INTERACTIONS OF STAPHYLOKINASE WITH HUMAN PLATELETS

The interactions of recombinant staphylokinase (SakSTAR) with human pl atelets were investigated in a buffer milieu, in a human plasma milieu in vitro, and in plasma from patients with acute myocardial infarctio n (AMI) treated with SakSTAR. In a buffer milieu, the activation rate of plasminogen by SakSTAR or streptokinase (SK) was not significantly altered bp addition of platelets. Specific binding of SakSTAR or SK to either resting or thrombin-activated platelets was very low. ADP-indu ced or collagen-induced platelet aggregation in platelet-rich plasma ( PRP) was 94 +/- 2.7% or 101 +/- 1.7% of control in the presence of 0.1 to 20 mu M SakSTAR, with corresponding values of 95 +/- 2.8% or 90 +/ - 4.6% of control in the presence of 0.1 to 4 mu M SK. No effects were observed on platelet disaggregation. ATP secretion following collagen -induced platelet aggregation was 4.3 +/- 0.26 mu M for SakSTAR (at co ncentrations of 0.1 to 20 mu M) and 4.4 +/- 0.35 mu M for SK (at conce ntrations of 0.1 to 4 mu M), as compared to 3.4 +/- 0.70 mu M in the a bsence of plasminogen activator. Fifty % lysis in 2 h (C-50) of 60 mu l I-125-fibrin labeled platelet-poor plasma (PPP) clots prepared from normal plasma or from plasma of patients with Glanzmann thrombasthenia and immersed in 0.5 ml normal plasma, was obtained with 12 or 16 nM S akSTAR and with 49 or 40 nM SK, respectively. C-50 values for lysis of 60 mu l PRP clots prepared from normal or patient plasma were also co mparable for SakSTAR (19 or 21 nM), whereas SK was 2-fold more potent toward PRP clots prepared from Glanzmann plasma as compared to normal plasma (C-50 of 130 versus 270 nM). No significant effect of SakSTAR o n platelet function was observed in plasma from patients with AMI trea ted with SakSTA, as revealed by unaltered platelet count, platelet agg regation and ATP secretion. Thus, no effects of high SakSTAR concentra tions were observed on human platelets in vitro, nor of therapeutic Sa kSTAR concentrations on platelet function in plasma.