Altered arachidonate metabolism by platelets in patients with myeloproliferative disorders.
Platelet lipoxygenase and cyclo-oxygenase pathways were investigated by the incubation of 1(-14) C-arachidonic acid with washed platelets in 33 patients with myeloproliferative disorders, including 14 patients with chronic myeloid leukemia (CML), 12 with polycythemia vera (PV), 4 with essential thrombocythemia (ET), and 3 with myelofibrosis (MF). In patients with MF and CML, mean activities of the lipoxygenase pathway were significantly lower when compared with normal controls (p less than 0.001 and p less than 0.01, respectively). When a normal range of the activity was defined as mean +/- 2 SD, all patients with MF, 8 with CML, 6 with PV, and 1 with ET showed decreased lipoxygenase activities, while activities of the cyclo-oxygenase pathway were decreased in one of each patient with CML, PV, and ET. In 4 of 10 patients with a selective lipoxygenase deficiency, platelets were aggregated by lower concentrations of arachidonic acid than those necessary to induce normal platelet aggregation. It is suggested that the lipoxygenase activity could modulate platelet functions through its effect on arachidonate metabolism by the cyclo-oxygenase pathway and that a selective lipoxygenase deficiency could offer a mechanism for hyperfunction of the platelet, which may lead to a thrombotic tendency, one of the common features of myeloproliferative disorders.
D000328:Adult; D000368:Aged; D001095:Arachidonic Acids / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D006801:Humans; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000097:blood*; D010974:Platelet Aggregation; D011458:Prostaglandins E / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism; D013997:Time Factors
D001095:Arachidonic Acids; D011458:Prostaglandins E; D011460:Prostaglandins F; D013929:Thromboxane B2; D008084:Lipoxygenase; D001241:Aspirin