Venous thrombosis prophylaxis by inflammatory inhibition without anticoagulation therapy

Wakefield, Thomas W.; Strieter, Robert M.; Schaub, Robert G.; Myers, Daniel D.; Prince, Martin R.; Wrobleski, Shirley K.; Londy, Frank J.; Kadell, Amy M.; Brown, Sandra L.; Henke, Peter K.; Greenfield, Lazar J.

doi:10.1016/s0741-5214(00)90162-9

Cited by 90 publications

(78 citation statements)

References 23 publications

(31 reference statements)

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“…Tissue factor and P-selectin appear to both be necessary for thrombus formation and they appear to both be resident on microparticles derived from monocytes, as indicated by the presence of monocyte proteins on the microparticles 19,20 . In a baboon venous stasis model of thrombosis, P-selectin inhibition was found to prevent thrombus development and facilitate clot resolution 24,25 . In most of these models, it is difficult to determine whether the tissue factor-P-selectin involvement in thrombus formation is due to cellular interactions or microparticles 26 .…”

Section: A the Role Of Blood Cells Versus Vascular Contribution To Vmentioning

confidence: 99%

Basic mechanisms and pathogenesis of venous thrombosis

2009

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In 1856 Virchow proposed a triad of causes for venous thrombosis, postulating that stasis, changes in the vessel wall or changes in the blood could lead to thrombosis. We now know that abnormally high levels of some coagulation factors and defects in the natural anticoagulants contribute to thrombotic risk. Among these, factor V Leiden, which renders factor Va resistant to activated protein C, is the most prevalent with approximately 5% of the Caucasian population having this genetic alteration. These genetically controlled variants in coagulation factors work in concert with other risk factors, such as oral contraceptive use, to dramatically increase thrombotic risk. While these abnormalities in the blood coagulation proteins are associated with thrombotic disease propensity, they are less frequent contributors to thrombosis than age or cancer. Cancer increases thrombotic risk by producing tissue factor to initiate coagulation, by shedding procoagulant lipid microparticles or by impairing blood flow. Age is the strongest risk factor for thrombosis. Among possible reasons are fragility of the vessels potentially contributing to stasis, increased coagulation factor levels, impaired function of the venous valves, decreases in the efficacy of natural anticoagulants associated with the vessel wall, increased risk of immobilization and increased risk of severe infection.

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Section: A the Role Of Blood Cells Versus Vascular Contribution To Vmentioning

confidence: 99%

Basic mechanisms and pathogenesis of venous thrombosis

2009

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“…In the present study, activated partial thromboplastin, thrombin clotting time, and template bleeding time were not significantly different between saline-treated and rPSGL-Ig (4 mg/kg)-treated animals. 16 …”

Section: Selectin Antagonistsmentioning

confidence: 99%

P-Selectin–Dependent Inhibition of Thrombosis During Venous Stasis

Eppihimer¹,

Schaub²

2000

ATVB

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Abstract-Leukocyte adhesion, transendothelial migration, and stasis are important components in the pathogenesis of deep vein thrombosis. Anesthetized cats were treated with saline, a recombinant soluble form of P-selectin glycoprotein ligand-1 (rPSGL-Ig), or an E-and L-selectin antibody (EL-246) before exposure and occlusion of a jugular vein. After 2 or 6 hours of occlusion, jugular veins were perfused with buffer, fixed, and prepared for scanning electron microscopy. In cats receiving saline, 2 and 6 hours of occlusion produced moderate levels of leukocyte and platelet adhesion and endothelial cell injury. Treatment of cats with rPSGL-Ig or EL-246 had no apparent effect on the magnitude of cell adhesion and endothelial cell injury compared with no treatment. After 6 hours of occlusion, the presence of a mural thrombus in untreated veins was observed and confirmed by scanning electron microscopy. Pretreatment of cats with rPSGL-Ig completely (4.0 mg/kg) or partially (1.0 mg/kg) prevented the occurrence of thrombi in the jugular veins. The reduction in thrombosis by rPSGL-Ig treatment after 6 hours of venous stasis, in the absence of any effect on leukocyte-mediated endothelial cell injury, suggests an antithrombotic mechanism of action for this protein.

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“…Several animal studies support this hypothesis: In a cat model, a recombinant soluble form of human SELPLG appeared to protect against myocardial ischemic reperfusion injury (Hayward et al 1999); and in a porcine model, recombinant soluble SELPLG-Ig was shown to have a beneficial effect on restenosis (Bienvenu et al 2001). Animal models have also suggested a key role for SELPLG in thrombogenesis, through its implication in the binding of platelets to neutrophils (Eppihimer & Schaub, 2000;Kumar et al 1999;Wakefield et al 2000).…”

Section: Introductionmentioning

confidence: 99%

SELPLG Gene Polymorphisms in Relation to Plasma SELPLG Levels and Coronary Artery Disease

Trégouët

Barbaux

Poirier

et al. 2003

Annals of Human Genetics

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SummaryP-selectin and P-selectin glycoprotein ligand (SELPLG, selectin P ligand) constitute a receptor/ligand complex that is likely to be involved in the development of atherosclerosis and its complications. While the genetic variability of P-selectin has already been investigated in depth, that of the SELPLG gene has not yet been extensively explored. The coding and regulatory sequences of the SELPLG were screened and nine polymorphisms were identified. The identified polymorphisms were genotyped in the AtheroGene study, a case-control study of coronary artery disease (CAD). Haplotype analysis revealed that two polymorphisms of SELPLG, the M62I and the VNTR, independently influenced plasma SELPLG levels. Conversely, haplotypes of SELPLG were not associated with CAD risk.

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Venous thrombosis prophylaxis by inflammatory inhibition without anticoagulation therapy

Cited by 90 publications

References 23 publications

Basic mechanisms and pathogenesis of venous thrombosis

Basic mechanisms and pathogenesis of venous thrombosis

P-Selectin–Dependent Inhibition of Thrombosis During Venous Stasis

SELPLG Gene Polymorphisms in Relation to Plasma SELPLG Levels and Coronary Artery Disease

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