PLATELET PHENOTYPING IN CARRIERS FOR GLANZMANNS-THROMBASTHENIA - A SIMPLE SCREENING-TEST FOR ASSESSMENT OF THE MOLECULAR DEFECT

Glanzmann's thrombasthenia (GT) is a recessive autosomal bleeding diso rder characterized by the abnormality of aggregation due to a platelet glycoprotein (GP) IIb-IIIa deficiency or a dysfunctional complex. Mol ecular abnormalities have been localized on the gene coding for GP IIb or IIIa. The aim of our work was an attempt to obtain indirectly info rmation on the putative localization of the molecular defect in patien ts with GT type I or II by the determination of the HPA-1 (GP IIIa) an d HPA-3 (CP IIb) alloantigenic systems' expression in GT carriers. If GT results from a defective GP IIb gene, a GT carrier would appear hom ozygous for HPA-3 by serology, because the normal gene will be express ed while the abnormal GP IIb gene product will not be present. Convers ely, if the abnormality is in the GP IIIa gene, such an individual wou ld appear homozygous for HPA-1. Therefore, the heterozygous status for HPA would result from the normal expression of the two genes for the considered alloantigenic system. Among the four families studied with informative members, our presumptions were strengthened by the prelimi nary genetic results in one family showing a mutation in the GP IIb ge ne. Thus, serology could be a simple screening test for the possible d efective gene responsible for GT allowing molecular investigation focu sing only on GP IIb or IIIa gene.