CIRCULATING INFLAMMATORY MEDIATORS REPROGRAM PLATELETS TOWARD A PRO-COAGULANT PHENOTYPE IN PHILADELPHIA-NEGATIVE MYELOPROLIFERATIVE NEOPLASMS

@article{vieira2026circulating,
  title = {{CIRCULATING INFLAMMATORY MEDIATORS REPROGRAM PLATELETS TOWARD A PRO-COAGULANT PHENOTYPE IN PHILADELPHIA-NEGATIVE MYELOPROLIFERATIVE NEOPLASMS}},
  author = {Beatriz De Castro VIEIRA and Vitor Leonardo BASSAN and Lorena Garcia AZEVEDO and Lilian Maria GARCIA RAMOS and Luciana Ambrósio CHAIM and Caroline FONTANARI and Lorena Lobo DE FIGUEIREDO-PONTES and Fabíola Attié DE CASTRO},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.107491},
  url = {https://doi.org/10.1016/j.htct.2026.107491},
  note = {CC BY},
}

TY  - JOUR
TI  - CIRCULATING INFLAMMATORY MEDIATORS REPROGRAM PLATELETS TOWARD A PRO-COAGULANT PHENOTYPE IN PHILADELPHIA-NEGATIVE MYELOPROLIFERATIVE NEOPLASMS
AU  - Beatriz De Castro VIEIRA
AU  - Vitor Leonardo BASSAN
AU  - Lorena Garcia AZEVEDO
AU  - Lilian Maria GARCIA RAMOS
AU  - Luciana Ambrósio CHAIM
AU  - Caroline FONTANARI
AU  - Lorena Lobo DE FIGUEIREDO-PONTES
AU  - Fabíola Attié DE CASTRO
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.107491
UR  - https://doi.org/10.1016/j.htct.2026.107491
AB  - Background and aims: Philadelphia-negative myeloproliferative neoplasms (MPN) is characterized by a persistent inflammatory milieu enriched in cytokines, chemokines, lipid mediators, growth factors, and other soluble mediators that can directly modulate and influence platelet and immune cell function. Although thrombosis remains the leading cause of morbidity and mortality in MPN, the mechanisms linking systemic inflammation to platelet dysfunction are not fully understood. We therefore quantified the levels of inflammatory plasma mediators of MPN patients and investigated whether these mediators could influence platelet function toward a pro-coagulant phenotype. Methods: Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were obtained by sequential centrifugation (200 × g for 15 min and 500 × g for 10 min, respectively). Healthy donor platelets isolated from the PRP were incubated with 10% PPP from heterologous healthy donors (n = 10) or patients with polycythemia vera (PV), essential thrombocythemia (ET), or primary myelofibrosis (MF) (n = 10 per group) for 30 min at 37°C. Platelet activation (CD62P, CD36, and CD63) and phosphatidylserine exposure (Annexin-V) were evaluated by flow cytometry. Circulating inflammatory mediators were quantified in the PPP using a multiplex bead-based immunoassay, while C-reactive protein (CRP) was measured by turbidimetry. Statistical comparisons among these data from control, PV, ET and MP were performed using the Mann-Whitney test. Results: Multiplex analysis identified distinct inflammatory signatures among MPN subtypes. PV and ET exhibited high circulating IL-1RI (PV: p = 0.0071; ET: p = 0.0340), IL-6 (PV: p = 0.0084; ET: p = 0.0162), and soluble MPO (PV: p = 0.0031; ET: p = 0.0035), whereas MF was characterized by reduced IL-1RII (p = 0.0004) and soluble CD14 (p = 0.0001), supporting disease-specific inflammatory remodeling. Although CRP levels did not differ significantly among groups, PV and MF showed a trend toward higher concentrations. Consistent with this inflammatory milieu, patients with MPN exhibited a significantly higher frequency of Annexin-V-positive platelets than controls at baseline (p < 0.0001), indicating that circulating platelets are intrinsically primed toward a pro-coagulant phenotype. Plasma priming assays further demonstrated that soluble mediators present in MPN plasma can reproduce this phenotype in healthy donor platelets, as evidenced by increased CD62P (p = 0.0079), CD36 (p = 0.0159), and CD63 expression (p = 0.0317) together with enhanced Annexin-V binding (p = 0.0020). Conclusions: The inflammatory plasma milieu of MPN patients can reprogram healthy platelets toward a pro-coagulant phenotype. Together with the distinct circulating inflammatory signatures identified across MPN subtypes, these findings demonstrate that plasma-derived inflammatory mediators actively drive platelet dysfunction and provide a mechanistic link between systemic inflammation and thromboinflammation. This inflammatory axis represents a promising source of biomarkers and potential therapeutic targets for preventing thrombotic complications in MPN.
SN  - 2531-1379
SN  - 2531-1387
ER  -