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Furthermore, Case?2 had mild hypogammaglobulinemia. Figure 3 The majority of primary CAD and WM-associated CAD cases (>70%) show cold agglutinins of monoclonal IgM-kappa antibodies. On the other hand, lymphoma-associated CAD is associated with monoclonal IgM-lambda antibodies [2]. Cold agglutinins associated ... In primary CAD, both the cold-reactive antibodies and the IgG-kappa antibodies on circulating red cells play a role in the various hematological/immunological abnormalities [12]. However, few studies have reported cooccurrence of CAD and megaloblastic anemia. Such an association in our cases might be incidental; however, given that CAD is an autoimmune disease caused by multiple autoantibodies, it may not be a coincidence, particularly as one study reported a case Dipivefrine of CAD with pernicious anemia [8]. It is possible that the megaloblastic anemia in our cases was actually pernicious anemia, a complex disorder consisting Forskolin of hematological, gastric, and immunological alterations, as we confirmed the evidence for antibodies against intrinsic factor or gastric parietal cells in Case??1, although antibodies against the intrinsic factor are not specific pernicious anemia. Other factors such as chronic use of alcohol in Case?1 and inappropriate dietary take in Case?2 might also have played an additional role for vitamin B12 deficiency and macrocytosis. Primary CAD could also be known CX-5461 concentration to be associated with other immunological aberrations. Previous studies report cases of CAD with agammaglobulinemia or CVID [9, 14, 15]. Indeed, autoimmune manifestations are associated with CVID in about 20% to 25% of cases [16]. Case?2 may have had CVID, which may show a link with the CAD development. In terms of treatment, conventional therapies for CAD are not very effective. However, a recent study showed that rituximab is effective [17]. Case?1 achieved remission lasting more than 2 years after receiving four doses of rituximab alone; however, Case?2 declined rituximab and his disease remains active. A combination of rituximab plus alkylating agents, such as oral cyclophosphamide [18], fludarabine [19], or bendamustine [20], appears to be an effective treatment for refractory CAD cases. It is possible that the patients described herein may require such intensive therapeutic measures in the future. Conflict of Interests The authors declare that there is no conflict of interests regarding the publication of this paper.""The aim of reporting these two cases is to stimulate the large group study for defining the proper role of screening for additional thrombophilic factors in patients of JAK2 positive MPNs. Both patients were