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 A₂/prostaglandin H₂ (TXA₂/PGH₂) receptors. A prospective correlation of preoperative platelet TXA₂/PGH₂ 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 TXA₂/PGH₂ receptor activity by equilibrium binding with ₁₂₅I-BOP, and aggregation to the TXA₂-mimetic U46619. Results: Preoperative platelet TXA₂/PGH₂ 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 TXA₂/PGH₂ 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 TXA₂/PGH₂ receptor levels and enhanced sensitivity of platelet aggregation to TXA₂ predict early arterial graft thrombosis. Specific TXA₂/PGH₂ receptor antagonism may prevent one of the mechanisms that contributes to early graft occlusion. (J Vasc Surg 1998;27:317-28.)