Clopidogrel is often co-prescribed with proton pump inhibitors (PPIs) to reduce gastrointestinal bleeding risk. However, some PPIs, especially pantoprazole, inhibit CYP2C19, potentially reducing clopidogrel's activation. Ilaprazole, a newer PPI primarily metabolized via CYP3A4, may offer reduced interaction. The study was an open-label, randomized trial that involved 36 healthy male volunteers, who were divided into three groups (n = 12 each): Group 1 (Clopidogrel + Placebo), Group 2 (Clopidogrel + Pantoprazole 40 mg), and Group 3 (Clopidogrel + Ilaprazole 10 mg). After 7 days of treatment, all participants received clopidogrel 75 mg on Day 8. Pharmacokinetic (PK) parameters were analyzed using LC-MS/MS and platelet aggregation by light transmission aggregometry at 0, 4, 10, and 24 h. Pantoprazole significantly reduced clopidogrel AUC (1.96 ± 0.20 vs 8.27 ± 1.04 ng·h/mL, P < .0005), Cmax (0.76 ± 0.04 vs 2.6 ± 1.01 ng/mL, P = .0136), and t1/2 (1.72 ± 0.11 vs 2.22 ± 0.17 h, P = .0312), indicating reduced bioavailability. Geometric mean ratio (GMR) analysis showed a marked reduction in clopidogrel exposure with pantoprazole (Cmax GMR 0.31, 90% CI 0.18-0.53; AUC GMR 0.24, 90% CI 0.19-0.29), and platelet aggregation was significantly higher at 4 and 10 h (P < .05). In contrast, ilaprazole preserved PK parameters (AUC 10.18 ± 1.41, Cmax 3.06 ± 1.05), GMRs near unity (Cmax 1.20, 90% CI 0.60-2.42; AUC 1.23, 90% CI 0.97-1.55), indicating no inhibitory effect and platelet inhibition comparable to placebo (P > .05) Ilaprazole did not affect clopidogrel pharmacokinetics or pharmacodynamics, suggesting it as a safer alternative to pantoprazole in dual antiplatelet therapy.

Aspirin treatment irreversibly inhibits cyclooxygenase activity, blocking thromboxane A2 (TxA2) synthesis and reducing thromboxane-prostanoid (TP) receptor-induced platelet activation. Aspirin resistance refers to the failure of regular aspirin doses to produce the expected antiplatelet effect. Aspirin-induced bleeding complications are frequently observed in patients receiving excessive doses or combined antiplatelet and anticoagulant therapy. Although selective TP receptor antagonists have been tested clinically, they are ineffective due to persistently high prostaglandin levels, causing unexpected signaling effects in platelets and other cell types. Hydroxyflavonoids are bioactive phytonutrients with antithrombotic effects, inhibiting TxA2-mediated platelet signaling and preventing abnormal platelet activation in cardiovascular diseases without major side effects. Using a recently published TP receptor crystal structure and docking studies with different flavonoid classes, including genistein and tectorigenin, we found that flavonoids occupy similar ligand-binding surface of TxA2, thereby preventing TxA2 binding. To evaluate our bioinformatics data, a mutant TP receptor variant was overexpressed in HEK293 cells, deleting interacting amino acids with hydroxyflavonoids, and stimulated with the TxA2 analog U46619. Intracellular Ca[2+] responses were measured in Fura-2-labeled cells. Amino acid substitutions in the extracellular domain, which did not influence U46619 binding, abolished hydroxyflavonoid-mediated inhibition of the TP receptor. These results suggest that hydroxyflavonoids directly bind to and inhibit the TP receptor. Using aggregometry and flow chamber assays, we confirmed that genistein and tectorigenin synergize with aspirin to inhibit platelet aggregation and thrombus growth in human and mouse platelets. Whether combined genistein-aspirin therapy improves antiplatelet responses in aspirin-resistant patients requires further investigation.

Eosinophilia is commonly associated with parasitic infections, allergic disorders and haematological conditions. Although bleeding in patients with eosinophilia is rare, platelet dysfunction may contribute, even when platelet counts are normal. We report the case of a 7-year-old boy with glucose-6-phosphate dehydrogenase deficiency who presented with recurrent spontaneous bruising over 6 months. Physical examination revealed multiple ecchymoses over the lower limbs, with no organomegaly or lymphadenopathy. Laboratory investigations revealed a normal platelet count, marked eosinophilia and prolonged bleeding time. Platelet function testing using whole blood impedance aggregometry (Chrono-Log) demonstrated reduced aggregation in response to multiple agonists, consistent with a selective impairment of aggregation to adenosine diphosphate and collagen. The patient was treated with anthelminthics, resulting in a significant reduction in the eosinophil count and resolution of bleeding symptoms. This case highlights that eosinophilia may be associated with acquired platelet dysfunction, even in the presence of normal platelet counts. Clinicians should consider platelet function testing in patients with unexplained bleeding and eosinophilia, as timely treatment of the underlying cause can lead to clinical improvement.

Background: Over the past two decades, the widespread use of flow diversion stents (FDS) has significantly expanded treatment options for patients with intracranial aneurysms (IA). However, FDS implementation requires antiplatelet therapy (APT), the optimal regimen for which remains undefined. This study aimed to evaluate light transmission aggregometry (LTA) as a routine tool for monitoring antiplatelet therapy during flow diversion to examine whether an LTA-based residual-reactivity cut-off is associated with thromboembolic complications and to assess the agreement between LTA and VerifyNow (VN) P2Y12 reaction units (PRU), rather than to establish definitive safety thresholds. Methods: A retrospective analysis was conducted across two expert centers on 771 patients. Based on selection criteria, 203 IA patients who underwent FDS implantation between 2019 and 2023 with LTA-guided APT (clopidogrel plus aspirin) were included; LTA was used for monitoring in all 203 patients, and a subset of 84 patients additionally underwent VerifyNow testing for method comparison. The primary outcome was clinically significant thromboembolic complications (TECs) leading to a reduction in quality of life by ≥1 point on the modified Rankin scale (mRS). The secondary outcome was intracranial hemorrhage. Results: Among the 203 patients (203 FDS implantations), dual aggregometry control (LTA + VN) was performed in 84 cases. At the 12-month follow-up, complete or near-complete aneurysm occlusion was radiologically confirmed in 83.7% of patients. A favorable functional outcome (mRS ≤ 2) at 12 months was observed in 97.5% of cases. Thromboembolic complications occurred in 7 patients (3.4%) and hemorrhagic complications in 4 (2.0%). On receiver operating characteristic (ROC) analysis, the control-LTA cut-off of 44% showed only weak, statistically non-significant discrimination for thromboembolic events (area under the curve, AUC 0.700, 95% confidence interval, CI 0.479-0.920; p = 0.073). In the 84 patients tested with both assays, LTA and VerifyNow PRU correlated only moderately (Spearman's ρ = 0.51; Pearson's r = 0.53) and showed wide Bland-Altman limits of agreement, indicating that the two methods are not clinically interchangeable. Conclusions: Routine platelet-function aggregometry may be a useful tool for monitoring APT during flow diversion. In this retrospective cohort, lower residual platelet reactivity on LTA was associated with fewer thromboembolic and hemorrhagic events; however, given the small number of outcome events (n = 7) and an LTA cut-off whose discriminative ability did not reach statistical significance, this association is exploratory and hypothesis-generating rather than an established safety threshold. LTA and VerifyNow PRU were not clinically interchangeable, so no VerifyNow cut-off is proposed. Prospective, adequately powered studies with outcomes stratified directly by each assay are required to define and validate clinically applicable thresholds.

Background: Stent thrombosis (ST) is a rare but serious complication following peripheral endovascular interventions. The prognostic role of high on-treatment platelet reactivity (HTPR) and the optimal antithrombotic strategy, including adjunctive anticoagulation, remain unclear. To evaluate (I) the prognostic value of ADP-induced platelet function in femoropopliteal ST compared to matched controls, and (II) the impact of post-ST oral anticoagulation (OAC) on clinical outcomes. Materials and methods: In this retrospective cohort study, 148 endovascular procedures in 67 patients with documented femoropopliteal ST were compared to 492 matched procedures without ST. Propensity-score-matching for age, sex, and lesion length/type yielded 113 pairs. ADP-induced platelet aggregation was assessed and compared between groups. Within the ST cohort, 12-month outcomes were additionally stratified according to the postprocedural antithrombotic regimen, with or without oral anticoagulation (OAC). Time-to-reintervention was analysed via Kaplan-Meier and Cox regression. Results: ADP-induced platelet reactivity did not differ significantly between ST and control groups (p = .58). Additionally, among ST patients, postprocedural OAC use had no significant impact on 12-month target lesion revascularization (TLR) rates (HR 0.96; 95% CI 0.57-1.62; p = .90), with consistent findings across subgroups (VKA, standard-/low-dose NOAC). Conclusions: In this matched cohort, ADP-induced platelet reactivity did not differ significantly in patients with femoropopliteal stent thrombosis compared to controls. Similarly, no consistent benefit of specific anticoagulation strategies on 12-month target lesion revascularization was observed. Therefore, these findings do not support routine platelet function testing or intensified anticoagulation solely based on a history of ST.

Nanoparticles are increasingly used in biomedical research and clinical applications, including diagnostics, drug delivery, and theranostics, where systemic administration via the bloodstream is often required. As a result, nanoparticles inevitably interact with blood components, making the assessment of their hemocompatibility and potential effects on blood microrheology an important nanosafety issue. In this exploratory in vitro study, we examined how different nanoparticles influence red blood cell (RBC) aggregation using laser tweezers and laser aggregometry. Magnetic and non-magnetic nanodiamonds, as well as zinc oxide nanoparticles, were tested at various concentrations in human whole blood. Laser tweezers were used to measure pairwise RBC interactions, including aggregation forces and characteristic aggregation time, while laser aggregometry assessed the aggregation index and critical shear stress in large cell ensembles. The presence of nanoparticles altered the measured parameters under the present experimental conditions. This study was performed using blood from a single healthy donor; therefore, the findings should be considered preliminary and interpreted with caution with respect to inter-individual variability. The presence of nanoparticles significantly altered the microrheological parameters of blood. Concentration ranges that did not induce statistically significant changes in RBC aggregation parameters under the present in vitro conditions were identified: up to 40 μg/mL for non-magnetic nanodiamonds, 80 μg/mL for magnetic nanodiamonds, and 20 μg/mL for ZnO.

Platelet function is regulated by numerous molecules, and congenital abnormalities of these molecules result in a variety of congenital platelet function disorders. Among these, Glanzmann thrombasthenia (GT), caused by a congenital deficiency or molecular abnormality in GPIIb-IIIa (αIIbβ3), and Bernard-Soulier syndrome (BSS), caused by a congenital deficiency or molecular abnormality in the GPIb-IX-V complex, are representative disorders that manifest as severe bleeding tendency from infancy. GT and BSS are diagnosed mainly by flow cytometry of membrane glycoproteins in addition to conventional light transmission aggregometry. Platelet transfusions are indicated for bleeding refractory to standard hemostatic measures, and recombinant factor VIIa (rFVIIa) has been shown to be effective in GT. rFVIIa has conventionally been used in GT patients refractory to platelet transfusion due to alloantibody production, but is now available in Japan regardless of alloantibody status or platelet transfusion refractoriness. rFVIIa should be considered especially in patients at risk of alloantibody production due to platelet transfusion.

Bleeding disorder of unknown cause (BDUC) constitutes the largest group of patients presenting with a mild-to-moderate bleeding tendency in tertiary care settings. Their clinical bleeding phenotype is characterized by mucocutaneous bleeding, as well as bleeding following surgical challenges or childbirth, and is associated with impaired health-related quality of life. Iron deficiency, with or without anemia, is common, particularly among women, who comprise up to 80% of BDUC cohorts and frequently report heavy menstrual bleeding. Diagnosing BDUC requires a rigorous exclusion of established hemostatic and non-hemostatic causes of bleeding. Common inherited bleeding disorders, including coagulation factor deficiencies (CFD), von Willebrand disease (VWD), and platelet function disorders (PFD), must be systematically excluded. CFD evaluation should extend beyond routine assays (prothrombin time, activated thromboplastin time, thrombin time), as clinically relevant mild reductions in factors VIII, IX, and XI may occur despite normal screening tests; and factor XIII deficiency is not detected by global assays. VWD assessment mandates measurement of VWF antigen and activity, with additional studies to define subtype when indicated. For PFD, light transmission aggregometry remains the reference gold standard. Substantial diagnostic overlap exists among these entities and BDUC, and repeated testing is often required. Investigations for rare causes such as hyperfibrinolysis or excess natural anticoagulants are typically limited to patients with distinctive phenotypes or strong family histories. Although the pathogenesis of BDUC remains incompletely understood, continued investigation into platelet biology, global hemostasis, and vascular contributions holds promise for uncovering therapeutic targets, ultimately improving management for this prevalent yet understudied condition.