Preoperative thromboxane A2/prostaglandin H2 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 expression of platelet thromboxane A(2)/prostaglandin H-2 (TXA(2)/PGH(2)) receptors. A prospective correlation of preoperative platelet TXA(2)/PGH(2) receptor-mediated activity with lower extremity graft patency was sought. Methods: Twenty-five patients who underwent infrainguinal bypass surgery for limb salvage were studied at an inpatient academic tertiary referral center and Department of Veterans Affairs Medical Center. Outcome 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 platelet TXA(2)/PGH(2) receptor density was higher (B-max, 3100 +/- 1300 vs 1500 +/- 1100 sites/platelet [mean +/- SD]; p = 0.004) in the five patients who had graft thrombosis within 3 months. The EC50 for U46619 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 receptor density. Early graft thrombosis was more likely in patients with a platelet TXA(2)/PGH(2) receptor density greater than 3000 sites/platelet (odds ratio, 76; 95% confidence interval, 3.9 to 1500) or an EC50 for U46619 less than 30 nmol/L (odds ratio, 16; 95% confidence interval, 1.4 to 180). Conclusions: Elevated platelet TXA(2)/PGH(2) receptor levels and enhanced sensitivity of platelet aggregation to TXA(2) predict early arterial graft thrombosis. Specific TXA(2)/PGH(2) receptor antagonism may prevent one of the mechanisms that contributes to early graft occlusion.