Key Points• Mixed, atypical, and warm immunoglobulin G plus C AIHA (;30% of cases) more frequently have a severe onset (Hb #6 g/dL) and require multiple therapy lines.• Infections, particularly after splenectomy, acute renal failure, Evans syndrome, and multitreatment, were predictors of fatal outcome.The clinical outcome, response to treatment, and occurrence of acute complications were retrospectively investigated in 308 primary autoimmune hemolytic anemia (AIHA) cases and correlated with serological characteristics and severity of anemia at onset. Patients had been followed up for a median of 33 months (range 12-372); 60% were warm AIHA, 27% cold hemagglutinin disease, 8% mixed, and 5% atypical (mostly direct antiglobulin test negative). The latter 2 categories more frequently showed a severe onset (hemoglobin [Hb] levels £6 g/dL) along with reticulocytopenia. The majority of warm AIHA patients received first-line steroid therapy only, whereas patients with mixed and atypical forms were more frequently treated with 2 or more therapy lines, including splenectomy, immunosuppressants, and rituximab. The cumulative incidence of relapse was increased in more severe cases (hazard ratio 3.08; 95% confidence interval, 1.44-6.57 for Hb £6 g/dL; P < .001). Thrombotic events were associated with Hb levels £6 g/dL at onset, intravascular hemolysis, and previous splenectomy. Predictors of a fatal outcome were severe infections, particularly in splenectomized cases, acute renal failure, Evans syndrome, and multitreatment (4 or more lines). The identification of severe and potentially fatal AIHA in a largely heterogeneous disease requires particular experienced attention by clinicians. (Blood. 2014;

In paroxysmal nocturnal hemoglobinuria (PNH) hemolytic anemia is due mainly to deficiency of the complement regulator CD59 on the surface of red blood cells (RBCs). Eculizumab, an antibody that targets complement fraction 5 (C5), has proven highly effective in abolishing complement-mediated intravascular hemolysis in PNH; however, the hematologic benefit varies considerably among patients. In the aim to understand the basis for this variable response, we have IntroductionParoxysmal nocturnal hemoglobinuria (PNH) is a hematologic disorder characterized by the clonal expansion of one or a few hematopoietic stem cells that are incapable of glycosylphosphatidylinositol (GPI)-anchor biosynthesis, due to an acquired somatic mutation in the phosphatidylinositol glycan class A (PIG-A) gene. [1][2][3][4][5][6] Affected progeny cells are deficient in all GPI-anchored surface proteins, including the complement regulators CD55 and CD59. 7-9 Thus, PNH red blood cells (RBCs) are exquisitely vulnerable to activated complement, and particularly to the membrane attack complex (MAC), 10,11 resulting in chronic intravascular hemolysis with recurrent exacerbations, and consequent anemia.Eculizumab (Soliris; Alexion Pharmaceuticals, Cheshire, CT) is a humanized monoclonal antibody against complement fraction 5 (C5), which inhibits MAC formation. 12 Eculizumab has proven highly beneficial in the treatment of transfusion-dependent PNH patients. [13][14][15] In a placebo-controlled phase 3 trial, eculizumab led to a marked decrease in transfusion requirement, and improvement in anemia, fatigue, pain, shortness of breath, and QoL measures. 15 These data were confirmed in 2 subsequent studies, 16,17 the last one also suggesting that eculizumab may reduce the occurrence of thromboembolic events. 17 In the face of such gratifying clinical results, it is clear that not all patients respond equally to the treatment. In some patients there is only little improvement of anemia, and some still require blood transfusion at times, with signs of persistent hemolysis (reticulocytosis, elevated unconjugated bilirubin). 15,16 In this work, we have investigated the notion that in patients with suboptimal hematologic response to eculizumab there may be extravascular hemolysis mediated by complement effector mechanisms other than MAC. 15 Based on flow cytometry analysis of complement fraction 3 (C3) on RBCs, we provide evidence of selective C3 opsonization of GPI-negative red cells, the extent of which tends to correlate with the clinical response to eculizumab, and may be the manifestation of a novel phenomenon in the pathophysiology of PNH. Methods PatientsThe study was conducted in 56 Italian PNH patients (Table 1); biologic samples were collected by venipuncture according to standard procedures, after informed consent was obtained in accordance with the Declaration of Helsinki as approved within the study protocol by the Institutional Review Board at the Federico II University of Naples. Twenty-eight patients were studied at diagnosis, before any t...

SummaryThe myelodysplastic syndromes (MDS) are clonal disorders characterised by ineffective haematopoiesis with high risk of leukaemia progression. The relevance of immune-dysregulation for emergence, dominance and progression of dysplastic clones has been suggested, but valuable criteria to obtain insight into these connections are lacking. This study showed significant increase of CD8 lymphocytes and mature B cells in the bone marrow (BM) compared to peripheral blood (PB) of low risk MDS patients. Different BM levels of Regulatory T cells (Treg) identified two sub-groups in these patients; only the sub-group with lower Treg percentage showed BM recruitment of CD8 lymphocytes. Different levels of CD54 on BM CD8 cells revealed two sub-groups of Intermediate-1 (Int-1) patients. The sub-group with higher CD54 expression on BM CD8 showed high levels of this molecule also on CD4 cells. BM recruitment of CD8 lymphocytes in the low risk group and/or the presence of high CD54 expression on BM CD8 in Int-1 patients were associated with more pronounced dyserythropoiesis and erythropoietin treatment. Our data shed light on the involvement of immune-mediated mechanisms in Low and Int-1 risk MDS patients and suggest that BM versus PB levels of immune effectors could represent useful criteria for a more homogeneous grouping of MDS patients.

Background/objectives:Anemia, leukopenia and, although less frequently, thrombocytopenia are possible hematological complications of anorexia nervosa considered strictly secondary to chronic malnutrition. This is a retrospective study on the prevalence of these disorders in a large cohort of 318 female patients with AN (20.4±5.6 years, body mass index (BMI) 15.9±1.6 kg/m2), recruited in the Outpatient Unit for Malnutrition secondary to Eating Disorders at the Department of Clinical Medicine and Surgery, Federico II University Hospital, since February 1991 to December 2012.Subjects/methods:Patients were studied on an outpatient basis after obtaining medical history, clinical examination, routine hematobiochemical and endocrine tests, electrocardiography, psychiatric interview and bioelectrical impedance analysis and, in particular, phase angle determination. All patients with other comorbidities, in particular with mean corpuscular volume <80 fl, were excluded for suspected genetic alteration in the synthesis of hemoglobin.Results:Hematologic data showed that 16.7% of patients had anemia, 7.9% neutropenia and 8.9% thrombocytopenia. These abnormalities were strictly related to the duration of illness (P=0.028), and to protein energy malnutrition, in particular, BMI and phase angle (P<0.001).Conclusions:Our study offers description of the incidence of hematologic defects in a selected and large sample of AN female patients, suggesting that its incidence is related to the degree and duration of protein energy malnutrition.

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