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    Comparative effects of unfractionated heparin and low molecular weight heparin on vascular endothelial cell tissue factor pathway inhibitor release: a model for assessing intrinsic thromboresistance

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    Authors
    Li, YouFu
    Rodriguez, Miguel
    Spencer, Frederick A.
    Becker, Richard C.
    UMass Chan Affiliations
    School of Medicine
    Cardiovascular Thrombosis Research Center, Laboratory for Vascular Biology Research
    Document Type
    Journal Article
    Publication Date
    2002-10-01
    Keywords
    Cells, Cultured
    Endothelial Cells
    Factor Xa Inhibitors
    Heparin, Low-Molecular-Weight
    Humans
    Lipoproteins
    Thrombosis
    Vascular Resistance
    Cardiology
    Cardiovascular Diseases
    Cell Biology
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    Link to Full Text
    http://dx.doi.org/10.1023/A:1023280811804
    Abstract
    OBJECTIVES: The purpose of our study was to characterize tissue factor pathway inhibitor (TFPI) release from human vascular endothelial cells following daily exposure to varying concentrations of unfractionated heparin (UFH) and low molecular weight heparin (LMWH). BACKGROUND: A "rebound" increase in ischemic/thrombotic events, including myocardial infarction and cardiovascular death, has been observed after the abrupt cessation of UFH. In a single center pilot study of patients with acute coronary syndromes (ACS) we reported that thrombin generation was evident within one (1) hour of UFH cessation, increased progressively over the subsequent 24 hours, correlated directly with factor VII activity and inversely with TFPI (concentration and activity). METHODS: Human umbilical vein endothelial cells were grown to confluence and incubated with varying concentrations of UFH or dalteparin, a low molecular weight haparin, for up to 144 hours. Daily samples of the cells supernatant were obtained and assayed for TFPI. Cellular reserve and responsiveness to recombinant endothelial cell growth factor (rEGF) stimulation were determined at 168 hours. RESULTS: In low concentrations (0.5 U/mL) UFH caused a progressive rise in TFPI concentration with a peak level of 6.36 +/- 0.5 ng/10(5) cells at 24 hours. By 72 hours of daily exposure, the levels declined to below control values and TFPI release following rEGF stimulation was reduced by approximately 60% compared to control (1.93 +/- 0.42 vs 4.3 +/- 0.78 ng/10(5) cells; p = 0.001). Initial endothelial cell release and rate of decline were more robust with high concentrations of UFH (5.0 U/ml). TFPI levels were above control values at each sampling time point up to 120 hours and cellular responsiveness to stimulation was preserved with dalteparin (compared to UFH) (p < 0.001). CONCLUSIONS: Thrombin generation and clinical events that occur during treatment with UFH and following its abrupt cessation may represent an acquired state of transiently impaired thromboresistance to the tissue factor-VIIa complex. The differing effects of UFH and LMWH on vascular endothelial cell TFPI synthesis, release and reserve with prolonged administration require further investigation.
    Source
    J Thromb Thrombolysis. 2002 Oct;14(2):123-9. Doi: 10.1023/A:1023280811804 Link to article on publisher's site
    DOI
    10.1023/A:1023280811804
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/49233
    PubMed ID
    12714831
    Notes

    Medical student Miguel Rodriguez participated in this study as part of the Senior Scholars research program at the University of Massachusetts Medical School.

    The author's last name is misspelled in the journal article and in PubMed.

    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1023/A:1023280811804
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    T.H. Chan School of Medicine Student Publications
    Senior Scholars Program

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