New and effective treatment of experimentally induced venous thrombosis with anti-inflammatory rPSGL-Ig.
BACKGROUND
P-selectin antagonism decreases thrombosis and inflammation in animal models of venous thrombosis (VT) prophylaxis. This study defines results using a P-selectin receptor antagonist for VT treatment.


METHODS
Eight juvenile baboons underwent 6 h of iliofemoral venous stasis to produce an occlusive VT. Two days later, animals were treated for 14 days with rPSGL-Ig, 4 mg/kg (n3), LMWH (n2) or saline (n3) and treatment continued weekly (rPSGL-Ig) or daily (LMWH, saline). The animals were examined and sacrificed 14 days after treatment initiation (n4) or on day 90 (n4).


RESULTS
Percent spontaneous vein reopening revealed a significant increase (p <0.05) in the proximal iliac vein in rPSGL-Ig and LMWH animals compared to controls (62%, 70% vs 8%), without differences in inflammation. No anticoagulation, thrombocytopenia, or wound complications were found in rPSGL-Ig animals. At 90 days, recanalization with iliac vein valve competence was found in treated animals.


CONCLUSIONS
rPSGL-Ig successfully treated established VT without anticoagulation.
Myers
Daniel
D
Jobst Vascular Laboratory, Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor 48109, USA.
Wrobleski
Shirley
S
Londy
Frank
F
Fex
Beverly
B
Hawley
Angela
A
Schaub
Robert
R
Greenfield
Lazar
L
Wakefield
Thomas
T
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D018925:Chemokines / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage; D007084:Iliac Vein / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000008:administration & dosage*; D010215:Papio; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000150:complications / Q000188:drug therapy*
D000893:Anti-Inflammatory Agents; D018925:Chemokines; D006495:Heparin, Low-Molecular-Weight; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein