Br J Clin Pharmacol. 2025 Sep 17. doi: 10.1002/bcp.70289. Online ahead of print.
ABSTRACT
Immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by platelet destruction. While most patients respond to first- or second-line therapies, a small subset is multirefractory. Fostamatinib, an oral spleen tyrosine kinase (SYK) inhibitor, is a therapeutic option in these cases. We report a case of an acute aortic dissection (AAD) occurring in a patient without traditional cardiovascular risk factors, 3 months after fostamatinib initiation. A 70-year-old woman with a 30-year history of ITP, unresponsive to multiple therapies, was treated with fostamatinib and achieved a complete haematologic response. She presented with sudden chest pain and was diagnosed with Stanford A (DeBakey type 1) AAD requiring emergency surgery. Histological analysis of her aortic tissue showed a 25% reduction in phosphorylated SYK expression compared to a control sample, without alteration in smooth muscle cell markers. The absence of predisposing conditions (hypertension, smoking, genetic disorders) led us to explore a potential link between fostamatinib and AAD. Experimental data suggest that SYK inhibition exacerbates aortic wall vulnerability, and off-target effects of fostamatinib on VEGF receptors may further weaken vascular integrity. This case highlights a possible association between fostamatinib and AAD, potentially mediated by SYK and VEGFR inhibition. While causality cannot be definitively established, clinicians should be vigilant when prescribing fostamatinib, even in patients without known risk factors for AAD. Further studies are needed to clarify the vascular safety profile of fostamatinib in ITP and other settings.
PMID:40962713 | DOI:10.1002/bcp.70289