A thorny matter: Spur cell anemia.

Spur cell anemia (SCA) is an acquired form of non-autoimmune hemolytic anemia that occurs in advanced liver disease. It is characterized by the presence of acanthocytes or spur cells, spiculated erythrocytes whose shortened life span causes anemia that is unresponsive to transfusion. SCA has been regarded as a rare condition with an ominous prognosis for which the only known cure is liver transplantation, but recent prospective studies have demonstrated the existence of a milder form of SCA in which there are smaller numbers of acanthocytes, but which is nevertheless associated with hemolysis and poor outcomes. This form of SCA appears to be considerably more common than the severe classical variant. The conventional understanding of the pathogenesis of SCA is that abnormalities of lipid metabolism are the primary event driving the formation of spur cells. However, the studies that underpin this theory are based on small numbers of patients with heterogeneous clinical features and inconsistent use of nomenclature for dysmorphic red blood cells. In this review, we discuss the evolution of the current understanding of SCA and therapeutic strategies that have been employed based on this understanding. Our goal is to raise awareness of this understudied condition that has significant implications for patient outcomes. Furthermore, we highlight the need for rigorous, contemporary research into the underlying cause or causes of SCA in order to develop an effective therapy for this disorder.

Plasma transfusion combined with chelating therapy alleviates fulminant Wilson's disease with a single Arg778Leu heterozygote mutation.

Wilson's disease (WD), resulting from homozygote and compound heterozygote mutations in ATB7B, is an autosomal recessive disease. WD associated acute liver failure (ALF) is fatal, and a revised Wilson's disease prognostic index (RWPI) >11 is a reliable indication of liver transplantation (LT) or artificial liver support (ALS). We described a WD patient who initially presented with ALF and severe hemolytic anemia. A single heterozygote c.2333G>T mutation (p. Arg778Leu, R778L) in ATP7B was screened by whole exome sequencing and validated by Sanger sequencing. Rapid diagnostic criteria (ALP/TBIL <4 and AST/ALT >2.2) are suitable for early diagnosis. Although the RWPI amounted to 15, the patient recovered after intermittent plasma transfusion and subsequent chelating therapy without LT or ALS. In conclusion, WD patients with a single R778L heterozygote mutation can present with ALF as the initial clinical manifestation, and intermittent plasma transfusion combined with chelating therapy may alleviate fulminant WD without LT or ALS.

Anemia hemolítica autoinmune como forma de presentación de enfermedad inflamatoria del intestino / Autoimmune hemolytic anemia as a form of presentation of inflammatory bowel disease

Las anemias hemolíticas autoinmunes son las caracterizadas por la destrucción de los hematíes debida a la producción de autoanticuerpos por el paciente, dirigidos contra sus propios antígenos eritrocitarios. La asociación con enfermedad inflamatoria del intestino está descrita, pero no es de las asociaciones más frecuentes. Se presenta un caso de una paciente de 64 años de edad, que acude por diarreas y decaimiento, aparecen evolutivamente durante su ingreso lesiones ulceradas orales y perianales. Los exámenes complementarios mostraron una anemia hemolítica Coombs positiva. Los estudios endoscópicos del tubo digestivo, mostraron ulceración continua de todo el colon desde el ciego hasta el ano y pérdida de las austras, imagenológicamente se hizo evidente el aumento de tamaño del bazo en el curso de la hemólisis. Recibió tratamiento con esteroides y mesalazina por vía oral, desaparecieron las manifestaciones de hemólisis extravascular y mejoró la sintomatología digestiva. Se concluyó histológicamente como una enfermedad inflamatoria intestinal tipo colitis ulcerosa(AU)

Autoimmune haemolytic anemias are those characterized by the destruction of the red cells due to the production of autoantibodies by the patient, against their own erythrocyte antigens. The association with inflammatory bowel disease is described but it is not the most frequent associations. We present a case of a 64-year-old patient who came with diarrhea and decay, oral and perianal ulcerated lesions appeared progressively during admission. Complementary tests showed a positive Coombs hemolytic anemia, endoscopic studies of the digestive tract, continuous ulceration of all the colon from the caecum to the anus and loss of the austras, with imaging came out the enlargement of the spleen in the course of the hemolysis. Was treated with steroids and mesalazine oraly, the manifestations of extravascular hemolysis disappeared and digestive symptoms improved. Was concluded histologically as an inflammatory bowel disease type ulcerative colitis(AU)

[Hemolytic anemia secondary to the placement of a portosystemic stented shunt]. / Anemia hemolítica secundaria a la colocación de Stent transyugular intrahepático porto sistémico.

INTRODUCTION: portal hypertension and variceal hemorrhage are common complications of hepatic cirrhosis, both associated with a high morbimortality. Portal system decompression by the placement of a transjugular intrahepatic portosystemic stented shunt, can reduce portal venus pressure and is effective controling complications of portal hypertension, like variceal hemorrhage and ascitis. The aim of this document is to describe a case of hemolytic anemia secondary to the placement of a transjugular intrahepatic portosystemic stented shunt. CLINICAL CASE: patient with portal hypertension secondary to liver cirrosis was given a transjugular intrahepatic portosystemic stented shunt for recurrent variceal hemorrhage. After the procedure, hemoglobin decreased 2 g/dL, associated with reticulocitosis, hipohaptoglobinemia, elevated lactic dehydrogenase and indirect hyperbilirrubinemia with negative Coombs test. The peripheral blood smear showed abnormal erythrocytes, with the prevalence of schistocytes. The final diagnosis was hemolytic anemia secondary to transjugular intrahepatic portosystemic stented shunt. CONCLUSIONS: the hemolytic anemia secondary to Transjugular Intrahepatic Portosystemic Stented Shunt is a rare complication. Usually, it has a benign prognosis, and it is self-limited once the stent is endothelialized.

Nitrofurantoin-induced microangiopathic haemolytic anaemia and thrombocytopaenia in a patient with systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) may develop thrombotic thrombocytopaenic purpura (TTP) or TTP-like illness manifested by microangiopathic haemolytic anaemia (MAHA) and thrombocytopaenia. The distinction between active SLE and TTP is difficult because these entities share similar clinical features. Drug-induced TTP caused by an immune-mediated reaction have been documented for several drugs. Herein, we report a middle-aged Hispanic woman with long-standing SLE, who developed a TTP-like illness characterised by MAHA and thrombocytopaenia after exposure to nitrofurantoin. The patient responded well to plasmapheresis and immunosuppressive therapy and has remained clinically stable after 18 months of follow-up. To our knowledge, this is the first case that reports the association between nitrofurantoin and a TTP-like presentation.

Use of capillary blood to diagnose hereditary spherocytosis.

We studied 31 children with hemolytic anemia, or with positive family history for hereditary spherocytosis (HS), to assess the reliability of capillary blood samples for the diagnosis. HS was diagnosed in 20 patients. Cryohemolysis (CH) was positive in 94% and eosin-5'-maleimide flow cytometry in 90% of them, whereas flow cytometric osmotic fragility was positive in 94%. Capillary blood sampling showed to be useful for the diagnosis. Simultaneous use of these three tests allows confirming diagnosis in 100% of patients. The use of very small blood volumes (300 µl) allows an earlier diagnosis in neonates and small infants.

[Analysis and perinatal outcome after intravascular transfusion]. / Análisis y resultados perinatales posteriores a una transfusión intravascular.

INTRODUCTION: the leading cause of fetal anemia is Rh isoimmunization. The timely diagnosis by ultrasound and intravascular transfusion improves the prognosis. OBJECTIVE: to evaluate the increase in hemoglobin in the fetus and correlate the red cell transfusion volume with elevation of hemoglobin and perinatal outcome. PATIENTS AND METHODS: prospective, case series study. We included 17 patients with fetal anemia detected by measuring the peak systolic velocity of middle cerebral artery and determination of fetal hemoglobin before and after cordocentesis. After confirmation of fetal anemia (Hb <10 g/dL), was held fetal transfusion with 50 mL/kg estimated fetal weight, with packed red blood cells type O Rh negative. RESULTS: In 17 cases fetal anemia was diagnosed, of which 11 (64%) had Rh isoimmunization and 6 (36%) were not immune. The 17 cases received 27 intravascular transfusions, in 75% hemoglobin rose to 10 g/dL, 45% in the first transfusion, 25% in the second and 10% in the third transfusion. Fetal hemoglobin between before and after transfusion was 6.5 and 12.9 g/dl, respectively (p<0.001) and allowed to continue the pregnancy from 3 to 12 weeks from the first transfusion. There were 4 deaths (2 stillbirths and 2 neonatal), but only one was related to the procedure. the survival rate was 76%, mortality in the presence of hydrops was 30% and no deaths in patients without hydrops. CONCLUSIONS: Mortality in fetal anemia was 23.6% and only one case was related to intravascular transfusion. In cases of survival to birth, pregnancy lasted >30 weeks gestation. Hemoglobin rose from 27 to 300% of the initial fetal hemoglobin. The presence of fetal hydrops significantly increases mortality.

Anemia hemolítica autoinmune como manifestación inicial de linfoma Hodgkin / Auto inmune hemolytic anemia how initial manifestation of Hodgkin lymphoma

Se presenta el caso de una paciente de 66 años de edad, a la que se le diagnóstica anemia hemolítica, la cual fue refractaria al tratamiento y requirió esplenectomía. Además presenta adenomegalias inguinales, cuya biopsia determina infiltración parcial por células linfoides B CD20+, con atipia, y CD30+, con factor de proliferación alto; en médula ósea se constata incremento de linfocitos T. Cuatro meses después, consulta por la aparición de adenopatías inguinales y axilares, de las cuales la biopsia reveló enfermedad de Hodgkin variante esclerosis nodular, y en médula ósea se evidenció infiltración por la enfermedad linfoproliferativa. Si bien es infrecuente la asociación entre anemia hemolítica y linfoma Hodgkin, debe tenerse en cuenta para llegar a la búsqueda oportuna de su causa y al diagnóstico de un probable proceso linfoproliferativo subyacente.

In this work we report and study a case of 66 year old woman, whit diagnosis of hemolytic anemia, which was refractory to treatment and she required splenectomy. The patient presented inguinal lymphadenopathy which biopsy has determined a partial infiltration of B-cells CD20+ and CD30+ with atypia and high growth factor. The bone marrow biopsy informed an increased number of T lymphocytes. Four month later, the patient complained due to the appearance of inguinal and axillaries lymph nodes, which biopsy revealed a nodular sclerosis Hodgkin lymphoma. The bone marrow biopsy showed infiltration by lymphoproliferative disease. Although the association between hemolytic anemia and Hodgkin lymphoma is less frequent, this fact should be taken into account in searching its cause and reaching the diagnosis of a probable underlying lymphoproliferative process.

[ABO hemolytic disease and developing of significant hyperbilirubinemia in term newborns: early predictive factors]. / Enfermedad hemolítica por incompatibilidad ABO y desarrollo de ictericia grave en recién nacidos de término: factores predictivos precoces.

UNLABELLED: Early hospital discharge has increased the risk of severe jaundice in term neonates with ABO incompatibility and hemolytic disease. AIMS: a) To identify predictive factors of severe hyperbilirubinemia (requiring phototherapy) in the first week of life; b) to determine the serum unconjugated bilirubin (UB) level cutoff at 24-36 hours that better predicts severe hyperbilirubinemia. METHOD: After parental consent was obtained, lab tests were measured at 24-36 hours, 3rd, 4-5th, 6-7th days of life. Predictive capacity of the serum UB level was assessed through the ROC curve analysis and estimation of the sensitivity, specificity and positive and negative predictive values of different serum UB level cut-offs. RESULTS: ABO incompatibility was identified in 172 (13.6%) of 1.263 healthy term newborns; 126 babies were included, 28 of them (22%) developed severe hyperbilirubinemia; 46 were excluded (33 did not grant consent, 11 were lost to follow up and 2 received NICU's care). These last had higher UB level at 24-36 hours than those that did not develop the condition during the first week of life. A serum UB value of 8.75 mg% at 24-36 hours showed the best performance: sensitivity 78%, specificity 83%, positive predicted value 45% and negative 95%. CONCLUSIONS: Serum UB at 24-36 hours of life might contribute to identify those term newborns with ABO incompatibility that have the highest risk of developing severe jaundice.

Fetal hydrops and other variables associated with the fetal hematocrit decrease after the first intrauterine transfusion for red cell alloimmunization.

OBJECTIVE: To evaluate the influence of fetal hydrops and other variables on fetal hematocrit (Hct) decrease after the first intrauterine transfusion (IUT) in alloimmunized pregnancies. METHODS: From 1996 to 2006, the data of all alloimmunized pregnancies submitted to IUT were assessed. Exclusion criteria included: fetuses submitted to intraperitoneal transfusion; pregnancies complicated by other fetal abnormalities; pregnancies submitted to only one IUT, and cases in which posttransfusion or pretransfusion blood samples were not obtained. Linear regression models were implemented to assess the relationship between the rate of Hct fall after the first IUT and the following variables: fetal hydrops; antibody titer; gestational age at the first IUT; number of days between the first and second IUT; pretransfusion and posttransfusion fetal Hct values. RESULTS: Fifty fetuses fulfilled the study criteria. The fetal Hct decrease after the first IUT was 1.21 (range 0.18-2.3) %/day. The variables independently associated with the fetal Hct drop after the first IUT were the fetal hydrops (p = 0.000), the pretransfusion fetal Hct (p = 0.001) and the posttransfusion fetal Hct (p = 0.016). CONCLUSION: Fetal hydrops, pretransfusion fetal Hct and posttransfusion fetal Hct seem to influence the fetal Hct decrease between the first and second IUT. These findings may be helpful for estimating the rate of fetal Hct drop and programming the following IUT.

Infecção pulmonar por Strongyloides stercoralis em paciente tratado com imunosupressores / Case report: Pulmonary infection by Strongyloides stercoralis in a patient treated with immunosupressors

Strongyloides stercoralis é um parasito predominantemente intestinal. Nos casos graves, pode evoluir para a forma disseminada, principalmente se houver utilização prolongada de glicocorticóides, medicamentos imunodepressores ou radioterapia. Relata-se, neste estudo, o caso de P.F.C.S., do sexo feminino, 16 anos, proveniente da comunidade Menino de Deus na ilha de Pratari, município de Manacapuru, estado do Amazonas, Brasil, com diagnóstico de anemia hemolítica auto-imune desde agosto de 2005. Nenhum dos exames parasitológicos de fezes apresentou positividade para Strongyloides stercoralis, tendo sido detectado apenas no exame de escarro. Foi tratada com tiabendazol, via oral, sem resultado favorável e evoluiu para óbito. Ficou evidenciada a importância da realização de exames complementares, como o parasitológico de fezes, antes da utilização de medicamentos indicados para o tratamento de anemia hemolítica.

Relationship between obstetric history and Rh(D) alloimmunization severity.

BACKGROUND: To evaluate the relationship between obstetric history and Rh(D) alloimmunization severity, employing the gestational age at the first intrauterine fetal transfusion (IUT) as an indicator of this severity. METHODS: From 1996 to 2006, Rh(D) alloimmunized pregnancies submitted to IUT had their data assessed. Gestational age at the first IUT was modeled as a linear outcome. The associations between obstetric history variables, anti-Rh(D) antibodies titer and gestational age at the first IUT were analyzed. Statistics are presented with 95% confidence intervals (P < 0.05). RESULTS: A total of 82 non-hydropic anemic fetuses, ensuing in 92.7% (n = 76) of perinatal survival, were submitted to IUT. Nineteen (23,2%) pregnant women did not present with any previous stillbirth, neonatal death, IUT, hydrops or neonatal exchange transfusion (group 1); and 63 (76.8%) reported at least one of these events (group 2). Gestational age at the first IUT differed significantly between the groups (P = 0.0001). For group 1, it ranged from 24 to 35 weeks (median 32.5 weeks), whereas for group 2 it ranged from 19 to 34 weeks (median 27 weeks). In the multivariated analysis, previous neonatal death (P = 0.040), previous IUT (P = 0.000) and previous neonatal exchange transfusion (P = 0.036) were independently associated with the gestational age at the first IUT. CONCLUSIONS: The evaluation of the obstetrical history is an important diagnostic tool for predicting Rh(D) alloimmunization severity. Alloimmunized pregnant women who reported previous neonatal death(s), neonatal exchange transfusion(s) or IUT(s) should receive a closer fetal surveillance due to the risk of a higher rate of fetal hemolysis and the need of an earlier IUT.

Fetal hematocrit decrease after repeated intravascular transfusions in alloimmunized pregnancies.

BACKGROUND: The aim of this study is to evaluate the fetal hematocrit (Hct) decrease along repeated intravascular intrauterine fetal transfusions (IUTs) and test the hypothesis that, after consecutive IUTs, there is a lower Hct drop off. METHODS: From July 1996 to June 2006, pregnancies submitted to IUT for fetal hemolytic anemia treatment had their data assessed. The daily rate of decrease in fetal Hct was calculated by dividing the difference between the posttransfusion Hct of the previous IUT and the pretransfusion Hct of the current IUT, by the number of days between the transfusions. Fetuses with other abnormalities or submitted to intraperitoneal transfusions were excluded. RESULTS: Eighty-one women were submitted to IUT during the alluded period, ensuing 296 intrauterine transfusions. The perinatal survival was 89.9% (n = 80), with 92.0% (n = 69) of nonhydropic fetuses survival. Hydropic fetuses showed higher hematocrit drop off than nonhydropic ones (P < 0.01). Compared to the interval between the first and second IUT, the daily fetal Hct decline was lower after the third one (P < 0.05). Stratifying by the presence of hydrops, nonhydropic fetuses showed a smaller decrease at the third and fourth intervals (P < 0.01 and P < 0.05, respectively). Among hydropic fetuses, there is a trend of smaller Hct decrease along successive IUTs (interval 3, P = 0.08; interval 4, P = 0.07; and interval 5, P = 0.10). CONCLUSIONS: Following some IUTs, fetal hematocrit decrease is lower and larger intervals between the transfusions could be accomplished. Multicenter studies should investigate an algorithm for timing subsequent IUTs, considering Doppler values, estimated fetal hematocrit decline and other parameters.

[Thrombotic microangiopathy in adults]. / Microangiopatía trombótica en adultos.

Thrombotic microangiopathic hemolytic anemias include thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) and pregnancy associated thrombotic microangiopathy (TMA). Eight adult patients (four males and four females) with TMA who were treated between 2003 and 2004 at the Hospital Italiano de Buenos Aires were reviewed. The average age was 40. Clinical diagnosis of TMA was made on admission in four patients. During their stay in hospital, 4 patients developed HUS characteristics, three as TTP and one presented pregnancy associated TMA. All of them revealed thrombocytopenia and microangiophatic hemolytic anemia. Renal impairment was the third most frequent characteristic at presentation. The patients with TTP revealed the most severe condition. All patients received daily plasma exchange. Immunosuppressants were also used. Four patients recovered completely, 2 passed away, one remains with renal impairment and requires hemodialysis, and a colectomy was performed on one of them. The TMA syndromes are occlusive disorders associated to platelet microvascular thrombi. Systemic and renal circulations are primarily affected. TTP/HUS might represent an overlapping spectrum of idiopathic or secondary disease. Prompt recognition and treatment are vital, because high mortality occurs due to these disorders. Among the differential diagnosis of TMA we can refer to sepsis, neoplasms, systemic vasculitis, eclampsia and others. The mainstay treatments are daily plasma exchange and infusion with fresh frozen plasma. Improving the management of these diseases is required considering their high morbidity and mortality.

Microangiopatía trombótica en adultos / Thrombotic microangiopathy in adults

Thrombotic microangiopathic hemolytic anemias include thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) and pregnancy associated thrombotic microangiopathy (TMA). Eight adult patients (four males and four females) with TMA who were treated between 2003 and 2004 at the Hospital Italiano de Buenos Aires were reviewed. The average age was 40. Clinical diagnosis of TMA was made on admission in four patients. During their stay in hospital, 4 patients developed HUS characteristics, three as TTP and one presented pregnancy associated TMA. All of them revealed thrombocytopenia and microangiophatic hemolytic anemia. Renal impairment was the third most frequent characteristic at presentation. The patients with TTP revealed the most severe condition. All patients received daily plasma exchange. Immunosuppressants were also used. Four patients recovered completely, 2 passed away, one remains with renal impairment and requires hemodialysis, and a colectomy was performed on one of them. The TMA syndromes are occlusive disorders associated to platelet microvascular thrombi. Systemic and renal circulations are primarily affected. TTP/HUS might represent an overlapping spectrum of idiopathic or secondary disease. Prompt recognition and treatment are vital, because high mortality occurs due to these disorders. Among the differential diagnosis of TMA we can refer to sepsis, neoplasms, systemic vasculitis, eclampsia and others. The mainstay treatments are daily plasma exchange and infusion with fresh frozen plasma. Improving the management of these diseases is required considering their high morbidity and mortality.

Microangiopatía trombótica en adultos / Thrombotic microangiopathy in adults

Thrombotic microangiopathic hemolytic anemias include thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) and pregnancy associated thrombotic microangiopathy (TMA). Eight adult patients (four males and four females) with TMA who were treated between 2003 and 2004 at the Hospital Italiano de Buenos Aires were reviewed. The average age was 40. Clinical diagnosis of TMA was made on admission in four patients. During their stay in hospital, 4 patients developed HUS characteristics, three as TTP and one presented pregnancy associated TMA. All of them revealed thrombocytopenia and microangiophatic hemolytic anemia. Renal impairment was the third most frequent characteristic at presentation. The patients with TTP revealed the most severe condition. All patients received daily plasma exchange. Immunosuppressants were also used. Four patients recovered completely, 2 passed away, one remains with renal impairment and requires hemodialysis, and a colectomy was performed on one of them. The TMA syndromes are occlusive disorders associated to platelet microvascular thrombi. Systemic and renal circulations are primarily affected. TTP/HUS might represent an overlapping spectrum of idiopathic or secondary disease. Prompt recognition and treatment are vital, because high mortality occurs due to these disorders. Among the differential diagnosis of TMA we can refer to sepsis, neoplasms, systemic vasculitis, eclampsia and others. The mainstay treatments are daily plasma exchange and infusion with fresh frozen plasma. Improving the management of these diseases is required considering their high morbidity and mortality.(AU)

Microangiopatía trombótica en adultos / Thrombotic microangiopathy in adults

Thrombotic microangiopathic hemolytic anemias include thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) and pregnancy associated thrombotic microangiopathy (TMA). Eight adult patients (four males and four females) with TMA who were treated between 2003 and 2004 at the Hospital Italiano de Buenos Aires were reviewed. The average age was 40. Clinical diagnosis of TMA was made on admission in four patients. During their stay in hospital, 4 patients developed HUS characteristics, three as TTP and one presented pregnancy associated TMA. All of them revealed thrombocytopenia and microangiophatic hemolytic anemia. Renal impairment was the third most frequent characteristic at presentation. The patients with TTP revealed the most severe condition. All patients received daily plasma exchange. Immunosuppressants were also used. Four patients recovered completely, 2 passed away, one remains with renal impairment and requires hemodialysis, and a colectomy was performed on one of them. The TMA syndromes are occlusive disorders associated to platelet microvascular thrombi. Systemic and renal circulations are primarily affected. TTP/HUS might represent an overlapping spectrum of idiopathic or secondary disease. Prompt recognition and treatment are vital, because high mortality occurs due to these disorders. Among the differential diagnosis of TMA we can refer to sepsis, neoplasms, systemic vasculitis, eclampsia and others. The mainstay treatments are daily plasma exchange and infusion with fresh frozen plasma. Improving the management of these diseases is required considering their high morbidity and mortality.(AU)

Erucismo por Lonomia spp em Teresópolis, RJ, Brasil: relato de um caso provável e revisão da literatura / Lonomia erucism in Teresópolis, Rio de Janeiro State, Brazil: report of a probable case and review

Relata-se o caso de um homem de 44 anos, natural do Rio de Janeiro, residente no município de Teresópolis (RJ), vítima de um provável acidente por lagarta do gênero Lonomia, que evoluiu com quadro caracterizado por anemia hemolítica, plaquetopenia e insuficiência renal aguda. O diagnóstico de erucismo por Lonomia foi estabelecido a partir da anamnese e das manifestações clínicas e laboratoriais. O esquema terapêutico, baseado em hemodiálise e hemotransfusão, resultou em excelente resposta clínica. São discutidos os aspectos clínicos e fisiopatológicos do erucismo por Lonomia.