Hemostatic effect of activated factor VII without promotion of thrombus growth in melagatran-anticoagulated primates.

Hemostatic effect of activated factor VII without promotion of thrombus growth in melagatran-anticoagulated primates. Research Abstract Details 

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Hemostatic effect of activated factor VII without promotion of thrombus growth in melagatran-anticoagulated primates. Abstract Text:

Gruber,Stefan Carlsson,Harry F ,Ulla Marzec,Troy C Sarich,Stephen R Hanson,

INTRODUCTION: Pharmacological enhancement of coagulation using activated prothrombin complex concentrate (APCC) or activated factor VII (FVIIa) might be useful hemostatic approaches to bleeding emergencies during anticoagulant therapy. However, any such intervention should not increase thrombotic risk. We therefore investigated their hemostatic and prothrombotic potential during propagation of large arterial-type thrombin in anticoagulated baboons. MATERIALS AND METHODS: High dose melagatran, a competitive inhibitor of thrombin (0.6 mg/kg/h), or inactivated FVIIa (FVIIai), a competitive inhibitor of FVIIa (2 mg/kg) were used for anticoagulation. APCC or FVIIa were administered to melagatran-anticoagulated animals only. Primary hemostasis was assessed as template bleeding time (BT). Thrombus formation was quantified as fibrin deposition (FD) and platelet deposition (PLD) in synthetic vascular grafts that were deployed for 40 min into arteriovenous shunts. RESULTS: Melagatran (n=11) prolonged BT to 279% (95% CI +/-140%; P<0.019), reduced FD to 33% [+/-8%; P<0.001]; and PLD to 39% [+/-11%; P<0.001] of untreated controls. FVIIai (n=3) prolonged BT (222% [+/-51%; P<0.010]) without inhibiting thrombus propagation. APCC (n=10) reduced the antithrombotic effect of melagatran (FD 52% [+/-9%; P<0.002], PLD 61% [+/-17%; P=0.028] versus melagatran alone) at a dose (250 U/kg) that had no effect on the BT (327% [+/-150%; P=0.607]. Meanwhile, FVIIa (n=12) normalized the BT to 115% (+/-32%; P<0.05) at a dose (270 microg/kg) that was not yet prothrombotic (FD 26% [+/-4%; P<0.001], PLD 39% [+/-9%; P=0.970]). CONCLUSION: Administration of FVIIa during antithrombotic treatment with direct thrombin inhibitors might support hemostasis before promoting the intraluminal expansion of thrombi.

Hemostatic effect of activated factor VII without promotion of thrombus growth in melagatran-anticoagulated primates. Publishing Authors By Initials

A Gruber,S Carlsson,HF ,U Marzec,TC Sarich,SR Hanson,

For similar natural sciences: time: time factors research abstracts see: natural sciences: time: time factors research

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Hemostatic effect of activated factor VII without promotion of thrombus growth in melagatran-anticoagulated primates. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Thrombosis research

VOLUME: 119

Page Numbers: 121-7

Journal Abbreviation: Thromb. Res.

ISSN: 0049-3848

DAY: 31

MONTH: 01

YEAR: 2006

Hemostatic effect of activated factor VII without promotion of thrombus growth in melagatran-anticoagulated primates. Information

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LANGUAGE: eng

NlmUniqueID: 326377

Hemostatic effect of activated factor VII without promotion of thrombus growth in melagatran-anticoagulated primates. Keywords Mesh Terms:

KEYWORDS: Time Factors

MESH TERMS: pathology

Chemical & Substance for Abstract: Hemostatic effect of activated factor VII without promotion of thrombus growth in melagatran-anticoagulated primates. Information

Substance Name: Factor VIIa

Registry Number: EC 3.4.21.21

Grant and Affiliation Information for Hemostatic effect of activated factor VII without promotion of thrombus growth in melagatran-anticoagulated primates.

AFFILIATION: Department of Biomedical Engineering, OGI School of Science and Engineering, Oregon Health and Science University, 20000 N.W. Walker Road, Beaverton, OR 97006-8921, USA. gruber@ohsu.edu

Country: United States

AGENCY: United States NCRR

GRANT: RR 00165

ACRONYM: RR

MEDLINETA: Thromb Res

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