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Increased promyelocytic-derived microparticles: a novel potential factor for coagulopathy in acute promyelocytic leukemia

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Abstract

The frequent serious bleeding and thrombotic complications in acute promyelocytic leukemia (APL) are major causes of early mortality, but the complex mechanisms causing the bleeding have not been completely elucidated. Because microparticles (MPs) are known to be elevated in thromboembolic disorders, we hypothesized a role for MPs in the pathogenesis of coagulopathy in APL. MPs were isolated from 30 APL patients and 20 healthy subjects and from cultured NB4/APL cells. The morphology of the MPs was examined, and they were quantified and analyzed for their thrombin-generating potential. We confirmed the existence of promyelocytic-derived MPs by morphology using transmission electron microscopy and laser scanning confocal microscopy. Counts of MPs in APL were elevated and were typically from promyelocytic cells (CD33+ TF+ MPs). Importantly, the CD33+ MPs strongly correlated with patient leukocyte count (R = 0.64, p = 0.002) and D-dimer (R = 0.51, p = 0.0038). Moreover, the MPs from patients with APL decreased the coagulation times and induced thrombin generation. APL MP-associated thrombin generation was reduced by 54 % when the extrinsic pathway was blocked using an anti-human tissue factor (TF) antibody. However, neither anti-factor XI nor anti-tissue factor pathway inhibitor had any significant inhibitory effect. Our results show that the procoagulant state in APL is partially due to the TF-dependent procoagulant properties of circulating promyelocytic-derived MPs. TF+ MPs may be a novel potential risk factor for coagulopathy in APL.

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Abbreviations

APL:

Acute promyelocytic leukemia

MPs:

Microparticles

DIC:

Disseminated intravascular coagulation

TF:

Tissue factor

TEM:

Transmission electron microscope

LSCM:

Laser scanning confocal microscopy

PS:

Phosphatidylserine

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Acknowledgments

This research was supported by the Natural Scientific Foundation of Heilongjiang Province (D200861, China), the Supporting Certification of Postdoctoral Heilongjiang Science Research Foundation (LBH-Q10029, China), and the Research Fund for the Doctoral Program of Higher Education (20112307110012, China). We thank Linfeng Cao, Xiuhua Liu, Yueqiu Teng, Zhiyu Liu, and Zhenkun Wang for excellent technical assistance.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Hematology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nan Gang District, Harbin, 150001, China

    Guibo Ma, Linlin Lv, Yujuan Gao & Yanhua Su

  2. Emory University School of Medicine, Atlanta, GA, USA

    Fang Liu

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  1. Guibo Ma
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  2. Fang Liu
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Correspondence to Yanhua Su.

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Ma, G., Liu, F., Lv, L. et al. Increased promyelocytic-derived microparticles: a novel potential factor for coagulopathy in acute promyelocytic leukemia. Ann Hematol 92, 645–652 (2013). https://doi.org/10.1007/s00277-013-1676-6

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