P-selectin/ PSGL-1 inhibitors versus enoxaparin in the resolution of venous thrombosis: a meta-analysis.
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, I(2)=97%) and similar to enoxaparin (IV 95% CI; 5.03 [-8.88-18.95], p=0.48, I(2)=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, I(2)=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, I(2)=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, I(2)=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).


CONCLUSIONS
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.
Ramacciotti
Eduardo
E
Jobst Vascular Surgery Research Laboratory, Section of Vascular Surgery, Cardiovascular Center, University of Michigan, Ann Arbor, Michigan 48109, USA. erama@med.umich.edu
Myers
Daniel D
DD
Wrobleski
Shirley K
SK
Deatrick
K Barry
KB
Londy
Frank J
FJ
Rectenwald
John E
JE
Henke
Peter K
PK
Schaub
Robert G
RG
Wakefield
Thomas W
TW
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects / Q000276:immunology; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D017984:Enoxaparin / Q000276:immunology / Q000494:pharmacology*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005682:Gadolinium / Q000494:pharmacology; D006470:Hemorrhage / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D006495:Heparin, Low-Molecular-Weight / Q000276:immunology / Q000494:pharmacology; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D018810:Magnetic Resonance Angiography / Q000009:adverse effects; D019007:P-Selectin / Q000187:drug effects* / Q000276:immunology* / Q000494:pharmacology; D010314:Partial Thromboplastin Time; D010690:Phlebography / Q000009:adverse effects; D051381:Rats; D019087:Selectins / Q000276:immunology / Q000494:pharmacology; D013918:Thrombin Time; D013927:Thrombosis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D014680:Veins / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology / Q000473:pathology*
D017984:Enoxaparin; D005338:Fibrin Fibrinogen Degradation Products; D006495:Heparin, Low-Molecular-Weight; D019007:P-Selectin; D019087:Selectins; C036309:fibrin fragment D; D005682:Gadolinium