Academic literature on the topic 'High on-clopidogrel platelet reactivity'
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Journal articles on the topic "High on-clopidogrel platelet reactivity"
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Wiśniewski, Adam, and Karolina Filipska. "The Phenomenon of Clopidogrel High On-Treatment Platelet Reactivity in Ischemic Stroke Subjects: A Comprehensive Review." International Journal of Molecular Sciences 21, no. 17 (September 3, 2020): 6408. http://dx.doi.org/10.3390/ijms21176408.
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Clopidogrel is increasingly being used for the secondary prevention of ischemic stroke according to the updated guidelines on acute stroke management. Failure to achieve a drug response is referred to as clopidogrel resistance. Similarly, a higher activation of platelets during clopidogrel therapy—high on-treatment platelet reactivity—is equivalent to a reduced effectiveness of a therapy. Clopidogrel resistance is considered to be a common and multifactorial phenomenon that significantly limits the efficacy of antiplatelet agents. The aim of the current study is to review the latest literature data to identify the prevalance and predictors of clopidogrel high on-treatment platelet reactivity among stroke subjects and to establish the potential impact on clinical outcomes and prognosis. Clinical databases were searched by two independent researchers to select relevant papers on the topic, including all types of articles. Several important predictors contributing to clopidogrel resistance were identified, including genetic polymorphisms, the concomitant use of other drugs, or vascular risk factors, in particular nonsmoking and diabetes. Clopidogrel high on-treatment platelet reactivity has a negative impact on the clinical course of stroke, worsens the early- and long-term prognoses, and increases the risk of recurrent vascular events. Platelet function testing should be considered in selected stroke individuals, especially those predisposed to clopidogrel resistance, for whom an improvement in the efficacy of antiplatelet therapy is essential. This particular group may become the greatest beneficiaries of the modification of existing therapy based on platelet function monitoring.
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Akinosoglou, Karolina, Angelos Perperis, Spyridoula Theodoraki, Dimitrios Alexopoulos, and Charalambos Gogos. "Sepsis favors high-on-clopidogrel platelet reactivity." Platelets 29, no. 1 (June 21, 2017): 76–78. http://dx.doi.org/10.1080/09537104.2017.1319919.
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Frelinger III, Andrew L., Alan D. Michelson, Stephen D. Wiviott, Dietmar Trenk, Franz-Josef Neumann, Debra L. Miller, Joseph A. Jakubowski, et al. "Intrinsic platelet reactivity before P2Y12 blockade contributes to residual platelet reactivity despite high-level P2Y12 blockade by prasugrel or high-dose clopidogrel." Thrombosis and Haemostasis 106, no. 08 (2011): 219–26. http://dx.doi.org/10.1160/th11-03-0185.
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SummaryIt was the objective of this study to determine whether the intrinsic platelet response to adenosine diphosphate (ADP) before thienopyridine exposure contributes to residual platelet reactivity to ADP despite high level P2Y12 blockade by prasugrel (60 mg loading dose [LD]), 10 mg daily maintenance dose [MD]) or high-dose clopidogrel (600 mg LD, 150 mg daily MD). High residual platelet function during clopidogrel therapy is associated with poor clinical outcomes. It remains unknown whether the relationship between platelet reactivity prior to treatment with clopidogrel (300 mg LD, 75 mg daily MD) and residual on-treatment platelet reactivity is maintained after more potent P2Y12 inhibition. PRINCIPLE-TIMI 44 was a randomised, double-blind, twophase crossover study of prasugrel compared with high-dose clopidogrel in 201 patients undergoing cardiac catheterisation for planned percutaneous coronary intervention. ADP-stimulated platelet-monocyte aggregates, platelet surface P-selectin and platelet aggregation were measured pre-treatment, during LD (6 h and 18–24 h) and MD (15 d). Correlations of pre-treatment to on-treatment values were determined by Spearman rank order. Prasugrel resulted in greater platelet inhibition than high-dose clopidogrel for each measure. However, for both drugs, pre-treatment reactivity to ADP predicted 6 h, 18–24 h and 15 day reactivity to ADP (correlations 0.24–0.62 for platelet-monocyte aggregates and P-selectin). In conclusion, a patient's intrinsic platelet response to ADP before exposure to thienopyridines contributes to residual platelet reactivity to ADP despite high level P2Y12 blockade with high-dose clopidogrel or even higher level P2Y12 blockade with prasugrel. Patients who are hyper-responsive to ADP pre-treatment are more likely to be hyper-responsive to ADP on-treatment, which may be relevant to therapeutic strategies.
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Kristensen, Steen, Willibald Hochholzer, Franz-Josef Neumann, and Dietmar Trenk. "High on-treatment platelet reactivity and P2Y12 antagonists in clinical trials." Thrombosis and Haemostasis 109, no. 05 (2013): 834–45. http://dx.doi.org/10.1160/th12-08-0588.
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SummaryDual antiplatelet therapy with aspirin and clopidogrel in patients undergoing percutaneous coronary intervention (PCI) and in patients with acute coronary syndromes (ACS) has substantially decreased the rate of cardiovascular events. Within the past decade, the variability in pharmacodynamic response as well as the moderate antiplatelet efficacy of clopidogrel has raised major concerns, since high on-clopidogrel platelet reactivity has consistently been associated with increased risk for ischaemic events in PCI patients. The variability in response could be linked to genetic polymorphisms impacting on activity of cytochrome P450 enzymes as well as clinical and demographic variables, but, taken together, factors identified so far can explain only up to approximately 12% of this variability in adenosine diphosphate-induced platelet aggregation on clopidogrel. Regulatory agencies as well as major cardiac societies suggest the use of other anti-platelet medications or alternative dosing strategies for clopidogrel in patients with reduced effectiveness of clopidogrel. This review will focus on the current status of alternate strategies for more sufficient suppression of high platelet reactivity.
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Hildemann, Steven, Christian Schulz, Daniela Fraccarollo, Corinna Schöpp, Ulrike Flierl, Kerstin Wissel, Jaroslav Pelisek, Steffen Massberg, Johann Bauersachs, and Andreas Schäfer. "Fractalkine promotes platelet activation and vascular dysfunction in congestive heart failure." Thrombosis and Haemostasis 111, no. 04 (2014): 725–35. http://dx.doi.org/10.1160/th13-08-0640.
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SummaryEndothelial dysfunction and enhanced platelet reactivity in congestive heart failure (CHF) contribute to poor prognosis. CHF patients display an impaired responsiveness to clopidogrel. Fractalkine activates platelets and elevated plasma levels of this chemokine are a feature of CHF. We here addressed the interrelation of fractalkine, platelet reactivity and clopidogrel efficacy in humans and rats with CHF. Fractalkine serum levels determined by ELISA were increased in CHF patients (CHF: 1548 ± 650 pg/ml; Control: 968 ± 575 pg/ml, p<0.01) and following CHF induction in rats (CHF: 1509 ± 753 pg/ ml; Sham: 1181 ± 275 pg/ml, p<0.05). Expression of fractalkine and its receptor CX3CR1 was enhanced in aortas of CHF rats as determined by immunofluorescence microscopy and molecular analysis. Fractalkine significantly aggravated endothelial dysfunction and augmented P-selectin expression on platelets from CHF rats. Platelet surface expression of CX3CR1 was increased in CHF rats, who displayed an impaired response to clopidogrel (platelet reactivity to ADP: CHF 30 ± 22%; Sham: 8 ± 5%, p<0.05). Similarly in humans with CHF, elevated fractalkine levels were accompanied by reduced clopidogrel responsiveness. Patients with high on-clopidogrel treatment platelet P2Y12 reactivity displayed higher fractalkine levels (1525 ± 487 pg/ml) than those with sufficient clopidogrel response (684 ± 315 pg/ml, p<0.01). In conclusion, in CHF fractalkine was increased on the endothelium and in blood serum, and platelet surface- expression of CX3CR1 was enhanced. Fractalkine diminished endothelial function beyond the impairment already observed in CHF and was associated with a reduced responsiveness to the platelet inhibitor clopidogrel. These findings may indicate a novel pathophysiological mechanism contributing to impaired clopidogrel responsiveness in CHF.
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Mangiacapra, Fabio, Bernard De Bruyne, Olivier Muller, Catalina Trana, Argyrios Ntalianis, Jozef Bartunek, Guy Heyndrickx, Germano Di Sciascio, William Wijns, and Emanuele Barbato. "High Residual Platelet Reactivity After Clopidogrel." JACC: Cardiovascular Interventions 3, no. 1 (January 2010): 35–40. http://dx.doi.org/10.1016/j.jcin.2009.10.024.
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Campo, Gianluca, Matteo Miccoli, Matteo Tebaldi, Jlenia Marchesini, Luca Fileti, Monia Monti, Marco Valgimigli, and Roberto Ferrari. "Genetic determinants of on-clopidogrel high platelet reactivity." Platelets 22, no. 6 (May 31, 2011): 399–407. http://dx.doi.org/10.3109/09537104.2011.579648.
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Nührenberg, Thomas, Michael Amann, Marco Cederqvist, Pascal Kleiner, Christian M. Valina, Dietmar Trenk, Franz-Josef Neumann, Willibald Hochholzer, and Christian Stratz. "Impact of reticulated platelets on antiplatelet response to thienopyridines is independent of platelet turnover." Thrombosis and Haemostasis 116, no. 11 (September 2016): 941–48. http://dx.doi.org/10.1160/th16-03-0191.
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SummaryReticulated platelets are associated with impaired antiplatelet response to thienopyridines. It is uncertain whether this interaction is caused by a decreased drug exposure due to high platelet turnover reflected by elevated levels of reticulated platelets or by intrinsic properties of reticulated platelets. This study sought to investigate if the impact of reticulated platelets on early antiplatelet response to thienopyridines is mainly caused by platelet turnover as previously suggested. Elective patients undergoing coronary intervention were randomised to loading with clopidogrel 600 mg or prasugrel 60 mg (n=200). Adenosine diphosphate (ADP)-induced platelet reactivity was determined by impedance aggregometry before, at 30, 60, 90, and 120 minutes and at day 1 after loading. Immature platelet count was assessed as marker of reticulated platelets by flow cytometry. Platelet reactivity increased with rising levels of immature platelet count in both groups. This effect was more distinctive in patients on clopidogrel as compared to patients on prasugrel. Overall, immature platelet count correlated well with on-treatment platelet reactivity at all timepoints (p < 0.001). These correlations did not change over time in the entire cohort as well as in patients treated with clopidogrel or prasugrel indicating an effect independent of platelet turnover (comparison of correlations 120 minutes/day 1: p = 0.64). In conclusion, the association of immature platelet count with impaired antiplatelet response to thienopyridines is similar early and late after loading. This finding suggests as main underlying mechanism another effect of reticulated platelets on thienopyridines than platelet turnover.Supplementary Material to this article is available online at www.thrombosis-online.com.
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Kuliczkowski, Wiktor, Ewa Żurawska-Płaksej, Maria Podolak-Dawidziak, Magdalena Cielecka-Prynda, Bożena Karolko, Jakub Dębski, Konrad Kaaz, et al. "Platelet Reactivity and Response to Aspirin and Clopidogrel in Patients with Platelet Count Disorders." Cardiology Research and Practice 2021 (April 17, 2021): 1–7. http://dx.doi.org/10.1155/2021/6637799.
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Background. Platelet reactivity and response to antiplatelet drugs, acetylsalicylic acid (ASA) and clopidogrel, in patients with thrombocytopenia and thrombocythemia can have a potentially important effect on the outcome. The effectiveness and safety of antiplatelet drugs in such patients has not been well examined. Measuring the effect of ASA and clopidogrel on platelets could help guide the therapy. Nevertheless, platelet response to antiplatelet drugs is not routinely measured in platelet count disorders and relevant evidence is scarce. Aims. The study aimed to measure platelet reactivity and response to ASA and clopidogrel in patients with platelet count disorders. Materials and Methods. This was a cross-sectional study of consecutive patients hospitalized in cardiology and hematology departments in the years 2018–2019. The study included patients with thrombocytopenia (PLT < 150 G/L) and thrombocythemia (PLT > 450 G/L) on ASA or dual antiplatelet therapy (DAPT; ASA plus clopidogrel). Controls included patients on antiplatelet drugs with normal platelet count. Platelet reactivity was measured in whole blood (Multiplate aggregometer, Roche, Switzerland) using arachidonic acid (AA), adenosine-5′-diphosphate (ADP), and thrombin receptor agonist peptide-6 (TRAP) as agonists. Platelet aggregation was expressed in arbitrary units (AU). AA-induced aggregation was used as a measure of response to ASA with a cut-off above 30 AU showing high on-treatment platelet reactivity to ASA (HTPR-A). ADP-induced aggregation measured response to clopidogrel with a cut-off above 48 AU for high on-treatment platelet reactivity to clopidogrel (HTPR-C). TRAP-induced aggregation measured baseline platelet reactivity not affected by oral antiplatelet drugs. Results. The study included 174 patients. There were 64 patients with thrombocytopenia, 30 patients with chronic thrombocythemia, and 80 controls. All patients were on 75 mg of ASA and 32% of them additionally on 75 mg of clopidogrel due to a history of recent coronary artery angioplasty. AA- and ADP-induced aggregation was comparable between thrombocytopenic patients and controls (median (IQR) 19 (7–28) vs. 23 (15–38) for AA AU and 32 (16–44) vs. 50 (32–71) for ADP AU, respectively), while it was significantly higher in thrombocythemic patients (median (IQR) 80 (79–118) for AA AU and 124 (89–139) for ADP AU). TRAP-induced aggregation showed significantly lowest aggregation in thrombocytopenic (median (IQR) 41 (34–60) for TRAP AU) and highest in thrombocythemic patients (median (IQR) 137 (120–180) for TRAP AU). HTPR-A was frequent in thrombocythemic patients in comparison with thrombocytopenic patients and controls (60% vs. 4% vs. 15%, respectively; p < 0.0002 ). HTPR-C was highly common in thrombocythemic patients and least common in thrombocytopenic ones in comparison with controls (80% vs. 8% vs. 40%, respectively; p < 0.001 ). Conclusion. Chronic thrombocytopenia does not significantly affect platelet reactivity and response to ASA and clopidogrel in comparison with controls. Thrombocytosis significantly increases platelet reactivity and attenuates response to both ASA and clopidogrel.
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Tousek, Petr, Viktor Kocka, Jakub Sulzenko, Frantisek Bednar, Hana Linkova, and Petr Widimsky. "Pharmacodynamic Effect of Clopidogrel in Patients Undergoing Transcatheter Aortic Valve Implantation." BioMed Research International 2013 (2013): 1–3. http://dx.doi.org/10.1155/2013/386074.
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The aim of this study was to analyze periprocedural and mid-term effect of clopidogrel on platelet function using the VerifyNow P2Y12point-of-care assay in patients undergoing TAVI. Platelet reactivity was measured at the beginning of the procedure after 300 mg clopidogrel bolus administration and during the follow-up (at 1 month after the procedure) in 52 patients undergoing TAVI using the Medtronic CoreValve prosthesis (Medtronic CoreValve). A cutoff value of 240 PRU was used to identify nonresponders to clopidogrel treatment with high residual platelet reactivity (HRPR). Baseline HRPR was identified in 80% of patients and in 72% of patients during 6-month follow-up. There was no significant difference in the pharmacodynamic effects of clopidogrel on platelet reactivity from baseline to 6-months follow-up (297±57vs.275±62;P=0.058). Ischemic event occurred only in 3 patients (5.8%) from the study group. In conclusion, majority of patients undergoing TAVI had high residual platelet reactivity after pretreatment with 300 mg of clopidogrel and during the 6-month follow-up at dual antiplatelet treatment. The noneffectiveness of clopidogrel in the TAVI population raises the question of the routine use of dual antiplatelet treatment in this setting.
Dissertations / Theses on the topic "High on-clopidogrel platelet reactivity"
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Li, R. H. L., J. A. Stern, V. Ho, F. Tablin, and S. P. Harris. "Platelet Activation and Clopidogrel Effects on ADP-Induced Platelet Activation in Cats with or without the A31P Mutation in MYBPC3." WILEY-BLACKWELL, 2016. http://hdl.handle.net/10150/622355.
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Background: Clopidogrel is commonly prescribed to cats with perceived increased risk of thromboembolic events, but little information exists regarding its antiplatelet effects. ObjectiveTo determine effects of clopidogrel on platelet responsiveness in cats with or without the A31P mutation in the MYBPC3 gene. A secondary aim was to characterize variability in feline platelet responses to clopidogrel. AnimalsFourteen healthy cats from a Maine Coon/outbred mixed Domestic cat colony: 8 cats homozygous for A31P mutation in the MYPBC3 gene and 6 wild-type cats without the A31P mutation. MethodsEx vivo study. All cats received clopidogrel (18.75 mg PO q24h) for 14 days. Before and after clopidogrel treatment, adenosine diphosphate (ADP)-induced P-selectin expression was evaluated. ADP- and thrombin-induced platelet aggregation was measured by optical aggregometry (OA). Platelet pVASP and ADP receptor response index (ARRI) were measured by Western blot analysis. ResultsPlatelet activation from cats with the A31P mutation was significantly (P = .0095) increased [35.55% (18.58-48.55) to 58.90% (24.85-69.90)], in response to ADP. Clopidogrel treatment attenuated ADP-induced P-selectin expression and platelet aggregation. ADP- and PGE(1)-treated platelets had a similar level of pVASP as PGE(1)-treated platelets after clopidogrel treatment. Clopidogrel administration resulted in significantly lower ARRI [24.13% (12.46-35.50) to 11.30% (-7.383 to 23.27)] (P = .017). Two of 13 cats were nonresponders based on OA and flow cytometry. Conclusion and Clinical ImportanceClopidogrel is effective at attenuating platelet activation and aggregation in some cats. Cats with A31P mutation had increased platelet activation relative to the variable response seen in wild-type cats.
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Grifoni, Elisa. "Funzione piastrinica e rischio di eventi avversi in pazienti con arteriopatia periferica sottoposti a rivascolarizzazione percutanea (Platelet function and risk of adverse events in peripheral artery disease patients undergoing percutaneous revascularization)." Doctoral thesis, 2018. http://hdl.handle.net/2158/1125789.
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Background and Aim: Lots of studies demonstrated that a different entity of on-treatment platelet function inhibition is associated with different clinical outcomes in patients with acute coronary syndromes. In particular, high on-treatment platelet reactivity (HPR) has been associated with an increased risk of ischemic complications (especially stent thrombosis), and there is a growing body of evidence that, on the contrary, low on-treatment platelet reactivity (LPR) could be associated with bleeding risk. Few data are available in the literature on the association between a different entity of platelet inhibition on-antiplatelet treatment and clinical outcomes in patients with peripheral artery disease (PAD).
Aim of this study was to evaluate, in patients with PAD undergoing percutaneous revascularization, the degree of on-treatment platelet reactivity, and its association with ischemic and hemorrhagic adverse events at follow-up.
Methods: In this observational, prospective, single center study, consecutive patients with PAD undergoing percutaneous transluminal angioplasty (PTA) with or without stenting, were enrolled. All patients were treated with dual antiplatelet therapy with aspirin and a P2Y12 inhibitor. Platelet function was assessed by Light Transmission Aggregometry (LTA) using arachidonic acid (AA) and adenosine diphosphate (ADP) as agonists of platelet aggregation, on blood samples obtained within 24 hours from PTA. HPR was defined by LTA ≥20% if induced by AA, and LTA ≥70% if induced by ADP. Follow-up was performed in order to record the occurrence of ischemic and bleeding events.
Results: The study enrolled 177 patients [118 males, median age 75 (IQR 68-81) years]. HPR by AA was found in 52% of patients, and showed a non significant association with older age and a higher prevalence of renal failure, whereas HPR by ADP was found in 32% of patients, and was significantly associated with older age. During follow-up [median duration 23 (IQR 13-27) months] 23 deaths (13%) were recorded; 27 patients (17.5%) underwent target limb revascularization, 2 (1.3%) amputation, and 6 (3.9%) myocardial revascularization. Twenty-four patients (15.6%) experienced a minor bleeding complication. At multivariate analysis HPR by AA and HPR by ADP were independent predictors of death [HR 3.75 (1.20-11.66), P=0.023 and HR 4.78 (1.57-14.52), P=0.006, respectively]. Moreover, patients with dual HPR both by AA and by ADP showed a significantly higher risk of death than those without (P<0.001). The median value of LTA by ADP was significantly lower in patients with bleeding complications than in those without [26.5 (22-39.2)% vs 62 (44.5-74)%, P<0.001). At ROC curve analysis the cut-off of platelet aggregation induced by ADP with the best sensitivity and specificity for increased risk of bleeding was 41%. LTA by ADP lower than 41% was independently associated with bleeding [HR 14.59 (2.55-24.01), P=0.001] at multivariate analysis.
Conclusions: In PAD patients undergoing PTA, HPR by ADP and AA were predictors of death, whereas LPR by ADP was predictor of bleeding complications. These results suggest the potential utility of assessing platelet function, even in the setting of PAD, in order to ensure the patient the best tailored antiplatelet therapy.
Book chapters on the topic "High on-clopidogrel platelet reactivity"
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Hernandiz, Amparo, Jose Luis Díez, Antonio Moscardo, Ana Latorre, Maria Dolores Domenech, Maria Teresa Santos, and Juana Valles. "Platelet Reactivity in Patients with Coronary Stenting Treated with Dual Antiplatelet Therapy and after Withdrawal of Clopidogrel: Impact of Bioactive Titanium Stent versus Everolimus-coated Stent." In Frontiers in Cardiovascular Drug Discovery: Volume 4, 65–82. BENTHAM SCIENCE PUBLISHERS, 2019. http://dx.doi.org/10.2174/9781681083995119040005.
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Objective:To study platelet reactivity at different times while on dual antiplatelet therapy (DAPT) with aspirin (ASA) and clopidogrel in patients treated with bioactive stents (TITAN2®) or everolimus-coated stents (XIENCE V®) and one month afterclopidogrel cessation. Background: Coronary intervention damages the endothelium and causes platelet response leading to thrombotic occlusion, which is prevented with DAPT. Methods:We studied 20 patients with bioactive stent and stable ischemia (BAS-SI group); 31 patients with bioactive stent and acute coronary syndrome (BAS-ACS group) and 31 patients with stable ischemia and everolimus-coated stent (EVE group). DAPT was administered (ASA 100 mg/day and clopidogrel 75 mg/day) for one year in BAS-ACS and EVE groups and for 1 month in BAS-SI group. Platelet aggregation induced by different agonists and platelet recruitment were analyzed at different times of DAPT and 1 month after clopidogrel cessation. Results: After one month of DAPT, platelet aggregation showed no difference between groups; at 12 months of DAPT, the response to collagen and ADP increased in EVE group. Platelet recruitment at 1 month was higher in the BAS-ACS than the other groups; after 12 months, recruitment increased in the EVE group with respect to BASACS. Platelet aggregation and recruitment in diabetics were significantly higher in all situations than in non-diabetic patients. Clopidogrel withdrawal increased ADPinduced aggregation and collagen-induced aggregation and recruitment. Conclusion: Platelet reactivity in patients with DAPT varies with time, depending on the subset of patients, the type of the stent implanted and the time after implantation.
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Guttmann, Oliver P., Ronald Binder, Oliver Gämperli, and Andreas Baumbach. "Antithrombotics for Acute and Chronic Coronary Syndromes." In Manual of Cardiovascular Medicine, 117–24. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780198850311.003.0014.
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Thrombus formation involves activation of aggregating platelets as well as the formation of fibrin after activation of the coagulation cascade. Fibrin eventually binds to glycoprotein IIB/IIIA receptors on platelets thereby forming a very solid occlusive clot. There are several molecules interfering with platelet activation: (1) aspirin, which blocks the formation of thromboxane A2; (2) clopidogrel, prasugrel, and ticagrelor which block P2Y12 receptors and their activation by ADP; (3) glycoprotein inhibitors that interfere with glycoprotein IIB/IIIA on platelets, the final common pathway of platelet activation, and finally (4) thrombin inhibitors blocking PAR-1 receptors on platelets. Commonly, after an acute coronary syndrome (ACS) or after percutaneous coronary interventions (PCI) or even bypass surgery, dual antiplatelet therapy (DAPT) is recommended consisting of aspirin plus a P2Y12 inhibitor. The duration of treatment after the acute event is commonly 12 months for those with ACS and 6 months for those with a high bleeding risk. In patients with high ischaemic risk, prolonged DAPT treatment can be considered, but often such patients also have a high bleeding risk. Intravenous platelet inhibitors, such as Reopro, tirofiban, and others, are used mainly during PCI, particularly in patients with ACS. Inhibitors of coagulation cascade, such as factor Xa or factor II inhibitors or vitamin K antagonists are mainly used in patients with ACS and concomitant atrial fibrillation. In these patients, mainly aspirin or in some the P2Y12 inhibitor is skipped for some weeks or months.
Conference papers on the topic "High on-clopidogrel platelet reactivity"
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Chong, B. H., F. Ismail, J. Cade, A. S. Gallus, S. Gordon, and C. N. Chesterman. "HEPARIN-INDUCED THROMBOCYTOPENIA: IN VITRO STUDIES WITH LOW MOLECULAR WEIGHT HEPARINOID, ORG 10172." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643926.
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Heparin-induced thrombocytopenia (HIT), an adverse effect of heparin therapy, may be associated with serious thrombosis resulting in severe disability or death. An IgG heparin-dependent antibody may be demonstrated in HIT by platelet aggregation studies with patient serum/plasma and standard (s) heparin. A recent study showed high cross-reactivity of the antibody with low molecular weight (LMW) heparins as most of the 22 patient sera tested gave a positive reaction with various LMW heparins including CY222, CY216, PK10169 and Kabi 2165 (Messmore HL et al, Blood 64(5), 1984 suppl). However, cross-reactivity rate with Org 10172, a LMW heparinoid which has strong anti-Xa but negligible antithrombin activity, is unknown. We tested the plasma of 17 patients with HIT for cross-reactivity with Org 10172. Although all 17 patient plasmas reacted positively with s.heparin (0.2 1.0 IU/ml), only 3 patient plasmas gave a positive but weaker reaction with Org 10172 (0.2-1.0 IU/ml).Further studies were performed to investigate the effect of adding Org 10172 (0.2 to 2.0 anti-Xa U/ml) to a reaction mixture of normal platelet-rich plasma, patient plasma and s.heparin (0.2 IU/ml). With 7 patient plasmas which showed no cross-reactivity with Org 10172, the antibody-induced platelet aggregation was inhibited when the concentration of Org 10172 exceeded 0.5 to 1.0 anti-Xa U/ml. When the study was repeated with other s.heparin concentrations (0.05, 0.1, 0.4 IU/ml), this inhibitory effect was again present provided the ratio of Org 10172 concentration (anti-Xa U/ml) to heparin concentration (IU/ml) exceeds 2.5 to 5. However, this inhibitory effect was not observed with the 3 patient plasmas which showed cross-reactivity with the heparinoid whqp. the same concentrations of Org 10172 were added. This inhibitory effect appeared to be specific for platelet aggregation induced by the heparin-dependent antibody as Org 10172 (<10 anti-Xa U/ml) did not affect platelet aggregation induced by collagen (2 ug/ml) and ADP (2.5 uM). These findings together with our experience of 3 cases of HIT successfully treated with Org 10172 suggest that this LMW heparinoid may be a useful drug for the treatment of HIT.
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Badimon, L., J. J. Badimon, and V. Fuster. "ACUTE THROMBOSIS IN STENOTIC AREAS: IMPORTANCE OF THE VASCULAR MATRIX EXPOSED TO BLOOD." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642842.
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The platelet response to angioplasty or spontaneous plaque rupture leads to acute thrombotic occlusion under certain conditions. We analyzed the role of local shear rate (flow and vessel cross-section related), the nature of the exposed matrix and the effect of thrombin inhibition in platelet acute response to injury. Collagen type I (exposed in plaque rupture) and de-endothelialized pig aorta (mild injury) were exposed to pig blood in a tubular perfusion chamber with well characterized flow conditions, placed within an extracorporeal circuit in swine (N=20). Platelet deposition was measured by labeling autologous platelets with Indium and optical morphometry of epoxy embedded specimens. Selected specimens were analyzed by electron microscopy. Unanticoagulated blood and blood from animals treated with 300u/Kg of heparin were perfused over the substrate for 3 and 10 min at local shear rates typical of unobstructed arteries (212s™1 - 424s™1) and of stenotic vessel (824s™1 - 1690s™1). Platelet deposition (Platelets × 106/cm2 ± SE) for 3 min perfusions were:Platelet deposition is dependent on the reactivity of the vascular matrix exposed to blood and on the local shear rate. The greatest rate of thrombus growth is observed with collagen and high shear rate conditions which may precipitate acute thrombotic occlusion in stenotic regions, mainly when the coagulation pathway is not inhibited (255×l06 platelets/ cm2 in 3 minutes. The relative contribution of rheology and the isolated components of the atherosclerotic plaque matrix exposed to blood in the onset of acute coronary syndromes will be differentiated with this experimental model.
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David, J. L., V. Legrand, and H. E. Kulbertus. "RELEVANCE OF FREE PLATELET COUNT RATIO (PCR) TO CIRCULATING PLATELET AGGREGATES (CPA) AND TO THE RELEASE OF B-THROMBOGLOBULIN(β-tg) INDUCED BY EXERCICE IN PATIENTS WITH CORONARY HEART DISEASE (CHD). EFFECTS OF TICLOPIDINE (T) TREATMENT." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643026.
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CPA are considered as a possible cause of blood flow impairment and as a risk factor of sudden death in patients with CHD. The relevance of a low PCR to the presence of CPA is still debated. Indeed in a critical and well designed evaluation of this index, Sanibaldi et al.(1986) have shown that PCR obtained by counting free platelets in diluted whole blood was not lowered in patients with “thrombotic tendency”. They suggested that low CPA reported in other clinical studies may result from an artifact of blood sampling or from ex-vivo procedures.In order to reevalute the meaning of a low PCR, selected patients with CHD have been submitted to an exercice resulting in platelet stimulation. Free platelets were counted, whole blood and plasma β-tg were simultaneously determined by RIA after careful blood sampling performed before the exercice, at its end and 30 min later. Patients were previously treated by Placebo (P)or by T 500 mg per day given in a cross-over double blind manner.It was shown that : 1) after P treatment, PCR was lowered and β-tg was increased, both significantly, at the end of exercice; 30 min later, PCR was normalized whereas β-tg remained high presumably because β-tg is not cleared from plasma within 30 min. 2) T treatment significantly inhibited both platelet responses.In conclusion, when platelets are submitted to systemic and sustained stimuli occurring during exercice stress, lowered PCR reflects the presence of circulating platelet aggregates which can be dispersed ex-vivo by EDTA. In these conditions, the meaning of this index is strongly confirmed by the simultaneous release of βtg. T treatment significantly reduces platelet reactivity to exer cice stress and may reduce the effects of platelet aggregation and release on compromised microcirculation.
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Kos, M., F. X. Hainz, I. Assmann, M. Kundi, I. Pabinger, S. Panzer, Ch Korninger, Ch Kunz, and K. Lechner. "RISK FACTORS FOR AIDS AND ARC IN MULTITRANSHJSED HAEMOPHILIACS: ASSOCIATION OF A WEAK GAG P 18 IN WESTERN BLOT (WB) AND IMMUNE THROMBOCYTOPENIA?" In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644680.
Full textAbstract:
Lymphocyte subsets, platelet counts, immune globulin levels and antibody to HIV (Elisa, WB) were determined in 87 multitransfused asymptomatic haemophiliacs in 1982/83. Between 1982 and 1987 6 patients developed AIDS and 5 ARC (3 immune thrombocytopenia and 2 lymphadenopathy). AIDS or ARC developed in seropositive patients only (11/49). Patients who subsequently developed AIDS or ARC showed significantly lower numbers of T helper lymphocytes (378/mm3 versus 605/mm3; p 0.01), lower platelet counts (157x109 versus 194x109; p 0.05) and higher levels of IgG (2528 mg/dl versus 1992 mg/dl; p 0.01). AIDS or ARC occured in 4 of 7 patients(57.1%) with a low HIV antibody level ( 2000), but only in 7 of 42 (16.6%) with a high level of antibody to HIV ( 2000). A weak gag p 24 in WB was found in 4 of 11 patients (36.3%) who subsequently acquired AIDS or ARC , while none of the patients whq remained asymptomatic displayed this reactivity pattern in WB. 9 patients showed a weak gag p 18 in WB. 8 of them (88.8%) have platelet counts below 120x109 /1, 3 developed imiruine thrombocytopenia with platelet counts of less than 50xl09. Oily 6 of 40 patients (15%) without this reactivity pattern in WB have platelet counts lower than 120x109 and none below 50xl09.We conclude that a weak gag p 24 in WB has a strong positive predictive power for the development of AIDS or ARC in seropositive haemophiliacs. A weak gag p 18 in WB could possibly be associated with the occurence of immune thrombocytopenia in these patients.
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FAUVEL-LAFEVE, F., and Y. J. LEGRAND. "IMMUNOCHEMICAL IDENTIFICATION OF A THROMBOSPONDIN -LIKE ANTIGEN IN ARTERIAL THROMBOGENIC MICROFIBRILS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643823.
Full textAbstract:
The biochemical structure of arterial microfibrils (MFS) is unknown. Presently, the most probable hypothesis is that elastin associated MFS contain several antigenic determinants with MW varying between 31 and 200 KD.From our previous studies we know that MFS extracted by 6 M GuCl contain a major glycoprotein with a 128 KD MV (GP128). GP 128 is essential for the reactivity of MFS towards blood platelets but due tc the high insolubility of the extracted material it was not possible to isolate and study this GP 128. We have used immunoblotting to determine if MFS contain determinants recognized by antibodies against connective tissue glycoproteins such as fibronectin, type VI collagen or anti-platelet thrombospondin (TSP). 'The results showed that MFS do not contain fibronectin or type VI collagen but that anti-TSP IgG reacted with GP 128. Furthermore, the Fab fragments from anti-TSP IgG inhibited platelet aggregation induced by MFS but not by collagen or ADP . In a second step,to raise antibodies against GP 128, we prepared blots from entire MFS, the nitrocellulose band corresponding to GP 128 was cut, dissolved in DMSO, and wrs injected to rabbits. Such obtained antibodies recognized only GP 128 in arterial MFS and also TSP in a platelet lysate confirming that GP 128 and TSP have a common antigenic structure. IgG from anti-GP 128 inhibit platelet aggregation induced by MFS but not by collagen or ADP. Previously reported observations showed that tissue TSP and endothelial cells derived GP 128 have a similar affinity for chromatography supports and have the same effect on platelet-MFS interactions. All these results led us to propose that TSP, GP 128, and MFS recognize a common determinant on platelet membrane. This assumption would be strenghened if GP 128 indeed is derived from tissue TSP.
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Schrör, K., P. Löbel, and E. Steinhagen-Thiessen. "SYNVINOLIN (SYN) IN TYPE Ha HYPERLIPOPROTEINAEMIA : NORMALIZED PLATELET HYPERREACTIVITY ASSOCIATED WITH AN IMPROVED RESPONSIVENESS AGAINST PGI2 AND ENHANCED PGI2 RECEPTORS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643460.
Full textAbstract:
Patients with familial hyperlipoproteinaemia (HLP) are at high risk for the premature development of atherosclerosis. This study was designed to investigate the effect of long-term treatment (8 months) with the HMG-CoA-reductase inhibitor SYN (20-40 mg/day) on platelet reactivity and PGIo receptors in 12 HLP patients (B) as compared with 11 untreated HLP patients (A) and 11 healthy subjects (C). Treatment with SYN reduced the plasma cholesterol to 234 ± 12 mg/dl as compared to 307 ± 21 (A) and 195 ± 14 mg/dl (C), respectively. Collagen (0.6 pg/ml) induced platelet thromboxane (TXB2) formation was 50±6 ng/ml in group A and significantly reduced to 32 ± 3 (B) which was not different from the 28±3 ng/ml in group C. Similar results were obtained by measuring pTatelet ATP secretion and aggregation. SYN treatment significantly improved the reduced number of PGI2 receptors (determined according to Schillinger & Prior, 1980) and normalized the iloprost (ILO, 30 nM) induced cAMP stimulation in platelet-rich plasma while the kg remained unchanged:These data demonstrate that SYN-treatment of HLP patients at doses that reduce plasma cholesterol by about 25% results in sig-ficant improvement of platelet function. This includes both normalization of platelet hyperreactivity against proaggregatory agents as well as platelet hyporeactivity aganist PGI2. The last effect might involve an increase of the (reduced) number of PGI2 receptors in HLP type IIa.
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Bini, A., R. Mesa-Tejada, J. Fenoglio, B. Kudryk, and K. L. Kaplan. "SPECIFIC DETECTION OF FIBRIN IN HUMAN TISSUES BY A NEW IMMUNOHISTOCHEMICAL TECHNIQUE." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643316.
Full textAbstract:
Human biopsy (30), surgical (50) and autopsy (14) specimens of different embryonic origin (skin, blood vessel, kidney, lymph nodes, prostate, lung, liver, and intestine) were stained by the avidin-biotin complex immunoperoxidase technique (ABC-IP) with monoclonal antibodies (MAbs). MAb T2G1 (recognizes 315-42 and detects fibrin II in tissues), MAb I8C6 (recognizes BS1-42 and indicates fibrinogen and fibrin I), MAb GC4 (specific for fragments D and D-D), and a polyclonal antiserum for fibrinogen. The method can be applied to frozen or Boilin’s fixed paraffin embedded tissues with good preservation of morphology and high sensitivity at the light microscopy level. The results were compared with conventional histochemical stains currently used in surgical pathology to demonstrate fibrin deposits in tissues. These stains are based on the acidophilic properties of fibrin (Fraser-Lendrum for “more recent” and Mallory’s PTAH for “older” fibrin). ABC-IP staining with MAb T2G1 clearly detected fibrin in areas where Lendrum and PTAH failed to reveal fibrin deposits, e.g., in the intercellular and pericellular matrix, as well as in areas where staining occurred with conventional techniques, indicating greater sensitivity of the ABC-IP method. Fibrin was specifically detected in strands or clumps in some areas of inflammation and granulation tissue and seemed to be associated with platelets and macrophages. Moreover, ABC-IP with MAb I8C6 and MAb GC4 permits the distinction between fibrinogen or fibrin I, and D and D dimer which are poorly reactive with the Lendrum and PTAH methods. The polyclonal antiserum for fibrinogen showed reactivity with all the material stained with the MAbs and with some additional areas due to the epitopes of fibrinogen and fibrin not detected by the monoclonals. The ABC-IP technique with MAbs allows specific demonstration of fibrin deposits in tissues. Moreover, these results indicate that this method facilitates the correlation of the morphologic appearance of fibrinogen) -related deposits in tissues with their molecular form and will be useful to elucidate the role of fibrin in diseases such as atherosclerosis, kidney disease, and tumors.