Am. J. Respir. Crit. Care Med., Volume 156, Number 6, December 1997, 1794-1799

Enhanced Thromboxane Biosynthesis in Patients with Chronic Obstructive Pulmonary Disease

GIOVANNI DAVÌ, STEFANIA BASILI, MARIO VIERI, FRANCESCO CIPOLLONE, STELLA SANTARONE, CESARE ALESSANDRI, PIERPAOLO GAZZANIGA, CORRADO CORDOVA, FRANCESCO VIOLI, and the Chronic Obstructive Bronchitis and Haemostasis Study Group

Istituto di Terapia Medica, Istituto di I Clinica Medica, Dipartimento di Medicina Sperimentale e Patologia, Istituto di Terapia Medica Sistematica, Università di Roma "La Sapienza", Rome; and Istituto Fisiopatologia Medica, Università di Chieti "G. D'Annunzio," Chieti, Italy

Thrombotic complications of pulmonary circulation occur in patients with chronic obstructive pulmonary disease (COPD). In the present study, we sought to evaluate in vivo platelet activation through the measurement of 11-dehydro-thromboxane (Tx) B₂, TxA₂ major metabolite in the urine, in 29 patients with COPD, compared with 29 sex- and age-matched healthy subjects. The urinary excretion of 11-dehydro-TxB₂ was significantly higher in patients with COPD than in control subjects: median (range), 753 (277-4,409) and 275 (129-612) pg/mg creatinine, respectively; p < 0.0001). Moreover, 11-dehydro-TxB₂ excretion was inversely related with arterial oxygen tension (rho = 0.46; p = 0.0145). In five of the 29 patients a short-term therapeutic course with oxygen supplementation induced a significant decrease of urinary 11-dehydro-TxB₂ excretion: median range, 941 (452-2,640) to 445 (166-1,560) pg/mg creatinine. Moreover, selective inhibition of platelet cyclooxygenase activity by low-dose aspirin was associated with more than 90% inhibition of thromboxane metabolite excretion, demonstrating its being of platelet origin. Plasma levels of prothrombin fragment F1+2 were higher in patients than in control subjects (2.6 ± 1.5 versus 0.9 ± 0.4 nM, p = 0.0001). No relation between 11-dehydro-TxB₂ excretion and plasma F1+2 levels was found. We conclude that platelet TxA₂ biosynthesis is enhanced in patients with COPD and may be influenced by arterial oxygen tension changes. Davì G, Basili S, Vieri M, Cipollone F, Santarone S, Alessandri C, Gazzaniga PP, Cordova C, Violi F, Chronic Obstructive Bronchitis and Haemostasis Study Group. Enhanced thromboxane biosynthesis in patients with chronic obstructive pulmonary disease.

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