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-Icy) or daily (LMWH, saline). The animals were examined and sacrificed I-l 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: rPSGLIg successfully treated established VT without anticoagulation.