Endothelial lesion and complement activation in patients with Scleroderma Renal Crisis / Lesão endotelial e ativação do complemento em pacientes com crise renal esclerodérmica

Abstract In kidney biopsies reviews, scleroderma renal crisis (SRC) is characterized by vascular endothelial injuries, C4d deposits on peritubular vessels, and acute and chronic injuries coexisting on the same biopsy. The clinical signs of thrombotic microangiopathy (TMA) are described in systemic sclerosis (SSc), nevertheless, it has not been related to acute injuries described on kidney biopsies. We report a case of SRC in a patient with scleroderma-dermatomyositis overlap syndrome, which also showed clinical and histopathological data of TMA. On fundus examination, a severe acute hypertensive retinopathy was found. The kidney biopsy showed severe endothelial damage with widening of mucoid cells at the level of the intima, focal concentric proliferation on most small arterioles, and C3, C4d, and IgM deposits along the capillary walls. The genetic study of complement only showed the presence of membrane cofactor protein (MCP) risk haplotypes, without other genetic complement disorders. We understand that in a patient with TMA and SSc, the kidney damage would be fundamentally endothelial and of an acute type; moreover, we would observe clear evidence of complement activation. Once further studies correlate clinical-analytical data with anatomopathological studies, it is likely that we will be forced to redefine the SRC concept, focusing on the relationship between acute endothelial damage and complement activation.

Resumo Nas revisões de biópsias renais, a crise renal esclerodérmica (CRE) é caracterizada por lesões endoteliais vasculares, depósitos de C4d em vasos peritubulares e lesões agudas e crônicas que coexistem na mesma biópsia. Os sinais clínicos de microangiopatia trombótica (MAT) são descritos na esclerose sistêmica (ES); no entanto, não foram relacionados às lesões agudas descritas nas biópsias renais. Relatamos um caso de CRE em um paciente com síndrome de superposição de esclerodermia-dermatomiosite, que também apresentou dados clínicos e histopatológicos de MAT. No exame de fundo do olho, foi encontrada uma retinopatia hipertensiva aguda grave. A biópsia renal mostrou lesão endotelial grave com alargamento das células mucoides ao nível da íntima, proliferação concêntrica focal na maioria das pequenas arteríolas e depósitos de C3, C4d e IgM ao longo das paredes dos capilares. O estudo genético do complemento mostrou apenas a presença de haplótipos de risco da proteína cofator de membrana (PCM), sem outros distúrbios genéticos do complemento. Entendemos que em um paciente com MAT e ES, o dano renal seria fundamentalmente endotelial e do tipo agudo; além disso, observaríamos evidências claras de ativação do complemento. Uma vez que novos estudos correlacionam dados clínico-analíticos com estudos anatomopatológicos, é provável que sejamos forçados a redefinir o conceito de CRE, enfocando a relação entre dano endotelial agudo e ativação do complemento.

Infección mortal por Clostridium perfringens con hemólisis tras quimioterapia en un adolescente / A fatal Clostridium perfringens infection with hemolysis after chemotherapy in an adolescent

La gangrena gaseosa, o mionecrosis clostridial, es una de las enfermedades infecciosas más graves, y se caracteriza por la rápida y progresiva destrucción de los tejidos blandos profundos y la producción de gas dentro de los tejidos. Presentamos un caso de gangrena gaseosa espontánea mortal causada por Clostridium perfringens en un paciente con leucemia linfocítica aguda durante la fase de quimioterapia de inducción de la remisión.

Gas gangrene, clostridial myonecrosis, is one of the most serious infectious diseases, characterized by rapidly progressive destruction of deep soft tissues and production of gas within the tissues. We presented a case of fatal spontaneous gas gangrene due to Clostridium perfringens in a patient with acute lymphoblastic leukemia during remission induction chemotherapy phase.

Anémies décompensées et transfusion sanguine chez les enfants de 0 à 59 mois (RD. Congo)

Introduction: L'anémie est un problème de santé publique, surtout dans les pays en voie de développement et chez les enfants de moins de 5 ans etles femmes enceintes.L'objectif de ce travail a été de déterminer le profil des anémies décompensées et les indications de la transfusion sanguine dans les anémies chez les enfants de 0 à 59 mois.Méthodes : il s'agissait d'une étude rétrospective et descriptive réalisée au Centre de Santé de Référence Katele (Moba, RDC) de janvier à décembre 2014. Notre échantillon était constitué de 730 enfants.Résultats :30,4% cas d'anémies décompensées ont été évoqués. Les enfants de 13 à 36 mois et de sexe féminin (54,5%)ont été plus concernés. Les signes de décompensation étaient constitués de tachycardie (98,2%), altération de l'état général (97,7%), pâleur cutanéo-muqueuse (96,8%), dyspnée (96,4%), battement des ailes du nez (92,8%) et souffle cardiaque systolique (46,9%). 17 enfants (7,7%) étaient amenés au stade de coma anémique et en majorité c'étaient des cas de transfert. Dans 39,6% il y avait d'antécédents transfusionnels et l'Hb était ≤ 5 g/dl dans 56,8% de cas. Le paludisme (p 0,000) est de façon significative la principale indication (91,0%) de transfusion sanguine, suivi de la malnutrition. La transfusion avait concerné 98,2% enfants. 10,4% de décès ont été notés.Conclusion :le paludisme était la principale étiologie des anémies décompensées. Des mesures préventives et d'amélioration de la prise en charge doivent être entreprises pour lutter contre les étiologies incriminées et diminuer la mortalité en dessous de 1 %. Les indications de la transfusion devraient être revues dans notre pratique hospitalière et la formation du personnel en médecine transfusionnelle s'avère à cet effet très utile

Anemia hemolítica secundaria a plastía mitral: caso clínico local y revisión de la literatura / Hemolytic anemia after mitral valve repair: case report

Una mujer de 54 años sometida a una reparación mitral se presenta 2 meses después con anemia hemolítica. El mecanismo de ésta correspondió a dehiscencia de la cuadrantectomía y a falta de endotelización de un sector del anillo, que se evidenció mediante ecografía transesofágica y se confirmó por hallazgos operatorios. Se resecó el anillo mitral y se implantó una prótesis de Saint Jude, y no hubo recurrencia de la hemólisis. Se incluye una discusión con revisión de la literatura.

A 54 year old woman was subjected to a mitral valve repair of a mixomatous degenerative valve with severe mitral insufficiency. Quadrantectomy, mitral chords transfer from P2 to a A2 and implantation of a rigid Edwards 28 ring were performed. Two months later the patient was diagnosed with severe hemolytic anemia. Trans esophageal echocardiography revealed severe mitral insufficiency and at surgery a dehiscence at the base of the qudrantectomy in addition to a non endothelysed sector of the mitral ring were found. A Saint-Jude mitral prosthesis was inserted. At follow up, no recurrence of hemolysis occurred.

Adult patent Ductus Arteriosus complicated by endocarditis and hemolytic anemia / Conducto arterioso patente complicado por endocarditis y anemia hemolítica en un adulto

An adult with a large patent ductus arteriosus may present with fatigue, dyspnea or palpitations or in rare presentation with endocarditis. The case illustrated unique role of vegetation of endocarditis in hemolytic anemia in adult with patent ductus arteriosus (PDA). Despite treatment of endocarditis with complete course of appropriate antibiotic therapy and normality of C- reactive protein, erythrocyte sedimentation rate and leukocytosis and wellness of general condition, transthoracic echocardiography revealed large vegetation in PDA lumen, surgical closure of PDA completely relieved hemolysis, and fragmented red cell disappeared from peripheral blood smear. The 3-month follow-up revealed complete occlusion of PDA and abolishment of hemolytic anemia confirmed by clinical and laboratory examination.

Un adulto con un gran ductus arterioso permeable puede presentar fatiga, disnea y palpitaciones y menos frecuentemente presentar endocarditis. El caso muestra el papel de la vegetación de la endocarditis en la anemia hemolítica con el conducto arterioso patente (CAP) en adultos. A pesar del tratamiento de la endocarditis con la terapia antibiótica completa, la normalidad en la proteína C-reactiva, la tasa de sedimentación globular y leucocitaria, y un estado de bienestar general del paciente, la ecocardiografía trans torácica reveló gran vegetación en el lumen de CAP y el cierre completo quirúrgico de PDA, sin hemólisis y la desaparición de glóbulos rojos fragmentados en frotis de sangre periférica. Los 3 meses de seguimiento revelaron oclusión completa de CAP y la desaparición de la anemia hemolítica confirmada por examen clínico y laboratorio.

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...

Deficiencia de glucosa 6 fosfato deshidrogenasa en niños: caso clínico / Glucose-6-phosphate dehydrogenase deficiency in children: a case report

Introduction: Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) is the most common red blood cell (RBC) enzyme disorder. The decrease as well as the absence of the enzyme increase RBC vulnerability to oxidative stress caused by exposure to certain medications or intake of fava beans. Among the most common clinical manifestations of this condition, acute hemolysis, chronic hemolysis, neonatal hyperbilirubinemia, and an asymptomatic form are observed. Objective: To analyze the case of a child who presented hemolytic crisis due to favism. Case report: A 2 year and 7 month old boy with a history of hyperbilirubinemia during the newborn period with no apparent cause, no family history of hemolytic anemia or parental consanguinity. He presented a prolonged neonatal jaundice and severe anemia requiring RBC transfusion. An intake of fava beans 48 h prior to onset of symptoms was reported. G6PD qualitative determination was compatible with this enzyme deficiency. Conclusion: G6PD deficiency can be highly variable in its clinical presentation, so it is necessary to keep it in mind during the diagnosis of hemolytic anemia at any age.

Introducción: La deficiencia de la glucosa 6-fosfato deshidrogenasa (G6PD) es el trastorno enzimático más frecuente del glóbulo rojo (GR). Tanto la disminución como la ausencia de la enzima aumentan la vulnerabilidad del GR al estrés oxidativo provocado por algunos fármacos o la ingesta de habas. Sus manifestaciones clínicas más frecuentes son hemolisis aguda, hemolisis crónica, hiperbilirrubinemia neonatal, y una forma asintomática. Objetivo: Presentar el caso de un niño que debutó como crisis hemolítica debida a favismo. Caso clínico: Varón 2 años 7 meses con antecedente de hiperbilirrubinemia en el período neonatal sin causa evidente, sin historia familiar de anemia hemolítica ni de consanguinidad paterna. Debutó con un cuadro de ictericia y anemia severa que requirió transfusión de GR. Como antecedente anamnéstico se detectó la ingesta de habas 48 h previo al inicio de los síntomas. La determinación cualitativa de G6PD fue compatible con deficiencia de esta enzima. Conclusión: La deficiencia de G6PD puede ser muy variable en su expresión clínica, por lo cual es necesario tenerla presente dentro del diagnóstico diferencial de las anemias hemolíticas a toda edad.

Anemia hemolítica grave causada por hemoglobina Southampton: Presentación de caso clínico / Severe hemolytic anemia due to hemoglobin Southampton: Case report

Las hemoglobinopatías estructurales son variantes de la hemoglobina caracterizadas por la síntesis de una molécula cualitativamente diferente de la normal. La mayoría son inocuas, mientras que otras ocasionan cambios fisicoquímicos que determinan manifestaciones clínicas de gravedad variable. En el caso de las hemoglobinas inestables, las alteraciones reducen la solubilidad y facilitan la formación de complejos de hemoglobina desnaturalizada (cuerpos de Heinz) que precipitan, lo cual daña la membrana y destruye prematuramente al eritrocito. Hasta la actualidad se han descrito 142 hemoglobinas inestables, muchas de ellas ocasionan hemólisis crónica, que puede exacerbarse por infecciones o por la ingesta de medicamentos o drogas oxidantes. La hemoglobina Southampton (también conocida como hemoglobina Casper) es una variante inestable que resulta de la sustitución de un residuo de leucina por uno de prolina, en el codón ß106 (CTG ?CCG, como consecuencia de la mutación c.320 T>C. Presentamos una niña con anemia hemolítica grave, esplenomegalia y requerimiento transfusional debidos a hemoglobina Southampton.

Variant hemoglobins are the result of different types of mutations that occur in the globin genes. In many cases, these hemoglobinopathies are harmless, while in others they determine alterations in the physical and chemical properties raising clinical manifestations of variable severity. In the unstable hemoglobinopathies, the changes reduce solubility, inducing the formation of precipitates of denaturated hemoglobin (Heinz bodies), which damage the membrane and finally destroy the red blood cells prematurely. Up to now, more than 142 different unstable hemoglobins have been described, most of them cause chronic hemolysis, increased by infections or drugs. We report the clinical presentation of an unstable hemoglobin (hemoglobin Southampton) in a girl with severe hemolytic anemia, splenomegaly and red blood cell requirement.

Enzyme kinetics and molecular modeling studies of G6PDMahidol associated with acute hemolytic anemia.

G6PDMahidol enzyme is the most common variant in the Achang Chinese ethnic group and clinically manifests as class II. In this study, G6PDMahidol enzyme was characterized by molecular modeling to understand its kinetics. G6PDMahidol, G6PDG487A and G6PDWT proteins were heterologously expressed in the G6PD-deficient DF213 E. coli strain, purified and their steady-state kinetic parameters were determined. Compared with G6PDWT, the Km and Vmax of NADP+ with G6PDG487A were about 28-fold and 12-fold lower, respectively. The Ki values of dehydroepiandrosterone (DHEA), NADPH and ATP with G6PDG487A showed 29.5-fold, 2.36-fold reduction and 1.83-fold increase, respectively. A molecular modeling of G6PDG487A was performed based on the X-ray structure of human G6PD (PDB: 2BH9). It is suggested that Ser-163 might affect the stability of G6PDG487A -helix d and -strand E, besides the conformation of -strand D. In conclusion, the biochemical and structural properties of G6PDG487A and G6PDWT enzymes are significantly different, which may be responsible for clinical diversity of G6PD deficiencies.

Primer caso de hemoglobina Koln (codon98 GTC mayor ATG) en Costa Rica / First case of hemoglobin Koln (codon98 GTC mayor ATG) in Costa Rica

La exposición a ciertos medicamentos puede provocar anemia hemolítica con presencia de cuerpos de Heinz en sangre periférica. Esta anemia puede presentarse por sobredosis de medicamentos, tanto en individuos sanos como en personas con deficiencias enzimáticas como la glucosa-6-fosfato deshidrogenasa, o en presencia de hemoglobinas inestables. Este reporte muestra un caso de anemia hemolítica con cuerpos de Heinz, debido a la presencia de una hemoglobina inestable, cuyos estudios moleculares y HPLC confirmaron el primer caso descrito de hemoglobina Koln (Val98Met) en Costa Rica.

Exposure to certain drugs may result in hemolytic anemia with the appearance of Heinz-bodies in red blood cells. Thistype of hemolytic anemia may occur by simple drug overdosage in absence of any known abnormality, such as innormal persons or in patients with erithroid enzyme defects (e.g. G6PD deficiency) or unstable hemoglobins.1 The present report shows a Heinz-body hemolytic anemia because of an abnormal hemoglobin. High pressure liquid chromatography (HPLC) and molecular analysis confirmed the first case of Hemoglobin Köln in Costa Rica.

PNH revisited: Clinical profile, laboratory diagnosis and follow-up.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolysis, marrow failure, nocturnal hemoglobinuria and thrombophila. This acquired disease caused by a deficiency of glycosylphosphatidylinositol (GPI) anchored proteins on the hematopoietic cells is uncommon in the Indian population. MATERIALS AND METHODS: Data of patients diagnosed with PNH in the past 1 year were collected. Clinical data (age, gender, various presenting symptoms), treatment information and follow-up data were collected from medical records. Results of relevant diagnostic tests were documented i.e., urine analysis, Ham's test, sucrose lysis test and sephacryl gel card test (GCT) for CD55 and CD59. RESULTS: A total of 5 patients were diagnosed with PNH in the past 1 year. Presenting symptoms were hemolytic anemia (n=4) and bone marrow failure (n=1). A GCT detected CD59 deficiency in all erythrocytes in 4 patients and CD55 deficiency in 2 patients. A weak positive PNH test for CD59 was seen in 1 patient and a weak positive PNH test for CD55 was seen in 3 patients. All patients were negative by sucrose lysis test. Ham's test was positive in two cases. Patients were treated with prednisolone and/or androgen and 1 patient with aplastic anemia was also given antithymocyte globulin. A total of 4 patients responded with a partial recovery of hematopoiesis and 1 patient showed no recovery. None of the patients received a bone marrow transplant. CONCLUSION: The study highlights the diagnostic methods and treatment protocols undertaken to evaluate the PNH clone in a developing country where advanced methods like flowcytometry immunophenotyping (FCMI) and bone marrow transplants are not routinely available.

Brucellosis triggering hemolytic anemia in glucose-6-phosphate dehydrogenase deficiency

To present a case of acute brucellosis triggering acute hemolytic anemia in a subject with glucose-6-phosphate dehydrogenase [G6PD] deficiency. A 17-year-old male patient presented with fever, malaise and jaundice. His blood and bone marrow cultures yielded Brucella species. In addition, he was found to have acute hemolytic anemia due to previously undiagnosed G6PD deficiency. He was started on folic acid supplementation and given a combination of doxycycline and rifampicin for 6 weeks. His response to antibiotic therapy was optimal; the hemolytic anemia resolved. There were no further episodes of hemolysis. This case showed that the differential diagnosis of acute hemolytic anemia in subjects with G6PD deficiency should include brucellosis, especially in regions where the infection is endemic

[Serious lead poisoning in oral and inhaled opium abuser]

A 25 year old man who referred with abdominal pain, nausea and progressive vomiting since 2 months ago and 7kg weight loss from this time. Also he was complaining from generalized bone pain especially back pain and jaundice. The patient has a long time history of addiction with oral and inhalation form of narcotics. In physical exam pallorness and icter of mucosa was observed. In mouth examination bluish pigmentation seen at the gum-tooth line. Hepatosplenomegaly and lymphadenopathy was not detected. Upper GI endoscopy was normal. And in lab tests hepatic aminotransferases were increased but alkalin phosphatase was in normal range also indirect billirubin was increased too. CBC test non auto immune hemolytic anemia was deteded, and direct and indirect combs test was negative. BMB and BMA evaluation hyperplasia of erythroid was shown. The patient had a history of smoking and oral narcotics use from 6 years ago. According to all symptoms with clinical doubt of lead poisoning the very high level of lead in narcotic sample was reported and in blood analysis very high level of lead [350mg/dl] was detected. The patient was treated with Ca.EDTA and BAL with decreasing lead level and the symptoms were recovered. There are some reports Similar this case [due to oral narcotics contain Lead] in Iran

Molecular basis of G6PD deficiency: Current status and its perspective

Glucose-6-phosphate dehydrogenase is an essential enzyme to cell growth. Its deficiency of enzyme plays an important role in senescence and death signaling. Also, it is actually the most common clinically important enzyme defect, not only in hematology, but also among all human known diseases. Clinical consequences of enzyme deficiency are: neonatal hyperbilirubinemia, acute hemolytic anemia, and chronic hemolytic anemia. The enzyme gene spans 18 kb on the X chromosome [xq28] and contains 13 exons. Its promoter is embedded in a CpG island that is conserved from mice to humans. The development of a number of PCR-based methods for the detection of known mutations in Glucose- 6-phosphate dehydrogenase has made it possible to detect enzyme deficiency and identify the specific mutation responsible with relative ease. We will discuss the mentioned clinical manifestations of glucose-6-phosphate dehydrogenase deficiency, Genetics, biochemistry and pathophysiology of the enzyme in details using newer published data and present most of the studies in Iranian population

Rubella infection with autoimmune hemolytic anemia.

A 4-yr-old boy developed autoimmune hemolytic anemia after rubella infection and clinical manifestations cleared up after decrease in rubella specific IgM titer without any specific therapy.

frequency and age presentation of G6PD deficiency in 200 patients of hemolytic anaemia

To determine the frequency of G6PD deficiency in the etiology of anaemia and jaundice and to determine the most common age of presentation with anaemia and jaundice due to G6PD deficiency in adults. We did a hospital based study in the department of Medicine Khyber Teaching Hospital Peshawar from June 2003 to December 2003. The data of adult patients with signs and symptoms of anaemia and jaundice was collected on structured proforma. The clinical presentation and laboratory investigation results were documented. Out of 200 patients studied, 24 [12%] patients were found to be deficient in G6PD enzyme. The male to female ratio was 21:3 [87.5% and 12.5%] respectively. The age of appearance of jaundice in adults varied [most common age from 13 to 17 years]. The most common signs and symptoms were jaundice, anaemia and haemoglobinuria. All G6PD deficient patients except one recovered spontaneously when the offending precipltating factor were stopped or treated. One [0.5%] died because of rapid fall of haemoglobin and delayed recognition of the condition and subsequent blood transfusion. G6PD deficiency is not an uncommon cause of jaundice and anaemia in our patients. The jaundice due to G6PD mainly affects the adults in 2nd or 3rd decade. Therefore all the children and adults with jaundice and anaemia should be screened for G6PD status

Anemia hemolítica por déficit de piruvato-cinasa como manifestación inicial de Enfermedad de Wilson: caso clínico / Hemolytic anemia by to deficit pyruvate kinase as initial manifestation of Wilson`s disease: Clinical case

Se presenta el caso de un paciente de 16 años con anemia hemolítica por déficit de piruvato cinasa como manifestación inicial de Enfermedad de Wilson. El diagnóstico se estableció con la presencia de anillo de Kayser Fleisher, niveles bajos de ceruloplasmina sérica y niveles altos de cobre urinario.