PMID- 8994426
OWN - NLM
STAT- MEDLINE
DCOM- 19970204
LR  - 20190623
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 95
IP  - 1
DP  - 1997 Jan 7
TI  - Effect of nonspecific binding to plasma proteins on the antithrombin activities 
      of unfractionated heparin, low-molecular-weight heparin, and dermatan sulfate.
PG  - 118-24
AB  - BACKGROUND: Nonspecific binding to plasma proteins decreases the anti-factor Xa 
      (anti-Xa) activity of unfractionated heparin (UFH) but not that of 
      low-molecular-weight heparin (LMWH). However, plasma proteins could influence the 
      anti-thrombin (anti-IIa) activity of LMWH. To explore this possibility, we 
      compared the effects of plasma proteins on the anti-IIa activities of UFH and 
      LMWH. We also examined their effects on the anti-IIa activity of dermatan sulfate 
      (DS) because, like UFH, DS binds to plasma proteins. METHODS AND RESULTS: There 
      was almost complete recovery of anti-IIa activity when UFH, LMWH, or DS was added 
      to plasma from each of 20 healthy volunteers. The addition of a chemically 
      modified heparin with low affinity for antithrombin III to plasma containing UFH 
      increased the anti-IIa activity in a concentration-dependent fashion by 
      displacing UFH from plasma proteins. In contrast, addition of low-affinity 
      heparin had no effect on the anti-IIa activity of LMWH. LMWH does not bind to 
      plasma proteins because the bulk of the LMWH chains are < 6000 D, and only 
      heparin fractions > 6000 D bind nonspecifically to plasma proteins. As further 
      evidence that plasma proteins do not influence the anti-IIa activity of LMWH, the 
      rate of thrombin inhibition in plasma in the presence of LMWH is virtually 
      identical to that in buffer containing physiological amounts of the major 
      antithrombins. In contrast, with UFH or DS, the rate of thrombin inhibition is 
      twofold slower in plasma than in buffer. CONCLUSIONS: Nonspecific binding of UFH 
      to plasma proteins most likely contributes to the variable anti-IIa response to 
      UFH in patients with thromboembolic disease. Although DS also binds to plasma 
      proteins, the clinical significance of this finding is unclear. In contrast, 
      because LMWH does not bind to plasma proteins, the anti-IIa activity of LMWH 
      should be just as predictable as its anti-Xa activity.
FAU - Cosmi, B
AU  - Cosmi B
AD  - McMaster University, Hamilton, Ontario, Canada.
FAU - Fredenburgh, J C
AU  - Fredenburgh JC
FAU - Rischke, J
AU  - Rischke J
FAU - Hirsh, J
AU  - Hirsh J
FAU - Young, E
AU  - Young E
FAU - Weitz, J I
AU  - Weitz JI
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Anticoagulants)
RN  - 0 (Blood Proteins)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 24967-94-0 (Dermatan Sulfate)
RN  - 81604-65-1 (Heparin Cofactor II)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Anticoagulants/metabolism/*pharmacology
MH  - Blood Proteins/*metabolism
MH  - Dermatan Sulfate/metabolism/*pharmacology
MH  - Drug Synergism
MH  - Heparin/metabolism/*pharmacology
MH  - Heparin Cofactor II
MH  - Heparin, Low-Molecular-Weight/metabolism/*pharmacology
MH  - Protein Binding
MH  - Thrombin/*antagonists & inhibitors
EDAT- 1997/01/07 00:00
MHDA- 1997/01/07 00:01
CRDT- 1997/01/07 00:00
PHST- 1997/01/07 00:00 [pubmed]
PHST- 1997/01/07 00:01 [medline]
PHST- 1997/01/07 00:00 [entrez]
AID - 10.1161/01.cir.95.1.118 [doi]
PST - ppublish
SO  - Circulation. 1997 Jan 7;95(1):118-24. doi: 10.1161/01.cir.95.1.118.