scholarly journals Sensitivity of Viscoelastic Tests to Platelet Function

2020 ◽  
Vol 9 (1) ◽  
pp. 189 ◽  
Author(s):  
Marco Ranucci ◽  
Ekaterina Baryshnikova
Keyword(s):  
Platelet Function ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Point Of Care ◽  
Dynamic Assessment ◽  
Antiplatelet Agents ◽  
Protease Activated Receptors ◽  
Specific Test ◽  
Clot Strength ◽  
P2y12 Inhibitors

Viscoelastic tests provide a dynamic assessment of coagulation, by exploring the time to clot formation and the clot strength. Using specific activators or inhibitors, additional factors can be explored, like the fibrinogen contribution to clot strength. Since the early days, various attempts have been done to measure platelet function with viscoelastic test. In general, the difference between the maximum clot strength and the fibrinogen contribution is considered an index of platelet contribution. However, this parameter does not clearly split platelet count from function; additionally, the extensive thrombin generation of standard activated viscoelastic tests activates platelet through the protease activated receptors, bypassing the other pathways. For this reason, standard viscoelastic tests cannot be used to assess platelet reactivity under the effects of aspirin or P2Y12 inhibitors. To overcome this limitation, a specific test was developed (thromboelastography platelet mapping). This test has been compared with the gold standard of light transmission aggregometry and with other point-of-care tests, with conflicting results. In general, the use of viscoelastic tests to assess the effects of antiplatelet agents is still limited. Conversely, platelet contribution to clot strength in the setting of coagulopathic bleeding is considered an important parameter to trigger platelet transfusion or desmopressin.

The use of the VerifyNow P2Y12 point-of-care device to monitor platelet function across a range of P2Y12 inhibition levels following prasugrel and clopidogrel administration

2008 ◽  
Vol 99 (02) ◽  
pp. 409-415 ◽  
Author(s):  
Christopher D. Payne ◽  
Ying G. Li ◽  
John T. Brandt ◽  
David S. Small ◽  
Nagy A. Farid ◽  
...  
Keyword(s):  
Platelet Function ◽  
Clinical Utility ◽  
Dynamic Range ◽  
Light Transmission ◽  
Point Of Care ◽  
Antiplatelet Agents ◽  
Limited Range ◽  
Treatment Regimens ◽  
Light Transmission Aggregometry

SummaryVariability in response to antiplatelet agents has prompted the development of point-of-care (POC) technology. In this study, we compared theVerifyNowTM P2Y12 (VN-P2Y12) POC device with light transmission aggregometry (LTA) in subjects switched directly from clopidogrel to prasugrel. Healthy subjects on aspirin were administered a clopidogrel 600 mg loading dose (LD) followed by a 75 mg/d maintenance dose (MD) for 10 days. Subjects were then switched to a prasugrel 60 mg LD and then 10 mg/d MD for 10 days (n=16), or to a prasugrel 10 mg/d MD for 11 days (n=19). Platelet function was measured by LTA andVN-P2Y12 at baseline and after dosing. Clopidogrel 600 mg LD/75 mg MD treatment led to a reduction in P2Y12 reaction units (PRU) from baseline. A switch from clopidogrel MD to prasugrel 60 mg LD/10 mg MD produced an immediate decrease in PRU, while a switch to prasugrel 10 mg MD resulted in a more gradual decline. Consistent with the reduction in PRU, device-reported percent inhibition increased during both clopidogrel and prasugrel regimens. Inhibition of platelet aggregation as measured by LTA showed a very similar pattern to that found with VN-P2Y12 measurement, irrespective of treatment regimens. The dynamic range of VN-P2Y12 appeared to be narrower than that of LTA. With two different thienopyridines, the VN-P2Y12 device, within a somewhat more limited range, reflected the overall magnitude of change in aggregation response determined by LTA. The determination of the clinical utility of such POC devices will require their use in clinical outcome studies.

Monitoring of antiplatelet therapy

2011 ◽  
Vol 31 (01) ◽  
pp. 41-51 ◽  
Author(s):  
H. Seidel ◽  
M. M. Rahman ◽  
R. E. Scharf
Keyword(s):  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Point Of Care ◽  
High Sensitivity ◽  
Antiplatelet Agents ◽  
Daily Practice ◽  
Adenosine Diphosphate ◽  
Poor Responders ◽  
Platelet Aggregometry

SummaryScreening of platelet function can be performed by point-of-care testing followed by platelet aggregometry in response to agonists such as collagen, adenosine diphosphate, epinephrine, and arachidonic acid. Despite in use for decades, this technique is not well standardized. Monitoring of antiplatelet therapy is increasingly applied in patients at high risk for re-thrombosis or bleeding. To assess pharmacological inhibition of platelet function, agonist-induced platelet aggregation, thromboxane B2 (TxB2) and vasodilator-stimulated protein phosphorylation (VASP) are being measured. While serum TxB2 levels of < 2 ng/ml reflect aspirin-induced inhibition of cyclo-oxygenase-1 activity with high sensitivity, VASP exhibits a wide variability upon treatment with clopidogrel or prasugrel. Multiple studies reveal an association between high residual platelet reactivity and adverse cardiovascular events in patients on antiplatelet therapy. However, despite the plethora of platelet function assays currently under investigation, their use in daily practice cannot be recommended. This is due to several reasons: (i) there is no consensus on the method and a respective cut-off value associated with clinical adverse outcome, and (ii) data demonstrating any benefit of tailored antiplatelet therapy and its monitoring (based on assessment of platelet functions) are still limited. Thus, appropriate identification of ‘resistant’ or ‘poor responders’ to antiplatelet agents remains challenging in clinical practice.

Effect of two doses of aspirin on thromboxane biosynthesis and platelet function in patients undergoing coronary surgery

2010 ◽  
Vol 103 (03) ◽  
pp. 516-524 ◽  
Author(s):  
Marta Brambilla ◽  
Alessandro Parolari ◽  
Marina Camera ◽  
Susanna Colli ◽  
Sonia Eligini ◽  
...  
Keyword(s):  
Platelet Function ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Point Of Care ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Platelet Inhibition ◽  
Aspirin Resistance ◽  
Platelet Activity ◽  
Single Centre Study

SummaryEarly post-operative aspirin improves survival in patients undergoing coronary artery bypass graft (CABG). However, most patients do not benefit of aspirin after CABG, still remaining at risk of thrombotic events due to insufficient platelet inhibition, specifically via the thromboxane (TX) pathway. We evaluated the effect of two aspirin doses (100 or 325 mg daily, enteric coated formulations) on platelet function and TX biosynthesis in patients after CABG and assessed whether the incidence of residual platelet reactivity could be reduced by the higher dose. Fifty-six patients undergoing CABG were randomly assigned to 100 or 325 mg aspirin daily for five days in a prospective single-centre study. Treatment effect was assessed by measuring either platelet function (light-transmission aggregometry and point-of-care PFA-100®) or TX biosynthesis in collagen-stimulated platelets, serum, urine, and in lipopolysaccharide (LPS)-cultured whole blood (WB). An insufficient TX inhibition was observed with 100 mg aspirin but not with the higher dose. The different effect of the two doses was, however, highlighted by either TX (platelet- or serum-derived) or by PFA-100® but not by the other assays. In conclusion, early after CABG, the incidence of residual platelet activity was lower in patients who received 325 mg aspirin. Moreover, evidence was provided that different methods yield different results in the detection of aspirin resistance, rendering them not interchangeable.

Identification of poor response to P2Y12 inhibitors in ACS patients with a new ELISA-based vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation assay

2013 ◽  
Vol 110 (11) ◽  
pp. 1055-1064 ◽  
Author(s):  
Jérémie Abtan ◽  
Johanne Silvain ◽  
Mathieu Kerneis ◽  
Stephen A. O’Connor ◽  
Olivier Barthélémy ◽  
...  
Keyword(s):  
Light Transmission ◽  
Platelet Reactivity ◽  
Poor Response ◽  
Threshold Value ◽  
Reactivity Index ◽  
Operating Characteristics ◽  
Specific Test ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
Vasp Phosphorylation

SummaryA new ELISA technique has been developed to measure the vasodilator-associated stimulated phosphoprotein (VASP) platelet reactivity index (PRI) in clopidogrel-treated patients. This technique has not been evaluated in acute coronary syndrome (ACS) patients or in prasugrel-treated patients. We assessed the accuracy of ELISA-VASP to identify high on-treatment platelet reactivity (HPR) in ACS patients in comparison with established platelet function tests. Platelet reactivity was measured in 240 ACS patients treated with clopidogrel (75 or 150 mg) or prasugrel (5 or 10 mg) using flow cytometry (FC-VASP) and the ELISA-VASP technique, light transmission aggregometry (LTA) and VerifyNow-P2Y12 assay (VN-P2Y12). When using the ELISA-VASP PRI, the rate of patients with HPR in the overall ACS population was 15.5%, including a 27% rate in clopidogrel-treated patients and a 4% rate in prasugrel-treated patients. There was a strong correlation between ELISA-VASP PRI and FC-VASP PRI (r = 0.83, r2 = 0.68 p < 0.0001) with an area under the receiver-operating characteristics (ROC) curve to identify HPR (VASP-PRI >50% with FC-VASP) of 0.94, p<0.0001. The threshold of 60% for ELISA-VASP PRI provided the best accuracy (likelihood ratio= 23.67) to identify patients with HPR when compared to FC-VASP, LTA or VN-P2Y12 assays. In conclusion, ELISA-VASP is a fast, easy-to-use and specific test to identify HPR in ACS patients on thienopyridines. A 60% threshold value displays the best accuracy to identify HPR in these patients.

Clopidogrel pretreatment in primary percutaneous coronary intervention: Prevalence of high on-treatment platelet reactivity and impact on preprocedural patency of the infarct-related artery

2013 ◽  
Vol 110 (07) ◽  
pp. 110-117 ◽  
Author(s):  
Javier Berdejo ◽  
Gerard Roura ◽  
Josep Gómez-Lara ◽  
Rafael Romaguera ◽  
Luis Teruel ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Primary Percutaneous Coronary Intervention ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Poor Response ◽  
Antiplatelet Agents ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Percutaneous Coronary ◽  
Infarct Related Artery

SummaryTo date, there is limited data on levels of platelet inhibition achieved in patients with ST-elevation myocardial infarction (STEMI) who are loaded with clopidogrel and aspirin (ASA) prior to undergoing primary percutaneous coronary intervention (P-PCI). The aim of this investigation was to evaluate the percentage of STEMI patients with high on-treatment platelet reactivity (HPR) to clopidogrel at the time of initiating P-PCI and its association with the initial patency of the infarct-related artery (IRA). This prospective pharmacodynamic study included 50 STEMI patients, previously naïve to oral antiplatelet agents, who received 500-mg ASA and 600-mg clopidogrel loading doses prior to P-PCI. Platelet function assessment was performed at the beginning of the procedure using various assays, including VerifyNow™ system (primary endpoint), light transmission aggregometry and multiple electrode aggregometry. The percentage of patients with suboptimal response to clopidogrel and ASA assessed with the VerifyNow™ system was 88.0% and 28.6%, respectively. Similar results were obtained with the other assays used. A higher percentage of patients with initial patency of the IRA was observed among those patients without HPR compared with those with HPR to clopidogrel (66.7% vs 15.9%; p=0.013), while no differences were observed regarding postprocedural angiographic or electrocardiographic outcomes. In conclusion, this study shows that a high percentage of STEMI patients have inadequate levels of clopidogrel-induced and, to a lesser extent, aspirin-mediated platelet inhibition when starting a P-PCI procedure, and suggests that a poor response to clopidogrel might be associated with impaired initial TIMI flow in the IRA.

Point-of-care genetic profiling and/or platelet function testing in acute coronary syndrome

2016 ◽  
Vol 115 (02) ◽  
pp. 382-391 ◽  
Author(s):  
Jean-Philippe Collet ◽  
Mathieu Kerneis ◽  
Jean-Sebastien Hulot ◽  
Stephen A. O’Connor ◽  
Johanne Silvain ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Point Of Care ◽  
Absolute Difference ◽  
Function Measurement ◽  
Genetic Profiling ◽  
Coronary Syndrome ◽  
Bedside Test ◽  
Function Testing

SummaryOur aim was to demonstrate that the sequential use of the Verigene® rapid CYP2C19 test for genetic profiling and the VerifyNowTM bedside test for platelet function measurement in ACS patients may optimise P2Y12 inhibition. “Rapid” (CYP2C19*1/*1 or CYP2C19*17 carriers, n=211) and “slow” metabolisers (CYP2C19*2 carriers, n=58) were first put on clopidogrel and prasugrel for ≥ 2 weeks, respectively. Patients with low platelet reactivity (PRU< 30) on prasugrel or high platelet reactivity (> 208 PRU) on clopidogrel were then switched to clopidogrel and prasugrel, respectively. Our objectives were (i) to demonstrate that the proportion of “rapid” metabolisers on 75 mg of clopidogrel within 30–208 (PRU) of P2Y12 inhibition is non-inferior to “slow” metabolisers on prasugrel 10 mg and (ii) to evaluate the same end-point after switching drugs. The proportion of “rapid” and “slow” metabolisers within 30–208 PRU of P2Y12 inhibition was 71 % and 56.9 %, respectively, an absolute difference of +14.1 % (95 % CI, –0.05 % to 28.28 %) with a non-inferiority margin greater than the predefined margin of –10 %. Among patients out of target, all but one “slow” metabolisers displayed low-on prasugrel platelet reactivity while the majority of “rapid” metabolisers (68 %) displayed high-on clopidogrel platelet reactivity. After switching, the proportion of patients within 30–208 PRU of P2Y12 inhibition was 83.6 % and 79.3 % in “rapid” and “slow” metabolisers, respectively (+4.3 %, 95 % CI –7.3 % to 15.9 %). In conclusion, this study demonstrates a loose relationship between genotype and platelet function phenotype approaches but that they are complementary to select prasugrel or clopidogrel MD in stented ACS patients.

scholarly journals Remote Assessment of Platelet Function in Patients with Acute Stroke or Transient Ischaemic Attack

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Philip M. Bath ◽  
Jane May ◽  
Katie Flaherty ◽  
Lisa J. Woodhouse ◽  
Natalia Dovlatova ◽  
...  
Keyword(s):  
Acute Stroke ◽  
Platelet Function ◽  
Multicentre Trial ◽  
Platelet Reactivity ◽  
Antiplatelet Agents ◽  
Surface Expression ◽  
Safety And Efficacy ◽  
Remote Assessment ◽  
Ischaemic Attack ◽  
Function Testing

Background. The TARDIS trial assessed the safety and efficacy of intensive versus guideline antiplatelet agents given for one month in patients with acute stroke or TIA. The aim of this substudy was to assess the effect of antiplatelet agents taken at baseline on platelet function reactivity and activation.Methods. Platelet function, assessed by remotely measured surface expression of P-selectin, was assessed in patients at their time of randomisation. Data are median fluorescence values.Results. The aspirin P-selectin test demonstrated that platelet expression was lower in 494 patients taking aspirin than in 162 patients not: mean 210 (SD 188) versus 570 (435), difference 360.3 (95% CI 312.2–408.4) (2p<0.001). Aspirin did not suppress P-selectin levels below 500 units in 23 (4.7%) patients. The clopidogrel test showed that platelet reactivity was lower in 97 patients taking clopidogrel than in 585 patients not: 655 (296) versus 969 (315), difference 314.5 (95% CI 247.3–381.7) (2p<0.001). Clopidogrel did not suppress P-selectin level below 860 units in 24 (24.7%) patients.Conclusions. Aspirin and clopidogrel suppress stimulated platelet P-selectin, although one-quarter of patients on clopidogrel have high on-treatment platelet reactivity. Platelet function testing may be performed remotely in the context of a large multicentre trial. Trial registrationISRCTN47823388.

Quantifying the Effect of Antiplatelet Therapy

2006 ◽  
Vol 105 (4) ◽  
pp. 676-683 ◽  
Author(s):  
Seema Agarwal ◽  
Margaret Coakely ◽  
Kalpana Reddy ◽  
Anne Riddell ◽  
Susan Mallett
Keyword(s):  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Light Transmission ◽  
Point Of Care ◽  
Perioperative Bleeding ◽  
Light Transmission Aggregometry ◽  
Function Analyzer ◽  
Platelet Function Analyzer ◽  
Ischemic Events ◽  
Good Agreement

Background Antiplatelet therapy with aspirin and clopidogrel is known to confer protection against ischemic events. Increasing numbers of patients are presenting for surgery while taking these drugs. This may lead to an increase in perioperative blood loss, particularly in those who have a heightened response to the drugs. Identifying these patients preoperatively would allow us to plan appropriate management. Methods The antiplatelet effect of aspirin and/or clopidogrel was measured using two point-of-care monitors: the platelet function analyzer (PFA-100; Dade, Miami, FL) and the modified thromboelastograph (mTEG; Haemoscope Corp., Niles, IL). This was compared with optical light transmission aggregometry. Results All people taking aspirin displayed a definitive aspirin effect on aggregometry (n = 20). Ninety percent of these were identified by modified thromboelastography (n = 18). Seventy percent were identified by the platelet function analyzer (n = 14). Fifty percent of people taking clopidogrel displayed a definitive response to the drug on aggregometry. Seventy percent of these were identified on modified thromboelastography (n = 7). None were identified by the platelet function analyzer. There was good agreement between the results of the aggregometry and modified thromboelastography in clopidogrel patients (kappa = 0.81). Conclusion The search for a point-of-care monitor of platelet function has been the focus of much research. This study has shown that the modified thromboelastograph can be used for monitoring the effect of clopidogrel as well as aspirin. It potentially has a wide scope to be used for the monitoring of effectiveness of therapy as well as a possible predictor of perioperative bleeding.

Intrinsic platelet reactivity before start with clopidogrel as predictor for on-clopidogrel platelet function and long-term clinical outcome

2015 ◽  
Vol 114 (07) ◽  
pp. 109-114 ◽  
Author(s):  
Christian M. Valina ◽  
Timo Bömicke ◽  
Michael Amann ◽  
Christian Stratz ◽  
Thomas Nührenberg ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Platelet Function ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Clinical Trial Registration ◽  
Coronary Stent Implantation ◽  
Insufficient Response ◽  
A Minor ◽  
Intrinsic Reactivity

SummaryHigh on-clopidogrel platelet reactivity is associated with worse clinical outcome. Previous data suggest that intrinsic platelet reactivity before initiation of clopidogrel contributes significantly to on-clopidogrel platelet reactivity. It is unknown whether intrinsic reactivity can sufficiently predict on-clopidogrel reactivity and therefore identify patients with insufficient response to clopidogrel before initiation of treatment and at risk for worse clinical outcome. This analysis included 765 consecutive patients undergoing elective coronary stent implantation. Platelet reactivity was assessed by light transmission aggregometry (5 µM ADP) before administration of clopidogrel 600mg and after intake of first maintenance dose of clopidogrel on day 1 following coronary stenting. Patients were followed for up to seven years. The combined primary endpoint was death of any cause or non-fatal myocardial infarction. Intrinsic and on-clopidogrel platelet reactivity were significant correlated (r=0.31; p < 0.001). Among all tested clinical and genetic factors including the cytochrome P450 2C19*2 polymorphism, intrinsic platelet reactivity was the strongest predictor for on-clopidogrel platelet reactivity. However, intrinsic platelet reactivity could only explain 8 % of variability of on-clopidogrel platelet function. Only on-treatment platelet reactivity was predictive for long-term clinical outcome (HR 1.47, 95 % CI 1.05–2.05; p = 0.02) whereas intrinsic platelet reactivity was not (HR 1.03, 95 % CI 0.74–1.43; p = 0.86). In conclusion, intrinsic platelet reactivity before initiation of clopidogrel is the strongest predictor of early on-clopidogrel platelet reactivity but can only explain a minor proportion of its variability and is not significantly associated with clinical outcome. Thus, baseline testing cannot substitute on-clopidogrel platelet function testing.Clinical Trial Registration: ClinicalTrials.gov (Identifier: NCT00457236).

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