Resistance to dual antiplatelet therapy (DAPT), including aspirin and clopidogrel, in patients who have undergone percutaneous coronary intervention (PCI) leads to the inability to prevent thrombotic complications. The present study aimed to evaluate early resistance to aspirin and clopidogrel in patients following PCI using the VerifyNow test and associated factors. A total of 50 patients diagnosed with acute coronary syndromes (ACS) who underwent emergency PCI and received DAPT were recruited in the present study. The detection of resistance to aspirin and clopidogrel was performed using the VerifyNow system. Resistance to aspirin was determined with VerifyNow Aspirin >550 aspirin reaction units (ARU). Resistance to clopidogrel was determined with VerifyNow P2Y12 >208 P2Y12 reaction units (PRU). The resistance rate to aspirin was 14%, while the resistance rate to clopidogrel was higher, at 34%. There were 2 patients with resistance to aspirin and clopidogrel (4%). Univariable logistic regression analysis revealed that diabetes, the use of β-blockers, and low levels of hemoglobin and hematocrit were associated with resistance to clopidogrel. Following multivariable logistic regression analysis, only the use of β-blockers was truly associated with resistance to clopidogrel. On the whole, the results of the present study may also prove to be helpful in the selection of therapeutic drugs for patients undergoing PCI and who are diagnosed with ACS.

BACKGROUND: Dual antiplatelet therapy is used to reduce the risk of thromboembolic complications in neuroendovascular surgery. However, the predictive utility of preoperative platelet-sensitivity testing for decreasing bleed risk in patients undergoing endovascular neurointervention remains unclear.
OBJECTIVE: We conducted a systematic review and meta-analysis to illustrate the association between platelet response and risk of hemorrhagic complications from neuroendovascular surgery, examine the efficacy of the VerifyNow platelet reactivity unit (PRU) assay in predicting hemorrhagic outcomes, and assess whether a clinically useful threshold for platelet response can be defined to standardize guidelines.
METHODS: PubMed, Embase, and Scopus were searched. Articles were screened for relevance by title and abstract, followed by full text.
RESULTS: Of 735 resultant articles, 17 studies of 2084 patients undergoing neuroendovascular intervention were included. Diagnoses included both intracranial and extracranial pathologies, of which 37.8% were treated with flow diversion, 22.4% with stent-assisted coil embolization, 14.3% with intracranial stenting, 12.8% with simple coil embolization, 5.8% with balloon-assisted coil embolization, 2.0% with extracranial stenting, and 4.8% with an alternate method. Precisely, 52.9% (9 out of 17) of studies determined platelet hyperresponse to be an independent predictor of postoperative hemorrhagic complications, with 11.8% (2 out of 17) of studies reporting a similar but non-statistically significant trend. 35.3% (6 out of 17) of studies found no relationship between platelet response and postoperative hemorrhagic complications. The estimated clinical threshold for PRU to prevent hemorrhagic complications varied considerably across studies (range: <46-118 PRU). Meta-analysis found platelet hyperresponse to have more than a 3-fold increased risk of hemorrhagic complications compared to normoresponders (relative risk = 3.2, p = 0.001).
CONCLUSIONS: Although this meta-analysis shows the predictive utility of the P2Y12 assay for postoperative hemorrhagic complications in neuroendovascular surgery, the optimal therapeutic threshold for minimizing bleeding risk is still uncertain. To better understand the utility of the P2Y12 assay in the perioperative period, further prospective research is needed.

BACKGROUND: Despite the heavily debated use of routine platelet-function testing, the VerifyNow Platelet Reactivity Unit (PRU) assay has been increasingly adopted as standard of care for assessing risk of postoperative thromboembolic complications of neuroendovascular surgery.
OBJECTIVE: We conducted a systematic review and meta-analysis to examine the relationship between platelet response and risk of ischemic events from neuroendovascular surgery, assess the efficacy of point-of-care platelet-function testing in predicting thromboembolic outcomes, and assess whether a clinically useful threshold for platelet response can be defined in order to standardize guidelines.
METHODS: PubMed, Embase, and Scopus were searched. Following deduplication, articles were first screened for relevance by title and abstract, followed by full text.
RESULTS: Of 735 resultant articles, 22 studies consisting of 3266 patients undergoing neuroendovascular intervention were included. Diagnoses included both intracranial and extracranial pathologies, of which 45.8% were treated with flow diversion, 16.4% with stent-assisted coil embolization, 15.8% with intracranial stenting, 12.0% with simple coil embolization, 3.4% with balloon-assisted coil embolization, 3.6% with extracranial stenting, and 3.0% with an alternate method. 54.5% (12/22) of studies determined platelet hyporesponse to be an independent predictor of postoperative thromboembolic complications, with 27.3% (6/22) of studies reporting a similar, but non-statistically significant trend. 18.2% (4/22) of studies found no relationship between platelet response and postoperative thromboembolic complications. The estimated clinical threshold for PRU to prevent thromboembolic complications varied greatly across studies (Range: > 144-295 PRU). Meta-analysis found platelet hyporesponse to have a 2.23-fold increased risk of thromboembolic complications compared to normoresponders (RR = 2.23, P = 0.03).
CONCLUSIONS: While PRU demonstrates a significant predictive value for postoperative thromboembolic complications of neuroendovascular surgery, the target therapeutic threshold for minimizing ischemic events remains unclear. Further studies, such as large multicenter cohorts of the existing data, are needed to standardize guidelines.

BACKGROUND: Dual antiplatelet therapy (DAPT) is standard care for intracranial stenting to prevent thrombotic complications. Clopidogrel resistance has resulted in patients receiving newer P2Y12 inhibitors like Prasugrel, which may reduce thrombotic complications but could increase haemorrhagic complications. This study, utilising platelet reactivity testing, compared thrombotic and haemorrhagic complications associated with Clopidogrel or 20 mg Prasugrel loading in patients treated with flow diverters (FD) for intracranial aneurysms.
METHODS: We retrospectively analysed prospectively collected data from 225 consecutive FD procedures. All patients received aspirin. 147 cases received Clopidogrel and 82 received Prasugrel. All patients had VerifyNow testing before the procedure.
RESULTS: P2Y12 non-responders were significantly more likely to have thrombotic complications than responders and hyper-responders (7% vs. 2%, p = 0.01). Low-dose Prasugrel resulted in a significantly lower rate of non-responders when compared with Clopidogrel (7% vs. 25%, p < 0.01). We found no statistically significant difference in rates of haemorrhage between the Clopidogrel and Prasugrel groups (2.4% vs. 3.9%, p = 0.47). There were 12 complications (≤7 days) in the Clopidogrel group versus 6 in the Prasugrel group (9% vs. 7.8%, respectively, p = 0.91) and a non-significant reduction in thrombotic complications in the Prasugrel group (5.2% vs. 3.9%, p = 0.88). No significant difference was shown in long-term complications between the groups (p = 0.33).
CONCLUSIONS: These results support the use of platelet reactivity testing and the safety of low-dose Prasugrel for FD treatment of intracranial aneurysms.

In the late 1990s, the antithrombotic antiplatelet agent, clopidogrel, a P2Y12 inhibitor, was introduced. Around the same time, there was an increase in a number of new methods to measure platelet function (e.g., PFA-100 in 1995), and this has continued. It became evident that not all patients responded to clopidogrel in the same way and that some patients had a relative \"resistance\" to therapy, termed \"high on-treatment platelet reactivity.\" This then led to some publications to advocate platelet function testing being used for patients on antiplatelet therapy. Platelet function testing was also suggested for use in patients awaiting cardiac surgery after stopping their antiplatelet therapy as a way of balancing thrombotic risk pre-surgery and bleeding risk perioperatively. This chapter will discuss some of the commonly used platelet function tests used in these settings, particularly those that are sometimes referred to as point-of-care tests or that require minimal laboratory sample manipulation. The latest guidance and recommendations for platelet function testing will be discussed following several clinical trials looking at the usefulness of platelet function testing in these clinical settings.

BACKGROUND: von Willebrand Factor (vWF) is a key protein mediating platelet adhesion on the surface of damaged endothelia. To the best of our knowledge, no trial exists that investigated the effect of platelet transfusion in combination with the administration of balanced vWF in severe blood loss, despite being widely used in clinical practice. The Basel Will-Plate study will investigate the impact of the timely administration of balanced vWF (1:1 vWF and FVIII) in addition to platelet transfusion on the need for blood and coagulation factor transfusion in patients admitted to the intensive care unit (ICU) who suffer from severe bleeding. The study hypothesis is based on the assumption that adding balanced vWF to platelets will reduce the overall need for transfusion of blood products compared to the transfusion of platelets alone.
METHODS: The Will-Plate study is an investigator-initiated, single-centre, double-blinded randomised controlled clinical trial in 120 critically ill patients needing platelet transfusion. The primary outcome measure will be the number of fresh frozen plasma (FFP) and red blood cell (RBC) transfusions according to groups. Secondary outcome measures include the number of platelet concentrates transfused within the first 48 h after treatment of study medication, quantity of blood loss in the first 48 h after treatment with the study medication, length of stay in ICU and hospital, number of revision surgeries for haemorrhage control, ICU mortality, hospital mortality, 30-day mortality and 1-year mortality. Patients will be followed after 30 days and 1 year for activities of daily living and mortality assessment. The sample size was calculated to detect a 50% reduction in the number of blood products subsequently transfused within 2 days in patients with Wilate® compared to placebo.
BACKGROUND: This study has been approved by the Ethics Committee of Northwestern and Central Switzerland and will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the ICH-GCP or ISO EN 14155 (as far as applicable) and all national legal and regulatory requirements. The study results will be presented at international conferences and published in a peer-reviewed journal.
BACKGROUND: ClinicalTrials.gov NCT04555785.
METHODS: Clinical Study Protocol Version 2, 01.11.2020. Registered on Sept. 21, 2020.

Clinical significance of increased clopidogrel response measured by VerifyNow P2Y12 assay is unclear; management guidelines are lacking in the context of neuroendovascular intervention. Our objective was to assess whether increased clopidogrel response predicts complications from endovascular aneurysm treatment requiring dual antiplatelet therapy. A single-institution, 9-year retrospective study of patients undergoing endovascular treatments for ruptured and unruptured aneurysms requiring aspirin and clopidogrel was conducted. Patients were grouped according to preoperative platelet inhibition in response to clopidogrel measured by the VerifyNow P2Y12 assay (VNP; P2Y12 reactivity units, PRU). Demographic and clinical features were compared across groups. Hemorrhagic complication rates (intracranial, major extracranial, minor extracranial) and thromboembolic complications (in-stent stenosis, stroke/transient ischemic attack) were compared, controlling for potential confounders and multiple comparisons. Data were collected from 284 patients across 317 procedures. Pre-operative VNP assays identified 9 % Extreme Responders (PRU ≤ 15), 13 % Hyper-Responders (PRU 16-60), 62 % Therapeutic Responders (PRU 61-214), 16 % Hypo-Responders (PRU ≥ 215). Increased response to clopidogrel was associated with increased risk of any hemorrhagic complication (≤60 PRU vs > 60 PRU; 39 % vs 24 %, P = 0.050); all intracranial hemorrhages occurred in patients with PRU > 60. Thromboembolic complications were similar between therapeutic and subtherapeutic patients (<215 PRU vs ≥ 215 PRU; 15 % vs 16 %, P = 0.835). Increased preoperative clopidogrel response is associated with increased rate of extracranial hemorrhagic complications in endovascular aneurysm treatments. Hyper-responders (16-60 PRU) and Extreme Responders (≤15 PRU) were not associated with intracranial hemorrhagic or thrombotic complications. Hypo-responders who underwent adjustment of antiplatelet therapy and neurointerventions did not experience higher rates of complications.

UNASSIGNED: Platelet function testing to monitor antiplatelet therapy is important for reducing thromboembolic complications, yet variability across testing methods remains challenging. Here we evaluated the agreement of four different testing platforms used to monitor antiplatelet effects of aspirin (ASA) or P2Y12 inhibitors (P2Y12-I).
UNASSIGNED: Blood and urine specimens from 20 patients receiving dual antiplatelet therapy were analyzed by light transmission aggregometry (LTA), whole blood aggregometry (WBA), VerifyNow PRUTest and AspirinWorks. Result interpretation based on pre-defined cutoff values was used to calculate raw agreement indices, and Pearson\'s correlation coefficient determined using individual units of measure.
UNASSIGNED: Agreement between LTA and WBA for P2Y12-I-response was 60% (r = 0.65, high-dose ADP; r = 0.75, low-dose ADP). VerifyNow agreed with LTA in 75% (r = 0.86, high-dose ADP; r = 0.75, low-dose ADP) and WBA in 55% (r = 0.57) of cases. Agreement between LTA and WBA for ASA-response was 45% (r = 0.09, high-dose collagen WBA; r = 0.19, low-dose collagen WBA). AspirinWorks agreed with LTA in 60% (r = 0.32) and WBA in 35% (r = 0.02, high-dose collagen WBA; r = 0.08, low-dose collagen WBA) of cases.
UNASSIGNED: Overall agreement varied from 35 to 75%. LTA and VerifyNow demonstrated the highest agreement for P2Y12-I-response, followed by moderate agreement between LTA and WBA. LTA and AspirinWorks showed moderate agreement for aspirin response, while WBA showed the weakest agreement with both LTA and AspirinWorks. The results from this study support the continued use of LTA for monitoring dual antiplatelet therapy, with VerifyNow as an appropriate alternative for P2Y12-I-response. Integration of results obtained from these varied testing platforms with patient outcomes remains paramount for future studies.

Clopidogrel, an antiplatelet agent used for secondary prevention of cerebrovascular diseases, is often taken with proton pump inhibitors (PPIs). Generally, the combined use of clopidogrel and PPIs causes adverse drug-drug interactions. VerifyNow is a quick and convenient method to confirm clopidogrel resistance (CR), which compromises adequate antithrombotic effects. We aimed to confirm CR, identify its factors, and determine the influence of the combination of ilaprazole and clopidogrel on clopidogrel using VerifyNow. In this retrospective study, we examined patients who were receiving clopidogrel after three months, starting within one week from the onset of cerebral infarction symptoms. Clinical records, imaging records, and diagnostic laboratory results, including P2Y12 reaction units (PRU), were compared and analyzed to check for CR. Additionally, the groups treated with either both ilaprazole and clopidogrel or with medications other than ilaprazole were comparatively analyzed. CR was defined as a PRU ≥240 after clopidogrel for three months. Among factors influencing CR by affecting clopidogrel metabolism, positive statistical correlations with age and alcohol consumption were confirmed. The diagnostic tests revealed a lower glomerular filtration rate and platelet count of the CR-positive group. This finding proved that the combination therapy of ilaprazole and clopidogrel is safe, as it does not interfere with the metabolism of clopidogrel.

Background: East Asian patients receiving treatment with the potent P2Y12 inhibitors prasugrel or ticagrelor experience more potent platelet inhibition than with clopidogrel. Methods: This study investigated differences in OPR rates with reduced doses of prasugrel (n = 38) or ticagrelor (n = 40) for maintenance therapy in 118 Korean ACS patients who had undergone PCI, in comparison to conventional-dose clopidogrel (n = 40). We assessed drug responses at one- and three-months post-PCI with VerifyNow and multiple electrode aggregometry assays. Results: At the one-month period, patients receiving standard-dose prasugrel or ticagrelor had lower platelet reactivity as determined by the three assays than those receiving the conventional dose of clopidogrel (VN: p = 0.000; MEA: p = 0.000; LTA: p = 0.000). At the 3-month point, platelet reactivity was lower in those receiving reduced-dose prasugrel or ticagrelor than the clopidogrel-treated patients (VN: p = 0.000; MEA: p = 0.012; LTA: p = 0.002). Prasugrel resulted in significantly lower platelet inhibition than ticagrelor as determined by VN and LTA (VN: p = 0.000; LTA: p = 0.003). At three months, there was a significant overall difference in OPR among the three groups when measured by VN (p < 0.001), but not when measured by MEA (p = 0.596). OPR in the reduced-dose prasugrel group was not significantly different to the clopidogrel group at three months (VN: p = 0.180; MEA: p = 0.711). OPR in the reduced-dose ticagrelor group was similar to clopidogrel as determined by MEA at three months, but was different when assessed by VN (VN: p = 0.000; MEA: p = 0.540). Compared to standard-dose, the reduced-dose prasugrel OPR rate was significantly increased (VN: p = 0.008; MEA: p = 0.020). Conclusions: OPR values for reduced-dose prasugrel and conventional-dose clopidogrel at three months were similar but higher than for reduced-dose ticagrelor as determined by VN, but no differences were noted by MEA. The MEA assay might have less sensitivity and consistency than the VN assay. Further studies are needed to explore this discrepancy.