ANTI-P-SELECTIN ANTIBODY DECREASES INFLAMMATION AND THROMBUS FORMATION IN VENOUS THROMBOSIS

Purpose: Venous thrombosis and inflammation are interrelated. P-select in contributes to activation of leukocyte-mediated inflammation. There fore, we hypothesized that the neutralization of P-selectin mould decr ease vein wall inflammation and thrombosis. Methods: Twelve baboons un derwent infrarenal inferior vena caval balloon occlusion to induce thr ombosis. Two groups of four baboons received neutralizing intravenous anti-P-selectin antibody (PSab) GA6 or CY1748 before occlusion and at days 2 and 4. Four baboons received saline control injections. One bab oon per group was killed at days 2, 6, and 13, and at 2 months. Analys is included phlebography, ultrasound, gadolinium (Gd)-enhanced magneti c resonance venography (reflecting vein wall inflammation), and histol ogic, morphometric, and protein evaluation of the vein wall. Thrombus presence or absence was assessed. Results: By day 2 in PSab baboons, v ein wall Gd enhancement was decreased in the mid-inferior vena cava an d the right iliac vein (P < 0.05; GA6 vs control baboons), normalizing by 2 months. The mid-inferior vena cava revealed fewer neutrophils an d total leukocytes in PSab baboons; however, for GA6 in the right ilia c vein these decreases were not present despite the absence of Gd enha ncement; they were decreased with CY1748. PSab baboons demonstrated si gnificantly less thrombus than control baboons (p < 0.01, GA6 and CY17 48 vs control baboons). Conclusions: Anti-P-selectin antibody decrease s vein wall inflammation and thrombus formation. Inhibition of P-selec tin may be useful in venous thrombosis prophylaxis.