Brain-Derived Neurotrophic Factor (BDNF) Is Associated with Platelet Activity and Bleeding Tendency in Patients with Gaucher Disease |
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Authors: | David Azoulay Mira Naamad Dafna Frydman Ellen Broide Ari Zimran Galia Stemer Shoshana Revel-Vilk |
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Affiliation: | 1.Hematology Unit and Laboratories, Galilee Medical Center, Nahariya 22100, Israel;2.Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel;3.Flow Cytometry Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel;4.Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel;5.Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel;6.Pediatric Hematology/Oncology Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel |
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Abstract: | Bleeding tendency, a prominent feature of patients with Gaucher disease (GD), is associated with abnormal platelet function. Brain-derived neurotrophic factor (BDNF) is a protein with neuroprotective potential stored in alpha granules of circulating platelets. Here we studied BDNF levels in 50 patients with type I GD (GD1) and their correlation with platelet activity and bleeding tendency. Flow cytometry was used to test unstimulated and stimulated measurement of platelet surface-activated expression of αIIbβ3 integrin, P-selectin and lysosomal-associated membrane protein (LAMP3/CD63). Serum and plasma BDNF levels were quantified using ELISA. The bleeding history was recorded by a bleeding questionnaire. Serum BDNF levels were positively correlated with platelet count and moderately correlated with unstimulated and stimulated platelet P-selectin expression. Patients with more than one bleeding manifestation were shown to have lower serum BDNF levels, albeit similar platelet count. Plasma BDNF levels were significantly elevated in splenectomized patients and showed a moderate positive correlation with stimulated platelet CD63 expression. These observations demonstrate the first association between BDNF levels in the peripheral blood with platelet dysfunction and increased bleeding manifestation. The role of measuring serum BDNF for assessing platelet alpha degranulation defects and bleeding risk in patients with GD and the general population needs further study. |
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Keywords: | Gaucher disease (GD) brain-derived neurotrophic factor (BDNF) alpha degranulation defect platelets |
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