Novel therapies in the pipeline: Directions of research into platelet inhibition

Abstract

Background: Ischemic stroke is one of the foremost causes of
death and disability in the industrialized world. Apart from
both primary and secondary prevention with oral antiplatelet agents, acute treatment is currently limited to recombinant
tissue plasminogen activator and interventional therapy. The
occurrence of re-thrombosis during and after these interventions clearly indicate the need for further application of novel
agents in the treatment of stroke.
Platelet Function: Current antiplatelet agents in use affect
platelet aggregation at different steps. The common limiting
factor is the observed occurrence of intracerebral hemorrhage
in the setting of acute stroke.
Platelet Inhibition: Selective inhibition of glycoproteins has
been employed already (GP IIb/IIIa inhibitors) but there are
other glycoproteins that can be targeted. This is based on
research that shows that monoclonal antibody mediated inhibition decreases the burden of disease in mouse models of
stroke. A new drug that targets the A1 domain of activated von
Willebrand factor that attaches to GP Ib is potentially another
way of solving the thrombosis puzzle with the promise that
intracerebral hemorrhage would be limited.
Conclusion: The continuing search for acceptable levels of
platelet inhibition during cerebral ischemic events while minimizing the risk of potentially fatal hemorrhagic side effects is
leading the way to selective targeting of the platelet signaling
cascade. This raises hope that future therapy will be more effective while having a more favorable safety profile.
Key words: platelet aggregation, platelet inhibition, anticoagulation drugs