ASSOCIATION OF PLATELET-DERIVED MICROVESICLES WITH HIGH ON-TREATMENT PLATELET REACTIVITY IN CONVALESCENT ISCHEMIC STROKE PATIENTS TREATED WITH ACETYLSALICYLIC ACID

2019 ◽  
Vol 72 (8) ◽  
pp. 1426-1436
Author(s):  
Justyna Rosińska ◽  
Joanna Maciejewska ◽  
Robert Narożny ◽  
Wojciech Kozubski ◽  
Maria Łukasik
Keyword(s):  
Platelet Aggregation ◽  
Treatment Failure ◽  
Acetylsalicylic Acid ◽  
Platelet Reactivity ◽  
Study Groups ◽  
Surface Expression ◽  
Cerebrovascular Diseases ◽  
Stroke Patients ◽  
Vascular Events ◽  
The Impact

Introduction: Elevated concentrations of platelet-derived microvesicles are found in cerebrovascular diseases. The impact of acetylsalicylic acid on these microvesicles remains inconsistent, despite its well-established effect on platelet aggregation. High residual platelet aggregation is defined as high on-treatment platelet reactivity, while “treatment failure” is the occurrence of vascular events despite antiplatelet treatment. The aim of this study was to determine whether the antiaggregatory effect of acetylsalicylic acid correlates with platelet-derived microvesicles in convalescent ischaemic stroke patients and cardiovascular risk factor controls as well as to evaluate the association between high on-treatment platelet reactivity and recurrent vascular events with the studied platelet-derived microvesicle parameters. Materials and methods: The study groups consisted of 76 convalescent stroke patients and 74 controls. Total platelet-derived microvesicles, annexino-positive microvesicles number, and platelet-derived microvesicles with surface expression of proinflammatory (CD40L, CD62P, CD31) and procoagulant (PS, GPIIb/IIIa) markers were characterized and quantified using flow cytometry. Cyclooxygenase-1-specific platelet responsiveness, with whole blood impedance platelet aggregation under arachidonic acid stimulation and the serum concentration of thromboxane B2, were evaluated. Results: Neither acetylsalicylic acid intake nor modification of its daily dose caused statistically significant differences in the studied microvesicle parameters. Additionally, no statistically significant differences in the studied microvesicle parameters were revealed between high on-treatment platelet reactivity and non-high on-treatment platelet reactivity subjects in either study subgroup. However, elevated concentrations of PAC-1+/CD61+, CD62P+/CD61+ and CD31+/CD61+ microvesicles were found in stroke patients with treatment failure, defined in this study as a recurrent vascular events in a one-year follow-up period. Conclusions: This study revealed no relationship between circulating microvesicle number and platelet aggregation. The procoagulant and proinflammatory phenotype of circulating platelet-derived microvesicles might contribute to acetylsalicylic acid treatment failure.

The Impact of Different Antimigraine Compounds on Platelet and Erythrocyte Aggregation

Cephalalgia ◽  
2006 ◽  
Vol 26 (8) ◽  
pp. 920-924 ◽  
Author(s):  
S Evers ◽  
T Heuel ◽  
A Frese ◽  
E Akova-Öztürk ◽  
I-W Husstedt
Keyword(s):  
Platelet Aggregation ◽  
Acetylsalicylic Acid ◽  
Healthy Subjects ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Erythrocyte Aggregation ◽  
Reactivity Index ◽  
Vascular Events ◽  
The Impact ◽  
Ergotamine Tartrate

Clinical and experimental data suggest that ergotamine compounds and triptans may contribute to vascular events such as myocardial infarction and stroke. The role of blood cell aggregation in this context is, however, not clarified. We aimed to evaluate the impact of different acute antimigraine compounds on platelet and erythrocyte aggregation in a human ex vivo experimental design. In 20 healthy subjects without migraine and in 20 healthy subjects with migraine without aura, platelet and erythrocyte aggregation were measured before and after intake of placebo, acetylsalicylic acid, ergotamine tartrate, zolmitriptan and sumatriptan. Platelet aggregation was measured by the so-called platelet reactivity index. Erythrocyte aggregation was measured by photometric assessment in an aggregometer. Ergotamine tartrate induced a significant increase of platelet aggregation, whereas acetylsalicylic acid induced a significant decrease in both subject groups. After placebo, after sumatriptan and after zolmitriptan, no significant changes of platelet aggregation were noted. Erythrocyte aggregation was affected by neither compound. We can conclude that platelet aggregation, but not erythrocyte aggregation, is increased after intake of ergotamine tartrate. This may in part contribute to vascular side-effects of this compound. Acetylsalicylic acid and the triptans appeared to be safe with respect to platelet and erythrocyte aggregation.

Abstract T P341: Impact Of Cytochrome P450 2C19 Polymorphism On High On-treatment Platelet Reactivity In Stroke Patients Treated With Clopidogrel

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Tomotaka Tanaka ◽  
Shigeki Miyata ◽  
Haruko Yamamoto ◽  
Toshiyuki Miyata ◽  
Kazuyuki Nagatsuka ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Platelet Rich Plasma ◽  
Metabolic Activation ◽  
Japanese Patients ◽  
Paraoxonase 1 ◽  
Loss Of Function ◽  
Stroke Patients ◽  
The Impact

BACKGROUND: Clopidogrel is one of the most commonly used anti-platelet drugs. Recent reports suggested the association of allelic variants of the genes modulating metabolic activation (CYP2C19 and paraoxonase-1) and bioavailability (ABCB1) of clopidogrel with high on-treatment platelet reactivity (HTPR), possibly resulting in the recurrence of thrombotic events. However, these studies mostly examined patients with coronary heart disease and the impact of these polymorphisms in stroke patients is largely unknown. METHODS: We conducted a multicenter, prospective cohort study of 518 Japanese patients from 14 hospitals who were administrated clopidogrel. Residual platelet reactivity was determined by a change in light transmission induced by platelet aggregation in platelet-rich plasma after adding ADP. The vasodilator-stimulated phosphoprotein (VASP) index was also measured using flow cytometry. We investigated the association of polymorphisms of aforementioned enzymes with HTPR. RESULTS: In terms of CYP2C19 loss-of-function polymorphisms (*2 and *3), the prevalence of intermediate (IM: *1*2 or *1*3) or poor (PM: *2*2, *2*3, or *3*3) metabolizer was much higher (IM: 47% or PM: 15%) in Japanese than in Caucasian populations. Residual platelet reactivity was significantly higher in PM and IM groups than that in the wild-type extensive metabolizer (EM: *1*1) group assessed by 5 μM ADP-induced platelet aggregation (PM: 69.4% ± 17.1%, IM: 59.7% ± 16.2%, EM: 51.5% ± 17.5%, p < 0.0001) and VASP index (PM: 66.6% ± 14.1%, IM: 52.4% ± 16.0%, EM: 42.9% ± 15.0%, p < 0.0001). Furthermore, HTPR determined by both assays was associated with the ABCB1 polymorphism (rs1045642) but not with the paraoxonase-1 Q192R mutation. CONCLUSIONS: Our results indicate that both CYP2C19 and ABCB1 polymorphisms significantly contribute to HTPR in stroke patients treated with clopidogrel. At present, we are monitoring these patients for a two-year period to determine whether these genetic variants and HTPR affect the recurrence of thrombotic events.

scholarly journals Impact of acetylsalicylic acid on primary prevention of cardiovascular diseases: A meta-analysis of randomized trials

2018 ◽  
Vol 26 (7) ◽  
pp. 746-749 ◽  
Author(s):  
Sunil Upadhaya ◽  
Seetharamprasad Madala ◽  
Ramkaji Baniya ◽  
Kalyan Saginala ◽  
Jahangir Khan
Keyword(s):  
Primary Prevention ◽  
Acetylsalicylic Acid ◽  
Hemorrhagic Stroke ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Vascular Events ◽  
Individual Participant ◽  
The Cost ◽  
The Impact ◽  
Key Questions

Numerous studies have investigated use of acetylsalicylic acid (ASA) for prevention of cardiovascular deaths. The vast majority of the work in this area has focused on secondary prevention. However, underuse of ASA still remains a major issue. Fewer studies have investigated the impact of ASA on primary prevention of cardiovascular death. A meta-analysis of individual participant data from six randomized studies, published in 2009, showed decrease in serious vascular events but at the cost of causing increased bleeding and hemorrhagic stroke. Recent studies have raised a number of key questions regarding the benefits and risks of using ASA for primary prevention.

scholarly journals Antiplatelet effects of citalopram in patients with ischaemic stroke: A randomized, placebo-controlled, double-blind study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kristian Lundsgaard Kraglund ◽  
Janne Kaergaard Mortensen ◽  
Søren Paaske Johnsen ◽  
Grethe Andersen ◽  
Erik Lerkevang Grove
Keyword(s):  
Platelet Aggregation ◽  
Ischaemic Stroke ◽  
Acute Ischaemic Stroke ◽  
Platelet Reactivity ◽  
Significant Inhibition ◽  
Controlled Study ◽  
Double Blind Study ◽  
Stroke Patients ◽  
Double Blind ◽  
Ssri Treatment

AbstractWe evaluated the effect of SSRI treatment on platelet aggregation in patients with ischaemic stroke and included patients from the randomized double-blind controlled study of citalopram in acute ischaemic stroke (TALOS). Patients on clopidogrel were included 6 months after acute ischaemic stroke. Platelet parameters, including P2Y12 platelet reactivity using the VerifyNow System, were measured at the last day of study treatment and repeated after a 14-day wash-out period. A total of 60 patients were included (n = 32 randomized to citalopram). Platelet aggregation levels did not differ between the citalopram group (mean 116, 95% CI 89 to 143) and the placebo group (mean 136, 95% CI 109 to 163) (On-treatment, p = 0.14). Similarly, there was no significant change in platelet aggregation in the citalopram group from on-treatment to post-treatment (mean difference 2.0; 95% CI −18 to 14). Platelet count, size and turnover were not affected by SSRI treatment. In conclusion, SSRI therapy did not lead to statistically significant inhibition of platelet aggregation in ischaemic stroke patients treated with clopidogrel.

scholarly journals Novel Predictors of Future Vascular Events in Post-stroke Patients—A Pilot Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Diana Schrick ◽  
Erzsebet Ezer ◽  
Margit Tokes-Fuzesi ◽  
Laszlo Szapary ◽  
Tihamer Molnar
Keyword(s):  
Ex Vivo ◽  
Platelet Reactivity ◽  
Recurrent Stroke ◽  
Stroke Patients ◽  
Vascular Events ◽  
Post Stroke ◽  
Coronary Syndrome ◽  
Impedance Aggregometry ◽  
Selection Of

Introduction: A modified platelet function test (mPFT) was recently found to be superior compared to impedance aggregometry for selection of post-stroke patients with high on-treatment platelet reactivity (HTPR). We aimed to explore some peripheral blood cell characteristics as predictors of recurrent ischemic episodes. The predictive value of mPFT was also assessed in a cohort followed up to 36 months regarding recurrent ischemic vascular events.Methods: As a novelty, not only whole blood (WB), but after 1-h gravity sedimentation the separated upper (UB) and lower half blood (LB) samples were analyzed including neutrophil antisedimentation rate (NAR) in 52 post-stroke patients taking clopidogrel. Area under the curve (AUC, AUCupper and AUClower, respectively) was separately measured by Multiplate in the WB, UB and LB samples to characterize ex vivo platelet aggregation in the presence of ADP. Next, the occurrence of vascular events (stroke, acute coronary syndrome, ACS) were evaluated during 36-month follow-up.Results: A total of 11 vascular events (stroke n = 5, ACS n = 6) occurred during the follow-up period. The AUCupper was significantly higher in patients with recurrent stroke compared to those with uneventful follow-up (p = 0.03). The AUCupper with a cut-off value ≥70 based on the mPFT, was able to predict all stroke events (p = 0.01), while the total vascular events were independently predicted by NAR with a sensitivity of 82% and specificity of 88%.Conclusions: A combination of NAR reflecting the inflammatory state and AUCupper indicating HTPR may provide a better prediction of recurrent ischemic events suggesting a better selection of patients at risk, thus providing an individually tailored vascular therapy.

Abstract T MP107: Ischemic Strokes While on Aspirin: Initiation of Clopidogrel Is Better than Re-initiation of Aspirin for Prevention of Future Vascular Events

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Meng Lee ◽  
Yi-Ling Wu ◽  
Jeffrey L Saver ◽  
Hsuei-Chen Lee ◽  
Jiann-Der Lee ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ischemic Stroke ◽  
Treatment Failure ◽  
Risk Reduction ◽  
Recurrent Stroke ◽  
Vascular Risk ◽  
Stroke Patients ◽  
Vascular Events ◽  
Index Stroke

Background: It is currently unclear about what to do for the patient who has a breakthrough ischemic stroke while receiving aspirin, the so-called ‘aspirin treatment failure’. Objective: To compare the effectiveness of clopidogrel vs. aspirin for vascular risk reduction among ischemic stroke patients who were on aspirin treatment at the time of the index stroke. Methods: We analyzed the Taiwan National Health Insurance registry which comprises beneficiaries aged ≥ 18 years. Code ICD-9 was used to identify a primary hospitalization diagnosis of ischemic stroke among subjects encountered between 2003 and 2009, and continuously treated with aspirin ≥ 30 days before the index stroke. Follow-up was from time of the index stroke to admission for recurrent stroke or myocardial infarction; withdrawal from the registry; and last medical claim before 1/1/2011. Patients were categorized into 2 groups based on whether clopidogrel or aspirin was prescribed during follow-up period. Patients were excluded if their Medication Possession Ratio was < 80% or they not taking clopidogrel or aspirin within 30 days before an endpoint. Primary endpoints were a major adverse cardiovascular event (MACE: composite of stroke and myocardial infarction) and a recurrent stroke alone. Multivariate-adjusted hazard ratio (HR) and 95% CI for the development of events were estimated using Cox models. Results: Among 2281 eligible patients, mean age was 72 years, 41% were female, and mean follow-up duration was 2.2 years. Compared to aspirin, clopidogrel was associated with a significantly lower occurrence of MACE (adjusted HR 0.67, 95% CI 0.55 to 0.81) and recurrent stroke (adjusted HR 0.67, 0.54 to 0.82). The pattern of benefit for clopidogrel users was consistent across several endpoints (Table). Conclusion: Among ischemic stroke patients with so called ‘aspirin treatment failure’, clopidogrel may a better choice than aspirin for future vascular risk reduction.

Abstract WP116: Association Between Smoking Status, Platelet Function and Clinical Outcomes of Ticagrelor versus Clopidogrel in Patients With Minor Stroke or Transient Ischemic Attack

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yingying Yang ◽  
Yilong Wang
Keyword(s):  
Clinical Outcomes ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Smoking Status ◽  
Minor Stroke ◽  
Carrier Status ◽  
Bleeding Events ◽  
Vascular Events ◽  
Treatment Groups ◽  
The Impact

Background: Association between smoking status, platelet function and clinical outcomes of ticagrelor versus clopidogrel in patients with minor stroke or transient ischemic stroke (TIA) remains unclear. Methods: A subgroup analysis was conducted of Platelet Reactivity in Acute Non-disabling Cerebrovascular Events (PRINCE) trial. PRINCE trial was a randomized, prospective, multicenter, open-label, active-controlled, and blind-endpoint trial, which randomized patients with acute minor stroke, or TIA, to ticagrelor plus aspirin or clopidogrel plus aspirin within 24 hours of symptoms onset. Patients who smoked at least one cigarette per day for at least one year in their lives were defined as smokers. Platelet reactivity was assessed by the VerifyNow P2Y12 assay at baseline, 7+2 days and 90±7 days. High-on-treatment platelet reactivity (HOPR) was defined as P2Y12 reaction units >208.Clinical outcomes included any stroke, composite clinical vascular events and bleeding events at 90 days. Results: Among 675 patients enrolled in the PRINCE trial, 370 patients (54.8%) were smokers. At 7+2 days, the proportion of HOPR in ticagrelor versus clopidogrel was significantly lower in smokers (5.2% versus 21.8%) and non-smokers (2.3% versus 34.4%). There were marginal significant interactions between treatment groups and smoking status for the proportion of HOPR ( P =0.058). There were significant interactions between treatment groups and carrier status of CYP2C19 LOF alleles for the proportion of HOPR among smokers ( P =0.04), but no significant interactions were found among non-smokers ( P =0.91). At 90±7 days, there were significant interactions between treatment groups and smoking status for the risk of new stroke (smokers, 7.0% versus 4.9%, hazard ratio [HR], 1.57 [95%CI, 0.65-3.79], P =0.39; non-smokers, 5.3% versus 13.5%, HR, 0.39 [95%CI, 0.17-0.91], P =0.01. P for interaction=0.02). Conclusions: Among patients with minor stroke or TIA, ticagrelor might be superior to clopidogrel in inhibiting platelet reactivity and reducing the risk of stroke, particularly in non-smokers. Carrier status of CYP2C19 LOF alleles might play a role in the impact of smoking status. Clinical Trial Registration : Clinicaltrials.gov NCT02506140.

Platelet Reactivity and CD39 Ectonucleotidase Activities in Cryptogenic Stroke

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3817-3817
Author(s):  
Aaron J. Marcus ◽  
Marinus Johan Broekman ◽  
Joan HF Drosopoulos ◽  
Kim E. Olson ◽  
Dianne Pulte ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Splice Variants ◽  
Platelet Reactivity ◽  
Platelet Rich Plasma ◽  
Cryptogenic Stroke ◽  
Area Under The Curve ◽  
Unknown Etiology ◽  
Stroke Patients ◽  
Atp Secretion

Abstract In the US, 780,000 people are diagnosed with stroke annually, of which 180,000 are recurrent. Nearly 90% of strokes are ischemic and 10% hemorrhagic. Roughly 30% of ischemic strokes are of unknown etiology or “cryptogenic”; this figure is even higher in younger adults. We sought to determine whether platelet activation and recruitment are increased in younger patients with cryptogenic stroke. In addition, we postulated a prothrombotic change in their endogenous CD39/NTPDase1 expression and nucleotidase activities (metabolism of ATP and ADP to AMP). Our sample consists of patients with cryptogenic stroke (n=40) and healthy controls (n=35), ages 18 to 64, participating in the THrombophilia In Cryptogenic stroKe (THICK) study. Extensive preliminary testing for humoral prothrombotic disorders did not account for almost half of the cerebral infarcts. This suggests that cryptogenic stroke may in part represent a disorder of enhanced platelet reactivity. We did indeed find that markers of platelet activation were higher in cases than controls as determined by platelet aggregation in platelet-rich plasma (lumiaggregometry) and FACS analyses. ATP secretion, a measure of platelet recruitment, was higher in stroke vs. control (no ASA) with 5 and 0.5 μg/ml collagen, and with 5 and 0.5 μM epinephrine. FACS analyses revealed that CD154, CD63, and monocyte-platelet aggregates were increased (P=0.18, 0.048 and 0.034). By contrast, neither platelet aggregation (expressed as area under the curve) in response to 0.5 μg/ml collagen nor circulating tissue factor activity were significantly higher in cases as compared to controls. Together these findings suggest a potential role for enhanced platelet activation and recruitment in younger cryptogenic stroke patients. In addition, we established that CD39/NTPDase1 is expressed on neutrophils (PMN), lymphocytes, and monocytes with ATPase and ADPase activities highest on B-lymphocytes, lower on PMN, lowest on T-lymphocytes. In stroke subjects, trends to higher total ADPase activities were observed in lymphocytes (P=0.09) and PMN (P=0.09). In contrast, ATPase activities were similar (P=0.81 and 0.68). Thus, the ratio of ADPase to ATPase activity was greater in stroke patients than controls (P=0.003 for lymphocytes; 0.13 for PMN) in apparent compensation for prothrombotic propensities. In general, these same trends were observed for direct comparisons of stroke patients to controls, whether on ASA or not. This is in apparent contrast to the data obtained previously with CAD patients in the acute phase (El-Omar et al, Thrombosis Res.116:199–206, 2005), and supports the need for additional studies of cryptogenic and atherothrombotic stroke patients in both acute and convalescent phases. Total CD39 expression (FACS, assessed with mAb BU61) was only marginally higher in lymphocytes of patients as compared to controls. The finding of increased activities, but similar expression supports our hypothesis that the enzymatic nucleotidase activities of CD39 are regulated via expression of our newly discovered CD39 splice variants. Ultimately, therapy with solCD39 to block platelet activation and recruitment may hold promise for patients with cryptogenic stroke.

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