Venous thrombosis prophylaxis by inflammatory inhibition without anticoagulation therapy

Objective: This study was performed to determine the effectiveness of recom binant P-selectin glycoprotein ligand Ig (rPSGL-Ig) pretreatment to decreas e thrombosis and inflammation in experimental venous thrombosis. rPSGL-Ig, a unique mucin-like glycoprotein, has a high affinity for P-selectin. Methods: Twelve juvenile baboons underwent inferior vena cava (IVC) thrombo sis with temporary 6-hour IVC balloon occlusion. Before balloon placement, the animals received rPSGL-Ig (4 mg/kg; n = 8) or saline solution for contr ol (n = 4). The animals underwent evaluation with duplex ultrasound scan im aging, magnetic resonance venography (MRV), phlebography, coagulation profi le, and tissue analysis at death for cytokines and vein wall leukocyte morp hometrics. With the MRV results, thrombus development, thrombus resolution, and inflammation (gadolinium; square millimeters of enhancement) were asse ssed. Results: Each animal provided vivo time points for evaluation (days 2 and 6 after balloon occlusion). A significant decrease in IVC thrombosis between balloons was found in the rPSGL-Ig animals (1 of 16) versus the control an imals (5 of 8; P < .01). The MRV results showed significantly less enhancem ent in the rPSGL-Ig animals at days 2 and 6 (P < .05). Spontaneous thrombus resolution (including balloon sites) was significantly greater from day 2 to day 6 in the rPSGL-Ig animals versus the control animals (23% vs 2%; P < .001), without pulmonary embolism. Lower interleukin-8, platelet factor n: and monocyte chemotactic protein-1 levels were found in rPSGL-Ig vein wall s without significant differences in vein wall leukocyte morphometrics. The re were significantly lower D-dimer levels in the rPSGL-Ig-treated animals (P < .05), but there were no differences in measurements of coagulation. Ad equate circulating rPSGL-Ig levels were documented. Conclusion: Pretreatment with rPSGL-Ig results in: (1) a significant inhibi tion of thrombosis and vein wall inflammation; (2) a decrease in vein wall cytokine expression; and (3) a promotion of thrombus resolution. Inflammato ry inhibition by rPSGL-Ig without anticoagulation therapy provides effectiv e venous thrombosis prophylaxis in experimental venous thrombosis.