PREOPERATIVE THROMBOXANE A(2) PROSTAGLANDIN H-2-RECEPTOR ACTIVITY PREDICTS EARLY GRAFT THROMBOSIS/

Purpose: This study was carried out to determine whether early failure of infrainguinal bypass grafts is associated with increased expressio n of platelet thromboxane A(2)/prostaglandin H-2 (TXA(2)/PGH(2)) recep tors. A prospective correlation of preoperative platelet TXA(2)/PGH(2) receptor-mediated activity with lower extremity graft patency was sou ght. Methods: Twenty-five patients who underwent infrainguinal bypass surgery for limb salvage were studied at an inpatient academic tertiar y referral center and Department of Veterans Affairs Medical Center. O utcome measures were primary graft patency rate at 3 months, platelet TXA(2)/PGH(2) receptor activity by equilibrium binding with I-125-BOP, and aggregation to the TXA(2)-mimetic U46619. Results: Preoperative p latelet TXA(2)/PGH(2) receptor density was higher (B-max, 3100 +/- 130 0 vs 1500 +/- 1100 sites/platelet [mean +/- SD]; p = 0.004) in the fiv e patients who had graft thrombosis within 3 months. The EC50 for U466 19 was lower (26 +/- 6 nmol/L vs 57 +/- 30 nmol/L; p < 0.05) in these patients as well, confirming the functional effect of the increased re ceptor density. Early graft thrombosis was more likely in patients wit h a platelet TXA(2)/PGH(2) receptor density greater than 3000 sites/pl atelet (odds ratio, 76; 95% confidence interval, 3.9 to 1500) or an EC 50 for U46619 less than 30 nmol/L (odds ratio, 16; 95% confidence inte rval, 1.4 to 180). Conclusions: Elevated platelet TXA(2)/PGH(2) recept or levels and enhanced sensitivity of platelet aggregation to TXA(2) p redict early arterial graft thrombosis. Specific TXA(2)/PGH(2) recepto r antagonism may prevent one of the mechanisms that contributes to ear ly graft occlusion.