PMID- 10691099
OWN - NLM
STAT- MEDLINE
DCOM- 20000323
LR  - 20131121
IS  - 0957-5235 (Print)
IS  - 0957-5235 (Linking)
VI  - 11
IP  - 1
DP  - 2000 Jan
TI  - Pharmacologic modulation of thrombin generation associated with human clots by 
      human purified antithrombin alone or in the presence of low molecular weight 
      heparin or unfractionated heparin.
PG  - 51-9
AB  - Procoagulant activities associated with human clots may contribute to thrombus 
      extension. We investigate the inhibition of clot-associated factor Xa and 
      thrombin activities by purified human antithrombin either alone or as combination 
      with a low molecular weight heparin (enoxaparin) as compared with unfractionated 
      heparin (UFH). The standard clots were prepared by recalcification of frozen 
      platelet-poor human plasma. Clot-associated thrombin was measured on the clot 
      after clot incubation in recalcified buffer or recalcified prothrombin solution. 
      The enzymatic reaction was measured using a specific substrate for thrombin (CBS 
      3447). The thrombin concentration was determined both on the clots and in the 
      reaction mixtures. In parallel, prothrombin fragment 1.2 and 
      thrombin-antithrombin complexes (TAT) were measured using enzyme-linked 
      immunosorbent assay methods. We demonstrated that in the presence of purified 
      human prothrombin and antithrombin (AT), a partial inhibition of clot associated 
      thrombin activity correlated with an increase of TAT complexes. However, 
      antithrombin was unable to inhibit thrombin generation induced by the 
      clot-associated factor Xa. Enoxaparin (low molecular weight heparin) and UFH did 
      not enhance clot-bound thrombin inhibition induced by AT. We conclude that 
      clot-bound thrombin is accessible to human antithrombin alone. AT is also able to 
      inhibit thrombin generated by factor Xa-associated clot. However, neither a low 
      molecular weight heparin or UFH enhanced the effect of AT alone.
FAU - Meddahi, S
AU  - Meddahi S
AD  - Laboratoire de Thrombose Experimentale, Institut des Cordeliers, Universite 
      Pierre et Marie Curie, Paris VI, France.
FAU - Bara, L
AU  - Bara L
FAU - Fessi, H
AU  - Fessi H
FAU - Samama, M M
AU  - Samama MM
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Blood Coagul Fibrinolysis
JT  - Blood coagulation & fibrinolysis : an international journal in haemostasis and 
      thrombosis
JID - 9102551
RN  - 0 (Antithrombins)
RN  - 0 (Enoxaparin)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Peptide Fragments)
RN  - 0 (Protein Precursors)
RN  - 0 (antithrombin III-protease complex)
RN  - 72270-84-9 (prothrombin fragment 1)
RN  - 78768-79-3 (prothrombin fragment 2)
RN  - 9000-94-6 (Antithrombin III)
RN  - 9001-26-7 (Prothrombin)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.- (Peptide Hydrolases)
RN  - EC 3.4.21.5 (Thrombin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Antithrombin III/drug effects/pharmacokinetics
MH  - Antithrombins/*pharmacology
MH  - *Blood Coagulation/physiology
MH  - Calcium/pharmacology
MH  - Enoxaparin/pharmacology
MH  - Heparin/*pharmacology
MH  - Heparin, Low-Molecular-Weight/pharmacology
MH  - Humans
MH  - Peptide Fragments/drug effects/pharmacokinetics
MH  - Peptide Hydrolases/drug effects/pharmacokinetics
MH  - Protein Binding
MH  - Protein Precursors/drug effects/pharmacokinetics
MH  - Prothrombin/drug effects/pharmacokinetics/pharmacology
MH  - Thrombin/*biosynthesis/*drug effects/pharmacokinetics
EDAT- 2000/02/26 09:00
MHDA- 2000/03/25 09:00
CRDT- 2000/02/26 09:00
PHST- 2000/02/26 09:00 [pubmed]
PHST- 2000/03/25 09:00 [medline]
PHST- 2000/02/26 09:00 [entrez]
PST - ppublish
SO  - Blood Coagul Fibrinolysis. 2000 Jan;11(1):51-9.