Increased Thromboxane Biosynthesis in Essential Thrombocythemia

Bianca Rocca; Giovanni Ciabattoni; Raffaele Tartaglione; Sergio Cortelazzo; Tiziano Barbui; Carlo Patrono; Raffaele Landolfi

doi:10.1055/s-0038-1649916

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1995; 74(05): 1225-1230
DOI: 10.1055/s-0038-1649916

Original Article

Clinical Studies

Schattauer GmbH Stuttgart

Increased Thromboxane Biosynthesis in Essential Thrombocythemia

Authors

Bianca Rocca

¹The Department of Medicine, Catholic University School of Medicine, Rome, Italy
Giovanni Ciabattoni

²The Department of Pharmacology, Catholic University School of Medicine, Rome, Italy
Raffaele Tartaglione

¹The Department of Medicine, Catholic University School of Medicine, Rome, Italy
Sergio Cortelazzo

³The Division of Hematology, Bergamo’;s Civil Hospital, Bergamo, Italy
Tiziano Barbui

³The Division of Hematology, Bergamo’;s Civil Hospital, Bergamo, Italy
Carlo Patrono

⁴The Department of Pharmacology, University of Chieti “G. D’Annunzio” School of Medicine, Chieti, Italy
Raffaele Landolfi

¹The Department of Medicine, Catholic University School of Medicine, Rome, Italy

Abstract

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Summary

In order to investigate the in vivo thromboxane (TX) biosynthesis in essential thromboeythemia (ET), we measured the urinary exeretion of the major enzymatic metabolites of TXB₂, 11-dehydro-TXB₂ and 2,3-dinor-TXB₂ in 40 ET patients as well as in 26 gender- and age-matched controls. Urinary 11-dehydro-TXB₂ was significantly higher (p <0.001) in thrombocythemic patients (4,063 ± 3,408 pg/mg creatinine; mean ± SD) than in controls (504 ± 267 pg/mg creatinine), with 34 patients (85%) having 11-dehydro-TXB₂ >2 SD above the control mean. Patients with platelet number <1,000 × 10₉/1 (n = 25) had significantly higher (p <0.05) 11 -dehydro-TXB2 excretion than patients with higher platelet count (4,765 ± 3,870 pg/mg creatinine, n = 25, versus 2,279 ± 1,874 pg/mg creatinine, n = 15). Average excretion values of patients 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/mg creatinine, n = 16, p <0.05). Low-dose aspirin (50 mg/d for 7 days) largely suppressed 11-dehydro-TXB₂ excretion in 7 thrombocythemic patients, thus suggesting that platelets were the main source of enhanced TXA₂ biosynthesis. The platelet count-corrected 11-dehydro-TXB₂ 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-TXB₂ excretion, belonged to the subgroup with age >55 and platelet count <1,000 × 109₉/1. We conclude that in essential thrombocythemia: 1) enhanced 11-dehydro-TXB₂ excretion largely reflects platelet activation in vivo;2) age as well as platelet count appear to influence the determinants of platelet activation in this setting, and can help in assessing the thrombotic risk and therapeutic strategy in individual patients.

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References

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