New Advances and Treatment in Thrombosis and Endothelial Injury Syndromes

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 1708

Special Issue Editors


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Guest Editor
Second Propedeutic Department of Internal Medicine, Hippocration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece
Interests: hematology; cellular therapies; endothelial injury; fungal infections; thrombosis; hemophilia

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Guest Editor
Third Department of Internal Medicine, Papageorgiou Hospital, Aristotle University of Thessaloniki, 56403 Thessaloniki, Greece
Interests: vascular pathology; endothelial dysfunction; hypertension; cardiovascular diseases; chronic inflammation; autoimmune rheumatic disorders
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Special Issue Information

Dear Colleagues,

Cardiovascular disease (CVD)—mainly arterial and venous thrombotic events—constitutes the leading cause of morbidity and mortality worldwide, not only in the general population but also among patients with chronic disorders such as autoimmune rheumatic diseases (ARDs) and hematological diseases. Despite significant advances in the prevention and management of arterial and venous thrombosis, critical gaps remain in our understanding of the molecular mechanisms that drive thrombotic risk, particularly in special populations. Moreover, the effects of emerging “cardioprotective” therapies, such as glucagon-like peptide-1 (GLP-1) receptor agonists, on thrombosis and vascular biology, as well as the molecular pathways underlying these effects, remain poorly understood.  

In particular, venous thromboembolism (VTE) represents a complex, multifactorial clinical entity, arising from both congenital and acquired prothrombotic mechanisms. Antiphospholipid syndrome (APS) is among the most common acquired causes of thrombophilia, manifesting with arterial or venous thrombosis, pregnancy morbidity, and microvascular involvement. Microvascular thrombosis is also a defining feature of thrombotic microangiopathies (TMAs), a heterogeneous group of disorders that includes thrombotic thrombocytopenic purpura (TTP), complement-mediated TMA [also referred to as atypical hemolytic uremic syndrome (aHUS)], and secondary TMAs associated with ARDs. In addition, transplant-associated TMA (TA-TMA) is a severe complication observed in recipients of hematopoietic cell transplantation (HCT). Thrombosis may also be the initial manifestation of paroxysmal nocturnal hemoglobinuria (PNH), a rare complement-mediated hematologic disorder. Despite the substantial therapeutic progress, data on the long-term cardiovascular burden and vascular sequelae of these conditions remain limited.  

Beyond thrombosis, endothelial dysfunction and injury are central to the pathogenesis of multiple clinical entities, including hypertension, ARDs, and complications related to HCT and novel cellular therapies. In ARDs, accumulating evidence highlights the prognostic and pathogenic role of endothelial injury biomarkers in the development of vascular complications. Importantly, the interplay between endothelial cells, the complement system, and thromboinflammatory pathways suggests that complement activation may represent a shared mechanistic link contributing to thrombosis and cardiovascular complications across diverse clinical settings.  

In this context, this Special Issue aims to provide a comprehensive platform for original research and high-quality reviews that advance our understanding of thrombosis, endothelial injury, and cardiovascular disease, with particular emphasis on molecular mechanisms and special populations.  

Topics of interest include, but are not limited to, the following:

  • Cardiovascular disease and thrombotic complications;
  • Arterial and venous thrombosis;
  • Endothelial dysfunction and vascular injury;
  • Antiphospholipid syndrome and acquired thrombophilia;
  • Thrombotic microangiopathies and complement-mediated disorders;
  • Cardiovascular disease in autoimmune, hematologic, and transplant populations;
  • Molecular and translational insights into thromboinflammation.

Dr. Paschalis Evangelidis
Dr. Panagiota Anyfanti
Guest Editors

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Keywords

  • antiphospholipid syndrome
  • autoimmune rheumatic diseases
  • cardiovascular disease
  • endothelial dysfunction
  • hematopoietic cell transplantation
  • thromboinflammation
  • thrombosis
  • thrombotic microangiopathies
  • venous thromboembolism

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Published Papers (2 papers)

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Research

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12 pages, 331 KB  
Article
Plasma Tissue Factor Pathway Inhibitor Levels Correlate with Disease Activity and Are Associated with Altered Thrombin Generation in Pediatric Inflammatory Bowel Disease
by Alexander Meyer, Benno Kohlmaier, Theresa Bauer, Siegfried Gallistl, Wolfgang Muntean, Barbara Silbernagel, Harald Haidl and Axel Schlagenhauf
Pharmaceuticals 2026, 19(5), 738; https://doi.org/10.3390/ph19050738 - 8 May 2026
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Abstract
Background: Patients with inflammatory bowel disease (IBD) exhibit a hypercoagulable state with increased thrombotic risk. Previous studies demonstrated elevated thrombin generation in pediatric IBD, paradoxically accompanied by prolonged lag time during active disease. We hypothesized that elevated tissue factor pathway inhibitor (TFPI) levels [...] Read more.
Background: Patients with inflammatory bowel disease (IBD) exhibit a hypercoagulable state with increased thrombotic risk. Previous studies demonstrated elevated thrombin generation in pediatric IBD, paradoxically accompanied by prolonged lag time during active disease. We hypothesized that elevated tissue factor pathway inhibitor (TFPI) levels during active inflammation contribute to this paradox. Methods: We prospectively enrolled 25 pediatric patients (10 Crohn’s disease [CD], 15 ulcerative colitis [UC]) aged 7–18 years with newly diagnosed IBD. Blood samples were collected at diagnosis and in remission. Thrombin generation was assessed using calibrated automated thrombography. Plasma levels of TFPI, tissue factor activity (TFA), vascular endothelial growth factor (VEGF), and interleukin-6 (IL-6) were measured. Results: TFPI levels correlated positively with thrombin generation lag time (r = 0.43, padj < 0.05) and disease activity scores (r = 0.54, padj < 0.05) in patients with active disease (PCDAI/PUCAI > 0). Longitudinal analysis of 16 patients achieving remission revealed elevated TFPI and prolonged lag time during active disease compared to quiescence (both padj < 0.05), while TFA did not change significantly. VEGF decreased significantly upon remission (padj < 0.05), whereas IL-6 showed no significant change. Conclusions: Elevated TFPI levels during active IBD likely contribute to the paradoxical prolongation of thrombin generation lag time. TFPI normalization upon remission reflects vascular inflammation resolution, suggesting TFPI as a potential biomarker and therapeutic target. Full article
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Review

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16 pages, 523 KB  
Review
Glucagon-like Peptide-1 Receptor Agonists and Platelet Function: Potential Benefits Beyond Glycemic Control
by Maria Xanthopoulou, Paschalis Evangelidis, Dimitrios Poulis, Eleni Gavriilaki, Nikolaos Kotsiou, Christina Antza, Vasilios Kotsis, Chrysoula Doxani, Theodoros Mprotsis, Elias Zintzaras and Panagiota Anyfanti
Pharmaceuticals 2026, 19(3), 462; https://doi.org/10.3390/ph19030462 - 12 Mar 2026
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Abstract
There is cumulative evidence that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can offer cardiovascular protection extending beyond glucose-lowering and weight reduction, but the underlying mechanisms contributing to these effects remain incompletely understood. Modulation of platelet function might contribute to the aforementioned benefits. In [...] Read more.
There is cumulative evidence that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can offer cardiovascular protection extending beyond glucose-lowering and weight reduction, but the underlying mechanisms contributing to these effects remain incompletely understood. Modulation of platelet function might contribute to the aforementioned benefits. In the current literature review article, we synthesized available preclinical and clinical data evaluating the effects of GLP-1 RAs on platelet activation and function. Preclinical data indicate that GLP-1 RAs might decrease platelet activation via both GLP-1 receptor-dependent and -independent mechanisms with the involvement of cyclic adenosine monophosphate signaling, increase in nitric oxide bioavailability, and suppression of thromboxane-mediated pathways, particularly under inflammatory or shear-stress conditions. Additionally, clinical studies, despite being limited and heterogeneous, support a reduction in platelet activation markers, even independently of glycemic control or weight loss. However, most of them are characterized by small sample sizes and significant heterogeneity among them. In summary, existing evidence suggests that GLP-1 RAs exhibit potential antiplatelet effects that could contribute to their cardioprotective profile. Larger, well-designed clinical studies are crucial to better understand the clinical importance of platelet modulation by GLP-1 RAs and their potential implications for cardiovascular risk reduction. Full article
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