PMID- 10947916
OWN - NLM
STAT- MEDLINE
DCOM- 20001201
LR  - 20191104
IS  - 0929-5305 (Print)
IS  - 0929-5305 (Linking)
VI  - 10
IP  - 1
DP  - 2000 Aug
TI  - Inhibition of platelet-dependent prothrombinase activity and thrombin generation 
      by glycoprotein IIb/IIIa receptor-directed antagonists: potential contributing 
      mechanism of benefit in acute coronary syndromes.
PG  - 69-76
AB  - The glycoprotein (GP) IIb/IIIa receptor antagonists used widely in the medical 
      treatment of acute coronary syndromes and during percutaneous coronary 
      interventions, prevent fibrinogen cross-linking and platelet aggregation, 
      critical initiating steps in arterial thrombosis. Their anticoagulant properties, 
      particularly when administered conjunctively with heparin preparations, are less 
      well-characterized. In a series of in vitro studies, increasing concentrations of 
      abciximab, tirofiban, and eptifibatide either alone or in combination with 
      unfractionated heparin (UFH) or fractionated heparin (enoxaparin) were added to 
      washed platelets suspended in Tyrode's buffer. Following platelet activation and 
      prothrombinase assembly, thrombin generation was determined by enzyme-linked 
      immunosorbent assay (ELISA). There was a concentration-dependent reduction in 
      platelet-dependent thrombin generation with each of the GPIIb/IIIa receptor 
      antagonists. The combination of tirofiban and UFH yielded percent, absolute and 
      relative reductions (compared with tirofiban alone) of 48.0%, 16.9%, and 35.2%, 
      respectively. The corresponding values for eptifibatide and abciximab were 38.0%, 
      13.5%, 35.5%, and 55.1%, 3.8%, 8.4%, respectively. Thrombin generation was 
      decreased by an additional 2 to 3% (absolute reduction) with high concentrations 
      of enoxaparin in combination with either eptifibatide or abciximab. Platelet 
      GPIIb/IIIa receptor antagonists, beyond their ability to prevent 
      fibrinogen-mediated aggregation, inhibit platelet-dependent prothrombinase 
      activity and thrombin generation in a concentration-dependent manner. Heparin 
      facilitates the existing anticoagulant properties, supporting combination therapy 
      in clinical practice. The potential added benefit of fractionated heparin over 
      UFH will require further investigation.
FAU - Li, Y
AU  - Li Y
AD  - Laboratory for Vascular Biology Research, Cardiovascular Thrombosis Research 
      Center, University of Massachusetts Medical School, Worcester, MA 01655, USA.
FAU - Spencer, F A
AU  - Spencer FA
FAU - Ball, S
AU  - Ball S
FAU - Becker, R C
AU  - Becker RC
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - J Thromb Thrombolysis
JT  - Journal of thrombosis and thrombolysis
JID - 9502018
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Anticoagulants)
RN  - 0 (Immunoglobulin Fab Fragments)
RN  - 0 (Peptides)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Platelet Glycoprotein GPIIb-IIIa Complex)
RN  - 42HK56048U (Tyrosine)
RN  - 9005-49-6 (Heparin)
RN  - 9035-58-9 (Thromboplastin)
RN  - EC 3.4.21.5 (Thrombin)
RN  - GGX234SI5H (Tirofiban)
RN  - NA8320J834 (Eptifibatide)
RN  - X85G7936GV (Abciximab)
SB  - IM
MH  - Abciximab
MH  - Acute Disease
MH  - Antibodies, Monoclonal/pharmacology
MH  - Anticoagulants/pharmacology
MH  - Blood Platelets/*metabolism
MH  - Coronary Disease/drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Eptifibatide
MH  - Heparin/pharmacology
MH  - Humans
MH  - Immunoglobulin Fab Fragments/pharmacology
MH  - Kinetics
MH  - Peptides/pharmacology
MH  - Platelet Aggregation Inhibitors/pharmacology
MH  - Platelet Glycoprotein GPIIb-IIIa Complex/*antagonists & inhibitors
MH  - Thrombin/*antagonists & inhibitors/biosynthesis
MH  - Thromboplastin/*antagonists & inhibitors/metabolism
MH  - Tirofiban
MH  - Tyrosine/analogs & derivatives/pharmacology
EDAT- 2000/08/18 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/08/18 11:00
PHST- 2000/08/18 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/08/18 11:00 [entrez]
AID - 10.1023/a:1018754906289 [doi]
PST - ppublish
SO  - J Thromb Thrombolysis. 2000 Aug;10(1):69-76. doi: 10.1023/a:1018754906289.