Subscribe to RSS
DOI: 10.1055/s-0038-1642568
Increased Response to Arachidonic Acid and U-46619 and Resistance to Inhibitory Prostaglandins in Patients with Chronic Myeloproliferative Disorders
Publication History
Received 02 July 1987
Accepted after revision 09 October 1987
Publication Date:
18 April 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/198801/lookinside/thumbnails/10-1055-s-0038-1642568-1.jpg)
Summary
In patients with myeloproliferative disorders (MPD) a group of related diseases of the bone marrow stem cell and recurrent haemorrhagic and/or thrombotic complications, the production of aggregating prostaglandins (PGs) may be normal or slightly reduced, while PGI2 production is normal. However, MPD platelet sensitivity to antiaggregatory PGs is still unknown.
We studied the potency of PGD2, PGI2 and PGEi as inhibitors of platelet aggregation induced by threshold aggregating concentrations of arachidonic acid and U-46619-analogue of the cyclic endoperoxide PGH2 in 20 patients with MPD in comparison with healthy controls, with the aim of evaluating the sensitivity of MPD platelets to antiaggregatory PGs. In these patients platelet prostanoid metabolism was normal. However, the functional response of platelets to aggregating and antiaggregating prostanoids was shifted towards potentially increased platelet aggregation response. These findings could have a clinical relevance in view of the haemostatic and thrombotic complications so frequent in MPD.
-
References
- 1 Moneada S, Vane JR. Arachidonic acid metabolites and the interactions between platelets and blood vessel wall. N Engl J Med 1979; 300: 1142-1147
- 2 Di GMinno, Silver MJ, de GGaetano. Prostaglandins as inhibitors of human platelet aggregation. Br J Haematol 1979; 43: 637-647
- 3 Moneada S, Grylewski RJ, Bunting S, Vane JR. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 1976; 263: 663-665
- 4 Oelz O, Oelz R, Knapp HR, Sweetman BJ, Oates JA. Biosynthesis of prostaglandin D2 . Prostaglandins 1977; 13: 225-234
- 5 Whittle B JR, Moneada S, Vane JR. Comparison of the effects of prostacyclin (PGI2), prostaglandin Ej and D2 on platelet aggregation in different species. Prostaglandins 1978; 16: 373-388
- 6 Sinzinger H, Kaliman J, Widhalm K, Pachinger O, Probst P. Value of platelet sensitivity to antiaggregatory prostaglandins (PGI2, PGE 1?PGD2) in 50 patients with myocardial infarction at young age.. Prostagland Med 1981; 7: 125-132
- 7 Fitscha P, Kaliman J, Sinzinger H. Platelet sensitivity to antiaggregatory prostaglandins (PGEj, D2,12) in patients with peripheral vascular disease.. Am J Hematol 1985; 19: 13-19
- 8 Cooper B, Schafer AI, Puchalsky D, Handin RI. Platelet resistence to prostaglandin D2 in patients with myeloproliferative disorders. Blood 1978; 52: 618-626
- 9 Barbui T, Cortelazzo S, Viero P, Bassan R, Dini E, Semeraro N. Thrombohaemorrhagic complications in 101 cases of myeloproliferative disorders: relationship to platelet number and function. Eur J Cancer Clin Oncol 1983; 19: 1593-1599
- 10 Cortelazzo S, Barbui T, Bassan R, Dini E. Abnormal aggregation and increased size of platelets in myeloproliferative disorders. Thromb Haemostas 1980; 43: 127-130
- 11 Born G VR, Cross MJ. The aggregation of blood platelets. J Physiol 1963; 168: 178-195
- 12 Di GMinno, Bertele V, Bianchi L, Barbieri B, Cerletti C, Dejana E, de GGaetano, Silver MJ. Effects of an epoxymethano stable analogue of prostaglandin endoperoxides (U-46619) on human platelets. Thromb Haemostas 1981; 45: 103-106
- 13 Bertelè V, Falanga A, Tomasiak M, Chiabrando C, Cerletti C, de GGaetano. Pharmacologic inhibition of thromboxane synthetase and platelet aggregation: modulatory role of cyclooxygenase products. Blood 1984; 63: 1460-1466
- 14 Patrono C, Ciabattoni G, Pinca E, Pugliesi F, Castrucci G, de ASalvo, Satta MA, Peskar A. Low dose aspirin and inhibition of thromboxane B2 production in healthy subjects. Thromb Res 1980; 17: 317-327
- 15 Weskler BB, Markus AJ, Jaffe EA. Synthesis of prostaglandin I 2(prostacyclin) by cultured human and bovine endothelial cells. Proc Natl Acad Sci USA 1977; 74: 3922-3926
- 16 Kwaan HC, Colwell JA, Cruz S. Increased platelet aggregation in diabetes mellitus. J Lab Clin Med 1972; 80: 236-246
- 17 Bensossuan D, Levy-Toledano S, Passa P, Caen J, Canivet J. Platelet hyperaggregation and increased plasma level of von Willebrand factor in diabetics with retinopathy. Diabetologia 1975; 11: 307-312
- 18 Halushka PV, Lurie D, Colwell JA. Increased synthesis of prostaglandin-E-like material by platelets from patients with diabetes mellitus. N Engl J Med 1977; 297: 1306-1310
- 19 Cortelazzo S, Viero P, Morelli C, Barbui T, de GGaetano. Normal vascular prostacyclin generation in patients with chronic myeloproliferative disorders. Thromb Res 1985; 39: 139-141