Atrial Fibrillation in Philadelphia Chromosome–negative Myeloproliferative Neoplasms: Thromboinflammatory Crosstalk with a Focus on the NLRP3 Inflammasome

Olga Demska; Marta Szandruk-Bender; Niels Eske Bruun; Vibe Skov; Lasse Kjær; Morten Kranker Larsen; Christina Ellervik; Sebastian Szmit; Hans Carl Hasselbalch; Marta Sobas

doi:10.1055/a-2767-0451

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost
DOI: 10.1055/a-2767-0451

Review Article

Atrial Fibrillation in Philadelphia Chromosome–negative Myeloproliferative Neoplasms: Thromboinflammatory Crosstalk with a Focus on the NLRP3 Inflammasome

Autor*innen

Olga Demska

¹Department of Hematology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland
Marta Szandruk-Bender

²Department of Pharmacology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
Niels Eske Bruun

³Department of Cardiology, Zealand University Hospital, Roskilde, Denmark
Vibe Skov

⁴Department of Hematology, Zealand University Hospital, Roskilde, Denmark
Lasse Kjær

⁴Department of Hematology, Zealand University Hospital, Roskilde, Denmark
Morten Kranker Larsen

⁴Department of Hematology, Zealand University Hospital, Roskilde, Denmark
Christina Ellervik

⁵Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

⁶Department of Clinical Biochemistry, Zealand University Hospital, Køge, Denmark

⁷Department of Laboratory Medicine, Boston Children's Hospital, Boston, Massachusetts, United States

⁸Department of Pathology, Harvard Medical School, Boston, Boston, Massachusetts, United States
Sebastian Szmit

⁹Department of Cardio-Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland

¹⁰Cardio-Oncology Unit, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
Hans Carl Hasselbalch

⁵Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

⁶Department of Clinical Biochemistry, Zealand University Hospital, Køge, Denmark
Marta Sobas

¹Department of Hematology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland

Abstract

The Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs) and atrial fibrillation (AF) share a common proinflammatory and prothrombotic phenotype. Despite this overlap, patients with coexisting MPNs and AF remain undertreated and poorly characterized, with no specific antithrombotic guidelines addressing this dual pathology. Emerging evidence identifies the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome as a central and common mediator of vascular diseases. This review explores the pathophysiologic convergence between MPNs and AF, with a focus on the NLRP3 inflammasome and its downstream cytokines (IL-1β, IL-18), as well as neutrophil extracellular traps (NETs), as unifying drivers of thrombosis, atrial remodeling, and clonal propagation. In MPNs, NLRP3 is activated by JAK2-driven inflammation and sterile danger signals, sustaining a cytokine milieu that promotes pyroptosis, fibrosis, and platelet–leukocyte–endothelial interactions. In AF, inflammasome overactivation in cardiomyocytes and fibroblasts contributes to ectopic activity, electrical remodeling, and fibrosis. NETs, which are enhanced by NLRP3, amplify thrombosis and may link the hematologic and cardiovascular components of the association between MPNs and AF. We critically evaluate the translational potential of inflammasome-derived biomarkers and identify NLRP3 inhibition as a promising adjunctive strategy in MPN patients with AF. The review calls for prospective studies to redefine antithrombotic management in this overlooked population, incorporating molecular, inflammatory, and arrhythmogenic risk dimensions.

Keywords

myeloproliferative neoplasms (MPNs) - atrial fibrillation - JAK2V617F mutation thromboinflammation - NLRP3 inflammasome

Volltext

Referenzen

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