The Fc region of anti-CD44 is critically required to ameliorate murine ITP. Passive antibody-mediated ITP was induced in C57BL/6 mice using anti-GPIIb/IIIa IgG1 (clone MWReg30) administered IV by tail vein injection. IgG1 anti-CD44 or equimolar quantities of deglycosylated (Degly.) or F(ab′)2 variants were administered IV by tail vein injection 30 minutes before anti-platelet antibody injection. Platelet counts were determined at 24 hours after anti-platelet antibody administration using a Z2 Coulter Counter. (A) Mice treated with unmodified IgG1 (Intact) anti-CD44 (α-CD44) or its deglycosylated variant. (B) Mice injected with unmodified IgG1 (Intact) α-CD44 or its F(ab′)2 fragment. Data are from 4 independent experiments with 2 mice per experiment (8 mice total) (A) or from 6 independent experiments with 1 or 2 mice per experiment (6-7 mice total). Error: mean ± standard error of the mean (SEM). ****P < .0001, ***P < .001, 1-way analysis of variance with Tukey’s post hoc test.