Abstract:
:Recent progress in the understanding of thrombus formation has suggested an important role of glycoprotein (GP)VI. In contrast to its pivotal role in collagen-induced platelet activation, it has been suggested that its blockade does not induce massive bleeding tendency. To demonstrate the dissociation between inhibitory effect on platelet aggregation and bleeding by GPVI blockade, we examined the effects of Fab fragment of OM2, an anti-human GPVI monoclonal antibody on ex vivo collagen-induced platelet aggregation and skin bleeding time after intravenous injection in cynomolgus monkeys. In a dose-escalation study, OM2 potently (> 80%) inhibited collagen-induced platelet aggregation at the cumulative dose of 0.2 mg/kg with a slight prolongation of bleeding time (1.3 times baseline value). Furthermore, at 18.8 mg/kg, the highest dose tested, prolongation of bleeding time was still mild (1.9 times). In contrast, abciximab, Fab fragment of anti-GPIIb/IIIa antibody prolonged bleeding time by 5.0 times at 0.35 mg/kg, the lowest effective dose on platelet aggregation. In a pharmacodynamic study, a bolus injection of OM2 at 0.4 mg/kg produced potent inhibition of collagen-induced aggregation up to six hours after injection, showing longer half-life than that of abciximab. The injection of OM2 Fab did not induce thrombocytopenia and GPVI depletion in monkeys. These results suggest that blockade of GPVI by antibody can exert a potent inhibitory effect on collagen-induced platelet aggregation with a milder prolongation of bleeding time than blockade of GPIIb/IIIa. This study indicates that OM2 has the potential to be developed as a new class of therapeutic tool.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Matsumoto Y,Takizawa H,Nakama K,Gong X,Yamada Y,Tandon NN,Kambayashi Jsubject
Has Abstractpub_date
2006-08-01 00:00:00pages
167-75issue
2eissn
0340-6245issn
2567-689Xpii
06080167journal_volume
96pub_type
杂志文章abstract::A method is described for the purification of antiactivator from bovine euglobulin-free serum by means of gelfiltration and ion exchange chromatography. The purified antiactivator has no antifibrinolytic activity. It has a molecular weight of about 115,000 and it appears to be a gamma globulin. The dissociation consta...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1979-10-31 00:00:00
abstract::The blockade of platelet membrane glycoprotein IIb/IIIa by a monoclonal antibody, 7E3, was measured by flow cytometry using a fluorescein isothiocyanate-conjugated disintegrin, FITC-crotavirin, as the probe. After treatment of platelets with 7E3 or 7E3 F(ab')2, there is a good correlation between the inhibition of pla...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1981-06-30 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:2002-02-01 00:00:00
abstract::Venous thromboembolic (VTE) complications in children and adolescents with acute lymphoblastic leukaemia (ALL) and T or B cell lymphoblastic lymphoma (T/B cell LL) can result not only in life-threatening acute complications but also contribute to significant long-term sequelae. The PREVAPIX-ALL study is an open-label ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1055/s-0039-1679938
更新日期:2019-05-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1986-12-15 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2003-04-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 指南,杂志文章
doi:
更新日期:2001-05-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH15-05-0381
更新日期:2016-01-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1989-02-28 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1984-08-31 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1987-08-04 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH14-04-0305
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1988-06-16 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2002-12-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2005-09-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,meta分析
doi:
更新日期:2001-07-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-02-0118
更新日期:2004-07-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:2006-10-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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更新日期:2000-10-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0040-1702225
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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