Compromised ITAM-based platelet receptor function in a patient with immune thrombocytopenic purpura

Elizabeth E. Gardiner*, M. Al-Tamimi, F. T. Mu, D. Karunakaran, J. Y. Thom, M. Moroi, R. K. Andrews, M. C. Berndt, R. I. Baker

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)


Background: Receptors on platelets that contain immunoreceptor tyrosine-based activation motifs (ITAMs) include collagen receptor glycoprotein (GP) VI, and FcγRIIa, a low affinity receptor for immunoglobulin (Ig) G. Objectives: We examined the function of GPVI andFcγRIIa in a patient diagnosed with immune thrombocytopenic purpura (ITP) who had unexplained pathological bruising despite normalization of the platelet count with treatment. Methods and Results: Patient platelets aggregatednormally in response to ADP, arachadonic acid and epinephrine, but not to GPVI agonists, collagen or collagen-related peptide, or to FcγRII-activating monoclonal antibody (mAb) 8.26, suggesting ITAM receptor dysfunction. Plasma contained an anti-GPVI antibody by MAIPA and aggregated normal platelets. Aggregating activity was partially (∼60%) blocked by FcγRIIa-blocking antibody, IV.3, and completely blocked by soluble GPVI ectodomain. Full-length GPVI on the patient platelet surface was reduced to ∼10% of normal levels, and a ∼10-kDa GPVI cytoplasmic tail remnant and cleaved FcγRIIa were detectable by western blot, indicating platelet receptor proteolysis. Plasma from the patient contained ∼150 ngmL-1 soluble GPVI by ELISA (normal plasma, ∼15 ngmL-1) and IgG purified from patient plasma caused FcγRIIa-mediated, EDTA-sensitive cleavage of both GPVI and FcγRIIa on normal platelets. Conclusions: In ITP patients, platelet autoantibodies can curtail platelet receptor function. Platelet ITAM receptor dysfunction may contribute to the increased bleeding phenotype observed in some patients with ITP.

Original languageEnglish
Pages (from-to)1175-1182
Number of pages8
JournalJournal of Thrombosis and Haemostasis
Issue number7
Publication statusPublished - Jul 2008
Externally publishedYes


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