Fibrinogen and ADP induced platelet aggregation

Abstract

Fibrinogen is required for ADP-induced aggregation of washed human platelets and enhances ADP-induced aggregation of rabbit platelets. To achieve these effects, fibrinogen had to be either present before ADP was added or added with the ADP. When fibrinogen was added after platelets had changed in shape in response to ADP, fibrinogen did not support ADP-induced aggregation. The association of 125I-fibrinogen with platelets during ADP-induced aggregation was investigated. A mixture of 125I-fibrinogen and trivalent 51Cr (as a measure of trapped fluid) was added to suspensions of washed human or rabbit platelets. Samples were taken for rapid centrifugation before and at several times after the addition of ADP. The percentage of labeled fibrinogen associated with the platelets was calculated. Fibrinogen associated transiently with platelets during their response to ADP. The largest amount of fibrinogen became associated with the platelets almost immediately after the addition of ADP; less fibrinogen was associated with the platelets at the peak of aggregation, and the associated fibrinogen was lost during platelet deaggregation. Association occurred only if conditions permitted platelet aggregation in response to ADP; inhibitory conditions included lack of divalent cations, inhibition of platelet metabolism, or the presence of inhibitors of platelet aggregation such as prostaglandin E1 or adenosine. Thus the association of fibrinogen with platelets appeared to take place during the initial changes induced by ADP. These results indicate that fibrinogen may be involved in transient linkages between platelets in ADP-induced aggregates.