THE POTENTIAL ROLE OF PLATELET PAI-1 IN T-PA MEDIATED CLOT LYSIS OF PLATELET-RICH PLASMA

The potential role of platelets in platelet rich plasma clot lysis ind uced by tissue plasminogen activator (t-PA) was investigated. At the v arious concentrations of both single chain t-PA (sct-PA) and two chain t-PA (tct-PA) (1.5nM, 3nM, and 6nM), we compared the t-PA mediated ly sis time of platelet rich plasma clot (PRP-clot) with that of platelet poor plasma clot (PPP-clot). At the concentrations ranged from 1.5 to 6 nM of both types of t-PA, the clot lysis time of PRP-clot was longe r than that of PPP-clot. This elongation was more significant in the t ct-PA induced clot lysis than that in the sct-PA induced clot lysis. A t the concentration of 3nM of tct-PA, the lysis time of PRP-clot was l onger by a factor of 30% in comparison with that of PPP-clot. When the release and the aggregation of platelets were blocked by prostaglandi n E1 (PGE1) and theophylline in this experiment, the lysis time of PRP -clot was essentially the same as that of PPP-clot. We then measured t he antigen levels of total PAI-1 and t-PA-PAI-1 complex in the lyzed s olutions of PRP-clot and PPP-clot to analyse the possible effect of pl asminogen activator inhibitor-1 (PAI-1) present in platelets. Most of PAI-1 in a PPP-clot lyzed sample existed as t-PA-PAI-1 complex. In the lyzed solution of PRP-clot, however, the antigen levels of both total PAI-1 and t-PA-PAI-1 complex were significantly higher than those in PPP-clot, and larger amounts of PAI-1 existed as free PAI-1 which poss esses activity. These data suggest that at least certain amounts of PA I-1 in platelets exist as an active form and inhibits t-PA activity re sulting in the prolongation of the clot lysis time. Activation of plat elets, therefore, seems to play an important role in the platelet rich plasma clot lysis induced by t-PA.