Diagnosis and Management of Preeclampsia: Suggested Guidance on the Use of Biomarkers / Diagnóstico e tratamento da pré-eclâmpsia: Sugestão para o uso adequado dos biomarcadores

Abstract Objective It is a challenge to consider preeclampsia (PE) diagnosis and management in low and middle-income settings, where it represents a major public health concern. The placenta is the underlying cause of disease, and the plasma concentrations of proangiogenic and antiangiogenic factors released by the placenta can reflect the risks of disease progression. Antiangiogenic proteins, such as soluble fms-like tyrosine kinase 1 (sFlt-1), and proangiogenic, like placental growth factors (PlGF), are directly and inversely correlated with the disease onset, respectively. Methods Narrative review on the use of biomarkers (sFlt-1 to PlGF ratio) with a suggested guidance protocol. Results Key considerations on the use of biomarkers: the sFlt-1/PlGF ratio is mainly relevant to rule out PE between 20 and 36 6/7 weeks in cases of suspected PE; however, it should not replace the routine exams for the diagnosis of PE. The sFlt-1/PlGF ratio should not be performed after confirmed PE diagnosis (only in research settings). In women with suspected PE, sFlt-1/PlGF ratio < 38 can rule out the diagnosis of PE for 1 week (VPN = 99.3) and up to 4 weeks (VPN= 94.3); sFlt-1/PlGF ratio > 38 does not confirm the diagnosis of PE; however, it can assist clinical management. In cases of severe hypertension and/or symptoms (imminent eclampsia), hospitalization is imperative, regardless of the result of the sFlt-1/PlGF ratio. Conclusion The use of biomarkers can help support clinical decisions on the management of suspected PE cases, especially to rule out PE diagnosis, thus avoiding unnecessary interventions, especially hospitalizations and elective prematurity

Resumo Objetivo um desafio considerar o diagnóstico e o tratamento da pré-eclâmpsia (PE) em locais de baixa e média renda, onde a doença representa um grande problema de saúde pública. A placenta é a causa subjacente da doença, e as concentrações plasmáticas de fatores pró-angiogênicos e antiangiogênicos liberados pela placenta podem refletir os riscos de progressão da doença. Proteínas antiangiogênicas, como a tirosina quinase fms solúvel tipo 1 (sFlt-1), e pró-angiogênicas, como o fator de crescimento placentário (PlGF), estão direta e inversamente correlacionados com o início da doença, respectivamente. Métodos Revisão narrativa sobre o uso de biomarcadores (razão sFlt-1/PlGF) com sugestão de protocolo de orientação para uso clínico. Resultados Principais considerações sobre o uso de biomarcadores: a razão sFlt-1/PlGF é principalmente relevante para descartar PE entre 20 e 36 6/7 semanas em casos de suspeita de PE; entretanto, não deve substituir os exames de rotina para o diagnóstico de PE. A relação sFlt-1/PlGF não deve ser realizada após a confirmação do diagnóstico de PE (apenas em ambientes de pesquisa). Em mulheres com suspeita de PE, a razão sFlt-1/PlGF < 38 pode descartar o diagnóstico de PE por 1 semana (VPN = 99,3) e até 4 semanas (VPN = 94,3); A relação sFlt-1/PlGF > 38 pode auxiliar no manejo clínico. Em casos de hipertensão grave e/ou sintomas (eclâmpsia iminente), a hospitalização é imprescindível, independentemente do resultado da relação sFlt-1/PlGF. Conclusão O uso de biomarcadores pode auxiliar na tomada de decisões clínicas no manejo de casos suspeitos de PE, principalmente para afastar o diagnóstico da doença, evitando intervenções desnecessárias, tais como internações e prematuridade iatrogênica.

Association of LEPTIN and other inflammatory markers with preeclampsia: A systematic review.

Background: Preeclampsia is a serious pregnancy complication that affects 5%-10% of the obstetric population. Objective: To study inflammatory markers associated with preeclampsia. Search Strategy: Searches of articles on the topic published over a 10-year period (2009-2019) were performed in three databases (PubMed, Cochrane, and Embase) using the keywords preeclampsia and inflammatory markers. The PubMed search using 10 years and humans as filters retrieved 124 articles. Using an advanced search strategy, 0 articles were identified in Embase and 10 articles in Cochrane. After screening and eligibility assessment, 13 articles were included in the systematic review and meta-analysis. Meta-analysis and quality assessment of the studies were performed using the Review Manager 5.3 program. Results: For meta-analysis, women with preeclampsia were compared to control women, i.e., pregnancies without arterial hypertension. Leptin levels were significantly higher (p < 0.0002) in women with preeclampsia compared to controls. Total cholesterol was also significantly elevated in women with preeclampsia (p < 0.0001). There was no significant difference in HDL between groups, but women with preeclampsia had significantly increased LDL (p < 0.01). The same was observed for triglycerides, which were significantly increased in women with preeclampsia (p < 0.04) compared to controls. Analysis of TNF-alpha, an important inflammatory marker, showed higher levels in women with preeclampsia (p < 0.03) compared to controls. The same was observed for another important inflammatory marker, interleukin 6, which was significantly increased in women with preeclampsia (p < 0.0002). There was a significant increase of C-reactive protein in women with preeclampsia (p < 0.003) compared to controls. Conclusion: Women with preeclampsia have increased levels of inflammatory markers compared to control women.

Diagnosis and Management of Preeclampsia: Suggested Guidance on the Use of Biomarkers.

OBJECTIVE: It is a challenge to consider preeclampsia (PE) diagnosis and management in low and middle-income settings, where it represents a major public health concern. The placenta is the underlying cause of disease, and the plasma concentrations of proangiogenic and antiangiogenic factors released by the placenta can reflect the risks of disease progression. Antiangiogenic proteins, such as soluble fms-like tyrosine kinase 1 (sFlt-1), and proangiogenic, like placental growth factors (PlGF), are directly and inversely correlated with the disease onset, respectively. METHODS: Narrative review on the use of biomarkers (sFlt-1 to PlGF ratio) with a suggested guidance protocol. RESULTS: Key considerations on the use of biomarkers: the sFlt-1/PlGF ratio is mainly relevant to rule out PE between 20 and 36 6/7 weeks in cases of suspected PE; however, it should not replace the routine exams for the diagnosis of PE. The sFlt-1/PlGF ratio should not be performed after confirmed PE diagnosis (only in research settings). In women with suspected PE, sFlt-1/PlGF ratio < 38 can rule out the diagnosis of PE for 1 week (VPN = 99.3) and up to 4 weeks (VPN= 94.3); sFlt-1/PlGF ratio > 38 does not confirm the diagnosis of PE; however, it can assist clinical management. In cases of severe hypertension and/or symptoms (imminent eclampsia), hospitalization is imperative, regardless of the result of the sFlt-1/PlGF ratio. CONCLUSION: The use of biomarkers can help support clinical decisions on the management of suspected PE cases, especially to rule out PE diagnosis, thus avoiding unnecessary interventions, especially hospitalizations and elective prematurity.

OBJETIVO: É um desafio considerar o diagnóstico e o tratamento da pré-eclâmpsia (PE) em locais de baixa e média renda, onde a doença representa um grande problema de saúde pública. A placenta é a causa subjacente da doença, e as concentrações plasmáticas de fatores pró-angiogênicos e antiangiogênicos liberados pela placenta podem refletir os riscos de progressão da doença. Proteínas antiangiogênicas, como a tirosina quinase fms solúvel tipo 1 (sFlt-1), e pró-angiogênicas, como o fator de crescimento placentário (PlGF), estão direta e inversamente correlacionados com o início da doença, respectivamente. MéTODOS: Revisão narrativa sobre o uso de biomarcadores (razão sFlt-1/PlGF) com sugestão de protocolo de orientação para uso clínico. RESULTADOS: Principais considerações sobre o uso de biomarcadores: a razão sFlt-1/PlGF é principalmente relevante para descartar PE entre 20 e 36 6/7 semanas em casos de suspeita de PE; entretanto, não deve substituir os exames de rotina para o diagnóstico de PE. A relação sFlt-1/PlGF não deve ser realizada após a confirmação do diagnóstico de PE (apenas em ambientes de pesquisa). Em mulheres com suspeita de PE, a razão sFlt-1/PlGF < 38 pode descartar o diagnóstico de PE por 1 semana (VPN = 99,3) e até 4 semanas (VPN = 94,3); A relação sFlt-1/PlGF > 38 pode auxiliar no manejo clínico. Em casos de hipertensão grave e/ou sintomas (eclâmpsia iminente), a hospitalização é imprescindível, independentemente do resultado da relação sFlt-1/PlGF. CONCLUSãO: O uso de biomarcadores pode auxiliar na tomada de decisões clínicas no manejo de casos suspeitos de PE, principalmente para afastar o diagnóstico da doença, evitando intervenções desnecessárias, tais como internações e prematuridade iatrogênica.

Clinical Experience Over 15 Years with the B-Lynch Compression Suture Technique in the Management of Postpartum Hemorrhage.

OBJECTIVE: To describe the clinical experience with the B-Lynch technique in the management of postpartum hemorrhage as well as the factors related to the indication of the technique and to present the success rates of the application of the B-Lynch technique. METHODS: Observational, retrospective, cross-sectional, and analytical study. Patient data was obtained through the study of medical records. The study population comprised of patients who underwent hemostatic suture using the B-Lynch technique, including 104 patients within the period from January 1, 2005, to December 31, 2019. RESULTS: Of the total of 104 patients, 82.7% did not present any complications. Blood transfusion and intensive care unit admission were the most prevalent complications, with 13.5% and 15.4%, respectively. Only 1% of the patients had puerperal and surgical site infections. The factors most related to the application of the technique were the presence of previous cesarean section (30.8%), use of oxytocin (16.3%), and preeclampsia (11.6%). Puerperal hysterectomy was performed in 4.8% of the patients due to failure of the method. CONCLUSION: The clinical experience with the B-Lynch technique was satisfactory since it presented few complications, with excellent results in hemorrhagic control. Previous cesarean section, the use of oxytocin, and preeclampsia stood out as factors related to the indication of the application of the technique, and the success rate in controlling postpartum hemorrhage was 95.2%.

OBJETIVO: Descrever a experiência clínica com a técnica de B-Lynch no manejo da hemorragia pós-parto e os fatores relacionados à indicação da técnica bem como apresentar as taxas de sucesso da aplicação da técnica de B-lynch. MéTODOS: Estudo observacional, retrospectivo, de corte transversal e analítico. Os dados foram obtidos por estudo de prontuário. A população do estudo foi constituída de pacientes submetidas à sutura hemostática com a técnica de B-Lynch, sendo incluídas 104 pacientes dentro do período de 01 de janeiro de 2005 a 31 de dezembro de 2019. RESULTADOS: Do total de 104 pacientes, 82,7% não apresentaram qualquer complicação. A transfusão de sangue e a internação na UTI foram as complicações mais prevalentes, com 13,5% e 15,4%, respectivamente. Apenas 1% teve infecção puerperal e do sítio cirúrgico. Os fatores mais relacionados com a aplicação da técnica foram a presença de cesárea anterior (30,8%), uso de ocitocina (16,3%) e pré-eclâmpsia (11,6%). A histerectomia puerperal foi realizada em 4,8% das pacientes por falha do método. CONCLUSãO: A experiência clínica com a técnica de B-Lynch foi satisfatória, pois apresentou poucas complicações, com excelentes resultados no controle hemorrágico. A cesárea anterior, o uso de ocitocina e a pré-eclâmpsia se destacaram como fatores relacionados à indicação da aplicação da técnica. A taxa de sucesso avaliada foi de 95,2%.

Clinical Experience Over 15 Years with the B-Lynch Compression Suture Technique in the Management of Postpartum Hemorrhage / Experiência clínica ao longo de 15 anos com a técnica de sutura compressiva de B-Lynch no manejo da hemorragia pós-parto

Abstract Objective To describe the clinical experience with the B-Lynch technique in the management of postpartum hemorrhage as well as the factors related to the indication of the technique and to present the success rates of the application of the B-Lynch technique. Methods Observational, retrospective, cross-sectional, and analytical study. Patient data was obtained through the study of medical records. The study population comprised of patients who underwent hemostatic suture using the B-Lynch technique, including 104 patients within the period from January 1, 2005, to December 31, 2019. Results Of the total of 104 patients, 82.7% did not present any complications. Blood transfusion and intensive care unit admission were the most prevalent complications, with 13.5% and 15.4%, respectively. Only 1% of the patients had puerperal and surgical site infections. The factors most related to the application of the technique were the presence of previous cesarean section (30.8%), use of oxytocin (16.3%), and pre-eclampsia (11.6%). Puerperal hysterectomy was performed in 4.8% of the patients due to failure of the method. Conclusion The clinical experience with the B-Lynch technique was satisfactory since it presented few complications, with excellent results in hemorrhagic control. Previous cesarean section, the use of oxytocin, and preeclampsia stood out as factors related to the indication of the application of the technique, and the success rate in controlling postpartum hemorrhage was 95.2%.

Resumo Objetivo Descrever a experiência clínica com a técnica de B-Lynch no manejo da hemorragia pós-parto e os fatores relacionados à indicação da técnica bem como apresentar as taxas de sucesso da aplicação da técnica de B-lynch. Métodos Estudo observacional, retrospectivo, de corte transversal e analítico. Os dados foram obtidos por estudo de prontuário. A população do estudo foi constituída de pacientes submetidas à sutura hemostática com a técnica de B-Lynch, sendo incluídas 104 pacientes dentro do período de 01 de janeiro de 2005 a 31 de dezembro de 2019. Resultados Do total de 104 pacientes, 82,7% não apresentaram qualquer complicação. A transfusão de sangue e a internação na UTI foram as complicações mais prevalentes, com 13,5% e 15,4%, respectivamente. Apenas 1% teve infecção puerperal e do sítio cirúrgico. Os fatores mais relacionados com a aplicação da técnica foram a presença de cesárea anterior (30,8%), uso de ocitocina (16,3%) e pré-eclâmpsia (11,6%). A histerectomia puerperal foi realizada em 4,8% das pacientes por falha do método. Conclusão A experiência clínica com a técnica de B-Lynch foi satisfatória, pois apresentou poucas complicações, com excelentes resultados no controle hemorrágico. A cesárea anterior, o uso de ocitocina e a pré-eclâmpsia se destacaram como fatores relacionados à indicação da aplicação da técnica. A taxa de sucesso avaliada foi de 95,2%.

Pre-eclampsia: Universal Screening or Universal Prevention for Low and Middle-Income Settings?

Pre-eclampsia (PE) is a severe disorder that affects up to 8% of all pregnancies and represents an important cause of maternal and perinatal morbidity and mortality. The screening of the disease is a subject of studies, but the complexity and uncertainties regarding its etiology make this objective a difficult task. In addition, the costs related to screening protocols, the heterogeneity of the most affected populations and the lack of highly effective prevention methods reduce the potential of current available algorithms for screening. Thus, the National Specialized Commission of Hypertension in Pregnancy of the Brazilian Association of Gynecology and Obstetrics Federation (Febrasgo, in the Portuguese acronym) (NSC Hypertension in Pregnancy of the Febrasgo) considers that there are no screening algorithms to be implemented in the country to date and advocates that Aspirin and calcium should be widely used.

A Pré-eclâmpsia (PE) é uma doença grave que acomete ∼ 8% das gestações e representa importante causa de morbimortalidade, tanto materna quanto perinatal. O rastreamento da doença é motivo de estudos, porém a complexidade e as incertezas quanto a sua etiologia tornam esse objetivo bastante difícil. Além disso, os custos relacionados com o rastreamento, a heterogeneidade das populações mais afetadas e ainda a falta de métodos de prevenção de grande eficácia reduzem o potencial dos algoritmos de rastreamento. Assim, a Comissão Nacional Especializada sobre Hipertensão na Gravidez da Federação Brasileira das Associações de Ginecologia e Obstetrícia (CNE Hipertensão na Gravidez da FEBRASGO) considera que não há algoritmos de rastreamento que possam ser aplicados no país nesse momento e defende a utilização dos métodos de prevenção como ácido acetilsalicílico e cálcio de maneira ampla.

Pre-eclampsia/Eclampsia.

Pre-eclampsia is a multifactorial and multisystemic disease specific to gestation. It is classically diagnosed by the presence of hypertension associated with proteinuria manifested in a previously normotensive pregnant woman after the 20th week of gestation. Pre-eclampsia is also considered in the absence of proteinuria if there is target organ damage. The present review takes a general approach focused on aspects of practical interest in the clinical and obstetric care of these women. Thus, it explores the still unknown etiology, current aspects of pathophysiology and of the diagnosis, the approach to disease prediction, its adverse outcomes and prevention. Management is based on general principles, on nonpharmacological and on pharmacological clinical treatment of severe or nonsevere situations with emphasis on the hypertensive crisis and eclampsia. Obstetric management is based on preeclampsia without or with signs of clinical and/or laboratory deterioration, stratification of gestational age in < 24 weeks, between 24 and less than 34 weeks, and ≥ 34 weeks of gestation, and guidance on route of delivery. An immediate puerperium approach and repercussions in the future life of pregnant women who develop preeclampsia is also presented.

A pré-eclâmpsia é uma doença multifatorial e multissistêmica específica da gestação. É classicamente diagnosticada pela presença de hipertensão arterial associada à proteinúria em gestante previamente normotensa após a 20a semana de gestação. A pré-eclâmpsia também é considerada na ausência de proteinúria se houver lesão de órgão-alvo. A presente revisão tem uma abordagem geral focada em aspectos de interesse prático na assistência clínica e obstétrica dessas mulheres. Assim, explora a etiologia ainda desconhecida, aspectos atuais da fisiopatologia e do diagnóstico e diagnóstico diferencial de convulsões, a abordagem da predição da doença, seus resultados adversos e prevenção. A conduta baseia-se em princípios gerais, tratamento clínico não farmacológico e farmacológico de situações graves ou não graves, com ênfase na crise hipertensiva e eclâmpsia. O controle obstétrico se fundamenta na pré-eclâmpsia sem ou com sinais de deterioração clínica e/ou laboratorial, estratificação da idade gestacional abaixo de 24 semanas, entre 24 e menos de 34 semanas e 34 ou mais semanas de gestação e orientação na via de parto. Uma abordagem imediata do puerpério e repercussões na vida futura de gestantes que desenvolvem pré-eclâmpsia também foram apresentadas.

Pré-eclâmpsia/eclâmpsia / Pre-Eclampsia/Eclampsia

A pré-eclâmpsia é uma doença multifatorial e multissistêmica específica da gestação. É classicamente diagnosticada pela presença de hipertensão arterial associada à proteinúria em gestante previamente normotensa após a 20a semana de gestação. A pré-eclâmpsia também é considerada na ausência de proteinúria se houver lesão de órgão-alvo. A presente revisão tem uma abordagem geral focada em aspectos de interesse prático na assistência clínica e obstétrica dessas mulheres. Assim, explora a etiologia ainda desconhecida, aspectos atuais da fisiopatologia e do diagnóstico e diagnóstico diferencial de convulsões, a abordagem da predição da doença, seus resultados adversos e prevenção. A conduta baseia-se em princípios gerais, tratamento clínico não farmacológico e farmacológico de situações graves ou não graves, com ênfase na crise hipertensiva e eclâmpsia. O controle obstétrico se fundamenta na pré-eclâmpsia sem ou com sinais de deterioração clínica e/ou laboratorial, estratificação da idade gestacional abaixo de 24 semanas, entre 24 e menos de 34 semanas e 34 ou mais semanas de gestação e orientação na via de parto. Uma abordagem imediata do puerpério e repercussões na vida futura de gestantes que desenvolvem pré-eclâmpsia também foram apresentadas.(AU)

Pre-eclampsia is a multifactorial and multisystemic disease specific to gestation. It is classically diagnosed by the presence of hypertension associated with proteinuria manifested in a previously normotensive pregnant woman after the 20th week of gestation. Pre-eclampsia is also considered in the absence of proteinuria if there is target organ damage. The present review takes a general approach focused on aspects of practical interest in the clinical and obstetric care of these women. Thus, it explores the still unknown etiology, current aspects of pathophysiology and of the diagnosis, the approach to disease prediction, its adverse outcomes and prevention. Management is based on general principles, on nonpharmacological and on pharmacological clinical treatment of severe or nonsevere situations with emphasis on the hypertensive crisis and eclampsia. Obstetric management is based on preeclampsia without or with signs of clinical and/or laboratory deterioration, stratification of gestational age in < 24 weeks, between 24 and less than 34 weeks, and ≥ 34 weeks of gestation, and guidance on route of delivery. An immediate puerperium approach and repercussions in the future life of pregnant women who develop preeclampsia is also presented.(AU)

Relapse of congenital thrombotic thrombocytopenic purpura, after spontaneous remission, in a second-trimester primigravida: case report and review of the literature / Recidiva, após remissão espontânea, de púrpura trombocitopênica trombótica congênita em primigesta no segundo trimestre de gestação: relato de caso e revisão da literatura

ABSTRACT CONTEXT: Thrombotic microangiopathy syndrome or thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) describes distinct diseases sharing common pathological features: microangiopathic hemolytic anemia and thrombocytopenia, without any other apparent cause. CASE REPORT: An 18-year-old second-trimester primigravida presented with a history of fifteen days of intense weakness, followed by diarrhea over the past six days. She reported having had low platelets since childhood, but said that she had never had bleeding or menstrual abnormalities. Laboratory investigation showed anemia with schistocytes, thrombocytopenia and hypohaptoglobulinemia. Red blood cell concentrate and platelet transfusions were performed. The hypothesis of TTP or HUS was put forward and ADAMTS13 enzyme activity was investigated. The patient evolved with increasing platelet counts, even without specific treatment, and she was discharged. One month afterwards, she returned presenting weakness and swollen face and legs, which had developed one day earlier. The ADAMTS13 activity was less than 5%, without presence of autoantibodies. Regarding the two previous admissions (at 9 and 16 years of age), with similar clinical features, there was spontaneous remission on the first occasion and, on the second, the diagnosis of TTP was suspected and plasmapheresis was performed, but ADAMTS13 activity was not investigated. CONCLUSION: To date, this is the only report of congenital TTP with two spontaneous remissions in the literature This report reveals the importance of suspicion of this condition in the presence of microangiopathic hemolytic anemia and thrombocytopenia without any other apparent cause.

RESUMO CONTEXTO: A síndrome de microangiopatia trombótica, ou púrpura trombocitopênica trombótica-síndrome hemolítico urêmica (PTT-SHU), descreve doenças diversas com clínica e achados patológicos comuns: anemia hemolítica microangiopática e trombocitopenia, na ausência de outra causa aparente. RELATO DO CASO: Primigesta de 18 anos no segundo trimestre apresenta-se com quadro de 15 dias de fraqueza intensa seguida por diarreia há seis dias. Relata ter plaquetas baixas desde a infância e nega sangramentos e anormalidades menstruais. Investigação laboratorial identificou anemia com esquizócitos, plaquetopenia e hipo-haptoglobulinemia. Foi realizada transfusão de plaquetas e concentrado de hemácias. A hipótese de PTT ou SHU foi aventada e realizou-se pesquisa da atividade da enzima ADAMTS13. A paciente evoluiu com elevação das plaquetas, mesmo sem tratamento específico, tendo alta. Retornou após um mês da alta com queixa de fraqueza há um dia e inchaço de face e pernas. A atividade da ADAMTS13 foi menor que 5%, sem autoanticorpos. Nas duas internações anteriores (aos 9 e 16 anos), com quadros similares, houve remissão espontânea na primeira internação e, na segunda, o diagnóstico de PTT foi suspeitado e foi realizada plasmaférese, porém sem a pesquisa da atividade da ADAMTS13. CONCLUSÃO: Até esta data, este é único relato de TTP congênita com duas remissões espontâneas na literatura. Este relato revela a importância da suspeição desta patologia na presença de anemia hemolítica microangiopática e trombocitopenia sem outra causa aparente.

Relapse of congenital thrombotic thrombocytopenic purpura, after spontaneous remission, in a second-trimester primigravida: case report and review of the literature.

CONTEXT: Thrombotic microangiopathy syndrome or thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) describes distinct diseases sharing common pathological features: microangiopathic hemolytic anemia and thrombocytopenia, without any other apparent cause. CASE REPORT: An 18-year-old second-trimester primigravida presented with a history of fifteen days of intense weakness, followed by diarrhea over the past six days. She reported having had low platelets since childhood, but said that she had never had bleeding or menstrual abnormalities. Laboratory investigation showed anemia with schistocytes, thrombocytopenia and hypohaptoglobulinemia. Red blood cell concentrate and platelet transfusions were performed. The hypothesis of TTP or HUS was put forward and ADAMTS13 enzyme activity was investigated. The patient evolved with increasing platelet counts, even without specific treatment, and she was discharged. One month afterwards, she returned presenting weakness and swollen face and legs, which had developed one day earlier. The ADAMTS13 activity was less than 5%, without presence of autoantibodies. Regarding the two previous admissions (at 9 and 16 years of age), with similar clinical features, there was spontaneous remission on the first occasion and, on the second, the diagnosis of TTP was suspected and plasmapheresis was performed, but ADAMTS13 activity was not investigated. CONCLUSION: To date, this is the only report of congenital TTP with two spontaneous remissions in the literature This report reveals the importance of suspicion of this condition in the presence of microangiopathic hemolytic anemia and thrombocytopenia without any other apparent cause.

Relationship between hypoxia and downstream pathogenic pathways in preeclampsia.

Defects in angiogenesis and mitochondrial function in the placenta contribute to the pathogenesis of preeclampsia; however upstream regulators of these pathways are not known. It has been argued that placental hypoxia secondary to abnormal spiral artery remodeling may play a causal role in the angiogenic and mitochondrial abnormalities noted in preeclampsia. The aim of this study was to evaluate the relationship between hypoxia-inducible factor-1α (HIF-1α) ¸ a surrogate of hypoxia, and soluble fms-tyrosine kinase 1 (sFlt1), a circulating anti-angiogenic factor, and microRNA 210 (miR-210), a microRNA that regulates mitochondrial function, in human placentas from preeclamptic and non-hypertensive pregnancies. We first confirmed a 2.5-fold upregulation of HIF-1α protein in placentas from preeclampsia when compared to non-hypertensive controls. Consistent with prior studies, we also observed a 10-fold upregulated sFlt1 mRNA and 2-fold upregulated miR-210 in preeclamptic tissue. Interestingly, while sFlt1 mRNA correlated with miR-210 in preeclampsia (R2 = 0.77, p = 0.0004), there were no significant correlations between these molecules and HIF1α expression. We conclude that non-hypoxia pathways may be involved in the abnormal angiogenic and metabolic alterations noted in preeclampsia.

Human fetal malformations associated with the use of an angiotensin II receptor antagonist: case report.

INTRODUCTION: The potential risks related to drug exposure during pregnancy represent a vast chapter in modern obstetrics and data regarding the safety of antihypertensive drugs during pregnancy are relatively scarce. CASE REPORT: A 37-year-old patient discovered her fifth pregnancy at our hospital after 26 weeks and 4 days of gestation. She reported a history of hypertension and was currently being treated with Losartan. Hospitalization was recommended for the patient and further evaluation of fetal vitality was performed. On the fourth day an ultrasound was performed, resulting in a severe oligohydramnios, fetal centralization and abnormal ductus venosus. After 36 hours, the newborn died. Pathologic evaluation: At autopsy, the skullcap had large fontanels and deficient ossification. The kidneys were slightly enlarged. A microscopic examination detected underdevelopment of the tubules and the presence of some dilated lumens. Immunohistochemical detection of epithelial membrane antigen was positive. Immunoreactivity of CD 15 was also assayed to characterize the proximal tubules, and lumen collapse was observed in some regions. DISCUSSION: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor antagonists (ARAs) are among the most widely prescribed drugs for hypertension. They are often used by hypertensive women who are considering become pregnant. While their fetal toxicity in the second or third trimesters has been documented, their teratogenic effect during the first trimester has only recently been demonstrated. CONCLUSION: Constant awareness by physicians and patients should be encouraged, particularly in regard to the prescription of antihypertensive drugs in women of childbearing age who are or intend to become pregnant.

Lipidomic assessment of plasma and placenta of women with early-onset preeclampsia.

INTRODUCTION: Adipose tissue is responsible for triggering chronic systemic inflammatory response and these changes may be involved in the pathophysiology of preeclampsia. OBJECTIVE: To characterize the lipid profile in the placenta and plasma of patients with preeclampsia. METHODOLOGY: Samples were collected from placenta and plasma of 10 pregnant women with preeclampsia and 10 controls. Lipids were extracted using the Bligh-Dyer protocol and were analysed by MALDI TOF-TOF mass spectrometry. RESULTS: Approximately 200 lipid signals were quantified. The most prevalent lipid present in plasma of patients with preeclampsia was the main class Glycerophosphoserines-GP03 (PS) representing 52.30% of the total lipid composition, followed by the main classes Glycerophosphoethanolamines-GP02 (PEt), Glycerophosphocholines-GP01 (PC) and Flavanoids-PK12 (FLV), with 24.03%, 9.47% and 8.39% respectively. When compared to the control group, plasma samples of patients with preeclampsia showed an increase of PS (p<0.0001), PC (p<0.0001) and FLV (p<0.0001). Placental analysis of patients with preeclampsia, revealed the PS as the most prevalent lipid representing 56.28%, followed by the main class Macrolides/polyketides-PK04 with 32.77%, both with increased levels when compared with patients control group, PS (p<0.0001) and PK04 (p<0.0001). CONCLUSION: Lipids found in placenta and plasma from patients with preeclampsia differ from those of pregnant women in the control group. Further studies are needed to clarify if these changes are specific and a cause or consequence of preeclampsia.

Human fetal malformations associated with the use of an angiotensin II receptor antagonist: Case Report / Malformações fetais associadas ao uso de antagonista dos receptores de angiotensina II: Relato de Caso

Introduction: The potential risks related to drug exposure during pregnancy represent a vast chapter in modern obstetrics and data regarding the safety of antihypertensive drugs during pregnancy are relatively scarce. Case report: A 37-year-old patient discovered her fifth pregnancy at our hospital after 26 weeks and 4 days of gestation. She reported a history of hypertension and was currently being treated with Losartan. Hospitalization was recommended for the patient and further evaluation of fetal vitality was performed. On the fourth day an ultrasound was performed, resulting in a severe oligohydramnios, fetal centralization and abnormal ductus venosus. After 36 hours, the newborn died. Pathologic evaluation: At autopsy, the skullcap had large fontanels and deficient ossification. The kidneys were slightly enlarged. A microscopic examination detected underdevelopment of the tubules and the presence of some dilated lumens. Immunohistochemical detection of epithelial membrane antigen was positive. Immunoreactivity of CD 15 was also assayed to characterize the proximal tubules, and lumen collapse was observed in some regions. Discussion: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor antagonists (ARAs) are among the most widely prescribed drugs for hypertension. They are often used by hypertensive women who are considering become pregnant. While their fetal toxicity in the second or third trimesters has been documented, their teratogenic effect during the first trimester has only recently been demonstrated. Conclusion: Constant awareness by physicians and patients should be encouraged, particularly in regard to the prescription of antihypertensive drugs in women of childbearing age who are or intend to become pregnant. .

Introdução: Os riscos relacionados à exposição de drogas durante a gestação representam um vasto capítulo na obstetrícia moderna e dados sobre a segurança de drogas anti-hipertensivas são relativamente escassos. Relato do caso: Paciente de 37 anos, hipertensa crônica, descobriu a gravidez com 26 semanas e 4 dias de gestação. Estava em uso regular de Losartana. Durante avaliação fetal ultrassonográfica, foi relatada a presença de grave oligoâmnio associado ao quadro de centralização fetal com alteração de ducto venoso, e, após 36 horas, verificou-se óbito neonatal. Necrópsia: Observou-se calota craniana com fontanelas amplas e ossificação deficiente. Rins levemente aumentados de volume e, à microscopia, hipodesenvolvimento de túbulos com presença de lúmen dilatado. Imunohistoquímica com expressão em túbulos distais de antígeno epitelial de membrana. Imunoperoxidade com expressão em túbulos proximais de CD 15 em células epiteliais e colapso de alguns lúmens fora observado. Discussão: Inibidores da conversão de angiotensina e antagonistas de receptor de angiotensina estão entre as drogas mais prescritas para hipertensão. Estas drogas são frequentemente prescritas para mulheres em idade fértil e que pretendem engravidar. Enquanto a toxicidade fetal destas, nos segundo e terceiro trimestres, já é conhecida, seus efeitos durante o primeiro trimestre foi apenas recentemente demostrado. Conclusão: A conscientização por parte de médicos e pacientes deve ser realizada de rotina, principalmente no que diz respeito à prescrição e utilização de drogas potencialmente teratogênicas ou fetotóxicas. Este cuidado deve ser redobrado para pacientes que estão ...