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Increased promyelocytic-derived microparticles: a novel potential factor for coagulopathy in acute promyelocytic leukemia.
- Source :
-
Annals of hematology [Ann Hematol] 2013 May; Vol. 92 (5), pp. 645-52. Date of Electronic Publication: 2013 Jan 24. - Publication Year :
- 2013
-
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.
- Subjects :
- Adolescent
Adult
Aged
Blood Coagulation Disorders epidemiology
Case-Control Studies
Cell Surface Extensions pathology
Cell Surface Extensions physiology
Cell-Derived Microparticles pathology
Cells, Cultured
Female
Granulocyte Precursor Cells pathology
Granulocyte Precursor Cells physiology
Humans
Leukemia, Promyelocytic, Acute blood
Leukemia, Promyelocytic, Acute pathology
Male
Middle Aged
Risk Factors
Young Adult
Blood Coagulation Disorders etiology
Cell-Derived Microparticles physiology
Granulocyte Precursor Cells ultrastructure
Leukemia, Promyelocytic, Acute complications
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0584
- Volume :
- 92
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Annals of hematology
- Publication Type :
- Academic Journal
- Accession number :
- 23344645
- Full Text :
- https://doi.org/10.1007/s00277-013-1676-6