Re-understanding of the mechanism of coagulation disorder in liver cirrhosis / 临床肝胆病杂志

The liver plays an important regulatory role in maintaining the dynamic balance of coagulation and anticoagulation in the body. Such dynamic balance is fragile in patients with liver cirrhosis， and the risk of bleeding can be increased due to reductions in coagulation factors and platelet count and excessive fibrinolysis； meanwhile， thrombus can be formed due to the increases in von Willebrand factor and coagulation factor Ⅷ， the reductions in anticoagulant protein C and anticoagulant protein S， the increase in thrombin-generating potential， and alterations in antifibrinolytic components. This article reviews the mechanisms of coagulation disorder in liver cirrhosis， so as to help clinicians with the prevention and treatment of bleeding or thrombotic disorders in patients with liver cirrhosis.

Screening for the etiology of non-cirrhotic splanchnic vein thrombosis should be taken seriously in clinical practice / 临床肝胆病杂志

Non-cirrhotic splanchnic vein thrombosis （NC-SVT） mainly includes portal vein thrombosis， superior mesenteric vein thrombosis， splenic vein thrombosis， and hepatic vein thrombosis （Budd-Chiari syndrome）， and its prevalence rate is increasing with the increase in the incidence rates of related underlying diseases. Due to the harm of NC-SVT， there have been significant improvements in the awareness and ability for diagnosis among clinicians. However， anticoagulation and intervention therapies for thrombosis are often taken seriously in treatment， while the screening for risk factors or underlying diseases leading to SVT is ignored， which may affect the treatment outcome of thrombus in some patients and delay the diagnosis and treatment of the underlying disease. This article mainly introduces the acquired， hereditary， systemic， and local underlying diseases associated with the development of NC-SVT.

Hemofilia adquirida tipo A

La hemofilia adquirida es un trastorno hemostático causado por la presencia de autoanticuerpos inhibidores contra el F VIII de la coagulación. Clínicamente se presenta como sangrado espontáneo, principalmente en piel y tejidos blandos, y a diferencia de la hemofilia congénita, la hemartrosis es rara. Se presenta el caso de un paciente de sexo masculino, de 60 años, previamente sano, que acude a consulta por cuadro de 8 días de evolución de aparición de hematomas a nivel de miembro superior e inferior. Durante su evolución presenta TTPA alargado y concentraciones bajas de F VIII.

Acquired hemophilia is a hemostatic disorder caused by the presence of inhibitory autoantibodies against coagulation F VIII. Clinically it presents as spontaneous bleeding, mainly in the skin and soft tissues, and unlike congenital hemophilia, hemarthrosis is rare. We present the case of a 60-year-old male patient, previously healthy, who came to the clinic due to an 8-day history of hematomas on the upper and lower limbs. During its evolution it presents prolonged APTT and low concentrations of F VIII.

Influência do tratamento fisioterapêutico na independência funcional de pessoas com hemofilia submetidas à sinovectomia radioativa / Influence of physiotherapeutic treatment on the functional independence of people with hemophilia submitted to radioactive sinovectomy

A sinovectomia radioativa (SR) é considerada o tratamento de eleição no controle da sinovite crônica não responsiva ao tratamento conservador, sendo recomendado tratamento fisioterapêutico para a melhora da funcionalidade. Objetivo: Verificar a influência do tratamento fisioterapêutico na independência funcional e saúde articular de hemofílicos após tratamento com SR. Método: Trata-se de um estudo descritivo, retrospectivo, analítico e metodologia quali-quantitativa. Realizou-se avaliação fisioterapêutica, aplicação do HJHS para avaliação da saúde articular e Escore FISH para avaliação da independência funcional. Os participantes foram subdivididos em dois grupos de acordo com a realização ou não da fisioterapia após a SR. Resultados: Participaram do estudo 8 pessoas com hemofilia A, sexo masculino, média de idade de 19±5,3 anos. Foram 12 articulações submetidas a SR, dessas 41,67% cotovelos, 33,33% joelhos e 25% tornozelos. Na comparação dos grupos, não houve diferença estatística entre os eles nas variáveis: saúde articular e a Independência Funcional. Conclusão: O estudo é uma primeira tentativa de descrever o impacto da fisioterapia na independência funcional e saúde articular de hemofílicos submetidos à SR. Embora possua limitações, foi possível observar que o grupo que não realizou fisioterapia apresentava melhor saúde articular e melhor independência funcional previamente à SR em comparação ao grupo que realizou fisioterapia; porém, o grupo fisioterapia apresentava pior quadro global, com a funcionalidade impactada por outras articulações e não somente aquela tratada com SR, apresentando maior número de articulações alvo.

Radioactive synovectomy (RS) is considered the treatment of choice in the control of chronic synovitis resistant to conservative treatment, and physiotherapy is recommended to improve functionality after procedure. Objective: The aim was to verify the effects of physiotherapy on functional independence and joint health after RS. Method: This is a descriptive, retrospective, analytical study with qualitative/quantitative methodology. Physiotherapeutic evaluation, Hemophilia Joint Health Score (HJHS) application for joint outcome assessment and Functional Independence Score in Hemophilia (FISH) were used to measure the patient's functional ability. The participants were divided into two groups: one group underwent a physiotherapy program and one not treated with physiotherapy after RS. Results: The study included 8 people with hemophilia A, all male, their mean age was 19±5.3 years. Twelve joints were submitted to RS, in which 41.67% elbows, 33.33% knees and 25% ankles. In the comparison of the groups, there was no statistically significant difference between them in joint health and functional independence. Conclusion: The study is a first attempt to describe the impact of physiotherapy on functional independence and joint health of hemophilic patients submitted to SR. Although this study has limitations, it was possible to observe that the group not treated with physiotherapy had better joint health and better functional independence prior to SR compared to the group that underwent physiotherapy, but the group treated with physiotherapy had worse overall health and have their functionality impacted by joints other than those treated with RS, presenting a higher number of target joints.

Comparison of coagulation function between adrenocorticotropic hormone independent Cushing syndrome and nonfunctional adrenal adenoma and its influence factors / 北京大学学报(医学版)

OBJECTIVE@#To investigate the coagulation function indicators and identify influence factors of hypercoagulability in patients with adrenocorticotropic hormone (ACTH) independent Cushing syndrome (CS).@*METHODS@#In our retrospective study, the electronic medical records system of Peking University First Hospital was searched for the patients diagnosed with ACTH independent CS on discharge from January 2014 to June 2019. Nonfunctional adrenal adenoma patients were chosen as control group and matched 1 ∶1 by body mass index (BMI), gender, and discharge date. Clinical features and coagulation function indicators were compared between the two groups.@*RESULTS@#In the study, 171 patients were included in each group. Compared with control group, activated partial thromboplastin time (APTT), and prothrombin time (PT) in ACTH independent CS group were significantly lower [(29.22±3.39) s vs. (31.86±3.63) s, P < 0.001; (29.22±3.39) s vs. (31.86±3.63) s, P < 0.001], and both D-dimer and fibrin degradation products (FDP) levels were significantly higher (P < 0.05). Percentage of APTT levels under the lower limit of reference range in the CS patients was significantly higher than that in nonfunctional group (21.6% vs. 3.5%, P < 0.001). Percentage of D-dimer levels over the upper limit of reference range in the CS patients was significantly higher than that in nonfunctional group (13.5% vs. 6.6%, P=0.041). There were three patients with deep venous thrombosis and one patient with pulmonary embolism in CS group, however none was in control group. The area under curve (AUC) of serum cortisol rhythm (8:00, 16:00 and 24:00) levels was negatively associated with the levels of PT (r=-0.315, P < 0.001) and APTT (r=-0.410, P < 0.001), and positively associated with FDP (r=0.303, P < 0.001) and D-dimer levels (r=0.258, P < 0.001). There were no differences in coagulation function indicators among different histopathologic subgroups (adrenocortical adenoma, adrenocortical hyperplasia, oncocytic adenoma, adrenocortical carcinoma). With Logistic regression analysis, the AUC of cortisol and glycosylated hemoglobin A1c (HbA1c) levels were independent risk factors for hypercoagulability in the ACTH independent CS patients (P < 0.05).@*CONCLUSION@#ACTH independent CS patients were more likely in hypercoagulable state compared with nonfunctional adrenal adenoma, especially in ACTH independent CS patients with higher levels of cortisol AUC and HbA1c. These patients should be paid attention to for the hypercoagulability and thrombosis risk.

Implementación de tromboelastografia para evitar la transfusión de plasmas fresco congelado en neonatos / Implementation of thrombelastography to avoid transfusion of fresh frozen plasma in neonates

Introducción: actualmente, la indicación principal para la transfusión de FFP es corregir la deficiencia de los factores de coagulación en pacientes con hemorragia activa o sugestión de esta, sin embargo, la práctica clínica ha demostrado que un porcentaje grande de las transfusiones de FFP en neonatología no siguen las recomendaciones de las guías actuales y, en su mayoría, son innecesarias. Objetivo: ampliar el conocimiento que se tiene sobre la transfusión de FFP en neonatología y la implementación de la tromboelastografía para evitar realizar estas intervenciones. Metodología: se realizó una revisión de la literatura en la base de datos PubMed y Elsevier, usando palabras clave como tromboelastografía, transfusión de plasma en neonatos, hemostasia neonatal. Conclusión: se evidenció que los tiempos de coagulación de los neonatos y prematuros sanos son más prolongados en comparación a los adultos, por ello facilita su errada cuando se habla de transfusión de FFP, de ahí que la TEG sea una buena herramienta para evaluar el estado coagulante de los neonatos de manera integral, sin abrir paso a errores de interpretación y facilitando la decisión de tratamientos en los pacientes en UCIN, antes de requerir transfusiones de FFP.

Introduction: Currently the main indication for FFP transfusion is to correct coagulation factor deficiency in patients with active bleeding or its suggestion, however, clinical practice has shown that a large percentage of FFP transfusions in neonatology do not they follow current guideline recommendations and are mostly unnecessary. Objective: To expand the knowledge about these transfusions in neonatology and the implementation of thrombelastography to avoid performing these interventions. Methodology: A review of the literature was carried out in the PubMed and Elsevier databases, using keywords such as "thrombelastography", "plasma transfusion in neonates", "neonatal hemostasis". Conclusion: It was evidenced that the coagulation times of healthy neonates and premature infants are longer compared to adults, thus facilitating their misinterpretation and limiting their use when talking about FFP transfusion, therefore TEG is a good tool. to evaluate the coagulation interpretación y limita su utilización status of neonates in a comprehensive manner, without giving way to interpretation errors and facilitating treatment decisions in patients in the NICU before requiring FFP transfusions.

Effect of restrictive fluid resuscitation on the coagulation function and hemodynamic parameters in patients with hemorrhagic traumatic shock

Abstract Objectives To investigate the changes in the coagulation function and hemodynamic parameters in patients with Hemorrhagic Traumatic Shock (HTS) after restrictive fluid resuscitation. Methods A total of 139 patients with HTS admitted to our hospital were enrolled, among which 69 HTS patients were divided into the control group and the remaining 70 HTS patients as the observation group. Patients in the control group underwent regular fluid resuscitation, while those in the observation group underwent restrictive fluid resuscitation. Results During treatment, 70 patients in the observation group had a lower bleeding amount, infusion amount, and blood transfusion volume than those in the control group (p < 0.05). After treatment, patients in the observation group had better hemodynamic parameters and blood coagulation than those in the control group (p < 0.05), and the incidence rate in the observation group was only 12.9%, which was significantly lower than 60.87% in the control group, while the cure rate in the observation group was 100%, which was significantly higher than that in the control group (p < 0.05). Conclusions Restrictive fluid resuscitation could remarkably increase the cure rate and reduce the bleeding amount during HTS treatment, thereby benefiting the recovery of the patient's blood coagulation.

COVID-19-associated coagulopathy and acute kidney injury in critically ill patients

ABSTRACT Objective The incidence of thrombotic events and acute kidney injury is high in critically ill patients with COVID-19. We aimed to evaluate and compare the coagulation profiles of patients with COVID-19 developing acute kidney injury versus those who did not, during their intensive care unit stay. Methods Conventional coagulation and platelet function tests, fibrinolysis, endogenous inhibitors of coagulation tests, and rotational thromboelastometry were conducted on days 0, 1, 3, 7, and 14 following intensive care unit admission. Results Out of 30 patients included, 13 (43.4%) met the criteria for acute kidney injury. Comparing both groups, patients with acute kidney injury were older: 73 (60-84) versus 54 (47-64) years, p=0.027, and had a lower baseline glomerular filtration rate: 70 (51-81) versus 93 (83-106) mL/min/1.73m2, p=0.004. On day 1, D-dimer and fibrinogen levels were elevated but similar between groups: 1780 (1319-5517) versus 1794 (726-2324) ng/mL, p=0.145 and 608 (550-700) versus 642 (469-722) g/dL, p=0.95, respectively. Rotational thromboelastometry data were also similar between groups. However, antithrombin activity and protein C levels were lower in patients who developed acute kidney injury: 82 (75-92) versus 98 (90-116), p=0.028 and 70 (52-82) versus 88 (78-101) µ/mL, p=0.038, respectively. Mean protein C levels were lower in the group with acute kidney injury across multiple time points during their stay in the intensive care unit. Conclusion Critically ill patients experiencing acute kidney injury exhibited lower endogenous anticoagulant levels. Further studies are needed to understand the role of natural anticoagulants in the pathophysiology of acute kidney injury within this population.

INFLUÊNCIA DOS DISTÚRBIOS HEREDITÁRIOS DE COAGULAÇÃO NO REPARO DE LESÕES PERIRRADICULARES / INFLUENCE OF HEREDITARY COAGULATION DISORDERS ON THE REPAIR OF PERIRRADICULAR INJURIES

Lesão perirradicular é uma doença de etiologia microbiana, cuja evolução possui forte relação com a resposta imunológica do hospedeiro, que ocorre no intuito de conter essa infecção. O tratamento endodôntico nesses casos tem como objetivo biológico final a desinfecção do sistema de canais radiculares para possibilitar o reparo da região periapical. Esse reparo é um processo complexo que consiste em hemostasia, inflamação, proliferação celular, maturação e remodelação. Diversos estudos vêm sendo realizados no intuito de relacionar fatores sistêmicos ou hábitos adquiridos com o desenvolvimento, diagnóstico, severidade e cura das lesões perirradiculares. Essas condições são referidas como modificadores da doença e podem esclarecer o surgimento de sintomatologia dolorosa em casos assintomáticos, a cura tardia de algumas lesões, e explicar o porquê alguns canais adequadamente tratados resultam em fracasso. As doenças hereditárias de coagulação causam alterações na hemostasia dos portadores, gerando propensão para sangramento abundante e modificações importantes na cicatrização de feridas. Essa revisão bibliográfica identificou as associações existentes entre os transtornos hereditários de coagulação mais comuns (hemofilias A e B e doença de von Willebrand) e o reparo de lesões endodônticas e concluiu que tal condição clínica pode afetar as respostas imunes, interferindo no reparo perirradicular.

Periradicular injury is a disease of microbial etiology, whose evolution has a strong relationship with the host's immune response, which occurs in order to contain this infection. The endodontic treatment in these cases has the ultimate biological objective of disinfecting the root canal system to enable repair of the periapical region. This repair is a complex process consisting of hemostasis, inflammation, cell proliferation, maturation and remodeling. Several studies have been carried out in order to relate systemic factors or acquired habits with the development, diagnosis, severity and cure of periradicular lesions. These conditions are referred to as disease modifiers and can clarify the onset of painful symptoms in asymptomatic cases, delayed healing of some lesions, and explain why some properly treated channels result in failure. Hereditary coagulation diseases cause changes in patients' hemostasis, generating a propensity for heavy bleeding and important changes in wound healing. This bibliographic review sought to identify the associations between the most common hereditary coagulation disorders (Hemophilia A and B and von Willebrand's disease) and the repair of endodontic lesions and concluded that such a clinical condition can affect immune responses, interfering with periradicular repair.

Blood diffusion to novel therapies: A quantitative analysis of scholarly output in Haemophilia from India

Lack of specific protein factors, such as factor VIII and factor IX, results in haemophilia, a genetic bleeding condition. Due to its genetics, haemophilia affects an individual, but we can see how it has an impact on a whole generation. The goal of this study is to determine the extent to which our Indian researchers have been able to advance this highly sought-after field. Although this study was intended to last 75 years, it had to be restricted to the years 1991 to 2021 due to a shortage of publications at the time of data mining. There was a total of 81 publications found, and after analysing them, it was found that India and the USA collaborated more frequently than France and the UK. The National Institute of Immunohaematology (NIIH), located in Mumbai, is India's most productive institution in terms of the number of publications or ongoing work. Haemophilia, factor viii, and gene therapy were the most commonly used keywords. Indian researchers still need to put in a lot of effort in this area because, according to studies from around the world, haemophilia is spreading like a fire. Continuous research and knowledge of the needs of the population are required if we are to improve not only our position in the world but also the way we are treated, which would make life better.

Rastreamento, Diagnóstico e Manejo da Fibrilação Atrial em Pacientes com Câncer: Evidências Atuais e Perspectivas Futuras / Screening, Diagnosis and Management of Atrial Fibrillation in Cancer Patients: Current Evidence and Future Perspectives

Resumo A fibrilação atrial (FA) é a arritmia cardíaca sustentada mais comum na população geral, tendo uma alta carga de morbimortalidade, e isso também é válido para pacientes com câncer. A associação entre FA e câncer vai ainda mais longe, com alguns estudos sugerindo que a FA pode ser um marcador de câncer oculto. Há, no entanto, uma notável escassez de dados sobre os desafios específicos do manejo da FA em pacientes com câncer. O reconhecimento e o manejo imediatos da FA nesta população especial podem diminuir a morbidade relacionada à arritmia e ter um importante benefício prognóstico. Esta revisão se concentrará nos desafios atuais de diagnóstico e manejo da FA em pacientes com câncer, com ênfase especial nas estratégias e dispositivos de rastreamento da FA e na terapia de anticoagulação com anticoagulantes orais não antagonistas da vitamina K (NOACs) para prevenção tromboembólica nesses pacientes. Alguns insights sobre as perspectivas futuras para a prevenção, diagnóstico e tratamento da FA nesta população especial também serão abordados.

Abstract Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in the general population, carrying a high morbimortality burden, and this also holds true in cancer patients. The association between AF and cancer goes even further, with some studies suggesting that AF can be a marker of occult cancer. There is, however, a remarkable paucity of data concerning specific challenges of AF management in cancer patients. AF prompt recognition and management in this special population can lessen the arrhythmia-related morbidity and have an important prognostic benefit. This review will focus on current AF diagnosis and management challenges in cancer patients, with special emphasis on AF screening strategies and devices, and anticoagulation therapy with non-vitamin K antagonist oral anti-coagulants (NOACs) for thromboembolic prevention in these patients. Some insights concerning future perspectives for AF prevention, diagnosis, and treatment in this special population will also be addressed.

Immature Platelet Fraction and Thrombin Generation: Preeclampsia Biomarkers / Fração de plaquetas imaturas e geração de trombina: Biomarcadores da pré-eclâmpsia

Abstract Preeclampsia, a human pregnancy syndrome, is characterized by elevated blood pressure and proteinuria after the 20th week of gestation. Its etiology remains unknown, and its pathophysiological mechanisms are related to placental hypoperfusion, endothelial dysfunction, inflammation, and coagulation cascade activation. Recently, the role of the complement system has been considered. This syndrome is one of the main causes of maternal and fetal mortality and morbidity. This article discusses the hypothesis of preeclampsia being triggered by the occurrence of inadequate implantation of the syncytiotrophoblast, associated with bleeding during the first stage of pregnancy and with augmented thrombin generation. Thrombin activates platelets, increasing the release of antiangiogenic factors and activating the complement system, inducing the membrane attack complex (C5b9). Immature platelet fraction and thrombin generation may be possible blood biomarkers to help the early diagnosis of preeclampsia.

Resumo A pré-eclâmpsia, uma síndrome da gestação humana, é caracterizada por elevação da pressão arterial e proteinúria patológica após a 20ª semana de gestação. Sua etiologia permanece desconhecida, e seus mecanismos fisiopatológicos estão relacionados à hipoperfusão placentária, disfunção endotelial, inflamação, e ativação da cascata de coagulação. Recentemente, o papel do sistema do complemento foi considerado. Essa síndrome é uma das principais causas de morbidade e mortalidade materna e fetal. Este artigo discute a hipótese de a pré-eclâmpsia ser desencadeada pela ocorrência da implantação inadequada do sinciciotrofoblasto, associada ao sangramento durante o primeiro trimestre da gravidez com aumento da geração de trombina. A trombina ativa plaquetas, aumentando a liberação de fatores antiangiogênicos na circulação e ativando o sistema do complemento, especialmente o complexo de ataque de membrana (C5b9). Portanto, a fração de plaquetas imaturas e a geração de trombina podem ser possíveis biomarcadores sanguíneos para auxílio no diagnóstico precoce da pré-eclâmpsia.

Enfermedad von Willebrand: consideraciones prácticas para el odontólogo. Revisión de literatura / von Willebrand disease: practical considerations for the dentist. Literature review

RESUMEN La enfermedad von Willebrand es el desorden hemorrágico hereditario más común, que se origina por la deficiencia del factor von Willebrand, la cual provoca una adhesión y agregación plaquetaria defectuosa. Se caracteriza por un tiempo de sangrado y tiempo parcial de tromboplastina prolongados, con bajos valores del factor VIII, y aumento de fragilidad capilar, pero con recuento normal de plaquetas. El tratamiento odontológico en un paciente con enfermedad von Willebrand, debe ser individualizado de acuerdo con la severidad de la condición del paciente, así como coordinado con el hematólogo, quien debe de determinar el tipo de enfermedad y la necesidad de la terapia de reemplazo del factor según diagnóstico específico previo al manejo de este. Mediante esta revisión bibliográfica se desea reforzar el conocimiento al odontólogo de este trastorno hemorrágico, ya que con ello se pueden evitar o minimizar posibles complicaciones de sangrado durante el tratamiento odontológico.

ABSTRACT von Willebrand disease is the most common inherited bleeding disorder, caused by von Willebrand factor deficiency, which causes defective platelet adhesion and aggregation. It is characterized by a prolonged bleeding time and partial thromboplastin time, with low levels of factor VIII, and increased capillary fragility, but with a normal platelet count. Dental treatment in a patient with von Willebrand disease must be individualized according to the severity of the patient's condition, as well as coordinated with the hematologist, who must determine the type of disease and the need for factor replacement therapy, prior to the patient management. Through this bibliographic review, it wants to reinforce the dentist's knowledge of this bleeding disorder, since this can prevent or minimize possible bleeding complications during dental treatment.

Trombosis de seno venoso asociada con infección por SARS-CoV-2 / Cerebral venous thrombosis associated with SARS-Cov-2 infection

RESUMEN INTRODUCCION: La trombosis del seno venoso se considera una de las causas más infrecuentes de enfermedad cerebrovascular (ECV), prevalente en la edad joven. Suele tener un inicio insidioso, lo cual dificulta su diagnóstico y el inicio oportuno del tratamiento, y se encuentra asociada con múltiples factores de riesgo, incluyendo estados de hipercoagulabilidad, como en aquellos pacientes que cursan con infección por SARS-CoV-2. REPORTE DE CASO: Se presentan dos casos clínicos de pacientes con alteraciones neurológicas, diplopia y estatus epiléptico, en quienes se documentó por medio de la sintomatologia y de estudios imagenológicos, trombosis venosas extensas de localización infrecuente, se descartaron las principales etiologías asociadas, y el único nexo asociado fue la infección por SARS-CoV-2. Ambos pacientes recibieron tratamiento con anticoagulación parenteral, al que respondieron de forma exitosa, por lo cual se logró el alta posteriormente con anticoagulación oral. DISCUSIÓN: Es imprescindible el conocimiento de esta enfermedad, asociada con una alta sospecha diagnóstica, dadas sus manifestaciones clínicas variadas y su asociación cada vez más frecuente con infección por covid-19.

ABSTRACT INTRODUCTION: Venous sinus thrombosis is considered one of the most infrequent causes of cerebrovascular disease (CVD), prevalent in young people. It usually has an insidious onset which difficult its diagnosis and timely initiation of treatment and is associated with multiple risk factors including hypercoagulable states, as in those patients with SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection. CASE REPORT: The following are 2 clinical cases of patients with neurological alterations, diplopia, and status epilepticus, in whom extensive venous thrombosis of infrequent location was documented through symptomatology and imaging studies, ruling out the main associated etiologies, with the only associated nexus: SARS-CoV-2 infection. Both patients received treatment with parenteral anticoagulation, responding successfully and were subsequently discharged with oral anticoagulation. DISCUSSION: It is essential to be aware of this disease associated with a high diagnostic suspicion given its varied clinical manifestations and its increasingly frequent association with COVID-19 infection.

Crisis celíaca y tetania aguda en pediatría. Reporte de un caso / Celiac crisis and acute tetany in pediatrics. Case report

RESUMEN La enfermedad celíaca es una enfermedad sistémica inmunomediada, con un gran espectro de presentaciones clínicas. El término crisis celíaca describe la forma aguda y potencialmente fatal. Clínicamente se caracteriza por diarrea severa, deshidratación y alteraciones metabólicas. Se reporta el caso de un paciente masculino de 7 años de edad que asiste a guardia con tetania, edema en miembros inferiores, esteatorrea y pérdida de peso de 8 meses de evolución, con hallazgos analíticos de hipocalcemia, hipomagnesemia, hipopotasemia y coagulopatía. El diagnóstico de crisis celíaca se realizó sobre la base de hallazgos serológicos y clínicos compatibles con enfermedad celíaca en el contexto de anomalías metabólicas graves y desnutrición aguda, confirmado posteriormente por anatomía patológica. La importancia de este reporte radica en repasar las características de esta grave entidad, que requiere un elevado índice de sospecha para su diagnóstico.

ABSTRACT Celiac disease is an immune-mediated systemic disease with a wide spectrum of clinical presentations. The term celiac crisis describes the acute and potentially fatal form. Clinically it is characterized by severe diarrhea, dehydration, and metabolic disturbances. The case of a 7-year-old male patient attending the ward with tetany, lower limb edema, steatorrhea and weight loss of 8 months of evolution is reported, with analytical findings of hypocalcemia, hypomagnesemia, hypokalemia and coagulopathy. The diagnosis of celiac crisis was made on the basis of serological and clinical findings compatible with celiac disease in the context of severe metabolic abnormalities and acute malnutrition, later confirmed by pathological anatomy. The importance of this report lies in reviewing the characteristics of this serious entity, which requires a high index of suspicion for its diagnosis.

A study on gene mutation of coagulation factor Ⅺ protein secretion disorder and its mechanism / 中华检验医学杂志

Objective:To investigate the molecular pathogenesis of a newly discovered gene mutation in a family with hereditary coagulation factor Ⅺ(FⅪ) deficiency.Methods:The proband was admitted to the First Affiliated Hospital of Wenzhou Medical University in September 2021 due to "calculus of intrahepatic duct". The patient had no symptoms of spontaneous bleeding.The clinical data and blood samples of the proband and her family members (10 persons in 3 generations) were collected.The activated partial thromboplastin time (APTT) and FⅪ activity (FⅪ:C) were performed by the one-stage clotting assay. FⅪ antigen (FⅪ:Ag) were detected by enzyme linked immunosorbent assay (ELISA). Genomic DNA extracted from peripheral blood cells of subjects was used as template to analyze F11 gene mutation by DNA direct sequencing. Bioinformatics software was used to analyze the effects of mutations on protein structure and function. Wild-type and mutant FⅪ protein expression vectors were constructed and transient transfected into HEK293T cells. The total RNA was extracted from positive transfected cells and then reversely transcribed into cDNA. The mRNA expression level of F11 gene in transfected cells was detected by real-time fluorescence quantitative PCR (qRT-PCR). The content of FⅪ:Ag and the expression of FⅪ protein in transfected cell lysates and culture supernatant were detected by ELISA and western blot.Results:The APTT of the proband was significantly prolonged to 107.9s (reference range 29.0-43.0s), while FⅪ:C and FⅪ:Ag were significantly decreased to 2% (reference range 84%-122%) and 5% (reference range 76%-127%), respectively. Gene sequencing analysis indicated that the proband had c.536C>T (p.Thr161Met) heterozygous missense mutation and c.1556G>A (p.Trp501Ter) heterozygous nonsense mutation in exon 6 and 13 of the F11 gene, respectively. Bioinformatics analysis showed that the amino acids at site 161 of FⅪ protein were threonine (Thr) in the matrix composed of five different species, indicating that Thr161 site was highly conserved among homologous genes in different species. p.Thr161Met heterozygous mutation affected the stability of local intermolecular structure of FⅪ protein. In vitro expression experiments of p.Thr161Met mutation showed that FⅪ protein had a normal synthesis in the cells but secretion dysfunction.Conclusions:c.536C>T (p.Thr161Met) heterozygous missense mutation and c.1556G>A (p.Trp501Ter) heterozygous nonsense mutation were mainly responsible for the decrease of FⅪ in this family. p.Thr161Met mutation was first reported in the world and did not affect the normal synthesis of FⅪ protein, but caused secretion dysfunction.

The Role of Platelet Exosomes in Atherogenic Thrombosis --Review / 中国实验血液学杂志

Exosomes are subtypes of extracellur vesicles containing a variety of cell-specific proteins, lipids and nucleic acids released during cell activation or apoptosis, and play the role of intercellur communication mediators in different physiological and pathological processes. With the development of research in recent years, the role of platelet-derived exosomes in cardiovascular diseases has attracted extensive attention. This paper reviews the role of platelet-derived exosomes in atherosclerotic thrombosis and the potential role of platelet-derived exosomes as biomarkers for the diagnosis and treatment of atherosclerotic thrombotic disease and the problems to be solved.

Correlation of muscle-derived microparticles and lactadherin proteins with hypercoagulability in patients with perihip fractures / 中华骨科杂志

Objective:To investigate the changes of skeletal muscle-derived microparticles (SKMPs) and their scaving proteins lactadherin in peripheral blood of patients with perihip fractures and their effects on blood coagulation. It provides a theoretical basis for clinical evaluation of hypercoagulability in patients with perioperative hip fractures.Methods:A total of 44 patients (72.87±13.9 years old) with perihip fractures from October 2020 to January 2021 were included in the fracture group, and 40 healthy people were included in the group without fracture. Activated clotting time (ACT) in fracture group and control group was measured by coagulation and platelet function analyzer. The level of SKMPs in peripheral venous blood was determined by flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of MPs scaving proteins lactadherin in peripheral blood of fracture group and control group.Results:A total of 44 patients with perihip fractures were included. There were 33 (75%) femoral neck fractures and 11 (25%) intertrochanteric fractures. SKMPs concentration in peripheral blood of perihip fracture group 175.73/μl; postoperative fracture group 124.28/μl; Normal control group 90.69/μl. ACT was (377.5±76.2) s in the perihip fracture group, (498.1±97.1) s in the post-fracture group, and (505.7±44.0) s in the control group. Correlation analysis showed that there was a linear relationship between SKMPs count and ACT value in fracture patients ( r=-0.52, P<0.001). There was no significant correlation between SKMPs concentration and ACT value in peripheral venous blood of the post-fracture group ( P>0.05); Lactadherin protein concentration in perihip fracture group: 2 779.61 pg/ml; Fracture postoperative group 1 985.38 pg/ml; Normal control group 1 651.19 pg/ml. There is a positive correlation between Lactadherin concentration and SKMPs concentration with a correlation coefficient of 0.70. Conclusion:SKMPs plays a role in the hypercoagulability of patients with perihip fractures. Decompensation of lactadherin protein may be one of the causes of perioperative hypercoagulation in patients with hip fractures.