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.