BACKGROUND: Gel and solid-phase testing platforms are commonly used for pretransfusion testing but are also prone to nonspecific reactivities (NSP) compared to tube testing. This study aims to characterize the features of NSPs in these platforms and how frequently NSPs precede specific antibody detection. METHODS: All antibody screens and identification panels performed between 5/2021-4/2023 by two automated and one manual platforms at a single institution were analyzed with IRB approval: solid-phase (Immucor, Norcross, GA), automated gel (Grifols, Los Angeles, CA), and manual gel (Ortho Diagnostics, Raritan, NJ). Testing platform, antibody identification, strength of reactivity, number of reactive reagent red cells, and RBC antibody history were extracted from chart review. Differences in reactivity strength were compared using the Kruskal-Wallis test, and differences in the number of cells used to establish diagnoses of NSPs were compared using two-way ANOVA. RESULTS: During the 24-month study period, a total of 156,247 antibody screens were performed with 5491 positive screens, and NSP was identified on 358/5491 panels (6.6%). 271/5491 (4.9%) panels had NSP detected on non-tube platforms: 95 on solid-phase, 123 on automated gel, and 53 on manual gel. The mean strength of reactivity by agglutination for NSP was 1.7, 0.5, and 1.4, respectively (p <
.002). In addition, 9/271 (3.3%) of all panels with NSP on gel or solid-phase were associated with the detection of specific alloantibodies in subsequent panels. CONCLUSION: Nonspecific reactions differ by platforms in specificity and strength. Solid-phase shows stronger reactivity, while automated gel has higher rates of positivity.