Primary immune thrombocytopenia (ITP) in childhood, typically presents as an acute self-limiting illness. However, secondary ITP is often a chronic disorder due to an underlying disease. Combined cytopenias in childhood, that is, secondary ITP occurring with auto-immune hemolytic anemia and/or auto-immune neutropenia, are often associated with disorders characterized by immune dysregulation. Such disorders include systemic lupus erythematosus, auto-immune lymphoproliferative syndrome, and common variable immune deficiency. Evans syndrome describes the combination of ITP, autoimmune hemolytic anemia, and/or autoimmune neutropenia. However, it is now clear that some patients with Evans syndrome have an underlying immunodeficiency. This report focuses on combined auto-immune cytopenias and highlights the challenges in their diagnosis and management.

To assess the efficacy and safety of monoclonal antibody rituximab combined with cyclophosphamide (CTX) in the treatment of refractory and recurrent autoimmune hemolytic anemia.Seven cases with refractory and recurrent autoimmune hemolytic anemia (including 1 case of Evans syndrome) were recruited during January, 2007 to December, 2010. Treatment regimens were as follows: rituximab: 375 mg/m², 1 time/week, 2-6 courses; CTX:1 g, 1/10 d, 2-7 courses; combined with intravenous immunoglobulin (IVIG) 5 g, 1 time/week, given 1 day after rituximab administration. The efficacy and safety of this regimen were assessed during follow-up.All the patients showed good responses (7/7). Six patients achieved complete remission (6/7) and one achieved partial remission (1/7). Average follow-up time for the patients was 27 months. All patients remained in remission during the 12-month follow-up visits. Two patients showed elevated indirect bilirubin and increased reticulocyte counts within 24 months. One patient achieved complete remission after additional rituximab therapy, and another patient remained partial remission after cyclosporine therapy. At the time of 36-month follow-up visit, the patient relapsed and was retreated with 3 courses of rituximab combined with CTX and eventually achieved partial remission. All patients tolerated the treatment well with few mild side effects.Rituximab combined with CTX is effective and relatively safe in patients with refractory and recurrent autoimmune hemolytic anemia. Additional treatment to relapse patients about 12 - 24 months after drug withdrawal continues to be effective.

Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia, classified into primary and secondary types. Secondary CAD accompanies infection or malignant disease, most often lymphoma, whereas primary CAD frequently represents a lymphoproliferative bone marrow disorder characterized by clonal expansion of B cells. Here, I describe a case of lymphoplasmacytic lymphoma (LPL) developed 6 years after amelioration of primary CAD by rituximab monotherapy. A 54-year-old Japanese woman was diagnosed with primary CAD characterized by a small fraction of B lymphocytes and kappa laterality in the peripheral blood. M-protein was not detected by immuno-electrophoresis. The patient achieved remission following two courses of rituximab monotherapy. The level of IgM was specifically decreased, although levels of IgG and IgA were slightly increased. Six years after rituximab monotherapy, she developed LPL without CAD recurrence. Flow cytometry performed on bone marrow specimens revealed that lymphoma cells were positive for CD19 and CD20 with kappa laterality. The lymphoma may have transformed from clonal B lymphocytes at presentation of CAD. Rituximab monotherapy induced remission of CAD by specific decrease of IgM level, but did not eliminate the clonal B lymphocytes that may have progressed to LPL. This experience may provide clues toward the understanding of the pathophysiology of primary CAD with clonal lymphoproliferative disease of the bone marrow.

Oxaliplatin in combination with a fluoropyrimide is a treatment option for colorectal cancer patients in the adjuvant and metastatic settings. Very few hematological emergencies have been reported associated with Oxaliplatin. These include autoimmune hemolytic anemia, thrombocytopenia and pancytopenia. We present a case report of a patient who developed hematuria and disseminated intravascular coagulation while receiving the second cycle of FOLFOX and bevacizumab for metastatic colon cancer.

Direct antiglobulin test (DAT) is a test that shows antibodies bound to the surface antigens of erythrocytes. In this article, our aim was to investigate whether a correlation exists between a DAT positive test and serum immunoglobulin (Ig) levels. In our clinic, all DAT positive patients were retrospectively studied. Patients who had not received a blood transfusion within the last three months and who were evaluated for Ig levels were enrolled in the study (n = 15). Of these subjects, 15 showed a DAT positive result. Ten patients did not show any clinical or laboratory signs of hemolysis, while five patients exhibited signs and symptoms of autoimmune hemolytic anemia (AIHA). While all subjects showed a DAT positive test result (Ig G ± C(3)), four patients without AIHA, and three patients with AIHA showed a positive indirect antiglobulin test (IAT). In patients with a higher level of immunoglobulin G (IgG), the treatment of the concomitant disease resulted in normalization of the IgG level and led to a negative DAT test. The conditions that lead to an elevation of Ig should be reviewed in patients who displayed a DAT positive test without hemolysis and who had not previously received a blood transfusion.

A 61-year-old woman with aplastic anemia was admitted to our hospital in October 2009 because of fever and abdominal pain. She had been treated with cyclosporin A without showing any effect. On admission, uterine cancer was diagnosed and the left uterine appendages were swollen. She was treated with cefepime for febrile neutropenia without effect, and left-sided adnexitis was diagnosed. After cefepime was changed to meropenem, marked plasmacytosis was observed in the peripheral blood (23%) and bone marrow (79%) with the appearance of skin eruption. Although the plasma cells were morphologically abnormal, the cytoplasmic immunoglobulin light chain deviation was not detected by flow cytometric analysis, and M protein was not found by serum immunoelectrophoresis. She was diagnosed with reactive plasmacytosis and treated with dexamethasone. The drug eruption and plasmacytosis improved soon after starting the treatment. Although reactive plasmacytosis is observed with a variety of conditions, including infection, neoplasms, autoimmune disorders, and hemolytic anemia, it has not been reported to accompany drug eruption. Reactive plasmacytosis is sometimes not possible to distinguish from plasma cell neoplasms on morphology alone and needs to be diagnosed comprehensively by using flow cytometric analysis and immunohistochemical evaluation.

Chronic lymphocytic leukemia (CLL) is frequently complicated during its course by autoimmune disorders (from 2 to 12% of cases), such as autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP). In particular, ITP has been reported in about 2–5% of CLL population. Recently, Cuker et al. reported the occurrence of ITP in 6/216 patients with relapsing-remitting multiple sclerosis in a phase 2 clinical trial of annual alemtuzumab. Alemtuzumab is an anti-CD52 monoclonal antibody used in CLL both as first-line treatment and in relapsed/refractory patients. We evaluated a cohort of 64 consecutive patients affected by relapsed-refractory CLL treated with low-dose alemtuzumab and we observed a incidence of ITP higher than predicted. Our data, associated with the report of Cuker et al., seem to suggest an important role of alemtuzumab in the pathogenesis of ITP which could be related to its induced dysregulation of T-lymphocyte activity.

Hyperchromasia of the red blood cells (RBC), defined as an elevation of the hyperchromic subpopulation, has been described for various medical conditions. However, neither the association of hyperchromasia with an altered RBC membrane nor with other medical conditions has been investigated in a systematic way so far. Since the percentage of hyperchromic RBC is measured on a routine basis by many hematologic laboratories, we evaluated the predictive value of this parameter for the detection of RBC disorders. An extensive workup of all patients undergoing standard hematogram during a period of 6 months at our institution with a fraction of hyperchromic RBC larger than 10 % was collected by reviewing the medical history and performing osmotic gradient ektacytometry on RBC from a part of these patients. Thirty-two thousand two hundred twenty-six individuals were screened; of which, 162 (0.5 %) showed more than 10 % hyperchromic RBC. All of the patients examined by ektacytometry featured abnormal membrane deformability. Hereditary spherocytosis was found in 19 out of these 32 patients, in most cases unknown to the patient and currently asymptomatic. Another 17.9 % of the patients with an elevated subpopulation of hyperchromic RBC suffered from viral infection (human immunodeficiency virus, hepatitis). Our study shows that an elevated proportion of hyperchromic erythrocytes larger than 10 % is associated with both hereditary and acquired RBC membrane disorders and further follow-up should be considered.