Abstract:
BACKGROUND:Coagulopathy is a major cause of early death when arsenic trioxide (As(2)O(3)) therapy fails. In addition to the procoagulant properties of blast cells, the cytotoxic therapy may contribute to the coagulation disorders. The aim of the present study was to evaluate the possible impact of As(2)O(3) on membrane alterations, including phosphatidylserine (PS) exposure and microparticle generation, and the consequent procoagulant properties of endothelial cells. METHODS:Procoagulant activity (PCA) of human umbilical vein endothelial cells (HUVECs) was assessed by measuring clotting time and through purified coagulation complex assays. PS exposure on HUVEC membrane was observed by confocal microscopy and quantified with flow cytometry. In addition, counts and PCA of endothelial microparticles were determined by flow cytometry and plasma coagulation assay. RESULTS:As(2)O(3) increased the ability of HUVECs to accelerate coagulation process and promote formation of coagulation complexes. Procoagulant activity corresponded to PS exposed on HUVECs. In coincidence with the PS externalization, As(2)O(3) increased the production of PS-bearing microparticles, which then accelerated fibrin strand formation significantly. By blocking PS, lactadherin was able to inhibit over 90% of the intrinsic tenase/prothrombinase activity of As(2)O(3)-treated HUVECs, and restored coagulation times of As(2)O(3)-treated cells and microparticles to control levels. CONCLUSIONS:As(2)O(3) increases PCA of HUVECs through PS exposure and PS-bearing microparticle generation, which might cause thrombosis and act as a contributing factor in As(2)O(3) therapy-related coagulopathy.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Zhou J,Li H,Fu Y,Shi J,Hou J,Zhang Y,Liu X,Song Pdoi
10.1016/j.thromres.2011.01.003subject
Has Abstractpub_date
2011-05-01 00:00:00pages
466-72issue
5eissn
0049-3848issn
1879-2472pii
S0049-3848(11)00004-1journal_volume
127pub_type
杂志文章abstract::A B S T R A C T Thrombotic events are a major cause of morbidity and mortality in cancer. While the association of venous thromboembolic events with cancer is well documented, in recent years arterial events (i.e. acute myocardial infarction and ischemic strokes) have also emerged as relatively common complications am...
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doi:10.1016/0049-3848(90)90222-x
更新日期:1990-12-01 00:00:00
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更新日期:2012-06-01 00:00:00
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更新日期:1982-11-01 00:00:00
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journal_title:Thrombosis research
pub_type: 杂志文章,评审
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更新日期:2013-05-01 00:00:00
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journal_title:Thrombosis research
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journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2011.10.010
更新日期:2012-03-01 00:00:00
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journal_title:Thrombosis research
pub_type: 杂志文章
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更新日期:2015-02-01 00:00:00
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pub_type: 杂志文章
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pub_type: 评论,信件
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pub_type: 杂志文章,评审
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更新日期:2012-10-01 00:00:00
abstract::Human apolipoprotein B was purified by barium sulphate adsorption, subsequent delipidation and gel filtration. The protein was then reconstituted in soya bean lecithin and its inhibitory effect towards thromboplastin was assayed by incubation with rabbit brain thromboplastin. The use of an antibody against human apoli...
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pub_type: 杂志文章
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更新日期:2018-07-01 00:00:00
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doi:10.1016/j.thromres.2019.09.005
更新日期:2019-11-01 00:00:00
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journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(87)90290-8
更新日期:1987-04-15 00:00:00
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更新日期:1994-09-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2002-09-15 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1999-12-01 00:00:00
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journal_title:Thrombosis research
pub_type: 杂志文章
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更新日期:1989-09-15 00:00:00
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journal_title:Thrombosis research
pub_type: 杂志文章
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更新日期:2015-04-01 00:00:00
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journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(95)93881-y
更新日期:1995-03-01 00:00:00
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journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2011.05.008
更新日期:2011-10-01 00:00:00
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journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(84)90258-5
更新日期:1984-06-15 00:00:00
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journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(89)90203-x
更新日期:1989-03-01 00:00:00
abstract::Activation of plasma plasminogen to plasmin is the objective of current strategies for thrombolytic therapy. Although thrombolytic activity in blood involves a large cellular component as well as that in plasma, the contribution of this cellular phase to clinical thrombolysis has not been examined. Using a 125I-fibrin...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(90)90128-y
更新日期:1990-07-15 00:00:00
abstract::Platelets from rats fed a diet high in linoleic acid (6%) bound increased amounts of fibrinogen on stimulation with ADP, compared to those from rats fed diets with low (2%) or no linoleic acid. However, this increased fibrinogen binding was associated with a decrease in platelet aggregation induced by ADP. Changes in ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(84)90107-5
更新日期:1984-04-01 00:00:00