Preeclampsia is a hypertensive disorder of pregnancy associated with significant maternal and fetal complications. Its pathogenesis involves endothelial dysfunction, abnormal placentation, and coagulation abnormalities, leading to increased thrombotic and hemorrhagic risks. This narrative review provides an in-depth overview of the pathophysiological mechanisms underlying preeclampsia, with a particular focus on its thrombotic and hemorrhagic complications. Treatment strategies are explored, with emphasis on the role of low-dose aspirin in reducing early-onset preeclampsia. However, aspirin’s effectiveness varies based on dosage and timing, with higher doses showing greater benefit in preventing severe preeclampsia. Despite aspirin’s widespread use, further optimization of its therapeutic role remains necessary to enhance maternal and fetal outcomes.

Chronic kidney disease (CKD) is a global health issue causing a significant health burden. CKD patients develop thrombotic and hemorrhagic complications, and cardiovascular diseases are associated with increased hospitalization and mortality in this population. The hemostatic alterations are multifactorial in these patients; therefore, the results of different studies are varying and controversial. Endothelial and platelet dysfunction, coagulation abnormalities, comorbidities, and hemoincompatibility of the dialysis membranes are major contributors of hypo- and hypercoagulability in CKD patients. Due to the tendency of CKD patients to exhibit a prothrombotic state and bleeding risk, they require personalized clinical assessment to understand the impact of antithrombotic therapy. The evidence of efficacy and safety of antiplatelet and anticoagulant treatments is limited for end-stage renal disease patients due to their exclusion from major randomized clinical trials. Moreover, designing hemocompatible dialyzer membranes could be a suitable approach to reduce platelet activation, coagulopathy, and thrombus formation. This review discusses the molecular mechanisms underlying thrombotic and hemorrhagic risk in patients with CKD, leading to cardiovascular complications in these patients, as well as the evidence and guidance for promising approaches to optimal therapeutic management.

Background and Aims. Cardiovascular disease and thrombosis are the leading cause of death in chronic kidney disease (CKD) patients. The end-stage renal disease patients undergoing hemodialysis (ESRD-HD) are predisposed to hemostatic dysfunction, also due to HD membrane bioincompatibility. In this study, we aimed to evaluate thrombin generation potential in patients at different stages of CKD, including ESRD-HD patients. Furthermore, in HD patients, we compared thrombin generation parameters in pre-hemodialysis (PRE-HD) vs. post-hemodialysis (POST-HD). We also focused on the impact of different HD membranes and vascular access on thrombin generation parameters in ESRD-HD patients.Methods. In this prospective observational study, we recruited 61 patients at different stages of CKD: 31 patients at stages I to V and 30 at ESRD-HD; we also evaluated 6 healthy controls. Thrombin generation by calibrated automated thrombin assay was evaluated in different classes of CKD and ESRD-HD; then, thrombin generation as well as total extracellular vesicles (EVs), platelets, endothelium, and leukocyte-derived microparticles (MPs) by flow cytometry were evaluated at PRE-HD and POST-HD in ESRD-HD patients.Results. Patients with CKD stages III, IV, V, and ESRD-HD exhibited significantly lower endogenous thrombin potential (ETP) than the control group, suggesting a reducing trend in thrombin generation potential along with decreasing renal function. Moreover, in ESRD-HD patients, a significant decrease in ETP (829.4±348.5 vs. 1083±342.7 nM•min; p < 0.005) and peak thrombin generation (185.5±84.14 vs. 257.7±55.40 nM; p < 0.005) together with a prolonged lag time (3.02±0.66 vs. 2.06±0.45 min; p < 0.0001) and time to peak (ttpeak) (5.86 ±1.57 vs. 4.25 ± 0.72 min; p < 0.0001) were observed at POST-HD compared to PRE-HD, indicating a lower thrombin generation potential after dialysis. The flow-cytometric analysis identified a clear split into two groups, with some patients showing a significant reduction in total EVs, platelets, endothelium, and leukocyte-derived MPs and activated platelet MPs at POST-HD compared with PRE-HD, and others showing a significant increase at POST-HD compared with PRE-HD, suggesting the variation in clinical characteristics of the patients and types of HD membrane might affect the EVs' release. In an exploratory analysis, we observed a significant reduction in ETP and thrombin peak, consistently with a prolonged lag time and ttpeak, in patients treated with polysulfone-based (PS) and polyethersulfone-based (PES) HD membranes at POST-HD than PRE-HD, whereas patients on heparin-coated acrylonitrile membrane (ACN) showed no significant difference in thrombin generation parameters between PRE-HD and POST-HD. ESRD-HD patients with arteriovenous fistula access showed significantly lower thrombin generation parameters at POST-HD than PRE-HD.Conclusions. Overall, these findings indicate lower thrombin generation parameters in patients with ESRD-HD compared with other CKD groups, suggesting a higher risk of bleeding of this population, particularly after HD, when thrombin generation further decreases. The alteration in thrombin generation potential in this population could be in part due to variation in HD membrane and vascular access type.

Background and Aims. Nanoplastics (NPs) are emerging environmental contaminants with potential cardiovascular effects, but their impact on platelet activation and cardiac remodeling remains poorly defined. Atrial fibrosis is a key mechanism underlying atrial fibrillation (AF), driven by fibroblast transition to a pro-fibrotic phenotype. Platelets contribute to thrombo-inflammation and may infiltrate atrial tissue, modulating fibroblast phenotype. We investigated whether polystyrene NPs (PS-NPs, 50 nm) induce platelet activation in vitro and in vivo and enhance platelet-fibroblast crosstalk, promoting pro-inflammatory and pro-fibrotic signaling.Methods. PS-NPs were administered intravenously in C57BL/6 mice, and serum thromboxane B₂ (TXB₂) was measured after 5 days as an index of platelet activation. Human isolated platelets were incubated with 50 nm PS-NPs (20 or 200 µg/mL) for 1 and 18 h at 37°C under rotational conditions and assessed for TXB₂ generation and P-selectin membrane translocation. Washed human platelets were exposed to fluorescent Dragon Green-labelled particles, and platelet-derived extracellular vesicles (EVs) release and NPs incorporation into EVs were evaluated. Human atrial fibroblasts (HCF) were incubated for 24 h with platelet releasate obtained following platelet-NP interaction to assess effects on cytokine production and Snail expression.Results. Single-dose i.v. PS-NP administration (20 or 200 µg/mL) in C57BL/6 mice increased TXB₂ generation after 5 days (2.15- and 2.21-fold vs. baseline, p<0.01). Consistently, human platelets exposed to PS-NPs (20 or 200 µg/mL) for 1 and 18 h showed a concentration-dependent significant increase of TXB₂ levels, even in the absence of platelet agonists. PS-NP exposure also significantly enhanced P-selectin surface expression at the highest concentration (p < 0.05). Exposure to PS-NPs did not significantly affect platelet-derived EV release at 1 h or 18 h. However, the percentage of NP-positive EVs increased from ~45% to ~80% (20 vs. 200 µg/mL; p < 0.01), suggesting interaction and/or incorporation into EVs. To investigate functional consequences of platelet activation induced by PS-NPs, HCF cells were treated with platelet releasate collected after platelet incubation with PS-NP. After 24 h, releasate from PS-NP unexposed platelets significantly upregulated the expression of inflammatory and remodeling markers, including interleukin (IL)-1α, IL-6, and IL-1β, as well as the fibroblast activation marker Snail. Notably, exposure of HCFs to releasate from PS-NP–treated platelets further enhanced the expression of inflammatory cytokines and Snail, with the strongest induction observed with releasate from platelets exposed to 200 µg/mL PS-NPs, indicating an additional effect of PS-NPs on platelet activation that translates into amplified fibroblast responses.Conclusions. PS-NPs promote platelet activation and enhance platelet–fibroblast crosstalk, amplifying thrombo-inflammatory and pro-remodeling signaling. Although the EV release was unchanged, the increase in NP-positive EVs suggests their incorporation into EVs and a potential role in their systemic distribution. By priming platelets toward a more reactive phenotype, PS-NPs may contribute to atrial remodeling, supporting their role as an underrecognized modulator of cardiovascular pathophysiology.

Preeclampsia (PE) is associated with enhanced platelet activation, with thromboxane A₂ playing a key pathogenic role. Urinary 11-dehydro-thromboxane B₂ (TXM) reflects in vivo platelet activation. Although low-dose aspirin (ASA) is recommended for PE prevention in high-risk pregnancies, variable thromboxane suppression may lead to persistent platelet activation. This study aimed at identifying platelet-derived predictors of PE in high-risk women receiving ASA and assessing biomarkers improving risk stratification. This observational study included 25 high-risk pregnant women on ASA and 12 with physiological pregnancies. Clinical evaluation and blood/urine sampling were performed at baseline (T0), and at 21 (T4) and 27 (T5) weeks. Urinary TXM and percentage inhibition (<75% = reduced inhibition) were assessed. Platelet biomarkers included thrombopoietin (TPO), glycocalicin (GC), P-selectin, and CD40L. Late-onset PE occurred in 6/25 (24%) high-risk women and in none of the controls. TXM levels were higher in high-risk versus physiological pregnancies (p=0.009), especially at T4-T5 (p<0.0001). Women developing PE had higher TXM at T4 (adjusted p=0.014) and lower TXM inhibition (51% vs 81%; p=0.020). Reduced inhibition (<75%) was associated with increased PE risk (44.4% vs 14.3%; OR 4.8). TPO showed a different longitudinal pattern according to PE occurrence (time-by-outcome interaction p=0.036). Glycocalicin showed higher estimated values at baseline in women who developed PE (p=0.048), but the time-specific contrast was attenuated after Holm adjustment (adjusted p=0.19). Incomplete thromboxane suppression during ASA therapy is associated with PE. TXM, together with opposite trends of TPO and GC, identifies a profile consistent with altered platelet homeostasis and possible changes in platelet turnover, potentially enhancing risk prediction in high-risk pregnancies.