PMID- 21086021
OWN - NLM
STAT- MEDLINE
DCOM- 20110425
LR  - 20230207
IS  - 1573-742X (Electronic)
IS  - 0929-5305 (Linking)
VI  - 31
IP  - 2
DP  - 2011 Feb
TI  - Heparin-associated anti-Xa activity and platelet-derived prothrombotic and 
      proinflammatory biomarkers in moderate to high-risk patients with acute coronary 
      syndrome.
PG  - 146-53
LID - 10.1007/s11239-010-0532-y [doi]
AB  - Heparin compounds, to include fractionated and unfractionated preparations, exert 
      both antithrombotic and antiinflammatory effects through combined inhibition of 
      factor Xa and thrombin. The contribution of modulated platelet activity in vivo 
      is less clearly defined. The SYNERGY library was a prospectively designed 
      repository for candidate clinical, hemostatic, platelet, and molecular biomarkers 
      from patients participating in SYNERGY--a large-scale, randomized clinical trial 
      evaluating the comparative benefits of unfractionated heparin (UFH) and 
      enoxaparin in high-risk patients with acute coronary syndrome (ACS). Samples were 
      collected from 201 patients enrolled at 26 experienced, participating sites and 
      shipped to established core laboratories for analysis of platelet, 
      endothelium-derived, inflammatory and coagulation activity biomarkers. Tissue 
      factor pathway inhibitor (TFPI)--a vascular endothelial cell-derived factor Xa 
      regulatory protein-correlated directly with plasma anti-Xa activity (unadjusted: 
      r = 0.23, P < 0.0001; adjusted: beta = 0.10; P = 0.001), as did TFPI-fXa complexes 
      (unadjusted: r = 0.34, P < 0.0001; adjusted: beta = 0.38; P = < 0.0001). In 
      contrast, there was a direct and inverse relationship between anti-Xa activity 
      and two platelet-derived biomarkers-plasminogen activator inhibitor-1 
      (unadjusted: r = -0.18, P = 0.0012; adjusted: beta = -0.10; P = 0.021) and soluble 
      CD40 ligand (unadjusted: r = -0.11, P = 0.05; adjusted: beta = -0.13; P = 0.049). 
      All measured analyte relationships persisted after adjustment for age, creatinine 
      clearance, weight, sex, and duration of treatment. Differences in biomarkers 
      between patients receiving UFH and those randomized to enoxaparin were not 
      observed. The ability of heparin compounds to affect the prothrombotic and 
      proinflammatory states which characterize ACS may involve factor Xa-related 
      modulation of platelet activation and expression. Whether this potentially 
      beneficial effect is direct or indirect and achieved, at least in part, through 
      the release of endothelial cell-derived coagulation regulatory proteins will 
      require further investigation.
FAU - Becker, Richard C
AU  - Becker RC
AD  - Division of Cardiology Medicine, Duke University Medical Center, Duke Clinical 
      Research Institute, Durham, NC 27715, USA. richard.becker@duke.edu
FAU - Mahaffey, Kenneth W
AU  - Mahaffey KW
FAU - Yang, Hongqiu
AU  - Yang H
FAU - Marian, A J
AU  - Marian AJ
FAU - Furman, Mark I
AU  - Furman MI
FAU - Michael Lincoff, A
AU  - Michael Lincoff A
FAU - Hazen, Stanley L
AU  - Hazen SL
FAU - Petersen, John L
AU  - Petersen JL
FAU - Reist, Craig J
AU  - Reist CJ
FAU - Kleiman, Neal S
AU  - Kleiman NS
CN  - SYNERGY Investigators
LA  - eng
GR  - R01 HL088498/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Thromb Thrombolysis
JT  - Journal of thrombosis and thrombolysis
JID - 9502018
RN  - 0 (Biomarkers)
RN  - 0 (Blood Coagulation Factor Inhibitors)
RN  - 0 (Enoxaparin)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Lipoproteins)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (SERPINE1 protein, human)
RN  - 0 (lipoprotein-associated coagulation inhibitor)
RN  - 147205-72-9 (CD40 Ligand)
RN  - EC 3.4.21.6 (Factor Xa)
SB  - IM
MH  - Acute Coronary Syndrome/blood/drug therapy
MH  - Aged
MH  - Biomarkers/blood
MH  - Blood Coagulation Factor Inhibitors/*blood
MH  - Blood Platelets/metabolism
MH  - CD40 Ligand/blood
MH  - Enoxaparin/*administration & dosage
MH  - Factor Xa/analysis
MH  - *Factor Xa Inhibitors
MH  - Female
MH  - Fibrinolytic Agents/*administration & dosage
MH  - Humans
MH  - Lipoproteins/*blood
MH  - Male
MH  - Middle Aged
MH  - Plasminogen Activator Inhibitor 1/blood
MH  - Platelet Activation/drug effects
MH  - Risk Factors
EDAT- 2010/11/19 06:00
MHDA- 2011/04/26 06:00
CRDT- 2010/11/19 06:00
PHST- 2010/11/19 06:00 [entrez]
PHST- 2010/11/19 06:00 [pubmed]
PHST- 2011/04/26 06:00 [medline]
AID - 10.1007/s11239-010-0532-y [doi]
PST - ppublish
SO  - J Thromb Thrombolysis. 2011 Feb;31(2):146-53. doi: 10.1007/s11239-010-0532-y.