Near-fatal cocaine intoxication in an infant with thrombotic microangiopathy associated with multiple organ failure / Intoxicação grave por cocaína em criança com microangiopatia trombótica associada à falência múltipla de órgãos

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.

Clinical characteristics and prognosis of anti-factor H antibody associated-atypical hemolytic uremic syndrome in children / 中华实用儿科临床杂志

Objective:To summarize the clinical data of anti-factor H antibody-associated atypical hemolytic uremic syndrome (aHUS) in children, and analyze the risk factors for disease recurrence and poor prognosis.Methods:A prospective cohort study was conducted on 52 children with anti-factor H antibody-associated aHUS in Beijing Children′s Hospital, Capital Medical University from November 2011 to November 2021.Patient information about the genetic background, clinical and renal pathological characteristics, treatment, and prognosis were collected.Then, the disease recurrence and prognosis were analyzed using the survival curve and Cox regression model. Results:In 52 children, there were 33 males and 19 females.The average age of onset for aHUS was 2.4-12.8 years, and 92.3%(48/52) of the children developed symptoms at the age of 4-12 years.The copy numbers of complement factor-H-related 1 (CFHR1) and complement factor-H-related 3 (CFHR3) genes were calculated in 42 children.Among the 42 cases, 18 cases (42.9%) had CFHR1 homozygous deletion, and 83.3% (15/18) of them also had CFHR3 homozygous deletion.All the patients were given plasma therapy.Besides, 76.9% (40/52) of the children were treated with immunosuppressive therapy (steroid and/or immunosuppressant) at the first onset of the disease.About 86.5%(45/52 cases) of the patients received immunosuppressive therapy in the course of disease, and the immunosuppressive treatment lasted for 6-20 months in total.The median follow-up time was 58 (28, 91) months.Among 52 patients, only 12 patients (23.1%) suffered disease recurrence.The relapse-free survival rate in children with CFHR1 homozygous deletion was significantly lower than that in children with non-homozygous deletion ( χ2=4.700, P=0.030). The relapse-free survival rate in children with CFHR1 and CFHR3 homozygous deletions was also significantly lower than that in other children ( χ2=4.181, P=0.041). At the end of the follow-up, 73.1%(38/52) of the children had normal renal function and no persistent proteinuria or hypertension.23.1%(12/52 cases) of the children had persistent proteinuria and/or hypertension.One child had Stage 3-4 chronic kidney disease, and 1 child was dialysis dependent. Conclusions:Anti-factor H antibody-associated aHUS is prone to occur in children aged between 4-12 years old, who respond well to plasma therapy and immunosuppressive therapy.Children with anti-factor H antibody-associated aHUS and CFHR1 and CFHR3 homozygous deletions have a high recurrence rate.Treatment with immunosuppressive therapy and assessment of the copy number of CFHR1 and CFHR3 genes in the early stage of the disease are important for preventing disease recurrence and improving prognosis.

Progress on diagnosis and treatment of kidney transplantation-associated thrombotic microangiopathy / 器官移植

Thrombotic microangiopathy (TMA) is a severe complication after kidney transplantation, mainly characterized by thrombocytopenia, microvascular hemolytic anemia and acute kidney injury, which may lead to kidney allograft failure or even death of the recipients. With the increasing quantity of solid organ transplantation in China and deeper understanding of TMA, relevant in-depth studies have been gradually carried out. Kidney transplantation-associated TMA is characterized with different causes and clinical manifestations. Non-invasive specific detection approach is still lacking. The diagnosis of TMA mainly depends on renal biopsy. However, most TMA patients are complicated with significant thrombocytopenia. Hence, renal puncture is a risky procedure. It is difficult to make a definite diagnosis. For kidney transplantation-associated TMA, plasma exchange, intravenous immunoglobulin and withdrawal of potential risk drugs are commonly employed. Nevertheless, the overall prognosis is poor. In this article, the classification of TMA after kidney transplantation, diagnosis and treatment of kidney transplantation-associated TMA were reviewed, aiming to provide reference for clinical diagnosis and treatment of kidney transplantation-associated TMA.

Diagnosis and treatment strategies for solid organ transplant recipients with SARS-CoV-2 infection / 器官移植

Due to long-term use of immunosuppressive agents, solid organ transplant recipients (SOTR) belong to high-risk populations of multiple pathogenic infection, including SARS-CoV-2. In addition, SOTR are constantly complicated by chronic diseases, such as hypertension and diabetes mellitus, etc. After infected with SARS-CoV-2, the critically ill rate and fatality of SOTR are higher than those of the general population, which captivates widespread attention from experts in the field of organ transplantation. Omicrone variant is currently the significant pandemic strain worldwide, rapidly spreading to more than 100 countries worldwide and causing broad concern. According to the latest international guidelines on the diagnosis and treatment of SARS-CoV-2 infection and relevant expert consensus in China combined with current domestic situation of SARS-CoV-2 pandemic and China's "diagnosis and treatment regimen for SARS-CoV-2 infection (Trial Version 10)", the epidemiology, clinical manifestations and prognosis, diagnosis, clinical classification and treatment of SARS-CoV-2 infection were briefly reviewed.

Advances in Diagnosis and Treatment of Transplant-Associated Thrombotic Microangiopathy --Review / 中国实验血液学杂志

Transplantation-associated thrombotic microangiopathy (TA-TMA) is one of the serious complications mostly occurring within 100 days after hematopoietic stem cell transplantation (HSCT). Risk factors of TA-TMA include genetic predispositions, GVHD, and infections. The pathophysiological mechanisms of TA-TMA start with endothelial injury caused by complement activation, which leads to microvascular thrombosis, and microvascular hemolysis, ultimately resulting in multi-organ dysfunction. In recent years, the development of complement inhibitors has markedly improved the prognosis of TA-TMA patients. This review will give an update on risk factors, clinical manifestations, diagnosis, and treatment of TA-TMA, so as to provide references for clinical practice.

Clinical characteristics and prognosis of 12 cases of lupus nephritis complicated with thrombotic microangiopathy / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical characteristics, pathological features, treatment regimen, and prognosis of children with lupus nephritis (LN) and thrombotic microangiopathy (TMA), as well as the treatment outcome of these children and the clinical and pathological differences between LN children with TMA and those without TMA.@*METHODS@#A retrospective analysis was conducted on 12 children with LN and TMA (TMA group) who were admitted to the Department of Nephrology, Children's Hospital of Nanjing Medical University, from December 2010 to December 2021. Twenty-four LN children without TMA who underwent renal biopsy during the same period were included as the non-TMA group. The two groups were compared in terms of clinical manifestations, laboratory examination results, and pathological results.@*RESULTS@#Among the 12 children with TMA, 8 (67%) had hypertension and 3 (25%) progressed to stage 5 chronic kidney disease. Compared with the non-TMA group, the TMA group had more severe tubulointerstitial damage, a higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score at onset, and higher cholesterol levels (P<0.05). There were no significant differences between the two groups in the percentage of crescent bodies and the levels of hemoglobin and platelets (P>0.05).@*CONCLUSIONS@#There is a higher proportion of individuals with hypertension among the children with LN and TMA, as well as more severe tubulointerstitial damage. These children have a higher SLEDAI score and a higher cholesterol level.

Three shades of black - secondary thrombotic microangiopathy

Thrombotic microangiopathy is a group of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia and organ damage. Wide age distribution and the heterogeneity in presentation demand a deeper understanding into the pathogenesis of TMA. Primary TMA is distinct from TMA associated with secondary causes and remains clinically occult till a precipitating factor aggravates it. The extent and severity of renal damage caused by each of them is also distinct. The first alerting signal could be the presence of schistiocytes on peripheral smear and arteriolar thrombi on light microscopy. Thus in secondary TMA, identification of the underlying disorder is indispensible for targeted management.

Atypical hemolytic uremia syndrome in a young adult male

Atypical hemolytic uremia syndrome (aHUS) is a rare and life-threatening disease, characterized by the same triad of hemolytic anemia, thrombocytopenia, and renal failure as seen in HUS. It differs in its etiology, being caused by a dysregulation of the complement pathway rather than Shiga-like toxin-producing Escherichia coli. Prognosis is poor, with 50% of cases progressing to end-stage renal disease (ESRD) and 25% succumbing in the acute phase. The treatment of choice is therapeutic plasma exchange which can lower mortality. Monoclonal antibody drugs such as eculizumab, which suppress the dysregulated complement pathway, help to prevent complement-mediated kidney injury. We report the case of a young adult male who presented with thrombocytopenia and worsening acute kidney injury and was diagnosed with aHUS based on high lactic dehydrogenase, low complement C3, and haptoglobin, as well as renal biopsy showing thrombotic microangiopathy

Chronic gemcitabine-induced thrombotic microangiopathy in the kidneys / Microangiopatía trombótica crónica localizada en riñones asociada al uso de gemcitabina

Abstract Thrombotic microangiopathies (TMAs) are characterized by microvascular occlusion secondary to diffuse endothelial damage which produces inflammation, platelet aggregation and red blood cell destruction, causing ischemic injury to the affected organ. They are clinically characterized by Coombs-negative microangiopathic hemolytic anemia, and multiple organ damage (mainly of the kidneys, central nervous system, cardiovascular apparatus and gastrointestinal tract). They may occur systemically or locally, and they have multiple etiologies. In patients with cancer, determining the cause of thrombotic microangiopathy is a great diagnostic challenge, with the most frequent etiologies being active malignant neoplasms, disseminated intravascular coagulation, infections and antineoplastic drugs. We present the clinical case of a patient with unresectable pancreatic adenocarcinoma on chronic gemcitabine treatment, and highlight the importance of suspecting and distinguishing chemotherapy-induced TMAs from neoplasm-induced TMAs, as their prognosis and treatment are very different. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2249).

Resumen Las microangiopatías trombóticas (MAT) se caracterizan por la oclusión microvascular como consecuencia de una lesión endotelial difusa que produce inflamación, agregación plaquetaria y destrucción de glóbulos rojos, causando daño isquémico del órgano afectado. Se caracterizan clínicamente por anemia hemolítica microangiopática, Coombs negativo, daño multiorgánico (principalmente de riñones, sistema nervioso central, aparato cardiovascular y tracto gastrointestinal). Su presentación puede ser sistémica o localizada y sus etiologías son múltiples. En los pacientes con cáncer es un gran reto diagnóstico establecer la causa de la microangiopatía trombótica, siendo las etiologías más frecuentes la neoplasia maligna activa, la coagulación intravascular diseminada, infecciones y medicamentos antineoplásicos. Se presenta el caso clínico de una paciente con adenocarcinoma cáncer de páncreas irresecable, en manejo crónico con gemcitabina y se resalta la importancia de sospechar y distinguir la MAT inducida por quimioterapia, de la causada por la neoplasia ya que el pronóstico y tratamiento son muy diferentes. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2249).

Hematopoietic stem cell transplantation associated thrombotic microangiopathy / 中国小儿急救医学

Hematopoietic stem cell transplantation related thrombotic microangiopathy (TA-TMA) is a clinical syndrome characterized by microvascular hemolytic anemia, thrombocytopenia and involvement of end organ.The pathogenesis of TA-TMA involves vascular endothelial cell injury and abnormal activation of complement system.The risk factors include conditioning regimens, graft-versus-host disease, immunosuppressants, infection and HLA compatibility.Timely diagnosis and early initiation of appropriate treatment are essential to prevent multiple organ dysfunction and eventual death.At present, the lack of clinical evidence of TA-TMA has led to the fact that its diagnostic criteria and treatment have not been unified.The diagnosis and treatment suggestions put forward by domestic and foreign experts are intended to help clinicians evaluate potential TA-TMA, establish diagnosis in time, and give reasonable treatment and management.

Role of complement activation in the pathogenesis of severe cardiorenal injury in patients with primary malignant hypertension / 中华肾脏病杂志

Objective:To investigate the role of complement activation in the pathogenesis of primary malignant hypertension (MHT) with nephrosclerosis complicated with severe cardiorenal injury.Methods:Data of MHT patients with nephrosclerosis proven by biopsy from January 2010 to December 2020 in the Beijing Anzhen Hospital, Capital Medical University were retrospectively analyzed. The expressions of complement-related component C4d, C1q, complement factor H-related protein 5, C3c and C5b-9 were detected by immunohistochemical staining. According to whether the patients were complicated with acute heart failure (AHF) and/or acute kidney injury (AKI), they were divided into severe cardiorenal injury group and non-severe cardiorenal injury group. The differences of clinicopathological data between the two groups were compared. According to the degree of C4d deposition in renal tissues, patients were divided into C4d diffused deposition group and non-C4d diffused deposition group. The severity of cardiorenal injury and the pathological characteristics of thrombotic microangiopathy in renal tissues were compared between the two groups.Results:A total of 33 patients were enrolled in this study, of which 17 cases (51.5%) were complicated with severe cardiorenal injury; AHF occurred in 16 patients (48.5%), AKI occurred in 8 patients (26.7%), and AHF and AKI were combined in 7 patients (21.2%). Compared with non-severe cardiorenal injury group, patients in severe cardiorenal injury group had higher levels of baseline lactate dehydrogenase [326.0 (217.0, 366.0) IU/L vs 197.0 (165.0, 220.0) IU/L, Z=37.000, P=0.002] and hemoglobin [(143.6±24.0) g/L vs (106.4±24.7) g/L, t=38.500, P<0.001], lower levels of 12 h urinary incontinence osmolality [400.0 (342.5, 504.0) mmol/L vs 476.0 (432.3, 616.5) mmol/L, Z=72.000, P=0.021] and serum albumin [(36.2±9.4) g/L vs (43.2±6.2) g/L, t=6.423, P=0.017], and thicker left ventricular posterior wall [(14.0±2.1) mm vs (12.1±1.1) mm, t=6.552, P=0.018]. The immunohistochemical results of kidney tissue showed that the proportions of C4d and C5b-9 diffused deposition in severe cardiorenal injury group were significantly higher than those in non-severe cardiorenal injury group (5/16 vs 0/15, P=0.043; 12/16 vs 5/15, P=0.032). Compared with non-C4d diffused deposition group, C4d diffused deposition group had higher incidence of AHF (5/5 vs 10/26, P=0.018), poorer heart function, more severe ventricular remodeling, and shorter history of hypertension [2.0 (0, 12.0) months vs 48.0 (9.5, 84.0) months, Z=22.500, P=0.022]. Conclusions:The incidence of severe cardiorenal injury in MHT patients with nephrosclerosis is about 51.5%. The proportion of diffuse deposition of complement activated components in renal tissues in patients with severe cardiorenal injury is higher than that in patients with non-severe cardiorenal injury. Overactivation of complement may be involved in the pathogenic process of severe heart and kidney injury caused by MHT.

Brote de 4 casos leptospirosis de un grupo familiar en zona rural tropical de Colombia: un reporte de caso / Outbreak of 4 leptospirosis cases in a family group in tropical rural zone of Colombia: a case report

La leptospirosis es una zoonosis con manifestaciones clínicas causadas por espiroquetas patógenas del género Leptospira spp. Su curso puede ser desde enfermedad leve hasta un síndrome ictero-hemorrágico severo denominado enfermedad de Weil. Se estudió un brote epidemiológico constituido por una serie de cuatro casos de leptospirosis de severidad moderada a severa, ocurridos en una zona rural de clima tropical en los llanos orientales de Colombia, a 450 metros sobre el nivel del mar en una familia visitante en Puerto Lleras, Meta, Colombia. Probablemente secundario al consumo de aguas contaminadas por orina de roedores. Las pacientes fueron ingresadas bajo la sospecha de un síndrome ictérico de origen infeccioso con un falso positivo para antígeno de superficie de hepatitis B. Dos pacientes desarrollaron síndrome de Weil asociado a microangiopatía trombótica por lo que requirieron manejo en unidad de cuidados intensivos (UCI) sin embargo, una de ellas fallece y las otras dos pacientes desarrollan signos y síntomas moderados evidenciando un curso variable de la enfermedad. En nuestro país existe una sobre notificación de síndromes febriles, ictéricos e icterohemorragicos de diferentes etiologías y difícil diagnóstico por lo que la leptospirosis tiende a ser confundida o ignorada como diferencial en muchos casos.

Leptospirosis is a zoonosis with clinical manifestations caused by pathogenic spirochetes of the genus Leptospira spp. Its course can range from mild illness to a severe jaundice-hemorrhagic syndrome called Weil's disease. An epidemiological outbreak consisting of a series of four cases of leptospirosis of moderate to severe severity, which occurred in a rural area with a tropical climate in the eastern plains of Colombia, at 450 meters above sea level, was studied in a visiting family in Puerto Lleras, Meta, Colombia. Probably secondary to the consumption of water contaminated by rodent urine. The patients were admitted on suspicion of an infectious jaundice syndrome with a false positive for hepatitis B surface antigen. Two patients developed Weil's syndrome associated with thrombotic microangiopathy, requiring ICU management, however, one of them died and the other two patients develop moderate signs and symptoms showing a variable course of the disease. In our country there is an overreporting of febrile, jaundice and jaundice syndromes of different etiologies and difficult diagnosis, so that leptospirosis tends to be confused or ignored as differential in many cases.

Púrpura trombocitopénica trombótica en un paciente con infección por VIH / Thrombotic thrombocytopenic purpura, in a HIV-infected patient: case report

Resumen Las manifestaciones hematológicas de la infección por el VIH son frecuentes y variadas debido a su capacidad de afectar prácticamente todas las líneas celulares. Dentro de éstas, la púrpura trombocitopénica trombótica (PTT) es una de las entidades que constituyen las microangiopatías trombóticas. Se caracteriza por la presencia de trombocitopenia y anemia hemolítica microangiopática con alteración de la función renal. Actualmente, la co-existencia de estas dos entidades es poco frecuente debido a la terapia anti-retroviral de alta efectividad (TARV) Presentamos el caso de un paciente de 28 años, quien consultó por fiebre asociada a episodios de gingivorragia, palidez mucocutánea generalizada y debilidad progresiva. Los estudios evidenciaron una anemia y trombocitopenia grave. Se encontraron esquistocitos y microesferocitos en el frotis de sangre periférica con actividad de la enzima ADAMTS 13 disminuida (6,8%). Se confirmó el diagnóstico de una PTT como manifestación inicial de una infección por VIH. Se indicó manejo con plasmaféresis e inicio de TARV con buena respuesta.

Abstract Hematological manifestations for human immunodeficiency virus (HIV) infection are frequent and diverse due to its ability to affect almost all cell lines. Among these, thrombotic thrombocytopenic purpura (TTP) is one of the thrombotic microangiopathies syndromes, characterized by the presence of thrombocytopenia and microangiopathic hemolytic anemia with impaired renal function. Nowadays, the relationship between these two entities is rare given the current highly active antiretroviral therapy (HAART). We report the case of a 28-year-old patient, who presented with fever associated with gingival bleeding, generalized mucocutaneous pallor and progressive weakness. Routine investigations showed anemia and severe thrombocytopenia, schistocytes and micro spherocytes in peripheral blood smear. Required blood transfusion, with decreased ADAMTS 13 enzyme activity (6.8%). With these findings,TTP was diagnosed as the initial manifestation of the HIV infection. The patient received management with five sessions of plasmapheresis and HAART with subsequent improvement.

Efficacy of individualized rituximab as the rescue therapy for active lupus nephritis with acute kidney injury / 中华肾脏病杂志

Objective:To investigate the efficacy and safety of individualized rituximab rescue therapy for active lupus nephritis with acute kidney injury (AKI).Methods:The clinical data of lupus nephritis patients with AKI treated with rituximab at the Kidney Disease Center of the First Affiliated Hospital of Zhejiang University School of Medicine from April 2017 to June 2020 were collected, and the renal remission rate and adverse events after rituximab treatment were analyzed retrospectively. The Kaplan-Meier method was used to calculate the cumulative incidence of patients' remission.Results:There were 13 patients enrolled, including 8 females, and aged (35.23±15.92) years old. The urinary protein/creatinine ratio was (5.22±1.57) g/g before rituximab treatment. Four patients were on dialysis at admission, and 9 patients without dialysis had serum creatinine of (223.22±85.73) μmol/L. Eight patients were confirmed as proliferative lupus nephritis by renal biopsies, including 7 cases with crescent formation and 1 case with thrombotic microangiopathy (TMA), and the other 5 cases without renal biopsies were clinically diagnosed as TMA. The dose of rituximab was (815±516) mg (200-2 100 mg), and all the patients reached the state of peripheral blood B cells clearance (CD19 + B cell count was<5/μl). After the first treatment of rituximab, the median time to B-cell clearance was 21(15, 35) days, and 8 patients reached B-cell depletion (CD19 + B cell count was 0). The remission rate was 12/13 (two cases reached complete remission, and 10 cases reached partial remission). Three cases stopped dialysis, and 1 case (with glomerulosclerosis of 52.94%) entered maintaining dialysis. The relapse times in the maintenance remission period of 7 patients with refractory lupus nephritis declined significantly from (1.57±0.53) times in a median history of 60(20, 109) months to (0.43±0.79) times in a median history of 18(10, 23) months after the use of rituximab ( P=0.015). After using rituximab, the incidence of infection was 7/13. The median time from the use of rituximab to infection was 26(4, 44) days. Pulmonary infection (5/13) was the most common type and all infected patients recovered after anti-infection treatment. Conclusions:Rituximab can be used in the treatment of active lupus nephritis with AKI, especially in patients with crescent formation and TMA, but the infection should be paid close attention to and prevented.

Clinical characteristics and early recognition of thrombotic microangiopathy in children with systemic lupus erythematosus / 中国小儿急救医学

Objective:To analyze the clinical characteristics of children diagnosed with systemic lupus erythematosus(SLE)complicated with thrombotic microangiopathy(TMA)for early recognition.Methods:We retrospectively reviewed the clinical records of 14 SLE patients with TMA hospitalized at Shanghai Children′s Medical Center, Shanghai Jiaotong University School of Medicine from December 2005 to October 2020.Results:The incidence of TMA was 5.65%(14/248)of the hospitalized patients with SLE and 7.87%(14/178)of the hospitalized patients with lupus nephritis.Four patients were boys while ten patients were girls.One boy was six years old and other 13 patients were from 11 to 18 years old.Their SLEDAI scores ranged from 14 to 31, and all of them were severe activity.Renal biopsy of 11 patients during TMA course all revealed lupus nephritis(type Ⅳ, n=8; type Ⅳ+ Ⅴ, n=3). These 14 SLE children were diagnosed with TMA within 3 days to 2 months after admission.At the beginning of the hospitalization, only six patients had both anemia and thrombocytopenia, while eight patients only had moderate anemia.All of the patients had obvious hypocomplementemia.Especially in the patients with first onset of SLE without treatment, their serum levels of C3 were less than 0.17 g/L and C4 were less than 0.07 g/L.Moreover, glomerular filtration rates of these patients were lower than that in normal range.The follow-up time were 0.2-11.3 years(median time was 2.6 years). After treatment, six patients obtained complete remission, and five patients obtained partial remission.One patient had sudden death during the 4th plasmapheresis, and the other two patients deteriorated. Conclusion:Children with SLE and TMA are mostly in severe disease activity, and renal pathology is type Ⅳ lupus nephritis.The SLE children with anemia should be paid special attention to the level of serum complement whether they have thrombocytopenia or not.If the level of serum complements decrease obviously, glomerular filtration rates should be monitored closely and schistocytes should be searched repeatedly in the blood smears of the peripheral blood to facilitate the early recognition of TMA.

Pathology of antibody-mediated rejection in renal allograft / 器官移植

Antibody-mediated rejection (AMR), also known as humoral rejection, is an immune injury caused by rejection involved with multiple humoral immune effectors, such as antibodies and complements, etc. AMR plays a pivotal role in hyperacute, acute and chronic rejection. In this article, the basic definition of AMR, the research progress and major achievements on AMR pathology according to Banff classification on allograft pathology (Banff classification), and main pathological characteristics of AMR in renal allograft were reviewed, aiming to provide reference for accurate diagnosis and timely treatment of AMR, and guarantee the long-term survival of renal graft and recipients.

Update on thrombocytopenia in pregnancy / Atualização sobre trombocitopenia na gravidez

Abstract Thrombocytopenia, defined as platelet count < 150,000mm3, is frequently diagnosed by obstetricians since this parameter is included in routine surveillance during pregnancy, with an incidence of between 7 and 12%. Therefore, decisions regarding subsequent examination and management are primordial. While most of the cases are due to physiological changes, as gestational thrombocytopenia, other causes can be related to severe conditions that can lead to fetal or maternal death. Differentiating these conditions might be challenging: they can be pregnancy-specific (pre-eclampsia/ HELLP syndrome [hemolysis, elevated liver enzymes, low platelets]), or not (immune thrombocytopenia purpura, thrombotic thrombocytopenic purpura or hemolytic uremic syndrome). Understanding the mechanisms and recognition of symptoms and signs is essential to decide an adequate line of investigation. The severity of thrombocytopenia, its etiology and gestational age dictates different treatment regimens.

Resumo Trombocitopenia, definida como uma contagem de plaquetária < 150.000mm3, é frequentemente diagnosticada pelos obstetras, uma vez que este parâmetro está incluído na vigilância de rotina durante a gravidez, com uma incidência de entre 7 e 12%. Assim, decisões relativas à avaliação e orientação subsequentes são primordiais. Embora a maioria dos casos ocorra devido a alterações fisiológicas, como a trombocitopenia gestacional, outras causas podem estar relacionadas com condições graves que podem levar à morte fetal ou materna. Distinguir entre estas entidades pode ser desafiante: elas podem ser específicas da gravidez (pré-eclâmpsia/síndrome HELLP [hemolysis, elevated liver enzymes, low platelets]) ou não (púrpura trombocitopênica imune, púrpura trombocitopênica trombótica ou síndrome hemolítico urêmico). Compreender os mecanismos e reconhecer os sinais e sintomas é essencial para decidir uma adequada linha de investigação. A severidade da trombocitopenia, a sua etiologia e a idade gestacional ditam regimes de tratamento diferentes.

Microangiopatía trombótica sistémica asociada a mutaciones del complemento en trasplante renal donante vivo. reporte de caso / Systemic thrombotic microangiopathy associated with complement pathway mutations in living donor kidney transplant. case report

RESUMEN El síndrome urémico hemolítico (SUH) se caracteriza por la presencia de anemia hemolítica, plaquetopenia e insuficiencia renal aguda. Si bien se distingue clásicamente en típico o infeccioso y atípico, es menester reconocer situaciones clínicas en las que se pone de manifiesto, como por ejemplo, embarazo, puerperio inmediato, tumores, trasplante, drogas, etc., condiciones clínicas que han sido denominadas amplificadoras del complemento. La recurrencia postrasplante delsíndrome urémico hemolítico atípico (SUHa) ha sido descrita en porcentajes variables en pacientes con mutaciones del factor H, factor B, factor I y C3, y gen de la trombomodulina, en reportes de casos aislados. Se presenta el caso de una paciente con enfermedad renal crónica (ERC) secundaria a agenesia renal, receptora preemptive de un riñón de donante vivo relacionado que presentó disfunción del injerto renal secundaria a microangiopatía trombótica, asociado a complicación neurológica, hemorragias, disfunción orgánica múltiple y óbito. Se describen los hallazgos del estudio genético y anatomopatológico de necropsia.

ABSTRACT Hemolytic uremic syndrome (HUS) is characterized by the presence of hemolytic anemia, thrombocytopenia and acute kidney injury. Although it is usually distinguished as typical or infectious and atypical, it is necessary to recognize clinical situations in which it is revealed, such as pregnancy, immediate postpartum period, tumors, transplantation, drugs, etc., i.e. clinical conditions that have been called complement-amplifying conditions. Post-transplantation recurrence of atypical hemolytic uremic syndrome (aHUS) has been described in variable percentages in patients with mutations of factor H, factor B, factor I and C3, and thrombomodulin gene, in reports of isolated cases. We present the case of a patient with chronic kidney disease (CKD) secondary to renal agenesis, a preemptive recipient of a related living donor kidney, which presented renal graft dysfunction secondary to thrombotic microangiopathy, associated with neurological complications, hemorrhages, multiple organ dysfunction and death. The findings of the genetic and pathological autopsy study are described.

The 476th case: skin rash, edema, thrombocytopenia and anemia / 中华内科杂志

The 21-year-old male patient was admitted to the Department of Rheumatology and Immunology at Peking Union Medical College Hospital with chief complaints of "skin rash for 1 year and edema for 2 months". He was diagnosed with systemic lupus erythematosus (SLE) with renal, cardiac and hematological involvement. Remission was not achieved after glucocorticoid pulse treatment. The patient experienced oliguria, malignant hypertension, accompanied by thrombocytopenia and low serum complements, and elevated lactate dehydrogenase and serum creatinine. Schistocytes were seen in the peripheral blood smear. Thrombotic microangiopathy (TMA) secondary to SLE was diagnosed. Though plasma exchange was partially effective, TMA could not be controlled yet. The activity of serum von Willebrand factor -cleaving protease (ADAMTS 13) was 100%, and ADAMTS 13 inhibitor was negative. Finally, remission of the disease was achieved after second glucocorticoid pulse therapy and rituximab treatment. At the 3-month follow-up, the patient′s condition was stable with mild anemia and normal platelet count. Patients with TMA secondary to SLE are heterogenous, while normal ADAMT 13 activity indicates poor prognosis. Early and aggressive treatment is important for disease control, and plasma exchange is helpful as a supportive care.

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

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

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