Circulation, Vol 84, 84-91, Copyright © 1991 by American Heart Association
DE Vaughan, E Van Houtte, PJ Declerck and D Collen
BACKGROUND. Streptokinase (SK) is a bacteria-derived protein and one of the
plasminogen activators that is currently available for therapeutic use.
Exposure to SK induces synthesis of specific antibodies that may initiate
platelet aggregation and paradoxical clot propagation during treatment.
METHODS AND RESULTS. Using platelet-rich plasma (PRP), we found that SK
(5,000 units/ml) but not urokinase (2,500 units/ml) or recombinant
tissue-type plasminogen activator (2,500 units/ml) caused platelet
aggregation in PRP from 14 of 100 normal volunteers. In 13 consecutive
patients treated with SK for acute myocardial infarction, SK-mediated
platelet aggregation was induced in five patients within 1 week after
treatment. SK-mediated platelet aggregation was associated with
significantly increased titers of both anti-SK antibodies and SK-
neutralizing activity in plasma; it was partially inhibited by aspirin (1
mM) and by aprotinin (500 kallikrein inhibitor units/ml) and completely
inhibited by tranexamic acid (1 mM) and by prostaglandin E1 (9 microM).
Addition of SK (1,000 or 5,000 units/ml) induce a statistically significant
dose-dependent thromboxane B2 release in mixtures of PRP with plasma from
subjects with SK-induced aggregation but not in samples of PRP mixed with
plasma from nonresponders; addition of recombinant tissue-type plasminogen
activator (1 or 50 micrograms/ml) did not induce thromboxane B2 release.
Mixing experiments with PRP and immunoglobulin G from reactive and
nonreactive donors revealed that SK-induced aggregation requires the
presence of anti-SK antibodies. When 125I-SK (50 nM) was used, platelets
preincubated with plasminogen (0.5 microM) bound 9,500 +/- 600 (mean +/-
SEM, n = 6) molecules SK/platelet, which increased to 25,000 +/- 3,100
molecules/platelet after thrombin stimulation. Tranexamic acid (1 mM)
blocked specific binding of SK to resting platelets. CONCLUSIONS. These
data demonstrate that SK-induced platelet aggregation is initiated by the
binding of anti-SK antibodies to the SK-plasminogen complex located on the
platelet surface. SK-induced platelet activation may limit the therapeutic
effectiveness of the drug, and in view of the high prevalence of
aggregation in a normal population, prospective evaluation of the effects
of platelet aggregation during treatment with SK is warranted.
ARTICLES
Streptokinase-induced platelet aggregation. Prevalence and mechanism
Center for Thrombosis and Vascular Research, University of Leuven, Belgium.
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