John Libbey Eurotext



Diagnosis of inherited platelet disorders in 1998 Volume 4, issue 3, Mai-Juin 1998


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The diagnosis of inherited platelet disorders has benefited from recent advances in our knowledge of the molecular basis of platelet function defects and from the development of new analytical methods such as flow cytometry that can be used in clinical situations. The disorders that are the best understood are those which concern the major platelet functions, for example aggregation (Glanzmann's thrombasthenia) and adhesion (Bernard-Soulier syndrome). However, a series of new disorders is emerging that concern primary receptors of platelets, such as those of ADP, collagen and thromboxane A2. Abnormalities of signalling pathways used by these receptors are also beginning to be defined. Genetic defects have been identified in storage pool diseases such as those associated with the Hermansky-Pudlak, Chediak-Higashi and Wiskott-Aldrich syndromes, although the role of the affected proteins in the development of the platelet defect requires characterization. The explanation for the development of giant platelet disorders remains an enigma. Together with classical approaches to studying platelet function and of evaluating platelet counts and size, which remain the basis of any initial diagnosis, flow cytometry permits an evaluation of the platelet content of membrane glycoproteins and of changes in their expression dependent on the activation state of the platelet, this latter capacity includes the ability to evaluate activation-dependent changes in the conformation of the GP IIb-IIIa complex. Western blotting allows an analysis of the tyrosine kinase dependent signalling pathways. Molecular biology procedures allow the screening of the principal genes coding for the major glycoproteins and family screening for known mutations. The use of new types of apparatus designed to replace the bleeding time and to perform a rapid initial screening is just beginning.