[Analysis of three Chinese pedigrees affected with Hereditary factor â ¦ deficiency due to compound heterozygous variants of F7 gene].

OBJECTIVE: To analyze the types of genetic variants and clinical characteristics of three Chinese pedigrees affected with Hereditary coagulation factor Ⅶ (FⅦ) deficiency. METHODS: Three pedigrees who had visited the First Affiliated Hospital of Wenzhou Medical University between December 2021 and October 2022 were selected as the study subjects. Prothrombin time (PT), activated partial thromboplastin time (APTT) and FⅦ activity (FⅦ:C) were measured in the three probands and their pedigree members. All exons and their flanking sequences were analyzed by direct sequencing, and candidate variants were verified by reverse sequencing. The corresponding variant loci in the family members were also analyzed. ClustalX-2.1-win was used to analyze the conservation of the variant loci. Varcards and Spcards online software was used to predict the pathogenicity of the variants. Pymol software was used to analyze the changes in protein structure and molecular forces. RESULTS: Three cases of hereditary FⅦ deficiency were found to have decreased FⅦ:C, prolonged PT and normal APTT. Genetic analysis identified a total of four genetic variants, and all three probands had harbored compound heterozygous variants of the F7 gene, including p.Cys389Gly and p.His408Gln in proband 1, p.Cys389Gly and IVS6+1G>T in proband 2, and IVS6+1G>T and IVS1a+5G>A in proband 3. Conservation analysis showed that both the p.Cys389 and p.His408 loci are highly conserved among orthologous species. Analysis with Varcards and Spcards software showed that these variants were pathogenic. Protein modeling analysis showed that the p.Cys389Gly and p.His408Gln variants may result in altered protein structures and changes in hydrogen bonds. CONCLUSION: The clinical manifestations of the three FⅦ-deficient probands may be attributed to the compound heterozygous variants of p.Cys389Gly/p.His408Gln, p.Cys389Gly/IVS6+1G>T and IVS6+1G>T/IVS1a+5G>A of the F7 gene. The combination of the three compound heterozygous variants was unreported previously.

Investigation of the Possible Causes of NRBC in ICU Patients and the Dynamic Trend of NRBC Count in Survival and Death Patients or with Different Underlying Diseases: A Retrospective Study.

Background: The mortality of intensive care unit (ICU) patients ranges from 5% to 30%, and nucleated red blood cells (NRBCs) were revealed to be related to mortality. However, few studies have discussed the causes of NRBC or compared the dynamic count among patients with underlying diseases. Aim: To explore the possible causes of NRBC in ICU patients and the dynamic trends between survival and death groups and underlying disease subgroups. Methods: A total of 177 ICU patients were retrospectively included. The possible causes of NRBC in ICU patients were discussed. The relationship between NRBC and in-hospital mortality and the dynamic trend of NRBC during hospitalization between the survival and death groups and underlying disease subgroups were compared. Results: The Acute Physiology and Chronic Health Evaluation II (APACHE II) score and Sequential Organ Failure Assessment (SOFA) score in the NRBC-positive group were higher (23.52 ± 9.39 vs. 19.62 ± 7.59; 13.50 (9.00-17.50) vs. 8.00 (6.00-12.00)). Red blood cell count (RBC), hemoglobin (Hb) level, oxygen saturation (SO2), oxygenation index (OI), and serum protein level were lower in the NRBC-positive group. However, D-dimer (D-D), liver and kidney function indices, lactate dehydrogenase (LDH), C-reactive protein (CRP), and procalcitonin (PCT) were higher than those in the NRBC-negative group. Correlation analysis showed that NRBC count was positively correlated with alkaline phosphatase (ALP) and red blood cell distribution width (RDW) and negatively correlated with SO2 (r = 0.431, P < 0.05; r = 0.363, P < 0.05; r = -0.335, P < 0.05). The mortality rate in the NRBC-positive group was higher, and the median survival time was shorter than that in the NRBC-negative group (77.9% vs. 95.7%, P < 0.001; 15 days vs. 8.5 days, P < 0.01). Univariate and multivariate Cox regression analyses showed that NRBC was an independent risk factor for in-hospital mortality (HR: 1.12 (1.03-1.22), P < 0.01). The NRBC count had different hazard ratios (HRs) for in-hospital mortality in the subgroups. Locally weighted scatterplot smoothing (LOWESS) analysis revealed that the NRBC count in the death group was higher and had a sharp upward trend before death, whereas that in the survival group was negative or stayed at a low level. The changing trend of the NRBC count was different in patients with different underlying diseases. Conclusion: The possible cause of NRBC in ICU patients was related to inflammation and hypoxia. The persistently high level and rapid upward trend of NRBC counts are risk factors for in-hospital mortality in ICU patients. The changing trend of the NRBC count varied in patients with different underlying diseases.

Prediction of severe illness due to COVID-19 based on an analysis of initial Fibrinogen to Albumin Ratio and Platelet count.

Concomitant coagulation disorder can occur in severe patients withCOVID-19, but in-depth studies are limited. This study aimed to describe the parameters of coagulation function of patients with COVID-19 and reveal the risk factors of developing severe disease. This study retrospectively analyzed 113patients with SARS-CoV-2 infection in Taizhou Public Health Center. Clinical characteristics and indexes of coagulation function were collected. A multivariate Cox analysis was performed to identify potential biomarkers for predicting disease progression. Based on the results of multivariate Cox analysis, a Nomogram was built and the predictive accuracy was evaluated through the calibration curve, decision curve, clinical impact curve, and Kaplan-Meier analysis. Sensitivity, specificity, predictive values were calculated to assess the clinical value. The data showed that Fibrinogen, FAR, and D-dimer were higher in the severe patients, while PLTcount, Alb were much lower. Multivariate Cox analysis revealed that FAR and PLT count were independent risk factors for disease progression. The optimal cutoff values for FAR and PLT count were 0.0883 and 135*109/L, respectively. The C-index [0.712 (95% CI = 0.610-0.814)], decision curve, clinical impact curve showed that Nomogram could be used to predict the disease progression. In addition, the Kaplan-Meier analysis revealed that potential risk decreased in patients with FAR<0.0883 and PLT count>135*109/L.The model showed a good negative predictive value [(0.9474 (95%CI = 0.845-0.986)].This study revealed that FAR and PLT count were independent risk factors for severe illness and the severity of COVID-19 might be excluded when FAR<0.0883 and PLT count>135*109/L.

A novel compound heterozygous mutations in protein C gene causing neonatal purpura fulminans.

: Neonatal purpura fulminans is a rare, life-threatening disease caused by severe congenital deficiency of protein C (PC) because of homozygous or compound heterozygous mutations in the PROC gene. Mutation analysis plays a critical role in diagnosing the disorder and offering prenatal guidance. In this study, we identified a genetic defect in the PROC gene leading to neonatal purpura fulminans. The propositus had very low PC activity (4%) and PC antigen activity (5%). DNA screening of the whole PROC gene revealed two compound heterozygous mutations in exon8 (c.795_796insA) and exon9 (c.1206_1207insG). These two variations led to the compound heterozygous mutations of Gly266Argfs4 and Pro405Alafs20, which were inherited from the patient's father and mother, respectively. His older sister is heterozygous for the Gly266Argfs4 mutation. The inserted nucleotides alter the protein by introducing a stop codon at the subsequent AA position, resulting in a truncated protein compared with the wild type. We deduced that the compound heterozygous mutations are responsible for the PC deficiency, the Gly266Argfs4 mutation has been confirmed to be a novel mutation.