Direct glycoprotein-specific platelet autoantibodies detected in a majority of patients with persistent...

Chemotherapy-induced thrombocytopenia (CIT) is common in patients with solid tumors and often necessitates chemotherapy dose reduction or delay, compromising cancer outcomes. Persistent CIT, defined by inadequate platelet recovery between cycles, is typically attributed to cumulative myelosuppression, although emerging data suggest that immune dysregulation may also contribute. Platelet autoantibody (PA) testing, well studied in immune thrombocytopenia (ITP), has not been systematically examined in persistent CIT.

To characterize the prevalence and patterns of direct glycoprotein (GP)-specific platelet autoantibodies in patients with persistent CIT and to compare these findings with an ITP cohort tested using the same assay.

We retrospectively identified adults with solid tumors and persistent CIT who underwent direct PA testing at our institution from 2018 to 2022. Testing for autoantibodies to GPIIb/IIIa, GPIb/IX, and GPIa/IIa was performed at a centralized reference laboratory. Results were compared with a reference cohort of 96 PA-positive ITP patients.

Fifty-five patients met the inclusion criteria. PA positivity was observed in 36 (65.4%) patients. Among PA-positive CIT patients, the mean number of autoantibody specificities was 2.2, with reactivity to GPIa/IIa detected in 97.2% of patients. Optical density values and the number of positive antibodies did not differ significantly from those of the ITP cohort.

A surprisingly high proportion of patients with persistent CIT demonstrated robust platelet autoantibodies comparable to those seen in ITP. These findings suggest a potential immune-mediated component in persistent CIT and warrant further investigation into the clinical relevance and therapeutic implications of platelet-directed autoimmunity in CIT.