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When GPVI Goes Rogue: Pathogenesis and Therapeutic Horizons in ITP
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DOI：10.1017/erm.2026.10047.png)
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Abstract
En 中文
Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by immune-mediated platelet destruction; impaired thrombopoiesis and a bleeding diathesis; with growing recognition of accompanying inflammatory and immunoregulatory disturbances. Despite the widespread use of corticosteroids; intravenous immunoglobulin (IVIG) and thrombopoietin receptor agonists (TPO-RAs); 30–50% of patients exhibit incomplete; unstable or transient platelet responses; underscoring a persistent unmet need for mechanism-informed therapeutic strategies. Current management paradigms remain largely focused on platelet count restoration rather than direct modulation of pathogenic platelet–immune crosstalk. Accumulating pre-clinical evidence; supported by limited clinical observations; implicates platelet glycoprotein VI (GPVI); a collagen receptor and immunothrombotic signalling hub; as a mechanistically relevant contributor to platelet hyperactivation; inflammatory amplification and aberrant platelet–leucocyte interactions in ITP. Experimental models indicate that GPVI-dependent signalling pathways can promote thromboinflammatory responses; facilitate immune cell engagement and influence platelet clearance dynamics; positioning GPVI as a plausible; albeit incompletely validated; therapeutic target. Emerging pre-clinical studies suggest that selective modulation of GPVI signalling may attenuate pathogenic platelet activation while preserving essential haemostatic function; thereby improving platelet survival and functional competence. This review integrates current insights into GPVI biology within the broader immunopathological landscape of ITP and evaluates innovative therapeutic concepts; including GPVI-targeted inhibitors deployed through nanocarrier systems; autologous platelet-mediated delivery and hydrogel-based protective platforms designed to enhance targeting precision and durability. We further discuss the rationale for combination strategies with established therapies and the potential utility of GPVI-linked biomarkers and platelet functional profiling to guide patient stratification. By reframing platelets as active immunoregulatory effectors rather than passive autoimmune targets; this review advances a mechanistic framework for next-generation; precision-oriented intervention in ITP. Although clinical validation remains limited; GPVI-centred strategies represent a rational and testable avenue for moving beyond symptomatic platelet augmentation towards disease-modifying immunothrombotic modulation.
Keywords:
drug delivery systems
glycoprotein VI
hitchhiking
hydrogel
immune thrombocytopenia
nanoparticle
platelet activation
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5.5
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2.2K
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