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Platelet glycoprotein VI‐related clinical defects
Author(s) -
Arthur Jane F.,
Dunkley Scott,
Andrews Robert K.
Publication year - 2007
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2007.06799.x
Subject(s) - gpvi , platelet , platelet membrane glycoprotein , collagen receptor , platelet activation , integrin , von willebrand factor , immunology , chemistry , medicine , receptor
Summary Human patients with defects associated with the platelet collagen receptor, glycoprotein (GP)VI, are rare and usually described as having a mild bleeding disorder. However, here we review clinical profiles of patients with familial or acquired GPVI defects, revealing the bleeding defect is often severe and associated with immune dysfunction. GPVI is a member of the immunoreceptor family, and co‐expressed on platelets with Fc receptor γ ‐chain (FcR γ ). Ligand binding to GPVI leads to activation of platelet integrins, in particular α IIb β 3 that mediates platelet aggregation; and activation of endogenous platelet metalloproteinases resulting in ectodomain shedding and release of a soluble GPVI fragment. Increasing evidence supports the functional importance of GPVI/FcR γ in thrombus formation at arterial shear rates, and expression levels of platelet GPVI may be a marker of thrombotic risk. Over the past 20 years, patients have been reported with GPVI‐related defects involving: (i) an acquired deficiency, resulting from (a) anti‐GPVI autoantibodies or (b) other causes; or (ii) a congenital deficiency, where (c) GPVI is not expressed or (d) is expressed in a dysfunctional form with defective signalling to α IIb β 3 . Clinical consequences of GPVI‐related defects may be uniquely informative about the role of platelet GPVI in health and disease.