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Background: This study investigated whether point-of-care platelet function measurements could predict favorable outcomes in patients with acute ischemic stroke (AIS). Antiplatelet agents, such as aspirin, are known to reduce the risk of recurrent stroke by 20–30%. However, identifying nonresponders to therapy remains a clinical challenge. The study aimed to assess the prognostic value of serial Platelet Function Analyzer (PFA)-100 measurements and hematological ratios in AIS patients. Methods: A prospective cohort study was conducted on 212 AIS patients in Taiwan. Platelet function was assessed at baseline, week 2, and week 4 using PFA-100. The primary outcome was functional recovery, defined by a modified Rankin Scale (mRS) score of 0–3, at 1-month and 1-year. Subgroup analyses compared outcomes between pre- and post-aspirin administrations. Statistical analyses examined the association between changes in platelet function and clinical outcomes. Results: Difference in collagen and epinephrine (CEPI) measurements between baseline and week 2 was associated with favorable mRS scores (p < 0.001). A difference in CEPI closure time greater than 99 seconds was most predictive of a favorable outcome with an adjusted odds ratio of 11.859 (95% CI 2.318–60.669) at 1-month follow-up. Subgroup analyses revealed predictive value in pre-aspirin measurements at 1-month follow-up (p = 0.007). Conclusions: Serial PFA-100 measurements and hematological biomarkers, specifically changes in on-treatment CEPI closure times, may help predict favorable clinical outcome in AIS patients. These findings suggest that dynamic platelet function assessment could play a role in optimizing antiplatelet therapy in AIS management. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aim Materials & methods Results Discussion & conclusion A wide variety of laboratory hemostasis tests is available, but the majority is plasma‐based, static and unable to assess platelet function and fibrin formation simultaneously. The Total Thrombus‐Formation Analysis System (T‐TAS) is a microchip‐based flow chamber system that simulates in vivo conditions for evaluating whole blood thrombogenicity.A comprehensive overview of its applicability in different thrombosis and hemostasis related clinical situations is lacking and therefore this scoping review was performed.A literature search was done using the electronic databases PubMed, Scopus and Embase on January 7, 2024. Original studies assessing the usefulness of the T‐TAS in thrombosis and hemostasis related clinical situations were eligible for this scoping review.A total of 28 studies were included; six studies investigating the role of the T‐TAS in congenital bleeding disorders, five studies using the T‐TAS to assess 1‐year bleeding risk in patients on antiplatelet or anticoagulant medications, four studies investigating the effects of thrombocytopenia and hemodialysis on thrombus formation as measured by the T‐TAS, 11 studies testing the applicability of the T‐TAS in the monitoring of anticoagulant and antiplatelet therapies and eventually two studies on the ability of the T‐TAS to assess the thrombogenicity in different disease entities.The T‐TAS method is an interesting technology that mimics the complex biological coagulation process using shear forces, creating a “blood vessel component on a chip”. More research is needed, but it could eventually function as a screening test for platelet function and coagulation. Moreover, it could be used to detect the presence of anticoagulant and/or antiplatelet medication. [ABSTRACT FROM AUTHOR]

The systematic review published in the Journal of Evidence-Based Medicine focuses on outcomes reporting in clinical trials of Chinese herbal medicine for ulcerative colitis (UC). The study highlights the challenges in standardizing outcome measures due to the lack of agreed-upon evaluation criteria, such as those in Chinese medicine. The review aims to summarize existing endpoint definitions, measurement tools, and efficacy outcomes reported in randomized controlled trials of Chinese herbal medicine for UC, emphasizing the need for a core outcome set to reduce heterogeneity and enhance study quality. The study included 1247 randomized controlled trials published between 2011 and 2022, with outcomes categorized into domains such as clinical composite outcomes, safety outcomes, CM symptoms/patterns outcomes, and others. [Extracted from the article]

Introduction: The recently developed platelet aggregation technique based on low-angle light scattering (LaSca) in diluted platelet-rich plasma (PRP) requires only a small sample volume and provides information about platelet aggregation and shape change. This study aimed to investigate the influence of preanalytical and analytical variables and to validate the method in a real-life pediatric hematology hospital setting. Methods: Platelet aggregation was induced by ADP in diluted PRP in the presence of 2 mM calcium at 23 °C. The study included healthy adults (n = 30), healthy children (n = 20), and pediatric patients with suspected or diagnosed platelet function abnormalities (n = 25). Results: The assay parameters were stable for at least 3 h after isolation of PRP and were sensitive to plasma dilution in the range of 2–8%. The initial aggregation velocity was significantly reduced in pediatric patients compared with healthy children (p < 0.05). ADP-induced light transmission amplitude was moderately correlated with LaSca amplitude of aggregation in healthy children (p = 0.52, p < 0.05) but not in pediatric patients. Conclusions: We standardized the protocol for platelet aggregation assessment by LaSca and characterized the influence of preanalytical and analytical variables on it. [ABSTRACT FROM AUTHOR]

Purpose: Platelets are key mediators in cardiovascular disease (CVD). Low cardiorespiratory fitness (CRF) is a risk factor for CVD. The purpose of our study was to assess if CRF associates with platelet function. Methods: Platelet assays and cardiopulmonary exercise testing were conducted in the Framingham Heart Study (N = 3014). Linear mixed effects models estimated associations between CRF (assessed by peak oxygen uptake [V̇O2]) and multiple platelet reactivity assays. Models were adjusted for multiple medications, risk factors, relatedness, and prevalent CVD. Results: Nineteen associations passed the significance threshold in the fully adjusted models, all indicating higher CRF associated with decreased platelet reactivity. Significant traits spanned multiple platelet agonists. Strongest associations were observed in multiplate whole blood testing after TRAP-6 (e.g., velocity, beta = -0.563, 95% CI = -0.735 to -0.391, P = 1.38E-10), ADP (e.g., velocity, beta = -0.514, 95% CI = -0.681 to -0348, P = 1.41E-09), collagen (e.g., velocity, beta = -0.387, 95% CI = -0.549 to -0.224, P = 3.01E-06), ristocetin (e.g., AUC, beta = -0.365, 95% CI = -0.522 to -0.208, P = 5.17E-06) and arachidonic acid stimulation of platelets (e.g., velocity, beta = -0.298, 95% CI = -0.435 to -0.162, P = 3.39E-04), and light transmission aggregometry (LTA) after ristocetin stimulation (e.g., max aggregation, beta = -0.362, 95% CI = -0.540 to -0.184, P = 6.64E-05). One trait passed significance threshold in the aspirin subsample (LTA ristocetin primary slope, beta = -0.733, 95% CI = -1.134 to -0.333, P = 3.30E-04) and another in a model including von Willebrand Factor levels as a covariate (U46619, a thromboxane receptor mimetic, AUC in the Optimul assay, beta = -0.36, 95% CI = -0.551 to -0.168, P = 2.35E-04). No strong interactions were observed between the associations and sex, age, or body mass index in formal interaction analyses. Conclusions: Our findings build on past work that shows CRF to be associated with reduced CVD by suggesting decreased platelet reactivity may play a mechanistic role. We found significant associations with multiple platelet agonists, indicating higher CRF may globally inhibit platelets; however, given multiple strong associations after TRAP-6 and ADP stimulation, PAR-1 and purinergic signaling may be most heavily involved. This is notable because each of these receptor pathways are tied to anticoagulant (DOAC/thrombin inhibitors) and antiplatelet therapies (P2Y12/PAR1/PAR4 inhibitors) for CVD prevention. [ABSTRACT FROM AUTHOR]

Hansamon Poparn,1,2 Yaowaree Kittikalayawong,1,2 Piti Techavichit,1,2 Supanun Lauhasurayotin,1,2 Kanhatai Chiengthong,1,2 Phumin Chaweephisal,2 Darintr Sosothikul1,2 1Division of Pediatric Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand; 2Integrative and Innovative Hematology/Oncology Research Unit, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, ThailandCorrespondence: Darintr Sosothikul, Division of Pediatric Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand, Tel/Fax +66 2-256-4949, Email dsosothikul@hotmail.com; Darintr.S@chula.ac.thAbstract: Since aspirin resistance is rarely assessed in pediatric patients and thrombosis might cause damage in vital organs, such as the myocardium or brain, we aimed to determine its incidence and the pivotal role of routine screening. The point-of-care test by platelet function analyzer (PFA-200) and bedside bleeding time (BT) was compared to standard whole blood impedance aggregometry (IA), the time-consuming and sophisticated assays. This single-center cross-sectional study was investigated in Thai children (≤ 15 years). All participants received at least five-day administrations of aspirin (3 to 5 mg/kg/day or equivalent to a single tablet of 81 mg) for any prior thrombotic risks. Platelet aggregation > 5 ohms on IA with 0.5 mM arachidonic acid, closure time < 180 seconds on collagen/epinephrine PFA-200, and modified Ivy BT ≤ 7 minutes, defined resistance. Of 37 patients, 2.7% had confirmed aspirin resistance to IA. Despite the 100% sensitivity, PFA-200 showed higher specificity than BT (83.3% vs 36.1%). However, both were not comparable (exact McNemar P < 0.05), with a slight/fair reliability (&kgreen;=0.215 vs &kgreen;=0.030 respectively). Aspirin resistance is uncommon in Thai children. Routine screening is discouraged but recommended only in cases with recurrent thrombosis despite good aspirin compliance or the presence of resistant risk factors. Although the gold standard IA could not be replaced, the rapid assay of PFA-200, not bedside BT, can potentially be considered a point-of-care alternative screening test to detect aspirin resistance in children.Keywords: aspirin, pediatrics, platelet function tests

Introduction: Clopidogrel hyperresponsiveness is a timely topic, with wide ranging reports of hemorrhagic complications, using various clopidogrel dosing strategies following neuroendovascular procedures. This study serves to investigate hemorrhagic complications using standard clopidogrel doses and timing of these complications in relation to the procedure. Materials and Methods: Retrospective cohort of consecutive adult patients undergoing flow diversion with Pipeline Embolization Device (PED) at an academic medical center, receiving on-label clopidogrel doses. Patients with clopidogrel hyperresponsiveness (VerifyNowTM P2Y12 reaction unit (PRU) ≤ 70) were compared to those who were normoresponsive. The primary outcome is the rate of hemorrhagic complications between groups. Results: Of 148 included patients, 54 (36.5%) were identified as clopidogrel hyperresponsive (PRU ≤ 70) and 94 (63.5%) as clopidogrel normoresponsive (PRU 71 – 194). There were no hemorrhagic complications observed in patients who were clopidogrel hyperresponsive, with 5 occurring in patients who were normoresponsive (P = 0.09). Three (60%) of the hemorrhages were intracranial with most occurring intra-procedure or within the first week of the procedure. Age > 60 years was the only candidate predictor for hemorrhagic complications (P = 0.004). Conclusion: Our findings are contradictory, with lower hemorrhagic complications in clopidogrel hyperresponders than prior literature, and most occurring intra-op or in the immediate acute post-op phase. [ABSTRACT FROM AUTHOR]

Abstract Background It is well-established that thrombus aspiration during primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) indicates a higher thrombus burden and necessitates more intensive antithrombotic therapy. The bidirectional association between adverse events in AMI patients and platelet reactivity is typically observed during dual antiplatelet therapy (DAPT). Objective To investigate platelet reactivity after DAPT in AMI patients with thrombus aspiration performed during PCI. Methods In this retrospective study, we examined 269 consecutive AMI patients who underwent PCI and recorded their demographic, clinical and laboratory data. The platelet reactivity was measured with thromboelastogram (TEM). Results Ultimately, 208 patients were included in this study and divided into a Thrombus Aspiration group (N = 97) and a PCI Alone group (N = 111) based on whether thrombus aspiration was performed or not. The adenosine diphosphate (ADP)-induced platelet inhibition rate in the Thrombus Aspiration group was higher than that in the PCI Alone group (P

Background: Carotid stenting requires dual antiplatelet therapy to effectively prevent thromboembolic complications. However, resistance to clopidogrel, a key component of this therapy, may lead to persistent risk of these complications. The aim of this study was to determine, if the implementation of routine platelet function testing and adjusting therapy was associated with lower incidence of thromboembolic complications and death. Methods: All consecutive patients treated with carotid artery stenting in a single institution over 8 years were enlisted in a retrospective study. Platelet function testing was performed, and efficient antiplatelet therapy was set before the procedure. Incidence of procedure-related stroke or death within periprocedural period (0–30 days) was assessed. The results were evaluated in relation to the findings of six prominent randomized control trials. Results: A total of 241 patients were treated for carotid stenosis, seven patients undergo CAS on both sides over time. There was 138 symptomatic (55,6%) and 110 asymptomatic stenoses (44,4%). Five thromboembolic complications (2,01%) occurred, four of them (1,61%) was procedure-related. Two patients died because of procedure-related stroke (0,82%). Incidence of procedure-related stroke or death was significant lower compared to the results of CREST study (2,01% vs. 4,81%, P = 0,0243) in the entire cohorts, and to the results of ICSS study in the symptomatic cohorts (2,86% vs. 7,37%, P = 0,0243), respectively. Conclusions: Tailored antiplatelet therapy in carotid stenting is safe and seems to be related with lower incidence of procedure-related death or stroke rate. Larger prospective studies to assess whether platelet function testing-guided antiplatelet therapy is superior to standard dual antiplatelet should be considered. [ABSTRACT FROM AUTHOR]

Objective: To verify the administration of a new nano delivery system coated with Tirofiban on preventing early thrombosis in vein graft. Methods: Forty New Zealand white rabbits were randomly divided into five groups with eight rabbits in each group. The rabbits of all groups underwent jugular vein transplantation, except group I with only neck opening and closing operation. Vein grafts of group II were preprocessed by intravenous injection of normal saline; group III were preprocessed by tirofiban alone; group IV were preprocessed by unloaded nanoparticles of PLGA-PEG; group V were preprocessed by PLGA-PEG coated with tirofiban. Coagulation and platelet function of peripheral and vein graft blood were detected at 1, 2, 4, 12 h and 1, 3, 7, 10, 14 days after operation. Patency rate of vein graft and blood flow index were measured by vascular ultrasound at third, seventh, 10th, and 14th days after operation; two rabbits in each group were randomly sacrificed at the corresponding time of detection. Pathological differences of vein grafts were observed by HE stainin. Results: The patency rate of vein grafts in group V was significantly higher than that in group II to IV. The platelet and platelet aggregation rate in group V were inhibited in vein graft blood significantly. The post-operative PT and APTT in vein graft blood in group V were increased obviously while the FBG, D-dimer and FDP were significantly inhibited. Except group I, the lumen loss rate of vein grafts in group V was significantly lower than that in other groups, and vein graft blood in group V had a significant lower expression of platelet P-selectin and GP IIb/IIIa receptor than that in other groups. Conclusion: This study proves that PEG-PLGA coated with tirofiban can effectively prevent early vein graft stenosis from thrombosis by inhibition of platelet function, coagulation function. [ABSTRACT FROM AUTHOR]

This research article explores the potential risk of pelvic hematoma following a prostatic urethral lift (PUL) procedure, which is used to treat benign prostate enlargement. The article identifies factors that can increase the risk of this complication, such as anatomical abnormalities and the use of certain medications. It emphasizes the importance of early diagnosis and monitoring, as well as individualized patient care. The article concludes by offering proactive management strategies to prevent complications and improve patient outcomes. The article was written by Vikas Kumar Panwar from the Department of Urology at the All India Institute of Medical Science and can be found on the website of the Investigative and Clinical Urology journal. [Extracted from the article]

Dual antiplatelet therapy (DAPT) use is the standard of practice after flow diversion (FD) for intracranial aneurysms (IAs). Yet, no consensus exists in the literature regarding the optimal regimen. Certain institutions utilize various platelet function testing (PFT) to assess patient responsiveness to DAPT. Clopidogrel is the most commonly prescribed drug during DAPT; however, up to 52% of patients can be non-responders, justifying PFT use. Additionally, prices vary significantly among antiplatelet drugs, often further complicated by insurance restrictions. We aimed to determine the most cost-effective strategy for deciding DAPT regimens for patients after IA treatment. A decision tree with Monte Carlo simulations was performed to simulate patients undergoing various three-month postoperative DAPT regimens. Patients were either universally administered aspirin alongside clopidogrel, ticagrelor, or prasugrel without PFT, or administered one of the former thienopyridine medications based on platelet reactivity unit (PRU) results after clopidogrel. Input data for the model were extracted from the current literature, and the willingness-to-pay threshold (WTP) was defined as $100,000 per QALY as per standard practice in the US. The baseline comparison was with universal clopidogrel DAPT without any PFT. Probabilistic and deterministic sensitivity analyses were performed to evaluate the robustness of the model. Utilizing PFT and switching clopidogrel to prasugrel if resistance is documented was the most cost-effective regimen compared to universal clopidogrel, with a base-case incremental cost-effectiveness ratio (ICER) of $-35,255 (cost $2,336.67, effectiveness 0.85). Performing PFT and switching clopidogrel to ticagrelor (ICER $-4,671; cost $2,995.06, effectiveness 0.84), universal prasugrel (ICER $5,553; cost $3,097.30, effectiveness 0.84), or universal ticagrelor (ICER $75,969; cost $3,801.36, effectiveness 0.84) were all more cost-effective than treating patients with universal clopidogrel (cost $3,041.77, effectiveness 0.83). These conclusions remain robust in probabilistic and deterministic sensitivity analyses. The most cost-effective strategy guiding DAPT after FD for IAs is to perform PFTs and switch clopidogrel to prasugrel if resistance is documented, alongside aspirin. The cost of PFT is strongly justified and recommended when deciding patient-specific DAPT regimens. [ABSTRACT FROM AUTHOR]

Background: It is well-established that thrombus aspiration during primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) indicates a higher thrombus burden and necessitates more intensive antithrombotic therapy. The bidirectional association between adverse events in AMI patients and platelet reactivity is typically observed during dual antiplatelet therapy (DAPT). Objective: To investigate platelet reactivity after DAPT in AMI patients with thrombus aspiration performed during PCI. Methods: In this retrospective study, we examined 269 consecutive AMI patients who underwent PCI and recorded their demographic, clinical and laboratory data. The platelet reactivity was measured with thromboelastogram (TEM). Results: Ultimately, 208 patients were included in this study and divided into a Thrombus Aspiration group (N = 97) and a PCI Alone group (N = 111) based on whether thrombus aspiration was performed or not. The adenosine diphosphate (ADP)-induced platelet inhibition rate in the Thrombus Aspiration group was higher than that in the PCI Alone group (P < 0.001). Furthermore, multivariate linear regression analysis revealed that the ADP-induced platelet inhibition rate was independently associated with leukocyte count, thrombus aspiration and the combination of aspirin and ticagrelor as DAPT after adjusting for potential covariates in all AMI patients. Conclusion: In conclusion, clinicians should exercise heightened attention towards the bleeding risk among patients undergoing PCI concomitant with Thrombus Aspiration postoperatively. [ABSTRACT FROM AUTHOR]

Introduction: Platelet transfusion is a standard treatment to prevent bleeding in patients with hematological malignancies. Although transfusions can improve platelet count, their impact on platelet function remains controversial. Methods: We conducted flow cytometry to assess platelet function before and after transfusion and performed subgroup analyses to examine differences based on blood type, corrected count increment (CCI), and platelet microparticles. Results: Overall, 50 patients who received prophylactic platelet transfusion were enrolled. CD42b expression increased, whereas CD41 expression decreased after transfusion. Apheresis platelets exhibited the lowest expression of PAC‐1 and P‐selectin when exposed to agonist stimulations. PAC‐1 expression increased under high adenosine diphosphate (ADP) stimulation, while P‐selectin expression increased under both high ADP and thrombin receptor‐activating peptide stimulation. In the subgroup analysis, patients with a CCI >4500 and those with the same blood types exhibited a more significant increase in PAC‐1 and P‐selectin expression under agonist stimulation. When comparing apheresis platelets collected on different days, only the percentage of platelet‐derived microparticles showed a significant increase. Conclusion: Prophylactic transfusion improved platelet function. Platelet function significantly improved in patients with a CCI >4500, those with the same blood types as that of apheresis platelets, or those with platelet‐derived microparticle levels <4.7%. No significant improvement in platelet function was noted after the transfusion of different blood types with acceptable compatibility or the transfusion of incompatible blood types. Our results suggest that transfusing platelets with the same blood type remains the optimal choice. [ABSTRACT FROM AUTHOR]

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no‐function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no‐function allele carriers. However, the influence of patient‐specific demographic, clinical, and other genetic factors on outcomes with genotype‐guided DAPT has not been defined. In addition, the impact of genotype‐guided de‐escalation from prasugrel or ticagrelor to clopidogrel in patients without a CYP2C19 no‐function allele has not been investigated in a diverse, real‐world clinical setting. The Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry is a multicenter US registry of patients who underwent PCI and clinical CYP2C19 testing. The registry is enrolling a diverse population, assessing atherothrombotic and bleeding events over 12 months, collecting DNA samples, and conducting platelet function testing in a subset of patients. The registry aims to define the influence of African ancestry and other patient‐specific factors on clinical outcomes with CYP2C19‐guided DAPT, evaluate the safety and effectiveness of CYP2C19‐guided DAPT de‐escalation following PCI in a real‐world setting, and identify additional genetic influences of clopidogrel response after PCI, with the ultimate goal of establishing optimal strategies for individualized antiplatelet therapy that improves outcomes in a diverse, real‐world population. [ABSTRACT FROM AUTHOR]

We report three unrelated cases of Hermansky-Pudlak (HP) characterized by novel mutations in HPS3 (compound heterozygosity for c.1457G>A and c.1813G>T), HPS6 (homozygous c.210_211insGGGCC), and HPS8 (homozygous c.299dupC in BLOC1S3) genes. No spontaneous bleeding tendency was observed despite the presence of several platelet function abnormalities. Screening test with PFA-100 failed to detect the abnormality. This report confirms the pattern of poor bleeding risk in patients with rare HP and the need for detailed platelet function studies despite normal hemostatic screening tests.

Background: Despite combined anticoagulation therapy consisting of a vitamin K antagonist and an antiplatelet agent, thromboembolic complications often occur in patients with a left ventricular assist device (LVAD). In addition, bleeding events are also common. Resistance to antiplatelet drugs is a well‐known phenomenon; however, the utilization of laboratory chemistry testing for the presence of such resistance, and then switching therapy, is controversial. Methods: We tested 132 patients with LVAD (HeartWare n = 57, HeartMate II n = 22, HeartMate 3 n = 53) on acetylsalicylic acid (ASA) therapy for resistance and followed them for a maximum of 7 years regarding pump thrombosis. Light transmission aggregometry (LTA) and impedance aggregometry (IPA) were performed for testing platelet function. Results: We could show that patients with ASA resistance displayed an increased risk of pump thrombosis, regardless of the test used (LTA: OR = 6.20, CI [1.86–20.64], p = 0.003; IPA: OR = 12.14, CI [3.00–49.07], p < 0.001). In patients with a HeartMate 3, we could not detect any pump thrombosis associated with aspirin resistance. Furthermore, there was no significant difference in bleeding events between patients with ASA resistance and ASA responders. Conclusion: Laboratory testing of ASA resistance seems to be a good tool to detect an increased risk of pump thrombosis, at least for patients with a HeartWare or HeartMate II. The extent to which these thromboses can be prevented with a change of medication has to be investigated in further studies. No pump thrombosis was detected in patients with a HeartMate 3, and the question should be asked as to what constellation of underlying and concomitant diseases must be present to justify ASA therapy for these patients. [ABSTRACT FROM AUTHOR]

Background: Platelet radiolabeling with radioisotopes is currently used for human platelet recovery and survival studies. Biotinylation enables ex vivo post‐transfusion platelet function testing. Whether platelet biotinylation itself affects platelet function is controversial. Study Design and Methods: Platelet concentrates from healthy humans were stored for 6 days. Samples were obtained at 1 or 2 and 6 days, and platelets were labeled following a radiolabeling protocol using saline instead of radioactive indium‐111 (sham radiolabeling [sham‐RL]). Alternatively, a newly developed biotinylation protocol, a washing protocol, or an unmanipulated control sample were used. Platelet function was assessed by flow cytometry after stimulation with platelet agonists and labeling of platelets with platelet activation markers. To test whether platelets can be activated after transfusion, labeled platelets were transfused into nonobese diabetic/severe combined immunodeficiency mice, and samples were obtained 1 h after transfusion. Results: The activation profile of biotinylated platelets was comparable to sham‐RL platelets before transfusion except for significantly less α‐degranulation and more phosphatidyl serine exposure on storage day 1/2. There was no significant difference between sham‐RL and biotinylated platelets on storage day 6. Sham‐RL and biotinylated platelets were significantly less activatable than washed and unmanipulated control platelets. After transfusion, the activation profile of biotinylated platelets was largely indistinguishable from unmanipulated ones. Discussion: The decrease in activation level in biotinylated platelets we and others observed appears mainly due to the physical manipulation during the labeling process. In conclusion, biotinylated platelets allow for post‐transfusion function assessment, a major advantage over radiolabeling. [ABSTRACT FROM AUTHOR]

Administration of acetylsalicylic acid (ASA) at early stage after surgery for spontaneous intracerebral hemorrhage (SICH) may increase the risk of postoperative intracranial bleeding (PIB), because of potential inhibition of platelet function. This study aimed to investigate whether early ASA administration after surgery was related to increased risk of PIB. This retrospective study enrolled SICH patients receiving surgery from September 2019 to December 2022 in seven medical institution. Based on postoperative ASA administration, patients who continuously received ASA more than three days within seven days post-surgery were identified as ASA users, otherwise as non-ASA users. The primary outcome was symptomatic PIB events within seven days after surgery. Incidence of PIB was compared between ASA users and non-ASA users using survival analysis. This study included 744 appropriate patients from 794 SICH patients. PIB occurred in 42 patients. Survival analysis showed no statistical difference between ASA users and non-ASA users in incidence of PIB (P = 0.900). Multivariate Cox analysis demonstrated current smoker (hazard ratio [HR], 2.50, 95%CI, 1.33–4.71, P = 0.005), dyslipidemia (HR = 3.03; 95%CI, 1.31–6.99; P = 0.010) and pre-hemorrhagic antiplatelet therapy (HR = 3.05; 95% CI, 1.64–5.68; P < 0.001) were associated with PIB. Subgroup analysis manifested no significant difference in incidence of PIB between ASA users and non-ASA users after controlling the effect from factors of PIB (i.e., sex, age, current smoker, regular drinker, dyslipidemia, pre-hemorrhagic antiplatelet therapy and hematoma location). This study revealed that early ASA administration to SICH patients after surgery was not related to increased risk of PIB. [ABSTRACT FROM AUTHOR]

Cerebral intraparenchymal hemorrhage due to electrode implantation (CIPHEI) is a rare but serious complication of deep brain stimulation (DBS) surgery. This study retrospectively investigated a large single-center cohort of DBS implantations to calculate the frequency of CIPHEI and identify patient- and procedure-related risk factors for CIPHEI and their potential interactions. We analyzed all DBS implantations between January 2013 and December 2021 in a generalized linear model for binomial responses using bias reduction to account for sparse sampling of CIPHEIs. As potential risk factors, we considered age, gender, history of arterial hypertension, level of invasivity, types of micro/macroelectrodes, and implanted DBS electrodes. If available, postoperative coagulation and platelet function were exploratorily assessed in CIPHEI patients. We identified 17 CIPHEI cases across 839 electrode implantations in 435 included procedures in 418 patients (3.9%). Exploration and cross-validation analyses revealed that the three-way interaction of older age (above 60 years), high invasivity (i.e., use of combined micro/macroelectrodes), and implantation of directional DBS electrodes accounted for 82.4% of the CIPHEI cases. Acquired platelet dysfunction was present only in one CIPHEI case. The findings at our center suggested implantation of directional DBS electrodes as a new potential risk factor, while known risks of older age and high invasivity were confirmed. However, CIPHEI risk is not driven by the three factors alone but by their combined presence. The contributions of the three factors to CIPHEI are hence not independent, suggesting that potentially modifiable procedural risks should be carefully evaluated when planning DBS surgery in patients at risk. [ABSTRACT FROM AUTHOR]

The crucial role of platelets in hemostasis and their broad implications under various physiological conditions underscore the importance of accurate platelet-function testing. Platelets are key to clotting blood and healing wounds. Therefore, accurate diagnosis and management of platelet disorders are vital for patient care. This review outlines the significant advancements in platelet-function testing technologies, focusing on their working principles and the shift from traditional diagnostic methods to more innovative approaches. These improvements have deepened our understanding of platelet-related disorders and ushered in personalized treatment options. Despite challenges such as interpretation of complex data and the costs of new technologies, the potential for artificial-intelligence integration and the creation of wearable monitoring devices offers exciting future possibilities. This review underscores how these technological advances have enhanced the landscape of precision medicine and provided better diagnostic and treatment options for platelet-function disorders. [ABSTRACT FROM AUTHOR]

This is a celebratory reprint of a historical paper published in STH in 1998. The original Abstract follows. The PFA-100 system is a platelet function analyzer designed to measure platelet-related primary hemostasis. The instrument uses two disposable cartridges: a collagen/epinephrine (CEPI) and a collagen/ADP (CADP) cartridge. Previous experience has shown that CEPI cartridges detect qualitative platelet defects, including acetylsalicylic acid (ASA)-induced abnormalities, while CADP cartridges detect only thrombocytopathies and not ASA use. In this seven-center trial, 206 healthy subjects and 176 persons with various platelet-related defects, including 127 ASA users, were studied. The platelet function status was determined by a platelet function test panel. Comparisons were made as to how well the defects were identified by the PFA-100 system and by platelet aggregometry. The reference intervals for both cartridges, testing the 206 healthy subjects, were similar to values described in smaller studies in the literature (mean closure time [CT] of 132 seconds for CEPI and 93 seconds for CADP). The use of different lot numbers of cartridges or duplicate versus singleton testing revealed no differences. Compared with the platelet function status, the PFA-100 system had a clinical sensitivity of 94.9% and a specificity of 88.8%. For aggregometry, a sensitivity of 94.3% and a specificity of 88.3% were obtained. These values are based on all 382 specimens. A separate analysis of sensitivity by type of platelet defect, ASA use versus congenital thrombocytopathies, revealed for the PFA-100 system a 94.5% sensitivity in identifying ASA users and a 95.9% sensitivity in identifying the other defects. For aggregometry, the values were 100% for ASA users and 79.6% for congenital defects. Analysis of concordance between the PFA-100 system and aggregometry revealed no difference in clinical sensitivity and specificity between the systems (p > 0.9999). The overall agreement was 87.5%, with a Kappa index of 0.751. The two tests are thus equivalent in their ability to identify normal and abnormal platelet defects. Testing 126 subjects who took 325 mg ASA revealed that the PFA-100 system (CEPI) was able to detect 71.7% of ASA-induced defects with a positive predictive value of 97.8%. The overall clinical accuracy of the system, calculated from the area under the receiver operating characteristic curve, was 0.977. The data suggest that the PFA-100 system is highly accurate in discriminating normal from abnormal platelet function. The ease of operation of the instrument makes it a useful tool to use in screening patients for platelet-related hemostasis defects. [ABSTRACT FROM AUTHOR]

The article provides an overview of the PFA-100 analyzer, a tool used for platelet function testing. It explains that prior to the development of the PFA-100, platelet function testing relied on less accurate methods. The FDA approved the PFA-100 in 1997 after studies showed its effectiveness in comparison to traditional methods. The article also discusses the challenges faced by the authors in implementing the PFA-100 in their clinical practice. Additionally, it mentions various studies that have used the PFA-100 to assess platelet function in different clinical settings, including the effects of chocolate milk consumption on blood donation and its correlation with platelet activation markers. Overall, the PFA-100 is described as a rapid and sensitive test that provides valuable insights into platelet function in both humans and animals. [Extracted from the article]

Clopidogrel is the most widely used P2Y12 receptor inhibitor (P2Y12i) as a part of dual antiplatelet therapy along with aspirin. Clopidogrel is a pro‑drug and is metabolized to its active metabolite by the hepatic enzyme cytochrome P4502C19 (CYP2C19). This active metabolite is responsible for the antiplatelet action of clopidogrel. Recent studies have demonstrated that single nucleotide polymorphisms in the CYP2C19 gene, including CYP2C19*2,*3,*4, and *5 alleles, result in reduced production of the active metabolite of clopidogrel, and hence reduced inhibition of platelet aggregation. This in turn enhances the incidence of stent thrombosis and recurrent cardiovascular (CV) events. We report a case of coronary stent thrombosis due to clopidogrel resistance proven by CYP2C19 genotyping. We then review the literature on clopidogrel resistance and its impact on CV outcomes. Subsequently, we discuss the methods of diagnosis of resistance, evidence from clinical trials for tailoring clopidogrel therapy, the role of potent P2Y12 inhibitors, the current guidelines, and future directions. [ABSTRACT FROM AUTHOR]

Reduced effect of antiplatelet therapy has been reported in patients with ST-segment elevation myocardial infarction (STEMI). Multiple factors may concur to explain this, including increased amount of highly reactive immature platelets. To investigate the association between immature platelets and reactivity determined with multicolour flow cytometry using the SYTO-13 dye in STEMI patients. We conducted an observational study of 59 patients with acute STEMI. Blood samples were obtained within 24 h after admission and after loading doses of dual antiplatelet therapy. For comparison, samples were obtained from 50 healthy individuals. Immature platelets and platelet reactivity were investigated using multicolour flow cytometry including the SYTO-13 dye that binds to platelet RNA and thus provides a method for subdividing platelets into immature and mature platelets. Additionally, we assessed platelet aggregation, serum-thromboxane B 2 levels and standard immature platelet markers. Immature platelets were more reactive than mature platelets in both STEMI patients and healthy individuals (p -values < 0.05). STEMI patients had lower platelet aggregation and thromboxane B 2 levels than healthy individuals. We found a positive association between automatically determined immature platelet markers and CD63 expression on activated platelets (Spearman's rho: 0.27 to 0.58, p -values < 0.05). Our study shows that immature platelets identified with a multicolour flow cytometric method using the SYTO-13 dye are more reactive than mature platelets in patients with acute STEMI and in healthy individuals. The presence of immature platelets may be important for the overall platelet reactivity, which may have implications for the effect of antiplatelet therapy. We included 59 patients diagnosed with acute ST-segment elevation myocardial infarction (STEMI) and 50 healthy individuals. Following blood sampling, we utilized whole blood multicolor flow cytometry, incorporating the SYTO-13 dye, which binds to platelet RNA. This approach allows us to subdivide platelets into immature and mature, enabling a comprehensive assessment of platelet reactivity across distinct platelet subpopulations. [Display omitted] • Reduced effect of antiplatelet therapy is observed in acute STEMI patients. • Immature platelets may influence platelet reactivity and the effect of antiplatelet therapy. • Results provided by a multicolour flow cytometric method using the SYTO-13 dye. • Immature platelets were more reactive than mature platelets in STEMI patients. • This study emphasizes the importance of immature platelets for the overall platelet reactivity. [ABSTRACT FROM AUTHOR]

Cirrhosis presents with thrombocytopenia and possibly thrombocytopathy. Previous studies exploring platelet function gave conflicting results and most controversies are explained by the variety of methods employed for investigation. We sought to assess in-vitro the overall platelet function in cirrhosis. We investigated 34 patients by using the following tests. (i)Aggregometry. (ii)Measurement of the content of platelet granules. (iii)Cytometric platelet activation. (iv)Plasmatic markers of in-vivo platelet activation. (v)Platelet procoagulant activity by thrombin generation (TG) in platelet-rich plasma (PRP). TG measured in PRP for patients and controls was similar. Platelets from patients with cirrhosis showed reduction of aggregation and secretion of ATP. Similar results were observed for platelet activation parameters such as P-selectin expression and PAC-1 platelet binding. Plasma levels of βeta-thromboglobulin and soluble P-selectin, were increased in patients- vs -controls. In contrast, there were no patients- vs -controls differences for plasmatic platelet-factor-4. Results are consistent with a state of in-vivo platelet activation and decreased in-vitro aggregation. Since bleeding events following invasive procedures are uncommon in cirrhosis, we speculate that in-vitro aggregometry testing does not reflect the situation occurring in-vivo. Results of the study and pathophysiological considerations support the conclusion that platelet function in cirrhosis as determined by aggregometry, although somewhat impaired, may support the overall hemostatic potential, which is needed for most invasive interventions. These conclusions are in line with the recommendations of international guidelines, warning against indiscriminate use of prophylactic preprocedural administration of platelets before invasive procedures. Decision on platelet support should not be made based on in-vitro laboratory testing for platelet function. • The role of platelet function in cirrhosis during procedures is poorly defined. • We investigated the overall platelet function with an array of laboratory methods. • Platelet function is impaired but does hardly represent the in-vivo situation. • Since perioperative bleeding is uncommon platelet function testing is not advised. [ABSTRACT FROM AUTHOR]

Background: Glycoprotein (GP)VI is a platelet-specific collagen receptor required for platelet activation during hemostasis. Platelet reactivity toward collagen is routinely assessed during diagnostic workup of platelet disorders. GPVI can be activated by inducing receptor clustering with suspensions of fibrillar collagen or synthetic cross-linked collagen-related peptide (CRP-XL). However, these suspensions are poorly standardized or difficult to produce. Nanobodies are small recombinant camelid-derived heavy-chain antibody variable regions. They are highly stable, specific, and ideal candidates for developing a stable GPVI agonist for diagnostic assays. Objectives: Develop a stable nanobody-based GPVI agonist. Methods: Nanobody D2 (NbD2) was produced as dimers and purified. Tetramers were generated via C-terminal fusion of dimers with click chemistry. Nanobody constructs were functionally characterized with light transmission aggregometry (LTA) in platelet-rich plasma and whole blood flow cytometry. Diagnostic performance was assessed in patients with inherited platelet function disorders with LTA and flow cytometry. Results: NbD2 was specific for human platelet GPVI. Dimers did not result in platelet activation in LTA or flow cytometry settings and fully inhibited CRP-XL-induced P-selectin expression and fibrinogen binding in whole blood and attenuated collagen-induced platelet aggregation in platelet-rich plasma. However, NbD2 tetramers caused full platelet aggregation, as well as P-selectin expression and fibrinogen binding. NbD2 tetramers were able to discriminate between inherited platelet function disorder patients and healthy controls based on fibrinogen binding, similar to CRP-XL. Conclusion: Nanobody tetramers to GPVI induce platelet activation and can be used to assess the GPVI pathway in diagnostic assays.

BACKGROUND: Posttraumatic venous thromboembolism (VTE) remains prevalent in severely injured patients despite chemoprophylaxis. Importantly, although platelets are central to thrombosis, they are not routinely targeted in prevention of posttraumatic VTE. Furthermore, platelets from injured patients show ex vivo evidence of increased activation yet impaired aggregation, consistent with functional exhaustion. However, the relationship of this platelet functional phenotype with development of posttraumatic VTE is unknown. We hypothesized that, following injury, impaired ex vivo platelet aggregation (PA) is associated with the development of posttraumatic VTE. METHODS: We performed a secondary analysis of 133 severely injured patients from a prospective observational study investigating coagulation and inflammation (2011-2019). Platelet aggregation in response to stimulation with adenosine diphosphate (ADP), collagen, and thrombin was measured at presentation (preresuscitation) and 24 hours (postresuscitation). Viscoelastic clot strength and lysis were measured in parallel by thromboelastography. Multivariable regression examined relationships between PA at presentation, 24 hours, and the change (δ) in PA between presentation and 24 hours with development of VTE. RESULTS: The 133 patients were severely injured (median Injury Severity Score, 25), and 14% developed VTE (all >48 hours after admission). At presentation, platelet count and PA were not significantly different between those with and without incident VTE. However, at 24 hours, those who subsequently developed VTE had significantly lower platelet counts (126 × 10 9 /L vs. 164 × 10 9 /L, p = 0.01) and lower PA in response to ADP ( p < 0.05), collagen ( p < 0.05), and thrombin ( p = 0.06). Importantly, the magnitude of decrease in PA (δ) from presentation to 24 hours was independently associated with development of VTE (adjusted odds ratios per 10 aggregation unit decrease: δ-ADP, 1.31 [ p = 0.03]; δ-collagen, 1.36 [ p = 0.01]; δ-thrombin, 1.41 [ p < 0.01]). CONCLUSION: Severely injured patients with decreasing ex vivo measures of PA despite resuscitation have an increased risk of developing VTE. This may have implications for predicting development of VTE and for studying platelet targeted chemoprophylaxis regimens. LEVEL OF EVIDENCE: Prognostic/Epidemiological; Level III.

Dual antiplatelet therapy (DAPT) is standard treatment for endoluminal stent insertion, and complete resistance to DAPT is rare. A case of in-stent thrombosis occurring 3 hours after stent-assisted coiling of internal carotid artery aneurysm is presented despite compliance with DAPT. Platelet function tests (PFTs) revealed complete clopidogrel and prasugrel resistance. [ABSTRACT FROM AUTHOR]

Introduction: Light transmission aggregometry (LTA) is important for diagnosing platelet function disorders (PFD) and von Willebrand disease (VWD) affecting ristocetin‐induced platelet aggregation (RIPA). Nonetheless, data is lacking on the utility of LTA for investigating thrombocytopenic patients and platelet rich plasma samples with low platelet counts (L‐PRP). Previously, we developed a strategy for diagnostic LTA assessment of L‐PRP that included: (1) acceptance of referrals/samples, regardless of thrombocytopenia severity, (2) tailored agonist selection, based on which are informative for L‐PRP with mildly or severely low platelet counts, and (3) interpretation of maximal aggregation (MA) using regression‐derived 95% confidence intervals, determined for diluted control L‐PRP (C‐L‐PRP). Methods: To further evaluate the L‐PRP LTA strategy, we evaluated findings for a subsequent patient cohort. Results: Between 2008 and 2021, the L‐PRP strategy was applied to 211 samples (11.7% of all LTA samples) from 192 unique patients, whose platelet counts (median [range] × 109/L) for blood and L‐PRP were: 105 [13–282; 89% with thrombocytopenia] and 164 [17–249], respectively. Patient‐L‐PRP had more abnormal MA findings than simultaneously tested C‐L‐PRP (p‐values <0.001). Among patients with accessible electronic medical records (n = 181), L‐PRP LTA uncovered significant aggregation abnormalities in 45 (24.9%), including 18/30 (60%) with <80 × 109 platelets/L L‐PRP, and ruled out PFD, and VWD affecting RIPA, in others. The L‐PRP LTA strategy helped diagnose VWD affecting RIPA, Bernard Soulier syndrome, familial platelet disorder with myeloid malignancy, suspected ITGA2B/ITGB3‐related thrombocytopenia, and acquired PFD. Conclusion: Diagnostic LTA with L‐PRP, using a strategy that considers thrombocytopenia severity, is feasible and informative. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate antiplatelet drug resistance utilizing light transmission-lumiaggregometry (LT-LA) and the Platelet Function Analyzer-100 (PFA-100) in patients undergoing cardiovascular surgery. Materials and Methods: The study included 60 patients diagnosed with stable coronary artery disease and peripheral vascular diseases that required surgery. Participants were divided into three groups: patients receiving aspirin (ASA) (n=21), patients receiving clopidogrel (CLO) (n=19), and patients receiving dual therapy (ASA+CLO) (n=20). Aggregation and secretion tests by LT-LA and closure time by the PFA-100 were used to measure antiplatelet drug resistance. Results: Based on the adenosine diphosphate (ADP)-induced aggregation test, 43% of patients were resistant to ASA, 22% to CLO, and 15% to dual therapy. Diabetes, hypertension, and hyperlipidemia were the most commonly identified comorbid disorders. In patients with comorbid risk factors, the median value of platelet aggregation response to ADP was significantly higher in the ASA group than in the CLO and dual therapy groups (p=0.0001). In patients receiving ASA monotherapy, the maximum amplitude of aggregation response to platelet agonists was ≥70% in 43% of patients for ADP and 28% for collagen by LT-LA. Elevated ADP (≥0.29 nmol) and collagen (≥0.41 nmol)-induced adenosine triphosphate release were found by LT-LA in 66% of patients utilizing an ADP agonist and 80% of patients using a collagen agonist undergoing ASA therapy. Closure times obtained with the PFA-100 were normal in 28% of patients using collagen-ADP cartridges and 62% of patients using collagen-epinephrine (CEPI) cartridges who received ASA. Recurrent thrombosis and bleeding were observed in 12 (20%) patients with cardiovascular disease. Three of these individuals (25%) showed ASA resistance with normal responses to ADP-induced aggregation (≥70%) and secretion (≥0.29 nmol), as well as normal CEPI closure times. Conclusion: Our findings suggest that antiplatelet drug monitoring by LT-LA and PFA-100 may be useful for high-risk and complicated cardiovascular patients. [ABSTRACT FROM AUTHOR]

The role of antiplatelet therapy in patients with acute coronary syndromes is a moving target with considerable novelty in the last few years. The pathophysiological basis of the treatment depends on platelet biology and physiology, and the interplay between these aspects and clinical practice must guide the physician in determining the best therapeutic options for patients with acute coronary syndromes. In the present narrative review, we discuss the latest novelties in the antiplatelet therapy of patients with acute coronary syndromes. We start with a description of platelet biology and the role of the main platelet signal pathways involved in platelet aggregation during an acute coronary syndrome. Then, we present the latest evidence on the evaluation of platelet function, focusing on the strengths and weaknesses of each platelet's function test. We continue our review by describing the role of aspirin and P2Y12 inhibitors in the treatment of acute coronary syndromes, critically appraising the available evidence from clinical trials, and providing current international guidelines and recommendations. Finally, we describe alternative therapeutic regimens to standard dual antiplatelet therapy, in particular for patients at high bleeding risk. The aim of our review is to give a comprehensive representation of current data on antiplatelet therapy in patients with acute coronary syndromes that could be useful both for clinicians and basic science researchers to be up-to-date on this complex topic. [ABSTRACT FROM AUTHOR]

Cancer-associated thrombosis (CAT) is a major cause of both morbidity and mortality in cancer patients. Platelet count has been investigated as a predictor of CAT in various settings while knowledge on platelet activation parameters is sparse. This report provides a systematic review and meta-analysis on available literature on associations between platelet count and/or function and arterial and venous thrombosis in adult cancer patients. The review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. PubMed and Embase were searched up to March 2022. The National Heart, Lung, and Blood Institute's tools were used for quality assessment. In total, 100 studies were included which investigated the association between CAT and platelet count (n = 90), platelet indices (n = 19), and platelet function/activation markers (n = 13) in patients with solid cancers (n = 61), hematological cancers (n = 17), or mixed cancer types (n = 22). Eighty-one studies had venous thrombosis as their outcome measure, while 4 had arterial thrombosis and 15 studies had both. We found significantly elevated odds ratio of 1.50 (95% confidence interval: 1.19–1.88) for thrombosis with higher platelet counts. We saw a tendency toward an association between markers of platelet activation in forms of mean platelet volume and soluble P selectin and both arterial and venous thrombosis. Only one study investigated dynamic platelet function using flow cytometry. In conclusion, platelet count is associated with CAT across different cancer types and settings. Platelet function or activation marker analysis may be valuable in assisting thrombosis risk assessment in cancer patients but is sparsely investigated so far. [ABSTRACT FROM AUTHOR]

Background: Transfusion of platelets is a life-saving medical strategy used worldwide to treat patients with thrombocytopenia as well as platelet function disorders. Summary: Until the end of 1960s, platelets were stored in the cold because of their superior hemostatic functionality. Cold storage of platelets was then abandoned due to better posttransfusion recovery and survival of room temperature (RT)-stored platelets, demonstrated by radioactive labeling studies. Based on these findings, RT became the standard condition to store platelets for clinical applications. Evidence shows that RT storage increases the risk of septic transfusion reactions associated with bacterial contamination. Therefore, the storage time is currently limited to 4–7 days, according to the national guidelines, causing a constant challenge to cover the clinical request. Despite the enormous efforts made to optimize storage conditions of platelets, the quality and efficacy of platelets still decrease during the short storage time at RT. In this context, during the last years, cold storage has seen a renaissance due to the better hemostatic functionality, reduced risk of bacterial contamination, and potentially longer storage time. Key Messages: In this review, we will focus on the impact of cold storage on the in vitro platelet functions as promising alternative storage temperature for future medical applications. [ABSTRACT FROM AUTHOR]

Aspirin (ASA) remains the most common antiplatelet agent used in children. VerifyNow Aspirin Test® (VN) assesses platelet response to ASA, with therapeutic effect defined by the manufacturer as ≤ 549 aspirin reaction units (ARU). Single-center, observational, analysis of 195 children (< 18 years-old) who underwent first VN between 2015 and 2020. Primary outcome was proportion of patients with ASA biochemical resistance (> 549 ARU). Secondary outcomes included incidence of new clinical thrombotic and bleeding events during ≤ 6 months from VN in those who received ASA monotherapy (n = 113). Median age was 1.8 years. Common indications for ASA included cardiac anomalies or dysfunction (74.8%) and ischemic stroke (22.6%). Median ASA dose before VN was 4.6 mg/kg/day. Mean VN was 471 ARU. ASA biochemical resistance was detected in 14.4% (n = 28). Of 113 patients receiving ASA monotherapy, 14 (12.4%) had a thrombotic event and 2 (1.8%) had a bleeding event. Mean VN was significantly higher at initial testing in patients experiencing thrombotic event compared to those without thrombosis (516 vs 465 ARU, [95% CI: 9.8, 92.2], p = 0.02). Multivariable analysis identified initial VN ASA result ≥ 500 ARU at initial testing as the only significant independent risk factor for thrombosis (p < 0.01). VN testing identifies ASA biochemical resistance in 14.4% of children. VN ASA ≥ 500 ARU rather than ≥ 550 ARU at initial testing was independently associated with increased odds of thrombosis. Designated cut-off of 550 ARU for detecting platelet dysfunction by ASA may need reconsideration in children. [ABSTRACT FROM AUTHOR]

Background: This is a sub‐analysis of the Personalized Antithrombotic Therapy for Coronary Heart Disease after PCI (PATH‐PCI) trial in China to explore the relationship between smoking and outcomes following personalized antiplatelet therapy (PAT) in chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI). Methods: As a single‐center, prospective, randomized controlled and open‐label trial, the PATH‐PCI trial randomized CCS patients undergoing PCI into standard group or personalized group guided by a novel platelet function test (PFT), from December 2016 to February 2018. All patients were divided into smokers and nonsmokers according to their smoking status. Subsequently, we underwent a 180‐day follow‐up evaluation. The primary endpoint was the net adverse clinical events (NACE). Results: Regardless of smoking status, in the incidence of NACE, there was a reduction with PAT but that the reductions are not statistically significant. In the incidence of bleeding events, we found no statistically significant difference between two groups (smokers: 2.0% vs. 1.4%, HR = 1.455, 95% confidence interval [CI]: 0.595−3.559, p =.412; nonsmokers: 2.2% vs. 1.8%, HR = 1.228, 95% CI: 0.530−2.842, p =.632). In smokers, PAT reduced major adverse cardiac and cerebrovascular events (MACCE) by 48.7% (3.0% vs. 5.9%, HR = 0.513, 95% CI: 0.290−0.908, p =.022), compared with standard antiplatelet therapy (SAT). PAT also reduced the major adverse cardiovascular events (MACE) but there was no statistically difference in the reductions (p >.05). In nonsmokers, PAT reduced MACCE and MACE by 51.5% (3.3% vs. 6.7%, HR = 0.485, 95% CI: 0.277−0.849, p =.011) and 63.5% (1.8% vs. 4.9%, HR = 0.365, 95% CI: 0.178−0.752, p =.006), respectively. When testing p‐values for interaction, we found there was no significant interaction of smoking status with treatment effects of PAT (pint‐NACE =.184, pint‐bleeding =.660). Conclusion: Regardless of smoking, PAT reduced the MACE and MACCE, with no significant difference in bleeding. This suggests that PAT was an recommendable regimen to CCS patients after PCI, taking into consideration both ischemic and bleeding risk. [ABSTRACT FROM AUTHOR]

Background: The clinical course of ischemic and hemorrhagic strokes can be influenced by the coagulation status of individual patients. The prior use of antiplatelet therapy (APT) such as acetylsalicylic acid (ASA) or P2Y12-antagonists has been inconsistently described as possibly increasing the risk of hemorrhagic transformation or expansion. Since clinical studies describing prior use of antiplatelet medication are overwhelmingly lacking specific functional tests, we aimed to implement testing in routine stroke care. Methods: We used fluorescence-activated cell sorting (FACS) with antibodies against CD61 for thrombocyte identification and CD62p or platelet activation complex-1 (PAC-1) to determine platelet activation. Aggregometry and automated platelet functioning analyzer (PFA-200) were employed to test thrombocyte reactivity. FACS and aggregometry samples were stimulated in vitro with arachidonic acid (AA) and adenosine diphosphate (ADP) to measure increase in CD62p-/PAC-1-expression or aggregation, respectively. Results: Between February and July 2023, 20 blood samples (n = 11 ischemic strokes; n = 7 hemorrhagic strokes; n = 2 controls) were acquired and analyzed within 24 h of symptom onset. N = 11 patients had taken ASA, n = 8 patients no APT and n = 1 ASA+clopidogrel. ASA intake compared to no APT was associated with lower CD62p expression after stimulation with AA on FACS analysis (median 15.8% [interquartile range {IQR} 12.6-37.2%] vs. 40.1% [IQR 20.3-56.3%]; p = 0.020), lower platelet aggregation (9.0% [IQR 7.0-12.0%] vs. 88.5% [IQR 11.8-92.0%]; p = 0.015) and longer time to plug formation with PFA-200 (248.0 s [IQR 157.0-297] vs. 121.5 s [IQR 99.8-174.3]; p = 0.027). Significant correlations were noted between AA-induced CD62p expression and aggregometry analysis (n = 18; ρ = 0.714; p < 0.001) as well as a negative correlation between CD62p increase and PFA clot formation time (n = 18; ρ = -0.613; p = 0.007). Sensitivity for ASA intake was highest for PFA (81.8% for values ≥155.5 s). The combination of ASA + clopidogrel also affected ADP-induced CD62p and PAC-1 expression. Conclusion: In the clinical setting it is feasible to use differentiated platelet analytics to determine alterations caused by antiplatelet therapy. Among the tests under investigation, PFA-200 showed the highest sensitivity for the intake of ASA in stroke patients. FACS analysis on the other hand might be able to provide a more nuanced approach to altered platelet reactivity. [ABSTRACT FROM AUTHOR]

This review elucidates the intricate relationship between dietary habits and platelet function, emphasizing the influential role of berries. Both macronutrients and micronutrients in our diet have been found to profoundly affect platelet reactivity and aggregation, presenting a potential therapeutic intervention for platelet-associated disorders. The article particularly highlights the bioactive compounds in berries, such as flavonoids, which have demonstrated a correlation with diminished platelet aggregation and reduced thrombotic risk. The underlying molecular mechanisms, including the modulation of platelet activation pathways, are elaborated upon. Furthermore, the potential clinical implications are explored, suggesting dietary modifications and berry supplementation as complementary approaches to manage platelet-associated conditions. In culmination, the importance of dietary habits, predominantly the consumption of berries, in modulating platelet functionality is underscored, proposing avenues for future investigations in nutritional genomics to devise personalized dietary guidelines. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic, inflammatory, immune-mediated disease with a specific cutaneous presentation. Increased platelet aggregation has been observed in patients with extensive psoriatic lesions. The aim of this study was to evaluate the clinical factors affecting platelet reactivity in patients with an exacerbation of psoriasis. Methods: This was a prospective, single-center, observational study, enrolling patients hospitalized for an aggravation of psoriasis. Enrolled patients underwent single platelet function testing with light transmission aggregometry on the first morning of hospitalization. Results: 120 patients were enrolled in the study. Of the compared subgroups, women had higher maximal platelet aggregation (MPA) than men (77% vs. 72%; p = 0.03), and those with BMIs < 25 kg/m2 showed higher platelet reactivity compared to subjects with BMIs ≥ 25 kg/m2 (75% vs. 73%; p = 0.02). There was a positive correlation between MPA and platelet count (r = 0.27; p < 0.01), as well as C-reactive protein concentration (r = 0.20; p = 0.03), while a negative correlation was observed with total cholesterol (r = −0.24; p = 0.01) and triglycerides (r = −0.30; p < 0.01). A two-step analysis based on multidimensional models with random effects revealed that every increase in the platelet count by 103/μL led to an increase in MPA by 0.07% (R2 = 0.07; p < 0.01), and an increase in triglycerides' concentration by 1 mg/dL was related to a reduction in MPA by 0.05% (R2 = 0.07; p < 0.01). Conclusions: The increased platelet reactivity observed in patients with psoriasis appears to be multifactorial and related to several clinical and laboratory features. Further research is warranted to put these findings into a clinical perspective. [ABSTRACT FROM AUTHOR]

Lipoprotein(a) [Lp(a)] is an independent, genetically determined, and causal risk factor for cardiovascular disease. Laboratory data have suggested an interaction of Lp(a) with platelet function, potentially caused by its interaction with platelet receptors. So far, the potential association of Lp(a) with platelet activation and reactivity has not been proven in larger clinical cohorts. This study analyzed intrinsic platelet reactivity before loading with clopidogrel 600 mg and on-treatment platelet reactivity tested 24 h following loading in patients undergoing elective coronary angiography. Platelet reactivity was tested by optical aggregometry following stimulation with collagen or adenosine diphosphate as well as by flow cytometry. Lp(a) levels were directly measured in all patients from fresh samples. The present analysis included 1912 patients. Lp(a) levels ranged between 0 and 332 mg/dl. There was a significant association of rising levels of Lp(a) with a higher prevalence of a history of ischemic heart disease (p

Postcraniotomy pain is a common problem frequently encountered by neurosurgeons. This is typically managed with opioids; however, opioids have been shown to increase intracranial pressure by way of hypercapnia and straining from the associated constipation. Additionally, opioids can confound and mask the neurologic examination of postcraniotomy patients, as well as be the nidus for a potential opioid addiction. Thus, alternative solutions for opioids have been a major topic of investigation within the neurosurgical community. Nonsteroidal anti-inflammatory drugs (NSAIDs) present as a potential solution due to their nonaddictive and analgesic properties, but utilization of NSAIDs in neurosurgical patients has been controversial given that NSAIDs alter platelet function. The degree to which NSAIDs alter platelet function and bleeding time to a clinically relevant manner has remained controversial, although several well-designed studies concluded that the utilization of NSAIDs in post-craniotomy patients does not increase the risk of postoperative bleeding. Herein, we review the pharmacology, efficacy, and safety of NSAIDs with a particular emphasis on NSAID use for postintracranial neurosurgical procedure pain management. [ABSTRACT FROM AUTHOR]

Cangrelor is a rapid-acting, intravenous P2Y12 inhibitor that can be used in patients after percutaneous coronary intervention who require mechanical circulatory support or as a bridge to procedure. We retrospectively reviewed adult patients who received platelet function testing (PFT) with the VerifyNow P2Y12 assay while on cangrelor from March 2021 through November 2022. All patients were initiated on 0.75 mcg/kg/min of cangrelor with P2Y12 reaction unit (PRU) values collected 12–24 h after initiation. Cangrelor doses were adjusted per protocol to maintain PRU values of 85–208. A total of 42 patients were included. Thirty-eight patients (90.5%) required temporary mechanical circulatory support while on cangrelor, and 4 patients (9.5%) received cangrelor as a bridge to procedure. The median cangrelor maintenance dose was 0.5 (interquartile range [IQR]: 0.375–0.75) mcg/kg/min, and the median time in therapeutic range with a PRU value between 85 and 208 was 66.6% (IQR: 39.6%-100%). No patients experienced stent thrombosis. A composite major adverse cardiovascular event occurred in 4 patients (9.5%), and major bleeding occurred in 16 patients (38.1%). Compared to empiric cangrelor dosing of 0.75 mcg/kg/min, PFT-guided cangrelor dose adjustment was associated with a median drug cost savings of $1605.60 (IQR: $0-4281.56). Utilizing PFT with cangrelor may allow for lower, individualized dosing while preventing stent thrombosis. [ABSTRACT FROM AUTHOR]

The objective of this survey was to gain a real-world perspective on coagulation testing by evaluating the availability of various coagulation laboratory tests, assessing specific analytic and postanalytic steps in clinical laboratories in Korea. Participants were surveyed using a 65-question questionnaire specifically focused on their coagulation testing practices related to prothrombin time (PT), activated partial thromboplastin time (aPTT), plasma-mixing studies, lupus anticoagulant (LA) tests, platelet function tests, coagulation factor assays, and the composition of hemostasis and thrombosis test panels. The survey was performed between July and September 2022. The survey achieved a 77.9% (81 of 104) response rate. PT or aPTT tests were performed directly at all participating institutions, followed by D-dimer and fibrinogen tests, platelet function test, and plasma-mixing studies in order of frequency. Variations existed in the performance of mixing test and LA assessment. Patterns of coagulating testing differed depending on the size of the hospital. The survey revealed that most laboratories conducted coagulation tests following the international guidelines such as Clinical Laboratory Standards Institute guidelines and the Korean Laboratory Certification system. However, some coagulation tests, including mixing test and LA tests, are yet to be standardized in Korea. Continuous education on coagulation test methods and internal and external quality control are required to encourage laboratories to enhance the performance of coagulation testing. [ABSTRACT FROM AUTHOR]

Aims: Calcium channel blockers (CCBs) are frequently co-administered with clopidogrel in cardiovascular disease. Although an inhibitory drug interaction exists between them, comprehensive large-scale studies for its validation are lacking. We investigated interactions between CCBs and clopidogrel using a large-scale national registry of patients who underwent percutaneous coronary intervention (PCI). Methods and Results: The Platelet function and genoType-Related long-term Prognosis-Platelet Function Test consortium investigates the association between platelet function test and long-term prognosis during dual antiplatelet therapy including clopidogrel in patients using drug-eluting stents. We compared the ex vivo platelet reactivity using the VerifyNow P2Y12 test and clinical outcomes between CCB users and non-users. Between 2003 and 2018, 11 714 patients were enrolled and categorized into two groups according to CCB usage. A composite endpoint encompassing all-cause mortality, myocardial infarction, stent thrombosis, or stroke was defined as a major adverse cardiac and cerebrovascular event (MACCE). During the 5-year follow-up period, no significant differences were observed in P2Y12 reaction units (215.8 ± 84.7 vs 218.4 ± 76.7, P =.156), MACCEs, major bleeding, or high platelet reactivity rates, even after adjusting for propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). When limited to the high platelet reactivity cohort (≥252 PRU), the results remained consistent for MACCE [PSM-adjusted, HR: 0.923 (0.644-1.323), P -value.663; IPTW-adjusted, HR: 1.300 (0.822-2.056), P -value.262]. Conclusions: CCB and clopidogrel co-administration does not appear to significantly impact clopidogrel responsiveness or clinical outcomes. Despite these promising results, further investigation may be warranted. Clinical trial registration: Platelet Function and genoType-Related Long-term progGosis in DES-treated Patients: A Consortium From Multi-centered Registries [PTRG-DES]; NCT04734028 [ABSTRACT FROM AUTHOR]

The article focuses on Glanzmann's thrombasthenia (GT), an autosomal recessive platelet function disorder, providing insights into its genetic basis, diagnostic criteria, and clinical manifestations. It further discusses the challenges and considerations in anaesthesia for patients with GT, emphasizing the need for meticulous planning, avoidance of certain anaesthetic procedures, and the importance of pre-operative testing to ensure safe perioperative management.

BACKGROUND: Volume indices and count of platelets through sickle cell anemia (SCA) steady state are modified by chronic hemolysis, red blood cell sickling, and vaso-occlusion induced by this structural hemoglobinopathy. The bone pain crises additionally change these parameters. The recognition of the modification in platelet indices has a significant impact on understanding the pathogenesis and outcome of sickle cell disease patients. OBJECTIVES: This study objective is to compare volume indices and count of platelets of SCA patients in steady and through bone pain crisis states. PATIENTS AND METHODS: This is a retrospective cohort study that included 82 SCA patients who received care between October 2022 and October 2023 at the Hereditary Blood Disease Center, Basra, Iraq Written consent was obtained from all the participants and legal guardians. The criteria of inclusion involved SCA patients of 13 years old and older who presented to the center at the period of the stdy. They had their platelet count and volume indices measured during the crises of bone pain and in the steady state later on. Platelet count, platelet distribution width (PDW), plateletcrit (PCT), mean platelet volume (MPV), and platelet-large cell ratio (P-LCR) were measured by the automatic analyzer. RESULTS: Through bone pain crises as well as steady state, patients had a normal mean platelet count in comparison to the reference values of non-SCA population. It was found that MPV, PDW, PCT, and P-LCR were different in a significant way between the steady and bone pain crisis states, with P ≤ 0.001 with the mean values of 9.69 ± 1.25 versus 11.09 ± 0.99 for MPV, 13.27 ± 0.46 versus 15.78 ± 0.65 for PDW, 0.31 ± 0.03 versus 0.36 ± 0.01 for PCT, and 0.16 ± 0.01 versus 0.18 ± 0 for P-LCR, respectively. CONCLUSIONS: Through the steady state as well as bone pain crisis, the platelet count of SCA patients showed a normal value according to the range of reference for the normal population with no SCA. The P-LCR, MPV, PCT, and PDW were different significantly between SCA two clinical states as they became higher through the state of bone pain crises. This finding reflects the increment in the activation of platelets and the existence of large platelets in circulation at the time of vaso-occlusive crises. [ABSTRACT FROM AUTHOR]

Objective To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with longterm clinical outcome in patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI). Methods In total, 675 patients were enrolled. Based on the platelet inhibition rate, patients were categorized into two groups: clopidogrel low responsiveness (CLR) and normal clopidogrel responsiveness (NCR). The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up treatment. Patients were classified into three groups (normal metabolizer, intermediate metabolizer, and poor metabolizer) based on the CYP2C19 genotype. We aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity. The cumulative rates of 12-month all-cause deaths, major adverse cardiovascular events (MACCEs), and bleeding events were calculated. Results CLR was observed in 44.4% of the overall population. Significant differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes (P < 0.05). At the 12-month follow-up, 13 patients (1.9%) died and 96 patients (14.2%) experienced MACCEs. Patients with CLR (9.6% vs. 11.7% vs. 22.1%, P < 0.05) or poor metabolizer (10.7% vs. 16.4% vs. 22.6%, P = 0.026) experienced a higher rate of MACCEs. A MACCEs risk score between zero and two was calculated. The highest incidence of MACCEs significantly increased with the 2-positive results, and the area under the curve (AUC) was 0.712 (95% CI: 0.650-0.774, P < 0.05). There was no significant difference between the group with a score of one and the occurrence of MACCEs (P > 0.05). Conclusions Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene polymorphism. CYP2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI, which is better than either test alone. [ABSTRACT FROM AUTHOR]