P49First UK Report of a Case of Glycoprotein VI Deficiency in a 33-Year-Old Patient with Moderate Thrombocytopenia and Autoantibodies Against the Immunoglobulin-Like Domains of the Receptor

Background  Studies of cases of acquired and inherited GPVI deficiency have made critical contributions to the understanding of the pivotal role of GPVI in collagen mediated platelet signaling.
Aim  To characterize the first UK case of GPVI deficiency.
Methods  Numerous platelet function tests and immunophenotyping assays, western blotting and genomic sequencing.
Results  A female patient of 33 years with mild thrombocytopenia (80–120 × 10⁹ L⁻¹), had experienced moderate bleeding with atypical locations, including bruises and petechiae on neck and chest, and a perineal haematoma and postnatal bleeding. Bone marrow examination revealed plentiful megakaryocytes, compatible with a state of compensated thrombocytolysis. PFA 100 response with the collagen/epinephrine cartridge was >295 seconds, and aggregometry showed a profoundly reduced response to collagen and collagen-related peptide. Response to ADP and PAR1 peptide was moderately reduced, but ristocetin induced agglutination was normal. By flow cytometry, normal surface expression was observed to many platelet receptors, including GPIIbIIIa, GPIaIIa and PECAM-1. Expression of PAR-1 was mildly reduced, whereas for GPVI a 90% reduction in surface expression was observed. Total GPVI levels as measured by blot densitometry were also reduced, although not as profoundly. The sequence of the GP6 exons was identical to the reference sequence. A potent GPVI autoantibody was detected in the patients' plasma by a sandwich ELISA (MAIPA), and reactivity was mapped to the collagen-binding domains using recombinant GPVI fragments.
Conclusions  The patient has GPVI autoantibodies of the IgG class, resulting in an acquired GPVI deficiency and with a bleeding phenotype apparently more severe than other reported cases of GPVI deficiency.