Glanzmann thrombasthenia: Integrin alpha(IIb)beta(3) deficiency

Integins, a family of noncovalently associated alpha beta heterodimeric adh esion receptors, are involved in a variety of pathological and physiologica l processes. The importance of integrins is evident in the severe pathogeni c consequences of their congenital deficiencies: Glanzmann thrombasthenia ( GT) and leukocyte adhesion deficiency. In this review, I have focused on GT , a rare autosomal recessive bleeding disorder characterized by the quantit ative and/or qualitative abnormality of integrin alpha (IIb)beta (3) (glyco protein IIb-IIIa). Molecular genetic analysis of GT, when caused by a quant itative abnormality of alpha (IIb)beta (3), provides important information regarding key structures for alpha (IIb)beta (3) biosynthesis. Of particula r interest is GT when caused by a qualitative abnormality of alpha (IIb)bet a (3) (GT variants). The analyses of GT variants provide new insight into t he regulation of alpha (IIb)beta (3) function and the interaction between a lpha (IIb)beta (3) and its ligands. This research could contribute to new a nd better alpha (IIb)beta (3) antagonists with minimal complications (such as bleeding and thrombocytopenia) for the prevention and treatment of patho logical thrombosis. Int J Hematol. 2000:72:448-454. (C)2000 The Japanese So ciety of Hematology.