scholarly journals Why Me? To Be an Ultra-Responder to Antiplatelet Therapy: A Case Report

2021 ◽  
Vol 12 ◽  
Author(s):  
Francesca Rosafio ◽  
Guido Bigliardi ◽  
Nicoletta Lelli ◽  
Laura Vandelli ◽  
Federica Naldi ◽  
...  
Keyword(s):  
Case Report ◽  
Primary Prevention ◽  
Cerebrovascular Disease ◽  
Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Cavernous Angioma ◽  
Platelet Inhibition ◽  
Sudden Onset ◽  
Platelet Aggregometry ◽  
Increased Risk

Background: Platelet function testing is a valid tool to investigate the clinical response to antiplatelet therapy in different clinical settings; in particular, it might supply helpful information in patients with cerebrovascular disease. Oral antiplatelet treatment, such as Aspirin (ASA) and Clopidogrel, is the gold standard in secondary stroke prevention of non-cardiogenic ischemic stroke; conversely, its application as a primary prevention therapy is not routinely recommended in patients with vascular risk factors. Multiple electrode platelet aggregometry (MEA) impedance aggregometer is a validated device to test platelet inhibition induced by ASA or Clopidogrel.Case Report: We report the case of a 78-year-old patient without relevant clinical history, taking ASA as primary prevention strategy, who was admitted for sudden onset of dysarthria and left facial hyposthenia during physical effort. Brain CT revealed two small subcortical bilateral spontaneous intracranial hemorrhages. Platelet aggregometry with MEA performed upon admission revealed a very strong platelet inhibition induced by ASA (result of the ASPI Test was 5 U, consistent with an ultra-responsiveness to ASA, and the cutoff value of correct responsiveness is <40 U). MRI at longitudinal follow-up revealed the presence of two small cavernous angioma underlying hemorrhagic spots.Conclusion: The evaluation of platelet reactivity in stroke patients undergoing antiplatelet therapies, not commonly performed in clinical practice, could be useful to optimize prevention strategies; the verification of the biological effectiveness of ASA or Clopidogrel could be a valid tool in the definition of each patient's risk profile, particularly in patients with cerebrovascular disease known to be at increased risk for both hemorrhagic and thrombotic complications.

Comparison of methods to evaluate clopidogrel-mediated platelet inhibition after percutaneous intervention with stent implantation

2009 ◽  
Vol 101 (02) ◽  
pp. 333-339 ◽  
Author(s):  
Sabine Steiner ◽  
Daniela Seidinger ◽  
Renate Koppensteiner ◽  
Thomas Gremmel ◽  
Simon Panzer ◽  
...  
Keyword(s):  
Stent Implantation ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Platelet Inhibition ◽  
Percutaneous Intervention ◽  
Adverse Outcomes ◽  
Gold Standard Method ◽  
Platelet Aggregometry ◽  
Increased Risk ◽  
The Impact

SummaryA high on-treatment residual ADP-inducible platelet reactivity in light transmission aggregometry (LTA) has been associated with an increased risk of adverse outcomes after percutaneous coronary intervention (PCI). However, LTA is weakly standardized, and results obtained in one laboratory may not be comparable to those obtained in another one. We therefore sought to determine the test correlating best with LTA to estimate clopidogrel-mediated platelet inhibition in 80 patients on dual antiplatelet therapy after elective percutaneous intervention with stent implantation. We selected the VerifyNow P2Y12 assay, the vasodilator-stimulated phosphoprotein phosphorylation assay, multiple electrode platelet aggregometry and the Impact-R for comparisons with LTA. Cut-off values for residual ADP-inducible platelet reactivity were defined according to quartiles of each assay. Sensitivities and specificities of the different platelet function tests were based on the results from LTA. The results from all four assays correlated significantly with those from LTA. The VerifyNow P2Y12 assay revealed the strongest correlation (r = 0.61, p < 0.001). Sensitivities and specificities ranged from 35% to 55%, and from 78.3% to 85%, respectively. In conclusion, although all assays correlated significantly with LTA, they need to be improved to become clinically used diagnostic tests. Further, it may be too early to define the gold standard method for assessing residual ADP-inducible platelet reactivity and generally acceptable cut-off values.

scholarly journals Use of Thromboelastography Platelet Mapping for Assessment of Individual Platelet Response Secondary to Oral Antiplatelet Therapy after Percutaneous Coronary Intervention: An Attempt to Start Personalized Antiplatelet Therapy in India

2021 ◽  
Author(s):  
Suvro Sankha Datta ◽  
Dibyendu De ◽  
Nadeem Afroz Muslim
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
P Value ◽  
Platelet Response ◽  
Percutaneous Coronary ◽  
The Individual ◽  
Platelet Functions

AbstractHigh on-treatment platelet reactivity (HPR) with P2Y12 receptor antagonists in patients treated with dual antiplatelet therapy (DAPT) is strongly associated with adverse ischemic events after percutaneous coronary intervention (PCI). This prospective study was conducted to assess individual platelet response and HPR to antiplatelet medications in post-PCI cases by thromboelastography platelet mapping (TEG-PM). Total 82 patients who were on aspirin and on either clopidogrel, prasugrel, or ticagrelor were evaluated. The percentage of platelet inhibition to arachidonic acid (AA) and adenosine disdiphosphate (ADP) was calculated by [100-{(MA ADP/AA–MA Fibrin) / (MA Thrombin–MA Fibrin) × 100}], taking 50% response as cut-off for HPR. HPR to clopidogrel and prasugrel was 14.29 and 12.5%, respectively. No HPR was detected to aspirin and ticagrelor. The mean percentage of platelet inhibition was significantly higher in patients with ticagrelor 82.99, 95% confidence interval (CI) of [77.3, 88.7] as compared with clopidogrel 72.21, 95% CI of [65.3, 79.1] and prasugrel 64.2, 95% CI of [52.5, 75.9] (p-value of 0.041 and 0.003, respectively). Aspirin along with ticagrelor is associated with a higher mean percentage of platelet inhibition, and lower HPR as compared with the usage of aspirin combined with clopidogrel or prasugrel. Additionally, it might also be concluded that TEG-PM could be used effectively to measure the individual platelet functions which would make oral antiplatelet therapy more personalized for cardiac patients.

Antiplatelet drugs in patients with enhanced platelet turnover: biomarkers versus platelet function testing

2015 ◽  
Vol 114 (09) ◽  
pp. 459-468 ◽  
Author(s):  
Susanne Gruber ◽  
Erik Grove ◽  
Thomas Weiss ◽  
Johann Wojta ◽  
Kurt Huber ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Platelet Reactivity ◽  
Platelet Inhibition ◽  
Antiplatelet Drugs ◽  
P2y12 Inhibitors ◽  
Reticulated Platelets ◽  
Increased Risk ◽  
Key Factor ◽  
Coronary Syndromes ◽  
Function Testing

SummaryPlatelets are key players in atherothrombosis. Antiplatelet therapy comprising aspirin alone or with P2Y12-inhibitors are effective for prevention of atherothrombotic complications. However, there is interindividual variability in the response to antiplatelet drugs, leaving some patients at increased risk of recurrent atherothrombotic events. Several risk factors associated with high on-treatment platelet reactivity (HTPR), including elevated platelet turnover, have been identified. Platelet turnover is adequately estimated from the fraction of reticulated platelets. Reticulated platelets are young platelets, characterised by residual messenger RNA. They are larger, haemostatically more active and there is evidence that platelet turnover is a causal and prognostic factor in atherothrombotic disease. Whether platelet turnover per se represents a key factor in pathogenesis, progression and prognosis of atherothrombotic diseases (with focus on acute coronary syndromes) or whether it merely facilitates insufficient platelet inhibition will be discussed in this state-of-the art review.

scholarly journals Multifactorial Background for a Low Biological Response to Antiplatelet Agents Used in Stroke Prevention

Medicina ◽  
2021 ◽  
Vol 57 (1) ◽  
pp. 59
Author(s):  
Adam Wiśniewski
Keyword(s):  
Ischemic Stroke ◽  
Secondary Prevention ◽  
Antiplatelet Therapy ◽  
Negative Impact ◽  
Platelet Reactivity ◽  
Antiplatelet Agent ◽  
Biological Response ◽  
Antiplatelet Agents ◽  
Platelet Inhibition ◽  
High Risk Group

Effective platelet inhibition is the main goal of the antiplatelet therapy recommended as a standard treatment in the secondary prevention of non-embolic ischemic stroke. Acetylsalicylic acid (aspirin) and clopidogrel are commonly used for this purpose worldwide. A low biological response to antiplatelet agents is a phenomenon that significantly reduces the therapeutic and protective properties of the therapy. The mechanisms leading to high on-treatment platelet reactivity are still unclear and remain multifactorial. The aim of the current review is to establish the background of resistance to antiplatelet agents commonly used in the secondary prevention of ischemic stroke and to explain the possible mechanisms. The most important factors influencing the incidence of a low biological response were demonstrated. The similarities and the differences in resistance to both drugs are emphasized, which may facilitate the selection of the appropriate antiplatelet agent in relation to specific clinical conditions and comorbidities. Despite the lack of indications for the routine assessment of platelet reactivity in stroke subjects, this should be performed in selected patients from the high-risk group. Increasing the detectability of low antiaggregant responders, in light of its negative impact on the prognosis and clinical outcomes, can contribute to a more individualized approach and modification of the antiplatelet therapy to maximize the therapeutic effect in the secondary prevention of stroke.

scholarly journals microRNAs as Promising Biomarkers of Platelet Activity in Antiplatelet Therapy Monitoring

2020 ◽  
Vol 21 (10) ◽  
pp. 3477
Author(s):  
Teresa L. Krammer ◽  
Manuel Mayr ◽  
Matthias Hackl
Keyword(s):  
Antiplatelet Therapy ◽  
Platelet Activation ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Therapy Monitoring ◽  
Platelet Inhibition ◽  
High Morbidity ◽  
Platelet Function Tests ◽  
Function Tests ◽  
Plasma Mirna

Given the high morbidity and mortality of cardiovascular diseases (CVDs), novel biomarkers for platelet reactivity are urgently needed. Ischemic events in CVDs are causally linked to platelets, small anucleate cells important for hemostasis. The major side-effect of antiplatelet therapy are life-threatening bleeding events. Current platelet function tests are not sufficient in guiding treatment decisions. Platelets host a broad spectrum of microRNAs (miRNAs) and are a major source of cell-free miRNAs in the blood stream. Platelet-related miRNAs have been suggested as biomarkers of platelet activation and assessment of antiplatelet therapy responsiveness. Platelets release miRNAs upon activation, possibly leading to alterations of plasma miRNA levels in conjunction with CVD or inadequate platelet inhibition. Unlike current platelet function tests, which measure platelet activation ex vivo, signatures of platelet-related miRNAs potentially enable the assessment of in vivo platelet reactivity. Evidence suggests that some miRNAs are responsive to platelet inhibition, making them promising biomarker candidates. In this review, we explain the secretion of miRNAs upon platelet activation and discuss the potential use of platelet-related miRNAs as biomarkers for CVD and antiplatelet therapy monitoring, but also highlight remaining gaps in our knowledge and uncertainties regarding clinical utility. We also elaborate on technical issues and limitations concerning plasma miRNA quantification.

The impact of renal function on platelet reactivity and clinical outcome in patients undergoing percutaneous coronary intervention with stenting

2014 ◽  
Vol 112 (12) ◽  
pp. 1174-1181 ◽  
Author(s):  
Nicoline Breet ◽  
Corine de Jong ◽  
Willem Jan Bos ◽  
Jochem van Werkum ◽  
Heleen Bouman ◽  
...  
Keyword(s):  
Renal Function ◽  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Light Transmittance ◽  
Clinical Trial Registration ◽  
Platelet Function Test ◽  
Increased Risk ◽  
Function Test ◽  
The Impact

SummaryPatients with chronic kidney disease (CKD) have an increased risk of cardiovascular disease. Previous studies have suggested that patients with CKD have less therapeutic benefit of antiplatelet therapy. However, the relation between renal function and platelet reactivity is still under debate. On-treatment platelet reactivity was determined in parallel by ADP- and AA-induced light transmittance aggregometry (LTA) and the VerifyNow® System (P2Y12 and Aspirin) in 988 patients on dual antiplatelet therapy, undergoing elective coronary stenting. Patients were divided into two groups according to the presence or absence of moderate/severe CKD (GFR<60 ml/min/1.73 m2). Furthermore, the incidence of all-cause death, non-fatal acute myocardial infarction, stent thrombosis and stroke at one-year was evaluated. Patients with CKD (n=180) had significantly higher platelet reactivity, regardless of the platelet function test used. Patients with CKD more frequently had high on-clopidogrel platelet reactivity (HCPR) and high on-aspirin platelet reactivity (HAPR) regardless of the platelet function test used. After adjustment for potential confounders, this was no longer significant. The event-rate was the highest in patients with both high on-treatment platelet reactivity (HPR) and CKD compared to those with neither high on-treatment platelet reactivity nor CKD. In conclusion, the magnitude of platelet reactivity as well as the incidence of HPR was higher in patients with CKD. However, since the incidence of HPR was similar after adjustment, a higher rate of co-morbidities in patients with CKD might be the major cause for this observation rather than CKD itself. CKD-patients with HCPR were at the highest risk of long-term cardiovascular events.Clinical Trial Registration: www.clinicaltrials.gov: NCT00352014.

Effects of aspirin and desmopressin on platelet reactivity in patients undergoing cardiac surgery with extracorporeal circulation

2011 ◽  
Vol 105 (01) ◽  
pp. 113-121 ◽  
Author(s):  
Eliane Kmitta ◽  
Sami Kueri ◽  
Tomasz Zietak ◽  
Dietmar Trenk ◽  
Cornelius Keyl
Keyword(s):  
Cardiac Surgery ◽  
Antiplatelet Therapy ◽  
Extracorporeal Circulation ◽  
Platelet Reactivity ◽  
Therapy Group ◽  
Artery Bypass ◽  
Bleeding Tendency ◽  
Platelet Aggregometry ◽  
Group A ◽  
Group B

SummaryThe effect of desmopressin on platelet function in patients with continued antiplatelet therapy undergoing cardiac surgery is discussed controversially. We assessed platelet reactivity in 86 patients undergoing elective coronary artery bypass grafting (CABG) under extracorporeal circulation. Twenty-nine of these patients were without preoperative antiplatelet therapy (group A), while 57 were treated with acetylsalicylic acid (ASA) 100 mg qd up to the day of surgery. Out of this cohort, 24 patients received no desmopressin perioperatively (group B), whereas 33 patients were treated with desmopressin 0.4 μg/kg after administration of protamine due to increased bleeding tendency (group C). Multiple electrode platelet aggregometry with arachidonic acid as agonist showed a marked decrease of platelet reactivity in patients without antiplatelet therapy immediately after extracorporeal circulation compared to preoperative control (375 ± 227 vs. 749 ± 330 AU*min, p<0.001). Platelet reactivity recovered to preoperative controls in group A at 24 hours after protamine administration (662 ± 295 AU*min). Platelet reactivity in patients on ASA was not decreased further after extracorporeal circulation (group B: 197 ± 126 vs. 251 ± 203 AU*min, p=0.14; group C: 212 ± 100 vs. 245 ± 248 AU*min, p=0.43) and improved significantly within 24 hours. A statistically significant effect of desmopressin, however, could not be determined (group B: 392 ± 223 AU*min; group C: 439 ± 324 AU*min at 24 hours after protamine, p=0.63 for between-subjects contrast). Our data suggest that desmopressin does not affect platelet reactivity in patients on ASA undergoing CABG and is, therefore, not useful in this clinical setting.

Individualised Antiplatelet Therapy – Is There a Role for Platelet Function Testing in Routine Clinical Practice?

2010 ◽  
Vol 5 (1) ◽  
pp. 96 ◽  
Author(s):  
Collet Jean-Philippe ◽  
Jochem Wouter van Werkum ◽  
◽  
Keyword(s):  
Clinical Practice ◽  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Point Of Care ◽  
Coronary Intervention ◽  
Platelet Function Testing ◽  
Increased Risk ◽  
Coronary Syndromes ◽  
Function Testing

Antiplatelet therapies are often used to minimise complications in patients with acute coronary syndromes or who are undergoing percutaneous coronary intervention with stenting. However, the occurrence of ‘high on-treatment platelet reactivity’ associated with the gold standard treatments aspirin and clopidogrel in a subset of individuals limits the efficacy of these drugs. This lack of response, which has been attributed to a genetic polymorphism, is associated with an increased risk of subsequent atherothrombotic events. In recent years, platelet function assays have been used to monitor antiplatelet inhibition. Various tests have been introduced that allow physicians to evaluate pharmacological response and potentially permit risk stratification of patients. While some of these assays have proved to be labour-intensive, the development of point-of-care assays may ease the time burden in clinical practice. Preliminary findings demonstrate the effectiveness of altering therapy based on assay results in terms of improving clinical outcomes, suggesting an important role for platelet function testing in the future of antiplatelet therapy.

Introduction of Routine Screening for Cerebrovascular Abnormailities in Sickle Cell Disease (SCD) Using Transcranial Doppler Ultrasonography (TCD).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3786-3786
Author(s):  
David C. Rees ◽  
Susan E. Height ◽  
Moira C. Dick ◽  
Swee Lay Thein ◽  
Josef Jarosz ◽  
...  
Keyword(s):  
Primary Prevention ◽  
Cerebrovascular Disease ◽  
Routine Screening ◽  
Blood Transfusions ◽  
College Hospital ◽  
Medical College ◽  
Increased Risk ◽  
The Usa ◽  
Vascular Laboratory ◽  
History Of

Abstract It is recommended both in the USA and Europe that children with SCD are scanned by TCD to identify increased risk of stroke and allow primary prevention. Although there are convincing trial data to support this, there is relatively little information on how this works in practice, with concerns about false positives, false negatives, implications of transfusion/chelation regimes. 20 months ago, a routine screening service was started for children with SCD attending Kings’s College Hospital (350 children). Scans were organised at clinic appointments and performed in the vascular laboratory by staff who had attended the training course at Medical College of Georgia. Scans followed the STOP protocol, and used TCD imaging, to visualise the vessels. 178 children without a history of stroke stroke have been scanned. 143 (80%) were normal, 12 (6.7%) had conditional results (TAMX&gt;170cm/s, &lt;200cm/s), 4 (2.2%) had abnormal results (TAMX&gt;200cm/s), 11 (6.2%) were unsatisfactory (not all vessels were seen), and 8 (4.5%) showed other abnormalities. Of the 12 with conditional scans, 8 have been repeated so far; of these, 3 were subsequently normal, and 5 persistently elevated; MRI/MRA scans were normal in 2 of these, and showed a probable right MCA stenosis in the 3rd; 2 are awaiting MRI/MRA. Of the 4 with abnormal scans, all were repeated and confirmed abnormal. On MRI/MRA two were shown to have extensive cerebrovascular disease with appearances of Moya Moya, and large, but clinically silent, cerebral infarcts. One had a normal MRI/MRA scan and decided against starting regular blood transfusions. One presented with left-hemiparesis before the repeat TCD, and MRI/MRA showed the new infarct and the stenosis also seen on TCD. Of the 11 unsatisfactory scans, 3 are awaiting repeat, 5 were normal on repeat, 1 was persistently unsatisfactory but had a normal MRI/MRA. 2 were persistently unsatisfactory and had abnormal MRI/MRA scans with stenosed vessels; one of these children presented with an extensive, hemiplegic stroke before repeat scanning or MRI/MRA was performed. All of the non-STOP abnormalities consisted of increased velocities and tortuosity/kinking in the proximal ICA and were not associated with significant intracranial abnormalities in any case. During the 20 months, 3 children presented with new overt strokes: two were identified on TCD, as mentioned above (1 with raised velocities and stroke prior to repeat scan, and 1 with unsatisfactroy examination). One presented with nephrotic syndrome and acute hemiplegia following normal TCD, and MRI/MRA showed normal blood vessels and an old infarct. 5 (2.8%) children started on regular blood transfusions: 3 presenting with strokes, and 2 with abnormal TCDs (who both had infarcts and Moya Moya on MRA/MRI). TCD is useful in routine service screening for cerebrovascular disease, in SCD. We found no patients who fulfilled typical STOP criteria for primary prevention, and our rate of abnormal scans was lower than predicted (2.2%); absent TCD traces/vessel images proved as significant as increased velocity in our patients. TCD also identified 2 pateints with clinically silent but extensive cerebrovascular disease, facilitating secondary prevention.

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