Platelet sequestration and activation during GalTKO.hCD46 pig lung perfusion by human blood is primarily mediated by GPIb, GPIIb/IIIa, and von Willebrand Factor

Background Here, we ask whether platelet GPI b and GPII b/ III a receptors modulate platelet sequestration and activation during Gal TKO . hCD 46 pig lung xenograft perfusion. Methods Gal TKO . hCD 46 transgenic pig lungs were perfused with heparinized fresh human blood. Results from perfusions in which α GPI b Fab (6B4, 10 mg/l blood, n = 6), α GPII b/ III a Fab (ReoPro, 3.5 mg/l blood, n = 6), or both drugs (n = 4) were administered to the perfusate were compared to two additional groups in which the donor pig received 1‐desamino‐8‐ d ‐arginine vasopressin ( DDAVP ), 3 μ g/kg (to pre‐deplete von Willebrand Factor ( pVWF ), the main GPI b ligand), with or without α GPI b (n = 6 each). Results Platelet sequestration was significantly delayed in α GPI b, α GPI b+ DDAVP , and α GPI b+α GPII b/ III a groups. Median lung “survival” was significantly longer (>240 vs. 162 min reference, p = 0.016), and platelet activation (as CD 62P and β TG ) were significantly inhibited, when pigs were pre‐treated with DDAVP , with or without α GPI b Fab treatment. Pulmonary vascular resistance rise was not significantly attenuated in any group, and was associated with residual thromboxane and histamine elaboration. Conclusions The GPI b‐ VWF and GPII b/ III a axes play important roles in platelet sequestration and coagulation cascade activation during Gal TKO . hCD 46 lung xenograft injury. GPI b blockade significantly reduces platelet activation and delays platelet sequestration in this xenolung rejection model, an effect amplified by adding α GPII b/ III a blockade or depletion of VWF from pig lung.