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1.
Obstet Gynecol ; 135(1): 46-58, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31809447

RESUMO

OBJECTIVE: To evaluate disease presentation, diagnosis, treatment, and clinical outcomes in pregnancy-associated atypical hemolytic uremic syndrome (aHUS). DATA SOURCES: We searched PubMed, MEDLINE, Cochrane Library, ClinicalTrials.gov, Web of Science, EMBASE and Google Scholar, from inception until March 2018. METHODS OF STUDY SELECTION: We included English-language articles describing aHUS in pregnancy or postpartum. The diagnosis of aHUS was characterized by hemolysis, thrombocytopenia, and renal failure and was distinguished from typical diarrhea-associated hemolytic uremic syndrome. Patients were excluded if individual data could not be obtained, the diagnosis was unclear, or an alternative etiology was more likely, such as thrombotic thrombocytopenic purpura or Shiga toxin-producing Escherichia coli. Reports were appraised by two reviewers, with disagreements adjudicated by a third reviewer. TABULATION, INTEGRATION, AND RESULTS: The search identified 796 articles. After review of titles, abstracts, and full text, we identified 48 reports describing 60 unique cases of pregnancy-associated aHUS, with 66 pregnancies. Twelve cases involved pregnancy in women with known aHUS, and 54 cases involved first-episode pregnancy-associated aHUS. Women with known aHUS, particularly those with baseline creatinine at or above 1.5 mg/dL, had a high rate of adverse pregnancy outcomes. For first-episode pregnancy-associated aHUS, diagnosis most often occurred postpartum (94%), after a cesarean delivery (70%), in nulliparous women (58%). Preceding obstetric complications were common and included fetal death, preeclampsia, and hemorrhage. Diagnosis was usually made clinically, based on the triad of microangiopathic hemolysis, thrombocytopenia, and renal failure. Additional testing included renal biopsy, complement genetic testing, and ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) testing. Treatment modalities included corticosteroids, plasma exchange, dialysis, and eculizumab. More women with first-episode pregnancy-associated aHUS achieved disease remission when treated with eculizumab, compared with those not treated with eculizumab (88% vs 57%, P=.02). CONCLUSION: Pregnancy-associated aHUS usually presents in the postpartum period, often after a pregnancy complication, and eculizumab is effective for achieving disease remission. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019129266.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/terapia , Complicações Hematológicas na Gravidez/diagnóstico , Complicações Hematológicas na Gravidez/terapia , Anticorpos Monoclonais Humanizados/uso terapêutico , Inativadores do Complemento/uso terapêutico , Feminino , Humanos , Troca Plasmática , Período Pós-Parto , Gravidez , Diálise Renal
2.
Eur J Ophthalmol ; 30(3): NP14-NP17, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30841747

RESUMO

PURPOSE: To report a case of Purtscher-like retinopathy due to atypical hemolytic uremic syndrome and the changes seen in the optical coherence tomography angiography before and after treatment with eculizumab. CASE DESCRIPTION: A 22-year-old man with an unremarkable medical history presented with acute, bilateral blurred vision and headache of 1-week duration. Best corrected visual acuity of 20/50 and 20/40, respectively, in the patient's right eye and left eye. Funduscopy revealed multiple cotton-wool spots associated with intrarretinal fluid. Swept source optical coherence tomography revealed multifocal retinal detachments with increased choroidal thickness. Optical coherence tomography angiography showed areas of ischemia in both capillary plexus. Due to concurrent symptoms and laboratory analysis, he was diagnosed with atypical hemolytic uremic syndrome and secondary Purtscher-like retinopathy; therefore, treatment with eculizumab was initiated. After 2 months revascularization of the previous ischemic areas was seen in the optical coherence tomography angiography that were correlated with best corrected visual acuity improvement. CONCLUSION: Our findings suggest that evaluation of the macular capillary plexus revascularization by optical coherence tomography angiography during the disease could help to predict an improvement of best corrected visual acuity in these patients and the measurement of choroidal thickness could give us information about the resolution of the pathologic process.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/complicações , Doenças Retinianas/diagnóstico , Doenças Retinianas/etiologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Angiografia por Tomografia Computadorizada , Angiofluoresceinografia/métodos , Seguimentos , Humanos , Masculino , Doenças Retinianas/tratamento farmacológico , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adulto Jovem
3.
BMJ Case Rep ; 12(12)2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31811102

RESUMO

Atypical haemolytic uraemic syndrome (aHUS) is a rare, acquired thrombotic microangiopathy, mediated by complement activation, in very sick patients. Moyamoya is similarly a rare disease in which stenosis or occlusion of segment(s) of the anterior cerebral circulation leads to the formation of many thin collaterals. Other reports have described an association between HUS and Moyamoya disease in the paediatric population. However, this case study presents the exceptionally rare presentation of an adult with aHUS and Moyamoya disease in a patient who was treated with rituximab for marginal zone B-cell lymphoma.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Linfoma de Zona Marginal Tipo Células B/complicações , Doença de Moyamoya/complicações , Síndrome Hemolítico-Urêmica Atípica/diagnóstico por imagem , Síndrome Hemolítico-Urêmica Atípica/terapia , Terapia Combinada , Diagnóstico Diferencial , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
4.
Obstet Gynecol ; 134(6): 1215-1218, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31764731

RESUMO

BACKGROUND: Untreated microangiopathic hemolytic anemia in pregnancy is associated with adverse maternal and perinatal outcomes. Accurate diagnosis is challenging owing to nonspecific clinical features and pathologic findings. Timely initiation of appropriate management is essential to optimize maternal and perinatal outcomes. CASE: A 26-year-old primiparous woman presented at 20 weeks of gestation with new-onset microangiopathic hemolytic anemia on a background of poorly controlled type 1 diabetes. She received eculizumab for presumed atypical hemolytic uremic syndrome. At 24 weeks of gestation, she developed superimposed early-onset preeclampsia; she delivered at 27 weeks of gestation after continuing eculizumab. CONCLUSION: Eculizumab may prolong pregnancy in early-onset preeclampsia. Additional research is needed to assess short-term and long-term maternal and newborn outcomes.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Diabetes Mellitus , Pré-Eclâmpsia/diagnóstico , Complicações na Gravidez , Diagnóstico Pré-Natal , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Síndrome Hemolítico-Urêmica Atípica/complicações , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Diagnóstico Diferencial , Feminino , Humanos , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Segundo Trimestre da Gravidez , Gravidez Prolongada
5.
Acta Med Port ; 32(10): 673-675, 2019 Oct 01.
Artigo em Português | MEDLINE | ID: mdl-31625881

RESUMO

The atypical hemolytic uremic syndrome comprises a thrombotic microangiopathy resulting from the complement alternate pathway hyperactivation. Its severity requires early diagnosis and treatment. The differential diagnosis includes typical hemolytic uremic syndrome (associated with Shiga toxin) and thrombotic thrombocytopenic purpura (associated with deficient activity of ADAMTS13). The only specific treatment currently available for atypical hemolytic uremic syndrome is eculizumab. We describe the case of a child with atypical hemolytic uremic syndrome diagnosed in the context of bloody diarrhea, complicated by neurological involvement that posed several diagnostic and therapeutic challenges.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Criança , Diagnóstico Diferencial , Feminino , Síndrome Hemolítico-Urêmica/diagnóstico , Humanos , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/etiologia
7.
Thromb Haemost ; 119(11): 1767-1772, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31587247

RESUMO

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy (TMA) characterized by the severe deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity (< 10%). Rapid ADAMTS13 testing is crucial for an early diagnosis and optimal management of acute TTP. We evaluated the performance of the HemosIL AcuStar ADAMTS13 activity assay (Instrumentation Laboratory, Bedford, Massachusetts, United States), a fully automated chemiluminescent immunoassay with an analytical time of 33 minutes. A method comparison study was performed on 176 samples from 49 healthy donors and 127 TMA patients (109 TTP, 7 atypical hemolytic uremic syndrome, 11 other TMAs), comparing this new assay with an in-house FRETS-VWF73 assay and a commercial enzyme-linked immunosorbent assay (ELISA) (TECHNOZYM ADAMTS-13 Activity, Technoclone GmbH, Vienna, Austria). Agreement between methods was assessed with focus on ADAMTS13 activity less than 10%, the medical decision level relevant for TTP diagnosis. The HemosIL AcuStar ADAMTS13 Activity showed good correlation with both the FRETS-VWF73 (r = 0.96) and ELISA (r = 0.96) methods. Slope of the Passing-Bablok regression was 1.05 for FRETS-VWF73 and 1.02 for ELISA, and absolute bias at the medical decision level was +0.1 and +0.3%, respectively. The study also revealed high agreement with FRETS-VWF73 (kappa 0.97) and ELISA (kappa 0.98) methods in classifying TTP patients with a severe deficiency of ADAMTS13 activity. Because of its short turnaround time and full automation, the HemosIL AcuStar ADAMTS13 activity assay might become the assay of choice to rapidly test ADAMTS13 activity in plasma and thus establish the diagnosis of acute TTP in emergency settings.


Assuntos
Proteína ADAMTS13/sangue , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Imunoensaio/métodos , Púrpura Trombocitopênica Trombótica/diagnóstico , Proteína ADAMTS13/deficiência , Síndrome Hemolítico-Urêmica Atípica/sangue , Síndrome Hemolítico-Urêmica Atípica/enzimologia , Automação Laboratorial , Biomarcadores/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Humanos , Medições Luminescentes , Valor Preditivo dos Testes , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/enzimologia , Reprodutibilidade dos Testes , Fatores de Tempo , Fluxo de Trabalho
8.
BMJ Case Rep ; 12(9)2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31519719

RESUMO

Atypical haemolytic uraemic syndrome (aHUS) is a disease of complement dysregulation and can be fatal if not treated in a timely manner. Although normally associated with triggers such as infection or pregnancy, this case demonstrates acute pancreatitis as the triggering event. The patient's initial presentation of thrombocytopaenia and acute renal failure was first attributed to a systemic inflammatory response syndrome due to pancreatitis, but with detailed history and further laboratory investigation, we were able to show that patient was having symptoms associated with aHUS. On early recognition of aHUS, this patient was able to receive the proper standard of care with eculizumab and had a full recovery while preventing renal failure. When patients present with thrombocytopaenia and renal failure in acute pancreatitis, we want to ensure physicians keep aHUS on the differential.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/etiologia , Pancreatite/complicações , Insuficiência Renal/etiologia , Trombocitopenia/etiologia , Doença Aguda , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/administração & dosagem , Inativadores do Complemento/uso terapêutico , Diagnóstico Diferencial , Humanos , Masculino , Pancreatite/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
9.
BMJ Case Rep ; 12(6)2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31253663

RESUMO

A 72-year-old woman was admitted to the hospital because of dorsal, lumbar and lower abdomen pain that had started 4 days before. She had a history of age-related macular degeneration (treated with intraocular bevacizumab). Blood tests showed anaemia, thrombocytopaenia, acute kidney injury, elevated liver enzymes and total bilirubin (mainly because of the indirect fraction). Viral serologies and ADAMTS13 activity levels were normal, and stool testing was negative for Escherichia coli-producing Shiga toxins. E. coli was isolated in urine. Atypical haemolytic uremic syndrome triggered by a urinary tract infection or by the vascular endothelial growth factor-inhibitor bevacizumab were the most likely hypothesis. The patient started urgent plasmapheresis and dialysis that lasted for a total of 18 days. There was complete remission and recovery of kidney function allowing for treatment discontinuation, and she was discharged home. After 6 months of follow-up, she shows no signs of relapse.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/complicações , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Infecções Urinárias/complicações , Idoso , Síndrome Hemolítico-Urêmica Atípica/terapia , Diagnóstico Diferencial , Feminino , Humanos , Plasmaferese/métodos , Diálise Renal/métodos , Infecções Urinárias/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/uso terapêutico
10.
Saudi J Kidney Dis Transpl ; 30(3): 701-705, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249236

RESUMO

In evaluating a patient with thrombotic microangiopathy (TMA), it is necessary to rule out thrombotic thrombocytopenic purpura before a diagnosis of atypical hemolytic uremic syndrome (aHUS) is made. There have been reports that mutations of complement factors can coexist with partial A Disintegrin and Metalloproteinase with a ThromboSpondin type 1 motif, member 13 deficiency. Here, we report the case of a 6-year-old girl who was initially diagnosed as nephrotic syndrome and developed TMA after five years of onset of illness. She had poor response to treatment and had multiple relapses due to associated complement factor mutation. Hence, genetic evaluation has to be considered in all children presenting with aHUS.


Assuntos
Proteína ADAMTS13/genética , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Proteínas do Sistema Complemento/genética , Mutação , Púrpura Trombocitopênica Trombótica/diagnóstico , Proteína ADAMTS13/deficiência , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/imunologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Criança , Proteínas do Sistema Complemento/imunologia , Diagnóstico Diferencial , Evolução Fatal , Feminino , Predisposição Genética para Doença , Humanos , Fenótipo , Valor Preditivo dos Testes , Púrpura Trombocitopênica Trombótica/genética , Púrpura Trombocitopênica Trombótica/terapia , Resultado do Tratamento
11.
J Pediatr Hematol Oncol ; 41(7): e459-e462, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30933023

RESUMO

Typical hemolytic uremic syndrome (HUS) in children is caused mostly by Escherichia coli 0157:H7 in our country. Atypical HUS (aHUS) causes include Streptococcus pneumoniae, methyl malonic aciduria, deficiency of ADAMST 13, and genetic or acquired disorder of the complement. Treatment of HUS relies on supportive measures while treatment of aHUS includes plasmapheresis and specific treatments. Recently, eculizumab has been proposed for the treatment of aHUS and many clinicians now believe that eculizumab should be the first-line standard of care. The purpose of this article is to illustrate the difficulties in the diagnostic process of HUS and therefore the subsequent problem to promptly choose the appropriate treatment. To date, workup of HUS continues to take many days leaving the clinicians with a choice between several therapeutic options. With the emergence of eculizumab, it becomes crucial to find faster diagnostic tools and to adapt HUS treatment protocols. We reported here clinical cases where eculizumab use was probably not appropriate once the correct diagnosis of typical HUS was made and cases where it would have been useful because of the late diagnosis of aHUS.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Síndrome Hemolítico-Urêmica/tratamento farmacológico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Pré-Escolar , Feminino , Síndrome Hemolítico-Urêmica/diagnóstico , Humanos , Lactente , Masculino
12.
BMC Nephrol ; 20(1): 125, 2019 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-30971227

RESUMO

BACKGROUND: There are limited long-term outcome data in eculizumab-treated patients with atypical hemolytic uremic syndrome (aHUS). We report final results from the largest prospective, observational, multicenter study of patients with aHUS treated with eculizumab. METHODS: Patients with aHUS who participated in any of five parent eculizumab trials and received at least one eculizumab infusion were eligible for enrollment in a long-term follow-up study. Rates of thrombotic microangiopathy (TMA) manifestations off versus on eculizumab were evaluated. Additional endpoints included change from baseline estimated glomerular filtration rate (eGFR), long-term renal outcomes, and serious targeted treatment-emergent adverse events. RESULTS: Among 93 patients (0-80 years of age), 51 (55%) remained on eculizumab and 42 (45%) discontinued; for those who discontinued, 21 (50%) reinitiated therapy. Patients who reinitiated eculizumab had similar baseline clinical characteristics to patients who remained on eculizumab, with higher likelihood of genetic/autoimmune complement abnormalities, more prior TMAs, and longer disease course versus those who did not reinitiate. Mean eGFR improved rapidly and remained stable for up to 6 years on eculizumab. In patients who discontinued, there was a trend toward decreasing renal function over time from discontinuation. Additionally, off-treatment TMA manifestation rates were higher in those aged < 18 years at diagnosis, with identified genetic/autoimmune complement abnormalities, or history of multiple TMAs prior to eculizumab initiation. The safety profile was consistent with previous studies. Three definite and one possible meningococcal infections related to eculizumab were reported and resolved with treatment. Three deaths unrelated to eculizumab were reported. CONCLUSIONS: The current study confirms the efficacy and safety of eculizumab in aHUS, particularly with regard to long-term renal function and TMA events. Pediatric age at disease onset and presence of genetic or autoimmune complement abnormalities are risk factors for TMA events off treatment. Overall, patients who discontinue eculizumab may be at risk for additional TMA manifestations and renal function decreases. Discontinuation of eculizumab, with careful monitoring, is an option in select patients with consideration of patient preference, organ function normalization, and risk factors for relapse, including mutational analysis, age of onset, and history of multiple TMA episodes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01522170 , January 31, 2012.


Assuntos
Anticorpos Monoclonais Humanizados , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Efeitos Adversos de Longa Duração , Microangiopatias Trombóticas , Adolescente , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Síndrome Hemolítico-Urêmica Atípica/complicações , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/epidemiologia , Criança , Inativadores do Complemento/administração & dosagem , Inativadores do Complemento/efeitos adversos , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Cooperação Internacional , Efeitos Adversos de Longa Duração/diagnóstico , Efeitos Adversos de Longa Duração/epidemiologia , Efeitos Adversos de Longa Duração/etiologia , Masculino , Conduta do Tratamento Medicamentoso , Avaliação de Processos e Resultados em Cuidados de Saúde , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/epidemiologia , Microangiopatias Trombóticas/etiologia
13.
J Emerg Med ; 56(4): 441-443, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30826084

RESUMO

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a complement-mediated disease manifesting in thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury. It has a higher incidence of extrarenal manifestations, including central nervous system findings like seizure or stroke, pancreatitis, and cardiac manifestations. CASE REPORT: We present a case of an unimmunized 14-month-old girl presenting with generalized seizure and ultimately diagnosed with aHUS. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: These atypical neurological symptoms can cause the diagnosis to be commonly missed in the emergency department. The etiology of approximately 60% of patients with aHUS can be attributed to genetic mutations in complement regulators including factor H, membrane cofactor protein, factor I, activator factor B, or C3. Although previously treated with plasma transfusion and immunosuppressants, eculizumab is a newer treatment that has been changing prognosis and management of aHUS, but it should be administered within 48 h of symptom onset for best efficacy.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/complicações , Convulsões/etiologia , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Tampões (Química) , Gluconato de Cálcio/uso terapêutico , Eletroencefalografia/métodos , Feminino , Humanos , Hiperpotassemia/tratamento farmacológico , Hiperpotassemia/etiologia , Hipnóticos e Sedativos/uso terapêutico , Incidência , Lactente , Midazolam/uso terapêutico , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia , Bicarbonato de Sódio/uso terapêutico , Trombocitopenia/etiologia , Vômito/etiologia
14.
Blood Coagul Fibrinolysis ; 30(2): 68-70, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30676336

RESUMO

: We bring the case of a 38-year-old man who was presented to the emergency department with nausea, fever, and choluria, 4 days after the ingestion of raw oysters. Analytical study revealed thrombocytopenia and acute kidney injury that were associated to a possible thrombotic microangiopathy. Therapeutic plasma exchange was started and resolution of the manifestations was obtained. To identify the cause of the thrombotic microangiopathy a molecular study was performed and a pathogenic variant in the MCP gene, c.287-2A>G (splice acceptor) in heterozygous state with a concomitant presence of both risk haplotypes, MCPggaac and Complement factor H (CFH)-H3 were identified. These findings make the diagnosis of atypical hemolytic-uremic syndrome (aHUS), and despite a relatively benign course with a positive response to plasma exchange without an evolution to renal failure was evident a recurrent profile of aHUS when associated with an infectious trigger.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Proteína Cofatora de Membrana/genética , Mutação , Lesão Renal Aguda/etiologia , Adulto , Síndrome Hemolítico-Urêmica Atípica/terapia , Haplótipos , Humanos , Masculino , Fenótipo , Troca Plasmática , Recidiva , Risco , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/genética
16.
Ther Apher Dial ; 23(1): 4-21, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30294946

RESUMO

Atypical hemolytic uremic syndrome (aHUS), a rare variant of thrombotic microangiopathy, is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. The condition is associated with poor clinical outcomes with high morbidity and mortality. Atypical HUS predominantly affects the kidneys but has the potential to cause multi-organ system dysfunction. This uncommon disorder is caused by a genetic abnormality in the complement alternative pathway resulting in over-activation of the complement system and formation of microvascular thrombi. Abnormalities of the complement pathway may be in the form of mutations in key complement genes or autoantibodies against specific complement factors. We discuss the pathophysiology, clinical manifestations, diagnosis, complications, and management of aHUS. We also review the efficacy and safety of the novel therapeutic agent, eculizumab, in aHUS, pregnancy-associated aHUS, and aHUS in renal transplant patients.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Síndrome Hemolítico-Urêmica Atípica , Via Alternativa do Complemento , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/etiologia , Síndrome Hemolítico-Urêmica Atípica/fisiopatologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Via Alternativa do Complemento/efeitos dos fármacos , Via Alternativa do Complemento/genética , Via Alternativa do Complemento/imunologia , Gerenciamento Clínico , Humanos , Fatores Imunológicos/farmacologia
17.
Nephrol Dial Transplant ; 34(3): 474-485, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30295827

RESUMO

BACKGROUND: Alport syndrome (AS) and atypical hemolytic-uremic syndrome (aHUS) are rare forms of chronic kidney disease (CKD) that can lead to a severe decline of renal function. Steroid-resistant nephrotic syndrome (SRNS) is more common than AS and aHUS and causes 10% of childhood-onset CKD. In recent years, multiple monogenic causes of AS, aHUS and SRNS have been identified, but their relative prevalence has yet to be studied together in a typical pediatric cohort of children with proteinuria and hematuria. We hypothesized that identification of causative mutations by whole exome sequencing (WES) in known monogenic nephritis and nephrosis genes would allow distinguishing nephritis from nephrosis in a typical pediatric group of patients with both proteinuria and hematuria at any level. METHODS: We therefore conducted an exon sequencing (WES) analysis for 11 AS, aHUS and thrombotic thrombocytopenic purpura-causing genes in an international cohort of 371 patients from 362 families presenting with both proteinuria and hematuria before age 25 years. In parallel, we conducted either WES or high-throughput exon sequencing for 23 SRNS-causing genes in all patients. RESULTS: We detected pathogenic mutations in 18 of the 34 genes analyzed, leading to a molecular diagnosis in 14.1% of families (51 of 362). Disease-causing mutations were detected in 3 AS-causing genes (4.7%), 3 aHUS-causing genes (1.4%) and 12 NS-causing genes (8.0%). We observed a much higher mutation detection rate for monogenic forms of CKD in consanguineous families (35.7% versus 10.1%). CONCLUSIONS: We present the first estimate of relative frequency of inherited AS, aHUS and NS in a typical pediatric cohort with proteinuria and hematuria. Important therapeutic and preventative measures may result from mutational analysis in individuals with proteinuria and hematuria.


Assuntos
Marcadores Genéticos , Mutação , Nefrite/diagnóstico , Nefrite/genética , Nefrose/diagnóstico , Nefrose/genética , Sequenciamento Completo do Exoma/métodos , Adolescente , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/genética , Criança , Pré-Escolar , Estudos de Coortes , Análise Mutacional de DNA , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Nefrite Hereditária/diagnóstico , Nefrite Hereditária/genética , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/genética , Prognóstico
18.
J Matern Fetal Neonatal Med ; 32(17): 2853-2859, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29606012

RESUMO

Objective: The aim of this case series is to raise awareness of obstetric-related atypical haemolytic uraemic syndrome (aHUS) amongst obstetricians and gynaecologists. Study design: Data from 20 consecutive patients, aged 19-38, with obstetric-aHUS manifestation during or immediately after pregnancy are reported. Patients were diagnosed and treatment was initiated between 2012 and 2016. Results: Presentation of aHUS was mainly preceded by preeclampsia and/or haemolysis, elevated liver enzymes and low platelet count syndrome, other obstetric complications, or by diarrhoea. Thrombotic microangiopathy (TMA) was evident in all patients with signs of microangiopathic haemolysis (sharp decline in haemoglobin; mean 67 g/L), elevated lactate dehydrogenase (LDH; mean 2953.1 U/L), schistocytosis, thrombocytopenia (mean platelet count 52.5 × 109/µL), and acute kidney injury (AKI) (hypercreatininaemia, mean 456.4 µmol/L; oliguria or anuria). The majority of patients (80%) initially presented with arterial hypertension. Diagnosis of obstetric-aHUS was complicated, as multiple organs were affected. Time taken to make the diagnosis of aHUS delayed the initiation of fresh-frozen plasma infusions and plasma exchange (80% of patients) and subsequent eculizumab treatment (40% of patients). Maternal mortality was high (35%) as was foetal mortality (25%). Conclusions: Obstetric-aHUS is a serious condition characterized by multiple organ failure (MOF) and a high mortality rate. Presentation of obstetric-aHUS is preceded by various precipitating factors, suggesting pregnancy complications, and not the pregnancy per se, often induce aHUS in women with a genetic predisposition to its development. A delay in the correct diagnosis and initiation of the most effective treatment can have serious consequences, reinforcing the need to raise awareness of obstetric-aHUS.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/mortalidade , Insuficiência de Múltiplos Órgãos/etiologia , Complicações na Gravidez/mortalidade , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/mortalidade , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/sangue , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Insuficiência de Múltiplos Órgãos/mortalidade , Morte Perinatal , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/tratamento farmacológico , Adulto Jovem
19.
J Pediatr Hematol Oncol ; 41(2): e111-e113, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29750742

RESUMO

We present the case of a 2-month-old infant presenting with pallor and laboratory results showing: hemoglobin 5.1 (10 to 1.5) g/dL, MCV 94.7 (75 to 105) fL, leukocytes 17.4 (7 to 15) ×10/µL, platelets 259 (150 to 450) ×10/µL, hyperbilirubinemia and renal dysfunction. A hemolytic anemia with tubular injury secondary to hemoglobinuria was suspected. Hyperhydration and packed cells were given but she deteriorated. Fluid overload with anuria further complicated the course necessating hemodialysis. Atypical hemolytic uremic syndrome was suspected and eculizumab was administered resulting in rapid improvement. Genetic analysis revealed a mutation in the gene encoding complement factor H and atypical hemolytic uremic syndrome was confirmed.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Síndrome Hemolítico-Urêmica Atípica , Mutação , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/patologia , Fator H do Complemento/genética , Feminino , Humanos , Lactente
20.
J Nephrol ; 32(1): 17-25, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30159857

RESUMO

Pregnancy can be a dangerous trigger for patients with paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), or hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome. Due to the possibility of several serious complications, pregnancy is somewhat discouraged in the presence of the above diseases. Eculizumab is a humanized antibody that may dramatically change the clinical course of PNH, aHUS and HELLP syndrome. However, data on the safety of eculizumab in pregnancy are scarce. In this narrative overview, we summarize current evidence on the use of eculizumab during pregnancy in women with PNH, aHUS and HELLP syndrome. Eculizumab is not present in breast milk, and the levels observed in umbilical cord blood samples are not sufficient to affect the concentrations of complement in newborns. Therefore, eculizumab may be regarded as safe in pregnancy. Nonetheless, given that data on eculizumab in pregnancy are limited, it is not possible to completely exclude risks for both mother and fetus in treating PNH, aHUS and HELLP syndrome.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Síndrome HELLP/tratamento farmacológico , Hemoglobinúria Paroxística/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/imunologia , Inativadores do Complemento/efeitos adversos , Feminino , Síndrome HELLP/diagnóstico , Síndrome HELLP/imunologia , Hemoglobinúria Paroxística/diagnóstico , Hemoglobinúria Paroxística/imunologia , Humanos , Segurança do Paciente , Gravidez , Medição de Risco , Fatores de Risco , Resultado do Tratamento
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