Arachidonic acid metabolism in platelets of patients with essential thrombocythaemia

Abstract

Platelet aggregation tests and studies comprising [ 14C] arachidonic acid [ 14C]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 [ 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<0.001). 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.