PMID- 11011805
OWN - NLM
STAT- MEDLINE
DCOM- 20010208
LR  - 20191104
IS  - 0094-6176 (Print)
IS  - 0094-6176 (Linking)
VI  - 26 Suppl 1
DP  - 2000
TI  - Comparative efficacy of different low-molecular-weight heparins (LMWHs) and drug 
      interactions with LMWH: implications for management of vascular disorders.
PG  - 39-46
AB  - The low-molecular-weight heparins (LMWHs) are more efficacious and safer than 
      unfractionated heparin (UFH) in the prevention and treatment of venous thrombosis 
      and to a certain extent in the treatment of acute ischemic syndromes. Because of 
      their predictable pharmacokinetics and bioavailability after subcutaneous 
      administration, LMWHs can be more convenient for outpatient use than UFH. 
      Differences in the manufacturing process of LMWHs result in significant 
      structural and molecular weight differences; thus, LMWHs have individual 
      biochemical and pharmacological profiles and are not interchangeable on the basis 
      of either mass or anti-Xa activity. Using thromboelastograph (TEG) and platelet 
      aggregometry, this investigation compared the in vitro efficacy among various 
      LMWHs and examined the interactions between LMWHs and platelet glycoprotein (GP) 
      IIb/IIIa antagonists. TEG was used to determine the ability of platelet and 
      fibrin interactions to augment blood clots, an effect measured under conditions 
      of maximal platelet activation during clot formation accelerated by recombinant 
      human tissue factor (TF). The comparative efficacy of LMWHs on different 
      mediator-induced clot retraction in human blood was assessed by TEG, which 
      demonstrated the potency of different LMWHs to inhibit various mediator-induced 
      clot formations under shear. Tinzaparin was relatively more effective in 
      inhibiting TF-, lipopolysaccharide-, factor (f) Xa-, and thrombin-induced clot 
      formation under shear. Under these conditions, platelets significantly enhance 
      clot strength (eightfold vs. platelet-free fibrin clots). LMWHs appear to have 
      broader efficacy than other anticoagulants. Abciximab and roxifiban further 
      inhibited clot strength by affecting the transmission of platelet contractile 
      force to fibrin by platelet GPIIb/IIIa receptors. Subtherapeutic doses of 
      tinzaparin combined with abciximab or roxifiban resulted in a distinct synergy 
      that improved anticoagulant and antiplatelet efficacy mediated by TF, fXa, or 
      thrombin. As these data suggest, the combination of low-dose tinzaparin with 
      low-dose GPIIb/IIIa antagonists (abciximab, roxifiban) may be efficacious in the 
      prevention and treatment of various thromboembolic disorders.
FAU - Mousa, S A
AU  - Mousa SA
AD  - DuPont Pharmaceuticals Co., Wilmington, DE 19880-0400, USA. 
      shaker.a.mousa@dupontpharma.com
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Semin Thromb Hemost
JT  - Seminars in thrombosis and hemostasis
JID - 0431155
RN  - 0 (Amidines)
RN  - 0 (Antifibrinolytic Agents)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Isoxazoles)
RN  - 0 (Platelet Glycoprotein GPIIb-IIIa Complex)
RN  - 7UQ7X4Y489 (Tinzaparin)
RN  - Q476FMZ72G (roxifiban)
SB  - IM
MH  - Amidines/pharmacology
MH  - Antifibrinolytic Agents/pharmacology
MH  - Blood Coagulation/drug effects
MH  - Clot Retraction
MH  - Dose-Response Relationship, Drug
MH  - *Drug Interactions
MH  - Drug Therapy, Combination
MH  - Heparin, Low-Molecular-Weight/*pharmacology
MH  - Humans
MH  - Isoxazoles/pharmacology
MH  - Kinetics
MH  - Platelet Aggregation/drug effects
MH  - Platelet Function Tests/instrumentation
MH  - Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors/metabolism
MH  - Thrombelastography/instrumentation
MH  - Tinzaparin
MH  - Vascular Diseases/drug therapy
EDAT- 2000/09/30 11:00
MHDA- 2001/03/03 10:01
CRDT- 2000/09/30 11:00
PHST- 2000/09/30 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2000/09/30 11:00 [entrez]
AID - 10.1055/s-2000-9492 [doi]
PST - ppublish
SO  - Semin Thromb Hemost. 2000;26 Suppl 1:39-46. doi: 10.1055/s-2000-9492.