Presence of platelet-associated anti-glycoprotein (GP)VI autoantibodies and restoration of GPVI expression in patients with GPVI deficiency

Mitsuyoshi Akiyama, H. Kashiwagi, K. Todo, Masaaki Moroi, M. C. Berndt, Hiroshi Kojima, Y. Kanakura, Yoshi Tomiyama

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Background: Glycoprotein (GP)VI deficiency is a rare platelet disorder with a mild bleeding tendency. However, its pathophysiology remains unclear. Objectives: We characterized a novel GPVI-deficient patient with immune thrombocytopenic purpura and searched for the presence of anti-GPVI autoantibodies in this and another patient with GPVI deficiency. Methods and results: A 12-year-old Japanese girl (case 1) with moderate thrombocytopenia and mild bleeding showed selectively impaired collagen-induced platelet aggregation. Flow cytometric analysis indicated that the patient had a defect in the expression of GPVI-FcRγ. An eluate of her platelet-associated IgG contained anti-αIIbβ3 autoantibodies. Moreover, using GPVI-FcRγ-transfected cells, we unexpectedly identified anti-GPVI antibodies against the soluble ectodomain of GPVI in the eluate, despite the patient's GPVI deficiency. In contrast, anti-GPVI antibodies were not detectable in her plasma. In another case of GPVI deficiency (case 2) without detectable plasma anti-GPVI antibodies, we again detected platelet-associated anti-GPVI antibodies. In a 2-year follow-up of case 1, the platelet count increased to within the normal range and the bleeding tendency improved. Interestingly, GPVI was again expressed on her platelets, in association with a decrease in the relative amount of anti-GPVI antibodies. Conclusions: This is the first demonstration of platelet-associated anti-GPVI antibodies in GPVI-deficient subjects, in one case with spontaneous restoration of GPVI expression. These results strongly suggest an autoimmune mechanism in GPVI deficiency.

Original languageEnglish
Pages (from-to)1373-1383
Number of pages11
JournalJournal of Thrombosis and Haemostasis
Issue number8
Publication statusPublished - 2009
Externally publishedYes


  • GPVI deficiency
  • Immune thrombocytopenic purpura
  • Platelet-associated autoantibody

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