Enhanced Thromboxane Biosynthesis in Patients with Chronic Obstructive Pulmonary Disease

Abstract

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.

Correlation between tumor necrosis factor-alpha and d-dimer levels in non-small cell lung cancer patients

“…Furthermore, the lack of a significant correlation between TATc and D-dimer levels suggests that these two analytical variables represent different pathological mechanisms of activated coagulation and fibrinolysis in patients with NSCLC. Elevated TATc levels were also found in COPD, which is not surprising, because of the occurrence of a pro-thrombotic state in this clinical setting [25][26][27][28]. The percentage of patients with positive TATc levels did not significantly differ between COPD and NSCLC patients, and median TATc levels of COPD patients were similar to those measured in plasma samples obtained from metastatic NSCLC patients.…”

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

“…However, the occurrence of platelet hyperreactivity has been demonstrated in ex vivo studies where platelets had an increased sensitivity to various agonists, and elevated levels of plasma b-TG and soluble P-selectin of platelet origin have been reported (Cordova et al, 1985;Ferroni et al, 2000). These reports reflect the occurrence of in vivo platelet activation as measured by increased synthesis of TxA 2 in patients with COPD, and the administration of a TxA 2 antagonist was beneficial in improving respiratory distress in patients with chronic pulmonary emphysema (Davi et al, 1997).…”

Pulmonary vascular changes in asthma and COPD

“…Prostacyclin is in homeostatic balance with thromboxane in the circulatory system [113,114], where thromboxane is mainly produced by thrombocytes via the COX pathway and known as a potent vaso-and bronchoconstrictor in both human and animals [115,116]. Patients with COPD have an increased amount of thromboxane metabolites in their urine [117], probably due to hypoxia and increased platelet aggregation, which correlates with the augmented amount of plaque in the vessels of these patients [118]. These data suggest that prostacyclin and thromboxane may be important markers in vascular inflammation and regulation of ongoing ECM changes in COPD.…”