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Elevated extracellular trap formation and contact system activation in acute leukemia

  • Tae Yeul Kim
  • Ja-Yoon Gu
  • Hye Soo Jung
  • Youngil Koh
  • Inho Kim
  • Hyun Kyung Kim
Article

Abstract

Leukemic cells release their nuclear contents into the extracellular space upon activation. The released nuclear contents, called extracellular traps, can activate the contact system of coagulation. This study accessed the extent of contact system activation, the levels of extracellular traps, and coagulation activation in hematologic malignancies including acute leukemia. In 154 patients with hematologic malignancies (acute leukemia, n = 29; myelodysplastic syndrome, n = 20; myeloproliferative neoplasms, n = 69; plasma cell myeloma, n = 36) and 48 normal controls, the levels of coagulation factors (fibrinogen and factor VII, VIII, IX, and XII), D-dimer, thrombin generation, extracellular trap markers (histone–DNA complex, cell-free dsDNA, leukocyte elastase), and contact system markers (activated factor XII [XIIa], high-molecular-weight kininogen, prekallikrein, bradykinin) were measured. Patients with acute leukemia showed the highest levels of peak thrombin, extracellular trap markers, and factor XIIa. Factor XIIa level was significantly associated with the presence of acute leukemia. The histone–DNA complex and cell-free dsDNA were revealed as significant associated factors with the factor XIIa level. Three markers of extracellular traps and two markers of thrombin generation significantly contributed to the hemostatic abnormalities in hematologic malignancies. Contact system was activated in acute leukemia and its activation was significantly associated with the extent of extracellular trap formation. This finding suggests that extracellular traps might be a major source of contact system activation and therapeutic strategies targeting extracellular trap formation or contact system activation may be beneficial in acute leukemia.

Keywords

Hematologic malignancies Acute leukemia Thrombin generation assay Contact system Neutrophil extracellular traps Thrombosis 

Notes

Acknowledgements

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health and Welfare, Republic of Korea (Grant No. HI17C1134).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Laboratory MedicineSeoul National University College of MedicineSeoulSouth Korea
  2. 2.Department of Internal MedicineSeoul National University College of MedicineSeoulSouth Korea

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