P-selectin antagonism has been shown to decrease thrombogenesis and inflammation in animal models of deep venous thrombosis (DVT).
To determine the effectiveness of P-selectin inhibitors versus saline and enoxaparin in venous resolution in nonhuman primate models of venous thrombosis.
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.
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 prolongation in TCT with P-selectin /PSGL-1 inhibitors over enoxaparin (p<0.0001).
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 increasing coagulation times.