These authors contributed equally.
Phosphatidylserine exposure and procoagulant activity in acute promyelocytic leukemia
Article first published online: 21 JAN 2010
© 2010 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 8, Issue 4, pages 773–782, April 2010
How to Cite
ZHOU, J., SHI, J., HOU, J., CAO, F., ZHANG, Y., RASMUSSEN, J. T., HEEGAARD, C. W. and GILBERT, G. E. (2010), Phosphatidylserine exposure and procoagulant activity in acute promyelocytic leukemia. Journal of Thrombosis and Haemostasis, 8: 773–782. doi: 10.1111/j.1538-7836.2010.03763.x
- Issue published online: 23 MAR 2010
- Article first published online: 21 JAN 2010
- Received 30 November 2009, accepted 11 January 2010
- factor Xase;
- tissue factor
Summary. Background: Acute promyelocytic leukemia (APL) frequently causes disseminated intravascular coagulation that can worsen with cytotoxic chemotherapy but improve with the therapeutic differentiating agents, all trans retinoic acid (ATRA) and arsenic trioxide (As2O3). APL cells display tissue factor but the relationship of tissue factor and other procoagulant activity to phosphatidylserine (PS) exposure is largely unknown. Methods: Lactadherin, a milk protein with stereospecific binding to phosphatidyl-L-serine, was used as a probe for PS exposure on an immortalized APL cell line (NB4) and on the cells of eight patients with APL. PS exposure was evaluated with flow cytometry, confocal microscopy, coagulation assays, and purified prothrombinase and factor (F) Xase assays. Results: Plasma procoagulant activity of NB4 and APL cells increased approximately 15-fold after exposure to etoposide or daunorubicin and decreased 80% after treatment with ATRA or As2O3. Procoagulant activity corresponded to exposed PS on viable APL cells. PS exposure decreased after treatment with ATRA or As2O3 and increased after treatment with daunorubicin or etoposide. Excess lactadherin inhibited 80–85% of intrinsic FXase, FVIIa-tissue factor and prothrombinase activities on both NB4 cells and APL cells. Confocal microscopy identified membrane patches that stained with lactadherin, but not annexin V, demonstrating focal, low-level PS exposure. Conclusions: PS is exposed on viable APL cells and is necessary for approximately 80% of procoagulant activity.