ARACHIDONIC-ACID METABOLISM IN PLATELETS OF PATIENTS WITH ESSENTIAL THROMBOCYTHEMIA

Platelet aggregation tests and studies comprising [C-14] arachidonic acid [C-14]AA incorporation, release and metabolism were performed in resting and thrombin-stimulated platelets of 11 patients with essential thrombocythaemia (ET) and 11 normal subjects. Nine patients had abnormal aggregation tests. Incorporation and distribution of [C-14]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<0.001). 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 patients 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 prostaglandin-synthetase 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.