In some cases, immune-mediated thrombocytopenia (ITP) is severe, and requires second-line therapies such as splenectomy and/or Rituximab. In most cases Rituximab is beneficial and safe but in some (though rare) it induces significant hypogammaglobulinemia and persistent decreases in the number of B cells. Patients in whom baseline levels of serum IgM or IgG are low become more prone to develop common variable immune deficiency (CVID) especially when more than one cycle of Rituximab is given. In a few case reports, immune-mediated thrombocytopenia was shown to precede the development of CVID. This could possibly develop following a second bout with Rituximab. The assessment of baseline serum immunoglobulins should be routine in all patients with chronic ITP and those who are candidates for Rituximab therapy.