{
  "abstract": "Background: Platelets from patients with thrombotic primary antiphospholipid syndrome (t-PAPS) display enhanced responsiveness to ADP, increased P2Y12 expression, and reduced intracellular cAMP and cGMP levels. Aims: To evaluate whether resistance to inhibitory adenosine signaling could contribute to platelet hyperreactivity in t-PAPS. Methods: Total IgG was purified from serum, and protein concentration was 250 µg/mL. Washed platelets from healthy donors were incubated either alone, with plasma or IgG purified from t-PAPS or controls (IgG-P and IgG-C) and incubated with adenosine (1 or 10 µM) before stimulation with ADP (3 or 10 µM). Platelet activation was quantified using CD62P and PAC-1. ATP release was measured using ATP Kit (A22066). Serum adenosine deaminase (ADA) levels were measured using the EBRAM® Adenosine Deaminase kit. Analyses of adenosine, inosine and AMP were conducted using a Vanquish ultra-high-performance liquid chromatography system coupled to a TSQ Quantis mass spectrometer. Results: At baseline, platelets exhibited 3.12% (SD 1.04) double positivity for P-selectin/PAC-1. Following stimulation with IgG-P and IgG-C, double positivity increased to 5.72% (SD 4.19) and 4.86% (SD 3.37), respectively. After the addition of ADP, activation increased further to 14.51% (SD 10.58) with IgG-P and 11.99% (SD 9.40) with IgG-C. Pre-incubation with adenosine reduced double positivity to 11.69% (SD 9.20) and 9.96% (SD 7.49) under IgG-P and IgG-C conditions, respectively. Overall, mean platelet activation across all conditions was significantly higher with IgG-P (8.76%) than with IgG-C (7.48%) (difference between means: −1.27; 95% CI: −2.132 to −0.4226; p = 0.005, two-way ANOVA). In the ATP release experiments involving plasma, it was observed that, under basal conditions, healthy platelets exhibited mean ATP levels of 478 nM (SD 98). Following incubation with control plasma, there was a marked reduction in ATP release to 90 nM (SD 101), whereas with plasma from t-PAPS, the release was 169 nM (SD 239.5). Upon the addition of 3 µM ADP, the response increased to 253 nM (SD 149) with control plasma and 399 nM (SD 287) with t-PAPS plasma. After incubation with 10 µM adenosine, ATP levels were 235 nM (SD 152) in the control group and 344 nM (SD 262) in t-PAPS. Overall, the mean ATP release across all conditions was 264 nM in the group stimulated with control plasma and 348 nM in the group stimulated with APS plasma (difference between means = -83.58; 95% CI -118.9 to -48.29; p < 0.0001; two-way ANOVA). ADA levels were higher in t-PAPS (median 13.2 U/L [IQR 10.9–17.0], n = 33) compared to controls (median 9.7 U/L [IQR 8.0–11.1], n = 31; p < 0.0001). Serum adenosine levels were significantly lower in t-PAPS, with a median of 0.096 µM (IQR 0.064–0.129), compared with 0.184 µM (IQR 0.080–0.637) in controls (p = 0.01). Inosine levels were similar between groups, with a median of 2.823 µM (IQR 1.195–6.804) in patients and 2.506 µM (IQR 1.434–8.237) in controls (p = 0.95). Serum cAMP levels were higher in t-PAPS, with a median of 0.032 µM (IQR 0.023–0.044), compared with 0.016 µM (IQR 0.012–0.017) in controls (p < 0.0001). Conclusion: Our results suggest that platelet hyperreactivity in t-PAPS is driven by complementary mechanisms involving both IgG-mediated platelet activation and impaired adenosine-mediated inhibition by plasma-derived factors.",
  "abstract_shown": true,
  "affiliations": [
    "Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil",
    "Departamento de Química Analítica, Instituto de Química, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Bruna Cardoso JACINTHO-ROBISON"
    },
    {
      "affs": [
        1
      ],
      "name": "Guilherme Garcia RAFAEL"
    },
    {
      "affs": [
        0
      ],
      "name": "Rafaela Gomes FRANÇA"
    },
    {
      "affs": [
        0
      ],
      "name": "Jose Diogo OLIVEIRA"
    },
    {
      "affs": [
        0
      ],
      "name": "Fabiola Zakia MONICA"
    },
    {
      "affs": [
        1
      ],
      "name": "Carla Beatriz Grespan BOTTOLI"
    },
    {
      "affs": [
        0
      ],
      "name": "Erich V DE PAULA"
    },
    {
      "affs": [
        0
      ],
      "name": "Fernanda Andrade ORSI"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ap81cbhv60dqq.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.108073",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926018201",
  "id": "ap81cbhv60dqq",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.108073",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC633-647.5"
    ],
    [
      "openalex",
      "2745|Systemic Lupus Erythematosus Research"
    ]
  ],
  "openalex": "W7223114009",
  "pdf_url": "https://www.sciencedirect.com/science/article/pii/S2531137926018201/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/ap81cbhv60dqq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:25Z",
      "native_id": "4b684321f5db4558acfea7d668365144",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.htct.2026.108073"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "lcc:RC633-647.5",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "ANTIBODIES AND PLASMA COMPONENTS CONTRIBUTE DIFFERENTLY TO PLATELET REACTIVITY IN THROMBOTIC ANTIPHOSPHOLIPID SYNDROME",
  "title_text": "ANTIBODIES AND PLASMA COMPONENTS CONTRIBUTE DIFFERENTLY TO PLATELET REACTIVITY IN THROMBOTIC ANTIPHOSPHOLIPID SYNDROME",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:25Z",
  "url": "https://research.draconitic.com/paper/ap81cbhv60dqq",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}