Arachidonic acid release and eicosanoid cascade activation in platelet aggregation and thrombosis: Biochemical pathways and inhibitors

Abstract

Platelet activation triggers arachidonic acid release and subsequent thromboxane A2 synthesis, amplifying aggregation responses essential for hemostasis but detrimental in thrombotic disease. This research characterized the phospholipase-cyclooxygenase pathway in human platelets and evaluated inhibitor effects on aggregation. Experiments at Tokyo Institute of Applied Sciences from September 2023 to January 2025 used washed human platelets stimulated with collagen, thrombin, or ADP. Arachidonic acid release reached 2.4 nmol/10⁸ platelets within 60 seconds of collagen stimulation, with thromboxane B2 production peaking at 185 ng/10⁸ platelets. Cytosolic phospholipase A2 inhibition reduced arachidonic acid release by 78%, while aspirin completely abolished thromboxane synthesis. Combined low-dose aspirin and phospholipase inhibitor achieved 94% aggregation inhibition compared to 67% with aspirin alone. These findings support dual-target approaches for antithrombotic therapy.