High Platelet Research Articles

Acute Promyelocytic Leukemia Asian Consortium study of arsenic trioxide in newly-diagnosed patients: impact and outcome.

The Acute Promyelocytic Leukemia Asian Consortium analyzed a contemporaneous cohort of newly-diagnosed APL patients treated with and without frontline arsenic trioxide (ATO) in six centers. The objectives were to define the impact of ATO on early deaths and relapses, and its optimal positioning in the overall treatment strategy. In a 21.5-year period, 324 males and 323 females at a median age of 45.5 (range: 18.1-91.8) years (low/intermediate risk, N=448; high-risk, N=199) were treated. Regimens included frontline all-trans retinoic acid (ATRA)/chemotherapy and maintenance with/without ATO (N=436); ATRA/intravenous-ATO/chemotherapy (ATRA/i.v.-ATO; N=61); and ATRA/oral-ATO/ascorbic acid with ATO maintenance (oral-AAA; N=150). The ATRA/chemotherapy group, compared with the ATO-containing (ATRA/i.v.-ATO and oral-AAA) groups, had significantly more frequent early deaths within 60 days (8.3% versus 3.3%; P=0.05); inferior 60-day survival (91.7% versus 98.4%/96%; P<0.001); inferior 5-year relapse-free survival (RFS) (76.9% versus 92.8%/97.8%; P<0.001) and inferior 5-year overall survival (OS) (84.6% versus 91.4%/92.3%; P=0.03). Addition of oral-ATO maintenance could partly mitigate the inferior 5-year RFS resulting from omission of ATO during induction (ATRA/chemotherapy/non-ATO maintenance versus ATRA/chemotherapy/ATO maintenance versus ATRA/i.v.-ATO versus oral-AAA: 71.1% versus 87.9% versus 92.8% versus 97.8%, P<0.001). The favorable survival impacts of ATO were observed in both low/intermediate-risk and high-risk patients, so that conventional risks (high leucocyte and low platelet counts) were overcome. Therefore, ATO decreased early deaths, improved 60-day survival, and resulted in significantly superior RFS and OS. Its benefits were most obvious in frontline treatment, but were still observed during maintenance. (ClinicalTrials.gov Identifier: NCT04251754).

Prognostic significance of hemoglobin, albumin, lymphocyte and platelet score in solid tumors: a pooled study

ObjectiveThe high hemoglobin, albumin, lymphocyte, and platelet (HALP) score has been reported to be a good prognostic indicator for several malignancies. However, more evidence is needed before it can be introduced into clinical practice. Here, we systematically evaluated the predictive value of HALP for survival outcomes in patients with solid tumors.MethodsThis study was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Assessing the Methodological Quality of Systematic Reviews (AMSTAR) Guidelines. In March 2024, an electronic literature search was performed for articles regarding the prognostic role of HALP in solid tumors. Data from studies with reported risk ratios (HRs) and 95% confidence intervals (CIs) were pooled in a meta-analysis. Study bias was assessed using the QUIPS tool.ResultsOf the 729 articles reviewed, 45 cohorts including data from 17,049 patients with cancer were included in the pooled analysis. The pooled results demonstrated that elevated HALP score was significantly associated with favorable overall survival (HR = 0.60, 95% CI 0.54-0.67, p &amp;lt; 0.01), cancer-specific survival (HR = 0.53, 95% CI 0.44- 0.64, p &amp;lt; 0.01), progression-free survival (HR = 0.62, 95% CI 0.54-0.72, p &amp;lt; 0.01), recurrence-free survival (HR = 0.48, 95% CI 0.30-0.77, p &amp;lt; 0.01), and disease-free survival (HR = 0.72, 95% CI 0.57-0.82, p &amp;lt; 0.01). Subgroup analyses based on various confounding factors further revealed the consistent prognostic impact of HALP on overall survival in patients with solid tumors.ConclusionsOur findings suggest that high HALP is associated with better survival outcomes in patients. The HALP score is a potential prognostic biomarker in solid tumors, but it needs to be further studied whether it can improve the established prognostic model.

Exploring the morphine-platelet activity association in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention

ST-segment elevation myocardial infarction (STEMI) is usually caused by a ruptured atherosclerotic plaque, with subsequent thrombus formation. Platelet inhibition and primary percutaneous coronary intervention (PCI) are essential treatments. Morphine, used to relieve pain and anxiety in STEMI patients, delays the onset of P2Y12 inhibitors. This study aimed to further explore the association between platelet activity and morphine treatment in patients with STEMI. In this sub-study of the VALIDATE-SWEDHEART trial, 89 STEMI patients treated with ticagrelor, and primary PCI were included. Platelet aggregation and biomarkers of platelet activity, coagulation, and inflammation (sP-selectin, thrombin-antithrombin complexes, prothrombin fragments 1 + 2, CD40L, CRP, beta-thromboglobulin, and pentraxin3) were assessed at three time points: before, one, and twelve hours after PCI. Of the 89 patients, 40 received morphine before hospital arrival. There were no significant differences in age, sex, medical history, or coronary disease extent. One hour after PCI, ADP-induced (36 vs 61, p < .001), arachidonic acid-induced (20 vs 36, p = .003), collagen-induced (48 vs 60, p = .03) aggregation, and the proportion of high on-treatment ADP-induced platelet reactivity (27% vs 60%, p = .001) were significantly higher in morphine-treated patients. No significant differences were found before or 12 hours after PCI. No significant differences in platelet activity biomarkers were observed. Morphine increased platelet aggregation in STEMI patients but did not affect biomarkers.

Fluid Dynamic and in Vitro Blood Study to Understand Catheter-Related Thrombosis.

Central venous catheters (CVCs) provide a direct route to the venous circulation but are prone to catheter-related thrombosis (CRT). A known CRT risk factor is a high catheter-to-vein ratio (CVR), or a large catheter diameter with respect to the indwelling vein size. In this study, the CVR's effect on CVC hemodynamics and its impact on CRT is investigated with in vitro and in silico experiments. An in vitro flow loop is used to characterize the hemodynamics around CVCs using particle image velocimetry. In addition, CRT is investigated using an in vitro flow loop with human blood and clinical catheters. The wall shear rate of flow around the CVC is computed numerically. CVRs of 0.20, 0.33, and 0.49 and Reynolds numbers of 200, 800, and 1300 are evaluated. No flow is used through CVC lumens to model chronic indwelling catheters. Results show CVR ≥ 0.33 promotes platelet-rich clot growth at the device tip and at an increased rate compared to lower CVR cases. A high wall shear rate gradient on the CVC tip and an extended wake distal to the tip exists for higher CVR cases, promoting the aggregation of platelets and subsequent stagnation for clot formation. Further, the combination of the CVR and Reynolds number are crucial to CRT potential, not the CVR alone. Specifically, thrombosis risk is increased with low (stasis driven) and/or high (platelet activation driven) flow conditions, with the CVR and CVC's geometry playing an additional role in promoting fluid mechanic driven thrombus development. A high CVR (≥ 0.33) and high flow condition (≥ 1300) results in the highest risk for clot growth at the tip of the device; other locations of the device are at risk for thrombus development in lower flow conditions, regardless of the CVR. The importance of the device geometry and flow in promoting thrombus and fibrin sheath formation is also shown for the device investigated. This work demonstrates that the CVR, flow, and device geometry affect CRT. For clinical cases with CVR ≥ 0.33 and/or Re ≥ 1300, the device tip may be monitored more consistently for clot formation. Thrombosis risks remain on the entire catheter, regardless of the flow condition, for a CVR = 0.49. Device placement should be chosen carefully with respect to the combination of the Reynolds number and CVR. Further study is needed on the effect of catheterization to confirm these findings.

Unveiling the hidden link: elevated platelets and T cell subsets in 5% of moderate COVID-19 patients 48 days post-onset.

Platelets are hyperactived during acute COVID-19, promoting clotting and modulating immune-cell responses. Immune thrombocytopenia in adults can manifest as an uncommon complication resulting from various viral infections or as a rare adverse event associated with vaccination. However, their role in convalescent COVID-19 patients remains underexplored. This study examines platelet dynamics early in the pandemic, 48 days post-symptom onset, in unvaccinated patients. This longitudinal study included 298 unvaccinated COVID-19 patients (17 mild, 281 moderate) from multiple centers. Clinical evaluations and peripheral lymphocyte subset analyses via flow cytometry were conducted upon admission and on day 48 post-symptom onset (DPSO 48). At DPSO 48, 5.3% of moderate COVID-19 patients exhibited high platelet counts (>300×109/L), associated with elevated total T-cells (26.4%), CD4 T-cells (24.4%), CD8 T-cells (36.9%), and Tregs (33.9%) compared to patients with normal platelet counts. However, the CD4/CD8 T-cell ratio and T-cell subset frequencies remained unaffected, indicating ongoing T-cell homeostasis restoration. Additionally, a significant positive correlation (r=0.636, p=0.03) was found between platelet counts and B cells in patients with elevated platelet counts. Platelets may play a pivotal role in immune regulation during the recovery phase of COVID-19. Targeting platelets and their secreted mediators could improve immune balance in patients with immune disorders, highlighting a potential therapeutic approach for enhancing recovery in post-COVID-19 patients.

Cooperative SIR dynamics as a model for spontaneous blood clot initiation

Blood clotting is an important physiological process to suppress bleeding upon injury, but when it occurs inadvertently, it can cause thrombosis, which can lead to life threatening conditions. Hence, understanding the microscopic mechanistic factors for inadvertent, spontaneous blood clotting, in absence of a vessel breach, can help in predicting and averting such conditions. Here, we present a minimal model – reminiscent of the SIR model – for the initiating stage of spontaneous blood clotting, the collective activation of blood platelets. This model predicts that in the presence of very small initial activation signals, collective activation of the platelet population is possible, but requires a sufficient degree of heterogeneity of platelet sensitivity. To propagate the activation signal and achieve collective activation of the bulk platelet population, it requires the presence of, possibly only few, hyper-sensitive platelets, but also a sufficient proportion of platelets with intermediate, yet higher-than-average sensitivity. A comparison with experimental results demonstrates a qualitative agreement for high platelet signalling activity.

Hematological Changes in Newly Diagnosed Pulmonary Tuberculosis Patients on Standard Anti-TB Treatment Regimen and their Influence on Smear Conversion

Pulmonary tuberculosis (PTB) mortality remains high despite the availability of effective anti-TB therapy. Disease and treatment-associated hematological derangements at diagnosis and during therapy might contribute to this high TB mortality rate. This paper aims to determine hematological changes in newly diagnosed pulmonary tuberculosis patients on standard anti-TB treatment regimen and their influence on smear conversion. The study adopted a longitudinal design in which 55 newly diagnosed HIV negative PTB patients were followed up to the fifth month of anti-TB therapy. Blood samples (5ml) were collected for diagnosis during the second and fifth months and analyzed using automated HumaCount 5D hematology analyzer. Data was analyzed using Kruskal-wallis test with Dunn’s multiple comparisons test in Graph-Pad prism version 6.0. Throughout therapy, there was a statistically significant time-dependent decrease in median total white blood cell counts from 6.82x103/ uL at diagnosis to 5.87x103/ uL at the fifth month (P=0.0358). This decrease in total WBC count was majorly driven by significant decrease in the neutrophil numbers from 4.31x103/ uL at diagnosis to 2.97x103/ uL at the fifth month. The proportion of patients who had anemia at the fifth month of treatment increased compared to the second month post intensive phase. There was also a significant decrease in MCV, MCH and MCHC at the second month compared to diagnosis. Moreover, the median platelet count, MPV, PDW and PCT% decreased from 314x103/ uL, 8.9 fL, 10.4 fL and 0.273 at diagnosis to 232x103/ uL, 10.15 fL, 12.5 fL and 0.235 at the fifth month, respectively. High WBC count, high platelet count, low lymphocyte count and low HGB at the end of month two of therapy were shown to increase the likelihood of sputum non-conversion (OR-2.42 (95% Ci 2.07-2.82)), (OR-1.5 (95% Ci 1.01-2.22)), (OR-1 (95% Ci 1-1)) and (OR-2.58 (95% Ci 1.68-3.95)), respectively (P&lt;0.05). A significant number of PTB patients presented with anemia, thrombocytosis and leukocytosis. The proportion of patients with anemia increased over time. The study recommends screening for hematological abnormalities in patients for tailored patient interventions for better clinical outcomes.

Abstract 4134589: Evaluating risk factors of embolism in patients with cardiac myxoma: A systematic review and meta-analysis

Background: Risk stratification for embolism in cardiac myxomas remains poorly explored. Goals: By this meta-analysis we studied the risk factors assicated with embolism among patients with cardiac myxoma. Methods: A comprehensive search was conducted across PubMed, Embase, Cochrane Library, and Google Scholar from their inception until January 2024. Statistical analyses were performed using Cochrane's RevMan 5.4 software. For each risk factor, the pooled odds ratio or mean difference was calculated along with the corresponding 95% confidence interval. Results: We included 18 studies in our analysis with a total population of 2601 out of which 525 patients (20.1%) had at least one episode of embolism. The pooled analyses showed that hypertension (p = 0.001), New York Heart Association I/II (p = 0.03), irregular tumor surface (p &lt;0.00001), hyperlipidemia (p &lt; 0.0001), coronary artery disease (p=0.01), high mean platelet volume (p=0.02), high tumor mobility (p&lt;0.00001), were significantly associated with increased incidence of embolism. Female gender (p = 0.03) was the only risk factor associated with reduced risk. Other factors like smoking, atrial fibrillation, tumor size, age, body mass index (BMI), diabetes, left ventricular ejection fraction (LVEF), left atrial diameter (LAD) were not significantly associated with embolism (p &gt; 0.05). Conclusion: Our study is the first to report significant pooled outcomes for gender, hyperlipidemia, coronary artery disease, mean platelet volume, and tumor mobility in the population discussed. Hypertension, New York Heart Association I/II, irregular tumor surface, hyperlipidemia, coronary artery disease, mean platelet volume and tumor mobility were significantly associated with high risk while female gender was associated with low risk of embolism. Patients with high-risk factors might benefit from early evaluation and definitive treatment (surgery).

Platelet count has a U-shaped association with mortality in hemodialysis patients

Our previous manuscript showed that thrombocytopenia predicts all-cause mortality in Chinese hemodialysis (HD) patients. Based on the role of platelets in coagulation, clot formation, and systemic inflammation, we speculate that high platelets increase risk of thrombo-embolic events, hence the mortality. However, research evidence is currently lacking. Therefore, we utilized data from a very large international cohort study to explore the association of platelet counts with mortality and cardiovascular (CV) death in hemodialysis (HD) patients. International data from 396 facilities enrolled in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phase 5 (2012–2015) were analyzed. Participants were divided into 3 groups according to their platelet counts (low: <100, normal: 100–300, high: >300*109). Associations between platelet counts and all-cause and CV mortality were analyzed using Cox regression, adjusted for confounders. There were 13,631 patients with median age of 65 years old. Males accounted for 61.2%. Mean platelet count was 205*109/L overall and ranged from 173 *109/L in China to 227 *109/L in Sweden. Overall, 2,348 (17.2%) patients died and 1017 (7.5%) died from CV disease. Both low (HR:1.48, 95% CI 1.21–1.80, p < 0.001) and high (HR:1.17, 95% CI 1.00- 1.35, p = 0.044) platelet counts were associated with higher all-cause mortality after adjustment for covariates; results for CV death were consistent. Platelet count has a U-shaped association with all-cause and CV mortality in HD patients, and thus may be used as an outcome predictor that is readily available among HD patients.

Application of Raman spectroscopy using an original optical sensor to assess the laboratory efficacy of antiplatelet drugs

The main method for monitoring the laboratory effectiveness of antiplatelet drugs in modern clinical practice is aggregometry, but this method is not without limitations. In this connection, there is an objective need to develop alternative methods. One of the promising areas is the method of Raman spectroscopy (RS).Objective: development of a method to detect high residual platelet reactivity (RPR) in patients with CVD receiving acetylsalicylic acid (ASA) or clopidogrel by giant Raman spectroscopy (GRS) using an original optical biosensor.Material sand Methods. Platelet-rich plasma of patients with cardiovascular diseases (CVD) was investigated by Raman spectroscopy using an original optical biosensor. Platelet aggregation activity was investigated using a Siemens PFA-200 aggregometer with three types of cartridges – Collagen/EPI, Collagen/ADP, and P2Y. Fisher’s linear discriminant analysis was performed using Statistica 13.0 package.Results. Raman spectra analysis using different values of frequency shifts (970 cm-1 or 1590 cm-1), allows to evaluate laboratory ineffectiveness separately for ASA and clopidogrel. Thus, the number of patients with high residual platelet reactivity (RPR) was 41.7 % ± 6.3 % with ASA and 36.7 % ± 6.2 % with clopidogrel therapy; similar values using aggregometry were 43.5 % ± 10.3 % and 30.4 % ± 9.6 %.Conclusion. Application of the method of Raman spectroscopy using the original optical biosensor allows to distinguish patients with high RPR in the population of patients with CVD receiving antiaggregant therapy.

Platelet to erythrocyte ratio and mortality in massively transfused trauma patients

BackgroundThe optimal transfusion ratio of platelets (PLT), plasma and red blood cells (RBC) in trauma patients with massive haemorrhage is still a subject of discussion. The objective of this study is to assess the effect of platelet transfusion on mortality in trauma patients who received massive transfusion. MethodsData were collected from four Dutch level-1 trauma centres. All trauma patients aged ≥ 16 years who received ≥ 6 RBC / 6 h from the time of injury were included. Patients were divided based on PLT:RBC ratio (no platelets, low (<1:5) and high (≥1:5)). Primary outcome measure was 6-hour mortality and secondary outcomes included mortality at other time points and transfusion characteristics. ResultsA total of 292 patients were included. Patients in the high PLT ratio group had lower mortality rates at six and 12 h as compared to the low PLT ratio and no PLT group. In the high PLT group mortality as a result of exsanguination (12 %) was significantly lower as compared to the low PLT group (23 %). High PLT ratio had lower probability for 6-hour mortality multivariable analysis. Higher plasma:RBC ratios were associated with lower mortality at all time points. ConclusionsAlthough the optimal patient specific transfusion strategy in patients with traumatic haemorrhage is still not resolved, these results show that higher PLT to RBC ratios are associated with lower early mortality.

Thrombocytopenia Predicts Poor Prognosis of Liver Transplantation

Background/AimPlatelets not only participate in physiological hemostasis but also play a major role in liver ischemia-reperfusion injury, liver damage, tissue repair, and liver regeneration. A decrease in platelet count can lead to spontaneous bleeding, infection, and other complications that can seriously impact patient prognosis. Thrombocytopenia has been associated with increased complications after partial hepatectomy, although the effects of thrombocytopenia on patient outcomes remain unclear. Therefore, this study aimed to examine the impact of thrombocytopenia on short- and long-term prognosis following liver transplantation (LT). MethodsThis was a retrospective analysis comprising 234 adult liver transplant recipients and conducted from January 2019 to June 2022. Preoperative and postoperative daily platelet counts were recorded up to the 30th postoperative day (POD). We defined people with platelet counts <70 × 109/L as the low platelet group, and people with platelet counts >70 × 109/L as the high platelet group. Multivariate analysis was carried out to determine whether low perioperative platelet count was a risk factor for postoperative complications, graft failure, and patient survival. ResultsOf the 234 patients analyzed in this study, approximately half (n = 112, 47.9%) developed persistent thrombocytopenia after LT. The most substantial decrease in platelet levels occurred on POD7. The cumulative survival rates at 1, 2, and 3 years in the high platelet group were higher than those in the low platelet group, 94%, 87%, and 85%, respectively, while those of the low platelet group were 84%, 78%, and 70% (P = .0014). In addition, the high platelet group had a lower incidence of biliary complications compared with the low platelet group (8% vs 19%, P = .020). At the same time, the high platelet group had a lower incidence of posttransplant lung infection (55% vs 75%, P = .040). ConclusionsThrombocytopenia is a common complication of LT. It indicates the severity of the postoperative course and is closely associated with patient survival. In particular, patients who undergo orthotopic liver transplantation (OLT) and have a platelet count <70 × 109/L on the POD7 have significant negative prognostic implications and should be further investigated.

Reduction of thrombus burden by cangrelor in ticagrelor-loaded st-elevation myocardial infarction patients with high residual platelet reactivity: the imaging sub-study of the ERMIT randomized trial

Abstract Background Residual high platelet reactivity (HPR) at the time of primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is associated with higher residual thrombus burden and the subsequent suboptimal reperfusion. Purpose We sought to determine the impact of intravenous Cangrelor on the residual post-PCI thrombus burden in patients with HPR admitted for primary PCI in a prespecified intracoronary optical coherence tomography (OCT) sub-study of the ERMIT randomized trial. Methods In the ERMIT trial patients pre-treated with ticagrelor and aspirin with residual HPR (baseline platelet reactivity unit &amp;gt;208) were randomly assigned in a 1:1 ratio to receive cangrelor on top of standard therapy or standard therapy alone prior to PCI. The primary endpoint of the sub-study was the relative thrombus volume quantified on OCT. Other OCT quantified parameters were predefined as secondary endpoints. Results After screening of 128 patients, a total of 60 patients with HPR were enrolled and randomized. The OCT sub-study included 53 patients, 29 in the cangrelor and 24 in the control group. As reported in the table, baseline characteristics were similar between the groups. The post-PCI PRU was dramatically lower in the cangrelor as compared to the standard group (p&amp;lt;0.001). The primary endpoint was 4.5% [3.4;7.2] versus 6.9% [5.2;8.5], (p=0.03) in the cangrelor and control groups respectively. All other imaging parameters confirmed the significantly lower thrombus burden in patients receiving cangrelor (Table). Conclusion The imaging sub-study of the randomized ERMIT trial shows that cangrelor use is associated with a more effective platelet inhibition and lower post-PCI residual thrombus burden in ticagrelor-loaded STEMI patients with residual HPR. The clinical implications of such finding warrant larger size trials.Table

Cangrelor use in ticagrelor-loaded ST-elevation myocardial infarction patients with high residual platelet reactivity: a randomized controlled trial

Abstract Background Despite the use of potent P2Y12 inhibitor, many patients still present with high platelet reactivity (HPR) at the time of primary percutaneous coronary intervention (PCI). HPR is associated with impaired myocardial reperfusion and the subsequent poor outcome. Purpose We sought to determine the impact of Cangrelor -a rapid and potent intravenous P2Y12 inhibitor- on myocardial reperfusion in patients with HPR admitted for primary PCI in a randomized trial. Methods Patients pre-treated with ticagrelor and aspirin with residual HPR (baseline platelet reactivity unit (PRU) &amp;gt; 208) were randomly assigned in a 1:1 ratio to receive cangrelor (experimental group) or not (control group) just before PCI. The primary endpoint was optimal myocardial reperfusion defined as a final myocardial blush grade (MBG) 3 assessed by an independent core laboratory. Results After screening of 128 patients, a total of 60 patients were with HPR were enrolled and randomized. The ticagrelor loading dose to PRU measurement times were 83 ± 32 and 90 ± 47 minutes in the experimental and control groups, respectively. Baseline PRU were 245 ± 30 and 252 ± 35 in the experimental and standard group, respectively. A final MBG 3 was observed in 21/30 (55%) and 17/30 (45%) the experimental and standard groups (p=0.29). A final TIMI flow grade 3 was observed in 30/30 (100%) and 27/30 (90%) the experimental and standard groups (p=0.24). Peak troponin levels after PCI were 51381 ± 50047 and 51078 ± 63960 ng/L (p=0.98) in the experimental and standard group, respectively. At the end of the PCI, control PRU were 36 ± 57 and 198 ± 107 (p&amp;lt;0.0001) in the experimental and standard group, respectively. One patient of the experimental group presented an in-hospital major bleeding (BARC 3). Conclusion In ticagrelor-loaded STEMI patients with residual HPR at the time of PCI, cangrelor use was associated with a more effective platelet inhibition but failed to significantly improve the rates of optimal final myocardial blush grades.

Remnant cholesterol is associated with platelet reactivity for patients with coronary artery disease underwent percutaneous coronary intervention

Abstract Background In recent years, remnant cholesterol has received increasing attention and has been shown to be associated with thrombotic and bleeding events in coronary clinical research, but the mechanisms are not fully understood. Aim To investigate the relationship between the remnant cholesterol (RC) and the platelet reactivity in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) who were receiving the dual antiplatelet therapy (DAPT). Methods: A total of 10,724 consecutive PCI patients in China from January 2013 to December 2013 were enrolled, among whom 6212 patients had the results of thromborlastogram (TEG) with DAPT for analysis. Low on-treatment platelet reactivity (LTPR) and high on-treatment platelet reactivity (HTPR) were defined as adenosine diphosphate-induced platelet maximum amplitude of TEG&amp;lt;31mm and &amp;gt;47mm, respectively. Results: A total of 6,212 PCI patients (mean age, 58.24±10.27 years;male, 77.5%) were finally enrolled for analysis. There were 2362 (38.02%) patients in LTPR group, and 1900 (30.59%) patients in HTPR group. For LTPR,when the RC is used as a continuous variable, the multivariate logistic regression showed that RC concentration was independently and negatively associated with LTPR (OR: 0.769, 95%CI 0.610-0.968, p=0.025). For quartiles of RC, the quartile 3 of RC was also associated with LTPR, compared with the lowest quartile (Q1) (OR: 0.854, 95%CI 0.732-0.996, p=0.044). For HTPR, when the RC is used as a continuous variable, the multivariate logistic regression showed that RC concentration was independently and positively associated with HTPR (OR: 1.492, 95%CI 1.162-1.916, p=0.002). For quartiles of RC, compared with the lowest quartile (Q1), the higher quartile of RC (Q2, Q3, Q4) was also associated with HTPR (ORQ2: 1.211, 95%CI 1.024-1.431, p=0.025; ORQ3: 1.380, 95%CI 1.165-1.634, p＜0.001; ORQ4: 1.391, 95%CI 1.143-1.692, p=0.001). Conclusions: In this large sample real-world study, we firstly reported that the lower RC concentration was an independent risk factor for LTPR, representing a higher risk of bleeding, whereas the higher RC concentration was an independent risk factor for HTPR, representing a higher risk of ischemic. These results suggest that higher or lower RC may increase the potential risk of bleeding or ischemia in patients with PCI, which provides new perspectives on individualized lipid-lowering and antithrombotic treatment strategies for patients with coronary artery disease.

Differential prognostic significance of platelet reactivity based on ischemic risk after percutaneous coronary intervention

Abstract Background High platelet reactivity (HPR) in patients underwent percutaneous coronary intervention (PCI) is a potential risk factor of adverse cardiovascular events. It is not well understood in which patients HPR is particularly clinically important. Purpose We aimed to elucidate the prognostic value of high platelet reactivity (HPR), across varying levels of ischemic risk categorized by the CHADS-P2A2RC score in a large registry. Methods We retrospectively analyzed 11,714 patients who underwent PCI in the PTRG-DES registry. Ischemic risk was stratified using the CHADS-P2A2RC score into low (score ≤ 1), moderate (score 2–3), and high (score ≥ 4) groups. HPR was defined as a P2Y12 Reaction Unit (PRU) value ≥252. The incidence of major adverse cardiac and cerebrovascular events (MACCE) during 5- year follow-up was the primary outcome. Results During the median follow-up of 37.6 months (IQR, 12.0–60.8), a total of 709 MACCEs (6.1%) (392 deaths [3.3%], 172 non-fatal MI [1.5%], 62 ST [0.5%] and 181 non-fatal stroke [1.5%]), and 324 cases of major bleeding (2.8%) occurred. The high-risk group has the highest incidence of MACCE during 5-year follow-up unadjusted HR of 4.206, 95% CI 3.204–5.521. Among the 2,577 low-risk patients, HPR did not significantly affect MACCE incidence (HR 1.366, 95% CI 0.798–2.336, p=0.253). In the moderate-risk cohort of 5,417 patients, HPR conferred a modest increase in MACCE risk (HR 1.289, 95% CI 1.008–1.649, p=0.043). Notably, the high-risk group demonstrated a significant association between HPR and MACCE (HR 1.385, 95% CI 1.135–1.692, p&amp;lt;0.001). Conclusion HPR is a potent risk factor of long-term outcomes following PCI, especially in patients with a high ischemic risk based on CHADS-P2A2RC scoring. The results highlight the varying impact of platelet reactivity depending on the level of ischemic risk, indicating the importance of tailored antiplatelet therapy in high-risk group to improve clinical outcomes.

Comparative effects of different antiplatelet strategies in carriers of CYP2C19 loss-of-function alleles: a network meta-analysis

Abstract Background Carriers of cytochrome 2C19 (CYP2C19) loss of function (LoF) alleles treated with clopidogrel have impaired drug metabolism resulting in reduced active metabolite levels, high platelet reactivity (HPR), and an increased risk of thrombotic events. Several alternative antiplatelet therapies have been proposed to overcome HPR in these patients, but their comparative effects remain poorly explored. Purpose To assess the comparative effects of different alternative antiplatelet agents in carriers of CYP2C19 LoF alleles undergoing percutaneous coronary interventions (PCI). Methods Randomized controlled trials (RCTs) comparing different oral antiplatelet therapies in carriers of CYP2C19 LoF alleles undergoing PCI were included. A frequentist network meta-analysis was conducted to estimate mean difference (MD) or odds ratios (OR) and 95% confidence intervals (CI). The primary outcome was platelet reactivity assessed by VerifyNow and reported as P2Y12 reaction unit (PRU). The secondary outcome was the rate of HPR as defined in each trial. Standard-dose of clopidogrel (75 mg daily) was used as reference treatment. Antiplatelet strategies were ranked according to P-scores, ranging between 0 (poor performance) and 1 (good performance). Results A total of 13 RCTs testing 6 alternative strategies (i.e., clopidogrel 150 mg, prasugrel 3.75 mg, 5 mg, and 10 mg, ticagrelor 90 mg bid, and adjunctive cilostazol 100 mg bid) were included in the network. Compared with standard-dose clopidogrel, the greatest reduction in PRU was observed with prasugrel 10 mg (MD -128.61; 95% CI -145.09; -111.49) and ticagrelor 90 mg bid (MD -125.61; 95% CI -170.66; -80.56), followed by prasugrel 5 mg (MD -118.03; 95% CI -143.15; -92.92) and prasugrel 3.75 mg (MD -73.00; 95% CI -108.97; -37.03). High-dose clopidogrel was associated with a modest (MD -32.11; 95% CI -51.33; -12.90) and adjunctive cilostazol with a non-significant (MD -44.11; 95% CI -98.05; -9.82) reduction in PRU compared with standard-dose clopidogrel (Figure 1). Rates of HPR were reduced with all treatments compared with standard-dose clopidogrel. Ranking of treatments for the primary endpoint showed that standard-dose prasugrel ranked as the best treatment (P-score=0.884), followed by ticagrelor (P-score=0.835), low-dose prasugrel (0.767), very-low dose prasugrel (P-score=0.474), cilostazol (P-score=0.306), high-dose clopidogrel (P-score=0.224), and standard-dose clopidogrel (P-score=0.009) (Figure 2). Conclusion Among carriers of CYP2C19 LoF alleles undergoing PCI, standard-dose prasugrel or ticagrelor are most effective in reducing platelet reactivity, followed by reduced-dose of prasugrel, while double-dose clopidogrel and adjunctive cilostazol showed only modest effects. The clinical implications of these pharmacodynamically effective strategies warrant further investigation.

Platelet Reactivity with MACE in Acute Coronary Syndrome Patients Post-PCI under Dual Antiplatelet Therapy: A Meta-Analysis.

Aim/Background Acute coronary syndrome (ACS), a condition characterized by acute cardiac ischemia, is among the major causes of death from cardiovascular diseases (CVD). However, whether there is a correlation between platelet reactivity and major adverse cardiovascular events (MACE) remains debatable, and whether platelet function tests should be tailored for ACS patients after percutaneous coronary intervention (PCI) is still under discussion. This study aims to investigate the relationship between platelet reactivity and the occurrence of MACE in ACS patients post-PCI and to discuss the implications of these findings. Methods Clinical studies on 'PCI, ACS, dual antiplatelet therapy (DAPT), platelet reactivity, major adverse cardiovascular events (MACE)' up to 31 October 2023, were systematically collected from Embase, PubMed, and the Cochrane Library. Twelve articles meeting predefined criteria were selected. Meta-analysis was performed using Review Manager 5.4 (Cochrane, London, UK) and Stata 15.0 (StataCorp LLC, College Station, TX, USA) to compute pooled effect sizes, assess heterogeneity, explore sources of heterogeneity, and evaluate publication bias. Results Twelve articles consisting of 9297 patients were included. The meta-analysis showed that ACS patients with high platelet reactivity (HPR) who received PCI and used DAPT for 1-2 years had a greater risk of MACE (risk ratio (RR) = 1.79, 95% confidence interval (CI): 1.30-2.46) compared to those with low platelet reactivity. Moreover, greater platelet reactivity was associated independently with all-cause mortality (RR = 2.26, 95% CI: 1.63-3.12), cardiac mortality (RR = 2.87, 95% CI: 2.16-3.8), myocardial infarction (RR = 1.98, 95% CI: 1.53-2.5), in-stent restenosis (RR = 1.87, 95% CI: 1.22-2.87), as well as stroke (RR = 1.62, 95% CI: 1.02-2.57), but not with coronary revascularization events (RR = 0.99, p = 0.96, 95% CI: 0.80-1.24). On the other hand, meta-regression revealed that region (p = 0.99), type of ACS patient (p = 0.16), drug regimen (p = 0.48), testing method (p = 0.51), sampling time (p = 0.70), follow-up time (p = 0.45), and PCI protocol (p = 0.27) were not sources of heterogeneity in the study. Conclusion The meta-analysis outcomes indicate that in ACS patients receiving PCI and using dual antiplatelet therapy for 1-2 years, HPR was independently positively correlated with major adverse cardiovascular events, all-cause (or cardiac) mortality, recurrent myocardial infarction, in-stent restenosis, and stroke. This suggests that platelet reactivity testing has clinical and translational significance in predicting patients' risk of adverse cardiovascular events.

Elevated Platelet Aggregation in Patients with Ovarian Cancer: More than Just Increased Platelet Count.

Background: Patients with ovarian cancer have high platelet counts, which correlate with disease burden, incidence, and lethality of blood clots (thrombosis). We hypothesized that elevated aggregation is associated with both increased platelet number and altered behavior of platelets in patients with ovarian cancer. Methods: Healthy controls and patients with suspected or diagnosed ovarian cancer were evaluated for complete blood counts. To evaluate the effects of platelet count versus platelet behavior, equal platelet-rich plasma (PRP) volumes versus equal platelet numbers were used in platelet aggregation assays. Arachidonic acid, adenosine diphosphate, and collagen platelet agonists were used to induce aggregation. Volunteers were grouped into healthy controls (23), benign/borderline cases (7), and cancer cases (25 ovarian, 1 colorectal, and 2 endometrial). Results: The rate and amount of platelet aggregation were higher in patients compared to healthy controls regardless of whether the same platelet number or PRP volume was used. Compared to healthy controls, patients with untreated ovarian cancer exhibited high levels of platelet activation markers, P-selectin (27.06 vs. 31.06 ng/mL, p = 0.03), and beta-thromboglobulin (3.073 vs. 4.091 µg/mL, p = 0.02) in their plasma. The significance of the elevation and its correlations with platelet number or PRP volume varied depending on the agonist. Platelet (305.88 vs. 134.12, p < 0.0001) and white blood cell (8.459 vs. 5.395, p < 0.01) counts (×109/L) were elevated pre-chemotherapy and decreased post-chemotherapy, respectively. Conclusions: Elevated platelet aggregation is caused by both altered platelet number and behavior in patients with ovarian cancer. These results support the study of antiplatelet agents for thrombosis prevention in these patients.

The first in-human study to evaluate the antiplatelet properties of the clopidogrel conjugate DT-678 in acute coronary syndrome patients and healthy volunteers.

DT-678 is a novel antiplatelet prodrug, capable of releasing the antiplatelet active metabolite of clopidogrel (AM) upon exposure to glutathione. In this study, we investigated factors responsible for clopidogrel high on-treatment platelet reactivity (HTPR) in acute coronary syndrome (ACS) patients and evaluated the capacity of DT-678 to overcome HTPR. A total of 300 consecutive ACS patients naive to P2Y12 receptor inhibitors were recruited and genotyped for CYP2C19 alleles. Blood samples were drawn before and after administration of 600-mg clopidogrel. Platelet reactivity index (PRI) and plasma AM concentrations were determined and grouped according to their CYP2C19 genotypes. DT-678 was applied ex vivo to whole blood samples to examine its inhibitory effects. To further examine the antiplatelet effectiveness of DT-678 in vivo, 20 healthy human subjects were recruited in a Phase I clinical trial, and each received a single dose of either 3-mg DT-678 or 75-mg clopidogrel. The pharmacokinetics and pharmacodynamics in different CYP2C19 genotype groups were compared. Statistical analyses revealed that CYP2C19 genotype, body mass index, hyperuricaemia, and baseline PRI were significantly associated with a higher risk of clopidogrel HTPR in ACS patients. The addition of DT-678 ex vivo decreased baseline PRI regardless of CYP2C19 genotypes, overcoming clopidogrel HTPR. This observation was further confirmed in healthy volunteers receiving 3mg of DT-678. These results suggest that DT-678 effectively overcomes clopidogrel HTPR resulting from genetic and/or clinical factors in Chinese ACS patients, demonstrating its potential to improve antiplatelet therapy.