A L Frelinger1,2, R F Grace2, A J Gerrits1,2, S L Carmichael1,2, E E Forde1,2, A D Michelson1,2. 1. Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States. 2. Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States.
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. Schattauer GmbH Stuttgart.
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. Schattauer GmbH Stuttgart.
Authors: Alexey A Martyanov; Daria S Morozova; Maria A Sorokina; Aleksandra A Filkova; Daria V Fedorova; Selima S Uzueva; Elena V Suntsova; Galina A Novichkova; Pavel A Zharkov; Mikhail A Panteleev; And Anastasia N Sveshnikova Journal: Int J Mol Sci Date: 2020-04-25 Impact factor: 5.923
Authors: Anastasia A Ignatova; Elena V Suntsova; Alexey V Pshonkin; Alexey A Martyanov; Evgeniya A Ponomarenko; Dmitry M Polokhov; Daria V Fedorova; Kirill A Voronin; Natalia N Kotskaya; Natalia M Trubina; Marina V Krasilnikova; Selima Sh Uzueva; Irina V Serkova; Galina S Ovsyannikova; Ksenia I Romanova; Lili A Hachatryan; Irina I Kalinina; Viktor E Matveev; Maya N Korsantiya; Natalia S Smetanina; Dmitry A Evseev; Maria N Sadovskaya; Kristina S Antonova; Anna L Khoreva; Pavel A Zharkov; Anna Shcherbina; Anastasia N Sveshnikova; Aleksey A Maschan; Galina A Novichkova; Mikhail A Panteleev Journal: Sci Rep Date: 2021-04-30 Impact factor: 4.379
Authors: Wobke E M van Dijk; Jelle S Nijdam; Saskia Haitjema; Mark C H de Groot; Albert Huisman; Marieke C Punt; Annemiek C C Evers; Roger E G Schutgens; A Titia Lely; Karin P M van Galen Journal: J Thromb Haemost Date: 2021-08-20 Impact factor: 16.036