Arachidonic acid metabolism in platelets of patients with essential thrombocythaemia.

Platelet aggregation tests and studies comprising [14C] arachidonic acid [14C]AA incorporation, release and metabolism were performed in resting and thrombinstimulated platelets of 11 patients with essential thrombocythaemia (ET) and 11 normal subjects. Nine patients had abnormal aggregation tests. Incorporation and distribution of [14C]AA in main platelet phospholipids (PLs) was similar in both groups. Activated platelets of patients with ET released more radioactivity from PLs that controls (13.7 +/- 5.4% versus 8.2 +/- 1.9%, p < 0.01). The formation of 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) was also increased (3.3 +/- 1.4% of total radioactivity versus 1.6 +/- 0.4% in controls (p < 0.0001). The same results were obtained for the generation of thromboxane B2 (p < 0.01). We did not detect differences in the formation of 12-L-hydroxy- 5,8,10,14-eicosatetraenoic acid (3.3 +/- 1.7% in patents versus 2.0 +/- 0.5% in controls). These results indicate that platelets of patients with ET have an increased activity of phospholipases and suggest a facilitated metabolism of arachidonate by the prostaglandinsynthetase pathway. Our results also demonstrate that impairment of aggregation tests in these patients was not due to a defective activity of the enzymes involved in the release and metabolism of AA by platelets.