, purified by Staph protein A chromatography, labeled with /sup 125/I, and used in a one-stage radioassay. Platelets from donors of appropriate red blood cell phenotypes were incubated with the antisera, centrifuged through phthalate esters, and assayed in a gamma scintillation counter. Dose response and saturation curve analysis demonstrate the presence of Lewis a antigen on platelets from Lea+ donors. Furthermore, platelets from an Le(a-b-) donor incubated in Le (a+b-) plasma adsorb Lea antigen in a similar manner to red blood cells. The clinical significance of these antigens in platelet transfusion remains undefined.

  14. Tocopherol concentrations in platelets in children. (United States)

    Tatsumi, K; Yaoi, K; Mino, M


    To determine the normal range of platelet tocopherol concentrations in childhood, 158 healthy children, 3 months to 15 years old, including 81 males and 77 females were examined and this population was compared with adults. In children, the mean platelet tocopherol concentration was 0.17 micrograms/mg protein, ranging from 0.07 to 0.39 micrograms/mg protein, with a nearly logarithmic distribution. Levels of less than 0.10 micrograms/mg protein were found in only 4 of the 158 subjects. This level may be too low in platelet concentrations for this population of children. Platelet and plasma tocopherol concentrations, and the ratio of plasma tocopherol to total lipids (tocopherol/lipid ratio) in children, excluding the infant group of less than 1 year old, were lower than those in adults. The findings from this population were quite consistent with those of a population previously investigated, with respect to the distribution of plasma and RBC tocopherol concentrations and the tocopherol/lipid ratio. The tocopherol concentrations in plasma, RBCs, and platelets in the infant group were higher than those in the other children's groups (more than 1 year old), and those concentrations were comparable to the adult ones. This may reflect the higher intake of alpha-tocopherol from the prepared formulas containing more than 1,000 micrograms/dl.

  15. Heparin-induced thrombocytopenia: towards standardization of platelet factor 4/heparin antigen tests. (United States)

    Greinacher, A; Ittermann, T; Bagemühl, J; Althaus, K; Fürll, B; Selleng, S; Lubenow, N; Schellong, S; Sheppard, J I; Warkentin, T E


    Laboratory confirmation of heparin-induced thrombocytopenia (HIT) is based on detection of heparin-dependent platelet-activating antibodies. Platelet factor 4 (PF4)/heparin enzyme-immunoassays (EIA) are a widely available surrogate for platelet-activating antibodies. Defining the optical density (OD) reactivity profiles of a PF4/heparin EIA in reference subject and patient populations and the correlation of the EIA results (expressed in OD units) with the prevalence of platelet-activating antibodies. Using quantile regression we determined the 97.5th percentile of PF4/heparin-immunoglobulin G (IgG) EIA reactivities in non-heparin-treated individuals [blood donors (n = 935)] and patients before heparin therapy (n = 1207). In patients with suspected HIT, we compared the correlation of EIA-IgG reactivities (Greifswald laboratory; n = 2821) and the heparin-induced platelet activation assay (HIPA) with the correlation of reactivities of another EIA-IgG (McMaster laboratory; n = 1956) with the serotonin-release assay (SRA). PF4/heparin-IgG EIA OD reactivities had a lower OD 97.5th percentile in blood donors compared with patient groups before heparin treatment (P 0.9) when normalized OD ranges (maximum OD divided by 10) were used instead of absolute OD values. Results of PF4/heparin-IgG EIA should not be reported as only positive or negative as there is no single acceptable cut-off value. Instead, reporting PF4/heparin-IgG EIA OD results in ranges allows for risk-stratified prediction for presence of platelet-activating antibodies. Use of normalized OD ranges permits a standardized approach for inter-laboratory comparisons. © 2010 International Society on Thrombosis and Haemostasis.

  16. Alterations of platelet functions in children and adolescents with iron-deficiency anemia and response to therapy. (United States)

    Mokhtar, Galila M; Ibrahim, Wafaa E; Kassim, Nevine A; Ragab, Iman A; Saad, Abeer A; Abdel Raheem, Heba G


    Several changes in platelets have been reported in patients with iron-deficiency anemia (IDA), so a relationship between iron metabolism and thrombopoiesis should be considered. We aimed to study the alterations of platelet functions in patients with IDA by assessment of platelet aggregation with epinephrine, adenosine diphosphate (ADP) and ristocetin and by measuring platelet function analyzer-100 (PFA-100) closure time together with the effect of iron therapy on the same tests. A follow-up study was conducted in Ain Shams University Children's hospital in the period from June 2011 to June 2012 including 20 patients with confirmed IDA and 20 healthy age- and sex-matched control. Bleeding manifestations were reported. Laboratory analysis included complete blood count, assessment of iron status by measuring serum iron, TIBC and ferritin, assessment of platelet functions by PFA-100 closure time and platelet aggregation with collagen, ADP and ristocetin. Patients with IDA were treated by oral iron therapy 6 mg/kg/day of ferrous sulfate and post-therapeutic re-assessment was done. Mean age of IDA patients was 5.7 ± 4.2 years. Bleeding manifestations were more common in patients group. Mean PFA-100 closure times (with epinephrine) were significantly longer in patients (179.1 ± 86.4 seconds) compared to control group (115 ± 28.5 seconds) (p iron deficiency and platelet functions. Subtle bleeding manifestations can occur in patients with IDA with delay in platelet aggregation and prolongation in PFA-100 closure times which can be reversed by iron therapy.

  17. Applications of Platelet-Rich Plasma in Lymphedema. (United States)

    Akgül, Ahmet; Cirak, Musa; Birinci, Tansu


    Platelet-rich plasma (PRP) is an autologous concentrated preparation of human platelets contained in a small volume of plasma that is characterized by hemostatic and tissue-repairing effects. Being enriched by various kinds of growth factors, and their tissue-repairing effects have made them the focus of attention for use in tissue regeneration. PRP has been safely used and documented in many different fields, including orthopedics, sports injuries, dental and periodontal surgery, and cosmetic, plastic, cardiovascular, general, and maxillofacial surgery. The current evidence obtained from in vitro and animal studies pointed out that PRP may potentially be used to regenerate injured lymphatic vessels to treat or prevent lymphedema. Therefore, we have reviewed existing literature on the clinical uses of PRP in lymphedema and inquired whether there is enough evidence to support the use of PRP in clinical practice as a treatment option. In contrast to in vitro and animal models, there is no clinical trial regarding the use of PRP in lymphedema treatment. Only two animal studies matched to our research yielded positive and promising results in terms of the potential role of PRP in future for lymphedema therapies. In the light of these findings, it is clear that this is an important issue that should be studied in greater depth to clarify the efficacy of PRP in the management of lymphedema.

  18. Photochemical inactivation of pathogenic bacteria in human platelet concentrates. (United States)

    Lin, L; Londe, H; Janda, J M; Hanson, C V; Corash, L


    Platelet concentrates (PC) may be infrequently contaminated with low levels of bacteria that can cause septicemia and death in patients receiving transfusion therapy. We evaluated the efficacy of a photochemical decontamination (PCD) technique using 8-methoxypsoralen (8-MOP) and long wavelength UV light (UVA) to inactivate bacteria in standard therapeutic PC. Twelve phylogenetically distinct pathogenic bacteria, 5 gram-positive and 7 gram-negative organisms, were seeded into PC to a final challenge dose ranging from 10(5) to 10(7) colony-forming units (CFU)/mL. Contaminated PC were treated with 8-MOP (5 micrograms/mL) and 5 J/cm2 of UVA, a PCD treatment regimen found to adequately preserve in vitro platelet function. Greater than 10(5) CFU/mL of all 5 gram-positive (Staphylococcus aureus, Streptococcus epidermidis, Streptococcus pyogenes, Listeria monocytogenes, and Corynebacterium minutissimum) and 2 of the gram-negative (Escherichia coli and Yersinia enterocolitica) organisms were inactivated. The remaining 5 gram-negative organisms were more resistant, with less than 10(1) to 10(3.7) CFU/mL inactivated under these conditions. The inactivation efficiency for this resistant group of gram-negative organisms was improved when PC were resuspended in a synthetic storage medium with reduced plasma protein concentration (15%) and an increased 8-MOP concentration (23.4 micrograms/mL). Illumination with 3 J/cm2 of UVA in this system inactivated greater than 10(5) CFU/mL of 4 resistant gram-negative organisms (Salmonella choleraesuis, Enterobacter cloacae, Serratia marcescens, and Klebsiella pneumoniae) and 10(4.1) CFU/mL of the most resistant gram-negative organism (Pseudomonas aeruginosa). This level of PCD treatment did not adversely affect in vitro platelet function. These results demonstrate that PCD using 8-MOP (5 to 23.4 micrograms/mL) effectively inactivated high levels of pathogenic bacteria in PC with adequate preservation of in vitro platelet properties.

  19. A manual method to obtain platelet rich plasma. (United States)

    Marques, Fabiana Paulino; Ingham, Sheila Jean McNeill; Forgas, Andrea; Franciozi, Carlos Eduardo da Silveira; Sasaki, Pedro Henrique; Abdalla, Rene Jorge


    This study is to report a manual method to obtain platelet rich plasma (PRP). For this study 61 ml of peripheral blood was obtained and submitted to centrifugation at 541g for 5 min. The centrifugation separates the blood into three components: red blood cells, buffy coat and platelet rich plasma. Blood and platelet rich plasma samples were sent to the Hospital's Laboratory and platelets and leukocytes were measured. A sample of 637 blood donors was evaluated. The platelet yield efficiency was 86.77% and the increase in platelet concentration factor was 2.89 times. The increase in leukocyte concentration factor was 1.97 times. The method described here produces leukocyte-rich and platelet-rich plasma with a high platelet and leukocyte increased factor. Level of Evidence IV, Controlled Laboratory Study.

  20. Exosomes: novel effectors of human platelet lysate activity

    National Research Council Canada - National Science Library

    Torreggiani, E; Perut, F; Roncuzzi, L; Zini, N; Baglìo, S R; Baldini, N


    Despite the popularity of platelet-rich plasma (PRP) and platelet lysate (PL) in orthopaedic practice, the mechanism of action and the effectiveness of these therapeutic tools are still controversial...

  1. Polyphosphate nanoparticles on the platelet surface trigger contact system activation

    NARCIS (Netherlands)

    Verhoef, Johan J F; Barendrecht, Arjan D; Nickel, Katrin F; Dijkxhoorn, Kim; Kenne, Ellinor; Labberton, Linda; McCarty, Owen J T; Schiffelers, Raymond; Heijnen, Harry F; Hendrickx, Antoni P; Schellekens, Huub; Fens, Marcel H; de Maat, Steven; Renné, Thomas; Maas, Coen


    Polyphosphate is an inorganic polymer that can potentiate several interactions in the blood coagulation system. Blood platelets contain polyphosphate, and the secretion of platelet-derived polyphosphate has been associated with increased thrombus formation and activation of coagulation factor XII.

  2. Characterization of Platelet Concentrates Using Dynamic Light Scattering

    National Research Council Canada - National Science Library

    Labrie, Audrey; Marshall, Andrea; Bedi, Harjot; Maurer-Spurej, Elisabeth


    .... ThromboLUX is a non-invasive, optical test utilizing dynamic light scattering to characterize a platelet sample by the relative quantity of platelets, microparticles, and other particles present in the sample...

  3. Xanthohumol, a Prenylated Flavonoid from Hops (Humulus lupulus, Prevents Platelet Activation in Human Platelets

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    Ye-Ming Lee


    Full Text Available Xanthohumol is the principal prenylated flavonoid in the hop plant (Humulus lupulus L.. Xanthohumol was found to be a very potent cancer chemopreventive agent through regulation of diverse mechanisms. However, no data are available concerning the effects of xanthohumol on platelet activation. The aim of this paper was to examine the antiplatelet effect of xanthohumol in washed human platelets. In the present paper, xanthohumol exhibited more-potent activity in inhibiting platelet aggregation stimulated by collagen. Xanthohumol inhibited platelet activation accompanied by relative [Ca2+]i mobilization, thromboxane A2 formation, hydroxyl radical (OH● formation, and phospholipase C (PLCγ2, protein kinase C (PKC, mitogen-activated protein kinase (MAPK, and Akt phosphorylation. Neither SQ22536, an inhibitor of adenylate cyclase, nor ODQ, an inhibitor of guanylate cyclase, reversed the xanthohumol-mediated inhibitory effect on platelet aggregation. Furthermore, xanthohumol did not significantly increase nitrate formation in platelets. This study demonstrates for the first time that xanthohumol possesses potent antiplatelet activity which may initially inhibit the PI3-kinase/Akt, p38 MAPK, and PLCγ2-PKC cascades, followed by inhibition of the thromboxane A2 formation, thereby leading to inhibition of [Ca2+]i and finally inhibition of platelet aggregation. Therefore, this novel role of xanthohumol may represent a high therapeutic potential for treatment or prevention of cardiovascular diseases.

  4. Use of Platelet Rich Plasma in an Isolated Complete Medial Collateral Ligament Lesion in a Professional Football (Soccer) Player: A Case Report


    Eirale, Cristiano; Mauri, Eduardo; Hamilton, Bruce


    Purpose Platelet-rich plasma (PRP) is derived from centrifuging whole blood to obtain a high platelet concentration containing numerous growth factors. Despite its widespread use, there is still a lack of high-level evidence regarding randomized clinical trials assessing the efficacy of PRP in treating ligament injuries. Although there is research showing an improvement in the early stages of healing in the animal model of acute medial collateral ligament (MCL) injury of the knee, there is no...

  5. Platelet counting with a laser nephelometer. (United States)

    Giannitsis, D J


    A method for platelet counting is described, based on the Laser nephelometric principle. Experimental results are reported, together with the practical considerations for the standardisation and correlation of the method, and for application of the method in the routine biochemical laboratory. Venous blood, taken with EDTA-NaCL solution according to Schulz et al (1071, Z. Klin. Chem. Klin. Biochem. 9, 329-333) is used. The blood is centrifuged at 100 g for 10 min and 10 microliter of the supernatant is added to 3000 microliter of a suspending medium (dilution 1:80); 300 microliter platelet suspension are read in a nephelometer cuvet or tube against blank. The number of platelets per liter blood are determined with the aid of a standard curve. The sensitivity and reproducibility of the method, and the correlation with the "electronic coulter counting" method are satisfactory.

  6. Adolescent menorrhagia due to platelet function disorder. (United States)

    Hossain, Nazli; Farzana, Tasneem; Khan, Nusrat Hasan; Shamsi, Tahir Sultan; James, Andra H


    The prevalence of menorrhagia in adolescent populations with bleeding disorders varies between 14% to 48%. The common conditions associated with menorrhagia include von Willebrand disease (VWD), platelet function disorders and coagulation factor deficiencies. The majority of studies, which have been conducted in the West, report VWD, as the most common inherited bleeding disorder leading to menorrhagia, whereas studies from South-East Asia have found platelet function disorder as the leading inherited bleeding disorder in women with menorrhagia. The other common conditions which can lead to increased blood loss in this age group are anovulatory bleeding and hormonal disorders. We report here three cases of adolescent menorrhagia due to platelet function disorders, along with review of literature.

  7. Cigarette smoking reduces platelet reactivity independently of clopidogrel treatment in patients with non-ST elevation acute coronary syndromes. (United States)

    Crimi, Gabriele; Somaschini, Alberto; Cattaneo, Marco; Angiolillo, Dominick J; Piscione, Federico; Palmerini, Tullio; De Servi, Stefano


    Smokers receiving clopidogrel show a lower residual platelet reactivity than non-smokers, a phenomenon generally ascribed to smoking-induced increased production of clopidogrel active metabolite, but also associated with the high hemoglobin levels of smokers, which decreases platelet reactivity in tests that measure platelet function in whole blood. We evaluated the impact of cigarette smoking and of hemoglobin levels on platelet reactivity index (PRI) measured by the vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay in whole blood samples from patients with non-ST elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary interventions, both before and after clopidogrel administration. PRI was measured in 718 clopidogrel-naïve NSTE-ACS patients, both before and 1 month after treatment with clopidogrel (75 mg daily). Smokers (n = 347, 48%) had significantly lower mean PRI levels at both baseline (57.7 ± 24.1 vs. 64.8 ± 19.8, p 15), the β coefficient of smoke on PRI was -8.51 [-11.90 to -5.11, p clopidogrel-treated smokers have lower platelet reactivity, measured by the VASP-P assay, compared to clopidogrel-treated non-smokers. However, smokers had lower platelet reactivity already before receiving clopidogrel treatment, suggesting that smoke affects platelet reactivity independently of its potential effect on the pharmacokinetics of clopidogrel. Our data also indicate that such an effect is not mediated by increased hemoglobin levels.



    De, Arun; Sanjeev; Saif; Farah; Piyush


    Platelets can play a crucial role in regenerative therapy as they are reservoirs of growth factors and cytokines which are the key factors for regeneration of the bone and maturation of the soft tissue. Platelet - rich fibr in (PRF) was first described by Choukroun et al. in France. It has been referred to as a second - generation platelet concentrate, which has been shown to have several advantages over traditionally prepared PRP. Platelet - rich fibrin (P...

  9. A Novel Platelet Concentrate: Titanium-Prepared Platelet-Rich Fibrin


    Mustafa Tunalı; Hakan Özdemir; Zafer Küçükodacı; Serhan Akman; Emre Yaprak; Hülya Toker; Erhan Fıratlı


    We developed a new product called titanium-prepared platelet-rich fibrin (T-PRF). The T-PRF method is based on the hypothesis that titanium may be more effective in activating platelets than the silica activators used with glass tubes in Chouckroun’s leukocyte- and platelet-rich fibrin (L-PRF) method. In this study, we aimed to define the structural characteristics of T-PRF and compare it with L-PRF. Blood samples were collected from 10 healthy male volunteers. The blood samples were drawn us...

  10. Nephropathy in type 1 diabetes is associated with increased circulating activated platelets and platelet hyperreactivity

    DEFF Research Database (Denmark)

    Tarnow, Inge; Michelson, Alan D.; Barnard, Marc R.


    -diabetic controls (P = 0.0075). There were no differences between groups in activated GPIIb/IIIa or in response to TRAP at any end-point. More patients with nephropathy received aspirin (71.4%) compared to normoalbuminuric patients (27.4%) (P ..., is associated with circulating activated platelets and platelet hyperreactivity to ADP, despite the confounding variable of more nephropathy patients receiving aspirin. This platelet activation is likely to contribute to the known increased risk of cardiovascular events in patients with diabetic nephropathy...

  11. Effects of Isotretinoin on the Platelet Counts and the Mean Platelet Volume in Patients with Acne Vulgaris

    Directory of Open Access Journals (Sweden)

    Arzu Ataseven


    Full Text Available Aim. The aim of this study was to evaluate the platelet counts and the mean platelet volume in patients who received isotretinoin for the treatment of acne vulgaris. Method. A total of 110 patients were included in this retrospective study. Complete blood count parameters were recorded prior to and three-months following the treatment. Results. Both platelet counts and the mean platelet volume were significantly decreased following the treatment. No significant differences were noted on the levels of hemoglobin, hematocrit, and white blood cell count. Conclusion. Platelet counts and mean platelet volume significantly decreased following isotretinoin treatment. Since the decrease of platelet counts and the mean platelet volume was seen concomitantly, it is concluded that the effect of isotretinoin was through the suppression of bone marrow.

  12. Effect of severe sepsis on platelet count and their indices

    African Journals Online (AJOL)


    Abstract. Background: Sepsis is a major disease affecting almost all organs and systems. Objectives: To examine platelet count and indices (mean platelet volume (MPV) and platelet distribution width (PDW)) in severe sepsis. Methods: Patients with criteria for sepsis at a first examination by an Infectious Diseases specialist ...

  13. Glycoprotein Ibalpha signalling in platelet apoptosis and clearance

    NARCIS (Netherlands)

    van der Wal, E.


    Storage of platelets at low temperature reduces bacterial growth and might better preserve the haemostatic function of platelets than current procedures. Incubation at 0C is known to expose ?-N-acetyl-D-glucosamine-residues on glycoprotein (GP)Ibalpha inducing receptor-clustering and platelet

  14. Platelet function and HIV: a case-control study.

    LENUS (Irish Health Repository)

    Satchell, Claudette S


    Cardiovascular disease and myocardial infarction are of increasing concern in HIV-infected populations. Although platelets mediate arterial thrombosis, central to myocardial infarction, data on platelet function in HIV infection are lacking. We hypothesized that HIV-infected patients would have altered platelet reactivity.

  15. Patterns and functional implications of platelets upon tumor "education". (United States)

    Zhang, Qun; Liu, Hongda; Zhu, Qingqing; Zhan, Ping; Zhu, Suhua; Zhang, Jianya; Lv, Tangfeng; Song, Yong


    While platelets are traditionally recognized to play a predominant role in hemostasis and thrombosis, increasing evidence verifies its involvement in malignancies. As a component of the tumor microenvironment, platelets influence carcinogenesis, tumor metastasis and chemotherapy efficiency. Platelets status is thus predictable as a hematological biomarker of cancer prognosis and a hot target for therapeutic intervention. On the other hand, the role of circulating tumor cells (CTCs) as an inducer of platelet activation and aggregation has been well acknowledged. The cross-talk between platelets and CTCs is reciprocal on that the CTCs activate platelets while platelets contribute to CTCs' survival and dissemination. This review covers some of the current issues related to the loop between platelets and tumor aggression, including the manners of tumor cells in "educating" platelets and biofunctional alterations of platelets upon tumor "education". We also highlight the potential clinical applications on the interplay between tumors and platelets. Further studies with well-designed prospective multicenter trials may contribute to clinical "liquid biopsy" diagnosis by evaluating the global changes of platelets. Copyright © 2017. Published by Elsevier Ltd.

  16. Biochemical and functional abnormalities in hypercholesterolemic rabbit platelets

    Energy Technology Data Exchange (ETDEWEB)

    Dalal, K.B.; Ebbe, S.; Mazoyer, E.; Carpenter, D.; Yee, T. (Lawrence Berkeley Laboratory, CA (USA))


    This study was designed to elucidate changes in rabbit platelet lipids induced by a cholesterol rich diet and to explore the possible correlation of these lipid changes with platelet abnormalities. Pronounced biochemical alterations were observed when serum cholesterol levels of 700-1000 mg% were reached. Hypercholesterolemic (HC) platelets contained 37% more neutral lipids and 16% less phospholipids than the controls. Lysolecithin, cholesterol esters and phosphatidylinositol (PI) levels were increased in HC platelets, and the levels of phosphatidylcholine (PC) were decreased. The cholesterol/phospholipid molar ratio of lipidemic platelets increased from 0.55 +/- 0.011 to 0.89 +/- 0.016 (P less than 0.01) in eight weeks. HC platelets had 90% more arachidonic acid (AA) in the PI than normal platelets. No significant changes in AA of PC were observed. Platelet function was monitored by the uptake and release of (14C)serotonin in platelet rich plasma (PRP), using varying concentrations of collagen as an aggregating agent. The uptake of (14C)serotonin in HC and normal platelets ranged from 78-94%. The percent of (14C)serotonin released from normal and HC platelets was proportional to the concentration of collagen. However, lipidemic platelets were hyperreactive to low concentrations of collagen. Incorporation of 50 microM acetylsalicylic acid into the aggregating medium suppressed the release of (14C)serotonin in normal PRP by more than 90%, but had only a partial effect on lipidemic PRP.

  17. Letter to editor Platelet volume evaluation in patients with sepsis ...

    African Journals Online (AJOL)

    I have read the article published by Guclu et al. with a great interest.1 They examined platelet indices in patients with sepsis. Mean platelet volume (MPV) and platelet distribution width (PDW) were significantly higher in patients with sepsis than in controls. MPV and PDW were significantly higher in patients with severe ...


    Directory of Open Access Journals (Sweden)

    Prasantha Kumar Thankappan


    Full Text Available BACKGROUND Stroke is a major cause of long term morbidity and mortality. Several factors are known to increase the liability to stroke. Platelets play a crucial role in the pathogenesis of atherosclerotic complications, contributing to thrombus formation. Platelet size (mean platelet volume, MPV is a marker and possible determinant of platelet function, large platelets being potentially more reactive. Hence an attempt has-been made to study the association if any between mean platelet volume and thrombotic stroke. The aim of this study was to determine whether an association exists between Mean Platelet Volume (MPV and thrombotic stroke. MATERIALS AND METHODS The study is a case control study and data was collected at Government Medical College Hospital, Kottayam, Kerala a tertiary care referral centre. The study was carried out among fifty patients diagnosed with thrombotic stroke and presenting to the hospital within forty eight hours of onset of symptoms. Fifty age group and sex matched controls were also recruited. Mean platelet volume was obtained using a SYSMEX automated analyser. RESULTS This study has shown a statistically significant relation between mean platelet volume and risk of thrombotic stroke but no statistically significant correlation between clinical severity of stroke and mean platelet volume. CONCLUSION This study has shown an elevation of MPV in acute phase of thrombotic stroke. Platelet mass was found to be more or less a constant. This study did not find a statistically significant correlation between clinical severity of stroke and mean platelet volume.

  19. Morphological and Functional Platelet Abnormalities in Berkeley Sickle Cell Mice (United States)

    Shet, Arun S.; Hoffmann, Thomas J.; Jirouskova, Marketa; Janczak, Christin A.; Stevens, Jacqueline R.M.; Adamson, Adewole; Mohandas, Narla; Manci, Elizabeth A.; Cynober, Therese; Coller, Barry S.


    Berkeley sickle cell mice are used as an animal model of human sickle cell disease but there are no reports of platelet studies in this model. Since humans with sickle cell disease have platelet abnormalities, we studied platelet morphology and function in Berkeley mice (SS). We observed elevated mean platelet forward angle light scatter (FSC) values (an indirect measure of platelet volume) in SS compared to wild type (WT) (37 ± 3.2 vs. 27 ± 1.4, mean ± SD; p Howell-Jolly bodies and “pocked” erythrocytes (p <0.001 for both) suggesting splenic dysfunction. SS mice also had elevated numbers of thiazole orange positive platelets (5 ± 1 % vs. 1 ± 1%; p <0.001), normal to low plasma thrombopoietin levels, normal plasma glycocalicin levels, normal levels of platelet recovery, and near normal platelet life spans. Platelets from SS mice bound more fibrinogen and antibody to P-selectin following activation with a threshold concentration of a protease activated receptor (PAR)-4 peptide compared to WT mice. Enlarged platelets are associated with a predisposition to arterial thrombosis in humans and some humans with SCD have been reported to have large platelets. Thus, additional studies are needed to assess whether large platelets contribute either to pulmonary hypertension or the large vessel arterial occlusion that produces stroke in some children with sickle cell disease. PMID:18374611

  20. Horizontal RNA transfer mediates platelet-induced hepatocyte proliferation

    NARCIS (Netherlands)

    Kirschbaum, Marc; Karimian, Golnar; Adelmeijer, Jelle; Giepmans, Ben N. G.; Porte, Robert J.; Lisman, Ton


    Liver regeneration is stimulated by blood platelets, but the molecular mechanisms involved are largely unexplored. Although platelets are anucleate, they do contain coding or regulatory RNAs that can be functional within the platelet or, after transfer, in other cell types. Here, we show that

  1. Tocotrienols-induced inhibition of platelet thrombus formation and platelet aggregation in stenosed canine coronary arteries

    Directory of Open Access Journals (Sweden)

    Papasian Christopher J


    Full Text Available Abstract Background Dietary supplementation with tocotrienols has been shown to decrease the risk of coronary artery disease. Tocotrienols are plant-derived forms of vitamin E, which have potent anti-inflammatory, antioxidant, anticancer, hypocholesterolemic, and neuroprotective properties. Our objective in this study was to determine the extent to which tocotrienols inhibit platelet aggregation and reduce coronary thrombosis, a major risk factor for stroke in humans. The present study was carried out to determine the comparative effects of α-tocopherol, α-tocotrienol, or tocotrienol rich fraction (TRF; a mixture of α- + γ- + δ-tocotrienols on in vivo platelet thrombosis and ex vivo platelet aggregation (PA after intravenous injection in anesthetized dogs, by using a mechanically stenosed circumflex coronary artery model (Folts' cyclic flow model. Results Collagen-induced platelet aggregation (PA in platelet rich plasma (PRP was decreased markedly after treatment with α-tocotrienol (59%; P P P P P Next, pharmacokinetic studies were carried out and tocol levels in canine plasma and platelets were measured. As expected, α-Tocopherol treatment increased levels of total tocopherols in post- vs pre-treatment specimens (57 vs 18 μg/mL in plasma, and 42 vs 10 μg/mL in platelets. However, treatment with α-tocopherol resulted in slightly decreased levels of tocotrienols in post- vs pre-treatment samples (1.4 vs 2.9 μg/mL in plasma and 2.3 vs 2.8 μg/mL in platelets. α-Tocotrienol treatment increased levels of both tocopherols and tocotrienols in post- vs pre-treatment samples (tocopherols, 45 vs 10 μg/mL in plasma and 28 vs 5 μg/mL in platelets; tocotrienols, 2.8 vs 0.9 μg/mL in plasma and 1.28 vs 1.02 μg/mL in platelets. Treatment with tocotrienols (TRF also increased levels of tocopherols and tocotrienols in post- vs pre-treatment samples (tocopherols, 68 vs 20 μg/mL in plasma and 31.4 vs 7.9 μg/mL in platelets; tocotrienols, 8.6 vs 1

  2. Balancing Potency of Platelet Inhibition with Bleeding Risk in the Early Treatment of Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Slattery, David E


    Full Text Available Objective: To review available evidence and examine issues surrounding the use of advanced antiplatelet therapy in an effort to provide a practical guide for emergency physicians caring for patients with acute coronary syndromes (ACS.Data Sources: American College of Cardiology/American Heart Association (ACC/AHA 2007 guidelines for the management of patients with unstable angina (UA and non-ST-segment elevation myocardial infarction (NSTEMI, AHA/ACC 2007 focused update for the management of patients with STEMI, selected clinical articles identified through the PubMed database (1965-February 2008, and manual searches for relevant articles identified from those retrieved.Study Selection: English-language controlled studies and randomized clinical trials that assessed the efficacy and safety of antiplatelet therapy in treating patients with all ACS manifestations.Data Extraction and Synthesis: Clinical data, including treatment regimens and patient demographics and outcomes, were extracted and critically analyzed from the selected studies and clinical trials. Pertinent data from relevant patient registries were also evaluated to assess current clinical practice.Conclusions: As platelet activation and aggregation are central to ACS pathology, antiplatelet agents are critical to early treatment. A widely accepted first-line treatment is aspirin, which acts to decrease platelet activation via inhibition of thromboxane A2 synthesis. Thienopyridines, which inhibit ADP-induced platelet activation, and glycoprotein (GP receptor antagonists, which bind to platelet GP IIb/IIIa receptors and hinder their role in platelet aggregation and thrombus formation, provide complementary mechanisms of platelet inhibition and are often employed in combination with aspirin. While the higher levels of platelet inhibition that accompany combination therapy improve protection against ischemic and peri-procedural events, the risk of bleeding is also increased. Thus, the

  3. Platelet-rich plasma modulates the secretion of inflammatory/angiogenic proteins by inflamed tenocytes. (United States)

    Andia, Isabel; Rubio-Azpeitia, Eva; Maffulli, Nicola


    Platelet-rich plasma therapies for tendinopathy appear to provide moderate pain reduction. However, the biological mechanisms behind the observed clinical effects remain poorly characterized. The purpose of this study was to explore whether platelet-rich plasma modifies the inflammatory/angiogenic status of already inflamed tenocytes by examining (1) gene expression; (2) modulation of chemokine and interleukin secretion; and (3) differences between healthy and tendinopathic tenocytes. Cells from both healthy and tendinopathic tendons were exposed to interleukin (IL)-1ß and after treated with platelet-rich plasma. Modifications in the expression of selected genes were assessed by real-time reverse transcription-polymerase chain reaction and changes in secretion of angiogenic/inflammatory molecules by enzyme-linked immunosorbent assay. Platelet-rich plasma-induced changes in tendinopathic cells were compared with normal after normalizing platelet-rich plasma data against IL-1ß status in each specific sample. In IL-1ß-exposed cells, platelet-rich plasma downregulates expression of IL-6/CXCL-6 (mean, 0.015; 95% confidence interval [CI], 0.005-0.025; p = 0.026), IL-6R (mean, 0.61; 95% CI, 0.27-0.95; p = 0.029), and IL-8/CXCL-8 (mean, 0.02; 95% CI, 0.007-0.023; p = 0.026). Secretion of IL-6/CXCL6, 0.35 (95% CI, 0.3-0.4; p = 0.002), IL-8/CXCL8, 0.55 (95% CI, 0.5-0.7; p = 0.01), and monocyte chemoattractant protein-1/CCL2, 0.40 (95% CI, 0.2-0.6; p = 0.001) was reduced by platelet-rich plasma, whereas vascular endothelial growth factor increased by twofold, (95% CI, 1.7-2.3; p plasma induces an immunomodulatory and proangiogenic phenotype consistent with healing mechanisms with few differences between tendinopathic and normal cells. Platelet-rich plasma injections in pathological and nearby tissue might help to recover tendon homeostasis.

  4. Platelet homeostasis is regulated by platelet expression of CD47 under normal conditions and in passive immune thrombocytopenia


    Olsson, Mattias; Bruhns, Pierre; Frazier, William A.; Ravetch, Jeffrey V.; Oldenborg, Per-Arne


    Interaction between target cell CD47 and the inhibitory macrophage receptor signal regulatory protein α (SIRPα) counteracts macrophage phagocytosis of CD47-expressing host cells. As platelets also express CD47, we asked whether inhibitory CD47/SIRPα signaling regulates normal platelet turnover and clearance of platelets in immune thrombocytopenic purpura (ITP). CD47-/- mice had a mild spontaneous thrombocytopenia, which was not due to a decreased platelet half-life as a result of increased ex...

  5. An exercise-based physical therapy program for patients with patellar tendinopathy after platelet-rich plasma injection

    NARCIS (Netherlands)

    van Ark, Mathijs; van den Akker-Scheek, Inge; Meijer, L.T.B.; Zwerver, Hans

    Objectives: To describe a post platelet-rich plasma (PRP) injection, exercise-based physical therapy program, investigate feasibility and report the first results of patellar tendinopathy patients treated with PRP injection combined with the physical therapy program. Study Design: Case-series.

  6. Use of second-generation platelet concentrate (platelet-rich fibrin and hydroxyapatite in the management of large periapical inflammatory lesion: A computed tomography scan analysis

    Directory of Open Access Journals (Sweden)

    Hemalatha Hiremath


    Full Text Available Periapical surgery is required when periradicular pathosis associated with endodontically treated teeth cannot be resolved by nonsurgical root canal therapy (retreatment, or when retreatment was unsuccessful, not feasible or contraindicated. Endodontic failures can occur when irritants remain within the confines of the root canal, or when an extraradicular infection cannot be eradicated by orthograde root canal treatment. Foreign-body responses toward filling materials, toward cholesterol crystals or radicular cysts, might prevent complete periapical healing. We present here a case report wherein, combination of platelet-rich fibrin (PRF and the hydroxyapatite graft was used to achieve faster healing of the large periapical lesion. Healing was observed within 8 months, which were confirmed by computed tomography, following improved bone density. PRF has many advantages over platelet-rich plasma. It provides a physiologic architecture that is very favorable to the healing process, which is obtained due to the slow polymerization process.

  7. Physiopathology of blood platelets and development of platelets substitutes. Progress report, August 1, 1976--October 31, 1977. [/sup 51/Cr

    Energy Technology Data Exchange (ETDEWEB)

    Baldini, M G


    Progress is reported on the following research projects: the effect of estrogen on platelet aggregability and thrombus formation; the antithrombotic effect of platelet inhibiting agents in a bench model of artificial kidney; the arrest of hemorrhage in severely alloimmunized thrombocytopenic patients; and in vivo elution of /sup 51/Cr from labeled platelets induced by antibody. (HLW)

  8. Reduced platelet hyperreactivity and platelet-monocyte aggregation in HIV-infected individuals receiving a raltegravir-based regimen

    NARCIS (Netherlands)

    Tunjungputri, R.N.; Ven, A.J. van der; Schonsberg, A.; Mathan, T.S.M.; Koopmans, P.P.; Roest, M.; Fijnheer, R.; Groot, P.G. de; Mast, Q. de


    OBJECTIVE: Platelets are key cells in atherosclerosis and acute cardiovascular events. Platelet hyperreactivity and increased platelet-monocyte aggregation (PMA) are found in HIV-infected patients and may contribute to the excess cardiovascular risk. The integrase inhibitor raltegravir (RAL) has

  9. Pharmacological intervention against bubble-induced platelet aggregation in a rat model of decompression sickness. (United States)

    Pontier, Jean-Michel; Vallée, Nicolas; Ignatescu, Mihaela; Bourdon, Lionel


    Decompression sickness (DCS) with alterations in coagulation system and formation of platelet thrombi occurs when a subject is subjected to a reduction in environmental pressure. Blood platelet consumption after decompression is clearly linked to bubble formation in humans and offers an index for evaluating DCS severity in animal models. Previous studies highlighted a predominant involvement of platelet activation and thrombin generation in bubble-induced platelet aggregation (BIPA). To study the mechanism of the BIPA in DCS, we examined the effect of acetylsalicylic acid (ASA), heparin (Hep), and clopidogrel (Clo), with anti-thrombotic dose pretreatment in a rat model of DCS. Male Sprague-Dawley rats (n = 208) were randomly assigned to one experimental group treated before the hyperbaric exposure and decompression protocol either with ASA (3×100 mg·kg(-1)·day(-1), n = 30), Clo (50 mg·kg(-1)·day(-1), n = 60), Hep (500 IU/kg, n = 30), or to untreated group (n = 49). Rats were first compressed to 1,000 kPa (90 msw) for 45 min and then decompressed to surface in 38 min. In a control experiment, rats were treated with ASA (n = 13), Clo (n = 13), or Hep (n = 13) and maintained at atmospheric pressure for an equivalent period of time. Onset of DCS symptoms and death were recorded during a 60-min observation period after surfacing. DCS evaluation included pulmonary and neurological signs. Blood samples for platelet count (PC) were taken 30 min before hyperbaric exposure and 30 min after surfacing. Clo reduces the DCS mortality risk (mortality rate: 3/60 with Clo, 15/30 with ASA, 21/30 with Hep, and 35/49 in the untreated group) and DCS severity (neurological DCS incidence: 9/60 with Clo, 6/30 with ASA, 5/30 with Hep, and 12/49 in the untreated group). Clo reduced fall in platelet count and BIPA (-4,5% with Clo, -19.5% with ASA, -19,9% with Hep, and -29,6% in the untreated group). ASA, which inhibits the thromboxane A2 pathway, and Hep, which inhibits thrombin

  10. [Single-donor (apheresis) platelets and pooled whole-blood-derived platelets--significance and assessment of both blood products]. (United States)

    Hitzler, Walter E


    current apheresis donation frequency. The donor pool must be increased by 24,576 donors, which means a 67% increase of the existing donor population. A transition to an ATK supply that can cover the entire demand can certainly be realized in a short period of time, while assuring a complete supply with PTK is not a realistic option. All existing studies advise taking extreme caution with any alternative to the current German gold standard for the treatment of hyporegenerative thrombocytopenia. A prophylactic transfusion of a non-pathogen-inactivated platelet concentrate with on average 3 x 10(11) platelets is recommended when the platelet count drops below the threshold of 10,000/microL. All other alternatives to this strategy show an increase in intracranial bleeding events. The existing studies on platelet dose (PLADO-Trial and StoP-Trial) do not recommend deviating from 3 x 10(11) platelets per unit. On the contrary, these studies demonstrate that the only practicable way is to individually correlate every platelet transfusion to the patient body surface. Considering the current knowledge, it is not justified to lower the standard dose and, for certain patient groups, to switch from prophylaxis to therapeutic platelet transfusion. Applying ATK or PTK with a lower platelet content and only for therapeutic purposes, could considerably increase the bleeding risk, especially for WHO grades III and IV. This will also affect all the patients who receive an induction treatment. Through pathogen reduction, in parallel with platelet loss (Apoptosis), the function of the treated platelets is impaired. Alternatively, the cell destruction caused during this process could result in a release of platelet microRNA directly into the supernatant or in microvesicles. This reduction of microRNA will affect the storage of the platelets. (ABSTRACT TRUNCATED)

  11. Hydrogen peroxide lowers ATP levels in platelets without altering adenyalte energy charge and platelet function. (United States)

    Holmsen, H; Robkin, L


    H2O2 irreversibly reduced metabolic platelet ATP levels with a corresponding accumulation of hypoxanthine. This process was enhanced by sodium azide or potassium cyanide and by increasing H2O2 concentrations. The adenylate energy charge was unaltered when less than two thirds of the metabolic ATP had disappeared but decreased markedly when more ATP disappeared. Platelet shape change, primary aggregation, dense granule and alpha-granule secretion were unaffected by H2O2-induced lowering of ATP provided that the adenylate energy charge did not fall by more than 5%; at greater adenylate energy charge reduction, platelet functions were inhibited. These results indicate that cell functions depend more on adenyalte energy charge than on the ATP level and expands the applicability of this view from bacterial systems to a mammalian cell, the human platelet.

  12. Simple platelet markers: Mean platelet volume and congestive heart failure coexistent with periodontal disease. Pilot studies. (United States)

    Czerniuk, Maciej R; Bartoszewicz, Zbigniew; Dudzik-Niewiadomska, Iwona; Pilecki, Tomasz; Górska, Renata; Filipiak, Krzysztof J


    Conducted pilot study concerning mean platelet volume parameter among patients suffering from congestive heart failure and periodontal disease. Examination of dynamic changes of platelet and periodontal markers in group of 50 patients before and an average of 6 months subsequent to professional periodontal treatment. Both platelet and periodontal parameters decreased after periodontal treatment, what is more, the decrease of mean platelet volume (MPV) value due to periodontal disease/mm improvement was shown to be statistically significant (p = 0.05). Improvement of periodontal status may influence decrease of MPV value andincrease of congestive heart failure treatment efficacy and effect patient comfort. It is a new, not frequently used pattern of chronic disease treatment optimalization.

  13. Platelet Aggregation in Rhesus Macaques (Macaca mulatta) in Response to Short-Term Meloxicam Administration (United States)

    Anderson, Keith E; Austin, Jamie; Escobar, Evelyn P; Carbone, Larry


    NSAID administration is often chosen as a method of minimizing pain and discomfort for nonhuman primates. Of concern when using NSAID is the potential for decreased platelet aggregation due to the inhibition of cyclooxygenases 1 and 2. In both dogs and humans, the use of NSAID that are selective for cyclooxygenase 2, like meloxicam, minimizes the inhibition of platelet aggregation in comparison to nonselective NSAID, like aspirin, that inhibit both isoforms of cyclooxygenase. In this study, we measured platelet aggregation in rhesus macaques (n = 6) by using the impedance method on a multiple-electrode aggregometer at baseline, at 1 and 4 d after initiating treatment with aspirin or meloxicam, and after a washout period. There was no statistical difference between aggregation at baseline and after 1 or 4 d of meloxicam treatment, but platelet aggregation decreased after both 1 and 4 d of aspirin therapy. Our data suggest that clinically significant postoperative hemorrhage is unlikely in rhesus macaques briefly treated with meloxicam. PMID:24041216

  14. In vitro anti-platelet potency of ticagrelor in blood samples from infants and children. (United States)

    Söderlund, Fredrik; Asztély, Anna-Karin; Jeppsson, Anders; Nylander, Sven; Berggren, Anders; Nelander, Karin; Castellheim, Albert; Romlin, Birgitta S


    Ticagrelor, a novel platelet inhibitor acting on the ADP-dependent P2Y12 receptor, is currently approved for treating adults with acute coronary syndrome. The effect of ticagrelor in children has not been explored. As a first step, we here evaluate if the in vitro anti-platelet potency of ticagrelor in blood samples from children of different age is different as compared with in blood samples from adults. Blood samples from 36 healthy children grouped by age (0-2 months, n=6; 2-6 months, n=6; 6months-2years, n=6; 2-6 years, n=10; 6-12 years, n=8) and 13 adults were collected for in vitro analysis using vasodilator stimulated phosphoprotein phosphorylation (VASP) assay in whole blood and ADP-induced light transmission aggregometry (LTA) in platelet rich plasma. Ticagrelor (0.01 - 10μmol/L) was added in vitro and its potency was assessed by calculating the concentration that provided 50% inhibition of the maximum response (IC50). The in vitro potency of ticagrelor in blood from adults and in blood from children of any age group were comparable, both when analyzed with LTA and with VASP. These in vitro results are consistent with the hypothesis that ticagrelor would achieve a comparable anti-platelet effect in children of different ages as in adults at equal plasma exposure. Copyright © 2015. Published by Elsevier Ltd.

  15. Investigation of interaction of human platelet membrane components with anticoagulant drugs Abciximab and Eptifibatide.

    Directory of Open Access Journals (Sweden)

    Anna Sankiewicz


    Full Text Available Abciximab (Abci and eptifibatide (Epti are antiaggregate drugs which may reduce thrombotic complications in acute coronary syndromes. The aim of this work was the investigation of the interaction between the phospholipid-GPIIb/IIIa glycoprotein complex and Abci or Epti, and the influence of these drugs on the phospholipid ratio in the platelet membrane. The interaction between the phospholipid-GPIIb/IIIa glycoprotein complex and antiaggregate drugs were investigated using the Surface Plasmon Resonance Imaging technique (SPRI. Phospholipids phosphatidylinositol (PI, phosphatidylserine (PS, phosphatidylethanolamine (PE, phosphatidylcholine (PC and sphingomyelin (SM were first immobilized onto the gold chip surface. The phospholipid ratio in the platelet membrane was determined by the HPLC. Only PI, PS, PE and PC were determined. Human platelets treated 'in vitro' with Abci or Epti exhibit changes in the phospholipid ratio in the platelet membrane. The ratio of PS decreases and PC rises. The SPRI distinctly shows interactions between phospholipids and glycoprotein GPIIb/IIIa, and between the phospholipid-glycoprotein GPIIb/IIIa complex and Abci or Epti. The interaction between phospholipids and glycoprotein GPIIb/IIIa is growing in the sequence: PI

  16. Influence of renal function and platelet turnover on the antiplatelet effect of aspirin. (United States)

    Würtz, Morten; Wulff, Lise N; Grove, Erik L; Kristensen, Steen D; Hvas, Anne-Mette


    Kidney disease predisposes to cardiovascular events. This study investigated the influence of renal function and platelet turnover on the antiplatelet effect of aspirin in patients with coronary artery disease. We included 124 aspirin-treated patients with coronary artery disease and normal to moderately reduced renal function. All tests were performed one hour after aspirin ingestion. Renal function was assessed using creatinine, estimated glomerular filtration rate (eGFR), and cystatin C. The antiplatelet effect of aspirin was evaluated using the VerifyNow Aspirin assay and multiple electrode aggregometry (MEA, Multiplate) induced by collagen (1.0 μg/mL) and arachidonic acid (1.0 mmol/L). Von Willebrand factor was measured as a marker of endothelial dysfunction. Platelet turnover was evaluated by measurements of immature, reticulated platelets. Renal function did not influence the antiplatelet effect of aspirin evaluated by MEA (r=-0.2-0.09, p=0.03-0.77) or the VerifyNow (r=-0.12-0.11, all p-values>0.1). In contrast, renal function correlated inversely with von Willebrand factor levels (r(creatinine)=0.48, pantiplatelet effect of aspirin may be explained by an increased number of immature platelets. Moderately impaired renal function was associated with high levels of von Willebrand factor, but not with a reduced antiplatelet effect of aspirin. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Towards Personalized Medicine Based on Platelet Function Testing for Stent Thrombosis Patients

    Directory of Open Access Journals (Sweden)

    Thea Cornelia Godschalk


    Full Text Available Stent thrombosis (ST is a severe and feared complication of coronary stenting. Patients who have suffered from ST are usually treated according to the “one-size-fits-all” dosing regimen of aspirin and clopidogrel. Many ST patients show high on-treatment platelet reactivity (HPR despite this antiplatelet therapy (APT. It has been shown that HPR is a risk factor for major adverse cardiac events. Therefore, ST patients with HPR are at a high risk for recurrent atherothrombotic events. New insights into the variable response to clopidogrel and the advent of stronger P2Y12 inhibitors prasugrel and ticagrelor have changed the attention from a fixed APT treatment strategy towards “personalized APT strategies.” Strategies can be based on platelet function testing, which gives insight into the overall response of a patient to APT. At our outpatient ST clinic, we practice personalized APT based on platelet function testing to guide the cardiologist to a presumed optimal antiplatelet treatment of ST patients. Beside results of platelet function testing, comedication, clinical characteristics, and genetics have to be considered to decide on personalized APT. Ongoing studies have yet to reveal the optimal personalized APT strategy for cardiologists to prevent their patients from atherothrombotic and bleeding events.

  18. Platelet counts on admission affect coronary flow, myocardial perfusion and left ventricular systolic function after primary percutaneous coronary intervention. (United States)

    Sharif, Dawod; Abu-Salem, Mira; Sharif-Rasslan, Amal; Rosenschein, Uri


    Patients with acute ST-elevation myocardial infarction (STEMI) and increased platelet count treated by fibrinolysis have worse outcomes. The aim of this study was to test the hypothesis that platelet blood count at admission in patients with acute STEMI treated by primary percutaneous coronary intervention affects coronary flow, myocardial perfusion and recovery of left ventricular systolic function. A total of 174 patients presenting with acute anterior STEMI and treated with primary percutaneous coronary intervention were included and divided into subgroups of admission platelet blood count of 400 K. Evaluation of coronary artery flow and myocardial blush grade was performed according to the TIMI criteria. Electrocardiographic ST elevation resolution post-primary percutaneous coronary intervention was evaluated. Doppler echocardiographic evaluation of left anterior descending coronary artery velocities early and late after primary percutaneous coronary intervention and assessment of left ventricular ejection fraction and wall motion score index (WMSI) of left ventricular and left anterior descending coronary artery territory were performed. Post-primary percutaneous coronary intervention TIMI, myocardial blush grade and ST elevation resolution were similar in all groups. Patients with platelet counts primary percutaneous coronary intervention, and higher prevalence of left anterior descending coronary artery velocity deceleration time exceeding 600 ms, (45.5% vs. 40%, P400 K presented with worse left ventricular ejection fraction, left ventricular WMSI and left anterior descending coronary artery WMSI, and before discharge this subgroup had worse left ventricular WMSI and left anterior descending coronary artery WMSI, Pprimary percutaneous coronary intervention with lower admission platelet count had higher left anterior descending coronary artery diastolic velocities, better myocardial perfusion with more patients having left anterior descending coronary artery

  19. Lipid profile of platelets and platelet-derived microparticles in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Qianghua Hu


    General significance: As far as we are aware, our study is the first study on platelet lipidomics in ovarian cancer. The importance of our findings for the future studies are: 1 a similar change in lipid profile of platelets and PMP may be responsible for hypercoagulability in other cancers, and 2 plasma level of high-risk lipids for venous thrombosis may be useful biomarkers.

  20. Radiation-induced volatile hydrocarbon production in platelets

    Energy Technology Data Exchange (ETDEWEB)

    Radha, E.; Vaishnav, Y.N.; Kumar, K.S.; Weiss, J.F.


    Generation of volatile hydrocarbons (ethane, pentane) as a measure of lipid peroxidation was followed in preparations from platelet-rich plasma irradiated in vitro. The hydrocarbons in the headspace of sealed vials containing irradiated and nonirradiated washed platelets, platelet-rich plasma, or platelet-poor plasma increased with time. The major hydrocarbon, pentane, increased linearly and significantly with increasing log radiation dose, suggesting that reactive oxygen species induced by ionizing radiation result in lipid peroxidation. Measurements of lipid peroxidation products may give an indication of suboptimal quality of stored and/or irradiated platelets.


    African Journals Online (AJOL)

    'AFRICAN JOURNAL OF CLINICAL AND EXPERIMENTAL MICROBIOLOGY MAY 2004 ISSN 1595-689X VOL.5 No.2 ... investigations by means of a questionnaire. .... platelet otomeh'ically. Protein concentration in platelet—rich plasma and in the discharged serotonin was determined serotonin, were determined by the ...

  2. Flavonoids and platelet aggregation: A brief review. (United States)

    Faggio, Caterina; Sureda, Antoni; Morabito, Silvia; Sanches-Silva, Ana; Mocan, Andrei; Nabavi, Seyed Fazel; Nabavi, Seyed Mohammad


    Platelets are small anucleated fragments derived from a megakaryocyte precursor. Platelets play a key role in many physiological functions especially in hemostasis and wound healing processes in order to maintain the integrity of the circulatory system. In addition, activated platelets release cytokines and chemokines which modulate the immune response and, in some cases of hyperactivation, they could be associated to the pathogenesis of inflammatory diseases. Flavonoids are polyphenolic compounds ubiquosly found in plants known to be potent antioxidants with positive effects against diverse diseases such as cancer, neurodegenerative or cardiovascular disease. It has been reported that some flavonoids possess anti-platelet aggregation effects though different pathways, being the inhibition of the arachidonic acid-based pathway the most representative mechanism of action. In the present review, the main sources of flavonoids, as well as their bioavailability and metabolism are summarized. Moreover, the available data about the anti-aggregation effects of flavonoids and the different mechanisms of action that has been proposed until now are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Platelets and the complement cascade in atherosclerosis. (United States)

    Patzelt, Johannes; Verschoor, Admar; Langer, Harald F


    Atherosclerosis and its late sequels are still the number one cause of death in western societies. Platelets are a driving force not only during the genesis of atherosclerosis, but especially in its late stages, as evidenced by complications such as arterial thrombosis, myocardial infarction, and ischemic stroke. Atherosclerosis is increasingly recognized as an inflammatory disease, influenced by various immune mechanisms. The complement system is part of our innate immune system, and its diverse roles in atherosclerosis have become evident over the past years. In this review we identify points of intersection between platelets and the complement system and discuss their relevance for atherosclerosis. Specifically, we will f