PMID- 11019977
OWN - NLM
STAT- MEDLINE
DCOM- 20010329
LR  - 20181130
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 84
IP  - 3
DP  - 2000 Sep
TI  - GPIIb-IIIa antagonist-induced reduction in platelet surface factor V/Va binding 
      and phosphatidylserine expression in whole blood.
PG  - 492-8
AB  - In addition to inhibition of platelet aggregation, GPIIb-IIIa antagonists may 
      reduce thrombotic events via other mechanisms. In a novel whole blood flow 
      cytometric system, we investigated the effects of GPIIb-IIIa antagonists, in the 
      presence or absence of thrombin inhibitors, on platelet surface-bound factor V/Va 
      and platelet surface phospholipids. Diluted venous blood was incubated with 
      either buffer or a GPIIb-IIIa antagonist (abciximab, tirofiban, or eptifibatide). 
      Some samples were pre-incubated with clinically relevant concentrations of 
      unfractionated heparin (UFH), a low molecular weight heparin, a direct thrombin 
      inhibitor, or buffer only. Platelets were then activated and labeled with mAb 
      V237 (factor V/Va-specific) or annexin V (binds phosphatidylserine), fixed, and 
      analyzed by flow cytometry. In the absence of thrombin inhibitors, GPIIb-IIIa 
      antagonists (especially abciximab) significantly reduced agonist-induced platelet 
      procoagulant activity, as determined by reduced binding of V237 and annexin V. At 
      high pharmacologic concentrations, unfractionated heparin and enoxaparin, but not 
      hirudin, further reduced factor V/Va binding to the surface of activated 
      platelets in the presence of GPIIb-IIa antagonists. Agonist-induced platelet 
      procoagulant activity was reduced in a patient with Glanzmann's thrombasthenia. 
      We conclude that GPIIb-IIIa antagonists reduce platelet procoagulant activity in 
      whole blood and heparin and enoxaparin augment this reduction. Fibrinogen binding 
      to GPIIb-IIIa is important in the generation of platelet procoagulant activity.
FAU - Furman, M I
AU  - Furman MI
AD  - Center for Platelet Function Studies, University of Massachusetts Medical School, 
      Worcester, PA 01655, USA. Furman@platelets.org
FAU - Krueger, L A
AU  - Krueger LA
FAU - Frelinger, A L 3rd
AU  - Frelinger AL 3rd
FAU - Barnard, M R
AU  - Barnard MR
FAU - Mascelli, M A
AU  - Mascelli MA
FAU - Nakada, M T
AU  - Nakada MT
FAU - Michelson, A D
AU  - Michelson AD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Immunoglobulin Fab Fragments)
RN  - 0 (Membrane Proteins)
RN  - 0 (Peptides)
RN  - 0 (Phosphatidylserines)
RN  - 0 (Platelet Glycoprotein GPIIb-IIIa Complex)
RN  - 42HK56048U (Tyrosine)
RN  - 9001-24-5 (Factor V)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.21.5 (Thrombin)
RN  - GGX234SI5H (Tirofiban)
RN  - NA8320J834 (Eptifibatide)
RN  - X85G7936GV (Abciximab)
SB  - IM
MH  - Abciximab
MH  - Antibodies, Monoclonal/pharmacology
MH  - Blood Platelets/metabolism
MH  - Collagen/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Eptifibatide
MH  - Factor V/*metabolism
MH  - Flow Cytometry
MH  - Humans
MH  - Immunoglobulin Fab Fragments/pharmacology
MH  - Infant, Newborn
MH  - Membrane Proteins/metabolism
MH  - Peptides/pharmacology
MH  - Phosphatidylserines/*blood
MH  - Platelet Glycoprotein GPIIb-IIIa Complex/*antagonists & inhibitors
MH  - Protein Binding
MH  - Thrombasthenia/blood
MH  - Thrombin/antagonists & inhibitors/pharmacology
MH  - Tirofiban
MH  - Tyrosine/*analogs & derivatives/pharmacology
EDAT- 2000/10/06 11:00
MHDA- 2001/04/03 10:01
CRDT- 2000/10/06 11:00
PHST- 2000/10/06 11:00 [pubmed]
PHST- 2001/04/03 10:01 [medline]
PHST- 2000/10/06 11:00 [entrez]
AID - 00090492 [pii]
PST - ppublish
SO  - Thromb Haemost. 2000 Sep;84(3):492-8.