Genetic analysis of two Chinese pedigrees affected with Hereditary hypofibrinemia due to missense variants / 中华医学遗传学杂志

OBJECTIVE@#To retrospectively analyze the clinical phenotypes and genetic variants in two Chinese pedigrees affected with Hereditary hypofibrinemia (IFD) and explore their molecular pathogenesis.@*METHODS@#Two probands and their pedigree members were admitted to the First Affiliated Hospital of Wenzhou Medical University on March 30, 2021 and May 27, 2021, respectively. Clinical phenotypes of the probands were collected, and blood clotting indexes of the probands and their pedigree members were determined. Variants of the FGA, FGB and FGG genes were analyzed by Sanger sequencing, and candidate variants were verified by sequence comparison. Bioinformatic software was used to analyze the conservation of the amino acids and pathogenicity of the proteins. Alteration in protein structure and intermolecular force before and after the variant was analyzed by simulating the protein model.@*RESULTS@#Proband 1, a 18-year-old male, had significantly low plasma fibrinogen activity (Fg:C) and plasma fibrinogen antigen (Fg:Ag), respectively at 0.80 g/L and 1.00 g/L. Proband 2, a 43-year-old male, had slightly low Fg:C and Fg:Ag at 1.35 g/L and 1.30 g/L, respectively. The Fg:C and Fg:Ag of proband 1's father, proband 2's father and son were also below the normal level. Genetic testing showed that proband 1 had harbored a heterozygous missense variant of c.688T>G (p.Phe230Val) in exon 7 of the FGG gene, which was inherited from his father. Proband 2, his father and son all had harbored a heterozygous variant of c.2516A>C (p.Asn839Thr) in exon 6 of the FGA gene. Homology analysis showed that the Phe230 and Asn839 residues were highly conserved among homologous species. Bioinformatic analysis predicted that both p.Phe230Val and p.Asn839Thr were pathogenic variants.@*CONCLUSION@#Analysis of protein simulation model showed that the p.Asn839Thr variant has changed the hydrogen bo`nd between the amino acids, thus affecting the stability of the protein structure. The heterozygous missense variants of p.Phe230Val and p.Asn839Thr probably underlay the IFD in the two pedigrees.

Prognostic Value of Pre-treatment Albumin/Fibrinogen Ratio in Patients with Diffuse Large B-cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the value of pre-treatment albumin/fibrinogen ratio (AFR) on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL).@*METHODS@#The data of DLBCL patients in the Affiliated Hospital of North Sichuan Medical College from April 2014 to March 2021 were retrieved, and 111 newly diagnosed patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with complete data were included in the study. The clinical, laboratory examination and follow-up data of the patients were collected, and the receiver operating characteristic curve (ROC) was drawn according to patients' AFR before treatment and the survival status at the end of the follow-up, which could be used to preliminarily evaluate the predictive value of AFR for disease progression and patients' survival outcome. Furthermore, the correlation of AFR with the clinical and laboratory characteristics, progression-free survival (PFS) and overall survival (OS) was analyzed, and finally, univariate and multivariate Cox proportional hazard regression models were used to analyze factors affecting PFS and OS of DLBCL patients.@*RESULTS@#The ROC curve indicated that AFR level had a moderate predictive value for PFS and OS in DLBCL patients, with the area under the curve (AUC) of 0.616 (P =0.039) and 0.666 (P =0.004), respectively, and the optimal cut-off values were both 9.06 for PFS and OS. Compared with high-AFR (≥9.06) group, the low-AFR (<9.06) group had a higher proportion of patients with Lugano III-IV stage ( P <0.001), elevated lactate dehydrogenase (P =0.007) and B symptoms (P =0.038). The interim analysis of response showed that the overall response rate (ORR) in the high-AFR group was 89.7%, which was significantly higher than 62.8% in the low-AFR group (P =0.001). With a median follow-up of 18.5 (3-77) months, the median PFS of the high-AFR group was not reached, which was significantly superior to 17 months of the low-AFR group (P =0.009). Similarly, the median OS of high-AFR group was not reached, either, which was significantly superior to 48 months of the low-AFR group (P < 0.001). In multivariate Cox regression analysis, AFR <9.06 was an independent risk factor both for PFS and OS (HR PFS=2.047, P =0.039; HR OS=4.854, P =0.001).@*CONCLUSION@#Pre-treatment AFR has a significant value for the prognosis evaluation in newly diagnosed DLBCL patients.

Clinical features of severe acute respiratory syndrome coronavirus 2 Omicron variant infection in children: an analysis of 201 cases / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection.@*METHODS@#A retrospective analysis was performed on the medical data of 201 children with coronavirus disease 2019 (COVID-19) who were hospitalized and diagnosed with SARS-CoV-2 Omicron variant infection in Quanzhou First Hospital from March 14 to April 7, 2022. Among the 201 children, there were 34 children with asymptomatic infection and 167 with symptomatic infection. The two groups were compared in terms of clinical features, results of experimental examinations, and outcome.@*RESULTS@#Of all the 201 children, 161 (80.1%) had a history of exposure to COVID-19 patients and 132 (65.7%) had a history of COVID-19 vaccination. Among the 167 children with symptomatic infections, 151 had mild COVID-19 and 16 had common COVID-19, with no severe infection or death. Among the 101 children who underwent chest CT examination, 16 had ground glass changes and 20 had nodular or linear opacities. The mean time to nucleic acid clearance was (14±4) days for the 201 children with Omicron variant infection, and the symptomatic infection group had a significantly longer time than the asymptomatic infection group [(15±4) days vs (11±4) days, P<0.05]. The group vaccinated with one or two doses of COVID-19 vaccine had a significantly higher positive rate of IgG than the group without vaccination (P<0.05). The proportions of children with increased blood lymphocyte count in the symptomatic infection group was significantly lower than that in the asymptomatic infection group (P<0.05). Compared with the asymptomatic infection group, the symptomatic infection group had significantly higher proportions of children with increased interleukin-6, increased fibrinogen, and increased D-dimer (P<0.05).@*CONCLUSIONS@#Most of the children with Omicron variant infection have clinical symptoms, which are generally mild. The children with symptomatic infection are often accompanied by decreased or normal blood lymphocyte count and increased levels of interleukin-6, fibrinogen, and D-dimer, with a relatively long time to nucleic acid clearance. Some of them had ground glass changes on chest CT.

Establishment of risk prediction nomograph model for sepsis related acute respiratory distress syndrome / 中华危重病急救医学

OBJECTIVE@#To explore the risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis and to construct a risk nomogram model.@*METHODS@#The clinical data of 234 sepsis patients admitted to the intensive care unit (ICU) of Tianjin Hospital from January 2019 to May 2022 were retrospectively analyzed. The patients were divided into non-ARDS group (156 cases) and ARDS group (78 cases) according to the presence or absence of ARDS. The gender, age, hypertension, diabetes, coronary heart disease, smoking history, history of alcoholism, temperature, respiratory rate (RR), mean arterial pressure (MAP), pulmonary infection, white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer, oxygenation index (PaO2/FiO2), lactic acid (Lac), procalcitonin (PCT), brain natriuretic peptide (BNP), albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr), acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA) were compared between the two groups. Univariate and multivariate Logistic regression were used to analyze the risk factors of sepsis related ARDS. Based on the screened independent risk factors, a nomogram prediction model was constructed, and Bootstrap method was used for internal verification. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated to verify the prediction and accuracy of the model.@*RESULTS@#There were no significant differences in gender, age, hypertension, diabetes, coronary heart disease, smoking history, alcoholism history, temperature, WBC, Hb, PLT, PT, APTT, FIB, PCT, BNP and SCr between the two groups. There were significant differences in RR, MAP, pulmonary infection, D-dimer, PaO2/FiO2, Lac, ALB, BUN, APACHE II score and SOFA score (all P < 0.05). Multivariate Logistic regression analysis showed that increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score were independent risk factors for sepsis related ARDS [RR: odds ratio (OR) = 1.167, 95% confidence interval (95%CI) was 1.019-1.336; MAP: OR = 0.962, 95%CI was 0.932-0.994; pulmonary infection: OR = 0.428, 95%CI was 0.189-0.966; Lac: OR = 1.684, 95%CI was 1.036-2.735; APACHE II score: OR = 1.577, 95%CI was 1.202-2.067; all P < 0.05]. Based on the above independent risk factors, a risk nomograph model was established to predict sepsis related ARDS (accuracy was 81.62%, sensitivity was 66.67%, specificity was 89.10%). The predicted values were basically consistent with the measured values, and the AUC was 0.866 (95%CI was 0.819-0.914).@*CONCLUSIONS@#Increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score are independent risk factors for sepsis related ARDS. Establishment of a risk nomograph model based on these factors may guide to predict the risk of ARDS in sepsis patients.

Genetic analysis of a Chinese pedigree affected with Congenital dysfibrinogenemia due to variant of FGG gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the coagulation deficit and genetic basis for a Chinese pedigree affected with Congenital dysfibrinogenemia (CD).@*METHODS@#Peripheral venous blood samples of the proband and her family members (including 4 individuals from three generations) were subjected to routine blood test and assays of liver and kidney functions and viral hepatitis to exclude related diseases. Clauss method and DFg-PT method were used to determine the fibrinogen activity (Fg:C), and an immunoturbidimetric assay was used to determine the level of fibrinogen antigen (Fg:Ag). All of the exons (22 in total) and their flanking sequences of the FGA, FGB and FGG genes were amplified by PCR and directly sequenced. Variants in the coding regions of the three genes and transcriptional splicing sites were screened by using Mutation SurveyorTM software.@*RESULTS@#The Clauss method showed that Fg:C was significantly reduced in the proband and her father, whilst her mother and son were normal. With the DFg-PT method, the proband, her parents and son were all within the normal range. The Fg:C/Fg:Ag ratio of the proband and her father was lower than 0.7, whilst her mother and son were above 0.7. No significant change in the prothrombin time, activated partial thromboplastin clotting time and thrombin time was noted. Two genetic variants were detected, which included a homozygous missense variant in the FGA gene [c.991A>G (p.Thr331Ala)], which was predicted to be benign, and a heterozygous missense variant of the γ chain of the FGG gene [c.1211C>G (p.Ser404Phe)], which is located in a conserved region and unreported in the CLINVAR/HGMD/EXAC/1000G databases and literature.@*CONCLUSION@#This pedigree has conformed to the autosomal dominant inheritance of CD. The c.1211C>T (p.Ser404Phe) missense variant of the γ chain of the FGG gene probably underlay the pathogenesis of CD in this pedigree. The variant was unreported previously and named as "Fibrinogen Harbin II Ser404Phe".

Clinical characteristics and diagnostic indicators of macrophage activation syndrome in patients with systemic lupus erythematosus and adult-onset Still's disease / 北京大学学报(医学版)

OBJECTIVE@#To analyze and compare the clinical and laboratory characteristics of macrophage activation syndrome (MAS) in patients with systemic lupus erythematosus (SLE) and adult-onset Still's disease (AOSD), and to evaluate the applicability of the 2016 European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organization classification criteria for MAS complicating systemic juvenile idiopathic arthritis (sJIA) in different auto-immune diseases contexts and to propose new diagnostic predictive indicators.@*METHODS@#A retrospective analysis was conducted on the clinical and laboratory data of 24 SLE patients with MAS (SLE-MAS) and 24 AOSD patients with MAS (AOSD-MAS) who were hospitalized at Peking University People's Hospital between 2000 and 2018. Age- and sex-matched SLE (50 patients) and AOSD (50 patients) diagnosed in the same period without MAS episodes were selected as controls. The cutoff values for laboratory indicators predicting SLE-MAS and AOSD-MAS were determined using receiver operating characteristic (ROC) curves. Furthermore, the laboratory diagnostic predictive values for AOSD-MAS were used to improve the classification criteria for systemic juvenile idiopathic arthritis-associated MAS (sJIA-MAS), and the applicability of the revised criteria for AOSD-MAS was explored.@*RESULTS@#Approximately 60% of SLE-MAS and 40% of AOSD-MAS occurred within three months after the diagnosis of the underlying diseases. The most frequent clinical feature was fever. In addition to the indicators mentioned in the diagnosis criteria for hemophagocytic syndrome revised by the International Society for Stem Cell Research, the MAS patients also exhibited significantly elevated levels of aspartate aminotransferase and lactate dehydrogenase, along with a significant decrease in albumin. Hemophagocytosis was observed in only about half of the MAS patients. ROC curve analysis demonstrated that the optimal discriminative values for diagnosing MAS was achieved when SLE patients had ferritin level≥1 010 μg/L and lactate dehydroge-nase levels≥359 U/L, while AOSD patients had fibrinogen levels≤225.5 mg/dL and triglyceride levels≥2.0 mmol/L. Applying the 2016 sJIA-MAS classification criteria to AOSD-MAS yielded a diagnostic sensitivity of 100% and specificity of 62%. By replacing the less specific markers ferritin and fibrinogen in the 2016 sJIA-MAS classification criteria with new cutoff values, the revised criteria for classifying AOSD-MAS had a notable increased specificity of 86%.@*CONCLUSION@#Secondary MAS commonly occurs in the early stages following the diagnosis of SLE and AOSD. There are notable variations in laboratory indicators among different underlying diseases, which may lead to misdiagnosis or missed diagnosis when using uniform classification criteria for MAS. The 2016 sJIA-MAS classification criteria exhibit high sensitivity but low specificity in diagnosing AOSD-MAS. Modification of the criteria can enhance its specificity.

Phenotype and genotype analyses of two pedigrees with inherited fibrinogen deficiency / 中华血液学杂志

Objective: To analyze the phenotype and genotype of two pedigrees with inherited fibrinogen (Fg) deficiency caused by two heterozygous mutations. We also preliminarily probed the molecular pathogenesis. Methods: The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and plasma fibrinogen activity (Fg∶C) of all family members (nine people across three generations and three people across two generations) were measured by the clotting method. Fibrinogen antigen (Fg:Ag) was measured by immunoturbidimetry. Direct DNA sequencing was performed to analyze all exons, flanking sequences, and mutated sites of FGA, FGB, and FGG for all members. Thrombin-catalyzed fibrinogen polymerization was performed. ClustalX 2.1 software was used to analyze the conservatism of the mutated sites. MutationTaster, PolyPhen-2, PROVEAN, SIFT, and LRT online bioinformatics software were applied to predict pathogenicity. Swiss PDB Viewer 4.0.1 was used to analyze the changes in protein spatial structure and molecular forces before and after mutation. Results: The Fg∶C of two probands decreased (1.28 g/L and 0.98 g/L, respectively). The Fg∶Ag of proband 1 was in the normal range of 2.20 g/L, while it was decreased to 1.01 g/L in proband 2. Through genetic analysis, we identified a heterozygous missense mutation (c.293C>A; p.BβAla98Asp) in exon 2 of proband 1 and a heterozygous nonsense mutation (c.1418C>G; p.BβSer473*) in exon 8 of proband 2. The conservatism analysis revealed that Ala98 and Ser473 presented different conservative states among homologous species. Online bioinformatics software predicted that p.BβAla98Asp and p.BβSer473* were pathogenic. Protein models demonstrated that the p.BβAla98Asp mutation influenced hydrogen bonds between amino acids, and the p.BβSer473* mutation resulted in protein truncation. Conclusion: The dysfibrinogenemia of proband 1 and the hypofibrinogenemia of proband 2 appeared to be related to the p.BβAla98Asp heterozygous missense mutation and the p.BβSer473* heterozygous nonsense mutation, respectively. This is the first ever report of these mutations.

Relationship between coagulation status, autoantibodies, and conception method with subchorionic hematoma / 中华妇产科杂志

Objective: To investigate the relationship between subchorionic hematoma (SCH) and coagulation status, autoantibodies, and conception method. Methods: A total of 100 pregnant women diagnosed with SCH from June 2020 to December 2021 in the Third Affiliated Hospital of Zhengzhou University were included in the SCH group, while 100 healthy pregnant women during the same period were selected as the control group. The coagulation status (including platelet, prothrombin time, thrombin time, activated partial thromboplastin time, fibrinogen, antithrombin Ⅲ, fibrin degradation products, D-dimer, homocysteine, protein S activity, protein C activity), the positive rate of autoantibodies [including antiphospholipid antibodies (anticardiolipin antibody and anti-β2 glycoprotein Ⅰ antibody), antinuclear antibody] and the mode of conception of the two groups were analyzed. Results: Compared to the control group, the SCH group had higher levels of platelet [(240±45)×109/L vs (227±37)×109/L], fibrinogen [(4.0±0.8) vs (3.6±0.7) g/L], D-dimer [(0.42±0.18) vs (0.31±0.15) mg/L], blood homocysteine [(8.9±4.2) vs (6.9±2.3) μmol/L], and lower level of protein S activity [(55±14)% vs (68±20)%], and there were significant differences between the two groups (all P<0.05). The SCH group had higher positive rates of autoantibodies [24.0% (24/100) vs 8.0% (8/100)], antiphospholipid antibodies [15.0% (15/100) vs 6.0% (6/100)], anti-β2 glycoprotein Ⅰ antibody [10.0% (10/100) vs 3.0% (3/100)], antinuclear antibody [11.0% (11/100) vs 2.0% (2/100)] and assisted reproduction rate [10.0% (10/100) vs 2.0% (2/100)] than those of the control group (all P<0.05). Conclusion: The occurrence of SCH is related to blood hypercoagulability, positive autoantibodies, and assisted reproduction.

A Family with Congenital Dysfibrinogenemia and Blood Transfusion / 中国实验血液学杂志

OBJECTIVE@#To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies.@*METHODS@#Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of FGA, FGB and FGG and their flanks were amplified by PCR and sequenced to search for gene mutations.@*RESULTS@#The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of FGA gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were FGA gene g.9308A/G (p.AαThr331Ala) and FGB gene g.12628G/A (p.BβArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery.@*CONCLUSION@#Heterozygous mutation of 6233G/A (p.AαArg35His) of FGA gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.

Construction of anomogram for predicting the prognosis of patients with sepsis-associated acute kidney injury / 中华危重病急救医学

OBJECTIVE@#To explore the risk factors for poor prognosis in sepsis-associated acute kidney injury (SA-AKI) and establish a nomogram predictive model.@*METHODS@#The clinical data of patients with SA-AKI admitted to the department of critical care medicine of Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2019 to September 2022 were retrospectively analyzed, including demographic information, worst values of blood cell counts and biochemical indicators within 24 hours of SA-AKI diagnosis, whether the patient received renal replacement therapy (RRT), mechanical ventilation, vasopressor therapy during hospitalization, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), fibrinogen-to-albumin ratio (FAR) within 24 hours of diagnosis, acute kidney injury (AKI) staging, total length of hospital stay, length of intensive care unit (ICU) stay, and others. According to the 28-day outcome, the patients were divided into survival group and death group, and the indicators between the two groups were compared. Univariate and multivariate Logistic regression analyses were used to screen for risk factors associated with mortality in SA-AKI patients. A nomogram predictive model for SA-AKI prognosis was constructed based on the identified risk factors. Receiver operator characteristic curve (ROC curve) and calibration plots were generated to evaluate the predictive value of the nomogram model for SA-AKI prognosis.@*RESULTS@#A total of 113 SA-AKI patients were included, with 67 in the survival group and 46 in the death group. The 28-day mortality among SA-AKI patients was 40.7%. The comparison between the two groups showed that there were statistically significant differences in age ≥ 65 years, AKI stage, mechanical ventilation, vasopressors, RRT, length of ICU stay, and laboratory indicators cystatin C (Cys C), fibrinogen (Fib), and FAR. Multivariate Logistic regression analysis showed that age ≥ 65 years [odds ratio (OR) = 7.967, 95% confidence interval (95%CI) was 1.803-35.203, P = 0.006], cystatin C (OR = 7.202, 95%CI was 1.756-29.534, P = 0.006), FAR (OR = 2.444, 95%CI was 1.506-3.968, P < 0.001), and RRT (OR = 7.639, 95%CI was 1.391-41.951, P = 0.019) were independent risk factors for mortality in SA-AKI patients. ROC curve analysis showed that the area under the ROC curve (AUC) for age ≥ 65 years, cystatin C, FAR, and RRT in predicting SA-AKI patient mortality were 0.713, 0.856, 0.911, and 0.701, respectively. A nomogram predictive model for SA-AKI patient prognosis was constructed based on age ≥ 65 years, cystatin C, FAR, and RRT, with an AUC of 0.967 (95%CI was 0.932-1.000) according to ROC curve analysis. The calibration plot indicated good consistency between predicted and actual probabilities.@*CONCLUSIONS@#Age ≥ 65 years, cystatin C, FAR, and RRT are independent risk factors for mortality in SA-AKI patients. The nomogram predictive model based on these four factors can accurately predict SA-AKI patient prognosis, helping physicians adjust treatment strategies in a timely manner and improve patient outcomes.

Effects of the ITGA2B Nonsense Mutation (c.2659C > T, p.Q887X) on Platelet Function in a Mouse Model of Glanzmann's Thrombasthenia Generated with CRISPR/Cas9 Technology / 中国实验血液学杂志

OBJECTIVE@#To construct a mouse model of Glanzmann's thrombasthenia (GT) with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation by CRISPR/Cas9 technology, and then further explore the expression and function of glycoprotein αIIbβ3 on the surface of platelet membrane.@*METHODS@#The donor oligonucleotide and gRNA vector were designed and synthesized according to the ITGA2B gene sequence. The gRNA and Cas9 mRNA were injected into fertilized eggs with donor oligonucleotide and then sent back to the oviduct of surrogate mouse. Positive F0 mice were confirmed by PCR genotyping and sequence analysis after birth. The F1 generation of heterozygous GT mice were obtained by PCR and sequencing from F0 bred with WT mice, and then homozygous GT mice and WT mice were obtained by mating with each other. The phenotype of the model was then further verified by detecting tail hemorrhage time, saphenous vein bleeding time, platelet aggregation, expression and function of αIIbβ3 on the surface of platelet.@*RESULTS@#The bleeding time of GT mice was significantly longer than that of WT mice (P<0.01). Induced by collagen, thrombin, and adenosine diphosphate (ADP), platelet aggregation in GT mice was significantly inhibited (P<0.01, P<0.01, P<0.05). Flow cytometry analysis showed that the expression of αIIbβ3 on the platelet surface of GT mice decreased significantly compared with WT mice (P<0.01), and binding amounts of activated platelets to fibrinogen were significantly reduced after thrombin stimulation (P<0.01). The spreading area of platelet on fibrinogen in GT mice was significantly smaller than that in WT mice (P<0.05).@*CONCLUSION@#A GT mouse model with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation has been established successfully by CRISPR/Cas9 technology. The aggregation function of platelet in this model is defective, which is consistent with GT performance.

Clinicopathological features of hepatic fibrinogen storage disease in children / 中华病理学杂志

Objective: To investigate the clinicopathological and molecular characteristics of hepatic fibrinogen storage disease (FSD) in children. Methods: The clinical, histopathologic, immunophenotypic, ultrastructural and gene sequencing data of 4 FSD cases were collected from September 2019 to January 2021 in the Children's Hospital of Fudan University, Shanghai, China. Retrospective analysis and literature review were conducted. Results: There were 4 cases of FSD, 3 males and 1 female, aged 3 years and 3 months to 6 years (median age, 3 years and 4 months). The clinical manifestations were abnormal liver function and abnormal blood coagulation function, for which 2 cases had family genetic history. Liver biopsies revealed that, besides liver steatosis, fibrosis and inflammation, there were single or multiple eosinophilic inclusion bodies of various sizes and surrounding transparent pale halo in hepatocytes. Immunohistochemistry showed that the inclusion bodies were positive for anti-fibrinogen. Under the electron microscope, they corresponded to the dilated cisternae of the rough endoplasmic reticulum, which were occupied by compactly packed tubular structures and arranged into a fingerprint-like pattern with curved bundles. Gene sequencing revealed that the 2 cases of FGG mutation were located in exon 8 c.1106A>G (p.His369Arg) and c.905T>C (p.Leu302Pro), and 1 case was located in exon 9 c.1201C>T (p.Arg401Trp). No pathogenic variant was detected in the other case. Conclusions: FSD is a rare genetic metabolic disease and clinically manifests as abnormal liver function with hypofibrinogenemia. In the background of liver steatosis, fibrosis and inflammation, there are eosinophilic inclusions with pale halo in the hepatocytic cytoplasm, which can be identified by anti-fibrinogen immunohistochemical staining. The fingerprint-like structures under electron microscope are helpful for the diagnosis, while FGG sequencing detects the pathogenic mutation of exon 8 or 9 that can clearly explain the phenotype. However, the diagnosis of FSD cannot be completely ruled out if the relevant mutations are not detected.

Biocompatibility evaluation of electrospun PLCL/fibrinogen nanofibers in anterior cruciate ligament reconstruction / 生物医学工程学杂志

The study aimed to evaluate the safety and function of poly(lactic-acid-co-ε-caprolactone) (PLCL)/fibrinogen nanofibers (P/F-Ns), and provide theoretical basis for the clinical application. The surface morphology, mechanical properties, the hydrophilicity and the fibrinogen content of P/F-Ns were tested by scanning electron microscope, the material testing machine, the contact angle meter and the microplate reader, respectively. The cell adhesion, proliferation and ligament remodeling genes expression of Hig-82 cells on P/F-Ns were conducted through cell counting kit-8 (CCK-8) and real-time quantitative PCR analyses, respectively. The results showed that with the increase of the fibrinogen content, the pore sizes and hydrophilicity of three P/F-Ns increased, but the mechanical properties decreased. Cell adhesion and proliferation tests showed that P/F-N-2 held the best ability to promote cell adhesion and proliferation. The ligament remodeling genes expressions of Hig-82 cells on P/F-N-1, P/F-N-2 and P/F-N-3 were all up-regulated compared to P/F-N-0 on days 3 and 7. All the three P/F-Ns containing fibrinogen (P/F-N-1, P/F-N-2 and P/F-N-3) had better biocompatibility compared to P/F-N-0, and could be efficiently applied to the reconstruction of anterior cruciate ligament.

The relationship between homocysteine, coagulation dysfunction and breast cancer risk / 中华肿瘤杂志

Objective: To investigate the correlation of homocysteine (HCY) and coagulation function index with the risk of breast cancer and its clinicopathological characteristics. Methods: The HCY, coagulation function test index, and clinicopathological information of female breast cancer patients (333 cases) treated in Tianjin Medical University Cancer Hospital from January 2018 to December 2018 were collected, and female patients with benign breast (225 cases) were selected during the same period for the control group. The t-test was used to compare measurement data with normal distribution, D-Dimer data were distributed discreetly and described by median, non-parametric Mann-Whitney U test was used to compare the two groups. The chi-square test was used to compare enumeration data, and the Logistic regression analysis was used for the risk analysis. Results: The levels of HCY, fibrinogen (Fbg), protein C (PC), and median D-Dimer (D-D) in peripheral blood of breast cancer patients group [(13.26±5.24) μmol/L, (2.61±0.83) g/L, (117.55±19.67)%, and 269.68 ng/ml, respectively] were higher than those in the control group [(11.58±0.69) μmol/L, (2.49±0.49) g/L, (113.42±19.82)% and 246.98 ng/ml, respectively, P<0.05]. The prothrombin time (PT), PT(INR), α2-antiplasmin (α2-AP) levels [(10.19±0.63) s, 0.91±0.07 and (110.64±13.93)%, respectively] were lower than those in the control group [(10.58±0.65) s, 0.93±0.01 and (123.81±14.77) %, P<0.05]. The serum levels of PC and median D-D in premenopausal breast cancer patients [(112.57±17.86)% and 242.01 ng/ml, respectively] were higher than those in the control group [(105.31±22.31)% and 214.75 ng/ml, respectively, P<0.05]. The levels of PT(INR), α2-AP [0.91±0.07 and (111.29±12.54)%, respectively] were lower than those of the control group[0.98±0.15 and (120.17±16.35)%, respectively, P<0.05]. The levels of HCY and median D-D in postmenopausal breast cancer patients [(14.25±5.76) μmol/L and 347.53 ng/ml, respectively] were higher than those in the control group [(11.67±2.38) μmol/L and 328.28 ng/ml, P<0.05]. The levels of PT, PT(INR), antithrombin Ⅲ (AT-Ⅲ), α2-AP levels [(10.18±0.66) s, 0.87±0.09, (97.30±12.84)% and (110.13±14.96)%] were lower than those in the control group [(10.38±0.61) s, 0.90±0.08, (102.89±9.12)%, and (127.05±12.38)%, respectively, P<0.05]. The levels of α2-AP and median D-D in T2-4 stage breast cancer patients [(111.69±14.41)% and 289.25 ng/ml, respectively] were higher than those in Tis-1 stage patients [(108.05±12.37)% and 253.49 ng/ml, respectively, P<0.05]. The levels of PT, PT (INR), Fbg, AT-Ⅲ, α2-AP, median D-D [(10.62±0.63) s, 0.95±0.06, (3.04±1.52) g/L, (103.21±9.45)%, (118.72±14.77)% and 331.33 ng/ml, respectively] in breast cancer patients with lymph node metastasis were higher than those of patients without lymph node metastasis [(10.42±0.58) s, 0.93±0.06, (2.52±0.54) g/L, (95.20±13.63)%, (106.91±13.13)% and 263.38 ng/ml, respectively, P<0.05]. In non-menopausal breast cancer patients, the level of HCY [(12.63±4.41) μmol/L] in patients with T2-4 stage was higher than that of patients with Tis-1 stage [(10.70±3.49) μmol/L, P=0.010], and the level of thrombin time [(19.35±0.90) s] of patients with T2-4 stage was lower than that of patients with Tis-1 stage [(19.79±1.23) s, P=0.015]. The levels of PT(INR), Fbg, AT-Ⅲ, α2-AP [0.97±0.56, (3.37±2.34) g/L, (102.38±8.77)% and (120.95±14.06)%] in patients with lymph node metastasis were higher than those of patients without lymph node metastasis [0.94±0.05, (2.36±0.48) g/L, (94.56±14.37)% and (109.51±11.46)%, respectively, P<0.05]. Among postmenopausal breast cancer patients, the levels of AT-Ⅲ and α2-AP in T2-4 stage patients [(98.48±11.80)% and (111.84±15.35)%, respectively] were higher than those in patients with the Tis-1 stage [(94.12±14.98)% and (105.49±12.89)%, respectively, P<0.05]. The levels of AT-Ⅲ and α2-AP in N1-3 stage patients [(103.74±9.94)% and (117.29±15.23)%] were higher than those in N0 stage patients [(95.75±13.01)% and (108.39±14.42)%, P<0.05]. Conclusions: HCY and abnormal coagulation function are related to the risk of breast cancer, T stage and lymph node metastasis in breast cancer patients.

Main Factors Influencing the Platelet Spreading / 中国实验血液学杂志

OBJECTIVE@#To explore the main factors of platelet spreading and provide the foundation for related research.@*METHODS@#Platelets (2×107/ml) were draw from C57BL/6J mouse and kept at 22 ℃ for 1-2 hours. Platelets (2×107/ml) were were allowed to adhere and spread on the fibrinogen-coated slides, after staining F-actin in platelets, the platelets were observed with the confocal microscopy. The effects of different concentrations of fibrinogen (10 μg/ml, 30 μg/ml, 100 μg/ml) and kinds of agonists ［thrombin(0.01,0.05,0.1 U/ml), ADP（5,10,20 μmol/L）, U46619（0.125,0.25,0.5 μmol/L）］ on platelets were analyzed. The platelet spreading was successful if the spreading rate was higher after treated with agonists.@*RESULTS@#Compared to the group which coated with 10 μg/ml and 100 μg/ml fibrinogen, the platelet density is optimal when coated with 30 μg/ml fibrinogen. In addition, under the stimulation of thrombin, ADP and U46619, the spreading rate of platelets showed a certain concentration-dependent increasing.@*CONCLUSION@#The platelet spreading is easily influenced by various factors, the platelet spreading can be induced successfully at 0.1 U/ml thrombin, 20 μmol/L ADP and 0.5 μmol/L U46619 on the slide coated with 30 μg/ml fibrinogen.

Association of inflammatory and coagulation biomarkers with mortality in patients aged 60 years or older and hospitalized with COVID-19 / Associação entre biomarcadores inflamatórios e da coagulação com mortalidade em pacientes com 60 anos de idade ou mais hospitalizados com COVID-19

Objectives: To analyze the association of inflammatory and coagulation biomarkers with mortality in geriatric patients with COVID-19. Methods: This is a retrospective cohort study of 206 patients aged 60 years or older who were hospitalized with COVID-19 at an intensive care unit. The analyzed variables were age, sex, length of hospital stay, and inflammatory biomarkers (C-reactive protein, neutrophil-to-lymphocyte ratio, procalcitonin, fibrinogen, ferritin, and d-dimer). We constructed a receiver operating characteristic curve and analyzed the area under the curve to evaluate the accuracy of biomarkers associated with mortality in patients with COVID-19. Results: Mean age was 72 (± 8) years. There were 101 deaths (49% of the total sample), which were significantly more frequent (p = 0.006) in the older age groups and were distributed as follows: 37.50% (60 ­ 69 years old); 50% (70 ­ 79 years old); 67.50% (80 ­ 89 years old); and 75% (over 90 years old). Mortality was associated with increased serum levels of procalcitonin, neutrophil-to-lymphocyte ratio, C-reactive protein, and d-dimer, and decreased fibrinogen levels. Neutrophil-to-lymphocyte ratio occupied the largest area under the receiver operating characteristic curve (area under the curve 0.859) in this group. Conclusions: In this study, inflammatory biomarkers neutrophil-to-lymphocyte ratio, procalcitonin, C-reactive protein, and d-dimer were associated with mortality in older patients with COVID-19 hospitalized at an intensive care unit, and neutrophil-to-lymphocyte ratio presented the best accuracy.

Objetivos: Analisar associação de biomarcadores inflamatórios e da coagulação com mortalidade em pacientes geriátricos com COVID-19. Metodologia: Estudo do tipo coorte retrospectiva de 206 pacientes com 60 anos de idade ou mais internados em unidade de terapia intensiva (UTI) com COVID-19. As variáveis analisadas foram idade, sexo, tempo de permanência hospitalar e biomarcadores inflamatórios, sendo esses proteína C reativa (PCR), relação neutrófilo-linfócitos (RNL), procalcitonina, fibrinogênio, ferritina e D-dímero. Empregou-se a curva ROC, com análise da área sob a curva (ACR), para avaliar a acurácia dos biomarcadores associados à mortalidade nos pacientes com COVID-19. Resultados: A média de idade foi de 72 (± 8) anos. Ocorreram 101 óbitos (49,02% da amostra total), significativamente mais frequente (p = 0,006) nas faixas etárias mais elevadas, distribuídos por faixa etária: 37,50% (60 ­ 69 anos); 50% (70 ­ 79 anos); 67,50% (80 ­ 89 anos); e 75% (nos maiores de 90 anos). A mortalidade foi associada a aumento dos níveis séricos dos biomarcadores procalcitonina, relação neutrófiloslinfócitos (RNL), proteína C reativa (PCR) e D-dímero, bem como diminuição dos níveis de fibrinogênio. A RNL ocupou a maior área sob a curva ROC (ACR 0,859) nesse grupo. Conclusões: Neste estudo, os biomarcadores inflamatórios RNL, procalcitonina, PCR e D-dímero foram associados com mortalidade em pacientes idosos portadores de COVID-19 internados em UTI, e a RNL foi a que apresentou a melhor acurácia.

Resilience and the reduction of occupational stress in Nursing / A resiliência e a redução do estresse ocupacional na Enfermagem / La resiliencia y la reducción del estrés laboral en Enfermería

Abstract Objective: to analyze the association between resilience and occupational stress of Nursing professionals from a general hospital. Method: an observational, cross-sectional study involving 321 Nursing professionals. The data collected were: socio-demographic and labour variables, stress and resilience, analyzed with descriptive and inferential statistics. Results: 54.5% of the participants presented moderate resilience and 36.4%, high; 73.5% were at risk of exposure to occupational stress; the relationship between psychological demands and professional category (p=0.009), between control over work and age (p=0.04), professional category (p<0.001), having a management position (p=0.009), being a specialist (p=0.006) and between social support and professional category (p<0.001), having a management position (p=0.03), daily working hours (p=0.03), being a specialist (p<0.001) were verified. There was an association between resilience Factor I - resolutions of actions and values and control over work (p=0.04) and social support (p=0.002). Conclusion: the Nursing professionals of a general hospital have moderate to high resilience which, associated with high control over their work and high social support, may contribute to the reduction of exposure to occupational stress.

Resumo Objetivo: analisar a associação entre resiliência e estresse ocupacional de profissionais de Enfermagem de um hospital geral. Método: estudo observacional, transversal, envolvendo 321 profissionais de Enfermagem. Os dados coletados foram: variáveis sociodemográficas e laborais, estresse e resiliência, analisadas com estatística descritiva e inferencial. Resultados: 54,5% dos participantes apresentaram resiliência moderada e 36,4%, alta; 73,5% estavam em risco de exposição ao estresse ocupacional; verificada a relação entre demandas psicológicas e categoria profissional (p=0,009), entre controle sobre o trabalho e idade (p=0,04), categoria profissional (p<0,001), exercer cargo de chefia (p=0,009), ser especialista (p=0,006) e entre suporte social e categoria profissional (p<0,001), exercer cargo de chefia (p=0,03), jornada diária de trabalho (p=0,03), ser especialista (p<0,001). Houve associação entre o Fator I de resiliência - resoluções de ações e valores e controle sobre o trabalho (p=0,04) e o apoio social (p=0,002). Conclusão: os profissionais de Enfermagem de um hospital geral apresentaram moderada a alta resiliência que, associada ao alto controle sobre o trabalho e ao elevado apoio social, pode contribuir para a redução da exposição ao estresse ocupacional.

Resumen Objetivo: analizar la asociación entre resiliencia y estrés ocupacional de profesionales de Enfermería de un hospital general. Método: estudio observacional y transversal, realizado en 321 profesionales de Enfermería. Los datos recolectados fueron: variables sociodemográficas y laborales, estrés y resiliencia, analizados con estadística descriptiva e inferencial. Resultados: 54,5% de los participantes presentaron resiliencia moderada y 36,4% alta; 73,5% estaban en riesgo de exposición al estrés ocupacional; fue verificada la relación entre demandas psicológicas y categoría profesional (p=0,009), entre control sobre el trabajo y edad (p=0,04), categoría profesional (p<0,001), ejercer cargo de jefatura (p=0,009), ser especialista (p=0,006) y entre soporte social y categoría profesional (p<0,001), ejercer cargo de jefatura (p=0,03), jornada diaria de trabajo (p=0,03), ser especialista (p<0,001). Se encontró asociación entre el Factor I de resiliencia [resolución de acciones y valores y control sobre el trabajo (p=0,04)] y el apoyo social (p=0,002). Conclusión: los profesionales de Enfermería de un hospital general presentaron de moderada a alta resiliencia, que asociada al alto control sobre el trabajo y al elevado apoyo social puede contribuir para la reducción de la exposición al estrés ocupacional.

Uso de concentrados de fibrinógeno para el tratamiento de la hipofibrinogenemia adquirida / Use of Fibrinogen Concentrates for the Treatment of Acquired Hypofibrinogenemia

Resumen Introducción: Un adecuado manejo del sangrado debe incluir la correcta valoración y eventual reposición de fibrinógeno. Las fuentes tradicionales de este elemento hemostático incluyen el plasma fresco congelado y los crioprecipitados. Los concentrados liofilizados de fibrinógeno humano (CFH) son una alternativa terapéutica novedosa en el mercado chileno. Objetivo: Este estudio describe el curso clínico de los primeros pacientes en nuestra institución requirentes de CFH, dentro de un algoritmo de reposición hemostática por metas. Materiales y Método: Serie de pacientes con hipofibrinogenemia secundaria a sangrado perioperatorio severo, en los que se utilizó CFH como método de reposición de fibrinógeno. Se utilizó tromboelastometría para definir dosis. Se registraron variables demográficas, operatorias, complicaciones y seguimiento hasta los 3 meses. Resultados: Se utilizaron CFH en 18 pacientes. La mediana de edad fue 40,7 (56,5-63) años y dos tercios de los pacientes fueron de sexo masculino. Fallecieron 5 pacientes de la serie. Todos los pacientes requirieron manejo posoperatorio en una unidad de cuidados intensivos. Ocho pacientes fueron sometidos a cirugía cardiaca. El uso de hemocomponentes y concentrados liofilizados fue heterogéneo, pero en todos los casos su uso fue determinado por tromboelastometría. Ningún paciente fue reintervenido a causa de sangrado posoperatorio. Conclusión: El uso de concentrados de fibrinógeno humano dentro de un algoritmo de manejo de sangrado guiado por tromboelastometría, es un recurso hemostático factible en la realidad nacional. El impacto clínico de esta intervención requiere una subsiguiente evaluación basada en la evidencia.

Introduction: An adequate bleeding management should include a proper assessment of fibrinogen values and consequent replacement. Traditional sources for this hemostatic element include fresh frozen plasma and cryoprecipitates. Lyophilized human fibrinogen concentrates are a novel therapeutic alternative for the chilean market. Aim: This study aims to describe the clinical course of the first patients in our institution receiving fibrinogen concentrates, included in a goal directed hemostatic management algorithm. Materials and Method: Case series of patients with hypofibrinogenemia secondary to severe perioperative bleeding, in which fibrinogen concentrate was used for fibrinogen replacement. Thromboelastometry was used to define dose regimens. Demographic and surgical variables, complications and follow-up up to 3 months were registered. Results: Fibrinogen concentrate was used in 18 patients. Median age was 40.7 (56.5-63) years, and two thirds of the patients were male. Five patients died. All of the cases required postoperative intensive care. Eight patients underwent cardiac surgery. There was a heterogenic use of blood derived products and lyophilized concentrates, but in all cases its use was guided by thromboelastometry. No patients needed a secondary exploration due to bleeding. Conclusion: The use of human fibrinogen concentrate included in a bleeding management algorithm is a feasible hemostatic resource in the chilean current situation. The clinical impact of this intervention requires further evidence-based evaluation.

Efecto de las diferentes drogas anticoagulantes sobre el ensayo de fibrinógeno derivado del tiempo de protrombina / Effect of different anticoagulant drugs on the prothrombin time-derived fibrinogen assay

Resumen El objetivo de este trabajo fue comparar los niveles de fibrinógeno (FBG) obtenidos por el método de Clauss con los obtenidos por el método de fibrinógeno derivado del tiempo de protrombina (FBG PT-d), con dos tromboplastinas, en pacientes anticoagulados con distintas drogas. Se estudiaron pacientes anticoagulados consecutivos: 105 con antagonistas de la vitamina K (AVK), 55 con heparina no fraccionada (HNF), 58 con heparina de bajo peso molecular (HBPM), 60 con rivaroxabán, 45 con apixabán, 60 con dabigatrán y 100 controles normales (CN). El FBG se determinó por el método de Clauss y FBG PT-d utilizando tromboplastina de cerebro de conejo o recombinante humana; los niveles de heparina, rivaroxabán y apixabán por método cromogénico anti Xa; el dabigatrán con el ensayo de tiempo de trombina diluido. Existió un sesgo positivo (p<0,001) al comparar el FBG PT-d vs. FBG por Clauss: CN: 13,7%, AVK: 31,8%, rivaroxabán: 34,8% y apixabán: 20,0% cuando se utilizó tromboplastina de conejo. En el caso de las muestras que contenían HBPM se observó este desvío con ambas tromboplastinas. El sesgo porcentual en presencia de dabigatrán y heparina no fraccionada no fue estadísticamente distinto del obtenido en el grupo control. El ensayo de FBG PT-d no debe utilizarse en pacientes anticoagulados con rivaroxabán, apixabán, HBPM o AVK, ya que sobreestima los niveles de FBG. El porcentaje de sesgo depende del tipo de tromboplastina utilizado y fue mayor con la de cerebro de conejo en el sistema de detección utilizado.

Abstract The aim of this study was to compare fibrinogen (FBG) results obtained by Clauss method (FBG-C) and by the prothrombin time-derived fibrinogen assay (FBG PT-d) with two thromboplastins in patients under anticoagulation. Consecutive anticoagulated patients were studied: 105 vitamin-K antagonist (VKA), 55 unfractioned heparin, 58 LMWH, 60 rivaroxaban, 45 apixaban and 60 dabigatran, and 100 healthy controls (NC). FBG-C was performed by Clauss and FIB PT-d with rabbit brain and human recombinant thromboplastins, respectively. Heparins, rivaroxaban and apixaban levels were measured by antiXa; dabigatran by thrombin diluted assay. A positive bias of FBG PT-d vs. FBG-C with both thromboplastins were seen in NC (13.7 and 19.0 % for HS and RP, respectively), but bias with HS in rivaroxaban, apixaban and VKA patients were significantly higher compared to NC: 34.8%, 20.0 % and 31.8 %, respectively. LMWH presented higher BIAS compared to NC with both thromboplastins. Samples with unfraction heparin and dabigatran presented similar bias to NC. FBG PT-d should not be used in patients under anticoagulant treatment because of an important overestimation of FBG could be obtained in these patients. The percentage of bias depends on the type of thromboplastin used; it was higher with rabbit brain thromboplastin in the detection system used.

Resumo O objetivo deste trabalho foi comparar os níveis de fibrinogênio (FBG) obtidos pelo método de Clauss com aqueles obtidos pelo método do fibrinogênio derivado do tempo de protrombina (FBG PT-d), com duas tromboplastinas, em pacientes anticoagulados com diferentes drogas. Pacientes anticoagulados consecutivos foram estudados: 105 com antagonista da vitamina K (AVK); 55 com heparina não fracionada (UFH); 58 com heparina de baixo peso molecular (HBPM), 60 com rivaroxabana, 45 com apixabana, 60 com dabigatrana e 100 controles normais (CN). FBG foi determinado pelo método de Clauss e FBG PT-d usando tromboplastina de cérebro de coelho ou tromboplastina humana recombinante; níveis de heparina, rivaroxabana e apixabana pelo método cromogênico anti-Xa; dabigatrana com ensaio de tempo de trombina diluída. Há um viés positivo (p<0,001) ao comparar o FBG PT-d vs FBG de Clauss: CN: 13,7%; AVK: 31,8%, rivaroxabana: 34,8% e apixabana 20,0% quando foi utilizada tromboplastina de coelho. No caso das amostras contendo HBPM, esse desvio foi observado com ambas as tromboplastinas. O viés percentual na presença de dabigatrana e heparina não fracionada não foi estatisticamente diferente daquela obtida no grupo controle. O ensaio de FBG PT-d não deve ser usado em pacientes anticoagulados com rivaroxabana, apixabana, LMWH ou VKA, pois superestima os níveis de FBG. A porcentagem de viés depende do tipo de tromboplastina utilizado e foi maior com a de cérebro de coelho, no sistema de detecção utilizado.

Predictor parameters for poor prognosis in patients with sudden sensorineural hearing loss: fibrinogen to albumin ratio vs C-reactive protein to albumin ratio / Parâmetros preditores de mau prognóstico em pacientes com perda auditiva neurossensorial súbita: relação fibrinogênio/albumina vs. relação proteina C-reativa/albumina

Abstract Introduction Prognosis of sudden sensorineural hearing loss may be predicted using several parameters of laboratory blood analysis. Objective To identify and investigate the most significant indicator parameters related to the poor prognosis of sudden sensorineural hearing loss. Methods Eighty-eight patients were included, and three groups were constituted: non-recovery group with14 patients, recovery group with 33 patients and control group with 41 individuals. We compared fibrinogen-to-albumin ratio, C-reactive protein-to-albumin ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, white blood cell and hemoglobin of the groups. Then, we investigated the most significant indicator parameters related to the poor prognosis of sudden hearing loss. Results The mean hemoglobin, mean platelet-lymphocyte ratio and median white blood cell values did not significantly differ among three groups (p = 0.36, p = 0.86 and p = 0.79, respectively). A significant difference of median fibrinogen-albumin ratio, C-reactive protein-albumin ratio, neutrophil-to-lymphocyte ratio was evident among three groups (p < 0.001, p = 0.003 and p = 0.002, respectively). Median fibrinogen-albumin ratio, C-reactive protein-albumin ratio and neutrophil-to-lymphocyte ratio values were significantly greater in the non-recovery group, compared with the controls (p < 0.001, p = 0.003 and p = 0.005, respectively). Median fibrinogen-to-albumin ratio, C-reactive protein-to-albumin ratio and neutrophil-to-lymphocyte ratio were significantly greater in the recovery group, compared with the controls (p < 0.001, p = 0.013 and p = 0.005, respectively). Moreover, the median fibrinogen-albumin ratio was significantly greater in the non-recovery group compared with the recovery group (p = 0.017). However, no statistically significant difference of median C-reactive protein-albumin ratio, neutrophil-to-lymphocyte was evident between the non-recovery and recovery groups (p = 0.15). Conclusion Increased levels of fibrinogen-albumin ratio may be predictive for poor prognosis in patients with sudden sensorineural hearing loss.

Resumo Introdução O prognóstico de perda auditiva neurossensorial súbita pode ser previsto com vários parâmetros da análise laboratorial do sangue. Objetivo Identificar e investigar os parâmetros indicadores mais significativos relacionados ao mau prognóstico da perda auditiva neurossensorial súbita. Método Foram incluídos 88 pacientes e três grupos foram constituídos: grupo não recuperado, com14 pacientes; grupo com recuperação, 33 pacientes, e grupo controle com 41 indivíduos. Foram comparadas a relação fibrinogênio/albumina, proteína C-reativa/albumina, relação neutrófilos/linfócitos, relação plaquetas/linfócitos, glóbulos brancos e hemoglobina dos grupos. Em seguida, investigamos os parâmetros indicadores mais significativos relacionados ao prognóstico ruim da perda súbita de audição. Resultados A média de hemoglobina, média da relação plaquetas/linfócitos e mediana dos valores de glóbulos brancos não diferiram significativamente entre os três grupos (p = 0,36, p = 0,86 e p = 0,79, respectivamente). Uma diferença significante da média da relação fibrinogênio/albumina, proteína C-reativa/albumina e neutrófilos/linfócitos foi evidente entre os três grupos (p < 0,001, p = 0,003 e p = 0,002, respectivamente). Os valores da mediana da relação fibrinogênio/albumina, proteína C-reativa/albumina e relação neutrófilos/linfócitos foram significantemente maiores no grupo sem recuperação, em comparação com os controles (p < 0,001, p = 0,003 e p = 0,005, respectivamente). As medianas da relação fibrinogênio/albumina, relação proteína C-reativa/albumina e relação neutrófilos/linfócitos foram significantemente maiores no grupo com recuperação, em comparação com os controles (p < 0,001, p = 0,013 e p = 0,005, respectivamente). Além disso, a mediana da relação fibrinogênio/albumina foi significantemente maior no grupo não recuperado comparado ao grupo com recuperação (p = 0,017). No entanto, não houve diferença estatisticamente significante da mediana da relação proteína-C reativa/albumina e relação neutrófilos/linfócitos entre os grupos sem recuperação e com recuperação (p = 0,15). Conclusão Níveis elevados de relação fibrinogênio/albumina podem ser preditores de mau prognóstico em pacientes com perda auditiva neurossensorial súbita.