P-selectin/ PSGL-1 Inhibitors versus enoxaparin in the resolution of venous thrombosis: A meta-analysis

Eduardo Ramacciotti, Daniel D. Myers, Shirley K. Wrobleski, K. Barry Deatrick, Frank J. Londy, John E. Rectenwald, Peter K. Henke, Robert G. Schaub, Thomas W. Wakefield

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: P-selectin antagonism has been shown to decrease thrombogenesis and inflammation in animal models of deep venous thrombosis (DVT). Objective: To determine the effectiveness of P-selectin inhibitors versus saline and enoxaparin in venous thrombus resolution in nonhuman primate models of venous thrombosis. Methods: Studies reporting vein re-opening, inflammation expressed as Gadolinium enhancement and coagulation parameters were searched in the literature and pooled into a meta-analysis using an inverse variance with random effects. Results: Five studies were identified comparing P-selectin/ PSGL-1 inhibitors versus saline or enoxaparin regarding venous thrombosis resolution. Vein re-opening was significantly higher on P-selectin/ PSGL-1 compounds, when compared to saline (Inverse Variance [IV] 95% CI; 44.37 [17.77_70.96], p = 0.001, I2 = 97%) and similar to enoxaparin (IV 95% CI; 5.03 [-8.88_18.95], p = 0.48, I2 = 41%). Inflammation, reflected as Gadolinium enhancement at magnetic resonance venography (MRV), was significantly decreased in the P-selectin treated group when compared to saline (IV 95% CI; -17.84 [-14.98 _ -8.30], p < 0.00001, I2 = 80%). No significant differences on vein wall inflammation were observed between P-selectin/ PSGL-1 inhibitors and enoxaparin treated animals (IV95% CI; -3.59 [-10.67_3.48], p = 0.32, I2 = 66%). In addition, there was no differences in the coagulation parameters (aPTT, TCT, BT, D-Dimer, fibrinogen, platelets) between P-selectin/ PSGL-1 inhibitors and enoxaparin (IV 95% CI; -1.12[-2.36_0.11], p = 0.07, I2 = 92%), although there was a trend showing less of a prolongation in TCT with P-selectin/PSGL-1 inhibitors compared to enoxaparin (p < 0.0001). Conclusion: P-selectin antagonism successfully paralleled the low-molecular-weight-heparin enoxaparin, for the treatment of DVT in nonhuman primate models, by decreasing both thrombus burden and inflammation without causing any bleeding complications and without increasing coagulation times.

Original languageEnglish (US)
JournalThrombosis Research
Volume125
Issue number4
DOIs
StatePublished - Apr 1 2010

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Enoxaparin
P-Selectin
Venous Thrombosis
Meta-Analysis
Inflammation
Veins
Gadolinium
Primates
Thrombosis
Phlebography
Low Molecular Weight Heparin
Fibrinogen
Magnetic Resonance Spectroscopy
Blood Platelets
Animal Models
Hemorrhage

Keywords

  • animal model
  • enoxaparin
  • inflammation
  • meta-analysis
  • P-selectin
  • venous thrombosis

ASJC Scopus subject areas

  • Hematology

Cite this

Ramacciotti, E., Myers, D. D., Wrobleski, S. K., Deatrick, K. B., Londy, F. J., Rectenwald, J. E., ... Wakefield, T. W. (2010). P-selectin/ PSGL-1 Inhibitors versus enoxaparin in the resolution of venous thrombosis: A meta-analysis. Thrombosis Research, 125(4). https://doi.org/10.1016/j.thromres.2009.10.022

P-selectin/ PSGL-1 Inhibitors versus enoxaparin in the resolution of venous thrombosis : A meta-analysis. / Ramacciotti, Eduardo; Myers, Daniel D.; Wrobleski, Shirley K.; Deatrick, K. Barry; Londy, Frank J.; Rectenwald, John E.; Henke, Peter K.; Schaub, Robert G.; Wakefield, Thomas W.

In: Thrombosis Research, Vol. 125, No. 4, 01.04.2010.

Research output: Contribution to journalArticle

Ramacciotti, E, Myers, DD, Wrobleski, SK, Deatrick, KB, Londy, FJ, Rectenwald, JE, Henke, PK, Schaub, RG & Wakefield, TW 2010, 'P-selectin/ PSGL-1 Inhibitors versus enoxaparin in the resolution of venous thrombosis: A meta-analysis', Thrombosis Research, vol. 125, no. 4. https://doi.org/10.1016/j.thromres.2009.10.022
Ramacciotti, Eduardo ; Myers, Daniel D. ; Wrobleski, Shirley K. ; Deatrick, K. Barry ; Londy, Frank J. ; Rectenwald, John E. ; Henke, Peter K. ; Schaub, Robert G. ; Wakefield, Thomas W. / P-selectin/ PSGL-1 Inhibitors versus enoxaparin in the resolution of venous thrombosis : A meta-analysis. In: Thrombosis Research. 2010 ; Vol. 125, No. 4.
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abstract = "Background: P-selectin antagonism has been shown to decrease thrombogenesis and inflammation in animal models of deep venous thrombosis (DVT). Objective: To determine the effectiveness of P-selectin inhibitors versus saline and enoxaparin in venous thrombus resolution in nonhuman primate models of venous thrombosis. Methods: Studies reporting vein re-opening, inflammation expressed as Gadolinium enhancement and coagulation parameters were searched in the literature and pooled into a meta-analysis using an inverse variance with random effects. Results: Five studies were identified comparing P-selectin/ PSGL-1 inhibitors versus saline or enoxaparin regarding venous thrombosis resolution. Vein re-opening was significantly higher on P-selectin/ PSGL-1 compounds, when compared to saline (Inverse Variance [IV] 95{\%} CI; 44.37 [17.77_70.96], p = 0.001, I2 = 97{\%}) and similar to enoxaparin (IV 95{\%} CI; 5.03 [-8.88_18.95], p = 0.48, I2 = 41{\%}). Inflammation, reflected as Gadolinium enhancement at magnetic resonance venography (MRV), was significantly decreased in the P-selectin treated group when compared to saline (IV 95{\%} CI; -17.84 [-14.98 _ -8.30], p < 0.00001, I2 = 80{\%}). No significant differences on vein wall inflammation were observed between P-selectin/ PSGL-1 inhibitors and enoxaparin treated animals (IV95{\%} CI; -3.59 [-10.67_3.48], p = 0.32, I2 = 66{\%}). In addition, there was no differences in the coagulation parameters (aPTT, TCT, BT, D-Dimer, fibrinogen, platelets) between P-selectin/ PSGL-1 inhibitors and enoxaparin (IV 95{\%} CI; -1.12[-2.36_0.11], p = 0.07, I2 = 92{\%}), although there was a trend showing less of a prolongation in TCT with P-selectin/PSGL-1 inhibitors compared to enoxaparin (p < 0.0001). Conclusion: P-selectin antagonism successfully paralleled the low-molecular-weight-heparin enoxaparin, for the treatment of DVT in nonhuman primate models, by decreasing both thrombus burden and inflammation without causing any bleeding complications and without increasing coagulation times.",
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T2 - A meta-analysis

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AU - Wrobleski, Shirley K.

AU - Deatrick, K. Barry

AU - Londy, Frank J.

AU - Rectenwald, John E.

AU - Henke, Peter K.

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AU - Wakefield, Thomas W.

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N2 - Background: P-selectin antagonism has been shown to decrease thrombogenesis and inflammation in animal models of deep venous thrombosis (DVT). Objective: To determine the effectiveness of P-selectin inhibitors versus saline and enoxaparin in venous thrombus resolution in nonhuman primate models of venous thrombosis. Methods: Studies reporting vein re-opening, inflammation expressed as Gadolinium enhancement and coagulation parameters were searched in the literature and pooled into a meta-analysis using an inverse variance with random effects. Results: Five studies were identified comparing P-selectin/ PSGL-1 inhibitors versus saline or enoxaparin regarding venous thrombosis resolution. Vein re-opening was significantly higher on P-selectin/ PSGL-1 compounds, when compared to saline (Inverse Variance [IV] 95% CI; 44.37 [17.77_70.96], p = 0.001, I2 = 97%) and similar to enoxaparin (IV 95% CI; 5.03 [-8.88_18.95], p = 0.48, I2 = 41%). Inflammation, reflected as Gadolinium enhancement at magnetic resonance venography (MRV), was significantly decreased in the P-selectin treated group when compared to saline (IV 95% CI; -17.84 [-14.98 _ -8.30], p < 0.00001, I2 = 80%). No significant differences on vein wall inflammation were observed between P-selectin/ PSGL-1 inhibitors and enoxaparin treated animals (IV95% CI; -3.59 [-10.67_3.48], p = 0.32, I2 = 66%). In addition, there was no differences in the coagulation parameters (aPTT, TCT, BT, D-Dimer, fibrinogen, platelets) between P-selectin/ PSGL-1 inhibitors and enoxaparin (IV 95% CI; -1.12[-2.36_0.11], p = 0.07, I2 = 92%), although there was a trend showing less of a prolongation in TCT with P-selectin/PSGL-1 inhibitors compared to enoxaparin (p < 0.0001). Conclusion: P-selectin antagonism successfully paralleled the low-molecular-weight-heparin enoxaparin, for the treatment of DVT in nonhuman primate models, by decreasing both thrombus burden and inflammation without causing any bleeding complications and without increasing coagulation times.

AB - Background: P-selectin antagonism has been shown to decrease thrombogenesis and inflammation in animal models of deep venous thrombosis (DVT). Objective: To determine the effectiveness of P-selectin inhibitors versus saline and enoxaparin in venous thrombus resolution in nonhuman primate models of venous thrombosis. Methods: Studies reporting vein re-opening, inflammation expressed as Gadolinium enhancement and coagulation parameters were searched in the literature and pooled into a meta-analysis using an inverse variance with random effects. Results: Five studies were identified comparing P-selectin/ PSGL-1 inhibitors versus saline or enoxaparin regarding venous thrombosis resolution. Vein re-opening was significantly higher on P-selectin/ PSGL-1 compounds, when compared to saline (Inverse Variance [IV] 95% CI; 44.37 [17.77_70.96], p = 0.001, I2 = 97%) and similar to enoxaparin (IV 95% CI; 5.03 [-8.88_18.95], p = 0.48, I2 = 41%). Inflammation, reflected as Gadolinium enhancement at magnetic resonance venography (MRV), was significantly decreased in the P-selectin treated group when compared to saline (IV 95% CI; -17.84 [-14.98 _ -8.30], p < 0.00001, I2 = 80%). No significant differences on vein wall inflammation were observed between P-selectin/ PSGL-1 inhibitors and enoxaparin treated animals (IV95% CI; -3.59 [-10.67_3.48], p = 0.32, I2 = 66%). In addition, there was no differences in the coagulation parameters (aPTT, TCT, BT, D-Dimer, fibrinogen, platelets) between P-selectin/ PSGL-1 inhibitors and enoxaparin (IV 95% CI; -1.12[-2.36_0.11], p = 0.07, I2 = 92%), although there was a trend showing less of a prolongation in TCT with P-selectin/PSGL-1 inhibitors compared to enoxaparin (p < 0.0001). Conclusion: P-selectin antagonism successfully paralleled the low-molecular-weight-heparin enoxaparin, for the treatment of DVT in nonhuman primate models, by decreasing both thrombus burden and inflammation without causing any bleeding complications and without increasing coagulation times.

KW - animal model

KW - enoxaparin

KW - inflammation

KW - meta-analysis

KW - P-selectin

KW - venous thrombosis

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