Thromboxane Synthesis and the Platelet Release Reaction in Bernard-Soulier Syndrome, Thrombasthenia Glanzmann and Hermansky-Pudlak Syndrome

Thromboxane (TX) synthesis was investigated in some characterized platelet disorders and correlated with release of ADP or [14C]serotonin and platelet aggregation. In a case with Bernard-Soulier syndrome TX-synthesis as well as ADP-[14C]serotonin release and platelet aggregation were found to be essentially normal when platelets were incubated with collagen, ADP, arachidonic acid or prostaglandin G2 (PGG2). In a case with Hermansky-Pudlak syndrome aggregation was normal with ADP, whereas aggregation with collagen and PGG2 was markedly decreased. Release of ADP and [14C]serotonin was found to be decreased with all investigated inducers in this platelet disorder, whereas TX-synthesis was normal with arachidonic acid and PGG2. In three cases with Glanzmann's thrombasthenia almost no aggregation was observed with any of these compounds. However, in this disorder platelet TX-formation from arachidonic acid or PGG2 was also normal whereas ADP and collagen both induced less TX-formation than in normal platelets. These results indicate that none of the investigated platelet disorders was associated with abnormal TX-synthesis from arachidonic acid as found in platelet cyclo-oxygenase deficiency. These observations provide further evidence for the hypothesis that the Bernard-Soulier syndrome and Glanzmann's thrombasthenia are primarily associated with glycoprotein abnormalities at receptor level (Nurden & Caen, 1974, 1975, 1976). A hypothetical model for the interrelationship of two specific glycoproteins and thromboxane-synthesis is discussed.