[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).

Intractable mechanical hemolytic anemia complicating mitral valve surgery: a case series study.

BACKGROUND: Intractable, mechanical hemolytic anemia (IMHA) is a rare catastrophic complication following mitral valve surgery. We analyzed patient characteristics and IMHA management by reoperations after mitral valve surgery. METHODS: We collected medical records from mitral valve patients requiring reoperation due to IMHA. INCLUSION CRITERIA: hemoglobin < 100 g/L; positive hemolysis tests and echocardiography results; and exclusion of other hemolysis causes. RESULTS: Data from 25 IMHA cases included 10 (40%) early onset (1.3 (0.3,3.0) months) and 15 (60%) late onset (120 (24,204) months) cases. Early IMHA etiologies included surgical defects (6, 60%), uncontrolled infection (3, 30%) and Bechet's disease (1, 10%). Late IMHA etiologies included degeneration (13, 87%), new infection (1, 7%) and trauma (1, 7%). There were more mechanical valves (15, 88%) than bio-valves (2, 12%); the main valvular dysfunction was paravalvular leak (16, 64%). IMHA manifestations included jaundice (18, 72%), dark urine (21, 84%), heart failure (16, 64%), acute kidney injury (11, 44%), hepatomegaly (15, 60%), splenomegaly (15, 60%) and pancreatitis (1, 4%). Laboratory results showed decreased hemoglobin (70 ± 14 g/L) and increased bilirubin (72 ± 57 µmol/L), lactate dehydrogenase (2607 ± 2142 IU/L) and creatinine (136 ± 101 µmol/L) levels. Creatinine level negatively correlated with hemoglobin level (B = -3.33, S.E. B = 1.31, Exp(B) = 368.15, P = 0.018). Preoperative medications included iron supplements (20, 80%), erythropoietin (16, 64%) and beta-blocker (22, 88%). Two patients died of cardiac causes before reoperation. The other 23 underwent reoperation with long surgical times (aortic cross clamp 124 ± 50 min, cardiopulmonary bypass 182 ± 69 min) and blood transfusions (red blood cells 6 (6, 8) units, plasma 600 (400,800) ml, platelet 1(0,2) units). Postoperative complications included cardiac dysfunction (5, 22%), arrhythmia (10, 43%), sepsis (6, 26%), pulmonary infection (5, 22%), gastrointestinal bleeding (3, 13%), cerebral hemorrhage (2, 9%), chronic renal dysfunction (1, 4%) and surgical hemorrhage (1, 4%). Five (33%) patients died after reoperation from cardiac dysfunction (3, 60%), septic shock (1, 20%) and self-discharge (1, 20%). CONCLUSIONS: IMHA induces severe multi-organ dysfunction, contributing to high mortality. Perioperative management should focus on etiological treatment, organ protection, and blood management.

Retrospective study of canine infectious haemolytic anaemia cases reveals the importance of molecular investigation in accurate postmortal diagnostic protocols.

Infectious haemolytic anaemia (IHA) in dogs share similar clinical signs including fever, lethargy, icterus, paleness of mucous membranes and splenomegaly. Postmortal findings are similar and, without additional diagnostic methods, an accurate aetiological diagnosis is difficult to achieve. In order to investigate causes of lethal IHA in Croatian dogs, we performed a retrospective study on archived formalin-fixed, paraffin-embedded tissue blocks (FFPEB) from dogs that died due to haemolytic crisis, using microscopic and molecular diagnostic tools to determine the aetiological cause of disease. Molecular analysis was performed on kidney, lung, myocardium and spleen on FFPEB from all dogs. The originally stated aetiological diagnosis of B. canis or leptospirosis was confirmed in only 53% of the dogs. PCR and sequencing revealed that, in addition to the expected pathogens, B. canis and Leptospira interrogans, the presence of previously undiagnosed "new" pathogens causing anaemia including Candidatus Neoehrlichia mikurensis and Anaplasma phagocytophilum. Furthermore, Theileria capreoli was detected for the first time in a dog with postmortal descriptions of lesions. Intensive extravascular hemolysis was noticeable as jaundice of the mucosa, subcutis and fat tissue, green or yellow discoloration of renal parenchyma caused by bilirubin excretion in the renal tubules and bile accumulation within the liver in 90% of the dogs. This work highlights the value of molecular diagnostics to complement traditional ante-mortem and post-mortem diagnostic protocols for the aetiological diagnosis of pathogens associated with IHA.

Catastrophic antiphospholipid syndrome: an update.

Catastrophic antiphospholipid syndrome (CAPS) is a rare variant that accounts for 1% of patients with APS. Despite its low frequency, the mortality-related is very high ranging from 50% of patients in the first series to 37% in the most recent data. The current knowledge of this potential devastating entity comes from the International Registry of patients with CAPS, named CAPS Registry. Small vessel thrombosis, laboratory features of microangiopathic haemolytic anemia, and development of multisystem involvement in a very short period of time are the main characteristics of this syndrome. Clinical manifestations are due to thrombosis but also, although the evidences are indirect, to excess of proinflammatory cytokines. Therefore, treatment strategy is based on the combination of anticoagulation, glucocorticoids, plasma exchange and/or intravenous immunoglobulins, the so-called triple therapy. In refractory cases or in those with initial life-threatening situation, rituximab may be an effective option. Recently, some cases of CAPS have been effectively treated with the addition of eculizumab to the triple therapy.

Active haematological manifestations of systemic lupus erythematosus lupus are associated with a high rate of in-hospital mortality.

The aim of this study was to estimate the impact of the haematological manifestations of systemic lupus erythematosus (SLE) on mortality in hospitalized patients. For that purpose a case-control study of hospitalized patients in a medical referral centre from January 2009 to December 2014 was performed. For analysis, patients hospitalized for any haematological activity of SLE ( n = 103) were compared with patients hospitalized for other manifestations of SLE activity or complications of treatment ( n = 206). Taking as a variable outcome hospital death, an analysis of potential associated factors was performed. The most common haematological manifestation was thrombocytopenia (63.1%), followed by haemolytic anaemia (30%) and neutropenia (25.2%). In the group of haematological manifestations, 17 (16.5%) deaths were observed compared to 10 (4.8%) deaths in the control group ( P < 0.001). The causes of death were similar in both groups. In the analysis of the variables, it was found that only haematological manifestations were associated with intra-hospital death (odds ratio 3.87, 95% confidence interval 1.8-88, P < 0.001). Our study suggests that apparently any manifestation of haematological activity of SLE is associated with poor prognosis and contributes to increased hospital mortality.

Delayed-onset hemolytic anemia in patients with travel-associated severe malaria treated with artesunate, France, 2011-2013.

Artesunate is the most effective treatment for severe malaria. However, delayed-onset hemolytic anemia has been observed in ≈20% of travelers who receive artesunate, ≈60% of whom require transfusion. This finding could discourage physicians from using artesunate. We prospectively evaluated a cohort of 123 patients in France who had severe imported malaria that was treated with artesunate; our evaluation focused on outcome, adverse events, and postartesunate delayed-onset hemolysis (PADH). Of the 123 patients, 6 (5%) died. Overall, 97 adverse events occurred. Among the 78 patients who received follow-up for >8 days after treatment initiation, 76 (97%) had anemia, and 21 (27%) of the 78 cases were recorded as PADH. The median drop in hemoglobin levels was 1.3 g/dL; 15% of patients with PADH had hemoglobin levels of <7 g/dL, and 1 required transfusion. Despite the high incidence of PADH, the resulting anemia remained mild in 85% of cases. This reassuring result confirms the safety and therapeutic benefit of artesunate.

Delayed anemia after treatment with injectable artesunate in the Democratic Republic of the Congo: a manageable issue.

Cases of delayed hemolytic anemia have been described after treatment with injectable artesunate, the current World Health Organization (WHO)-recommended first-line drug for the treatment of severe malaria. A total of 350 patients (215 [61.4%] < 5 years of age and 135 [38.6%] ≥ 5 years of age) were followed-up after treatment with injectable artesunate for severe malaria in hospitals and health centers of the Democratic Republic of the Congo. Complete series of hemoglobin (Hb) measurements were available for 201 patients. A decrease in Hb levels between 2 and 5 g/dL was detected in 23 (11.4%) patients during the follow-up period. For five patients, Hb levels decreased below 5 g/dL during at least one follow-up visit. All cases of delayed anemia were clinically manageable and resolved within one month.

Presence of spur cells as a highly predictive factor of mortality in patients with cirrhosis.

BACKGROUND AND AIM: The presence of spur-cell anemia (SCA) is due to lipid disturbances of the erythrocyte membrane and may develop in patients with advanced liver cirrhosis. The accurate predicting value of SC for survival has not been clarified. The aim of this study was to evaluate SCA as a prognostic indicator in patients with cirrhosis. METHODS: We prospectively evaluated clinical, laboratory parameters, and survival in patients with cirrhosis, with or without SCA, during the period 2008-2011. Patients who had at admission renal failure, other causes of hemolytic anemia, hepatocellular carcinoma, sepsis, and/or active bleeding, were excluded. One hundred sixteen patients with cirrhosis were included. The presence of SCA (SC rate higher or equal to 5% [≥ 5%]) was diagnosed in 36 (31%) patients. RESULTS: Patients with SCA compared to those without had more advanced liver disease (higher Model for End-Stage Liver Disease [MELD], P < 0.001), higher total bilirubin (P < 0.001), and International Normalized Ratio (P < 0.001). Patients with SCA had worse survival (log rank P < 0.001). Survival of patients with SCA at the first, second, and third month of follow-up was 77%, 45%, and 33%, respectively. In multivariate Cox's regression analysis, the presence of SCA was an independent predictor of mortality (hazard ratio = 3.17 [95% CI 1.55-6.48]). CONCLUSIONS: The presence of spur-cell anemia is not uncommon in cirrhosis and seems to be strongly associated with mortality. SCA can be used in combination with MELD as an additional predictor of early mortality.

Increased perinatal loss after intrauterine transfusion for alloimmune anaemia before 20 weeks of gestation.

OBJECTIVES: To evaluate and compare perinatal outcome after intrauterine transfusions (IUT) performed before and after 20 weeks of gestation. To analyse contributing factors. DESIGN: Retrospective analysis. SETTING: The Dutch referral centre for fetal therapy. POPULATION: IUTs for fetal alloimmune anaemia. METHODS: Fetuses were divided into two groups: fetuses requiring the first IUT before 20 weeks of gestation (Group 1) and those in which the IUTs started after 20 weeks (Group 2). The cause of perinatal loss was classified as procedure-related (PR) or not procedure-related (NPR). The cohort was divided into two periods to describe the change of perinatal loss over time. MAIN OUTCOME MEASURES: Perinatal loss of fetuses requiring the first IUT before 20 weeks of gestation, compared with perinatal loss later in gestation. RESULTS: A total of 1422 IUTs were performed in 491 fetuses. Perinatal loss rate in Group 1 was higher (7/29 24% versus 35/462 8%, P = 0.002). Especially NPR was higher for IUTs performed before 20 weeks (4/37 11% versus 19/1385 1%, P < 0.001). Kell alloimmunisation was overrepresented in Group 1 (7/29 24% versus 52/462 11%, P = 0.04). In a multivariate regression analysis, only hydrops was independently associated with perinatal loss (P = 0.001). In recent years, a decline in total perinatal loss was found (36/224 16% versus 6/267 2%, P < 0.001), but perinatal loss in Group 1 did not decline (4/224 1.8% versus 3/267 1.1%, P = 0.5). CONCLUSIONS: Perinatal loss after IUT performed before 20 weeks of gestation is increased compared with loss after IUT performed later in gestation. In addition, we confirmed earlier observations that hydrops is a major contributor to adverse outcome. Early and timely detection and treatment may prevent hydrops and improve outcome.

Suppression of hepcidin expression and iron overload mediate Salmonella susceptibility in ankyrin 1 ENU-induced mutant.

Salmonella, a ubiquitous Gram-negative intracellular bacterium, is a food borne pathogen that infects a broad range of hosts. Infection with Salmonella Typhimurium in mice is a broadly recognized experimental model resembling typhoid fever in humans. Using a N-ethyl-N-nitrosurea (ENU) mutagenesis recessive screen, we report the identification of Ity16 (Immunity to Typhimurium locus 16), a locus responsible for increased susceptibility to infection. The position of Ity16 was refined on chromosome 8 and a nonsense mutation was identified in the ankyrin 1 (Ank1) gene. ANK1 plays an important role in the formation and stabilization of the red cell cytoskeleton. The Ank1(Ity16/Ity16) mutation causes severe hemolytic anemia in uninfected mice resulting in splenomegaly, hyperbilirubinemia, jaundice, extramedullary erythropoiesis and iron overload in liver and kidneys. Ank1(Ity16/Ity16) mutant mice demonstrated low levels of hepcidin (Hamp) expression and significant increases in the expression of the growth differentiation factor 15 (Gdf15), erythropoietin (Epo) and heme oxygenase 1 (Hmox1) exacerbating extramedullary erythropoiesis, tissue iron deposition and splenomegaly. As the infection progresses in Ank1(Ity16/Ity16), the anemia worsens and bacterial load were high in liver and kidneys compared to wild type mice. Heterozygous Ank1(+/Ity16) mice were also more susceptible to Salmonella infection although to a lesser extent than Ank1(Ity16/Ity16) and they did not inherently present anemia and splenomegaly. During infection, iron accumulated in the kidneys of Ank1(+/Ity16) mice where bacterial loads were high compared to littermate controls. The critical role of HAMP in the host response to Salmonella infection was validated by showing increased susceptibility to infection in Hamp-deficient mice and significant survival benefits in Ank1(+/Ity16) heterozygous mice treated with HAMP peptide. This study illustrates that the regulation of Hamp and iron balance are crucial in the host response to Salmonella infection in Ank1 mutants.

Thrombotic microangiopathy in sickle cell disease crisis.

Thrombotic microangiopathy (TMA) in patients with sickle cell disease (SCD) is a rare complication. These patients manifest microangiopathic hemolytic anemia (MAHA) with laboratory evidence of hemolytic anemia, schistocytosis, and thrombocytopenia. This is the first report of the syndrome in a group of these patients. A retrospective chart analysis of 10 consecutively diagnosed patients in SCD crisis who were referred for therapeutic plasma exchange (TPE) after developing MAHA was done. Patients had chest pain, respiratory distress, fever, pulmonary infiltrates, jaundice, and neurological dysfunction with abnormal liver function and coagulation tests. MAHA was diagnosed after a median hospital stay of 5 days. Nine patients recovered completely following TPE with fluid replacement by fresh frozen plasma with or without cryo-poor plasma. Incomplete response to TPE in one case was due to the development of fresh complications. During a median follow-up period of 77 months, there was one recurrent episode and one death in SCD crisis but without evidence of MAHA. TMA is not a very rare complication among Bahraini SCD patients in crisis. Characteristic features of this disorder are acute chest syndrome, organ failure, leuco-erythroblastosis, and a combination of thrombocytopenia, LDH level >1,000 U/l, and schistocytes in blood smears. Management with TPE usually leads to complete recovery with little chance of short-term recurrence. Multiple pathogenetic mechanisms leading to increased von Willebrand factor and its multimers may form the basis of this syndrome.

ROCK1 functions as a critical regulator of stress erythropoiesis and survival by regulating p53.

Erythropoiesis is a dynamic, multistep process whereby hematopoietic stem cells differentiate toward a progressively committed erythroid lineage through intermediate progenitors. Although several downstream signaling molecules have been identified that regulate steady-state erythropoiesis, the major regulators under conditions of stress remain poorly defined. Rho kinases (ROCKs) belong to a family of serine/threonine kinases. Using gene-targeted ROCK1-deficient mice, we show that lack of ROCK1 in phenylhydrazine-induced oxidative stress model results in enhanced recovery from hemolytic anemia as well as enhanced splenic stress erythropoiesis compared with control mice. Deficiency of ROCK1 also results in enhanced survival, whereas wild-type mice die rapidly in response to stress. Enhanced survivability of ROCK1-deficient mice is associated with reduced level of reactive oxygen species. BM transplantation studies revealed that enhanced stress erythropoiesis in ROCK1-deficient mice is stem cell autonomous. We show that ROCK1 binds to p53 and regulates its stability and expression. In the absence of ROCK1, p53 phosphorylation and expression is significantly reduced. Our findings reveal that ROCK1 functions as a physiologic regulator of p53 under conditions of erythroid stress. These findings are expected to offer new perspectives on stress erythropoiesis and may provide a potential therapeutic target in human disease characterized by anemia.

Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria.

BACKGROUND: In the era of eculizumab, identifying patients with paroxysmal nocturnal hemoglobinuria who may benefit from allogeneic stem cell transplantation is challenging. DESIGN AND METHODS: We describe the characteristics and overall survival of 211 patients transplanted for paroxysmal nocturnal hemoglobinuria in 83 EBMT centers from 1978 to 2007. Next, we conducted a comparison with a cohort of 402 non-transplanted patients with paroxysmal nocturnal hemoglobinuria diagnosed between 1950 and 2005 in 92 French centers. We compared the occurrence of complications (i.e. thromboembolism and aplastic anemia) using either an individual or a stratum-matching procedure. RESULTS: After a median follow-up of 5 years, the 5-year overall survival rate ± standard error (%) was 68 ± 3 in the transplanted group (54 ± 7 in the case of thromboembolism, 69 ± 5 in the case of aplastic anemia without thromboembolism and 86 ± 6 in the case of recurrent hemolytic anemia without thromboembolism or aplastic anemia). Only thromboembolism as the indication for transplantation was associated with worse outcome (P=0.03). We identified 24 pairs of transplanted and non-transplanted patients with thromboembolism for the matched comparison, with worse overall survival for the transplanted patients (hazard ratio=10.0; 95% confidence interval, 1.3-78.1; P=0.007). This was confirmed by the global matching procedure (P=0.03). As regards aplastic anemia without thromboembolism, 30 pairs were identified for the matched comparison. It was not observed that transplanted patients had a significantly worse overall survival (hazard ratio=4.0; 95% confidence interval, 0.9-18.9; P=0.06). A global matching procedure was not feasible. CONCLUSIONS: Allogeneic stem cell transplantation is probably not a suitable treatment option for life-threatening thromboembolism in paroxysmal nocturnal hemoglobinuria.

Canine idiopathic immune-mediated haemolytic anaemia: a review with recommendations for future research.

Idiopathic immune-mediated haemolytic anaemia (IMHA) is one of the most common immune-mediated diseases of dogs. The aim of this article is to review current knowledge of canine IMHA, its etiology, clinical presentation, diagnosis, complications, and treatment, in an attempt to establish why its outcome is still so poor. Clinical signs of anaemia develop within 3 days and dogs present with a median haematocrit of 13%, leucocytosis, a left shift, and reticulocytosis. Coagulation test results support the presence of disseminated intravascular coagulation. About 50% of dogs die in the first 2 weeks after presentation, and analysis of risk factors suggests that mortality is associated with hypercoagulability, inflammatory response, and liver and kidney failure. A positive direct agglutination test, spherocytosis, and true autoagglutination are widely accepted tests to demonstrate anti-erythrocyte antibodies, but are not yet standardized. To date, there is no evidence to support the efficacy of immunomodulators in addition to corticosteroids in the treatment of IMHA. Despite numerous investigations, the prognosis of IMHA remains dismal. There is an urgent need to validate and standardize diagnostic tests and criteria, and clinical trials might benefit from stratifying dogs by mortality risk. Analysis of samples from well-defined cases of canine IMHA might provide insight into the aetiology and pathophysiology of IMHA.

NT-pro brain natriuretic peptide levels and the risk of death in the cooperative study of sickle cell disease.

Epidemiological studies support a hypothesis that pulmonary hypertension (PH) is a common complication of sickle cell disease (SCD) that is associated with a high risk of death and evolves as a complication of haemolytic anaemia. This fundamental hypothesis has been recently challenged and remains controversial. In order to further test this hypothesis in a large and independent cohort of SCD patients we obtained plasma samples from the Cooperative Study of Sickle Cell Disease (CSSCD) for analysis of a biomarker, N-terminal-pro brain natriuretic peptide (NT-proBNP), which is elevated in the setting of pulmonary arterial and venous hypertension. A NT-pro-BNP value previously identified to predict PH in adults with SCD was used to determine the association between the risk of mortality in 758 CSSCD participants (428 children and 330 adults). An abnormally high NT-proBNP level ≥160ng/l was present in 27·6% of adult SCD patients. High levels were associated with markers of haemolytic anaemia, such as low haemoglobin level (P<0·001), high lactate dehydrogenase (P<0·001), and high total bilirubin levels (P<0·007). A NT-proBNP level ≥160ng/l was an independent predictor of mortality (RR 6·24, 95% CI 2·9-13·3, P<0·0001). These findings provide further support for an association between haemolytic anaemia and cardiovascular complications in this patient population.

Low-dose rituximab and alemtuzumab combination therapy for patients with steroid-refractory autoimmune cytopenias.

Treatment of autoimmune cytopenias remains unsatisfactory for patients refractory to first-line management. We evaluated the safety and efficacy of low-dose rituximab plus alemtuzumab in patients with steroid-refractory autoimmune hemolytic anemia and immune thrombocytopenic purpura. Nineteen of 21 included patients were assessable for response (11 with immune thrombocytopenic purpura, 8 with autoimmune hemolytic anemia). Treatment with 10 mg of alemtuzumab subcutaneously on days 1 to 3, plus 100 mg of rituximab intravenously weekly in 4 doses, was administered. The overall response rate was 100%, with complete response in 58%. The median response duration was 46 weeks (range, 16-89 weeks). Median follow-up was 70 weeks (range, 37-104 weeks). Most toxicity was grade 1 fever related to the first dose. Six patients developed infections. The combination of rituximab and alemtuzumab is feasible and has an acceptable safety profile and remarkable clinical activity in this group of patients. This study is registered at www.clinicaltrials.gov as #NCT00749112.

Evaluation of prognostic factors and establishment of a prognostic scoring system for canine primary immune-mediated hemolytic anemia.

Clinical courses of primary immune-mediated hemolytic anemia (pIMHA) in dogs are highly variable, however, limited information is available to predict their accurate prognoses. To evaluate the prognostic significance of clinical factors and to propose a scoring system to predict prognoses, the medical records of seventy-one dogs with pIMHA were reviewed. Overall mortality rate of dogs with pIMHA was 39% and most of the dogs died within 3 months from diagnosis. Sex, body weight, seasonality, packed corpuscular volume (PCV), platelet count (PLT), total plasma protein (TP), blood urea nitrogen, albumin, total bilirubin, sodium ion, prothrombin time, and fibrin/fibrinogen degradation products before immunosuppressive treatment can influence on survival time in dogs with pIMHA. A prognostic scoring system using a combination of sex, seasonality, PCV, PLT and TP can be statistically significant for raising the accuracy of prognostic prediction. Using the scoring system for prognostication in dogs with pIMHA may enable veterinarians to predict a prognosis easily and accurately.

Anemia in cats with hemotropic mycoplasma infection: retrospective evaluation of 23 cases (1996-2005).

This study summarizes the diagnostic findings from all anemic cats diagnosed with hemotropic mycoplasma (HM) infections at the Western College of Veterinary Medicine-Veterinary Teaching Hospital between 1996 and 2005. The objectives were to determine the frequency of HM-induced anemia among all cats presented with anemia during this period, the clinical findings and risk factors associated with clinical HM infection, and factors affecting or predicting survival. Medical records were examined from 23 cats with HM-induced anemia from the total of 170 cats diagnosed with anemia during this period. The frequency of HM-induced anemia was 14% (23/170) among all anemic cats. Cats with HM-induced anemia were less likely to be purebred (P = 0.04) than other cats with anemia. Of the cats with HM-induced anemia, those with positive retroviral status (P = 0.01), concurrent illness (P < 0.01), or lack of erythroid regeneration (P = 0.01) were most likely to die. The 1-year survival of HM-infected cats was 65% (13/20).

Features associated with, and the impact of, hemolytic anemia in patients with systemic lupus erythematosus: LX, results from a multiethnic cohort.

OBJECTIVE: To examine the clinical and genetic correlates of hemolytic anemia and its impact on damage accrual and mortality in systemic lupus erythematosus (SLE) patients. METHODS: SLE patients (American College of Rheumatology [ACR] criteria) of Hispanic (Texan or Puerto Rican), African American, and Caucasian ethnicity from the LUMINA (LUpus in MInorities, NAture versus nurture) cohort were studied. Hemolytic anemia was defined as anemia with reticulocytosis (ACR criterion). The association between degrees of hemolytic anemia and socioeconomic/demographic, clinical, pharmacologic, immunologic, psychological, and behavioral variables was examined by univariable and multivariable (proportional odds model) analyses. Genetic variables (FCGR and Fas/Fas ligand polymorphisms) were examined by 2 degrees of freedom test of association and Cochran-Armitage trend tests. The impact of hemolytic anemia on damage accrual and mortality was examined by multivariable linear and Cox regression analyses, respectively. RESULTS: Of 628 patients studied, 90% were women, 19% were Texan Hispanic, 16% were Puerto Rican Hispanic, 37% were African American, and 28% were Caucasian. Sixty-five (10%) patients developed hemolytic anemia at some time during the disease course, 83% at or before diagnosis. Variables independently associated with degrees of hemolytic anemia were African American ethnicity, thrombocytopenia, and the use of azathioprine. Hemolytic anemia was associated with damage accrual after adjusting for variables known to affect this outcome; however, hemolytic anemia was not associated with mortality. CONCLUSION: The association of hemolytic anemia with thrombocytopenia suggests a common mechanism in their pathophysiology. Hemolytic anemia is an early disease manifestation and is associated with African American ethnicity and the use of azathioprine; it appears to exert an impact on damage but not on mortality.