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.

Púrpura trombótica trombocitopénica en pediatría. Reporte de un caso / Thrombotic thrombocytopenic purpura in pediatrics. A case report

La púrpura trombótica trombocitopénica es una entidad poco frecuente en pediatría, pero de alta mortalidad sin tratamiento adecuado y oportuno. Se caracteriza por presentar anemia hemolítica microangiopática asociada a signos y síntomas neurológicos, cardíacos, abdominales y menos frecuentemente renales; puede estar acompañada de fiebre. En niños, el diagnóstico se basa en los hallazgos clínicos y de laboratorio. La actividad de ADAMTS13 <10 % apoya, pero no confirma el diagnóstico y, dada la gravedad de la patología, el resultado no debe retrasar el inicio del tratamiento. Se presenta una paciente de 15 años, previamente sana, con signos neurológicos asociados a anemia hemolítica y trombocitopenia. Durante su internación, se arribó al diagnóstico de púrpura trombótica trombocitopénica adquirida.

Thrombotic thrombocytopenic purpura is a rare disease in pediatrics, but it has a high mortality if not managed in an adequate and timely manner. It is characterized by microangiopathic hemolytic anemia associated with neurological, cardiac, abdominal, and less frequently, renal signs and symptoms; it may be accompanied by fever. In children, diagnosis is based on clinical and laboratory findings. ADAMTS13 activity < 10% supports the diagnosis but does not confirm it and, given its severity, the result should not delay treatment initiation. Here we describe the case of a previously healthy 15-year-old female patient with neurological signs associated with hemolytic anemia and thrombocytopenia. During hospitalization, she was diagnosed with acquired thrombotic thrombocytopenic purpura.

Hipernatremia en pacientes con estado crítico por afecciones neurológicas

Fundamento: los trastornos del sodio son los más comunes y menos entendidos en pacientes con lesión cerebral aguda debido al papel principal que desempeña el sistema nervioso central en la regulación de la homeostasis del sodio y agua lo que puede llevar a complicaciones graves y resultados adversos, incluyendo la muerte. Objetivo: determinar la contribución a la mortalidad de la hipernatremia en pacientes con estado crítico por afecciones neurológicas. Métodos: estudio observacional analítico sobre 55 pacientes que ingresaron en las unidades de atención al grave del Hospital Universitario Arnaldo Milián Castro, entre octubre del 2020 y mayo del 2022, con independencia del valor del sodio plasmático a su admisión en el servicio, así como durante su estadía en las unidades de atención al grave. Se emplearon métodos estadísticos univariados y bivariados en el análisis de los datos. Resultados: el promedio de edad fue de 60±16 años. Los diagnósticos más relevantes fueron la hemorragia intraparenquimatosa (56,37 %), el trauma craneoencefálico y el accidente cerebrovascular isquémico (ambos 30 %). Las concentraciones plasmáticas de sodio mostraron diferencias significativas (pX2= 0,000), siendo la media mayor a las 24 horas de ingreso (174,2±133,6) y la menor al 5to día (102,9±72,9). Existió correlación significativa entre las concentraciones plasmáticas de sodio al ingreso ( 24 h y 72 h) y el estado al egreso. En el análisis bivariado individual por período, solo a las 24 horas hubo relación significativa, en este periodo la hipernatremia contribuyó a la mortalidad en 1,78 veces más que en aquellos que no tenían el sodio elevado (OR=1,78 con IC: 1,39-3,4). Conclusiones: la hipernatremia en el paciente con estado crítico por afecciones neurológicas se asocia con incremento de la mortalidad.

Background: sodium disorders are the most common and least understood in patients with acute brain injury due to the major role played by the central nervous system in regulating sodium and water homeostasis, which can lead to serious complications and adverse outcomes, including death. Objective: to determine the hypernatremia contribution to mortality in patients with neurological conditions in critical state. Methods: longitudinal analytical observational study on 55 patients who were admitted to the acute care units at the Arnaldo Milián Castro University Hospital, between October 2020 and May 2022, regardless of the plasma sodium value upon admission to the service, as well as during their stay in the critical care units. Univariate and bivariate statistical methods were used in data analysis. Results: the average age was 60 ± 16 years. The most relevant diagnoses were intraparenchymal hemorrhage (56.37%), head trauma, and ischemic stroke (both 30%). Plasma sodium concentrations showed significant differences (pX2= 0.000), with the highest average at 24 hours of admission (174.2 ± 133.6) and the lowest at the 5th day (102.9 ± 72.9). There was a significant correlation between plasma sodium concentrations at admission, 24h and 72h with the state at discharge. In the individual bivariate analysis by period, there was only a significant relationship after 24 hours. In this period, hypernatremia contributed 1.78 times more to mortality than in those who did not have elevated sodium (OR=1.78 with CI: 1,39-3,4). Conclusions: hypernatremia in critically ill patients with neurological conditions is associated with increased mortality.

Isquemia arterial aguda trombótica de los miembros inferiores / Acute thrombotic arterial ischemia of the lower limbs

Introducción: La enfermedad arterial periférica es una de las afecciones más prevalentes. Resulta habitual su coexistencia con la enfermedad vascular en otras localizaciones. El diagnóstico precoz tiene importancia para mejorar la calidad de vida del paciente y reducir el riesgo de eventos secundarios mayores, como el infarto agudo de miocardio o el ictus. Objetivo: Caracterizar el comportamiento de la isquemia arterial aguda trombótica en miembros inferiores en pacientes que ingresaron en el Instituto Nacional de Angiología y Cirugía Vascular. Métodos: Se realizó un estudio observacional, descriptivo y retrospectivo, con el fin de determinar factores pronósticos en la evolución final del tratamiento quirúrgico de la isquemia arterial aguda trombótica en miembros inferiores, en pacientes que ingresaron en los servicios de Arteriología y Angiopatía Diabética del Instituto Nacional de Angiología y Cirugía Vascular durante un período de cuatro años. Resultados: El grupo de edades más afectado estuvo entre 40 y 59 años, con un predomino del sexo masculino. El hábito de fumar fue el factor de riesgo vascular más frecuente; y la amputación mayor, el procedimiento quirúrgico más empleado, por lo que el patrón oclusivo femoropoplíteo resultó el más prevalente. Conclusiones: Predominaron el sexo masculino, el hábito de fumar, la amputación mayor y el patrón oclusivo femoropoplíteo(AU)

Introduction: Peripheral arterial disease is one of the most prevalent conditions. Its coexistence with vascular disease in other locations is common. Early diagnosis is important to improve the patient's quality of life and reduce the risk of major secondary events, such as acute myocardial infarction or stroke. Objective: To characterize the behavior of acute thrombotic arterial ischemia in lower limbs in patients admitted to the National Institute of Angiology and Vascular Surgery. Methods: An observational, descriptive and retrospective study was conducted in order to determine prognostic factors in the final evolution of surgical treatment of acute thrombotic arterial ischemia in the lower limbs in patients admitted to the Arteriology and Diabetic Angiopathy services of the National Institute of Angiology and Vascular Surgery for a period of four years. Results: The most affected age group was the one of 40 to 59 years, with a predominance of males. Smoking was the most frequent vascular risk factor; and major amputation, the most used surgical procedure, so the femoropopliteal occlusive pattern was the most prevalent. Conclusions: Male sex, smoking habit, major amputation and femoropopliteal occlusive pattern predominated(AU)

Hemolytic-uremic syndrome: 24 years' experience of a pediatric nephrology unit / Síndrome hemolítico-urêmica: 24 anos de experiência de uma unidade de nefrologia pediátrica

Abstract Introduction: A better understanding of hemolytic-uremic syndrome (HUS) pathophysiology significantly changed its treatment and prognosis. The aim of this study is to characterize the clinical features, severity, management, and outcomes of HUS patients. Materials and Methods: Retrospective study of HUS patients admitted to a Pediatric Nephrology Unit between 1996 and 2020. Demographic and clinical data regarding etiology, severity, treatment strategies, and patient outcome were collected. Results: Twenty-nine patients with HUS were admitted to our unit, but four were excluded. Median age at diagnosis was two years (2 months - 17 years). Clinical manifestations included diarrhea, vomiting, oliguria, hypertension, and fever. During the acute phase, 14 patients (56%) required renal replacement therapy. Infectious etiology was identified in seven patients (five Escherichia coli and two Streptococcus pneumoniae). Since 2015, 2/7 patients were diagnosed with complement pathway dysregulation HUS and there were no cases of infectious etiology detected. Six of these patients received eculizumab. The global median follow-up was 6.5 years [3 months-19.8 years]. One patient died, seven had chronic kidney disease, four of whom underwent kidney transplantation, one relapsed, and seven had no sequelae. Conclusion: These results reflect the lack of infectious outbreaks in Portugal and the improvement on etiological identification since genetic testing was introduced. The majority of patients developed sequels and mortality was similar to that of other countries. HUS patients should be managed in centers with intensive care and pediatric nephrology with capacity for diagnosis, etiological investigation, and adequate treatment. Long-term follow-up is essential.

Resumo Introdução: Um melhor entendimento da fisiopatologia da síndrome hemolítico-urêmica (SHU) mudou significativamente seu tratamento e prognóstico. Este estudo teve como objetivo caracterizar condições clínicas, gravidade, manejo e desfechos de pacientes com SHU. Materiais e Métodos: Estudo retrospectivo de pacientes com SHU admitidos numa Unidade de Nefrologia Pediátrica entre 1996-2020. Foram coletados dados demográficos e clínicos sobre etiologia, gravidade, estratégias de tratamento, desfechos de pacientes. Resultados: 29 pacientes com SHU foram admitidos em nossa unidade, mas quatro foram excluídos. A idade mediana ao diagnóstico foi dois anos (2 meses-17 anos). Manifestações clínicas incluíram diarreia, vômitos, oligúria, hipertensão e febre. Durante a fase aguda, 14 pacientes (56%) necessitaram de terapia renal substitutiva. Identificou-se a etiologia infecciosa em sete pacientes (cinco Escherichia coli; dois Streptococcus pneumoniae). Desde 2015, 2/7 pacientes foram diagnosticados com SHU por desregulação da via do complemento e não foram detectados casos de etiologia infecciosa. Seis desses pacientes receberam eculizumab. A mediana global de acompanhamento foi 6,5 anos [3 meses-19,8 anos]. Um paciente faleceu, sete apresentaram doença renal crônica, sendo quatro submetidos a transplante renal, uma recidiva e sete sem sequelas. Conclusão: Estes resultados refletem a ausência de surtos infecciosos em Portugal e a melhoria na identificação etiológica desde que os testes genéticos foram introduzidos. A maioria dos pacientes desenvolveu sequelas e a mortalidade foi semelhante à de outros países. Pacientes com SHU devem ser manejados em centros com cuidados intensivos e nefrologia pediátrica com capacidade para diagnóstico, investigação etiológica e tratamento adequado. O acompanhamento alongo prazo é essencial.

Trombocitosis esencial de aparición durante el embarazo. Reporte de caso y revisión de la bibliografía / Essential thrombocytosis of pregnancy onset. Case report and literature review

Resumen ANTECEDENTES: La coexistencia de neoplasias mieloproliferativas durante el embarazo puede derivar en complicaciones para la madre y el feto, de ahí la indispensable necesidad de detectarlas oportunamente. CASO CLÍNICO: Paciente de 30 años, primigesta. En el control prenatal se detectó una elevación significativa de plaquetas y leucocitos. Luego de descartar un proceso infeccioso e interconsulta con el hematólogo se le indicó un antiagregante plaquetario. El embarazo transcurrió sin complicaciones de tipo trombótico o hemorrágico y finalizó mediante cesárea a las 40 semanas, indicada por falta de progresión del trabajo de parto. Posteriormente se inició el tratamiento específico para la enfermedad y seguimiento. METODOLOGÍA: La búsqueda de artículos publicados durante los últimos 20 años se efectuó en las bases de datos PubMed y Clínical Key con los MeSH "essential thrombocytemia AND pregnancy", "hematological neoplasms AND pregnancy". RESULTADOS: Se obtuvieron 14 artículos de los que se excluyeron 3 por no incluir a mujeres embarazadas. La revisión final fue de 11 artículos. CONCLUSIONES: El seguimiento correcto del control prenatal permite advertir las complicaciones médicas independientes del embarazo. Cuando así sucede es posible la intervención oportuna y la participación de otros especialistas que confirmen el diagnóstico para, en conjunto, tomen la mejor decisión en beneficio de la madre y su hijo por nacer.

Abstract BACKGROUND: The coexistence of myeloproliferative neoplasms during pregnancy may lead to maternal and fetal complications, and early detection is essential. CLINICAL CASE: A 30-year-old primigravida. Prenatal examination revealed a significant increase in platelets and leukocytes. After exclusion of an infectious process and consultation with the haematologist, she was prescribed an antiplatelet agent. The pregnancy proceeded without thrombotic or haemorrhagic complications and was terminated by caesarean section at 40 weeks, indicated for lack of progress in labour. Specific treatment of the disease and follow-up were then initiated. METHODOLOGY: Articles published in the last 20 years were searched in PubMed and Clinical Key databases using MeSH "essential thrombocythemia AND pregnancy", "haematological neoplasms AND pregnancy". RESULTS: We obtained 14 articles, of which 3 were excluded because they did not include pregnant women. The final review consisted of 11 articles. CONCLUSIONS: Correct follow-up of antenatal care can warn of medical complications independent of pregnancy. In this case, timely intervention and involvement of other specialists is possible to confirm the diagnosis and make the best joint decision for the benefit of the mother and her unborn child.

Effect of Synergistic Treatment with Qingjin Huazhuo Formula （清金化浊方） on Thrombotic Events in Hospitalized Patients of Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Phlegm Heat Stasis Obstructing in the Lung Syndrome： A Retrospective Cohort Study / 中医杂志

ObjectiveTo analyze the effect and possible mechanism of the synergistic treatment with Qingjin Huazhuo Formula （清金化浊方， QHF） on the occurrence of thrombotic events in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease （AECOPD） and phlegm heat stasis obstructing in the lung syndrome. MethodsIn a retrospective cohort study， 305 AECOPD inpatients with the syndrome of phlegm heat stasis obstructing in the lung were included. According to whether using QHF （the course of treatment ≥ 7 days）， they were divided into the exposure group （193 cases） and the non-exposure group （112 cases）. Totally， 109 pairs of cases were obtained by 1∶1 propensity score matching （PSM）. After matching， the occurrence of thrombotic events during hospitalization， the remission of main symptoms or signs （including cough， expectoration， wheezing， cyanosis） after 10 days （±3 days） of treatment， and the difference of the indicators including D-dimer， percentage of neutrophils （NEUT%）， C-reactive protein （CRP）， arterial partial pressure of oxygen （PaO2）， and arterial partial pressure of carbon dioxide （PaCO2） before treatment and after 10 days （±3 days） of treatment during the first auxiliary examination. ResultsAfter matching， the incidence of thrombotic events during hospitalization in the exposure group （5 cases， 4.59%） were lower than that of the non-exposure group （15 cases， 13.76%， P＜0.05）. The exposure factor that taking QHF for 7 days or above was a protective factor for thrombotic events in AECOPD hospitalized patients with phlegm heat stasis obstructing in the lung syndrome （RR = 0.333， 95% CI 0.126 to 0.885）. The remission rates of cough （100/109， 91.74%）， expectoration （103/109， 94.50%）， wheezing （102/109， 93.58%）， and cyanosis （97/109， 88.99%） in the exposure group were significantly higher than those in the non-exposure group （90/109， 82.57%； 94/109， 86.24%； 89/109， 81.65%； 86/109， 78.90%） after treatment （P＜0.05）. After treatment， the levels of D-dimer， NEUT%， CRP and PaCO2 in both groups significantly decreased （all P＜0.05）， and the level of PaO2 significantly increased （P＜0.05）. The difference of the levels of D-dimer， NEUT% and PaO2 in the exposure group before and after treatment were larger than those in the non-exposure group （P＜0.05）， while the pre-post difference of CRP and PaCO2 were not significantly different between the two groups （P＞0.05）. ConclusionThe synergistic treatment with QHF can effectively reduce the occurrence of thrombotic events， alleviate the clinical symptoms or signs such as cough， expectoration， wheezing， and cyanosis， and can improve lung function in hospita-lized patients with AECOPD and phlegm heat stasis obstructing in the lung syndrome. Its mechanism may be related to improving blood coagulation and inflammatory status.

A Retrospective Study on the Characteristics of Traditional Chinese Medical Syndromes in 3088 Cases of Atherosclerotic Cerebral Infarction / 中医杂志

ObjectiveTo investigate the characteristics of traditional Chinese medicine syndrome and the evolution of pathogenesis in different stages of atherosclerotic thrombotic cerebral infarction （ATCI）. MethodsClinical data of 3088 ATCI patients from 8 hospitals in 6 provinces and cities were collected from the hospital information system during January 1， 2015 to December 31， 2019. After staging and counting clinical symptoms， common factors were extracted using the principal component analysis method in factor analysis. Cluster analysis was then carried out on the basis of the factor analysis. The results of the combination of the evidence element identification， cluster analysis and expert discussion were used to discuss the evidence of the different disease stages of atherosclerotic cerebral infarction. ResultsOf the 3088 ATCI patients included， 2290 cases were in the acute phase and 798 in the non-acute phase. Excluding the main symptoms of ischaemic stroke， such as numbness and weakness of limbs， unfavourable movement， unfavourable speech and dizziness， we identified 84 indicators with a frequency ≥5% of the four diagnostic information variables. Of these， 36 indicators were observed in the acute phase and 35 in the non-acute phase. Factor analysis extracted 14 common factors from each phase. We selected factors with a loading coefficient ＞0.3 for evidence determination. These 14 groups of common factors were used as variables for clustering. After clustering， the acute， non-acute phase were each divided into 5 categories. Based on a combination of clinical practice and expert opinion， the symptoms identified in the acute period were syndrome of deficiency of both qi and yin， syndrome of blockade of wind-phlegm-static blood （36.07%）， syndrome of qi deficiency and blood stasis （20.74%）， syndrome of upward disturbance of wind-fire （15.15%）， syndrome of stirring wind due to yin deficiency （9.43%）， and syndrome of spleen deficiency and liver hyperactivity （3.80%）. In the non-acute phase， the symptoms were qi and yin deficiency with syndrome of qi stagnation and blood stasis （45.49%）， syndrome of deficiency of both qi and yin （20.05%）， syndrome of qi stagnation and blood stasis （16.42%）， spleen-kidney deficiency syndrome （8.52%）， and syndrome of hyperactivity of liver yang （4.89%）. ConclusionThe acute phase of AICI is mainly characterized by blood stasis， fire， internal wind， hyperactivity of yang， qi deficiency and yin deficiency， while the non-acute phase is characterized by yin deficiency， qi deficiency， blood stasis and qi stagnation. The main pathomechanism of ATCI involves deficiency of qi and yin， as well as obstruction of the channels by phlegm and blood stasis， and the fundamental pathomechanism is deficiency of qi and yin.

Renal thrombotic microangiopathy induced by targeted therapy combined with immunotherapy: a case report / 中华肾脏病杂志

Targeted therapy and immunotherapy have achieved great success in treating various solid and non-solid tumors, but the incidence of drugs-related adverse events is relatively high. The paper reports a case of renal thrombotic microangiopathy in an intrahepatic cholangiocarcinoma patient who underwent targeted therapy combined with immunotherapy. During the treatment, the tumor burden relieved continuously, but the patient developed proteinuria, edema and hypertension. The ADAMTS13 activity and inhibitors were normal, while the antiphospholipid antibody was positive. The patient was finally diagnosed as glomerular thrombotic microangiopathy with immune complex deposition by renal biopsy. After the cease of the antineoplastic agents and treatment with "cordyceps preparations" and "α-keto acids", the patient's blood pressure dropped to normal, her urine protein turnned to weakly positive, and her renal function remained stable.

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.

Platelet-endothelial aggregation receptor 1 and its mediated signalling pathway Advances in the study of the role of platelets and endothelial cells / 中国临床药理学与治疗学

Platelet-aggregation receptor 1 (PEAR1) is a transmembrane receptor identified in 2005 and expressed mainly on platelets and endothelial cells. PEAR1 is a receptor protein that contacts platelets with each other and plays an important role in platelet activation and aggregation. Endothelial cells play an important role in maintaining vascular tone and vascular repair, and PEAR1 regulates the process of tumourigenesis and development by affecting their proliferation and associated neovascularisation. In recent years, PEAR1 has gradually been recognized as a potential target for antithrombotic drugs. This review focuses on elucidating the mechanisms of platelet endothelial aggregation receptor 1 and related signaling pathways in platelets and endothelial cells, and provides new ideas for the study of drug therapy for tumour-associated thrombosis.

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.

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.

A combined regimen based on bortezomib and glucocorticoids for 6 patients with recurrent/refractory immune thrombotic thrombocytopenic purpura / 中华血液学杂志

Objective: To observe the efficacy and adverse reactions of a combination therapy regimen based on bortezomib and glucocorticoids in recurrent/refractory immune thrombocytopenic purpura (iTTP) . Methods: Six patients with recurrent/refractory TTP were included and treated with a glucocorticoid and two courses of bortezomib-based regimen. The clinical remission status of patients, changes in ADAMTS13 activity/ADAMTS13 inhibitor, and the occurrence of treatment-related adverse reactions were observed. Results: Of the 6 patients, 2 were males and 4 were females, with a median age of 21.5 (18-68) years. Refractory TTP was found in 1 case and recurrent TTP in 5 cases. Glucocorticoids were administered with reference to prednisone at 1 mg·kg(-1)·d(-1), and gradually reduced in dosage after achieving clinical remission. Bortezomib is subcutaneously administered at 1.3 mg/m(2) on days 1, 4, 8, and 11 with a 28-day treatment course consisting of 2 courses. Six patients achieved clinical remission after receiving bortezomib as the main treatment. ADMATS13 activity returned to normal in all patients with TTP after treatment, and the ADAMTS13 inhibitor turned negative. Thrombocytopenia is the most common adverse reaction after treatment, with other adverse reactions, including peripheral neuritis and abdominal pain, but ultimately all patients returned to normal. In a median follow-up of 26 (9-41) months, 5 patients maintained sustained remission, and 1 patient relapsed after 16 months of bortezomib treatment. Conclusion: Combination therapy of bortezomib and glucocorticoids has a satisfactory therapeutic effect and controllable adverse reactions for recurrent/refractory iTTP.

Clinical diagnosis and treatment of hereditary thrombocytopenia and purpura: a report of five cases and literature review / 中华血液学杂志

Objective: To report the clinical manifestations and laboratory features of five patients with congenital thrombotic thrombocytopenic purpura (cTTP) and explore its standardized clinical diagnosis and treatment along with a review of literature. Methods: Clinical data of patients, such as age of onset, disease manifestation, personal history, family history, and misdiagnosed disease, were collected. Treatment outcomes, therapeutic effects of plasma infusion, and organ function evaluation were observed. The relationship among the clinical manifestations, treatment outcomes, and ADAMTS13 gene mutation of patients with cTTP was analyzed. Additionally, detection of ADAMTS13 activity and analysis of ADAMTS13 gene mutation were explored. Results: The age of onset of cTTP was either in childhood or adulthood except in one case, which was at the age of 1. The primary manifestations were obvious thrombocytopenia, anemia, and different degrees of nervous system involvement. Most of the patients were initially suspected of having immune thrombocytopenia. Acute cTTP was induced by pregnancy and infection in two and one case, respectively. ADAMTS13 gene mutation was detected in all cases, and there was an inherent relationship between the mutation site, clinical manifestations, and degree of organ injury. Therapeutic or prophylactic plasma transfusion was effective for treating cTTP. Conclusions: The clinical manifestations of cTTP vary among individuals, resulting in frequent misdiagnosis that delays treatment. ADAMTS13 activity detection in plasma and ADAMTS13 gene mutation analysis are important bases to diagnose cTTP. Prophylactic plasma transfusion is vital to prevent the onset of the disease.

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.

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.

Microangiopatía trombótica como complicación de una pancreatitis aguda / Thrombotic microangiopathy as a complication of acute pancreatitis / Microangiopatia trombótica como complicação da pancreatite aguda

La púrpura trombótica trombocitopénica (PTT) es una microangiopatía trombótica poco frecuente, que se caracteriza por anemia hemolítica y plaquetopenia, con una elevada morbimortalidad. Su forma más frecuente es la PTT inmune, también denominada adquirida, provocada por la deficiencia de la enzima disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) secundaria a la presencia en plasma de autoanticuerpos. Presentamos el caso de un paciente con diagnóstico de pancreatitis aguda (PA) complicada con PTT, asociación de presentación excepcional en la práctica clínica.

Summary: Thrombotic thrombocytopenic purpura is rather an unusual thrombotic microangiopathy characterized by hemolytic anemia and plateletopenia which results in high morbimortality rates. The most frequent form of this disease is immune thrombotic thrombocytopenic purpura, also known as acquired thrombotic thrombocytopenic purpura, which is caused by enzime deficiency disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) that is secondary to antibodies in plasma. The study presents the case of a patient with a diagnosis of acute pancreatitis with a rare complication of thrombotic thrombocytopenic purpura which is exceptional in the clinical practice.

A púrpura trombocitopênica trombótica (PTT) é uma microangiopatia trombótica rara, caracterizada por anemia hemolítica e trombocitopenia, com alta morbimortalidade. Sua forma mais comum é a TTP imune, também conhecida como adquirida, que é causada pela deficiência da enzima ADAMTS13 (em inglês A disintegrin-like and metalloprotease with thrombospondin type 1 motif no. 13) secundária à presença de autoanticorpos no plasma. Apresentamos o caso de um paciente com diagnóstico de pancreatite aguda (PA) complicada por PTT, associação com apresentação excepcional na prática clínica.

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