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Blood, 1 July 2004, Vol. 104, No. 1, pp. 107-114.
Prepublished online as a Blood First Edition Paper on March 9, 2004; DOI 10.1182/blood-2003-11-3842.
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Submitted November 12, 2003
Accepted February 18, 2004
Severe Deficiency of Glycoprotein VI in a Patient with Gray Platelet Syndrome
Paquita Nurden*, Martine Jandrot-Perrus, Robert Combrie, Joelle Winckler, Veronique Arocas, Christelle Lecut, Jean-Max Pasquet, Thomas J Kunicki, and Alan T Nurden
IFR4, Laboratoire d'Hematologie, Hopital Cardiologique, Pessac, France
E348 INSERM, Faculte Xavier Bichat, Paris, France
FRE 2617 CNRS, Universite de Bordeaux2, Bordeaux, France
The Roon Research Center for Arteriosclerosis and Thrombosis, The Scripps Research Institute, La Jolla, CA, USA
* Corresponding author; email: Paquita.Nurden{at}cnrshl.u-bordeaux2.fr.
We report a novel case of gray platelet syndrome (GPS) where a severe deficiency of the platelet collagen receptor, glycoprotein (GP) VI, accompanies classical symptoms of a low platelet count and platelets lacking  -granules. Dense granules were normally present. Platelet aggregation with collagen was severely decreased, as was the response to convulxin (Cvx), a GPVI agonist. Quantitative analysis of GPVI using FITC-Cvx in flow cytometry showed its virtual absence on the patient's platelets. The GPVI deficiency was confirmed using monoclonal antibodies in Western blotting, and in immunogold labeling on frozen-thin sections where internal pools of GPVI were confirmed for normal platelets. The Fc receptor  -chain, constitutively associated with GPVI in normal platelets, was present in subnormal amounts, and the phospholipase C2-dependent activation pathway appeared to function normally. No autoantibodies to GPVI were found in the patient's serum using MAIPA. Sequencing of coding regions of the GPVI gene failed to show abnormalities, and mRNA for GPVI was present in the patient's platelets pointing to a probable acquired defect in GPVI expresion. Our results may provide a molecular explanation for the subgroup of patients with severely deficient collagen-induced platelet aggregation as previously described for GPS in the literature.
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