Immunothrombosis and its underlying biological mechanisms

Abstract The evolutionary conserved link between coagulation and innate immunity is a biological process characterized by the thrombosis formation stimulus of immune cells and specific thrombosis-related molecules. In physiological settings, the relationship between the immune system and thrombosis facilitates the recognition of pathogens and damaged cells and inhibits pathogen proliferation. However, when deregulated, the interplay between hemostasis and innate immunity becomes a pathological process named immunothrombosis, which is at the basis of several infectious and inflammation-related thrombotic disorders, including coronavirus disease 2019 (COVID-19). In advanced stages, alterations in both coagulation and immune cell function due to extreme inflammation lead to an increase in blood coagulability, with high rates of thrombosis and mortality. Therefore, understanding underlying mechanisms in immunothrombosis has become decisive for the development of more efficient therapies to treat and prevent thrombosis in COVID-19 and in other thrombotic disorders. In this review, we outline the existing knowledge on the molecular and cellular processes involved in immunothrombosis, focusing on the role of neutrophil extracellular traps (NETs), platelets and the coagulation pathway. We also describe how the deregulation of hemostasis is associated with pathological conditions and can significantly aggravate a patient's condition, using COVID-19 as a clinical model.

Resuscitation effect of sodium bicarbonate Ringer's solution on traumatic hemorrhagic shock in patients / 中国基层医药

Objective:To investigate the resuscitation effect of sodium bicarbonate Ringer's solution on traumatic hemorrhagic shock in patients.Methods:A randomized controlled trial was conducted on 70 patients with traumatic hemorrhagic shock who were admitted to Yiwu Central Hospital between February 2021 and February 2022. The patients were randomly assigned to a control group ( n = 35) and an observation group ( n = 35) using the random number table method. Both groups received routine treatment. The control group was given adequate resuscitation by intravenous injection of a compound sodium chloride injection, while the observation group received restricted resuscitation with sodium bicarbonate Ringer's solution. Related clinical indicators, coagulation function, lactate levels, hemorheological indicators, and incidence of complications were compared between the two groups. Results:The blood oxygen saturation, shock index, pulse pressure difference, and urine output in the observation group were (76.53 ± 2.56)%, (0.43 ± 0.07), (38.56 ± 6.52) mmHg (1 mmHg = 0.133 kPa), and (35.62 ± 4.21) mL/h, respectively. These values were all superior to those in the control group [(65.32 ± 3.21)%, (1.21 ± 0.13), (23.56 ± 4.23) mmHg, (23.65 ± 5.68) mL/h, t = 16.15, 31.25, 11.42, 10.06, all P < 0.001]. The prothrombin time, fibrinogen, activated partial thromboplastin time, and thrombin time in the observation group were (17.65 ± 0.83) seconds, (1.69 ± 0.89) g/L, (39.68 ± 0.52) seconds, and (17.86 ± 0.74) seconds, respectively. These values were significantly superior to those in the control group [(14.56 ± 0.86) seconds, (1.32 ± 0.23) g/L, (35.26 ± 0.16) seconds, and (16.02 ± 0.05) seconds, t = 15.30, 2.38, 48.06, 14.68, all P < 0.05]. The lactate level in the observation group was significantly lower than that in the control group [(2.24 ± 0.53) mmol/L vs. (2.94 ± 0.78) mmol/L, t = 4.39, P < 0.05]. The platelet cohesion, red blood cell deformability, and blood viscosity in each group were significantly reduced, and these indices in the observation group were superior to those in the control group ( t = 13.71, 5.64, 5.67, all P < 0.001). The incidence of complications in the observation group was significantly lower than that in the control group (8.6% (3/35) vs. 60.0% (21/35), χ2 = 10.08, P < 0.05). Conclusion:Restricted resuscitation with sodium bicarbonate Ringer's solution can improve clinical indicators, coagulation function, and lactate levels in patients with traumatic hemorrhagic shock. It can effectively improve hemodynamic indicators and reduce the incidence of complications. It is worthy of clinical promotion.

Relationship between blood indicators and course of nontraumatic osteonecrosis of femoral head in different stages:multiple logistic regression analysis / 中国组织工程研究

BACKGROUND:Up to now,there is no literature on the relationship between blood laboratory tests and the course of nontraumatic osteonecrosis of femoral head in different stages.It is necessary to further explore and analyze so as to better clarify the influencing factors of nontraumatic osteonecrosis of femoral head. OBJECTIVE:To analyze the relationship between blood laboratory indicators and the course of nontraumatic osteonecrosis of the femoral head by the Association Research Circulation Osseous(ARCO),thus exploring the influencing factors of blood laboratory indicators on the course of nontraumatic osteonecrosis of the femoral head. METHODS:This study used a retrospective study design.A total of 2 103 patients with osteonecrosis of the femoral head were retrieved from Wangjing Hospital of China Academy of Chinese Medical Sciences database,and 1 075 patients with nontraumatic osteonecrosis of the femoral head were ultimately included based on inclusion and exclusion criteria.Patient age,gender,body mass index,and blood laboratory test results were collected.Blood laboratory tests included low-density lipoprotein,total cholesterol,triglycerides,high-density lipoprotein,apolipoprotein β,apolipoprotein α1,uric acid,total protein quantitative,alkaline phosphatase,activated partial thromboplastin time,prothrombin time,prothrombin time International Normalized Ratio,prothrombin time activity,fibrinogen quantitative,coagulation time of thrombin,D-dimer,total iron binding capacity,and platelet count.The indicators of patients with different age groups and different ARCO stages were compared,and multiple Logistic regression analysis was applied to explore the influencing factors of ARCO stages in osteonecrosis of the femoral head. RESULTS AND CONCLUSION:(1)There were statistical differences in total cholesterol,uric acid,prothrombin time,prothrombin time International Normalized Ratio,and D-dimer among ARCO stages in the young group(P<0.05).Among young patients in ARCO stage II,total cholesterol levels were higher than those in ARCO stage III(P<0.05).Uric acid levels in ARCO stage IV were higher than those in ARCO stage II and III(P<0.05).Prothrombin time and prothrombin time International Normalized Ratio were shorter in ARCO stage IV and II than in ARCO stage III(P<0.05).D-dimer levels were higher in ARCO stage III and IV than in ARCO stage II(P<0.05).(2)There were statistically significant differences in high-density lipoprotein,coagulation time of thrombin,and D-dimer among ARCO stages in the middle-aged group(P<0.05).Among middle-aged patients in ARCO stage IV,high-density lipoprotein levels were higher than those in ARCO stages II and III(P<0.05).Coagulation time of thrombin was shorter in ARCO stage IV than in ARCO stage III(P<0.05).D-dimer levels were higher in ARCO stages IV than in ARCO stages II and III(P<0.05).(3)The uric acid,activated partial thromboplastin time,D-dimer,and platelet count in the elderly group showed statistically significant differences(P<0.05).The uric acid level in ARCO stage IV was higher than that in ARCO stage II and III patients in the elderly group(P<0.05),while the activated prothrombin time in ARCO stage II patients was shorter than that in ARCO stage III patients in the elderly group(P<0.05).The D-dimer level in ARCO stage III and IV patients was higher than that in ARCO stage II patients in the elderly group(P<0.05).The platelet count in ARCO stage IV was lower than that in ARCO stage III patients in the elderly group(P<0.05).(4)Multiple logistic regression analysis showed that total cholesterol and platelet count may be protective factors for course of nontraumatic osteonecrosis of the femoral head,while D-dimer,uric acid,overweight,and young and middle age may be risk factors for course of nontraumatic osteonecrosis of the femoral head.(5)It is indicated that total cholesterol,high-density lipoprotein,uric acid,prothrombin time,prothrombin time International Normalized Ratio,and D-dimer are statistically significant among patients with different ARCO stages.Total cholesterol and platelet count may be protective factors for the course of nontraumatic osteonecrosis of the femoral head,while D-dimer,uric acid,overweight,and middle-aged and young age groups may be hazard factors for the course of nontraumatic osteonecrosis of the femoral head.

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.

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.

Establishment and of preliminary verification of automatic auditing rules for routine coagulation assays / 中国医学装备

Objective:To establish auto verification rules for the routine coagulation assays,and to provide reference for clinical laboratories to improve the quality and efficiency of results verification.Methods:A total of 24,510 specimens of sodium citrate anticoagulation routine coagulation test from the laboratory departments of eight hospitals including the First Medical Center,Chinese PLA General Hospital during January to March 2020 were collected and randomly divided into a rule establishment group and a rule verification group,with 6,670 specimens in the rule establishment group,including 2,056 Delta checks,and 17,840 specimens in the rule validation group,including 3,210 Delta checks.The activities of prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(Fib),thrombin time(TT),D-dimer(DD)and/or antithrombin(AT)were detected by Stago STA R Max automatic coagulation analyzer and supporting reagents.Taking the manual verification results as the standard,the auto verification and manual false negative rate(invalid verification),false positive rate(invalid interception),pass rate,positive coincidence rate,negative coincidence rate,verification consistency rate and specimen turnaround time(TAT)of the two groups were calculated.Results:The auto verification rules and the application process were preliminarily established,including internal quality control,alarm information,auto verification scope,critical value and deviation value inspection.In the rule establishment group,the single item pass rate was 82.6%-92.4%,and the overall pass rate was 73.8%.The consistency rate between auto verification and manual verification was 98.2%,and the positive coincidence rate and negative coincidence rate were 24.4%and 73.8%,respectively.In the rule verification group,the single item pass rate was 86.4%-91.5%,and the overall review pass rate was 71.5%.By simulating the application of auto verification rules,the average TAT of two hospitals among the eight hospitals was shortened by 1.5 hours and 2.1 hours,respectively.Conclusion:The application of auto verification rules can reduce workload of manual verification,and significantly shorten the TAT,and improve the report efficiency of the laboratory.

Role of Erbin in liver tissues in blood coagulation of septic mice / 中华麻醉学杂志

Objective:To evaluate the role of ERBB2 interacting protein (Erbin)in liver tissues in blood coagulation of septic mice.Methods:Thirty SPF healthy male C57BL/6 mice and 30 Erbin knockout mice, aged 8-10 weeks, weighing 20-30 g, were divided into wild-type+ sham operation group (WT+ Sham group), wild-type+ sepsis group (WT+ SEP group), Erbin gene knockout+ sham operation group (EKO+ Sham group) and Erbin gene knockout+ sepsis group (EKO+ SEP group) by a random number table method, with 15 animals in each group. The mouse sepsis model was prepared by the cecal ligation and perforation method in anesthetized animals. Eye blood samples were collected at 24 h after surgery and liver tissues were obtained for microscopic examination of histopathological changes (by HE staining) which were scored and for determination of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities (by colorimetry), expression of Erbin and tissue factor (TF) (by Western blot), expression of tissue plasminogen activator (t-PA) and fibrinogen (Fib)mRNA (by quantitative polymerase chain reaction), concentrations of PT, APTT, thrombin time (TT) and Fib (by automatic coagulation analyzer), and plasma TF and interleukin-6 (IL-6) concentrations (by enzyme-linked immunosorbent assay).Results:Compared with WT+ Sham group, the lung injury score was significantly increased, the expression of TF, t-PA mRNA and FGA mRNA was up-regulated, PT, APTT and TT were prolonged, the plasma Fib concentration was increased, and the activities of ALT and AST and concentrations of TF and IL-6 in plasma were increased in WT+ SEP group ( P<0.05). Compared with WT+ SEP group, the lung injury score was significantly increased, the expression of TF, t-PA mRNA and FGA mRNA was up-regulated, PT, APTT and TT were prolonged, the plasma Fib concentration was increased, and the activities of ALT and AST and concentrations of TF and IL-6 in plasma were increased in EKO+ SEP group ( P<0.05). Conclusions:Erbin in liver tissues exerts an endogenous protective effect on blood coagulation by inhibiting the up-regulation of TF expression in septic mice.

Quality of life in children and adolescents with blood coagulation disorders and hemoglobinopathies

Abstract The aim of this study was to evaluate the impact of oral conditions and health-related quality of life (HRQoL) on oral health-related quality of life (OHRQoL) in children and adolescents with blood coagulation disorders and hemoglobinopathies (BCDH). The study was cross-sectional and included 61 individuals aged 2 to 18 years with BCDH. Exams for dental caries (dmft/DMFT index), oral hygiene (simplified oral hygiene index - OHI-S), and gingival health (modified gingival index - MGI) were performed. The pediatric quality of life inventory™ (PedsQL™) generic core scale and oral health scale were used to measure HRQoL and OHRQoL. Spearman's correlation coefficient (ρ) and the Mann-Whitney test (α = 0.05) were conducted to assess the relationship between covariates and the PedsQL™ oral health scale. The mean PedsQL™ oral health scale score was 76.66 (SD = 21.36). Worse OHRQoL was correlated with poor oral hygiene (ρ = -0.383; p: 0.004), poor gingival health (ρ = -0.327; p = 0.014), and better HRQoL (ρ = 0.488; p < 0.001). Greater untreated dental caries experience was associated with worse OHRQoL (p = 0.009). Worse oral health status in children and adolescents with BCDH negatively impacts OHRQoL, and OHRQoL and quality of life analyzed from a generic perspective are positively correlated constructs in this population.

Emicizumab prophylaxis in people with hemophilia A and inhibitors: a systematic review and meta-analysis

ABSTRACT BACKGROUND: Until recently, the treatment of people with hemophilia A and inhibitors (PwHAi) was based on the use of bypassing agents (BPA). However, the advent of emicizumab as prophylaxis has demonstrated promising results. OBJECTIVES: We aimed to compare the bleeding endpoints between PwHAi on BPA and those on emicizumab prophylaxis. DESIGN AND SETTING: Systematic review of interventions and meta-analysis conducted at the Universidade Federal de Goiás, Goiânia, Goiás, Brazil. METHODS: The CENTRAL, MEDLINE, Scopus, and LILACS databases were searched on February 21, 2023. Two authors conducted the literature search, publication selection, and data extraction. The selected publications evaluated the bleeding endpoints between PwHAi on emicizumab prophylaxis and those on BPA prophylaxis. The risk of bias was evaluated according to the Joanna Briggs Institute criteria. A meta-analysis was performed to determine the annualized bleeding rate (ABR) for treated bleeds. RESULTS: Five publications (56 PwHAi) were selected from the 543 retrieved records. Overall, bleeding endpoints were lower during emicizumab prophylaxis than during BPA prophylaxis. All the publications had at least one risk of bias. The only common parameter for the meta-analysis was the ABR for treated bleeds. During emicizumab prophylaxis, the ABR for treated bleeds was lower than during BPA prophylaxis (standard mean difference: −1.58; 95% confidence interval −2.50, −0.66, P = 0.0008; I2 = 68.4%, P = 0.0031). CONCLUSION: Emicizumab was superior to BPA in bleeding prophylaxis in PwHAi. However, both the small population size and potential risk of bias should be considered when evaluating these results. SYSTEMATIC REVIEW REGISTRATION: CRD42021278726, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278726.

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.

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.

Factor XIII deficiency, a rare coagulopathy: case reports / Deficiência do fator XIII, uma coagulopatia rara: relato de casos

Introduction: Hereditary Factor XIII (FXIII) deficiency is a rare autosomal recessive hemostatic disorder with an estimated incidence of one case per two million individuals and a higher prevalence in descendants of consanguineous relationships. Possible clinical manifestations include intracranial hemorrhage, umbilical cord bleeding at birth, hematoma, spontaneous abortions, and menometrorrhagia. Objective: To highlight the peculiarities of this hemostatic disorder, as well as the recommended management. Case Report: The authors describe two cases of FXIII deficiency with different hemorrhagic manifestations. Case 1 presented extensive spontaneous hematoma in the right thigh, while Case 2 had umbilical cord bleeding at birth and intracranial hemorrhage, requiring hemotherapy support. Both patients had normal results in screening laboratory tests for coagulation disorders. Coagulation factor serum levels and diagnostic assessments identified mild Factor XIII deficiency in Case 1 and severe deficiency in Case 2. The patient in Case 1 is under regular control and follow-up, while the patient in Case 2 is on a monthly prophylactic regimen with FXIII infusion. Conclusion: The diagnosis of FXIII deficiency in patients with significant bleeding should be considered if screening coagulation tests are normal. The Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis has established an algorithm for laboratory diagnosis and identification of different forms of FXIII deficiency. Quantitative determination of FXIII activity, antigenic assays, and molecular studies are necessary.

Introdução: A deficiência hereditária do Fator XIII (FXIII) é uma rara desordem autossômica recessiva da hemostasia, com uma incidência estimada de um caso a cada dois milhões de pessoas e uma maior prevalência em descendentes de relacionamentos consanguíneos. Possíveis manifestações clínicas incluem: hemorragia intracraniana, sangramento do cordão umbilical no nascimento, hematoma, abortos espontâneos e menometrorragia. Objetivo: Ressaltar as particularidades desse distúrbio hemostático, assim como o manejo preconizado. Relato de caso: Os autores descrevem dois casos de deficiência de FXIII com diferentes manifestações hemorrágicas. O Caso 1 apresentou extenso hematoma espontâneo na coxa direita, enquanto o Caso 2 apresentou sangramento do cordão umbilical ao nascer e hemorragia intracraniana, necessitando de suporte hemoterápico. Ambos os pacientes apresentavam resultados normais nos testes laboratoriais de triagem para distúrbios de coagulação. As dosagens séricas de fatores de coagulação e de diagnóstico identificaram deficiência leve do Fator XIII no Caso 1 e grave no Caso 2. O paciente do Caso 1 está sob controle e acompanhamento regular, enquanto o paciente do Caso 2 está em regime profilático mensal com infusão de FXIII. Conclusão: O diagnóstico de Deficiência de FXIII em pacientes com sangramento importante deve ser considerado se os testes de coagulação de triagem forem normais. O Comitê Científico e de Padronização da Sociedade Internacional de Trombose e Hemostasia estabeleceu um algoritmo para o diagnóstico laboratorial e identificação de diferentes formas de deficiência FXIII. A determinação quantitativa da atividade do FXIII, ensaios antigênicos e estudos moleculares são necessários.

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.

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.

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.