Utility of point of care assessment of platelet reactivity (using the PFA-100®) to aid in diagnosis of stroke (original) (raw)

Platelet function testing in transient ischaemic attack and ischaemic stroke: A comprehensive systematic review of the literature

Platelets, 2015

The majority of patients with ischaemic cerebrovascular disease (CVD) are not protected from further vascular events with antiplatelet therapy. Measurement of inhibition of platelet function ex vivo on antiplatelet therapy, using laboratory tests that correlate with the clinical effectiveness of these agents, would potentially enable physicians to tailor antiplatelet therapy to suit individuals. A systematic review of the literature was performed to collate all available data on ex vivo platelet function/reactivity in CVD patients, especially those treated with aspirin, dipyridamole or clopidogrel. Particular emphasis was paid to information from commonly available whole blood platelet function analysers (PFA-100 Õ , VerifyNow Õ and Multiplate Õ). Data on pharmacogenetic mechanisms potentially influencing high on-treatment platelet reactivity (HTPR) on antiplatelet therapy in CVD were reviewed. Two-hundred forty-nine potentially relevant articles were identified; 93 manuscripts met criteria for inclusion. The prevalence of ex vivo HTPR in CVD varies between 3-62% with aspirin monotherapy, 8-61% with clopidogrel monotherapy and 56-59% when dipyridamole is added to aspirin in the early, subacute or late phases after TIA/stroke onset. The prevalence of HTPR on aspirin was higher on the PFA-100 than on the VerifyNow in one study (p50.001). Furthermore, the prevalence of HTPR on aspirin was lower when one used 'novel longitudinal' rather than 'cross-sectional, case-control' definitions of HTPR on the PFA early after TIA or stroke (p ¼ 0.003; 1 study). Studies assessing the influence of genetic polymorphisms on HTPR in CVD patients are limited, and need validation in large multicentre studies. Available data illustrate that an important proportion of CVD patients have ex vivo HTPR on their prescribed antiplatelet regimen, and that the prevalence varies depending on the definition and assay used. Large, adequately-sized, prospective multicentre collaborative studies are urgently needed to determine whether comprehensive assessment of HTPR at high and low shear stress with a range of user-friendly whole blood platelet function testing platforms, in conjunction with pharmacogenetic data, improves our ability to predict the risk of recurrent vascular events in CVD patients, and thus enhance secondary prevention following TIA or ischaemic stroke.

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

Stroke Research and Treatment

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) ...

Platelet function/reactivity testing and prediction of risk of recurrent vascular events and outcomes after TIA or ischaemic stroke: systematic review and meta-analysis

Journal of Neurology, 2020

Background: The prevalence of ex-vivo 'high on-treatment platelet reactivity (HTPR)' and its relationship with recurrent vascular events/outcomes in patients with ischaemic cerebrovascular disease (CVD) is unclear. Methods: A systematic review and meta-analysis was performed in accordance with the PRISMA statement. MEDLINE, EMBASE and Cochrane Library were searched for completed manuscripts until May 2019 on TIA/ischaemic stroke patients, ≥18 years, treated with commonly-prescribed antiplatelet therapy, who had platelet function/reactivity testing and prospective follow-up data on recurrent stroke/TIA, myocardial infarction, vascular death or other cerebrovascular outcomes. Data were pooled using random-effects metaanalysis. Primary outcome was the composite risk of recurrent stroke/TIA, myocardial infarction or vascular death. Secondary outcomes were recurrent stroke/TIA, severe stroke (NIHSS>16) or disability/impairment (modified Rankin scale ≥3) during follow-up. Results: Antiplatelet-HTPR prevalence was 3-65% with aspirin, 8-56% with clopidogrel and 1.8-35% with aspirin-clopidogrel therapy. Twenty studies (4,989 patients) were included in our meta-analysis. There was a higher risk of the composite primary outcome (OR 2.93, 95%CI: 1.90-4.51) and recurrent ischaemic stroke/TIA (OR 2.43, 95%CI: 1.51-3.91) in patients with vs. those without 'antiplatelet-HTPR' on any antiplatelet regimen. These risks were also more than twofold higher in patients with vs. those without 'aspirin-HTPR' and 'dual antiplatelet-HTPR', respectively. Clopidogrel-HTPR status did not significantly predict outcomes, but the number of eligible studies was small. The risk of severe stroke was higher in those with vs. without antiplatelet-HTPR (OR 2.65, 95%CI:1.00-7.01). Discussion: Antiplatelet-HTPR may predict risks of recurrent vascular events/outcomes in CVD patients. Given the heterogeneity between studies, further prospective, multi-centre studies are warranted.

Association of platelet count and mean platelet volume (MPV) index with types of stroke

Caspian Journal of Internal Medicine, 2020

Background: Stroke is known to be the third most prominent cause of death in the developing countries and the most common debilitating neurologic disease. This study aimed to investigate the association of platelet count (PC) and mean platelet volume (MPV) index with various stroke types. Methods: This cross-sectional study was carried out on patients over the age of 18 years who presented with signs and symptoms of the first acute stroke. Exclusion criteria were underlying chronic liver or renal disease and the time more than 6 hours from symptom initiation, hematological and infectious disorders in patients. After recording of demographic data, a complete blood cell count (CBC) test was performed. Results: From 150 patients, who enrolled in the study, 54.7% of patients were males. The initial brain CT scan was normal in 13 (8.7%) patients and showed evidence of brain infarction and intracranial hemorrhage in 84 (56%) and 53 (35.3%) patients respectively. Patients with intracranial hemorrhage had significantly higher mean of MPV index than the patients with normal brain-CT scan and patients with evidence of brain infarction (p<0.001). Conclusion: The MVP index can be a predictor of the type of hemorrhagic or ischemic finding in emergency CT scan in stroke patients. This relationship may help to better understand the physiopathologic role of platelets in the development of stroke (hemorrhagic or ischemic), but will not replace cerebral computed tomography to diagnose the type of stroke, or it may not initiate treatment for hemorrhagic stroke.

Clinical Implications of Changes in Individual Platelet Reactivity to Aspirin Over Time in Acute Ischemic Stroke

Stroke; a journal of cerebral circulation, 2015

Time-dependent changes in individual platelet reactivity have been detected in patients with coronary artery disease. Therefore, we sought to evaluate the time-dependent changes in platelet reactivity to aspirin during the acute stage after ischemic stroke and the clinical implications of variable patient responses to aspirin in acute ischemic stroke. We conducted a single-center, prospective, observational study. The acute aspirin reaction unit (ARU) was measured after 3 hours of aspirin loading, with higher values indicating increased platelet reactivity despite aspirin therapy. The follow-up ARU was measured on the fifth day of consecutive aspirin intake. The numeric difference between the follow-up ARU and the acute ARU was defined as ∆ARU and was stratified into quartiles. Early neurological deterioration was regarded as an early clinical outcome. Both the acute ARU (476±69 IU) and the follow-up ARU (451±68 IU) were measured in 349 patients in this study. Early neurological det...

The mean platelet volume on admission predicts unfavorable stroke outcomes in patients treated with IV thrombolysis

Clinical Interventions in Aging, 2019

The role of biomarkers in the prediction of acute ischemic stroke (AIS) outcome or response to thrombolytic therapy (with recombinant tissue plasminogen activator [rt-PA]) remains limited. The aim of this study was to evaluate whether mean platelet volume (MPV) could predict short-term functional outcome in patients with AIS following rt-PA treatment. Patients and methods: This was a retrospective analysis of 237 AIS patients (mean age 71.04±0.8 years, 50.6% women) consecutively admitted to a tertiary care center between 2011 and 2015. Results: The mean MPV in the cohort was 9.8±0.35 fL (lowest tertile ,7.29 fL, median 7.29-8.8 fL, and highest tertile .8.8 fL). Patients in the lowest tertile compared to median and highest tertiles were less often dependent (modified Rankin scale [mRS] $3) at admission (87.2% vs 96.1% and 96.1%, respectively, P=0.04) and less often had a poor stroke outcome (mRS 4-6) at discharge (28.2% vs 55.3% and 44.7%, P,0.01). However, there was no significant difference between tertiles with regard to AIS etiology, CT (Alberta Stroke Program Early CT) score, frequency of stroke due to large artery occlusion, risk of secondary hemorrhage, and early neurologic deterioration. Multivariable analysis after adjustment for confounders showed that patients in the second and third tertiles had a significantly higher risk of poor stroke outcome (OR =1.9, 95% CI =1.01-4), lack of early improvement (OR =1.91, 95% CI =1.05-3.47), lower chance of good outcome (mRS 0-2; OR =0.38, 95% CI =0.18-0.78), or minor stroke at discharge (OR =0.47, 95% CI =0.26-0.84). Receiver operating characteristic analysis for prediction of poor stroke outcome showed that the optimal cutoff point of MPV was 8.8 fL (area under the curve 0.586 [0.512-0.659], P=0.03) with a sensitivity of 82.7% and a specificity of 43.9%. Conclusion: Disabling or fatal ischemic stroke in thrombolyzed patients was observed more often in patients with high admission MPV. The prognostic value of MPV was independent of other well-defined individual risk factors.

The mean platelet volume and plateletcrit as predictors of short-term outcome of acute ischemic stroke

The Egyptian Journal of Neurology, Psychiatry and Neurosurgery, 2019

Background: Activation of the platelet plays an important role in the process of atherosclerosis. Mean platelet volume (MPV) is significantly associated with the poor outcome of acute ischemic stroke while the results of studies about the relationship between plateletcrit (PCT) and stroke outcome were inconsistent. The aim of this work is to determine whether an association exists between MPV and plateletcrit (PCT) and outcome of acute ischemic stroke. Methods: We examined 157 patients with ischemic stroke, admitted to the Sohag University Hospital. The diagnosis of stroke was performed clinically according to The World Health Organization and confirmed by brain CT and MRI when needed. Platelet indices including MPV and PCT were assessed immediately (within 2 h) after admission. After 3 months, the functional outcome was assessed using the modified Rankin Scale (mRS) with assessment of the relationship between platelet indices and stroke outcome. Results: About 50% of the participants have favorable outcome. MPV was significantly higher in the unfavorable group (10.4 ± 2.3 fL) than in the favorable one (8.7 ± 1.3 fL) (P < 0. 001). MPV was an independent predictor of poor short-term outcome of acute stroke after controlling for confounders like diabetes mellitus. The mean PCT was significantly higher in the unfavorable group (0.28 ± 0.1%) than in the favorable one (0.25 ± 0.1%) (P = 0. 04) but not considered as an independent predictor of poor short-term outcome of acute stroke. Conclusions: MPV and PCT were significantly correlated with poor functional outcome, only MPV was an independent predictor of poor short-term outcome of acute stroke after controlling for confounders like DM, and these platelet indices can be used as a prognostic tool.

Hyperresponsiveness of platelets in ischemic stroke

Thrombosis and Haemostasis, 2007

Platelet activation and aggregation arecritical in thepathogenesis of acute ischemic cerebrovascular diseases.Theaim of our study was to characterize plateletfunctioninpatientswith acute ischemic strokeortransient ischemic attack (TIA),and to evaluate thee ffecto fp lateleta ctivation on clinical outcome.One hundredt hirty-eight consecutivep atientsw ith TIA( n=74) or stroke(n=64) were enrolledinthis study.Plateletaggregation in response to ADP,epinephrine,arachidonic acid, or collagen, and expression of plateleta ctivation receptors (CD62P,C D63, LIBS-1 and PAC-1) in the acute phaseand at three monthsfollow-up were evaluated. Platelets derived from strokep atients were morehyperaggregableinresponsetoagonists in the acute

The mean platelet volume on admission predicts unfavorable stroke outcomes in patients treated with IV thrombolysis

Clinical Interventions in Aging

The role of biomarkers in the prediction of acute ischemic stroke (AIS) outcome or response to thrombolytic therapy (with recombinant tissue plasminogen activator [rt-PA]) remains limited. The aim of this study was to evaluate whether mean platelet volume (MPV) could predict short-term functional outcome in patients with AIS following rt-PA treatment. Patients and methods: This was a retrospective analysis of 237 AIS patients (mean age 71.04±0.8 years, 50.6% women) consecutively admitted to a tertiary care center between 2011 and 2015. Results: The mean MPV in the cohort was 9.8±0.35 fL (lowest tertile ,7.29 fL, median 7.29-8.8 fL, and highest tertile .8.8 fL). Patients in the lowest tertile compared to median and highest tertiles were less often dependent (modified Rankin scale [mRS] $3) at admission (87.2% vs 96.1% and 96.1%, respectively, P=0.04) and less often had a poor stroke outcome (mRS 4-6) at discharge (28.2% vs 55.3% and 44.7%, P,0.01). However, there was no significant difference between tertiles with regard to AIS etiology, CT (Alberta Stroke Program Early CT) score, frequency of stroke due to large artery occlusion, risk of secondary hemorrhage, and early neurologic deterioration. Multivariable analysis after adjustment for confounders showed that patients in the second and third tertiles had a significantly higher risk of poor stroke outcome (OR =1.9, 95% CI =1.01-4), lack of early improvement (OR =1.91, 95% CI =1.05-3.47), lower chance of good outcome (mRS 0-2; OR =0.38, 95% CI =0.18-0.78), or minor stroke at discharge (OR =0.47, 95% CI =0.26-0.84). Receiver operating characteristic analysis for prediction of poor stroke outcome showed that the optimal cutoff point of MPV was 8.8 fL (area under the curve 0.586 [0.512-0.659], P=0.03) with a sensitivity of 82.7% and a specificity of 43.9%. Conclusion: Disabling or fatal ischemic stroke in thrombolyzed patients was observed more often in patients with high admission MPV. The prognostic value of MPV was independent of other well-defined individual risk factors.