The concentrations of complement proteins C3 and C4 should be determined, but normal levels do not exclude CAD.[4], [6], [31] and [39] Confirming DAPT the presence

of a clonal lymphoproliferative disorder has potential therapeutic consequences, even though negative findings may be a matter of sensitivity and do not exclude primary CAD.[6] and [31] Capillary electrophoresis or agarose electrophoresis with immunofixation should always be performed. If no monoclonal band can be detected on electrophoresis, immunofixation should still be done. A trephine biopsy should be examined by an experienced lymphoma pathologist, and we also recommend flow cytometric immunophenotyping of bone marrow lymphocytes.[8] and [9] History and clinical examination, supplemented by

radiological imaging as required, will usually be sufficient to exclude cases of secondary chronic CAS described below. The diagnostic criteria for primary CAD are summarized in Table 3.[6] and [31]Fig. 2 shows a diagnostic algorithm. Importantly, in order to achieve sufficient sensitivity, serum for immunoglobulin analyses and CA titration must be obtained from blood specimens kept at 37–38 °C from sampling until serum has been removed from the clot. After primary CAD was shown to be a clonal lymphoproliferative disease, there has been some confusion in the literature regarding the terms ‘secondary’ versus ‘primary’. Patients with chronic CAD recognized by us and others as having a clonal B-cell disorder, most Fulvestrant nmr often non-progressive and clinically non-malignant, undoubtedly represent the same majority that has traditionally been diagnosed with primary or idiopathic CAD.[1], [6], [8] and [36] In these patients, the disease should still be called primary CAD. The term ‘secondary’

chronic CAS should be reserved for those patients Glutamate dehydrogenase in whom the cold-antibody mediated hemolytic anemia complicates an overt and well-defined malignant disease different from LPL and MZL.[1], [6], [31], [42], [47] and [48] Among 295 consecutive individuals with AIHA described by Dacie, 7 patients (2.4%) were classified as having CAS secondary to malignant disease.1 In the very large series of AIHA by Sokol’s group, the frequency seemed higher.2 CAS has been described in patients diagnosed with diffuse large B-cell lymphoma, Hodgkin’s lymphoma, carcinomas, sarcomas, metastatic melanoma and chronic myeloproliferative disorders.[1], [2], [12], [13], [47], [48], [49] and [50] For the following reasons, however, both the reported frequencies and some of the assumed associations should be regarded uncertain. First, particularly in case reports, patients may simply have suffered from two independent diseases; cancer and primary CAD. Second, sufficient details have often not been provided to critically review the diagnosis of the co-existing or underlying malignancy.