Enhanced thromboxane biosynthesis in patients with chronic obstructive pulmonary disease. The Chronic Obstructive Bronchitis and Haemostasis Study Group.
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
G
Dipartimento di Medicina Sperimentale e Patologia, Università di Roma La Sapienza, Italy.
Basili
S
S
Vieri
M
M
Cipollone
F
F
Santarone
S
S
Alessandri
C
C
Gazzaniga
P
P
Cordova
C
C
Violi
F
F
D000368:Aged; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism; D003404:Creatinine / Q000652:urine; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000097:blood / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010102:Oxygen Inhalation Therapy; D010446:Peptide Fragments / Q000032:analysis; D015539:Platelet Activation; D011516:Prothrombin / Q000032:analysis; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D013931:Thromboxanes / Q000096:biosynthesis*
D016861:Cyclooxygenase Inhibitors; D010446:Peptide Fragments; D013931:Thromboxanes; C045879:prothrombin fragment 1.2; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D011516:Prothrombin; D003404:Creatinine; D001241:Aspirin