Absence of bleeding upon dual antiplatelet therapy in a patient with a immune GPVI deficiency

Abstract

Acquired deficiencies in platelet glycoprotein VI are rare and have not been found associated with other defects. Here we report the case of a 64-year old male patient presenting an immune GPVI deficiency associated to a mutation in the alpha-actinin gene and who has been treated with dual anti platelet therapy without bleeding.

Introduction: Glycoprotein (GP) VI, a pluripotent receptor interacting with collagen and fibrin(ogen) is responsible for thrombus formation, growth and stability (1-4). It is co-expressed with the Fc receptor γ (FcRγ) chain (5). GPVI is not critical for haemostasis since subjects with a GPVI deficiency usually present low or even no bleeding tendency (6, 7). Acquired GPVI deficiency due to antibody-induced GPVI depletion is the most frequent finding. At least 10 patients have been described with an acquired GPVI deficiency, most often associated to immune thrombocytopenia, moderate bleeding and impaired collagen-induced platelet aggregation (7). Several mechanisms leading to the GPVI deficiency are proposed including antibody-triggered GPVI internalization and/or shedding of the extracellular domain (8, 9). We report the case of a patient presenting an acquired GPVI deficiency different from those previously described: (i) he is male whereas all previous cases were female, (ii) he is heterozygous for a mutation in α (alpha)-actinin-1 gene and (iii) he was treated with dual antiplatelet therapy with no haemorrhagic manifestation.

Keywords:

• glycoprotein VI
• Immune deficiency
• Dual antiplatelet therapy

Acknowledgements

The authors would like to thank Prof. Marie-Christine Alessi, Aix Marseille University INSERM, INRA, C2VN, Hematology Laboratory APHM, CHU Timone Marseille France for genetic analysis, Prof. Elizabeth Gardiner ACRF Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia, for the kind gift of the antibody against the intracellular domain of GPVI, and Sébastien Dupont Université de Paris, UMRS1148, INSERM, Paris, France for the dosage of soluble GPVI.

Conflict Of Interest

Martine Jandrot-Perrus founder and Scientific Adviser Acticor Biotech. SL, DF, PG, PN, NA: no conflict of interest.

Role And Contribution Of Each Author

SL, DF performed experiments, PG, PN and NA made clinical observations, PN and MJP conceived the experiments, MJP and NA wrote the manuscript, PN reviewed the manuscript.

Supplementary Material

Supplemental data for this article can be accessed on the publisher’s website.