The response of human platelets to low temperature (below 15 degrees C) requires that they are stored at elevated temperatures and limits their storage time to 5 days for use in transfusion. Prolonged storage at room temperature leads to loss of platelet function and risk of septic conditions. The need for improved platelet storage is an important issue, and finding a key component allowing platelets to be maintained at low temperatures would have significant practical benefit. Developing such a component is challenging, because the process of cold-activation resembles that of a physiological agonist-mediated activation, but without a specific receptor that can be inhibited. A component preventing platelets' low temperature response will potentially inhibit their physiological function, making them less useful after transfusion. In the present study, we report that pretreatment of platelets with flavonoids before chilling prevents an increase in cytosolic calcium concentration, actin polymerization and platelet shape change. After warming, platelets that were chilled in the presence of flavonoids retain a normal shape change and aggregation response after stimulation by thrombin. Additionally, cold platelet activation does not increase platelet procoagulant activity evaluated by annexin V-FITC binding in the presence and absence of flavonoids. These data confirm the important links that exist between agonist- and cold-mediated platelet activation, suggesting a possible advantage of incorporating the use of flavonoids to allow platelet hypothermic-storage.