Constitutional thrombocytopathies (Glanzmann's thrombasthenia and Bernard-Soulier syndrome) from the initial description to the development of new antithrombotic agents

The study of exceptional thrombocytopathies has led to considerable progress in the understanding of normal and pathologic haemostasis. Thus, precise structure/function relationships were able to be established The lack or the abnormalities of the glycoprotein IIb/IIIa complex is responsible for the complete defect in platelet aggregation characterizing Glanzmann's Thrombasthenia, while the lack or the abnormalities of the glycoprotein Ib/IX/V complex is responsible for the defect in platelet adhesion to the subendothelium noted in the Bernard-Soulier syndrome. The bases for these abnormalities are now known at the molecular level. Recent data also underline the role of these glycoproteinic complexes as receptors for platelet activation; besides an involvement of the GPIIb/IIIa complex in adhesion and of the GPIb/IX/V complex in platelet aggregation, von Willebrand factor dependent, were newly evidenced. New antithrombotic agents directed against the GPIIb/IIIa complex arp currently being tested in large clinical trials, especially in cardiovascular diseases. In the future, the inhibition of the GPIb-IX-V/von Willebrand factor axis should permit the development of a new class of antithrombotics, perhaps even more promising since they will act at the very early phases of primary hemostasis.