Platelet Function in ITP, Independent of Platelet Count, Is Consistent Over Time and Is Associated with Both Current and Subsequent Bleeding Severity

Abstract

Background Treatment decisions for patients with immune thrombocytopenia (ITP) are difficult because patients with similarly low platelet counts differ in their bleeding tendency. We recently reported that platelet function tests, independent of platelet count, are associated with concurrent bleeding severity, suggesting that these tests may be useful indicators of future bleeding in ITP.

Objectives To test this hypothesis, we evaluated the consistency of these platelet function tests over time and their association with subsequent bleeding severity.

Methods Bleeding score and platelet biomarkers were evaluated in a cross-sectional study of children with ITP at two visits separated by a median of 10 months.

Results and Conclusions Correlations between Visit 1 and Visit 2 results for immature platelet fraction, circulating and agonist-stimulated platelet surface P-selectin, and activated GPIIb–IIIa and GPIbα indicated consistency of the platelet phenotype over time. Consistent with our previous findings, platelet biomarkers at each visit were significantly associated with the concurrent bleeding score. Furthermore, increased P-selectin on circulating platelets and reduced agonist-stimulated P-selectin and activated GPIIb–IIIa-positive platelets at Visit 1 were significantly associated with bleeding scores at Visit 2 and remained significantly associated with bleeding severity after adjustment for platelet count. These results suggest a mechanistic link between desensitization of agonist receptors and increased bleeding severity. In summary, platelet function in ITP, independent of platelet count, is consistent over time and is associated with both concurrent and subsequent bleeding severity. These findings support further evaluation of platelet function testing to help guide patient management in ITP.

Keywords

bleeding - immune thrombocytopenia - platelet - risk factor

Authors' Contributions

A. L. Frelinger conceived the studies, analysed and interpreted the data, and wrote the manuscript. R. F. Grace and A. D. Michelson conceived the studies, interpreted the data and provided critical revisions to the manuscript. A. J. Gerrits, S. L. Carmichael and E. E. Forde performed the research and contributed to the manuscript.

Note

This work was supported in part by a research grant from Sysmex to Boston Children's Hospital (Drs. Michelson and Frelinger principal investigators).

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