INCREASED THROMBOXANE BIOSYNTHESIS IN ESSENTIAL THROMBOCYTHEMIA

In order to investigate the in vivo thromboxane (TX) biosynthesis in e ssential thrombocythemia (ET), we measured the urinary excretion of th e major enzymatic metabolites of TXB(2), 11-dehydro-TXB(2) and 2,3-din or-TXB(2) in 40 ET patients as well as in 26 gender- and age-matched c ontrols. Urinary 11-dehydro-TXB(2), was significantly higher (p < 0.00 1) in thrombocythemic patients (4,063 +/- 3,408 pg/mg creatinine; mean +/- SD) than in controls (504 +/- 267 pg/mg creatinine), with 34 pati ents (85%) having 11-dehydro-TXB(2) >2 SD above the control mean: Pati ents with platelet number <1,000 x 10(9)/1 (n = 25) had significantly higher (p < 0.05) 11-dehydro-TXB(2) excretion than patients with highe r platelet count (4,765 +/- 3,870 pg/mg creatinine, n = 25, versus 2,2 79 +/- 1,874 pg/mg creatinine, n = 15). Average excretion values of pa tients aging >55 was significantly higher than in the : younger group (4,784 +/- 3,948 pg/mg creatinine, n = 24, versus 2,405 +/- 1,885 pg/m g creatinine, n = 16, p < 0.05). Low-dose aspirin (50 mg/d for 7 days) largely suppressed 11-dehydro-TXB(2) excretion in 7 thrombocythemic p atients, thus suggesting that platelets were the main source of enhanc ed TXA(2) biosynthesis. The platelet count-corrected 11-dehydro-TXB(2) excretion was positively correlated with age (r = 0.325, n = 40, p < 0.05) and inversely correlated with platelet count (r = -0.381, n = 40 , p < 0.05). In addition 11 out of 13 (85%) patients having increased count-corrected 11-dehydro-TXB(2) excretion, belonged to the subgroup with age >55 and platelet count <1,000 X 10(9)/1. we conclude that in essential thrombocythemia: 1) enhanced 11-dehydro-TXB(2) excretion lar gely reflects platelet activation in vivo; 2) age as well as platelet count appear to influence the determinants of platelet activation in t his setting, and can help in assessing the thrombotic risk and therape utic strategy in individual patients.