[Breast cancer-related thrombotic microangiopathy: A review]. / Cancer du sein et microangiopathies thrombotiques paranéoplasiques.

Thrombotic Microangiopathies (TM) have been described since the 1960s. They are characterized by presence of mechanical haemolytic anemia associated with peripheral thrombocytopenia. TM in cancer can be related to several causes, whose cancer himself: cancer-related microangiopathic haemolytic anaemia (MAHA). Incidence of cancer related MAHA remains unknown. Cancer-related MAHA are mainly observed in mucin-producer adenocarcinomas, such as gastric (half of reported cases) and breast cancer. We conducted a review of all original published cases of TM reported in breast cancer, and we specifically investigated BC-MAHA cases. A Medline search identified 158 MAHA cases including 118 BC-MAHA, and 40 drug-related MAHA. Most of BC-MAHA occur in disseminated cancers, mainly with medullar involvement, and/or bone metastasis. Patients typically suffer from poor general state, bone pain, and/or dyspnea. Laboratory abnormalities such as myelemia or erythromyelemia in peripheral blood are frequently observed. Incidence of coagulation disorders is increased, compared to other MAHA causes. BC-MAHA prognosis is dramatically poor. Treatments classically used in other MAHA causes, such as plasmapheresis or immunoglobulins, are inefficient. Urgent anti-neoplastic therapy may be the only effective treatment, associated to symptomatic therapies (transfusions, blood pressure control).

Characteristics and outcome of breast cancer-related microangiopathic haemolytic anaemia: a multicentre study.

BACKGROUND: Cancer-related microangiopathic haemolytic anaemia (MAHA) is a rare but life-threatening paraneoplastic syndrome. Only single cases or small series have been reported to date. We set up a retrospective multicentre study focusing on breast cancer-related MAHA. METHODS: Main inclusion criteria were known diagnosis of breast cancer, presence of schistocytes and either low haptoglobin or cytopenia and absence of any causes of MAHA other than breast cancer, including gemcitabine- or bevacizumab-based treatment. Patient characteristics, treatments and outcome were retrieved from digital medical records. RESULTS: Individual data from 54 patients with breast cancer-related MAHA were obtained from 7 centres. Twenty-three (44%) patients had a breast tumour with lobular features, and most primary tumours were low grade (grade I/II, N = 39, 75%). ER+/HER2-, HER2+ and triple-negative phenotypes accounted for N = 33 (69%), N = 7 (15%) and N = 8 (17%) cases, respectively. All patients had stage IV cancer at the time of MAHA diagnosis. Median overall survival (OS) was 28 days (range 0-1035; Q1:10, Q3:186). Independent prognostic factors for early death (≤ 28 days) were PS > 2 (OR = 7.0 [1.6; 31.8]), elevated bilirubin (OR = 6.9 [1.1; 42.6]), haemoglobin < 8.0 g/dL (OR = 3.7 [0.9; 16.7]) and prothrombin time < 50% (OR = 9.1 [1.2; 50.0]). A score to predict early death displayed a sensitivity of 86% (95% CI [0.67; 0.96]), a specificity of 73% (95% CI [0.52; 0.88]) and an area under the curve of 0.90 (95% CI [0.83; 0.97]). CONCLUSIONS: Breast cancer-related MAHA appears to be a new feature of invasive lobular breast carcinoma. Prognostic factors and scores may guide clinical decision-making in this serious but not always fatal condition.

A comparative study between the disease characteristics in adult-onset and childhood-onset systemic lupus erythematosus in Egyptian patients attending a large university hospital.

INTRODUCTION: Disease features and laboratory abnormalities differ among adult-onset and childhood-onset systemic lupus erythematosus (aSLE and cSLE). Socioeconomic status both independent of, and in combination with, ethnicity influences the disease phenotype and outcome. OBJECTIVE: To compare the various disease features among patients with cSLE and aSLE in a limited monetary income Egyptian cohort attending a large free-of-charge university hospital. Patients and methods: Retrospective analysis of the medical records of 714 SLE patients attending Cairo University Hospitals from January 2000 to December 2019. Of them 602 (400 with aSLE and 202 with cSLE) were enrolled in the study. RESULTS: The mean age of disease onset was 28.27 ± 10.55 among aSLE patients compared to 12.88 ± 4.26 years among cSLE patients. Disease duration was 12.03 ± 5.05 and 4.14 ± 3.18 years in aSLE and cSLE, respectively. Female to male ratio was 15:1 among patients with aSLE, as compared to 2.67:1 among cSLE (<0.001). Arthritis (69%), oral ulcers (48.5%), neuropsychiatric (18.3%) and thrombotic manifestations of antiphospholipid syndrome (12%) were significantly more frequent in aSLE. On the other hand, renal (67.8%), serositis (49.6%), fever (49%), lymphopenia (40.6%), hemolytic anemia (38.6%), and discoid lupus (13.4%) were significantly more frequent in cSLE. Weight loss, malar rash, photosensitivity, thrombocytopenia, leucopenia and lymphadenopathy were not significantly different between the two groups. Hypocomplementemia, proteinuria, urinary sediments, hematuria were significantly more frequent in cSLE. For those patients with renal involvement, who underwent renal biopsy (58.3% in aSLE and 63.5% in cSLE), there was no significant difference with regard to the different histopathological classes. Anti-Smith, anti-cardiolipin antibodies and rheumatoid factor were significantly more frequent among aSLE patients, while anti-La antibodies were more frequent among cSLE patients. CONCLUSION: Arthritis was the most common clinical manifestation over time in aSLE compared to renal involvement in cSLE. Renal disease tends to be more active in cSLE. The differences in disease manifestations between this cohort and other studies can be attributed to the ethnic and socioeconomic disparities.

Autoimmune Cytopenias and Associated Conditions in CVID: a Report From the USIDNET Registry.

PURPOSE: Autoimmune cytopenia is frequently a presenting manifestation of common variable immune deficiency (CVID). Studies characterizing the CVID phenotype associated with autoimmune cytopenias have mostly been limited to large referral centers. Here, we report prevalence of autoimmune cytopenias in CVID from the USIDNET Registry and compare the demographics and clinical features of patients with and without this complication. METHODS: Investigators obtained demographic, laboratory, and clinical data on CVID patients within the USIDNET Registry. Patients were considered to have autoimmune cytopenia if they had a diagnosis of hemolytic anemia, immune thrombocytopenia (ITP), or autoimmune neutropenia. Baseline characteristics and associated complications of those with autoimmune cytopenia (+AC) and those without (-AC) were compared. RESULTS: Of 990 CVID patients included in the analysis, 10.2% (N = 101) had a diagnosis consistent with autoimmune cytopenia: ITP was diagnosed in 7.4% (N = 73), hemolytic anemia in 4.5% (N = 45), and autoimmune neutropenia in 1% (N = 10). Age at diagnosis, gender, and baseline Ig values did not differ between the +AC and -AC groups. The +AC group was significantly more likely to have one or more other CVID-associated non-infectious complications (OR = 2.9; 95%-CI: 1.9-4.6, P < 0.001), including lymphoproliferation, granulomatous disease, lymphomas, hepatic disease, interstitial lung diseases, enteropathy, and organ-specific autoimmunity. CONCLUSIONS: Autoimmune cytopenias are a common manifestation in CVID and are likely to be associated with other non-infectious CVID-related conditions. In light of prior studies showing increased morbidity and mortality in CVID patients with such complications, a diagnosis of autoimmune cytopenia may have prognostic significance in CVID.

Clinico-Haematological Features of Paroxysmal Nocturnal Haemoglobinuria.

The aim of this study was to determine the frequency of various clinico-haematological features in patients suffering from paroxysmal nocturnal haemoglobinuria (PNH). It was an observational study carried out from October 2008 - January 2016. All the patients of PNH, diagnosed on the basis of clinical and laboratory findings and confirmed by CD55 and CD59 deficiency on red cells by means of flow cytometry, were included in the study. A total of 22 patients were diagnosed which included 18 (81.8%) males and 4 (18.1%) females. Median age was 27 years. Pallor, fever, fatigability and haemoglobinuria were the most common clinical features. Pancytopenia was seen in 13 (59.09%) and hypocellular marrow was found in 14 (63.6%) patients. One patient presented with Budd Chiari syndrome.

Secondary autoimmune cytopenias in chronic lymphocytic leukemia.

Secondary autoimmune cytopenias in chronic lymphocytic leukemia are distinct clinical entities that require specific management. These autoimmune disorders have a complex pathogenesis that involves both the leukemic cells and the immune environment in which they exist. The mechanism is not the same in all cases, and to varying degrees involves the chronic lymphocytic leukemia (CLL) cells in antibody production, antigen presentation, and stimulation of T cells and bystander polyclonal B cells. Diagnosis of autoimmune cytopenias can be challenging as it is difficult to differentiate between autoimmunity and bone marrow failure due to disease progression. There is a need to distinguish these causes, as prognosis and treatment are not the same. Evidence regarding treatment of secondary autoimmune cytopenias is limited, but many effective options exist and treatment can be selected with severity of disease and patient factors in mind. With new agents to treat CLL coming into widespread clinical use, it will be important to understand how these will change the natural history and treatment of autoimmune cytopenias.

Frequency of neutropenia among Turkish and Syrian pediatric thalassemia patients under deferiprone monotherapy.

Weekly monitoring of absolute neutrophil count (ANC) under deferiprone therapy in thalassemia patients is recommended to avoid agranulocytosis adverse event. Actually, this recommendation may not be applicable in clinical setting. Our study aimed to establish incidence of neutropenia under deferiprone (DFP) monotherapy when it was monitored bimonthly due to socioeconomic conditions effecting local and refugee thalassemic patients including Syrian origin (SYR; n = 26) and Turkish origin (TR; n = 26) groups. Patients on DFP were followed up for 12 months. Fifteen neutropenic episodes were seen in 5 patients. All 5 patients (4 from SYR group and 1 from TR group) had splenomegaly and hypersplenism, and neutropenia ceased in 4 patients after splenectomy despite continuation of deferiprone. In the TR group, the frequency of patients who have neutropenia (absolute neutrophil count [ANC] <1500/mm(3)) was 3.8% (n = 1) in the 1st month, no patients in TR group had neutropenia until 10th month when again there was 1 patient with mild neutropenia. In SYR group, the frequency of patients who have neutropenia was 3.8% (n = 1), 7.7% (n = 2), and 11.5% (n = 3) in the 1st, 2nd, and 3rd months, respectively, and was found to be 3.8% (n = 1) between 6 and 12 months. Whether or not DFP therapy should be interrupted in case of mild neutropenia and the frequency of monitoring ANC in real-life conditions should be documented with further studies. Other causes of neutropenia in DFP-treated patients should also be kept in mind.

Cancer risk in East Asian patients associated with acquired haemolytic anaemia: a nationwide population-based cohort study.

BACKGROUND: This study investigated whether patients with acquired haemolytic anaemia (AHA) would have elevated cancer risk including that for non-haematological solid tumours. We further examined whether the cancer risk would be different between patients with autoimmune type AHA (AIHA) and patients of non-AIHA. METHODS: Using nationwide population-based insurance claims data of Taiwan we identified a cohort of patients with AHA with no pre-existing cancer, (n = 3902) and a comparison cohort (n = 39020) without AHA, frequency-matched by gender, age, urbanization of residency and diagnosis date. Incidence and Cox method estimated adjusted hazard ratios (aHR) of cancers controlling covariates by the end of 2010 were calculated. Risks between patients with AIHA and non-AIHA were compared. Sensitivity analysis was carried out to measure the risk of cancer between patients with and without AHA by follow-up years. RESULTS: Patients with AHA had a 90% greater incidence of cancer than controls, with an aHR of 1.78 (95% confidence interval (CI), 1.50-2.12)]. The overall aHRs of cancer for patients with AIHA and non-AIHA were 2.01 (95% CI, 1.56-2.59) and 1.87 (95% CI, 1.53-2.29), respectively, compared with the comparison cohort. The aHRs for lymphatic-haematopoietic malignancy were 19.5 and 9.59 in the AIHA and non-AIHA cohorts, respectively. No hazard of colorectal, lung, liver or breast cancer was significant. CONCLUSIONS: There is a near 2-fold elevated risk for subsequent cancer in patients with AHA, particularly for lymphatic-haematopoietic malignancy, which is much greater for patients with AIHA than non-AIHA. These findings can help clinicians decide patient-centred personalized long-term management.

Adverse event monitoring of the human papillomavirus vaccines in Scotland.

BACKGROUND: Human papillomavirus (HPV) vaccines are currently utilised globally in national immunisation programmes. While evidence from clinical trials and epidemiological studies suggest that the HPV vaccines are both effective and safe, concerns about the safety of the vaccine and scientifically unproven associations with severe adverse events following immunisation have led to dramatic decreases in vaccine uptake in Japan and acceptance issues in other countries. AIM: In Scotland, we utilised hospital admissions data to assess the impact of the HPV immunisation programme on the incidence of 60 diagnoses between 2004 and 2014 in both girls and boys; with boys acting as a comparator group. METHODS: Tabular and graphical outputs of the number of admissions, the incidence and the incidence ratio of 59 diagnoses were created to assess trends before and after the introduction of the HPV vaccine. Data linkage was utilised to investigate further the increase in Bell palsy diagnoses. RESULTS: Fifty-four diagnoses showed no change in incidence following the introduction of the national immunisation programme, and while small increases in incidence were observed for Bell palsy, coeliac disease, ovarian dysfunction, juvenile onset of type 1 diabetes, demyelinating disease and juvenile rheumatoid arthritis, none was statistically significant. CONCLUSIONS: Consistent with previous evidence, we present disaggregate data that reiterate the safety of both HPV vaccines.

C1q nephropathy and isolated CD59 deficiency manifesting as necrotizing crescentic glomerulonephritis: A rare association of two diseases.

C1q nephropathy is a recently described clinico-pathologic entity with a variable clinical presentation and pathology. Crescentic glomerulonephritis (GN) has been reported in only two patients in the available literature. CD59 deficiency, along with lack of CD55, is responsible for paroxysmal nocturnal hemoglobinuria (PNH). Few cases of isolated CD59 deficiency have been described with PNH-like features. A middle-aged adult male presented with rapidly progressive renal failure. Serological investigations were negative. A renal biopsy revealed necrotizing crescentic GN with rupture of Bowman's capsule. Immunofluorescence on the frozen sections showed dominant mesangial deposits of C1q along with IgM. Hematological work-up of the patient revealed isolated CD59 deficiency. Hence, a final diagnosis of C1q nephropathy and CD59 deficiency manifesting as crescentic GN and hemolytic anemia was made. The co-existence of two rare disorders, C1q nephropathy and CD59 deficiency, in a patient with necrotizing crescentic GN is described for the first time to the best of our knowledge. The pathogenetic link of these two entities with the clinical manifestation requires further study.

Pediatric systemic lupus erythematosus in a single nephrology unit.

Clinical manifestations of systemic lupus erythematosus (SLE) are widely variable, and its course is unpredictable. SLE that begins in childhood has been considered more severe than SLE with onset during adulthood. Our aim was to determine the presentation and the outcome of SLE of 26 children (20 females and 6 males, with a female to male ratio of 3.8:1) with SLE in our center, their ages ranging from 5 - 18 years and followed from 2005 till October 2011. They were diagnosed according to the American Rheumatism Association's revised criteria. Complete blood count, erythrocyte sedimentation rate, C3, urine analysis, 24-h urinary protein, antinuclear antibodies, anti-ds DNA and renal biopsy were obtained for the patients. We found that the most extra-renal manifestation of SLE was fever (57.7%), while lupus nephritis (LN) was the most commonly affected organ (50%). Hemolytic anemia was the most common hematological abnormality (80.8%), while immunological characteristics were positive in all the patients. Remission in patients without LN was more than 5.3-times the remission in LN patients. The outcome of the patients without LN was better than the patients with LN.

Síndrome hemolítico urémico en niños en los últimos 10 años en el hospital Gustavo Fricke / Hemolytic Uremic Syndrome in Children in the last 10 years at hospital Gustavo Fricke

El síndrome hemolítico urémico se caracteriza por la presencia de anemia hemolítica microangiopática, trombocitopenia e injuria renal aguda. Es una de las causas más frecuentes de falla renal aguda en pacientes pediátricos. Objetivo: Conocer las características clínicas y la evolución de los pacientes con SHU hospitalizados en nuestro hospital. Material y Método: Se revisaron 55 historias clínicas de los pacientes egresados con el diagnostico de SHU en el Hospital Dr. Gustavo Fricke entre el año 2001 y 2011 y se extrajo la información más relevante sobre la presentación clínica y la evolución de esta enfermedad durante la hospitalización. Resultados: 4 pacientes fallecieron (5,7 por ciento). Un 62 por ciento presentó una diarrea aguda disentérica; 30,9 por ciento hipertensión arterial y 11 por ciento convulsiones. Un 84 por ciento fue transfundido con glóbulos rojos, 45 por ciento requirió terapia de sustitución renal. La duración de la hospitalización fue de 14 días en promedio. Al año solo un 66 por ciento permanecían en control médico. Conclusiones: El SHU continúa siendo una de las causas más frecuentes de injuria renal aguda con requerimiento de diálisis en nuestro hospital. La mayoría de los pacientes sufre anemias severas con necesidad de trasfusión de glóbulos rojos. La mortalidad es similar a la reportada en otros centros...

Hemolytic Uremic Syndrome (HUS) is characterized by the presence of hemolytic microangiopathic anemia, thrombocytopenia and acute renal failure. Is one of the most frequent causes of acute renal failure in pediatric patients. Objective: Know clinical characteristics and evolution of patients with HUS hospitalized at Hospital Dr. Gustavo Fricke. Material and Methods: 55 medical records of discharged patients with the diagnosis of HUS in Dr. Gustavo Fricke Hospital between 2001 and 2011 were reviewed. We extracted the most relevant information on clinical presentation and evolution of this disease during hospitalization. Results: 4 patients died (5.7 percent). 62 percent presented an acute dysenteric diarrhea; 30.9 percent evolved with hypertension and 11 percent presented seizures. 84 percent were transfused with red blood cells, 45 percent required renal replacement therapy. The hospital stay was 14 days on average. After one year, only 66 percent remained in medical control. Conclusions: HUS remains one of the most frequent causes of acute kidney injury who required dialysis at our hospital. Most patients have severe anemia requiring transfusion of RBCs. Mortality is similar to that reported in other centers...

Record fragmentation due to transfusion at multiple health care facilities: a risk factor for delayed hemolytic transfusion reactions.

BACKGROUND: Patients transfused at more than one health care facility face safety risks, because their transfusion record is fragmented. Blood group antibodies documented at one facility may be unknown to others. Because many antibodies are evanescent, access to prior antibody records is important for preventing incompatible transfusions and delayed hemolytic reactions. The study goal was to quantify multisite transfusion activity and its impact on antibody record accuracy. STUDY DESIGN AND METHODS: Patients (n = 100) undergoing hospital transfusion testing were surveyed to determine the locations and dates of any prior transfusions. Also, transfusion records were examined to determine whether patients (n = 200) known to be alloimmunized at one hospital had antibody testing done at another nearby hospital and, if so, how often the results were discrepant. RESULTS: Twenty-three percent (23/100) of patients undergoing type-and-screen testing reported receiving transfusions at 24 other facilities. Locations of transfusions that occurred elsewhere were 54.2% (13/24) at eight other in-state hospitals, 12.5% in bordering states, 20.8% in more distant states, and 12.5% during military service. Twenty-one percent (42/200) of patients known to be alloimmunized at one hospital had antibody test results on record at another nearby hospital. Antibody discrepancies were noted in 64.3% (27/42) of cases. The most common discrepancy was the failure of one facility to detect an antibody. CONCLUSION: Multisite transfusions were common. For patients seen at both of two nearby hospitals, antibody records were frequently discrepant. The findings support the need for interfacility sharing of transfusion records, particularly at the regional level.

Updated clinical classification of pulmonary hypertension.

In 1998, a clinical classification of pulmonary hypertension (PH) was established, categorizing PH into groups which share similar pathological and hemodynamic characteristics and therapeutic approaches. During the 5th World Symposium held in Nice, France, in 2013, the consensus was reached to maintain the general scheme of previous clinical classifications. However, modifications and updates especially for Group 1 patients (pulmonary arterial hypertension [PAH]) were proposed. The main change was to withdraw persistent pulmonary hypertension of the newborn (PPHN) from Group 1 because this entity carries more differences than similarities with other PAH subgroups. In the current classification, PPHN is now designated number 1. Pulmonary hypertension associated with chronic hemolytic anemia has been moved from Group 1 PAH to Group 5, unclear/multifactorial mechanism. In addition, it was decided to add specific items related to pediatric pulmonary hypertension in order to create a comprehensive, common classification for both adults and children. Therefore, congenital or acquired left-heart inflow/outflow obstructive lesions and congenital cardiomyopathies have been added to Group 2, and segmental pulmonary hypertension has been added to Group 5. Last, there were no changes for Groups 2, 3, and 4.

Incidence and pattern of hemolytic anemia after minor ABO-mismatched living-donor lobar lung transplantation.

PURPOSE: Living-donor lobar lung transplantation (LDLLT) has been successfully performed in Japan. In LDLLT, the recipient usually receives one lower lobe from each of two donors; however, finding two ABO-matched donors is often difficult. Solid organ transplants from donors with minor ABO-mismatches can be complicated by hemolysis. We investigated the incidence of de novo anti-ABO antibody production and hemolysis in patients receiving LDLLT across minor ABO-mismatches. METHODS: We evaluated 23 patients who underwent LDLLT between June 2008 and December 2011, including 11 patients who underwent minor ABO-mismatched transplantation. We measured the anti-A/B antibody serum titers, hemoglobin concentrations and indirect bilirubin levels. RESULTS: None of the patients showed any clinical signs of hemolytic anemia (mean follow-up period; 16 months). Two of the 11 patients (18 %) receiving minor ABO-mismatched LDLLTs showed a small amount of de novo anti-B antibodies for a transient period. These patients showed gradual progression of anemia, and weak de novo anti-A/B antibodies were detected with column agglutination technology. The patients received only 2 U of washed type O red blood cells; thereafter, the hemolytic anemia did not develop further in either case. CONCLUSION: LDLLT across minor ABO-mismatches results in the transient appearance of weak de novo anti-A/B antibodies with a low incidence; thus, this procedure can be a safe treatment.

[Risk of development of clinical and pathogenetic features of anemia on the background of basic therapy of inflammatory bowel disease].

Anemia in IBD is the result of a combination of iron deficiency and anemia of chronic disease. Therapy of IBD is relief of inflammation, but the drugs usage may cause the development hemolytic anemia and myelodysplastic syndrome. We studied the effect of basic therapy on the incidence of anemia and assess the impact of modern biological therapies on the main markers of AHZ. A total of 153 patients with ulcerative colitis (UC) and 53 patients with Crohn's disease (CD), which at the time of the study received basic anti-inflammatory therapy for at least 1 year. All patients underwent blood tests, iron metabolism parameters were determined by the level of erythropoietin and G-gepsidina C reactive protein. Modern biological therapy increases the effectiveness of the treatment of anemia in patients with IBD. The use of Remicade gives a quick positive response, which is due to the decrease of gepsidin negative influence on iron metabolism and unlocking the synthesis of erythropoietin. The use of MSCs does not inhibit the synthesis of erythropoietin, and is likely to stimulate erythropoiesis at the erythroblast precursors.

Antibiotic hypersensitivity in CF: drug-induced life-threatening hemolytic anemia in a pediatric patient.

Adverse reactions to antibiotics in patients with cystic fibrosis (CF) are a growing concern. We report the case of a pediatric patient with CF with multiple comorbidities and a history of drug reactions, who developed life-threatening piperacillin-induced immune hemolytic anemia. We review drug-induced hemolytic anemia (DIIHA) in particular, and antibiotic hypersensitivity in CF in general, including the frequency, pathogenesis, and risk factors. Finally, we discuss the treatment options and propose an algorithm for the management of drug-induced hypersensitivity reactions in patients with CF.

Prevalence and significance of G6PD deficiency in patients of an urban HIV clinic.

The rationale to screen for glucose-6-phosphate dehydrogenase (G6PD) deficiency in HIV-infected individuals is their increased likelihood to receive oxidant drugs and subsequent potential of hemolytic events. However, current guidelines regarding who should be screened are conflicting. The authors examined the prevalence of G6PD deficiency and the frequency of hemolytic events in an urban HIV clinic. They used data from a military database as a comparison. In both cohorts, a relatively high number of black females were found to be G6PD deficient (10% and 13%), which was similar to the rate in men (15% and 12%). No white females were G6PD deficient. The authors identified 8 drug-related hemolytic events in HIV clinic patients. Two patients necessitated blood transfusions; both were triggered by trimethoprim/sulfamethoxazole (TMP/SMX). Although G6PD screening prior to the use of TMP/SMX is not often considered by clinicians, the authors' finding of 2 hemolytic events requiring transfusion suggests this would be beneficial.

[Prevalence of anemia in Japan].

The frequency of anemia in Japan is statistically higher than that of foreign countries. Especially, Japanese females frequently fall ill with iron deficiency anemia(IDA) because of decreased intake of iron. Secondary anemia is of the second-highest frequency. While primary hematological disorders account for only a small fraction of whole anemic patients, aplastic anemia is relatively frequent in the world-wide statistics. The frequency of myelodysplastic syndromes is now increasing with aging of the population. It is important to sustain our effort in assembling the data as to the prevalence of anemia.

The prognostic significance of a positive direct antiglobulin test in chronic lymphocytic leukemia: a beneficial effect of the combination of fludarabine and cyclophosphamide on the incidence of hemolytic anemia.

Autoimmune hemolytic anemia (AHA) is a common complication in chronic lymphocytic leukemia (CLL). The UK LRF CLL4 trial is the largest prospective trial in CLL to examine the prognostic impact of both a positive direct antiglobulin test (DAT) and AHA. Seven-hundred seventy-seven patients were randomized to receive chlorambucil or fludarabine, alone or with cyclophosphamide (FC). The incidence pretreatment of a positive DAT was 14%. Ten percent developed AHA. The DAT correctly predicted the development, or not, of AHA after therapy in 83% of cases, however only 28% of DAT-positive patients developed AHA. Of 299 patients tested both before and after treatment, those treated with single-agent fludarabine were most likely to remain DAT positive and to change from negative to positive. Patients treated with chlorambucil or fludarabine were more than twice as likely to develop AHA as those receiving FC. In a multivariate analysis, stage C disease and high beta2 microglobulin were independent predictors of a positive DAT result. AHA, or a positive DAT, with or without AHA, independently predicted for reduced overall survival (OS). Four deaths, all on fludarabine monotherapy, were attributed to AHA. In conclusion, DAT status at the time of initiation of therapy provides a new prognostic indicator, although FC may protect against AHA. This trial was registered at http://isrctn.org as no. 58585610.