Background: Immune thrombocytopenia (ITP) is an acquired autoimmune disorder that is associated with an increased risk of venous and arterial thrombosis. Fostamatinib, a Syk inhibitor, is an alternative ITP treatment with reported response rates of 40%.

This study aimed to evaluate the efficacy of fostamatinib and to explore its effect on patients' platelet characteristics and procoagulant profiles.

Methods: This prospective study was approved by the Ethics Committee at Hospital Universitario La Paz.

In a cross-sectional study, we examined 30 patients with ITP who were receiving fostamatinib treatment at our hospital between 2022 and 2025. We assessed platelet characteristics by flow cytometry, including markers of platelet activation (fibrinogen receptor activation by PAC-1 binding, basal and TRAP-induced P-selectin and CD63 exposure), active caspases 3, 7, 8 and 9, and sialic acid exposure (as determined by RCA binding to galactose residues). The kinetics of clot formation were evaluated using rotational thromboelastometry (ROTEM), which was performed using fresh platelet rich plasma adjusted to 25×10⁹ platelets/L using the patient's own platelet-poor plasma (PPP). Thrombin generation was also evaluated in association with either plasma or the phosphatidylserine (PS) of microparticles (MPs) using calibrated automated thrombinography (CAT). A longitudinal study was performed in a subgroup of 16 patients with ITP, in which platelet features and coagulation parameters were evaluated before, and at 3 and 6 months of treatment with fostamatinib or after its discontinuation.

The results were expressed as the ratio between the patient values and the mean of the values of the healthy controls analysed simultaneously. Statistical analysis was performed using IBM SPSS v21 and R Studio v3.0.1.

Results: The 30 patients with ITP who were included in the cross-sectional study had a mean age of 56 ± 21 years, and 50% were women. The median number of prior treatment lines was three (interquartile range: 2.25), which is consistent with a heavily pretreated cohort. Treatment response to fostamatinib was observed in 68% (19/28 patients, two patients were unevaluable due to early discontinuation due to toxicity). Nine patients (32%) did not respond or relapsed. Notably, 83% of patients received concomitant ITP treatment. Three patients (including one who had undergone splenectomy) had experienced thromboembolic events while taking thrombopoietin receptor agonists. No thrombotic events were reported during fostamatinib therapy.

No association was found between response to fostamatinib treatment and platelet features or coagulation parameters, except for shorter Lag Time (LT) in thrombin generation associated with PS content of microparticles (MPs) in relapsed patients.

In the longitudinal study, fostamatinib treatment in responders was associated with a significant decrease in basal PAC-1 binding, basal P-selectin expression and CD63 expression, as well as decreased caspase-8 activity. There were no changes in platelet membrane sialylation. Furthermore, fostamatinib treatment led to a reduction in endogenous thrombin potential (ETP) and peak thrombin concentration, as analysed by CAT using PPP with 4 µM PS and 1 pM tissue factor (TF), as well as MP reagent with 1 pM TF. No changes were observed in ROTEM parameters.

Conclusions: Fostamatinib treatment in ITP appears to reduce platelet apoptosis, which is associated with treatment refractoriness. The observed decrease in platelet apoptosis along with reduced fibrinogen receptor activation and diminished thrombin generation, supports the favorable profile of fostamatinib in patients at risk for thrombosis. To our knowledge, this is the first study to characterize the coagulation profile in patients under fostamatinib therapy.

This work was carried out with the support of project PI22/01489, funded by the Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union.

This content is only available as a PDF.
2025
Sign in via your Institution