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Cellular origin and procoagulant activity of tissue factor-exposing microparticles in cancer patients

Kleinjan, A., Berckmans, R. J., Böing, A. N., Sturk, A., Büller, H. R., Kamphuisen, P. W. & Nieuwland, R., 1-Apr-2012, In : Thrombosis Research. 129, p. 161 1 p.

Research output: Contribution to journalMeeting AbstractAcademic

  • A. Kleinjan
  • R.J. Berckmans
  • A.N. Böing
  • A. Sturk
  • H.R. Büller
  • P.W. Kamphuisen
  • R. Nieuwland
Background: In patients with cancer, tissue factor-exposing microparticles (TF-exposing MP) have been associated with disease progression and thrombosis. The cellular origin and coagulant activity of TF-exposing MP, however, remain disputed. Therefore, we investigated the cellular origin of the TF-exposing MP and the procoagulant activity in cancer patients. Methods: The cellular origin of TF-exposing MP was investigated by flow cytometry in a cohort of 209 cancer patients (59 pancreatic, 97 gastrointestinal, 23 breast, 15 lung, 5 prostate cancer and 10 other types), and 22 healthy controls. We first determined the numbers of TF-exposing MP in plasma from all patients and measured TF-exposing MP coagulant activity in a fibrin generation test. Based on previous results, a prolongation of the clotting time in the presence of an inhibitory antibody against factor VIIa above 13% was considered abnormal. Second, we selected those patients with numbers of TF-exposing MP above the 95th percentile, and determined the cellular origin of TF-exposing MP in these patients. Results: The numbers of TF-exposing MP were increased in the cancer patients compared to the healthy subjects (median: 2.0 vs 0.40×105/mL; p=0.01). 30% of the cancer patients had an abnormal FGT test, indicating TF-exposing MP coagulant activity. There was no correlation between the number and coagulant activity of TF-exposing MP (r=0.029, p=0.685). 13 patients had TF-exposing MP above the 95th percentile. Of these TF-exposing MP, 5.9% (median; interquartile range (IQR) 0.69-54) double stained with CD227 (MUC-1) and 19% (0.62-41) with CD24, both markers of cancer cells (Fig. 1). Furthermore, 28% (11-63) of the TF-exposing MP stained for CD61, platelet glycoprotein IIIa, 3.9% (0.39-55) for the monocyte LPS-receptor (CD14), while 3.0% (1.4-3.5) of TF-MP stained for the erythrocyte marker CD235, and 0.97% (0.53-4.5) for the granulocyte marker CD66b. (Figure presented) Discussion: Levels of TF-exposing MP in cancer patients are higher than in healthy subjects. Strikingly, but not unexpectedly, we could not demonstrate a relationship between levels of TF-exposing MP and coagulant activity. Therefore, at least part of the TF exposed on circulating MP may be involved in other TF-dependent functions, such as angiogenesis or signal transduction. Most TF-exposing MP seem to originate from cancer cells, as they stained double positive with typical tumour cell markers such as CD227 and CD24. However, most TF-exposing MP also labelled positive for typical blood cell CD antigens, therefore these microparticles might be of mixed cellular origin, being shed after a tumour cell has incorporated blood cell characteristics. This phenomenon is specific rather than an artefact, since no double-labelling was observed with some markers such as CD235.
Original languageEnglish
Pages (from-to)161
Number of pages1
JournalThrombosis Research
Volume129
Publication statusPublished - 1-Apr-2012

    Keywords

  • thromboplastin, procoagulant, coagulating agent, marker, blood clotting factor 7a, antibody, leukocyte antigen, fibrin, glycoprotein IIIa, receptor, cell marker, cancer patient, human, thrombosis, hemostasis, neoplasm, patient, normal human, blood cell, tumor cell, cancer cell, prostate cancer, monocyte, thrombocyte, lung, disease course, blood clotting time, breast, signal transduction, plasma, erythrocyte, flow cytometry, granulocyte, angiogenesis, artifact, cancer tissue

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