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ABSTRACT Objective: To report a pediatric case of drug-induced thrombotic microangiopathy caused by cocaine Case description: We report a nine-month-old patient who developed thrombotic microangiopathies after extreme cocaine intoxication, multiple organ dysfunction syndrome with hemodynamic dysfunction, anuric renal failure, liver failure, encephalopathy, and myocardial injury, corresponding phenotypically to thrombocytopenia-associated multiple organ failure. The patient received continuous venous hemofiltration and therapeutic plasma exchange, recovering satisfactorily. She was discharged after 30 days of hospitalization under the guidance of the childcare service, and was healthy after one year of follow-up. Toxicological samples confirmed high levels of cocaine and derivatives in blood, urine and hair. Comments: To our knowledge, this is the first reported pediatric case. There are particularities of cocaine intoxication pathophysiology that can trigger thrombotic microangiopathies because of vasoconstriction, direct endothelial injury, platelet activation, and increasing von Willebrand factor and fibrinogen levels. All of which results in a prothrombotic state, inflammatory dysregulation, and microvascular thrombi. The increasing use of cocaine, especially among young adults, puts children at high risk of toxicity, either by passive unintentional exposure, or abuse due to the increased availability in homes.
RESUMO Objetivo: Relatar um caso pediátrico de microangiopatia trombótica induzida por drogas causada por cocaína Descrição do caso: Relatamos uma paciente de nove meses de idade que desenvolveu microangiopatia trombótica após intoxicação extrema por cocaína, síndrome de disfunção de múltiplos órgãos com disfunção hemodinâmica, insuficiência renal anúrica, insuficiência hepática, encefalopatia e lesão miocárdica, correspondendo fenotipicamente à falência múltipla de órgãos associada à trombocitopenia. A paciente recebeu hemofiltração venosa contínua e plasmaférese terapêutica, recuperando-se satisfatoriamente. Recebeu alta após 30 dias de internação sob orientação do serviço de puericultura e estava saudável após um ano de seguimento. Amostras toxicológicas confirmaram altos níveis de cocaína e derivados no sangue, urina e cabelos. Comentários: Até onde sabemos, este é o primeiro caso pediátrico relatado. Existem particularidades da fisiopatologia da intoxicação por cocaína que podem desencadear a microangiopatia trombótica devido à vasoconstrição, lesão endotelial direta, ativação plaquetária e aumento do fator de von Willebrand e dos níveis de fibrinogênio. Tudo isso resulta em um estado pró-trombótico, desregulação inflamatória e trombos microvasculares. O uso crescente de cocaína, principalmente entre adultos jovens, coloca as crianças em alto risco de toxicidade, seja por exposição passiva não intencional ou abuso devido à maior disponibilidade nas residências.
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La púrpura trombótica trombocitopénica es una entidad poco frecuente en pediatría, pero de alta mortalidad sin tratamiento adecuado y oportuno. Se caracteriza por presentar anemia hemolítica microangiopática asociada a signos y síntomas neurológicos, cardíacos, abdominales y menos frecuentemente renales; puede estar acompañada de fiebre. En niños, el diagnóstico se basa en los hallazgos clínicos y de laboratorio. La actividad de ADAMTS13 <10 % apoya, pero no confirma el diagnóstico y, dada la gravedad de la patología, el resultado no debe retrasar el inicio del tratamiento. Se presenta una paciente de 15 años, previamente sana, con signos neurológicos asociados a anemia hemolítica y trombocitopenia. Durante su internación, se arribó al diagnóstico de púrpura trombótica trombocitopénica adquirida.
Thrombotic thrombocytopenic purpura is a rare disease in pediatrics, but it has a high mortality if not managed in an adequate and timely manner. It is characterized by microangiopathic hemolytic anemia associated with neurological, cardiac, abdominal, and less frequently, renal signs and symptoms; it may be accompanied by fever. In children, diagnosis is based on clinical and laboratory findings. ADAMTS13 activity < 10% supports the diagnosis but does not confirm it and, given its severity, the result should not delay treatment initiation. Here we describe the case of a previously healthy 15-year-old female patient with neurological signs associated with hemolytic anemia and thrombocytopenia. During hospitalization, she was diagnosed with acquired thrombotic thrombocytopenic purpura.
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Humanos , Feminino , Adolescente , Púrpura Trombocitopênica Trombótica/complicações , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , Anemia Hemolítica/diagnóstico , PediatriaRESUMO
Thrombotic thrombocytopenic purpura is a rare disease in pediatrics, but it has a high mortality if not managed in an adequate and timely manner. It is characterized by microangiopathic hemolytic anemia associated with neurological, cardiac, abdominal, and less frequently, renal signs and symptoms; it may be accompanied by fever. In children, diagnosis is based on clinical and laboratory findings. ADAMTS13 activity < 10% supports the diagnosis but does not confirm it and, given its severity, the result should not delay treatment initiation. Here we describe the case of a previously healthy 15-year-old female patient with neurological signs associated with hemolytic anemia and thrombocytopenia. During hospitalization, she was diagnosed with acquired thrombotic thrombocytopenic purpura.
La púrpura trombótica trombocitopénica es una entidad poco frecuente en pediatría, pero de alta mortalidad sin tratamiento adecuado y oportuno. Se caracteriza por presentar anemia hemolítica microangiopática asociada a signos y síntomas neurológicos, cardíacos, abdominales y menos frecuentemente renales; puede estar acompañada de fiebre. En niños, el diagnóstico se basa en los hallazgos clínicos y de laboratorio. La actividad de ADAMTS13 <10 % apoya, pero no confirma el diagnóstico y, dada la gravedad de la patología, el resultado no debe retrasar el inicio del tratamiento. Se presenta una paciente de 15 años, previamente sana, con signos neurológicos asociados a anemia hemolítica y trombocitopenia. Durante su internación, se arribó al diagnóstico de púrpura trombótica trombocitopénica adquirida.
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Anemia Hemolítica , Pediatria , Púrpura Trombocitopênica Trombótica , Feminino , Humanos , Criança , Adolescente , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , Púrpura Trombocitopênica Trombótica/complicações , Anemia Hemolítica/diagnósticoRESUMO
Abstract Thrombotic microangiopathies are disorders characterized by nonimmune microangiopathic hemolytic anemia, thrombocytopenia, and multi-systemic failure. They are classified as thrombotic thrombocytopenic purpura, atypical hemolytic-uremic syndrome, and typical hemolytic uremic syndrome. The latter is associated with intestinal infections by Shiga toxin-producing bacteria. Typical hemolytic uremic syndrome in adults is an extremely rare condition, characterized by high morbidity and mortality. It has been seldom described in solid organ transplant recipients. Here is presented the case of a kidney transplant recipient who had typical hemolytic uremic syndrome with multisystem commitment, refractory to management and with a fatal outcome.
Resumo Microangiopatias trombóticas são distúrbios caracterizados por anemia hemolítica microangiopática não imune, trombocitopenia e insuficiência multissistêmica. Elas são classificadas como púrpura trombocitopênica trombótica, síndrome hemolítico-urêmica atípica e síndrome urêmica hemolítica típica. Essa última está associada a infecções intestinais por bactérias produtoras da toxina Shiga. A síndrome hemolítica urêmica típica em adultos é uma condição extremamente rara, caracterizada por alta morbimortalidade. Esta é raramente descrita em receptores de transplantes de órgãos sólidos. Apresentamos aqui o caso de um receptor de transplante renal que apresentava síndrome hemolítico-urêmica típica com comprometimento multissistêmico, refratário ao tratamento, e com desfecho fatal.
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Humanos , Adulto , Púrpura Trombocitopênica Trombótica , Transplante de Rim , Escherichia coli Shiga Toxigênica , Síndrome Hemolítico-Urêmica Atípica , Anemia HemolíticaRESUMO
Congenital thrombotic thrombocytopenic purpura (cTTP) is an inherited disease that is sometimes fatal in early childhood. cTTP is similar to idiopathic thrombotic thrombocytopenic purpura (iTTP); both are characterized by varying levels of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and end-organ damage secondary to occlusion of the microvasculature. cTTP is caused by a partial or total deficiency or loss of function of ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13). We report the case of a 33-year-old woman who was mistakenly diagnosed with primary immune thrombocytopenia (ITP) during childhood. The patient was referred to our center with dyspnea, fatigue, fever, and jaundice with no clinical bleeding. Laboratory features were compatible with MAHA; ADAMTS-13 activity was at 0%, with negativity for ADAMTS-13 antibodies. We concluded the final diagnosis was cTTP. The triggering factor identified for MAHA was a double infection: central venous catheter bacterial infection and atypical pneumonia. After 7 days of treatment with antibiotics and ongoing total plasma exchange (TPE), the patient responded favorably. Our patient received fresh frozen plasma (FFP) infusion once every 2 weeks, and prophylactic voriconazole remained under control at the time of writing. As demonstrated in this case, effective treatment of the trigger cause helps reduce the need for continuous FFP exposure and controls the MAHA.
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Introducción: La púrpura trombocitopénica trombótica puede presentarse en menos del 2 por ciento de los pacientes con lupus eritematoso sistémico. Esta asociación implica un aumento de la mortalidad y un periodo de remisión más prolongado. Objetivo: Se presenta el caso de paciente peruana que desarrolló esta asociación y presentó complicaciones relacionadas con shock séptico. Caso clínico: Paciente femenina, con antecedente de púrpura trombocitopénica inmunológica y lupus eritematoso sistémico, acudió a emergencia por presentar palidez cutánea generalizada, petequias en miembros inferiores y hematuria. Posteriormente, su estado de salud se complicó con un shock séptico y deterioro del nivel de conciencia. Por todo esto, es referida a un hospital de mayor complejidad y hace su ingreso a la unidad de cuidados intensivos. La clínica y los exámenes de laboratorio revelaron hallazgos compatibles con púrpura trombocitopénica trombótica (anemia grave, plaquetopenia, esquistositosis) y lupus eritematoso sistémico activo grave. Antes de ser referida, recibió pulsos de metilprednisona y prednisona. Ya en unidad de cuidados intensivos, se cambió a soporte ventilatorio y tratamiento antibiótico. Con el diagnóstico presuntivo de púrpura trombocitopénica trombótica, asociada a lupus eritematoso sistémico activo grave, se inició tratamiento oportuno con plasmaféresis, corticoterapia y ciclofosfamida. La paciente recuperó los niveles plaquetarios y el nivel óptimo de conciencia. Actualmente acude a controles. Conclusiones: La púrpura trombocitopénica trombótica es una emergencia hematológica con alta mortalidad en ausencia de tratamiento. Su reconocimiento oportuno, sin dosificación de la proteína ADAMTS13, en esta asociación poco frecuente con lupus eritematoso sistémico es importante en el buen pronóstico del paciente(AU)
Introduction: Thrombotic thrombocytopenic purpura may occur in less than 2 percent of patients with systemic lupus erythematosus. This association implies an increase in mortality and a longer remission period. Objective: We present the case of a Peruvian woman who developed this association, and complicating herself with septic shock. Clinical case: A female patient, with a history of immunological thrombocytopenic purpura and systemic lupus erythematosus, comes to the emergency room due to generalized skin pallor, lower limb petechiae and hematuria. Subsequently, her state of health gets complicated with a septic shock and deterioration of the level of consciousness. For all of this, she was referred to a hospital of greater complexity and makes admission to an intensive care unit. Clinical and laboratory tests revealed findings compatible with thrombotic thrombocytopenic purpura (severe anemia, platelet disease, schistositosis) and severe active systemic lupus erythematosus. Before being referred, she received pulses of methylprednisone and prednisone. When already in the intensive care unit, it was changed to ventilatory support andantibiotic treatment. With the presumptive diagnosis of thrombotic thrombocytopenic purpura, associated with severe active systemic lupus erythematosus, a timely treatment was initiated with plasmapheresis, corticosteroids and cyclophosphamide. The patient recovered platelet levels and optimal level of consciousness. She is currently going to controls. Conclusions: Thrombotic thrombocytopenic purpura is a hematological emergency with high mortality in the absence of treatment. Its timely recognition, without dosing of ADAMTS13 protein, in this rare association with systemic lupus erythematosus is important in the good prognosis of the patient(AU)
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Humanos , Feminino , Púrpura Trombocitopênica/complicações , Plasmaferese/métodos , Unidades de Terapia Intensiva , Lúpus Eritematoso Sistêmico/complicações , Púrpura Trombocitopênica/tratamento farmacológicoRESUMO
SUMMARY: GDM is linked with overexpression of inflammatory cytokines and increased oxidative stress, leading to endothelial dysfunction and vascular disorder. Weaimed to examine the expression of ADAMTS13 and PCNA in the placentas of gestational diabetes mellitus (GDM) patients to investigate the effects of hypoxia, induced by GDM, on proliferation and extracellular matrix formation in the maternal and fetal placenta cells. A total of 60 placentas were collected from pregnant women admitted to the obstetrics clinic. Thirty of them were diagnosed with GDM, and 30 of them were diagnosed with non-GDM patients. Samples were fixed in 10 % formaldehyde, after routine follow-up, embedded in paraffin wax. Sections of 5 µm were cut stained with Mayer Hematoxylin-Eosin, examined under a light microscope. Sections for immunohistochemical analysis were cut and processed for antigen retrievalin citrate solution. Sections were incubated with ADAMTS13 and PCNA primary antibodies, counterstained with hematoxylin, and evaluate under a light microscope. In histopathological examination, the non-diabetic placentas showed that decidua cells in the maternal region were polygonal with oval nuclei and organized in groups. In the GDM group, there were pyknosis and apoptotic changes in decidua cell nuclei. Vacuolar areas were observed in large cavities in maternal connective tissue. Inflammation and dilatation with congestion were observed in the blood vessels of the villus. In the GDM group, positive ADAMTS13 expression was observed in the decidua cells vascular endothelial cells, and surrounding connective tissue fibroblast cells. In the GDM group, a significant increase in PCNA expression was observed in decidua cells, connective tissue cells and endothelial cells. Functional changes in ADAMTS13 proteases and PCNA were thought to induce maternal and fetal complications by stimulating extracellular matrix development.
RESUMEN: La diabetes gestacional está relacionada con la sobreexpresión de citocinas inflamatorias y aumento del estrés oxidativo, lo que lleva a una disfunción endotelial y un trastorno vascular. Nuestro objetivo fue examinar la expresión de ADAMTS13 y PCNA en las placentas con diabetes mellitus gestacional (DMG) para investigar los efectos de la hipoxia inducida por DMG sobre la proliferación y formación de matriz extracelular en células placentarias maternas y fetales. Se recolectaron un total de 60 placentas de mujeres embarazadas ingresadas a la consulta de obstetricia. Treinta de ellas fueron diagnosticadas con DMG y 30 diagnosticadas sin DMG. Las muestras se fijaron en formaldehído al 10 %, y luego de un seguimiento de rutina, fueron embebidas en parafina. Se cortaron secciones de 5 µm teñidas con hematoxilina-eosina de Mayer, las que fueron examinadas bajo un microscopio óptico. Se cortaron y procesaron las secciones para el análisis inmunohistoquímico para la recuperación de antígeno en solución de citrato. Las secciones se incubaron con anticuerpos primarios ADAMTS13 y PCNA, se contratiñeron con hematoxilina y se evalua- ron con un microscopio óptico. En el examen histopatológico, las placentas no diabéticas mostraron que las células de la decidua en la región materna eran poligonales con núcleos ovalados y organizadas en grupos. En el grupo de DMG, se observó picnosis y cambios apoptóticos en los núcleos de las células de la decidua. Se observaron áreas vacuolares en el tejido conectivo materno. En los vasos sanguíneos de las vellosidades se observó inflamación y dilatación con congestión. En el grupo de DMG, se observó expresión positiva de ADAMTS13 en las células de la decidua, en las células endoteliales vasculares y en los fibroblastos del tejido conectivo circundante. En el grupo de DMG se observó un aumento significativo de la expresión de PCNA en células de la decidua, células de tejido conectivo y en las células endoteliales. Se considera que los cambios funcionales en las proteasas ADAMTS13 y PCNA inducen a complicaciones maternas y fetales al estimular el desarrollo de la matriz extracelular.
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Humanos , Feminino , Gravidez , Adulto , Placenta/metabolismo , Diabetes Gestacional/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteína ADAMTS13/metabolismoRESUMO
Sickle cell disease (SCD) comprises a group of genetic disorders characterized by the presence of the hemoglobin (Hb) S in homozygosis or in heterozygosis with some other Hb variant or in interaction with thalassemia. SCD is characterized by a very complex pathophysiology, which determines a wide variability of clinical manifestations, including a chronic state of hypercoagulability responsible for the increased risk of thromboembolic events. ADAMTS13 and von Willebrand factor (VWF) play an important role in arterial and venous thrombosis. Thus, the aim of this study was to understand how the ADAMTS13-VWF axis behaves in sickle cell disease, as well as whether there is an association of these markers with the use of hydroxyurea (HU). This is a cross-sectional study conducted with 40 patients diagnosed with SCD and 40 healthy individuals. The analysis of the ADAMTS13-VWF axis was comparatively performed between groups of patients and controls and, afterwards, between patients with SCD who were users and non-users of HU. ADAMTS13 activity, ADAMTS13 activity/VWF:Ag, and ADAMTS13:Ag/VWF:Ag ratios were significantly lower and VWF:Ag levels significantly higher in SCD patients when compared to the controls. There was no statistically significant difference in ADAMTS13:Ag and VWF collagen binding (VWF:CB) levels between the groups evaluated. Among the categories of HU use, there was no statistically significant difference in any of the evaluated markers. As a conclusion, we could observe that the ADAMTS13-VWF axis is altered in SCD when compared to healthy individuals and that there is no association between these markers and the use of HU.
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Proteína ADAMTS13/sangue , Anemia Falciforme/sangue , Fator de von Willebrand/metabolismo , Adolescente , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Estudos Transversais , Feminino , Humanos , Hidroxiureia/administração & dosagem , Masculino , Trombose Venosa/sangue , Trombose Venosa/etiologiaRESUMO
Introduction: Introduction: Thrombotic microangiopathies (TMAs) are rare disorders associated with fatal outcomes if left uncared for. However, healthcare problems in developing countries tend to limit medical assistance to patients. Methods: Methods: We prospectively studied an Argentine cohort of 294 consecutive patients from 2013 to 2016. Patients' subcategory classification relied on clinical symptoms and presence or absence of trigger events associated with TMA. Results: Main suspected disorders were the primary TMAs known as thrombotic thrombocytopenic purpura (TTP) (n = 72/294, 24%) and atypical haemolytic uraemic syndrome (aHUS) (n = 94/294, 32%). In acute phase, demographic parameters for acquired TTP (aTTP) (n = 28) and aHUS (n = 47) showed that both groups were characterised by a young median age (37 and 25 years, respectively) and female predominance (60% and 86%). Median of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 activity was significantly lower in aTTP than in aHUS group (1.4% vs 83%) and was associated with a more severe thrombocytopenia (15 × 109 vs 53 × 109/L). Creatinine (Cr) and urea (Ur) were significantly increased in aHUS compared to aTTP subjects (Cr: 3.7 vs 0.7 mg/dL, Ur: 118 vs 33 mg/dL). Gastrointestinal and neurological symptoms were more frequent in aHUS and aTTP, respectively. Conclusion: The first description of a TMA cohort in Argentina revealed similar clinical presentations to those of other countries.
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Resumen Introducción: El tipo de grupo sanguíneo entre otros factores, influye en los niveles plasmáticos del Factor de von Willebrand (FvW), su actividad biológica podría incidir en el desarrollo de eventos trombóticos y hemorrágicos. Objetivo: Describir las características y los mecanismos de reacciones postrasduccionales del grupo sanguíneo que permiten la variación en la concentración plasmática del FvW. Materiales y métodos: Revisión teórico descriptiva de tipo documental. Las bases de datos consultadas fueron Medline, Lilacs, ScienceDirect, Scopus, SciELO, Proquest, Ovid y Pubmed. Como criterio de selección se incluyeron artículos en idioma inglés y español a partir del año 2010 y algunos anteriores como referente histórico. Resultados: Se describieron los principales mecanismos e investigaciones que evidencian la influencia del tipo de grupo sanguíneo ABO en los niveles plasmáticos del FvW, así como la estructura y función de dicha proteína. Conclusiones: Las concentraciones plasmáticas del FvW pueden depender del tipo de grupo sanguíneo, la edad, sexo, embarazo, ciclo menstrual, variación de proteínas y factores bioquímicos e inmunológicos. Se podría tener en cuenta el tipo de grupo sanguíneo de los pacientes como un posible factor predictor a futuro de complicaciones clínicas tanto trombóticas como hemorrágicas.
Abstract Introduction: The type of blood group among other factors influences the plasma levels of von Willebrand Factor (FvW) and its biological activity could influence the development of thrombotic and hemorrhagic events. Objective: To describe the characteristics and mechanisms of post-translational reactions of the blood group that generate variation in the plasma concentration of FvW. Materials and methods: A descriptive theoretical review of documentary type. The databases consulted were Medline, Lilacs, ScienceDirect, Scopus, SciELO, Proquest, Ovid and Pubmed. As a selection criterion, articles in English and Spanish were included beginning in 2010 and some previous ones as historical reference. Results: The main mechanisms and investigations that show the influence of the ABO blood group type on the plasma levels of FvW, as well as the structure and function of this protein were described. Conclusions: FvW plasma concentrations may depend on the type of blood group, age, sex, pregnancy, menstrual cycle, protein variation and biochemical and immunological factors. The type of blood group of patients could be considered as a possible future predictor of both thrombotic and hemorrhagic clinical complications.
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Humanos , Antígenos de Grupos Sanguíneos , Fator de von Willebrand , Trombofilia , Proteína ADAMTS13RESUMO
ABSTRACT Background: Thrombotic thrombocytopenic purpura (TTP) is a potentially fatal disease that requires early diagnosis and treatment that can be made possible by applying the PLASMIC score. This study aims to evaluate this score applicability for patients with suspected TTP in a developing country. Methods: This was a retrospective study performed at a tertiary hospital in the northeastern region of Brazil. Patients were analyzed in two groups: ADAMTS13 activity <10% and activity >10%. Patients were stratified according to the PLASMIC score, and the level of agreement between the PLASMIC score and the ADAMTS13 activity was evaluated. Results: Eight patients with thrombotic microangiopathy were included. Four patients had ADAMTS13 activity <10%, all with a PLASMIC score =6. The other four had ADAMTS13 activity >10%, all with a score <6. Based on a score =6 for presumptive diagnosis of TTP, we attained a 100% diagnostic accuracy in our sample. The PLASMIC score was also able to accurately predict response to plasma exchange and the risk of long-term unfavorable outcomes. Conclusions: The reproducibility of the PLASMIC score was quite satisfactory in our sample. It accurately discriminates between patients who had ADAMTS13 deficiency and those with normal enzyme activity, precluding the need for specific laboratory evaluation, which is not always available. This score can be useful for an early diagnosis and indicates which patients will benefit from the treatment in developing countries.
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Humanos , Masculino , Feminino , Gravidez , Adolescente , Adulto , Pessoa de Meia-Idade , Púrpura Trombocitopênica Trombótica , Ativador de Plasminogênio Tecidual , Microangiopatias Trombóticas/terapia , Proteína ADAMTS13RESUMO
BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a potentially fatal disease that requires early diagnosis and treatment that can be made possible by applying the PLASMIC score. This study aims to evaluate this score applicability for patients with suspected TTP in a developing country. METHODS: This was a retrospective study performed at a tertiary hospital in the northeastern region of Brazil. Patients were analyzed in two groups: ADAMTS13 activity <10% and activity >10%. Patients were stratified according to the PLASMIC score, and the level of agreement between the PLASMIC score and the ADAMTS13 activity was evaluated. RESULTS: Eight patients with thrombotic microangiopathy were included. Four patients had ADAMTS13 activity <10%, all with a PLASMIC score =6. The other four had ADAMTS13 activity >10%, all with a score <6. Based on a score =6 for presumptive diagnosis of TTP, we attained a 100% diagnostic accuracy in our sample. The PLASMIC score was also able to accurately predict response to plasma exchange and the risk of long-term unfavorable outcomes. CONCLUSIONS: The reproducibility of the PLASMIC score was quite satisfactory in our sample. It accurately discriminates between patients who had ADAMTS13 deficiency and those with normal enzyme activity, precluding the need for specific laboratory evaluation, which is not always available. This score can be useful for an early diagnosis and indicates which patients will benefit from the treatment in developing countries.
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Von Willebrand disease (VWD) is a common cause of bleeding worldwide. Analysis of von Willebrand factor (VWF) multimer distribution (VWF:MD) is essential to properly classify and treat different types of VWD, and it is performed using a SDS agarose gel electrophoresis followed by Western blotting, a handmade technique that demands days to be completed and requires skillful execution. Aiming both to facilitate gel production and to shorten the preparation time, we developed an uncomplicated technique to provide agility in the analysis of VWF:MD, so that it can be easily accomplished in the routine practice of hemostasis laboratories. On that account, we used a commercial vertical mini-gel electrophoresis system for SDS-PAGE and a semi-dry transfer system, which allowed us to analyze VWF:MD of various samples in a period shorter than 12â¯h. This technique differentiated VWF:MD in human and animal plasmas under normal, congenital and acquired (experimental envenomation by Bothrops jararaca snake) conditions. This optimized method is cheap, rapid, reproducible, easy to be performed, and uses electrophoresis and Western blotting systems available in most laboratories. All these advantages encourage hemostasis professionals to use it in their routine practices. In order to facilitate the setup and accomplishment of the whole procedure step by step, videos were appended to the article.
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Eletroforese em Gel Bidimensional/métodos , Doenças de von Willebrand/diagnóstico , Fator de von Willebrand/metabolismo , Animais , Humanos , Masculino , Ratos , Ratos Wistar , Doenças de von Willebrand/patologia , Fator de von Willebrand/análiseRESUMO
Von Willebrand disease (VWD) is a common cause of bleeding worldwide. Analysis of von Willebrand factor (VWF) multimer distribution (VWF:MD) is essential to properly classify and treat different types of VWD, and it is performed using a SDS agarose gel electrophoresis followed by Western blotting, a handmade technique that demands days to be completed and requires skillful execution. Aiming both to facilitate gel production and to shorten the preparation time, we developed an uncomplicated technique to provide agility in the analysis of VWF:MD, so that it can be easily accomplished in the routine practice of hemostasis laboratories. On that account, we used a commercial vertical mini-gel electrophoresis system for SDS-PAGE and a semi-dry transfer system, which allowed us to analyze VWF:MD of various samples in a period shorter than 12?h. This technique differentiated VWF:MD in human and animal plasmas under normal, congenital and acquired (experimental envenomation by Bothrops jararaca snake) conditions. This optimized method is cheap, rapid, reproducible, easy to be performed, and uses electrophoresis and Western blotting systems available in most laboratories. All these advantages encourage hemostasis professionals to use it in their routine practices. In order to facilitate the setup and accomplishment of the whole procedure step by step, videos were appended to the article.
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BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a hematologic disease that can be fatal if not treated early. We aimed to describe the clinical characteristics of Mexican patients with idiopathic TTP. STUDY DESIGN AND METHODS: We conducted a retrospective study, including all adult patients diagnosed with idiopathic TTP from 2011 to 2017 in two Mexican centers. We further compared our results with the published literature. RESULTS: Twenty patients were included; 70% were female, with a median age of 38.5 years at diagnosis (range 16-63). The median time from onset of symptoms to hospital admission was 1.5 days (range 0-16). Most patients (85%) presented with at least one systemic manifestation at admission (including fever) and 90% had neurological symptoms, most of them major (70%) including loss of consciousness, transient focal abnormalities, headache, and confusion. Only one patient (5%) had the classical pentad at the time of admission. Kidney failure was present in 25% of patients and hemorrhagic symptoms in 60%. Digestive and cardiorespiratory symptoms were less common (45% and 15%, respectively). Median platelet count and lactate dehydrogenase were 10 500/µL and 1319 IU/L, respectively. Eighty percent of patients achieved remission following treatment. Patients admitted within the first 48 hours (after the onset of symptoms) tended to have better overall survival. CONCLUSION: Clinical presentation in Mexican TTP patients is similar to that in other countries. Early admission and a high suspicion for the disease will avoid delays in the initial work-up and initiation of therapy, further improving prognosis.
Assuntos
Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , Adolescente , Adulto , Diagnóstico Precoce , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Prognóstico , Púrpura Trombocitopênica Trombótica/patologia , Estudos Retrospectivos , Prevenção Secundária , Adulto JovemRESUMO
BACKGROUND: Thrombotic thrombocytopenic purpura is a very rare hereditary blood deficiency disorder of ADAMTS13 (von Willebrand factor-cleaving protease) and a life-threatening thrombotic microangiopathy characterized by thrombocytopenia and microangiopathic hemolytic anemia. The deficiency in ADAMTS13 metalloprotease, which cleaves the von Willebrand factor, may be congenital or acquired. The congenital form is caused by inherited mutations in the ADAMTS13 gene. The diagnosis is challenging due to the nonspecific signs and symptoms, as well as the rarity of the disease. CASE PRESENTATION: We present an unusual case of a 20-year-old feoderm woman from northeast region of Brazil who manifested thrombocytopenia during her pregnancy which was believed to be immune thrombocytopenic purpura. CONCLUSIONS: Considering the importance of a differential diagnosis of thrombotic microangiopathic disorders, congenital thrombotic thrombocytopenic purpura may mimic the signs and symptoms of pre-eclampsia/eclampsia, hemolysis with elevated liver enzymes and low platelet count syndrome, and atypical hemolytic-uremic syndrome. It should be considered in suspect cases in patients with an ADAMTS13 activity at 5% without ADAMTS13 antibodies.
Assuntos
Proteína ADAMTS13/deficiência , Complicações Hematológicas na Gravidez/diagnóstico , Púrpura Trombocitopênica Trombótica/diagnóstico , Cesárea , Diagnóstico Tardio , Diagnóstico Diferencial , Feminino , Humanos , Recém-Nascido , Megacariócitos/citologia , Troca Plasmática , Gravidez , Complicações Hematológicas na Gravidez/sangue , Complicações Hematológicas na Gravidez/terapia , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/genética , Púrpura Trombocitopênica Trombótica/terapia , Ultrassonografia Pré-Natal , Adulto JovemRESUMO
Objectives The aim of this study was to investigate plasma ADAMTS-13 activity in patients with proliferative lupus nephritis and to evaluate the role of clinical, laboratory and pathological features, especially the vascular lesions in lupus nephritis. Methods Plasma samples from 163 class III and IV lupus nephritis patients confirmed by biopsy examinations and 98 normal controls were collected. ADAMTS-13 activity was evaluated by a residual collagen binding assay. IgG autoantibodies against ADAMTS-13 were detected by ELISA using recombinant ADAMTS-13 as a solid-phase ligand. Levels of vWF were measured by ELISA. Their associations with clinical, laboratory and pathological features were further assessed. Results Plasma ADAMTS-13 activity in lupus nephritis patients was significantly lower than that in normal controls (84 ± 21% vs. 90 ± 13%, p = 0.005). IgG ADAMTS-13 autoantibodies were detected in only three patients. The plasma level of vWF was significantly higher in the lupus nephritis group than in normal controls (1.00 ± 0.79 vs. 0.70 ± 0.30, p = 0.025). Plasma ADAMTS-13 activity was negatively correlated with the level of serum creatinine and proteinuria ( r = -0.354, p < 0.001; r = -0.200, p = 0.011, respectively). Patients with a higher level of ADAMTS-13 activity had significantly higher levels of factor H (401.51 ± 183.01 µg/ml vs. 239.02 ± 155.45 µg/ml, p = 0.005). Plasma ADAMTS-13 activity was negatively associated with total pathological AI scores ( r = -0.326, p < 0.001), endocapillary hypercellularity ( r = -0.419, p < 0.001), cellular crescents ( r = -0.274, p < 0.001), subendothelial hyaline deposits ( r = -0.266, p = 0.001), interstitial inflammatory cell infiltration ( r = -0.304, P < 0.001), tubular atrophy ( r = -0.199, p = 0.011), acute glomerular vascular lesions ( r = -0.344, p < 0.001) and acute renal vascular lesions ( r = -0.338, p < 0.001). No association was found between level of vWF and plasma ADAMTS-13 activity ( r = 0.033, p = 0.671). Low level of ADAMTS-13 activity was a risk factor for renal outcomes ( p = 0.039, HR = 0.047, 95% CI: 0.120-1.005). Conclusions Decreased ADAMTS-13 activity was found in patients with proliferative lupus nephritis, and plasma ADAMTS-13 activity was closely associated with renal injury indices, especially pathological vascular scores. The role of ADAMTS-13 in the disease remains to be further investigated.
Assuntos
Proteína ADAMTS13/sangue , Autoanticorpos/sangue , Rim/patologia , Nefrite Lúpica/sangue , Nefrite Lúpica/patologia , Adolescente , Adulto , Idoso , China , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Nefrite Lúpica/complicações , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Microangiopatias Trombóticas/epidemiologia , Adulto Jovem , Fator de von Willebrand/metabolismoRESUMO
INTRODUCTION: Some studies suggest that thrombotic thrombocytopenic purpura (TTP) occurs more often in African Americans. However there is low evidence for this in the literature. The aim of our study was to describe the clinical and biological characteristics of TTP in the Afro-Caribbean population of Martinique. METHODS: We retrospectively analysed all patients with TTP diagnosed at the Fort-de-France hospital between 2008, January 1st and 2015, December 31st. Diagnosis was confirmed if ADAMTS-13 activity was<10 %. RESULTS: Ten patients were included, corresponding to an average annual incidence of 3.2 cases/year/million individuals. None of the patient presented with the association of the five characteristic features of TTP. Microangiopathic haemolytic anaemia and severe peripheral thrombocytopenia (median: 13G/L) was the main presentation leading to diagnosis. There was no kidney involvement in 90 % of all patients, but severe neurological manifestations occurred in 70 %. Classical management including corticosteroids and plasma exchanges allowed clinical remission in 6 out of the 10 cases. If necessary, rituximab or cyclophosphamide was used. The overall survival rate was 90 %. CONCLUSION: In Martinique, the incidence of TTP is twice that reported in similar studies in France. Clinical manifestations seem to differ by more common and more severe neurological involvement. Mortality is low, in part, due to optimal care.
Assuntos
Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/epidemiologia , Púrpura Trombocitopênica Trombótica/terapia , Proteína ADAMTS13/análise , Proteína ADAMTS13/sangue , Adolescente , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Martinica/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: We evaluated the association between plasma levels of VWF, ADAMTS13 and d-Dimer, which consist on endothelial dysfunction and hypercoagulability biomarkers, and cystatin C with retinopathy in type 1 diabetic patients. METHODS: Patients were classified according to presence (n=55) or absence (n=70) of retinopathy. Plasma levels of VWF, ADAMTS13, d-Dimer and cystatin C were evaluated by ELISA and ADAMTS13 activity was evaluated by FRET. RESULTS: Plasma levels of VWF (p=0.033), ADAMTS13 activity (p=0.014), d-Dimer (p=0.002) and cystatin C (p<0.001) were elevated in diabetic patients with retinopathy compared to those without this complication. The multivariate logistic regression analysis showed that ADAMTS13 activity (p=0.031) d-Dimer (p=0.015) and cystatin C (p=0.001) remained associated with retinopathy after adjustment for age, diabetes duration, use of statin, use of ACEi or angiotensin antagonist, use of acetylsalicylic acid and glomerular filtration rate. CONCLUSION: ADAMTS13 activity, d-Dimer and cystatin C are associated with retinopathy in type 1 diabetic patients and are promising biomarkers for the diagnosis and monitoring of diabetic retinopathy.
Assuntos
Proteína ADAMTS13/sangue , Cistatina C/sangue , Diabetes Mellitus Tipo 1/complicações , Retinopatia Diabética/sangue , Retinopatia Diabética/complicações , Desintegrinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fator de von Willebrand/análise , Proteína ADAMTS13/metabolismo , Adulto , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Retinopatia Diabética/diagnóstico , Ensaio de Imunoadsorção Enzimática , Feminino , Transferência Ressonante de Energia de Fluorescência , Humanos , Masculino , Adulto JovemRESUMO
INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is characterized by a reduction in the von Willebrand cleavage protein ADAMTS-13, mainly as a consequence of autoimmunity. Plasma exchange (PEx) is standard, achieving complete remission (CR) in 77-83% of cases, but rates are variable depending on ADAMTS-13 activity and relapse is frequent in patients with <10%. Thus, an effective front-line immunosuppressive treatment is needed. MATERIALS AND METHODS: We administered PEx daily until CR and rituximab 100 mg/dose/week for 4 consecutive weeks to 10 patients with a first TTP episode and 1 relapsed patient (8 females (72%) and 3 males (28%)). Median age was 34 years (15-46) and laboratory parameters at diagnosis were as follows: platelets 11 × 10(9)/l (range 7-27.4 × 10(9)/l), lactate dehydrogenase 1822â U/l (range 705-8220â U/l, normal 70-180â U/l), and haemoglobin 6â g/dl (range 4.2-11.8â g/dl). ADAMTS-13 activity was determined in eight patients and was <10% in all. ADAMTS-13 autoantibody titre was determined in seven patients and was >15â units/ml in all (ref: negative <12, undetermined 12-15, positive >15â units/ml); Shiga toxin was negative in all patients. The median number of PEx until CR was 7 (range 4-12); prednisone 1â mg/kg was administered to six patients. RESULTS: The median follow-up was 22 months (range 4-49) and the estimated 2-year relapse-free survival was 89%; one HIV+ patient relapsed at 8 months follow-up. No complications related to PEx or rituximab were reported. CONCLUSIONS: Our study suggests that low-dose rituximab and PEx are effective as front-line treatment for acute TTP; however, a prospective trial is needed to demonstrate whether low-dose rituximab is as effective as the conventional dose.