Reproducibility of Platelet Functional Assays under Agonist and Shear Conditions - Methods for Characterizing Platelet Reactivity.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3531-3531
Author(s):  
Donald L. Yee ◽  
Angela Bergeron ◽  
Carol Sun ◽  
William May ◽  
Jennifer Wood ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Clinical Laboratory ◽  
Interindividual Variability ◽  
Platelet Reactivity ◽  
Bimodal Distribution ◽  
Variance Component Analysis ◽  
Repeated Testing ◽  
Thrombotic Risk ◽  
Functional Assays

Abstract Clinical laboratory tests that reliably measure the contribution of platelets to thrombotic risk are virtually non-existent. Optimal testing of “platelet hyperreactivity” requires assays that are able to identify reproducible differences among individuals. We have studied over 280 healthy individuals with a panel of over 100 assays of platelet function. This panel includes measurements of aggregation, activation, receptor density and other candidate markers of platelet reactivity. Platelets were studied under conditions of agonist stimulation (including arachidonic acid, ADP, epinephrine, collagen, collagen related peptide and ristocetin) and under shear (from 0 to 10,000 sec-1). We assessed the reproducibility of these assays by studying a subgroup of 27 individuals (mean age=33 years, range=24–53 years, 30% males) four times each (108 total sets of studies). The time between each phlebotomy was one week. Subjects were asked to fast overnight and to refrain from certain exposures (e.g. heavy exercise, caffeine use) immediately prior to testing. The reproducibility of assay results was assessed using variance component analysis. We observed significant interindividual variability in most assays of platelet aggregation and activation. We established agonist concentrations that yield wide interindividual variability in maximal platelet aggregation. When these data are depicted on a histogram, a bimodal distribution is observed, with one group of subjects clearly demonstrating lower inherent aggregation (< 40%) and the other group exhibiting higher levels (>60%) (see figure for epinephrine example). We determined shear rates (0 to 2000 sec-1) and identified platelet receptors (CD32, GPIa-IIa, GPIb-IX-V) and markers of platelet activation (CD62P under shear and ADP stimulation) that maximized detection of differences between individuals while minimizing variations within subjects. Individual subjects demonstrated consistent results over time on repeated testing. We have thus identified a subset of platelet assays that demonstrate striking interindividual variability (overall coefficients of variation range from 0.15 to 0.9) while maintaining good reproducibility (contribution of intraindividual to overall variance < 35%). Other functional assays we have tested demonstrated poor reproducibility, such that they should not be utilized as measures of platelet reactivity. Using assay conditions and techniques not routinely utilized in clinical practice (but that could easily be adapted for such use), we have shown that different individuals demonstrate distinct levels of platelet reactivity. Despite only minimal restrictions on environmental exposures for these healthy subjects studied repeatedly over several weeks, these assays appear to reliably characterize individuals’ platelet reactivity and are appropriate candidates for its measurement in populations of patients at risk for thrombosis or bleeding. As these assays facilitate categorization of platelet reactivity, they may also be useful for the study of genetic and environmental influences on platelet function. Figure Figure

scholarly journals COVID-19 induces a hyperactive phenotype in circulating platelets

2020 ◽  
Author(s):  
Shane P Comer ◽  
Sarah Cullivan ◽  
Paulina B Szklanna ◽  
Luisa Weiss ◽  
Steven Cullen ◽  
...  
Keyword(s):  
Intensive Care ◽  
Platelet Function ◽  
Clinical Laboratory ◽  
Platelet Reactivity ◽  
Severe Disease ◽  
Blood Parameters ◽  
Full Blood Count ◽  
Specific Marker ◽  
Platelet Activity ◽  
Thrombotic Risk

Background Coronavirus disease 2019 (COVID-19), caused by novel coronavirus SARS-CoV-2, has to date affected over 13.3 million globally. Although high rates of venous thromboembolism and evidence of COVID-19-induced endothelial dysfunction have been reported, the precise aetiology of the increased thrombotic risk associated with COVID-19 infection remains to be fully elucidated. Objectives Here, we assessed clinical platelet parameters and circulating platelet activity in patients with severe and non-severe COVID-19. Methods An assessment of clinical blood parameters in patients with severe COVID-19 disease (requiring intensive care), patients with non-severe disease (not requiring intensive care), general medical in-patients without COVID-19 and healthy donors was undertaken. Platelet function and activity were also assessed by secretion and specific marker analysis. Results We show that routine clinical blood parameters including increased MPV and decreased platelet:neutrophil ratio are associated with disease severity in COVID-19 upon hospitalisation and intensive care unit admission. Strikingly, agonist-induced ADP release was dramatically higher in COVID-19 patients compared with non-COVID-19 hospitalized patients and circulating levels of PF4, sP-selectin and TPO were also significantly elevated in COVID-19. Conclusion Distinct differences exist in routine full blood count and other clinical laboratory parameters between patients with severe and non-severe COVID-19. Moreover, we have determined that COVID-19 patients possess hyperactive circulating platelets. These data suggest that abnormal platelet reactivity may contribute to hypercoagulability in COVID-19. Further investigation of platelet function in COVID-19 may provide additional insights into the aetiology of thrombotic risk in this disease and may contribute to the optimisation of thrombosis prevention and treatment strategies.

Effects of Ticlopidine of Platelet Function in Men with Stable Angina Pectoris

1985 ◽  
Vol 54 (04) ◽  
pp. 808-812 ◽  
Author(s):  
Ulf Berglund ◽  
Henning von Schenck ◽  
Lars Wallentin
Keyword(s):  
Platelet Aggregation ◽  
Angina Pectoris ◽  
Platelet Function ◽  
Plasma Levels ◽  
Platelet Reactivity ◽  
Inhibitory Effect ◽  
Controlled Study ◽  
Double Blind ◽  
Platelet Factor

SummaryThe effects of ticlopidine (T) (500 mg daily) on platelet function were investigated in a double-blind placebo-controlled study in 38 middle-aged men with stable incapacitating angina pectoris. The in vitro platelet reactivity to aggregating agents, the platelet sensitivity to prostacyclin and the plasma levels of platelet specific proteins and fibrinogen were determined before and after 4 and 8 weeks of treatment. T exerted a potent inhibitory effect on ADP- and collagen-induced platelet aggregation. The effect of T was proportional to the pretreatment reactivity to ADP and collagen. The inhibitory effect of T on the epinephrine response was less pronounced. The plasma levels of beta-thromboglobulin, platelet factor 4 and fibrinogen were not influenced by T. The platelet inhibition of prostacyclin was potentiated by T, and it was demonstrated that T and prostacyclin had synergistic inhibitory effects on platelet aggregation.

Novel 12-LOX Inhibitor ML355 Attenuates Platelet Reactivity and Impairs Thrombus Growth, Stability and Vessel Occlusion In Vivo

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3442-3442 ◽  
Author(s):  
Reheman Adili ◽  
Theodore R Holman ◽  
Michael Holinstat
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Adhesion ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Thrombus Formation ◽  
Vessel Occlusion ◽  
Growth Stability

Abstract Background: Adequate platelet reactivity is required for platelet adhesion and aggregation at the site of vascular injury to maintain hemostasis. However, excessive platelet reactivity can also lead to the formation of occlusive thrombi, the predominate underlying cause of myocardial infarction and stroke. While current anti-platelet treatments limit platelet function, they often result in an increased risk of bleeding. 12-lipoxygenase (12-LOX), an oxygenase highly expressed in the platelet, has been demonstrated by our lab and others to regulate PAR4 and GPVI-mediated platelet reactivity suggesting a role of 12-LOX in regulation of vivo thrombosis. However, the ability to pharmacologically target 12-LOX in vivo has not been established to date. Aims: To determine how 12-LOX regulates thrombus formation in vivo and whether platelet 12-LOX is an effective target for anti-platelet therapeutics, wild-type (WT) or 12-LOX deficient (12-LOX-/-) mice were treated with or without the 12-LOX inhibitor, ML355, and were assessed for inhibitory effects on platelet activation in vitro, ex-vivo and in vivo. Methods: The effect of the novel 12-LOX inhibitor ML355 on human platelet function was assessed in vitro by platelet aggregometry, ex vivo by perfusion chamber. In vivo thrombus formation and vessel occlusion in small and large vessels were studied in 12-LOX-/-, WT mice and mice treated with ML355 using intravital microscopy using the FeCl3 injury models. Results: Using in vitro platelet aggregation assays, ML355 dose dependently inhibited thrombin, PAR1-AP, and PAR4-AP-induced aggregation in washed human platelets. Interestingly, the negative regulatory effects of ML355 inhibition of 12-LOX can be overcome by high concentration of thrombin. Additionally, ML355 was able to attenuate ADP-induced platelet aggregation both in platelet-rich-plasma and whole blood. In ex vivo flow chamber assays, platelet adhesion and thrombus formation on collagen-coated surfaces at high shear was attenuated in both mouse and human whole blood after incubation with ML355. Further, platelet aggregation and thrombus growth in 12-LOX-/- mice was impaired in FeCl3-induced mesenteric or carotid artery thrombosis models. Thrombi in 12-LOX-/- mice were unstable and frequently form emboli, which resulted in impaired vessel occlusion or reopening. Additionally, thrombus formation and vessel occlusion was impaired in ML355 treated WT mice. Conclusions: The highly selective 12-LOX inhibitor ML355 inhibits platelets aggregation induced by various platelet agonists and ML355 inhibition of platelet function is not agonist specific. Platelet function at high shear in ex vivo conditions in both mice and human was attenuated in the presence of ML355. Thrombus growth, stability, and vessel occlusion was impaired in mice deficient for 12-LOX. Finally, the highly selective 12-LOX inhibitor ML355 attenuates thrombus formation and prevents vessel occlusion in vivo. Our data strongly indicates 12- LOX is an important determinant of platelet reactivity and inhibition of platelet 12-LOX may represent a new target for anti-platelet therapeutics. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Study of Haemostatic Parameters in Patients with Philadelphia-Negative Myeloproliferative Neoplasms. Correlation with, Clinical, Laboratory, Molecular, and Treatment Characteristics

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4304-4304
Author(s):  
Nefeli Giannakopoulou ◽  
Marianna Politou ◽  
Panagiotis Theodorou Diamantopoulos ◽  
Dimitris Korakakis ◽  
Maria Efstathopoulou ◽  
...  
Keyword(s):  
Platelet Function ◽  
Clinical Laboratory ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasms ◽  
Molecular Characteristics ◽  
Healthy Controls ◽  
Vascular Events ◽  
Thrombotic Risk ◽  
Symptomatic Carotid Stenosis ◽  
Α Angle

Abstract Introduction Patients with Philadelphia-negative myeloproliferative neoplasms (PN-MPN) namely polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (MF) are at a higher risk for arterial and venous thrombosis that constitute a major cause of morbidity and mortality. Global coagulation assays such as thromboelastography, may be more efficient to evaluate the patient's thrombotic risk. The aim of the present study was to examine the hemostatic profile of patients with PN-MPN and correlate it with clinical, laboratory, treatment, and molecular characteristics including mutational analysis of JAK2, MPL, CALR, and polymorphisms of poly(ADP ribose) polymerase (PARP1), since a correlation of specific mutations with PARP1 polymorphisms has been reported in the literature. Materials and methods The study included adult patients with a confirmed diagnosis of PN-MPN according to the revised 2016 WHO classification. A written informed consent was obtained from all patients. The presence of splenomegaly, vascular events, PN-MPN specific therapy, and anticoagulation treatment were recorded. All the patients were assessed with complete blood count, routine coagulation tests [PT, INR, aPTT and fibrinogen, D-Dimers analyzed with the automatic coagulation analyzer Sysmex (Siemens)], platelet function performed with PFA-100 (COL, EPI, ADP), and global hemostatic potential assessed with ROTEM® Tromboelastometry (EXTEM), recording clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), lysis index at 30 (LI30) and 60 (LI60) minutes, and α angle. Mutation profiles of JAK2, MPL and CALR were defined using peripheral blood DNA. JAK2 and MPL mutations were detected using a standard PCR and CALR mutations using an HRMA-PCR assay. The rs1136410/PARP-1 (V762A) single nucleotide polymorphism (SNP), was detected with an RFLP method using the enzyme AciΙ (New England Biolabs, USA) and the digestion products were evaluated by polyacrylamide gel electrophoresis. Statistical analysis was performed using IBM SPSS statistics, version 23.0 (IBM Corporation, North Castle, NY, USA). Results Seventy-four patients were included in the study (22 PV, 47 ET, 5 MF) with a median age of 63 years (25-87) and 68 healthy controls for the SNP/PARP1 study. At the time of sample collection, 71 (95.9%) patients were under treatment [hydroxyurea (HU), 57 (77.0%); anagrelide, 19 (25.7%); ruxolitinib, 9 (12.2%); interferon alpha, 2 (2.7%); an alkylating agent, 4 (5.4%)]. In terms of anticoagulation, 47 (63.5%) patients were on aspirin, 4 (5.4%) on clopidogrel, 7 (9.5%) on a combination of the two, 3 (4.1%) on a vitamin K antagonist, and 2 (2.7%) on a Xa-inhibitor. Twenty-two (29.7%) patients had abnormally high D-Dimers (>0,5mg/l). Nineteen (25.7%) patients had developed thrombosis after diagnosis (8, ischemic stroke; 4, coronary artery disease (CAD); 3, deep vein thrombosis (DVT); 1, symptomatic carotid stenosis; 2, a combination of stroke and CAD; 1, a combination of CAD and DVT). Among 69 patients who were not receiving anticoagulation, 5 (7,2%) had an abnormal CT, 4 (5,7%) had abnormal CFT, 3 (4,3%) had an increased α angle, and 18 (26%) had an increased MCF value. Women had shorter CFT, higher α angle, and higher MCF (p<0.05 for all parameters). Patients with ET had higher MCF compared to PV and MF. Patients with mutated JAK2, CALR, or MPL had higher WBC and shorter CFT (p<0.05). Patients receiving anagrelide or alkylating agents, had statistically significant shorter CFTs, higher α angles, and higher MCFs compared to the ones receiving HU. Among 54 patients taking aspirin COL-EPI was normal in 10. Among 11 patients taking clopidogrel COL-ADP was normal in 5, implying that the antiplatelet treatment may not be sufficient in certain cases. No correlations were found between PARP1 polymorphic status and any of the studied parameters, nor between patients and healthy controls. Discussion Global assays such as thromboelastography are more useful than conventional hemostatic laboratory tests in depicting the hypercoagulable state in MPN. They may be useful in combination with other parameters such as the mutational status in identifying patients with MPN at higher risk for thrombosis and guide clinicians for the type of treatment (both cytoreductive and anticoagulants). Tests of platelet function assessment may help the clinicians adjust the type and dose of antiplatelet therapy. Disclosures No relevant conflicts of interest to declare.

Platelet Function in CKD: A Systematic Review and Meta-Analysis

2021 ◽  
pp. ASN.2020101440
Author(s):  
Constance C.F.M.J. Baaten ◽  
Marieke Sternkopf ◽  
Tobias Henning ◽  
Nikolaus Marx ◽  
Joachim Jankowski ◽  
...  
Keyword(s):  
Systematic Review ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Meta Analysis ◽  
Uremic Toxins ◽  
Extensive Literature ◽  
Direct Effects ◽  
Platelet Activity

BackgroundPatients with CKD are at high risk for thrombotic and hemorrhagic complications. Abnormalities in platelet function are central to these complications, but reports on platelet function in relation to CKD are conflicting, and vary from decreased platelet reactivity to normal or increased platelet responsiveness. The direct effects of uremic toxins on platelet function have been described, with variable findings.MethodsTo help clarify how CKD affects platelet function, we conducted a systematic review and meta-analysis of platelet activity in CKD, with a focus on nondialysis-induced effects. We also performed an extensive literature search for the effects of individual uremic toxins on platelet function.ResultsWe included 73 studies in the systematic review to assess CKD’s overall effect on platelet function in patients; 11 of them described CKD’s effect on ex vivo platelet aggregation and were included in the meta-analysis. Although findings on platelet abnormalities in CKD are inconsistent, bleeding time was mostly prolonged and platelet adhesion mainly reduced. Also, the meta-analysis revealed maximal platelet aggregation was significantly reduced in patients with CKD upon collagen stimulation. We also found that relatively few uremic toxins have been examined for direct effects on platelets ex vivo; ex vivo analyses had varying methods and results, revealing both platelet-stimulatory and inhibitory effects. However, eight of the 12 uremic toxins tested in animal models mostly induced prothrombotic effects.ConclusionsOverall, most studies report impaired function of platelets from patients with CKD. Still, a substantial number of studies find platelet function to be unchanged or even enhanced. Further investigation of platelet reactivity in CKD, especially during different CKD stages, is warranted.

Residual platelet reactivity is an independent predictor of myocardial injury in acute myocardial infarction patients on antiaggregant therapy

2007 ◽  
Vol 98 (10) ◽  
pp. 844-851 ◽  
Author(s):  
Rita Paniccia ◽  
Emilia Antonucci ◽  
Serena Poli ◽  
Anna Maria Gori ◽  
Serafina Valente ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Platelet Function ◽  
Clinical Laboratory ◽  
Independent Predictor ◽  
Platelet Reactivity ◽  
Platelet Rich Plasma ◽  
Antiplatelet Agents ◽  
The Other ◽  
Group A ◽  
Group B

SummaryIn this study we sought to evaluate if platelet function measured after percutaneous coronary intervention (PCI) affects the severity of myocardial infarction (MI), measured by markers of cardiac necrosis. We measured platelet function by both a point-of-care assay (PFA-100) and platelet-rich plasma aggregation by two agonists (arachidonic acid –AA- and 2 and 10 μM ADP) in 367 patients with MI after PCI (200 patients on dual antiplatelet agents – group A- and 167 on dual antiplatelet agents plus GpIIb/ IIIa inhibitors – group B). One hundred twenty-one (32.9%) patients were found to have a residual platelet reactivity (RPR) by PFA (CT/EPI <203 sec): 74/200 (37%) in group A and 47/167 (28.1%) in group B (p=0.07). In 129 (35.1%) patients we found a RPR by AA-PA: 80/200 (40%) in group A and 49/167 (29.3%) in group B (p<0.05). Seventeen out of 367 (4.6%) were found to have a RPR by ADP2-PA [15/200 (7.5%) in group A and 2/167 (1.2%) in group B; p<0.005] and 88/367 (23.9%) by ADP10-PA [64/200 (32%) in group A and 24/167 (14.4%) in group B, p<0.0001]. CK-MB and cTnI mean peak values were significantly higher in the first tertile of CT/ADP and CT/EPI distribution with respect to the other tertiles and they were significantly higher in patients with RPR by CT/EPI in both groupA and group B patients. CK-MB and cTnI peak values were significantly higher in the third tertile of AA-PA,ADP 2 μM-PA and ADP 10 μM-PA distribution with respect to the other tertiles and were significantly higher in patients with RPR by AA-PA and by ADP 10-PA in both group A and group B patients. Multivariate analysis revealed platelet function as an independent predictor of CK-MB and cTnI peak values in both groups of patients independently of clinical, laboratory ad procedural parameters. In conclusion, we found that the severity of MI in patients with MI undergoing primary PCI is influenced by a persistent platelet activation on multiple antiplatelet therapy.

Enhanced platelet MRP4 expression and correlation with platelet function in patients under chronic aspirin treatment

2016 ◽  
Vol 116 (12) ◽  
pp. 1100-1110 ◽  
Author(s):  
Isabella Massimi ◽  
Lavinia Lotti ◽  
Flavia Temperilli ◽  
Massimo Mancone ◽  
Gennaro Sardella ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Thrombus Formation ◽  
Independent Mechanism ◽  
Mrna And Protein Expression ◽  
Low Levels ◽  
Cox 1

SummaryPlatelet 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 (ASA<1 month patients) and aspirinated 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 ASA<1 month patients. Platelets obtained from ASA>2 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.

scholarly journals Head-to-Head Comparison of Consensus-Recommended Platelet Function Tests to Assess P2Y12 Inhibition—Insights for Multi-Center Trials

2020 ◽  
Vol 9 (2) ◽  
pp. 332
Author(s):  
Jean-Christophe Bélanger ◽  
Fabio Luiz Bandeira Ferreira ◽  
Mélanie Welman ◽  
Rahma Boulahya ◽  
Jean-François Tanguay ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Receptor Activation ◽  
P2y12 Receptor ◽  
Reactivity Index ◽  
Specific Method ◽  
Vasp Phosphorylation ◽  
Receptor Inhibitor

The vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation level is a highly specific method to assess P2Y12 receptor inhibition. Traditionally, VASP phosphorylation is analyzed by flow cytometry, which is laborious and restricted to specialized laboratories. Recently, a simple ELISA kit has been commercialized. The primary objective of this study was to compare the performance of VASP assessment by ELISA and flow cytometry in relation to functional platelet aggregation testing by Multiplate® whole-blood aggregometry. Blood from 24 healthy volunteers was incubated with increasing concentration of a P2Y12 receptor inhibitor (AR-C 66096). Platelet function testing was carried out simultaneously by Multiplate® aggregometry and by VASP assessment through ELISA and flow cytometry. As expected, increasing concentrations of the P2Y12 receptor inhibitor induced a proportional inhibition of platelet aggregation and P2Y12 receptor activation across the modalities. Platelet reactivity index values of both ELISA- and flow cytometry-based VASP assessment methods correlated strongly (r = 0.87, p < 0.0001) and showed minimal bias (1.05%). Correlation with Multiplate® was slightly higher for the flow cytometry-based VASP assay (r = 0.79, p < 0.0001) than for the ELISA-based assay (r = 0.69, p < 0.0001). Intraclass correlation (ICC) was moderate for all the assays tested (ICC between 0.62 and 0.84). However, categorization into low, optimal, or high platelet reactivity based on these assays was strongly concordant (κ between 0.86 and 0.92). In conclusion, the consensus-recommended assays with their standardized cut-offs should not be used interchangeably in multi-center clinical studies but, rather, they should be standardized throughout sites.

scholarly journals Platelet reactivity with a third generation thienopyridine drug versus with a second-generation thienopyridine drug

2020 ◽  
Vol 11 (3) ◽  
pp. 3704-3709
Author(s):  
Feryal Hashim Rada
Keyword(s):  
Platelet Aggregation ◽  
Second Generation ◽  
Clinical Laboratory ◽  
Platelet Reactivity ◽  
Laboratory Data ◽  
Minor Bleeding ◽  
Third Generation ◽  
Group A ◽  
Treatment Analysis ◽  
Group B

Prasugrel is a third generation thienopyridine drug and Clopidogrel is a second-generation thienopyridine drug. Both drugs used for reducing platelet aggregation in patients with coronary artery diseases.The aim of this study is to investigate the antiplatelet efficacy and safety of Prasugrel 5mg daily as compared to Clopidogrel 75 mg daily for period along to 12 days treatment.Fifty patients, (10 females, 40 males), their ages ranging from (50- 60) years with stable angina were recruited from IbnAlbitar Center for Cardiac Surgery and enrolled in this case study.Of whom 25 patients (group A) received a dose of 75 mg daily of Clopidogrel and other 25 patients (group B) were on a dose of 5 mg daily of Prasugrel for a period of 12 days .Clinical laboratory data of lipid profile, renal function, and prothrombine time obtained at baseline (before treatment). While Platelet aggregation percent measured at the baseline and after 12 days of treatment.The maximal platelet aggregation percent for group A was fell from 78 % ± 6.3 (baseline) to 43.5% ± 5.8 (after 12 days treatment).While patients of group B showed dropping in the maximal platelet aggregation percent from 76 % ± 7.4 (baseline) to 27.3 % ± 5.7 (after 12 days treatment). Analysis of adverse events showed three patients with minor bleeding occurred during Prasugrel treatment, and no bleeding occurred during Clopidogrel treatment. Compared with Clopidogrel 75mg treatment, Prasugrel 5mg treatment for 12 days averted platelets accumulation more quickly and steadily.

scholarly journals COVID-19 induces a hyperactive phenotype in circulating platelets

PLoS Biology ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. e3001109
Author(s):  
Shane P. Comer ◽  
Sarah Cullivan ◽  
Paulina B. Szklanna ◽  
Luisa Weiss ◽  
Steven Cullen ◽  
...  
Keyword(s):  
Intensive Care ◽  
Clinical Laboratory ◽  
Platelet Reactivity ◽  
Blood Parameters ◽  
Full Blood Count ◽  
Specific Marker ◽  
Platelet Activity ◽  
Platelet Factor ◽  
Thrombotic Risk ◽  
Severity Of The Disease

Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected over 30 million globally to date. Although high rates of venous thromboembolism and evidence of COVID-19-induced endothelial dysfunction have been reported, the precise aetiology of the increased thrombotic risk associated with COVID-19 infection remains to be fully elucidated. Therefore, we assessed clinical platelet parameters and circulating platelet activity in patients with severe and nonsevere COVID-19. An assessment of clinical blood parameters in patients with severe COVID-19 disease (requiring intensive care), patients with nonsevere disease (not requiring intensive care), general medical in-patients without COVID-19, and healthy donors was undertaken. Platelet function and activity were also assessed by secretion and specific marker analysis. We demonstrated that routine clinical blood parameters including increased mean platelet volume (MPV) and decreased platelet:neutrophil ratio are associated with disease severity in COVID-19 upon hospitalisation and intensive care unit (ICU) admission. Strikingly, agonist-induced ADP release was 30- to 90-fold higher in COVID-19 patients compared with hospitalised controls and circulating levels of platelet factor 4 (PF4), soluble P-selectin (sP-selectin), and thrombopoietin (TPO) were also significantly elevated in COVID-19. This study shows that distinct differences exist in routine full blood count and other clinical laboratory parameters between patients with severe and nonsevere COVID-19. Moreover, we have determined all COVID-19 patients possess hyperactive circulating platelets. These data suggest abnormal platelet reactivity may contribute to hypercoagulability in COVID-19 and confirms the role that platelets/clotting has in determining the severity of the disease and the complexity of the recovery path.

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