Arachidonic acid metabolism in the platelets of hemophiliacs with prolonged bleeding times

The bleeding time has been said to be normal in hemophilia. However, we and others have recently reported a prolonged bleeding time unrelated to the ingestion of non-steroidal anti-inflammatory agents or to recent transfusions in 16-20% of patients with hemophilia. To determine whether this abnormality might be due to impaired biosynthesis of thromboxane (TXA₂) from the cyclooxygenase pathway, or 12-hydroxy eicosotetraenoic acid (12-HETE) from the alternative lipoxygenase pathway, we studied the in vitro metabolism of arachidonic acid (AA) in platelets from four hemophiliacs with repeatedly prolonged bleeding times. All studies were performed on an aliquot of platelet-rich plasma obtained from a single venepuncture, the same morning the bleeding time was measured. High pressure liquid chromtograms of the reaction products generated following the incubation of [¹⁴C]-AA with washed platelets from all four subjects were identical to those obtained from two hemophiliacs with normal bleeding times and from normal controls. In addition, metabolites of the cyclooxygenase and lipoxygenase pathways were normal in these patients when assessed by prelabeling their platelets with [¹⁴c]-AA and then stimulating maximally with thrombin. We conclude that the prolonged bleeding times observed in these hemophiliacs cannot be attributed to the presence of a cyclooxygenase inhibitor such as aspirin.