Streptokinase-induced platelet aggregation. Prevalence and mechanism

Area of Science:

• Immunology
• Hematology
• Pharmacology

Background:

• Streptokinase (SK) is a bacterial plasminogen activator used therapeutically.
• Antibody formation against SK can lead to platelet aggregation and paradoxical clot formation.
• Understanding SK's effects on platelets is crucial for its safe and effective use.

Purpose of the Study:

• To investigate the mechanism of SK-induced platelet aggregation.
• To determine the role of anti-SK antibodies in this process.
• To identify potential inhibitors of SK-mediated platelet activation.

Main Methods:

• Platelet-rich plasma (PRP) aggregation assays with SK, urokinase, and recombinant tissue-type plasminogen activator.
• Analysis of anti-SK antibody titers and neutralizing activity in patients treated with SK.
• Inhibition studies using aspirin, aprotinin, tranexamic acid, and prostaglandin E1.
• Measurement of thromboxane B2 release and SK binding to platelets.

Main Results:

• SK induced platelet aggregation in 14% of normal volunteers and 38% of patients treated for myocardial infarction.
• Aggregation correlated with increased anti-SK antibodies and was inhibited by tranexamic acid and prostaglandin E1.
• SK-induced aggregation required anti-SK antibodies and involved thromboxane B2 release.
• SK binds to plasminogen on platelet surfaces, with binding blocked by tranexamic acid.

Conclusions:

• SK-induced platelet aggregation is mediated by anti-SK antibodies binding to the SK-plasminogen complex on platelets.
• This immune response may reduce therapeutic efficacy and warrants further investigation.
• Prospective studies are needed to evaluate platelet aggregation during SK treatment.