Results Of Platelet Function Tests Research Articles

The Impact of Preprocedural Platelet Function Testing on Periprocedural Complication Rates Associated With Pipeline Flow Diversion: An International Multicenter Study.

Dual antiplatelet therapy (DAPT) is necessary to minimize the risk of periprocedural thromboembolic complications associated with aneurysm embolization using pipeline embolization device (PED). We aimed to assess the impact of platelet function testing (PFT) on reducing periprocedural thromboembolic complications associated with PED flow diversion in patients receiving aspirin and clopidogrel. Patients with unruptured intracranial aneurysms requiring PED flow diversion were identified from 13 centers for retrospective evaluation. Clinical variables including the results of PFT before treatment, periprocedural DAPT regimen, and intracranial complications occurring within 72 h of embolization were identified. Complication rates were compared between PFT and non-PFT groups. Differences between groups were tested for statistical significance using the Wilcoxon rank sum, Fisher exact, or χ 2 tests. A P -value <.05 was statistically significant. 580 patients underwent PED embolization with 262 patients dichotomized to the PFT group and 318 patients to the non-PFT group. 13.7% of PFT group patients were clopidogrel nonresponders requiring changes in their pre-embolization DAPT regimen. Five percentage of PFT group [2.8%, 8.5%] patients experienced thromboembolic complications vs 1.6% of patients in the non-PFT group [0.6%, 3.8%] ( P = .019). Two (15.4%) PFT group patients with thromboembolic complications experienced permanent neurological disability vs 4 (80%) non-PFT group patients. 3.7% of PFT group patients [1.5%, 8.2%] and 3.5% [1.8%, 6.3%] of non-PFT group patients experienced hemorrhagic intracranial complications ( P > .9). Preprocedural PFT before PED treatment of intracranial aneurysms in patients premedicated with an aspirin and clopidogrel DAPT regimen may not be necessary to significantly reduce the risk of procedure-related intracranial complications.

High Platelet Reactivity Combined with CYP2C19 Genotype in Predicting Outcomes in East Asian Patients Undergoing Percutaneous Coronary Intervention.

Loss-of-function (LoF) alleles of cytochrome P450 2C19 (CYP2C19), which are prevalent in East Asians, are linked to high platelet reactivity (HPR) phenotype and poor prognosis. We aimed to investigate the incremental predictive value of HPR combined with CYP2C19 genotype in predicting outcomes after drug-eluting stent (DES) implantation. The patients treated with platelet function and genotype-related long-term prognosis in drug-eluting stent (PTRG-DES) consortium enrolled a total of 13,160 Korean patients treated with DES who had platelet function test (PFT) or CYP2C19 genotype, of which, 6,717 patients with PFT and genotype together were categorized. HPR was defined as VerifyNow ≥ 252 P2Y12 reaction unit. The primary outcome was the incidence of major adverse cardiac and cerebrovascular event (MACCE) 5 years after treatment. The patients with both HPR and CYP2C19 LoF/LoF had the highest MACCE rates (6.2%) and increased MACCE risk (adjusted hazard ratio: 1.89, 95% confidence interval: 1.20-2.91, P = 0.006) compared with those without both HPR and CYP2C19 LoF/LoF. There was no effect of interaction between HPR and CYP2C19 genotype on the primary outcome (P = 0.424). Adding combined HPR and CYP2C19 genotype to the conventional model had an incremental influence in predicting MACCE and stent thrombosis. Compared to the model including HPR or CYP2C19 genotype alone, a combination model significantly improved the risk stratification for stent thrombosis but not MACCE. In DES-treated East Asian patients, the combined evaluation of PFT results and CYP2C19 genotyping might improve risk prediction of ischemic events during clopidogrel treatment.

Use of Tirofiban to Prevent Ischemic Events in Patients with CYP2C19 Loss-of-Function Alleles during Flow Diversion of Intracranial Aneurysm: A Multicenter Cohort Study.

To analyze the effect of tirofiban on ischemic events in CYP2C19 loss-of-function (LOF) allele carriers during pipeline embolization device (PED) implantation. Demographic information, imaging data, ischemic complications, CYP2C19 genotyping, and platelet function test results were collected from patients with PED-treated intracranial aneurysms at three centers. Multivariate logistic regression was used to analyze risk factors for ischemic events. Patients were grouped according to LOF alleles and antiplatelet drugs, the baseline information of LOF allele carriers and non-carriers were compared, and the efficacy of tirofiban was analyzed by comparing the incidence of ischemic events in each group. In total, 278 patients were included in the study, 24 of whom had an ischemic event. 157 (56.5%) patients carried the LOF allele and were more likely to develop resistance to clopidogrel (P < 0.001) and hypertension (P = 0.010). Multivariate logistic regression analysis revealed that the independent risk factors for ischemic events were age of > 55years (OR = 3.308, P = 0.028), LOF alleles (OR = 3.960, P = 0.036), and clopidogrel nonresponsiveness (OR = 3.301, P = 0.014). For LOF allele carriers, prophylactic use of tirofiban after PED implantation helped to reduce ischemic events (4.3% vs. 16.4%, P = 0.039). This study supports CYP2C19 genotyping before flow diversion because LOF alleles increase the risk of ischemic events. Prophylactic use of tirofiban may help reduce ischemic events in LOF allele carriers.

P212 EFFICACY AND SAFETY OF GENOTYPE–GUIDED AND PLATELET FUNCTION TEST–GUIDED ANTI–P2Y12 THERAPY IN PATIENTS UNDERGOING PCI: A META–ANALYSIS OF RCTS

Abstract Clopidogrel is the most commonly used anti–P2Y12 drug in DAPT. Impaired pharmacological response and antithrombotic efficacy associated with cytochrome–P450 and/or ABCB1 gene mutations is observed in about 1/3 of treated patients. To circumvent this problem, guided therapy has been tested, based on either identification of predisposing gene mutations or results of platelet function tests (PFTs). Patients with with predisposing gene mutations or high platelet reactivity on clopidogrel (HPR) were treated with alternative, potentially more effective regimens: higher clopidogrel doses, prasugrel, ticagrelor, or additional cylostazol. In this meta–analysis, we tested the efficacy and safety of these two different strategies of guided therapy separately. We searched relevant articles published in English until October 1th 2022 on MEDLINE, Embase and Central. Articles included all RCTs comparing standard anti–P2Y12 therapy (ST) versus genotype–guided or PFTs–guided anti–P2Y12 therapy in patients with acute coronary syndromes (ACS) or chronic coronary artery disease (CCAD) undergoing PCI. Two reviewers independently assessed study eligibility and risk of bias, and extracted data. Hazard ratios with 95% CI were calculated based on fixed effects models. Efficacy outcomes comprised major adverse cardiovascular events (MACE) as defined in each study. Main safety outcome included major bleedings (MB) according to BARC. Different sub–analyses were also performed based on type of anti–P2Y12 drug in ST, type of alternative drug, type of PFT, patients’ ethnicity, prevalence of ACS. We retrieved 6 RCTs testing genotype–guided anti–P2Y12 therapy on 10443 patients and 14 RCTs testing PFTs–guided anti–P2Y12 therapy on 11596 patients. MACE were lower in genotype–guided therapy than in ST, RR 0.68 (95% CI, 0.49–0.94) while MB did not significantly differ between the two groups, RR 0.88 (95% CI, 0.63–1.23). MACE and MB did not significantly differ between PFTs–guided anti–P2Y12 therapy and ST: RR 0.83 (95% CI, 0.58–1.18) and 1.24 (95% CI, 1.00–1.53), respectively. Sub–analyses revealed that MACE were lower in PFTs–guided anti–P2Y12 therapy compared to ST in patients of Asian descent. In conclusion, gentotype–guided anti–P2Y12 therapy reduced the incidence of MACE without increasing MB, compared with ST, in patients with ACS or CCAD undergoing PCI; in contrast, PFTs–guided anti–P2Y12 therapy did not affect the incidence of MACE or MB in these patients.

Toward Personalized DAPT: Is There an Inter-Manufacturer Difference in Generic Clopidogrel Response?

To compare rates of clopidogrel response among patients receiving medication produced by 2 different manufacturers after acute coronary syndrome (ACS) and/or percutaneous coronary intervention. This quality-improvement project included 515 adult patients receiving clopidogrel for ACS or ischemic heart disease and referred for coronary angiography/ percutaneous coronary intervention. The project was divided into 2 phases: (1) retrospective collection of baseline data (April 2019-October 2020); and (2) two 12-week, prospective phases in which all clopidogrel in the hospital was restricted to a single manufacturer at a time (November 2020-May 2021). The primary outcome was clopidogrel response measured by platelet function testing, defined as adenosine diphosphate (ADP) response <40% on light transmission aggregometry. Of 515 total patients included in both phases (mean age, 64.5 ± 11.4 years; 351 men [68.2%]; 450 with ACS [87.4%]), 52% were found to be clopidogrel responders based on results of platelet function testing. Among 135 patients in the prospective phase, there was a significantly lower proportion of patients who were clopidogrel responders in the Manufacturer 1 group compared with the Manufacturer 2 group (34.8% vs 55.1%, respectively; P=.03). After adjustment for age, sex, body mass index, aspirin response, therapeutic hypothermia, left heart catheterization indication, clopidogrel loading dose, time between loading dose and lab measurement, and manufacturer, aspirin response (odds ratio 0.96; 95% confidence interval, 0.95-0.97; P<.001) and manufacturer (odds ratio, 2.45; 95% confidence interval, 1.18-5.22; P=.02) were associated with clopidogrel response. In a large public hospital, we observed that pharmacodynamic response to clopidogrel varied by drug manufacturer. Further investigation and/or regulation is needed to minimize inter-manufacturer variability.

Is there an inter-manufacturer difference in generic clopidogrel response?

Abstract Background Differences in platelet aggregation response to generic clopidogrel by manufacturer has not been investigated. Purpose Compare rates of clopidogrel response among patients receiving medication produced by two different manufacturers after acute coronary syndrome and/or percutaneous coronary intervention. Methods This quality improvement project included 515 adult patients receiving clopidogrel for acute coronary syndrome or ischemic heart disease and referred for coronary angiography/percutaneous coronary intervention at a large, public hospital. The project was divided into two phases: 1. retrospective collection of baseline data; 2. two 12-week, prospective phases in which all clopidogrel in the hospital was restricted to a single manufacturer at a time. The primary outcome was clopidogrel response measured by platelet function testing defined as ADP response &amp;lt;40% on light transmission aggregometry between two manufacturer groups. Aspirin response defined as arachidonic acid response &amp;lt;20% was also measured. Results Of 515 total patients included in both phases (mean [SD] age, 64.5 [11.4] years; 351 [68.2%] men; 450 [87.4%] ACS), 52% were found to be clopidogrel responders based on results of platelet function testing (Table 1 – select variables). Among 135 patients in the prospective phase, there was a significantly lower proportion of patients who were clopidogrel responders in the Manufacturer 1 group compared to the Manufacturer 2 group (34.8% vs. 55.1%, p=0.03) (Table 2 – select variables). After adjustment for age, sex, BMI, aspirin response, therapeutic hypothermia, LHC indication, clopidogrel loading dose, time between loading dose and lab measurement, and manufacturer, aspirin response (OR [95% CI]: 0.96 [0.95–0.97], p&amp;lt;0.001) and manufacturer (OR [95% CI]: 2.45 [1.18–5.22], p=0.02) were associated with clopidogrel response. Conclusions In a large public hospital, we observed that pharmacodynamic response to clopidogrel varied by drug manufacturer. Further investigation and/or regulation is needed to minimize inter-manufacturer variability. Funding Acknowledgement Type of funding sources: None.

Characterization of antiplatelet response to low-dose cangrelor utilizing platelet function testing in neuroendovascular patients.

The optimal antiplatelet therapy for emergent neuroendovascular stenting is uncertain. Cangrelor is an intravenous P2Y12 inhibitor that is an attractive option due its favorable pharmacokinetic profile and ease of measurability but optimal dosing remains unclear. The primary objective of this study is to characterize the dose response of low dose cangrelor (<2mcg/kg/min) with the utilization of platelet function testing (PFT). A retrospective review of all patients treated with cangrelor for either procedural stenting or bridging was conducted between January 1st, 2019 and October 31st, 2020. Seventy-two patients met inclusion criteria. An in-depth analysis of dose response to low dose cangrelor based on PFT was performed. Neuroendovascular patients treated with cangrelor. Albany Medical Center Hospital. Patients who underwent procedural stenting were given a bolus of 5mcg/kg and an initial infusion rate of either 0.75mcg/kg/min or 1mcg/kg/min. Patients who were bridged with cangrelor were administered an initial infusion rate of 0.75 mcg/kg/min or 1mcg/kg/min. Twelve patient's doses were titrated to achieve a platelet reactivity unit (PRU) between 50-150; three patient's doses were titrated multiple times. Based on initial PFT results, utilizing the 1mcg/kg/min maintenance dose resulted in more patients being in the acceptable (10-180) and desired (50-150) PRU range than the 0.75mcg/kg/min dose (47% vs 56% and 70% vs 80%, respectively). Final recorded PRU results showed that 64% of patients had PRUs in the optimal range (50-150) and 88% of patients had PRUs in the desire range (10-180). Utilizing low doses of cangrelor with platelet function testing is an option during emergent neuroendovascular stenting and bridging. Cangrelor demonstrates significant variability in response at low doses and exhibits a dose response relationship when PFT is utilized.

The routine use of platelet function tests in elective coronary artery bypass grafting: A prospective observational trial.

Preoperative use of platelet function tests contributes to the decrease of re-intervention rate due to bleeding and the necessity of transfusion in coronary artery bypass grafting (CABG) patients. The aim was to investigate the predictive value and to justify routine preoperative use of multiple electrode aggregometry in these patients. A prospective observational trial which included 416 consecutive patients subjected to elective isolated CABG was conducted. The Multiplate® test was used to assess platelet function. Platelet function test results, postoperative blood loss, and transfusion requirements were compared between high and low bleeding risk patients. Receiver operating characteristic analysis was performed toassess the sensitivity and specificity of the arachidonic acid (ASPI)and adenosine di-phosphate high sensitive (ADPHS)tests. ADPHS and ASPI test results significantly predicted total bleeding > 1000 ml(AUC, 0.685, p < .001; 0.695, p = .039). Sensitivity and specificity were 62.9% and 40.0%, for ADPHS ≤602, and 70.8% and 41.8%, for ASPI ≤ 453. The sensitivity and specificity of cut-off values recommended by the manufacturer were 84.2% and 40.0% for ADPHS ≤ 500, while for ASPI < 600 the values were 54.7% and 62.2%. More platelets and cryoprecipitate were transfused in patients with ADPHS ≤ 602.5 (p < .001; p = .035). Patients with ADPHS ≤ 500 had a higher rate of red blood count, platelet and cryoprecipitate transfusion (p<.001p<.001; p = .013).The manufacturer's ASPI test cut-off values showed no statistically significant prediction for a higher transfusion rate. Preoperative platelet function tests should be conducted systematically for all elective CABG patients who were on dual antiplatelet therapy after adjusting test cut-off values for each population.

Platelet Function Test Use for Patients with Coronary Artery Disease in the Early 2020s.

In the field of antithrombotics, precision medicine is of particular interest, as it may lower the incidence of potentially life-threatening side effects. Indeed, antiplatelet drugs such as P2Y12 inhibitors are one of the most common causes of emergency admissions for drug-related adverse events. The last ten years have seen a continuous debate on whether platelet function tests (PFTs) should be used to tailor antiplatelet drugs to cardiovascular patients. Large-scale randomized studies investigating the escalation of antiplatelet therapies according to the results of PFTs were mostly negative. Potent P2Y12 inhibitors are recommended as a first-line treatment in acute coronary syndrome patients, bringing the bleeding risk at the forefront. De-escalation from prasugrel or ticagrelor to clopidogrel is now considered, with or without the use of a PFT. This review covers recent advances in escalation and de-escalation strategies based on PFTs in various clinical settings. It also describes the main features of the most popular platelet function tests as well as the potential added value of genetic testing. Finally, we detail practical suggestions on how PFTs could be used in clinical practice.

Variability of Platelet Reactivity on Antiplatelet Therapy in Neurointervention Procedure.

As more intracranial aneurysms and other cerebrovascular pathologies are treated with neurointervention procedure, thromboembolic events that frequently lead to serious neurological deficit or fatal outcomes are increasing. In order to prevent the thromboembolic events, antiplatelet therapy is used in most procedures including coil embolization, stenting, and flow diversion. However, because of variable individual pharmacodynamics responses to antiplatelet drugs, especially clopidogrel, it is difficult for clinicians to select the adequate antiplatelet regimen and its optimal dose. This article reviews the neurointervention literature related to antiplatelet therapy and suggests a strategy for tailoring antiplatelet therapy in individual patients undergoing neurointervention based on the results of platelet function testing.

Whole blood aggregometry prior to Pipeline embolization device treatment of intracranial aneurysms: defining an optimal platelet inhibition cutoff value for clopidogrel.

Dual antiplatelet therapy is required for the treatment of intracranial aneurysms with the Pipeline embolization device (PED). Platelet function testing (PFT) is often used to assess the efficacy of the antiplatelet regimen prior to PED placement. The optimal impedance values for whole blood aggregometry in this setting have not been defined. A retrospective review of a prospectively maintained database was performed for the years 2011-2015 to identify patients with intracranial aneurysms treated with the PED who underwent pretreatment PFT using whole blood aggregometry. Antiplatelet therapy was not altered based on PFT results; all patients remained on standard doses of aspirin and clopidogrel. Clinical, radiographic, and laboratory data were analyzed to identify the optimal cutoff impedance value for clopidogrel responsiveness using the receiver operating characteristic curve and Youden's index. Forty-nine patients underwent 53 endovascular procedures for the treatment of 76 aneurysms using the PED. The majority of these aneurysms were located in the anterior circulation (90.8%) and affected the internal carotid artery (89.5%). Patients in 30 procedures (56.6%) were identified as clopidogrel responders based on the manufacturer cutoff value (< 6 Ω). Thromboembolic complications occurred in 13 (24.5%) procedures; patients in 6 (11.3%) cases were symptomatic and those in 3 (5.7%) cases had ischemic strokes. Eleven of the 13 (84.6%) thromboembolic complications occurred in clopidogrel nonresponders. An impedance value of ≥ 6 Ω was independently associated with thromboembolic complications. The optimal electrical impedance value was identified as ≥ 6 Ω (sensitivity 84.6%, specificity 70.0%, area under the curve 0.77) for identifying clopidogrel nonresponders. Thromboembolic complications are more common following PED placement in patients who do not respond adequately to clopidogrel. Clopidogrel nonresponders can be identified using pretreatment whole blood aggregometry. The optimal cutoff value to categorize a patient as a clopidogrel nonresponder when using whole blood aggregometry is ≥ 6 Ω.

Platelet function testing: dead or alive

Background High on-treatment platelet reactivity (HTPR) to antiplatelet medication leads to ischemic events, whereas low on-treatment platelet reactivity (LTPR) increases bleeding risk. However, various trials have failed to demonstrate superiority of tailored antiplatelet regimens (ARCTIC, ANTARCTIC, Trigger-PCI, and GRAVITAS). TROPICAL-ACS was the first study that demonstrated the benefit of tailoring antiplatelet medication according to platelet function analysis. A potential reason may be that different platelet function assays were used in these trials. Objectives To evaluate whether the results of platelet function tests are comparable. Patients/Methods We tested three commonly used assays - light transmission aggregometry (LTA), (Multiplate impedance aggregometry [MP]), and vasodilator-stimulated phosphoprotein phosphorylation assay (VASP) - in 23 patients receiving dual antiplatelet therapy with aspirin and clopidogrel. Results With LTA, HTPR occurred in 57% of patients; with VASP, it occurred in 43% of patients; and with MP, it occurred in 13% of patients. According to LTA, only 35% of patients were in the therapeutic window; according to VASP, 57% of patients were in the therapeutic window; and according to MP, 48% of patients were in the therapeutic window. With LTA, LTPR occurred in 9% of patients; with VASP, it occurred in 0% of patients; and with MP, it occurred in 39% of patients. Therefore, the prevalences of HTPR and LTPR differed significantly between assays. Remarkably, in 17% of patients, one assay showed HTPR whereas another showed LTPR. Conclusions The results of different platelet function assays differ substantially. Up to now, only TROPICAL-ACS had demonstrated a benefit of tailoring antiplatelet medication according to platelet function analysis. Future trials are needed to evaluate whether the platelet function assay used in TROPICAL-ACS is the 'correct' one and revives platelet function testing.

Safety of Prasugrel loading in ruptured blister like aneurysm treated with a Pipeline device.

Blister like aneurysm (BLA) is extremely challenging to treat; endoluminal reconstruction has emerged as the most promising treatment method. When to treat after the ictus, the timing of administration of antiplatelet and causal relationship between platelet function testing results and thrombo-embolism is unclear. We theorized that Prasugrel with a lower incidence of resistance may be a safe suitable alternative to clopidogrel in patients treated with a flow diverter(FD). Prospectively collected data from consecutive patients treated for a ruptured blister with an FD was reviewed. Device deployment was timed to be at 2 h following Prasugrel loading. Thrombo-embolic and hemorrhagic complications, and occlusion rates were documented. Nine patients were included. Most were females (55%); the median age was 55 (43, 65). The median Fischer grade was 3 (2, 4). A single pipeline device was deployed in all within 24 h of admission; the median time from ictus to device deployment was 4 days (2, 30). There were no thrombo-embolic or hemorrhagic complication. Complete occlusion was noted in 89% (n = 9). Prasugrel loading timed 2 h prior to stent delivery did not increase thrombo-embolic or hemorrhagic complications. Single stent that is well apposed against the wall appears to be an effective treatment strategy to treat BLA. Advances in knowledge: Treatment of acutely ruptured BLA with a single pipeline device deployed at 2 h after Prasugrel loading appears to be safe.

Genome-wide and candidate gene approaches of clopidogrel efficacy using pharmacodynamic and clinical end points—Rationale and design of the International Clopidogrel Pharmacogenomics Consortium (ICPC)

The P2Y12 receptor inhibitor clopidogrel is widely used in patients with acute coronary syndrome, percutaneous coronary intervention, or ischemic stroke. Platelet inhibition by clopidogrel shows wide interpatient variability, and high on-treatment platelet reactivity is a risk factor for atherothrombotic events, particularly in high-risk populations. CYP2C19 polymorphism plays an important role in this variability, but heritability estimates suggest that additional genetic variants remain unidentified. The aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify genetic determinants of clopidogrel pharmacodynamics and clinical response. Based on the data published on www.clinicaltrials.gov, clopidogrel intervention studies containing genetic and platelet function data were identified for participation. Lead investigators were invited to share DNA samples, platelet function test results, patient characteristics, and cardiovascular outcomes to perform candidate gene and genome-wide studies. In total, 17 study sites from 13 countries participate in the ICPC, contributing individual patient data from 8,829 patients. Available adenosine diphosphate-stimulated platelet function tests included vasodilator-stimulated phosphoprotein assay, light transmittance aggregometry, and the VerifyNow P2Y12 assay. A proof-of-principle analysis based on genotype data provided by each group showed a strong and consistent association between CYP2C19*2 and platelet reactivity (P value=5.1 × 10-40). The ICPC aims to identify new loci influencing clopidogrel efficacy by using state-of-the-art genetic approaches in a large cohort of clopidogrel-treated patients to better understand the genetic basis of on-treatment response variability.

Platelet Function Testing: A Role for Personalised Therapy in Coronary Disease

Whilst there exist general guidelines regarding administration of antiplatelet therapy to prevent thrombotic events in patients with cardiovascular disease, the optimal therapy for a particular individuals in particular settings remains unclear. For patients with acute coronary syndrome (ACS) or those undergoing percutaneous coronary intervention (PCI), the use of potent antiplatelet agent combinations is recommended. However, some patients continue to have thrombotic events or experience bleeding events, which have been linked to the widely known variability in individual response to antiplatelet therapy, particularly to clopidogrel. Platelet function tests (PFTs) have been used in an attempt to predict ongoing thrombotic risk and to monitor the response to antiplatelet drugs. Although the cause of both thrombotic and bleeding events is multifactorial in origin, the observation that enhanced platelet reactivity is associated with recurrent thrombosis and reduced platelet reactivity with bleeding has raised hopes of identifying those at risk through the use of PFTs. Consequently, there was initial enthusiasm for the use of PFTs to guide individualized antiplatelet therapy. Few studies have been conducted, but the alteration of treatment based on the results of PFTs has not been shown to influence outcomes. Inherent limitations of the studies utilizing PFTs may indeed have contributed to the failure of this approach. Further, there are important limitations to the relevance of currently available PFTs to the in vivo situation. Refinement of existing techniques to allow the use of native blood, high shear, use of a global stimulus instead of individual agonists, assessment of thrombin generation by activated platelets, and assessment of fibrinolytic potential, should be considered to make these tests more physiological. Perhaps the results of PFTs need to be considered in combination with other prognostic factors in a more complex prediction model. The present manuscript provides an overview on the role of and value of available PFTs in contemporary clinical practice, with particular focus on possible individualized antiplatelet regimens in high risk patients.

Parent vessel occlusion after Pipeline embolization of cerebral aneurysms of the anterior circulation.

OBJECTIVE The Pipeline Embolization Device (PED) is now a well-established option for the treatment of giant or complex aneurysms, especially those arising from the anterior circulation. Considering the purpose of such treatment is to maintain patency of the parent vessel, postembolization occlusion of the parent artery can be regarded as an untoward outcome. Antiplatelet therapy in the posttreatment period is therefore required to minimize such events. Here, the authors present a series of patients with anterior circulation aneurysms treated with the PED who subsequently experienced parent vessel occlusion (PVO). METHODS The authors performed a retrospective review of all anterior circulation aneurysms consecutively treated at a single institution with the PED through 2014, identifying those with PVO on follow-up imaging. Aneurysm size and location, number of PEDs used, and follow-up digital subtraction angiography results were recorded. When available, pre- and postembolization platelet function testing results were also recorded. RESULTS Among 256 patients with anterior circulation aneurysms treated with the PED, the authors identified 8 who developed PVO after embolization. The mean aneurysm size in this cohort was 22.3 mm, and the number of PEDs used per case ranged from 2 to 10. Six patients were found to have asymptomatic PVO discovered incidentally on routine follow-up imaging between 6 months and 3 years postembolization, 3 of whom had documented "delayed" PVO with prior postembolization angiograms confirming aneurysm occlusion and a patent parent vessel at an earlier time. Two additional patients experienced symptomatic PVO, one of which was associated with early discontinuation of antiplatelet therapy. CONCLUSIONS In this large series of anterior circulation aneurysms, the authors report a low incidence of symptomatic PVO, complicating premature discontinuation of postembolization antiplatelet or anticoagulation therapy. Beyond the subacute period, asymptomatic PVO was more common, particularly among complex fusiform or very large-necked aneurysms, highlighting an important phenomenon with the use of PED for the treatment of anterior circulation aneurysms, and suggesting that extended periods of antiplatelet coverage may be required in select complex aneurysms.

Assessment of platelet function in healthy cats in response to commonly prescribed antiplatelet drugs using three point-of-care platelet function tests.

Objectives The objective was to determine if decreased platelet function could be detected after treatment with aspirin and/or clopidogrel in healthy cats using three point-of-care platelet function tests that evaluate platelet function by different methods: Multiplate (by impedance), Platelet Function Analyzer 100 (by mechanical aperture closure) and Plateletworks (by platelet counting). Methods Thirty-six healthy cats were randomly assigned to receive one of three oral treatments over an 8 day period: (1) aspirin 5 mg q72h; (2) aspirin 20.25 mg q72h; or (3) clopidogrel 18.75 mg q24h. Cats treated with 5 and 20.25 mg aspirin also received clopidogrel on days 4-8. Platelet aggregation in response to adenosine diphosphate and collagen ± arachidonic acid was assessed on days 1 (baseline), 4 and 8. Aspirin and clopidogrel metabolites were measured by high-performance liquid chromatography. Platelet function in response to treatment was analyzed by ANCOVA, linear regression and Spearman correlation. Results The only solitary aspirin effect was detected using Plateletworks with collagen in cats treated with 20.25 mg. The only effect detected by Multiplate was using arachidonic acid in cats treated with both aspirin 20.25 mg and clopidogrel. All clopidogrel treatment effects were detected by Platelet Function Analyzer 100, Plateletworks (adenosine diphosphate) and Plateletworks (collagen). Drug metabolites were present in all cats, but concentrations were minimally correlated to platelet function test results. Conclusions and relevance Platelet Function Analyzer 100 and Plateletworks using adenosine diphosphate ± collagen agonists may be used to detect decreased platelet function in response to clopidogrel treatment. Either aspirin is not as effective an antiplatelet drug as clopidogrel, or the tests used were not optimal to measure aspirin effect. Cats with heart disease are commonly prescribed antiplatelet drugs to decrease the risk of aortic thromboembolism. Platelet Function Analyzer 100 and Plateletworks may be useful for confirming clopidogrel treatment in these cats.

Simultaneous subacute coronary artery stent thrombosis in a carrier of two CYP2C19 loss–of function polymorphisms (*2/*3)

Simultaneous subacute coronary artery stent thrombosis in a carrier of two CYP2C19 loss–of function polymorphisms (*2/*3)

Platelet Function Tests.

Traditionally developed for diagnosis of bleeding disorders, platelet function assays have become increasingly used in basic research on platelet physiology, in phenotype-genotype associations in bleeding disorders, in drug development as surrogate endpoints of efficacy of new antiplatelet therapy, and to an extent, in the monitoring of antiplatelet therapy in clinical practice to predict thrombotic and bleeding risk. A multiplicity of platelet function assays is available to measure the level of platelet activity in various settings. These include assays that are restricted to a specialized laboratory as well as point-of-care instruments meant to investigate platelet function at patient bedside. Unlike tests that determine a defined quantity or measurement of a clinical biomarker (e.g., cholesterol or blood pressure), platelet function testing assesses the dynamics of living cells, which immediately presents a series of unique problems to any laboratory or clinic. This article presents currently used platelet function assays and discusses important variables to take into account when performing these assays, including preanalytical issues and difficulties in interpreting platelet function test results.

EVALUATION OF PLATELET AGGREGATION IN CLINICAL PRACTICE

Evaluation of platelet function with subsequent modification of antiplatelet therapy regimen is one of the areas of personalized medicine. Analysis of the causes of inadequate antiplatelet action of clopidogrel, the association of residual platelet reactivity with clinical outcomes and a review of the research on the change of antiplatelet therapy in patients with ischemic heart disease after percutaneous interventions based on the results of platelet function testing, were the aim of this review.