Coagulant activity and cellular origin of circulating tissue factor exposing microparticles in cancer patients - two forms of TF-exposing microparticles

A. Kleinjan, A. N. Boing, M. Di Nisio, D. Twint, P. W. Kamphuisen, P. Nanayakkara, H. R. Buller, R. Nieuwland

Research output: Contribution to journalMeeting AbstractAcademic

Abstract

Background: Because plasma of cancer patients presenting with venous thrombosis contains high numbers of tissue factor (TF)-exposing microparticles (TF-MP1), TF-MP have been causally linked to the occurrence of venous thrombosis in cancer patients. The relationship between numbers of TF-exposing MP and the TF-MP dependent coagulant activity, however, is unclear. In addition, to which extent TF-MP originate from cancer cells is also unknown. Aim: We investigated the relationship between TF-MP numbers and coagulant activity, and the cellular origin of circulating TF-MP in cancer patients. Methods: Citrate-anticoagulated blood was collected via a single blood withdrawal from cancer patients undergoing chemotherapy. The number of TF-MP was measured by flow cytometry and TF-MP coagulant activity was measured in a fibrin generation test (FGT) in the presence or absence of an inhibitory antibody to human factor VII. Patients were categorised as having a low or high number of TF-MP (≤ or > 95th percentile), and as having low or high TF-MP coagulant activity (≤ or > 13% TF-dependent prolongation of clotting time as determined by FGT). The cellular origin was determined by flow cytometry in those patients with number of TF-MP above the 95th percentile of the total cohort. Results: Of the total cohort of 209 cancer patients, 98 had metastasis (47%). Overall, no correlation was present between the numbers of TF-MP and the coagulant activity (r = 0.029, P = 0.69). When comparing patients with a high and low number of TF-MP, respectively three of the 12 (25%) and 60 of the 192 (31%) patients had high TFMP coagulant activity. Conversely, when comparing patients with high and low TF-MP coagulant activity, respectively only three of the 63 (4.8%) and nine of the 141 (6.4%) patients had a high number of TF-exposing MP. There was a marked variation between patients with regard to the cellular origin of the TF-MP. Of the 13 patients with high TF-MP numbers, the cellular origin of TF in five patients was variable and added up to above 100%; including 67% and 44% staining for two independent tumor markers, 66% for a platelet marker, and 59% for a monocyte marker (all medians). In the other eight patients, the origin of > 25% of TF-MP could be established, and most of these TF-MP originated from platelets and no tumor-derived vesicles were detectable. Summary/Conclusions: Because increased numbers of TF-MP and coagulant activity are almost mutually exclusive, we postulate that two forms of TF associated with MP circulate in cancer patients, a coagulant form which is present in minute quantities and below the detection limit of flow cytometry, and a non-coagulant form which is detectable by flow cytometry. Taken together, although at least part of the TFMP can derive from tumor cells, the cellular origin of circulating and coagulant TF-exposing MP in cancer patients remains to be elucidated.
Original languageEnglish
Pages (from-to)265
Number of pages1
JournalJournal of Thrombosis and Haemostasis
Volume11
Publication statusPublished - Jul-2013

Keywords

  • thromboplastin
  • coagulating agent
  • marker
  • blood clotting factor 7
  • antibody
  • fibrin
  • citric acid
  • tumor marker
  • cancer patient
  • human
  • society
  • thrombosis
  • hemostasis
  • patient
  • flow cytometry
  • vein thrombosis
  • thrombocyte
  • blood
  • blood clotting time
  • tumor cell
  • limit of detection
  • monocyte
  • chemotherapy
  • neoplasm
  • staining
  • metastasis
  • cancer cell
  • plasma

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