Abemaciclib increases the risk of venous thromboembolism in breast cancer: Integrate meta-analysis, pharmacovigilance database analysis, and in vitro validation.

BACKGROUND: Recently, cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have emerged as a novel treatment strategy for breast cancer. However, increasing reports of CDK4/6i-associated venous thromboembolism (VTE) have garnered attention. This study assessed CDK4/6i-associated VTE in breast cancer, and examined the effect of CDK4/6i on platelet/coagulation function for the first time in vitro. METHODS: PubMed and Embase databases were searched for studies published from the establishment of the database to December 31, 2022 for randomized controlled trials (RCTs) and real-world studies of CDK4/6i in patients with breast cancer, and the data obtained from the included studies were used for meta-analysis. A disproportionality analysis by extracting adverse drug reaction signals of CDK4/6i-associated VTE from the FDA Adverse Event Reporting System (FAERS) database was also conducted. Additionally, the in vitro effect of CDK4/6i on platelet function was assessed based on platelet aggregation tests and flow cytometry, and coagulation function was assessed based on the blood clotting function test. FINDINGS: A total of 16,903 patients in 13 RCTs and 6,490 patients in 9 real-world studies were included in the meta-analysis. In RCTs, VTE occurred in 193 (2.1 %) and 55 (0.7 %) patients in the CDK4/6i and control groups, respectively. In real-world studies, the aggregate incidence rate of VTE was 4.2 % (95 % CI: 2.1, 6.3). The meta-analysis of RCTs revealed that abemaciclib (Odds ratio [OR]: 4.40 [95 % CI: 2.74,7.05], p < 0.001) and palbociclib (OR: 2.35 [95 % CI: 1.34, 4.12], p < 0.01) significantly increased the risk of VTE in patients with breast cancer compared to placebo. FAERS database analysis revealed that abemaciclib (reporting odds ratio [ROR]: 1.63 [95 % CI: 1.36, 1.97]; IC025: 0.67) and ribociclib (ROR: 1.17 [95 % CI: 1.0, 1.39]; IC025: 0.18) demonstrated a significantly increased signal of VTE. Similarly, findings from in vitro experiments demonstrated that abemaciclib enhanced agonist-induced platelet activation, especially when collagen was used as the inducer, and this effect became more prominent with increasing its concentration. INTERPRETATION: Use of abemaciclib may increase the risk of VTE in patients with breast cancer, which may be partially attributed to the effect of abemaciclib on platelet function. Close monitoring of VTE occurrence is highly recommended while using abemaciclib, especially in patients at a high risk of VTE.

Considerations in Antiplatelet Therapy in Women Undergoing Treatment of Acute Coronary Syndrome or Percutaneous Coronary Intervention.

Antiplatelet therapy is integral to reduce the risk of future ischemic events following acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI); this aim must be balanced by limiting the risk of bleeding. Women with ACS or undergoing PCI have distinct platelet physiology, vascular anatomy, and clinical profiles that can influence the selection of an appropriate regimen. There are procedural techniques that can enhance safety in women. The poor inclusion of women in ACS and PCI trials limits our understanding of the ideal antiplatelet regimen in women, and future studies must find ways to increase the participation of female patients.

Enhanced platelet function through CAR-T cell therapy in relapsed/refractory multiple myeloma.

The influence of chimeric antigen receptor T (CAR-T) cell therapy on platelet function in relapsed/refractory (R/R) multiple myeloma (MM) has not been thoroughly investigated. Our cohort comprised fifty MM patients treated with CAR-T cells. The mean platelet closure time (PCT) induced by collagen/adenosine diphosphate (CADP) in peripheral blood was significantly prolonged before lymphodepletion (195.24 ± 11.740 s) and notably reduced post-CAR-T cell therapy (128.02 ± 5.60 s), with a statistically significant improvement (67.22, 95% CI 46.91-87.53, P < 0.001). This post-treatment PCT was not significantly different from that of healthy controls (10.64, 95% CI 1.11-22.40, P > 0.05). Furthermore, a pronounced enhancement in PCT was observed in patients with a response greater than partial remission (PR) following CAR-T cell infusion compared to pre-treatment values (P < 0.001). An extended PCT was also associated with a less favorable remission status. In patients with cytokine release syndrome (CRS) grades 0-2, those with a PCT over 240.5 s exhibited a shorter progression-free survival (PFS), with median PFS times of 10.2 months for the PCT > 240.5 s group versus 22.0 months for the PCT ≤ 240.5 s group. Multivariate analysis revealed that a PCT value exceeding 240.5 s is an independent prognostic factor for overall survival (OS) in R/R MM patients after CAR-T cell therapy. The study demonstrates that CAR-T cell therapy enhances platelet function in R/R MM patients, and PCT emerges as a potential prognostic biomarker for the efficacy of CAR-T cell therapy.

Sensitive objective markers for measuring aspirin responsiveness in pregnancy: An explorative scoping review.

BACKGROUND: Aspirin is frequently used in pregnancy to decrease the risk of developing pre-eclampsia. Studies have highlighted this potential benefit which in theory happens by inhibition of platelet function. However, questions remain on the appropriate dosing and the reliability of serum markers in determining aspirin responsiveness in pregnancy (ARP). OBJECTIVE: review the literature on ARP and identify the gaps, followed by investigating the objective biomarkers used to assess ARP. This includes the factors associated such as aspirin formulations, doses, and patient comorbidities. METHODS: A comprehensive search was conducted using keywords such as 'aspirin', 'pregnancy', and 'responsiveness' in relevant databases such as PubMed, SCOPUS, Cochrane from inception to March 2024. Our inclusion criteria enrolled pregnant women aged 18 years old and above, irrespective of their trimester status, who were prescribed aspirin for any medical indication. RESULTS: The research findings encompass three key areas. Firstly, examination of the impact of different aspirin formulations on responsiveness revealed no significant differences between different formulations. Secondly, nine papers were identified with varied dosages of administered aspirin, highlighting a need for standardized approach to dosing, and investigating higher dosing and its impact. Thirdly, there is a lack of consensus on biomarkers used to assess ARP. Finally, this synthesis sheds light on prognostic factors of developing aspirin non-responsiveness, such as medical comorbidities. CONCLUSION: This scoping review identifies several residual uncertainties on ARP. The main gaps are validation of serum markers, understanding the influence of underlying morbidity on ARP, and determining appropriate aspirin dosing in pregnancy.

Impact of renal replacement therapy modality on coagulation and platelet function in critically ill patients: A prospective observational study.

BACKGROUND: Renal replacement therapy (RRT) may affect coagulation and platelet function in critically ill patients. However, the mechanism and the difference in the impact on coagulation between intermittent hemodialysis (iHD) and continuous renal replacement therapy (CRRT) remains unclear. This study aimed to investigate and compare the impact of iHD and CRRT on coagulation and platelet function. METHODS: Critically ill patients undergoing RRT were classified into the iHD group or the CRRT group. After the first blood sampling, patients underwent either a single session of hemodialysis or 48 h of CRRT, then a second blood sample was taken. Rotational thromboelastometry (ROTEM), platelet aggregometry and conventional coagulation tests were performed. The primary outcome was a change in extrinsically activated ROTEM (EXTEM) clotting time (CT). RESULTS: 60 dialysis sessions from 56 patients were finally included, with 30 dialysis sessions per group. EXTEM CT was prolonged significantly after dialysis in the iHD group (90 [74, 128] vs. 74 [61, 91], p < 0.001), but did not change in the CRRT group (94.4 ± 29.4 vs. 91.6 ± 22.9, p = 0.986). The platelet aggregation did not change after both iHD and CRRT. A change in EXTEM CT was significantly greater in the iHD group compared to the CRRT group (p = 0.006). The difference in the incidence of bleeding events was insignificant between the two groups (p = 0.301). CONCLUSIONS: EXTEM CT was significantly prolonged after iHD, but this change was not shown after CRRT. Platelet function was not affected by both dialysis modalities.

The Significance of Platelet Indices in the Evaluation of Thrombocytopenia.

INTRODUCTION: Thrombocytopenia, characterized by a low platelet count, poses a risk of abnormal bleeding. Traditional diagnostic methods focus on platelet count alone, but emerging evidence suggests that platelet indices like mean platelet volume (MPV) and platelet distribution width (PDW) could provide valuable insights. This study aims to investigate the role of platelet indices in thrombocytopenia assessment, exploring their potential as additional diagnostic and prognostic markers. METHODOLOGY: Over a five-month period, this prospective study enrolled 80 adult patients with thrombocytopenia. Platelet indices were measured using an automated blood cell analyzer (SYSMEX XN 1000; Sysmex Corporation, Kobe, Japan), and statistical analyses were performed using the Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 23.0, Armonk, NY). RESULTS: The study participants showed significant age differences between hypoproductive and hyperproductive thrombocytopenia groups but no significant gender-based disparities. While platelet count and plateletcrit (PCT) didn't differ significantly between groups, individuals with hyperdestructive thrombocytopenia had higher MPV values. Platelet indices varied across clinical conditions, highlighting their potential diagnostic and prognostic value. CONCLUSION: Platelet indices like MPV, along with platelet count and PCT, offer insights into thrombocytopenia causes and prognosis. Further research is needed to confirm these findings, but integrating platelet indices into clinical practice could inform treatment decisions and reduce unnecessary procedures like bone marrow biopsies and imaging studies.

Genetic factors related to aspirin resistance using the Multiplate® device in Hong Kong Chinese patients with stable coronary heart disease.

Objective: Associations between single nucleotide polymorphisms (SNPs) and aspirin resistance (AR) have been studied with variable results. The associations of genetic variants with AR may be helpful to explain why some individuals demonstrate aspirin insensitivity with this anti-platelet therapy. The purpose of this research was to investigate the effect of different genotypes in candidate genes on aspirin response in patients taking long-term aspirin therapy by measuring the serum thromboxane B2 (TXB2) and platelet function using the Multiplate® analyser. Methods: A total of 266 patients with stable coronary heart disease (CHD) taking low-dose aspirin for long periods of time and without any other anti-platelet drugs medications were enrolled into the study. They were required to take 80 mg of aspirin every morning for a week including the day before blood tests. Blood samples were collected 24 h after the last dose. The 80 mg dose of aspirin was taken orally and blood samples were collected again 1 h later. The serum TXB2 levels were measured in samples at 24 h post-dose and 1 h post-dose using the EIA kit and platelet activity was determined using the Multiplate® Impedance Platelet Aggregometry (ASPI) assay. Genotyping assays were performed by the TaqMan SNP genotyping technique. Results: Of the 266 patients, only 251 patients were enrolled in the present study. The PTGS1/COX1-1676 A > G (rs1330344) and the PTGS2/COX2-765 G > C (rs20417) SNPs showed significant associations with the ASPI measurements in samples taken at 24 h post-dose, but not with the values at 1 h post-dose or with the TXB2 levels (P < 0.05). Conclusions: Our results suggest that polymorphisms in the PTGS1/COX1 and the PTGS2/COX2 genes may be associated with reduced anti-aggregatory effects and increased the risk of AR, but future larger-scale cohort studies are necessary for further validation.

Clopidogrel Hyperresponsiveness and Hemorrhagic Complications Using On-Label Clopidogrel Dosing after Pipeline Embolization.

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.

The effects of ambient particulate matter air pollution on platelets and hemostasis.

Introduction: Elevated ambient pollution exposure is potentially linked to thromboembolism. However, the mechanisms by which particulate matter (PM) interferes with the balance of hemostatic system remain unclear. This study investigates PM-mediated hemostatic changes in individuals across unique seasonal variations of ambient pollution. Methods: This prospective study was conducted between February and July 2020 during alterations in ambient pollution in Chiang Mai, Thailand. Blood tests from 30 healthy subjects were assessed at four-week intervals, four times in total. Various coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), von Willebrand factor (vWF), platelet count, and platelet functions, were evaluated. A mixed-effects model was used to analyze the impact of high PM2.5 and PM10 on hemostatic parameters. Results: Thirty male subjects with mean age of 38.9 ± 8.2 years, were included. High levels of PM2.5 and PM10 were significantly associated with PT shortening, with no such effect observed in aPTT. PM2.5 and PM10 values also positively correlated with vWF function, while vWF antigen levels remained unchanged. Soluble P-selectin showed a strong positive association with PM2.5 and PM10 levels. Platelet function analysis revealed no correlation with PM values. Conclusion: Short-term exposure to elevated PM2.5 and PM10 concentrations was linked to shortened PT and enhanced vWF function in healthy individuals. Exploring the impact of these changes on clinically relevant thrombosis is crucial. Additional studies on the pathogenesis of pollution-related thrombosis are warranted for maintaining good health.

Thrombus aspiration is associated with improved platelet inhibition rate following dual antiplatelet therapy in acute myocardial infarction patients.

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.

Does one size really fit all? The case for personalized antiplatelet therapy in interventional cardiology.

Cardiovascular disease is the leading cause of death worldwide. Dual antiplatelet therapy (DAPT), with aspirin plus a P2Y12 inhibitor, is currently recommended as a default for patients after acute coronary syndrome (ACS) and following percutaneous coronary intervention (PCI). However, controversies arise over the role of aspirin, the optimal duration of DAPT after drug-eluting stent (DES) implantation, the choice of P2Y12 inhibitor and the variability in individual responses to antiplatelet agents. Recent data indicate that monotherapy with a P2Y12 inhibitor may have adequate anti-ischemic effects with lower bleeding risk. Additionally, discrepancies in DAPT duration recommendations and the optimal P2Y12 inhibitor, provides more uncertainty. We ask the question "does one size really fits all?" or should a more personalized strategy should be implemented.

Diseases affecting the heart and blood circulation are the leading cause of death worldwide. Treatment with drugs that prevents platelets from clumping (called antiplatelets) like aspirin plus another drug group (called P2Y12 inhibitors) like clopidogrel, ticagrelor and prasugrel, is currently recommended as a default for patients after heart attack and/or in whom coronary stents are inserted. However, it is very well documented that the response of any individual to these drugs is highly variable, and that the patients who don't respond as well to them are at increased risk of having clot events in their coronary arteries. On the other hand, people who respond to the drugs very sensitively have a higher bleeding risk. Despite these observations, there is no attempt to test the response of individuals patients to their antiplatelet drugs in routine practice. This review article looks in detail and whether the currently used strategy of "One size fits all" should be changed, given that there may well now be the chance to perform routine testing on everyone, and personalize their treatment accordingly.

Whole Blood Aggregometry in Mice.

Aggregometry plays a crucial role in both clinical diagnostics and research within hematology, serving as a fundamental tool for understanding platelet function and its implications in physiological and pathological processes. In research, aggregometry provides insights into platelet aggregation dynamics and aids in understanding the underlying mechanisms of hemostasis, thrombosis, and related disorders. Light transmission aggregometry (LTA) and lumi-aggregometry, as well as whole blood aggregometry, are commonly employed methods. While LTA and lumi-aggregometry allow for specific platelet function assessment under controlled conditions, whole blood aggregometry provides a more physiologically relevant approach by evaluating platelet aggregation within the context of whole blood. Although both methodologies offer unique advantages, whole blood aggregometry allows for preservation of the native cellular environment, simplicity, and potential for better clinical correlation. In a clinical setting, with human blood samples, protocols are established for both LTA and whole blood aggregometry as they are frequently used diagnostic tools. A protocol for LTA and lumi-aggregometry in murine models has been described; however, to date, there is no standardized protocol for whole blood aggregometry in murine models accessible to hematology researchers. This article aims to outline a simple, basic protocol for murine whole blood aggregometry, offering an alternative method to the commonly used LTA aggregometry in research settings. Standardizing whole blood aggregometry protocols in murine models could enhance experimental reliability and facilitate translational research efforts in hematology. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Whole blood aggregometry in mice Support Protocol: Phenylhydrazine-induced anemia in wild-type mice Basic Protocol 2: Hematocrit percentage in mice.

ECMO produces very rapid changes in primary hemostasis detected by PFA-200 during lung transplantation: An observational study.

BACKGROUND: The pathology of primary hemostasis is a common complication of extracorporeal membrane oxygenation (ECMO) support. Scientific data describing its changes in patients on short-term ECMO support and the ability and speed of the restoration of its functions are limited. AIMS: The aim of this study was to describe the pathology of primary hemostasis induced by short-term ECMO support and its development over time using PFA-200, ROTEM platelet, and von Willebrand factor (vWF) analyses. METHODS: In patients undergoing lung transplantation surgery using intraoperative veno-arterial ECMO support, blood samples were analyzed using the following tests: PFA-200, ROTEM platelet tests, vWF antigen, ristocetin cofactor (RCo), and collagen-binding protein (CB) before, during, and after ECMO support. RESULTS: Blood samples from 32 patients were analyzed. All 3 PFA-200 tests (COL/EPI, COL/ADP, and COL/P2Y) showed significant deterioration during ECMO support with rapid restoration after ECMO cessation (p < 0.05), suggesting an ECMO-induced primary hemostasis disorder. A significant increase of vWF antigen after ECMO cessation (p < 0.05) was found with an increase of RCo and CB levels, although it was not significant (p > 0.05). CONCLUSIONS: Short-term ECMO support induces primary hemostasis pathology. It occurs immediately after initiation but is rapidly restored after ECMO cessation, which is detectable by PFA-200. Despite there being persistent platelet dysfunction after ECMO cessation, as seen with the ROTEM platelet results, the increased levels of vWF antigen might explain the normal results of primary hemostasis detected by PFA-200.

Clopidogrel resistance and its relevance: Current concepts.

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.

An in vitro study of coagulation evaluation in obstetric hemorrhage for pregnancy-induced hypertension with coagulation and platelet function analyzer.

This study aimed to establish in vitro hemodilution and resupplementation assays for obstetric hemorrhage in pregnancy-induced hypertension (PIH) and to monitor the coagulation function dynamically using a coagulation and platelet function analyzer. Forty-seven singleton pregnant women were divided into normal (n = 24) and PIH (n = 23) groups. Peripheral blood samples were used to construct the assays, and the activated clotting time (ACT), clotting rate (CR), and platelet function index (PF) were measured. The results showed that the baseline ACT was higher in the PIH group (p < 0.01). Hemodilution assays showed decreased ACT and increased CR and PF, with ACT changes significantly lower in the PIH group (p < 0.05). CR changed most in both groups at lower dilution ratios (35% to 50%), while ACT changed most at a higher dilution ratio (75%). In the resupplementation assay, ACT exhibited the most significant response. The analyzer effectively detected differences between pregnant women with and without PIH. Thus, we need to pay more attention to the changes of ACT in the actual clinical application to assess the coagulation status of parturients.

Advances in Platelet-Dysfunction Diagnostic Technologies.

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.

Role of Cyp2c19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

PURPOSE OF REVIEW: Identification of a reliable discriminatory test to accurately stratify patient responses to antiplatelet therapy following coronary revascularization has become increasingly desirable to optimize therapeutic efficacy and safety. RECENT FINDINGS: The expansion of platelet function testing to include genotype assessment has been an evolutionary journey, initially fraught with confounding results. However, more recent and rigorous data analysis suggests that genotype testing- guided, tailored antiplatelet therapy may hold promise in optimizing treatment of patients after coronary intervention. Current evidence increasingly supports the use of genotype guided CYP2C19 testing to better match the post coronary intervention patient with the most efficacious and least risky antiplatelet inhibitor. The risk stratification of poor, intermediate, and good metabolizers of these drugs with such testing promises to yield clinical dividends in terms of morbidity, mortality and cost control, in this growing patient population.

Defining light transmission aggregometry cutoff values for clopidogrel and aspirin resistance in flow diversion treatment of intracranial aneurysms.

OBJECTIVE: Concern about thromboembolic events after flow diversion (FD) warrants dual antiplatelet therapy for 3 to 6 months. Platelet function tests are routinely performed prior to the procedure to detect clopidogrel responsiveness, as resistance is associated with CYP2C19 gene polymorphisms. This study aimed to identify optimal cutoff values in light transmission aggregometry (LTA) for clopidogrel and aspirin as predictive indicators of thromboembolic complications. METHODS: The authors conducted a retrospective analysis of aneurysms treated with FD between 2013 and 2023 at a single academic institution. Patients with LTA data for adenosine diphosphate (ADP) and arachidonic acid (ARA) were included, excluding those with aborted procedures. Receiver operating characteristic curves were plotted for ADP and ARA assays to determine optimal cutoff values. RESULTS: A total of 442 patients harboring 552 aneurysms treated in 485 procedures were selected for this analysis. Complete and near-complete aneurysm occlusion on the last radiological follow-up was achieved in 81.8% of aneurysms in a median last imaging follow-up of 13.9 months. A good functional outcome (modified Rankin Scale score ≤ 2) was achieved in 96.3% of patients on the last follow-up. Thromboembolic complications occurred in 4.9% of procedures, and intracranial hemorrhagic complications in 1.9%. For the ADP assay, a value ≥ 40% reached a sensitivity of 82.1% and a specificity of 42.9% with a positive likelihood ratio (LR) of 1.50. For the ARA assay, a value ≥ 13.5% reached a sensitivity of 82.1% and a specificity of 45.6% with a positive LR of 1.51. CONCLUSIONS: This study analyzed the largest FD-treated cohort in which optimal LTA platelet function thresholds for clopidogrel were evaluated and is the first to assess LTA values for aspirin. The authors found that values ≥ 40% for clopidogrel and ≥ 13.5% for aspirin were optimal for predicting thromboembolic complications after FD in treating aneurysms.

Comparative studies between humans and golden Syrian hamsters via thromboelastography.

BACKGROUND: Thromboelastography (TEG) is a widely utilized clinical testing method for real-time monitoring of platelet function and the thrombosis process. Lipid metabolism disorders are crucial risk factors for thrombosis. The lipid metabolism characteristics of hamsters resemble those of humans more closely than mice and rats, and their relatively large blood volume makes them suitable for studying the mechanisms of thrombosis related to plasma lipid mechanisms. Whole blood samples from golden Syrian hamsters and healthy humans were obtained following standard clinical procedures. TEG was employed to evaluate coagulation factor function, fibrinogen (Fib) function, platelet function, and the fibrinolytic system. METHODS: The whole blood from hamster or healthy human was isolated following the clinical procedure, and TEG was employed to evaluate the coagulation factor function, Fib function, platelet function, and fibrinolytic system. Coagulation analysis used ACLTOP750 automatic coagulation analysis pipeline. Blood routine testing used XN-2000 automatic blood analyzer. RESULTS: TEG parameters revealed that hamsters exhibited stronger coagulation factor function than humans (reaction time [R], p = 0.0117), with stronger Fib function (alpha angle, p < 0.0001; K-time [K], p < 0.0001). Platelet function did not differ significantly (maximum amplitude [MA], p = 0.077). Hamsters displayed higher coagulation status than humans (coagulation index [CI], p = 0.0023), and the rate of blood clot dissolution in hamsters differed from that in humans (percentage lysis 30 min after MA, p = 0.02). Coagulation analysis parameters indicated that prothrombin time (PT) and activated partial thromboplastin time (APTT) were faster in hamsters than in humans (PT, p = 0.0014; APTT, p = 0.03), whereas the Fib content was significantly lower in hamsters than in humans (p < 0.0001). No significant difference was observed in thrombin time (p = 0.1949). CONCLUSIONS: In summary, TEG could be used to evaluate thrombosis and bleeding parameters in whole blood samples from hamsters. The platelet function of hamsters closely resembled that of humans, whereas their coagulation function was significantly stronger.

Use of Thromboelastography in Coronary Artery Bypass Grafting in a Patient With Factor â ¤ Deficiency With Platelet Function Disorders: A Case Report and Literature Review.

Reports on cases of factor Ⅴ (FⅤ) deficiency complicated by platelet function disorders in patients undergoing cardiac surgery are rare, and the utilization of thromboelastography in such cases is limited. This case presents a unique case of FⅤ deficiency complicated by platelet function disorders, highlighting the significance of tailored transfusion strategies guided by thromboelastography (TEG). A 64-year-old hemodialysis patient who was diagnosed with FⅤ deficiency 24 years prior presented for an on-pump coronary artery bypass graft. The decrease in FⅤ activity on preoperative examination was mild. Based on this finding, it was determined that preoperative fresh frozen plasma supplementation was not required. However, the case was complicated by platelet function disorders; therefore, a preoperative transfusion of platelet concentrate was performed to correct the decreased platelet function, enabling subsequent surgery. Intraoperative and postoperative transfusion strategies were guided by TEG. This study highlights TEG-guided transfusion management as a viable option for patients with FⅤ deficiency complicated by platelet function disorders.