Impaired α-Granule Secretion Dominates Longitudinal Agonist-Induced Platelet Dysfunction in Gaucher Disease.

چکیده اصلی

Bleeding in Gaucher disease (GD) is not fully explained by thrombocytopenia and coagulation disorders. Previous studies have shown impaired agonist-induced cluster of differentiation (CD) 62P (CD62P/P-selectin) responses, but their persistence over time is unknown. This retrospective longitudinal observational study characterized platelet activation and secretion responses over time and factors associated with persistent abnormalities. Whole-blood flow cytometry studies from 333 patients with GD with at least two assessments were analyzed. Platelet activation complex-1 (PAC1), CD62P, and CD63 responses were categorized longitudinally. Patients contributed 949 visits over a median follow-up of 2.3 years. Persistent CD62P abnormality was most frequent (92/333, 27.6%), compared with PAC1 (45/329, 13.7%) and CD63 (9/328, 2.7%). PAC1 abnormalities were more often dynamic, whereas CD62P abnormalities were frequent and persistent, most often involving thrombin receptor-activating peptide 6 (TRAP-6) and cross-linked collagen-related peptide (CRP-XL). Lower platelet count was independently associated with persistent CD62P abnormality, although approximately half of affected patients had platelet counts ≥150 × 109/L. Treatment throughout follow-up was associated with lower odds of persistent CD62P and CD63 abnormalities. Impaired CD62P expression was the predominant persistent abnormality, consistent with preferential impairment of α-granule secretion. Platelet function changed over time, supporting reassessment in patients with bleeding manifestations and before procedures when previous testing is remote or clinical status has changed.

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