Platelets are of key importance in arterial thrombosis and to prevent bleeding

Myocardial infarction and stroke, which are caused by arterial thrombosis in heart and brain, represent one of the most common causes of mortality and morbidity in the western world. Arterial thrombosis is also a major complication of atherosclerosis. There is no doubt that blood platelets are the central players in the pathogenesis of thrombosis. They rapidly aggregate at an injured or atherosclerotic vessel wall, form a thrombus and steer the formation of fibrin clots.
Upon vascular injury, functional platelets are imperative to promptly arrest bleeding. Inherited or acquired platelet defects are therefore associated with mild to severe bleeding disorders. By contrast, upon rupture of an unstable atherosclerotic plaque, platelets form an occlusive thrombus preventing oxygen supply to brain or heart, which results in myocardial infarction or stroke.
In order to prevent these events, essentially all patients with risk for arterial thrombosis are massively treated with antiplatelet medications. These agents target specific cellular components crucial for platelet functionality, and include aspirin (blocking thromboxane formation), clopidogrel & prasugrel (blocking ADP receptors) and tirofiban (blocking platelet-platelet binding via fibrinogen). However, many other platelet membrane receptors and intracellular enzymes have not or insufficiently been tested for therapeutic use. Relevant are adhesive glycoproteins (GPIb-IX-V, GPVI, integrins), platelet products with autocrine activity (Gas6, proteases, shed ligands), and many signal transduction proteins.
Although the current anti-platelet treatments do reduce the mortality and morbidity in different groups of patients, they are not fully effective. Many problems remain to be solved, including drug resistance, efficacy and safety, dosage, administration requirements and combination therapy.
Importantly, none of the current therapies adequately meets the most sought requirement, namely: the ability to inhibit the platelet contribution to thrombosis without increasing bleeding. Therefore novel, improved anti-platelet therapies are urgently needed. The development of such agents presupposes accurate understanding of the mechanisms of platelet activation, aggregation, and thrombus formation.