Elevated Fibrinogen Levels Research Articles

Dexamethasone in critical coronavirus disease-2019 cases: Insights from a cross-sectional study

Objective: The objective of the study is to describe the clinical and laboratory characteristics of critically ill coronavirus disease-2019 (COVID-19) patients treated with dexamethasone in an intensive care unit (ICU) to provide a support tool for clinical decision-making. Design: A survey was conducted among hospitalized patients from November 2020 to March 2021, with data collected through patient interviews, medical records, and laboratory tests. Setting: This is a large hospital serving as a reference center for COVID-19 care in Bahia, Brazil. Patients: A convenience sample of 22 patients admitted to the COVID-19 ICU who signed informed consent to participate in the study. Methods: A cross-sectional study of patients admitted to the ICU with COVID-19. Data were analyzed using statistical methods. Results: The most common comorbidities among patients were hypertension (54%), diabetes (36%), and cardiovascular disease (27%). Among the deaths recorded, 55% of patients had hypertension, 44% had diabetes and/or required insulin therapy, 33% had a history of cardiovascular disease (including atrial fibrillation and congestive heart failure), and 22% had a history of stroke. Renal dysfunction (elevated creatinine); liver function abnormalities (increased alanine aminotransferase and aspartate aminotransferase); and elevated levels of ferritin, fibrinogen, and D-dimer were identified as potential indicators of disease progression. Among these factors, only elevated creatinine demonstrated a statistically significant association with an increased mortality risk. Conclusion: These findings provide a better understanding of the clinical course of severe acute respiratory syndrome coronavirus 2 infections and suggest that laboratory medicine is crucial in supporting clinical decision-making and advancing scientific and healthcare knowledge during the early phases of the COVID-19 pandemic. Relevance for patients: Identifying key risk factors, such as renal dysfunction, can improve early intervention and personalized treatment for critically ill COVID-19 patients.

Mendelian randomization assessing causal relationship between fibrinogen levels and ischemic stroke.

High fibrinogen levels are associated with an increased risk of ischaemic stroke (IS). We used mendelian randomisation (MR) to explore a potential causal relationship. Data for assessing the relationship between gene variant, disease and biological levels needed for a MR approach was collected using a meta-analytical approach. Inverse-variance weighted (IVW) approach was used for the main analyses and alternative approach for sensitivity analyses. The relationship between fibrinogen levels and IS was assessed using Odds Ratio (OR), while mean difference (g/L) was used for the relationship between SNP (rs1800790) and fibrinogen levels. The variant FGB rs1800790 SNP was interrogated as an instrumental variable of fibrinogen levels. A meta-analysis with 24 studies (12 case-control and 12 cohort studies, totalling 20,902 cases and 76,510 controls was conducted. Homozygotes (AG) of rs1800790 have 0.14g/L (95%CI: 0.08-0.19, P<0.001) and minor allele (AA) have 0.18g/L (95%CI: 0.01-0.35, P=0.037) higher levels of plasma fibrinogen concentration compared with homozygous for the major allele (GG). The risk of IS was significantly increased in 1-g/L (OR=1.83, 95%CI: 0.92-3.62, P=0.084), or 1-SD of fibrinogen levels (OR=1.39, 95%CI: 1.03-1.87, P=0.030), or above median levels (OR=1.22, 95%CI: 1.02-1.46, P=0.029) or categorical levels tertiles (OR=1.50, 95%CI: 1.26-1.79, P<0.001). Each 1-g/L increase in fibrinogen levels was causally associated with a higher risk of ischemic stroke (OR=2.28, 95%CI: 1.53-3.03, P<0.001) in the Mendelian randomisation analysis. Elevated fibrinogen levels are a causative risk factor for ischaemic stroke with each 1g/L increase doubling its risk.

Вплив полідезоксирибонуклеотиду на вміст цитокінів у пацієнтів з ревізійною ринопластикою

Polydeoxyribonucleotide (PDRN) drugs are actively used in global practice after rhinoplasty. Current research focuses on analyzing the immunological aspects of the inflammatory response and the effect of PDRN on tissue repair. 63 patients who underwent revision rhinoplasty using a rib graft were under supervision. Patients were divided into two groups for further studies according to the fibrinogen levels. All patients were evaluated for cytokines levels TNF-α, TGF-β1 “DRG Diagnostic Inc.” (Germany), IL-6, IL-10, IL-13 “IBL International” (Germany), IL-12, IL-18 “ElabScience” (USA). In patients with revision rhinoplasty in whom an increased level of fibrinogen was found, after the use of PDRN there was a decrease in the concentration of M1 cytokines of the macrophage phenotype (IL-6, IL-12, IL-18, and TNF-α) and an increase in the concentration of M2 cytokines of the macrophage phenotype (IL-10, IL-13, TGF-β1). In patients with revision rhinoplasty in whom the level of fibrinogen was normal, the use of PDRN did not affect the level of cytokines, which was characterized by the absence of probable changes in the serum concentration of cytokines M1 (IL-6, IL-12, IL-18) and M2 of the macrophage phenotype (IL- 10, IL-13, TGF-β1). In patients with an elevated level of fibrinogen, there is also a decrease in the level of the angiogenic factor VEGF, the use of the drug PDRN led to an increase in its level. The obtained results may represent a new therapeutic approach to reducing the number of complications in reconstructive rhinoplasty. However, further research is needed to understand the mechanisms of action of PDRN, as well as possible advantages or disadvantages of its use.

Caffeic Acid Phenethyl Ester Protects Neurons Against Oxidative Stress and Neurodegeneration During Traumatic Brain Injury.

Traumatic brain injury (TBI) is an inflammatory disease causing neurodegeneration. One of the consequences of inflammation is an elevated blood level of fibrinogen (Fg). Earlier we found that extravasated Fg induced an increased expression of neuronal nuclear factor kappa B (NF-κB) p65. In the present study, we aimed to evaluate the effect of caffeic acid phenethyl ester (CAPE), an inhibitor of NF-κB, on Fg-induced neurodegeneration in vitro and in mice with mild-to-moderate TBI. Primary mouse brain cortical neurons were treated with Fg (0.5 or 1 mg/mL) in the presence or absence of CAPE. A cortical contusion injury -induced model of TBI in C57BL/6 mice was used. Mice were treated with CAPE for two weeks. The generation of reactive oxygen species (ROS) and neuronal viability were assessed. Mice memory was assessed using novel object recognition and contextual fear conditioning tests. The generation of ROS and viability of neurons in vitro and in the brain samples were assessed. Data showed that CAPE attenuated the Fg-induced generation of ROS and neuronal death. CAPE improved the cognitive function of the mice with TBI. The results suggest that Fg-induced generation of ROS could be a mechanism involved in cognitive impairment and that CAPE can offer protection against oxidative damage and neurodegeneration.

Variability in Coagulation Profiles in Patients with Chronic Kidney Disease and Peripheral Artery Disease.

Chronic Kidney Disease (CKD) has been associated with a prothrombotic state. CKD affects hemostasis through altered platelet function and coagulation factors. Traditional tests provide limited insight into these changes. We used Thromboelastography (TEG) to evaluate coagulation profiles in CKD and non-CKD patients, comparing parameters based on glomerular filtration rate (GFR) to better understand clotting dynamics. The aim of the study was to evaluate coagulation profiles in patients across GFR categories using Thromboelastography (TEG), which enables comprehensive assessment of clot formation dynamics. We prospectively evaluated patients with peripheral artery disease undergoing revascularization (December 2020-2023). Patients were stratified by GFR into three groups: >60 mL/min, 30-59 mL/min, and <30 mL/min. Pre- surgical blood samples were analyzed using TEG parameters, including Maximum Amplitude (MA), Citrated Functional Fibrinogen (CFF), and Functional Fibrinogen Levels (FLEV). Statistical analysis employed Kruskal-Wallis tests. Among 254 patients (182 with GFR >60, 56 with GFR 30-59, and 16 with GFR <30), those with declining kidney function showed progressively higher values in CRT MA (62.80 vs 65.85 vs 67.85 mm, p=0.0021), CK MA (61.10 vs 64.00 vs 66.70 mm, p=0.0063), CFF MA (21.40 vs 24.10 vs 33.70 mm, p=0.0017), and CFF FLEV (390.5 vs 487.2 vs 556.6 mg/dL, p=0.0029). This pattern persisted in patients on mono antiplatelet therapy (MAPT). Patients receiving MAPT showed consistently higher coagulation marker levels compared to those on dual antiplatelet therapy (DAPT), particularly in severe renal impairment (GFR <30). Patients with decreased kidney function demonstrated relative hypercoagulability compared to those with normal kidney function, as evidenced by elevated fibrinogen levels and stronger blood clots. While DAPT was associated with lower coagulation marker levels compared to MAPT, platelet reactivity remained similar across GFR categories. However, these laboratory findings did not translate into increased clinical events, with no significant differences in bleeding episodes (p=0.436) or arterial thrombotic events (p=0.095) across GFR categories.

Association between clinical laboratory indicators and WOMAC scores in Qatar Biobank participants: The impact of testosterone and fibrinogen on pain, stiffness, and functional limitation.

The association between baseline laboratory parameters and experienced well-being in healthy individuals remains uncertain. This study explored the relationship between clinical laboratory profiles and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for pain, stiffness, and physical functional limitation in healthy individuals in Qatar. Clinical laboratory data were collected from 1,764 Qatar Biobank participants who also completed the WOMAC questionnaire: lipid profiles (high-density lipoprotein, low-density lipoprotein, cholesterol, and triglycerides), endocrine markers (TSH, T3, T4, estradiol, and testosterone), and two inflammatory markers (CRP and fibrinogen). Multiple linear regression was used with 11 clinical indicators as independent variables and the subscale and total WOMAC scores as dependent variables. Multivariate effects of each indicator on the outcomes were assessed, and univariate effects were examined when significant. Testosterone had a significant impact on all WOMAC subscales (pain, stiffness, and functional limitation) and the total WOMAC score. Higher testosterone levels were associated with a reduction in pain (β = -0.03, t = -3.505, p < 0.001, 95% CI = -0.052, -0.015), stiffness (β = -0.01, t = -2.265, p = 0.024, 95% CI = -0.018, -0.001), physical dysfunction (β = -0.08, t = -3.265, p = 0.001, 95% CI = -0.135, -0.034), and total WOMAC scores (β = -0.127, t = -3.444, p < 0.001, 95% CI = -0.199, -0.055). Elevated fibrinogen levels were associated with an increase in stiffness (β = 0.155, t = 2.241, p = 0.025, 95% CI = 0.019, 0.290), physical dysfunction (β = 1.17, t = 2.808, p = 0.005, 95% CI = 0.354, 1.997), and total WOMAC scores (β = 1.610, t = 2.691, p = 0.007, 95% CI = 0.437, 2.784). Testosterone may protect against pain, stiffness, and physical dysfunction, while high fibrinogen levels might be a surrogate of systemic inflammation that enhances stiffness and limits physical function. Measuring multiple clinical and laboratory markers in healthy individuals may enhance our understanding of the molecular mechanisms underlying pain.

A Clinical Study to Evaluate the Anti-inflammatory Effect of Lactoferrin + Disodium Guanosine Monophosphate Therapy in the Patients with Chronic Kidney Disease.

India is impacted by the increasing burden of chronic kidney disease (CKD) and end-stage renal disease (ESRD), necessitating efficient management and therapy. CKD is characterized by elevated levels of inflammatory biomarkers, specifically IL-1β, IL-1RA, IL-6, TNF-α, TGF-β, and fibrinogen. The aim of this research is to determine the antiinflammatory effects of lactoferrin + disodium guanosine monophosphate therapy in CKD patients. The objective of this study is to examine the efficacy of this therapy versus conservative CKD management alone in reducing inflammation. This study intends to examine the possible benefits of study drug in treating inflammation associated with CKD by analyzing its effect on inflammatory markers including IL-6 and TNF-α. This randomized, open-label, parallel group, two-arm clinical study, comprising of 40 patients with CKD, with 20 patients in each group. The groups were well-matched in terms of demographic characteristics. Conception, screening, randomization, and follow-up visits including physical examinations, laboratory investigations, and medication dispensation were all carried out over a 29-week period. Creatinine clearance, estimated glomerular filtration rate (eGFR), estimated urine urea nitrogen, and inflammatory markers (IL-6, IL-10, TNF-α, CRP) were analyzed at time of screening and at 3 and 6-month postrandomization. The study found a significant decrease in inflammatory markers, including TNF-α, IL-6, and IL-10, in the group receiving study drug, indicating its potential as an antiinflammatory intervention for managing CKD. Secondary endpoints, including hemoglobin (Hb) and e-GFR levels, showed nonsignificant improvements in the study group compared to the control group. No significant adverse events were reported during the study. The study highlights the potential antiinflammatory effects of the lactoferrin + disodium guanosine monophosphate therapy in individuals with CKD. The findings suggest that study drug may be a viable intervention for managing inflammation in CKD patients. Further research is needed to validate these results and explore its long-term effects in CKD management.

Risk factors for the development of thromboembolic complications in patients with polytrauma

Annotation. Skeletal injuries in polytrauma occur in 73-95% of cases and quite often lead to irreversible shock. In their structure, bone fractures of the lower limbs and pelvis occur with a frequency of 65-75% and, to a large extent, are one of the main causes of venous thromboembolism. The aim of our study was to determine risk factors for thromboembolic complications among patients with polytrauma. Our study involved 163 patients who met the criteria for inclusion in the study and were treated at the Odesa City Clinical Hospital № 11 from 2013 to 2022. The age structure of the victims differed significantly in the study groups. Thus, in the experimental group, the average age of the victims was 46.8±7.5 years, and in the control group, the average age was 38.7±6.2 years (р≤0.05). Among patients in the experimental group, BMI was 27.8±3.2 kg/m², and in the control group, this indicator was 24.9±3.0 kg/m² (р≤0.05). Modern prophylactic regimens have reduced the frequency of preoperative DVT in polytrauma patients, but orthopedists should still pay attention to patients aged &gt;46 years, BMI &gt; 26 kg/m2, time from injury to surgery &gt;9 days, and elevated levels of platelets and fibrinogen. A better understanding of these risk factors may help surgeons refine the risk stratification profile and guide early multidisciplinary management of patients with polytrauma and venous thromboembolism.

Platelets, Biomarkers of Coagulation and Fibrinolysis, and Early Coronary Stent Thrombosis.

Background/Objectives: Acute stent thrombosis (ST) is a rare yet severe complication following percutaneous coronary intervention (PCI). Herein, we investigated the possible association between routinely available coagulation and fibrinolysis markers with early ST. Methods: Within a single-center registry, we investigated the association between the preprocedural platelet count, plasma levels of fibrinogen and D-Dimer, and the incidence of early ST in the first 30 days after PCI. Results: Out of 10,714 consecutive patients who underwent PCI using drug-eluting stents (DESs), the preprocedural platelet count, fibrinogen, and D-Dimer measurements were available in 6337, 6155, and 956 patients, respectively. Fifty-eight patients (0.92%) experienced an early ST within 30 days after PCI. Compared with those without ST, patients with early ST showed significantly elevated preprocedural platelet counts (p < 0.05) and fibrinogen levels (p < 0.05). D-Dimer levels were not associated with early ST. Patients in the fifth quintile of platelet count had a significantly increased risk for early ST (HR 2.43; 95% CI 1.43-4.14; p = 0.001) compared with patients in the lower four quintiles. In addition, patients in the fifth quintile of fibrinogen also had a significantly increased risk for early ST (HR 1.86; 95% CI 1.07-3.26; p < 0.05) compared with patients in the lower four quintiles. These associations were independent of clinical risk factors, the number of stents, the presence of acute coronary syndromes, and white blood cell count. Conclusions: Preprocedural platelet counts and fibrinogen plasma levels can identify patients at elevated risk of early ST after implantation of DESs in addition to procedure-level and device-related risk factors.

COMPARATIVE EVALUATION OF THE PERIODONTAL STATUS AND SERUM PARAMETERS IN NORMAL BODY MASS INDEX AND OBESE CHILDREN

Objective: Childhood obesity is a growing global health concern, with established associations to both systemic and oral health complications. This study aimed to compare periodontal status and inflammatory biomarkers between obese and non-obese children. Materials and methods: Fifty-two children (26 obese, 26 non-obese) were included, with key parameters such as Plaque Index (PI), Bleeding on Probing (BOP), Probing Depth (PD), and Clinical Attachment Loss (CAL) assessed to evaluate periodontal health. Paraclinical indicators including fibrinogen, C-reactive protein (CRP), and vitamin D (25(OH)D) levels were also measured. Results and Discussion: Results demonstrated that obese children exhibited significantly higher values for PI, BOP, PD, and CAL, indicating poorer periodontal health. Elevated serum fibrinogen and CRP levels, coupled with lower vitamin D levels in obese children, underscored a state of chronic inflammation and potential nutrient deficiency associated with obesity. Conclusion: These findings highlight the need for a multidisciplinary approach to managing obesity and promoting oral health, suggesting that early intervention in dietary and lifestyle factors could mitigate these risks.

Relationship between Fibrinogen Values and Sensitivity and Specificity of STS Score, Euroscore for Patients Undergoing Open Heart Surgery

Background/Aim: Cardiovascular diseases are a leading cause of mortality worldwide, with surgical interventions playing a crucial role in outcomes. Despite technological advancements and improved operator experience, perioperative and postoperative risks remain significant, particularly for high-risk patients. Fibrinogen, an acute-phase reactant, increases during inflammation and plays a role in coagulation. This study investigates the prognostic impact of fibrinogen levels on the outcomes of cardiac surgery and evaluates its relationship with established risk classification systems. Materials and Methods: This observational cohort study included 105 patients who underwent cardiac surgery between May 2018 and December 2023. Patients with coronary bypass grafting and valve surgery were included, while those with transplantation, congenital heart surgery, or other significant conditions were excluded. Patient data, including demographic information, comorbidities, laboratory parameters, and surgical details, were collected. The fibrinogen cutoff value was determined using the Youden index. Statistical analyses were performed using SPSS 23.0, with p-values &lt; 0.05 considered significant. Results: Of the 116 individuals screened, 105 were included in the study. The HighFib group (&gt;3.8 g/dL) showed higher rates of complications, such as low cardiac output, prolonged mechanical ventilation, and atrial fibrillation, compared to the LowFib group (&lt;3.8 g/dL). The HighFib group also had lower preoperative hemoglobin levels and higher Euroscore values. Logistic regression analysis demonstrated that both fibrinogen levels and established risk scores were significant predictors of postoperative complications. Conclusion: Elevated fibrinogen levels are associated with increased postoperative complications in cardiac surgery patients. Fibrinogen, alongside traditional risk scores, can be a valuable predictor of adverse outcomes. Prospective studies are needed to further validate these findings and establish optimal fibrinogen management strategies in cardiac surgery.

Correlation between admission blood glucose, fibrinogen, and slow blood flow during primary PCI for acute ST segment elevation myocardial infarction.

Coronary slow flow (CSF) is a common phenomenon of coronary microcirculation dysfunction, and is closely related to elevated blood glucose and fibrinogen (FIB) levels. However, whether immediate blood glucose and FIB levels affect coronary blood flow during primary percutaneous coronary intervention (PCI) remains unclear. To explore the correlation between admission blood glucose (ABG), fibrinogen (FIB) and slow blood flow during primary PCI for acute ST segment elevation myocardial infarction (STEMI). A total of 497 patients who underwent coronary angiography in the cardiology department of the 904th Hospital of the Joint Logistics Support Force from December 2018 to December 2022 due to STEMI were selected consecutively, and then were divided into two groups based on whether slow blood flow occurred during primary PCI: slow blood flow group (n = 117) and control group (n = 380). Detecting the ABG, FIB and other indicators of patients in each group, and using logistic regression analysis and receiver operating characteristic (ROC) curve to analyze independent risk factors for slow blood flow during primary PCI, and further evaluating the prognosis of patients. The levels of ABG and FIB in patients with slow blood flow were significantly higher than those in the control group (P < 0.05). The results of multivariate logistic regression analysis suggested that FIB and ABG were independent risk factors for slow blood flow during primary PCI (both P < 0.05). ROC curve analysis showed that ABG, FIB, and their combination all had predictive value for slow blood flow during primary PCI (all P < 0.05), and the area under the curve (AUC) of the combined indicator was higher than that of any single indicator, with statistical significance (P < 0.05). KM curve analysis suggested that the prognosis of patients in slow blood flow group were poor. Both elevated ABG and FIB could predict slow blood flow during primary PCI, and the diagnostic value of the combined indicator was superior to that of any single indicator, which could be used for the evaluation of slow blood flow during primary PCI, so as to evaluate the prognosis of patients with STEMI.

The high levels of fibrinogen and platelets are associated with poor survival in nephroblastoma in children.

Pediatric nephroblastoma is the most common abdominal malignancy in children. Hyperfibrinogenemia and thrombocytosis are often associated with malignancy and poor prognosis. This study aimed to investigate the relationship between high fibrinogen and platelet levels and the clinicopathologic features as well as overall survival in pediatric nephroblastoma. We recruited a total of 129 nephroblastoma patients in this research. The patients were evaluated retrospectively using the Kaplan-Meier method and Log rank test to investigate the correlation between patient survival and fibrinogen and platelet levels. A multivariate Cox regression model and a predictive nomogram have also been constructed. Our findings indicated that fibrinogen levels were associated with Children's Oncology Group (COG) stage (P<0.001), pathological typing (P<0.001), hematuresis (P=0.002), hypertension (P=0.02), and venous thrombosis (P<0.001). Platelet levels were associated with COG stage (P<0.001), pathological typing (P<0.001), hematuresis (P=0.001), and venous thrombosis (P<0.001). Elevated fibrinogen and platelet levels are associated with poor overall survival (P<0.001). Multivariate analysis also indicated that elevated fibrinogen and platelet were independent risk factors (P=0.02, and P<0.001). The nomogram model demonstrates its application value in predicting the prognosis of pediatric nephroblastoma. The calibration curve validates that the predictions made by the nomogram model are in agreement with the actual observed survival outcomes. High levels of platelets and fibrinogen may have negative effects on the prognosis of children with nephroblastoma.

Distinct Hemostasis and Blood Composition in Spiny Mouse Acomys cahirinus.

The spiny mouse (Acomys species) is capable of scarless wound regeneration through largely yet unknown mechanisms. To investigate whether this capacity is related to peculiarities of the hemostatic system, we studied the blood of Acomys cahirinus in comparison to Mus musculus (Balb/c) to reveal differences in blood composition and clotting in both males and females. In response to surgical manipulations, blood clots formed in wounds of Acomys comprised a stronger hemostatic seal with reduced surgical bleeding in comparison with Balb/c. Acomys demonstrated notably shorter tail bleeding times and elevated clottable fibrinogen levels. Histological analysis revealed that clots from Acomys blood had densely packed fibrin-rich clots with pronounced fibrin segregation from erythrocytes. Acomys exhibited superior plasma clot stiffness as revealed with thromboelastography. The latter two characteristics are likely due to hyperfibrinogenemia. Light transmission platelet aggregometry demonstrated that ADP-induced platelet aggregates in Acomys males are stable, unlike the aggregates formed in the plasma of Balb/c undergoing progressive disaggregation over time. There were no apparent distinctions in platelet contractility and baseline expression of phosphatidylserine. Hematological profiling revealed a reduced erythrocytes count but increased mean corpuscular volume and hemoglobin content in Acomys. These results demonstrate the distinctive hemostatic potential of Acomys cahirinus, which may contribute to their remarkable regenerative capacity.

Dysregulated Coagulation in Parkinson's Disease.

Parkinson's disease (PD), a prevalent neurodegenerative disorder characterized by dopaminergic neuron degeneration and α-synuclein accumulation, has been increasingly associated with coagulation dysfunction. This review synthesizes emerging evidence linking dysregulated coagulation to PD pathophysiology. We examine the alterations in coagulation parameters, including elevated fibrinogen levels, impaired fibrinolysis, and platelet dysfunction, which collectively contribute to a hypercoagulable state in PD patients. Epidemiological studies have revealed a higher incidence of thrombotic events, such as deep vein thrombosis (DVT) and stroke, among PD patients, suggesting significant comorbidity between PD and coagulation disorders. This review explores the potential pathophysiological mechanisms underlying this association, focusing on the roles of inflammation and oxidative stress. Additionally, we discuss the limitations of current research and propose future directions. This comprehensive analysis underscores the importance of understanding the coagulation-neurodegeneration axis in PD, which may lead to novel diagnostic and therapeutic strategies for this debilitating condition.

Relationship between plasma fibrinogen level and obstructive sleep apnea

BackgroundObstructive sleep apnea (OSA), which causes recurring hypoxemia owing to upper airway closure, is one of the most frequent sleep disorders. OSA patients are more prone to suffer cardiovascular disease (CVD) and stroke. One primary mechanism connecting OSA with cardiovascular problems is the prothrombotic state. Our goal in this research is to confirm the relationship between plasma fibrinogen levels and OSA.ResultsA case–control study involved 20 adults, non-obese participants who had been recently diagnosed with OSA, had never been treated for OSA before, and did not have any other preexisting conditions, and 20 controls underwent measurement of plasma fibrinogen levels following whole night polysomnography. The patient's plasma fibrinogen levels were substantially more significant than the controls' (399.8 ± 54.7 versus 309.8 ± 26.7 mg/dL, respectively), with a p-value of less than 0.001. Plasma fibrinogen levels in moderate and severe OSA (383.6 ± 20.6 mg/dL and 454.4 ± 25.6 mg/dL, respectively) were significantly higher than in controls (309.8 ± 26.7 mg/dL) (p < 0.001 and p < 0.001) and mild OSA patients (335 ± 27.8 mg/dL) (p = 0.013 and p < 0.001). Plasma fibrinogen levels were not significantly different between the controls and patients with mild OSA (p = 0.219). Apnea–hypopnea index, arousal index, and oxygen desaturation index showed positive correlations with plasma fibrinogen (r = 0.953, 0.888, and 0.894, p = < 0.001, < 0.001, and < 0.001, respectively). The total sleep time, sleep efficiency, N3%, REM%, and lowest oxygen saturation showed negative correlations (r = − 0.860, − 0.877, − 0.611, − 0.844, and − 0.745, p = < 0.001, < 0.001, < 0.001, and < 0.001, respectively).ConclusionElevated levels of plasma fibrinogen in individuals with moderate-to-severe OSA may be attributed to sleep apnea and these increased levels could serve as a significant risk factor that establishes a connection between OSA and pathology of the cardiovascular and cerebrovascular systems. These results could significantly affect OSA diagnosis, therapy monitoring, and outcome.

Relationship between Deep Vein Thrombosis and Serial Chest CT Severity Scores in COVID-19 Patients

Aim: We aimed to evaluate risk factors for deep vein thrombosis (DVT) in lower extremities veins in COVID-19 patients and the relationship between DVT with chest CT severity scores (CT-SS). To our knowledge, our study is the first to investigate the relationship between the occurrence of DVT and serial chest CT-SS in COVID-19 patients. Methods: We conducted a retrospective analysis of 131 COVID-19 patients (≥18 years) admitted to our hospital. Two radiologists examined chest CT scans and calculated CT-SS using a visual scoring system. Color Doppler ultrasounds of lower extremity veins were performed for DVT. CT Pulmonary Angiographies (CTPA) were performed on patients clinically suspected of pulmonary embolism (PE). Results: A total of 131 patients were included in our study. 71/131 (54.2%) of the patients were male. 18/131 (13.7%) patients were treated in ICU and 18 (13.7%) patients died. 21/131 patients had DVT (16%) in their lower extremities. Chest CTA was performed in 44/131 (33.6%) patients and PE was detected in 10/44 patients (22.7%). PE was considerably more common in patients with DVT (p = 0.009). The occurrence of DVT was significantly associated with high first chest CT-SS (p=0.002). However, there was no association between the DVT and second and third CT-SS. Significant associations were found between the development of DVT with elevated serum D-Dimer, CRP and fibrinogen levels (p

High Intraocular Concentration of Fibrinogen Regulates Retinal Function Via the ICAM-1 Pathway.

Diabetic retinopathy (DR) is a significant complication of diabetes mellitus that can lead to progressive visual impairment. This study aimed to elucidate the role of fibrinogen, a protein whose serum and intraocular concentrations are elevated in patients with diabetes and DR, in the pathogenesis of DR. The changes in the protein levels of the neuronal marker tubulin-β3 (TUBB3) and retinal response induced by the intravitreal injections of 1× phosphate-buffered saline, 40mg/mL of fibrinogen, and 40mg/mL of fibrinogen in combination with anti-intracellular adhesion molecule-1 (ICAM-1) antibody in normal mice were observed using immunofluorescence, western blotting, and electroretinography. High concentrations of fibrinogen led to a decrease in the expression of TUBB3 in immunofluorescence and western blotting. The amplitudes of the positive scotopic threshold response and b-wave were notably reduced after the injection of fibrinogen, indicating potential damage to the retinal ganglion cells. The co-administration of anti-ICAM-1 antibody effectively mitigated these fibrinogen-induced changes, indicating that fibrinogen-induced damage is mediated via the ICAM-1 pathway. The present study underscores the significance of elevated intraocular fibrinogen levels as a pathogenic factor in DR. Involvement of the fibrinogen/ICAM-1 pathway presents new avenues for therapeutic intervention, especially in patients with treatment-resistant conditions.

The effects of an aggressive breast tumor on thrombosis after antithrombin downregulation in a hypercoagulable mouse model

BackgroundDespite improvements in therapy, breast cancer still contributes to high mortality rates. Survival of these patients becomes progressively worse upon diagnosis with cancer-associated thrombosis (CAT). Unfortunately, the mechanism causing CAT has remained unclear. ObjectiveSet up an acute and non-invasive hypercoagulable mouse model with an aggressive breast cancer and study the mechanism of cancer-associated thrombosis. MethodsMice were grafted with the aggressive breast cancer cell line MDA-MB-231 or sham-treated. Subsequently, an acute imbalance in coagulation was introduced by injecting a synthetic small interfering (si) RNA targeting hepatic Serpinc1 to knockdown antithrombin – a condition known to predispose to cause a hypercoagulant state in vivo. ResultsSilencing Serpinc1 with siRNA decreased plasma antithrombin levels. siRNA treatment had no short-term effects on tumor characteristics, but increased distant metastasis within the timeframe of this study. The systemic pro-inflammatory status, with elevated platelet counts and fibrinogen levels in tumor-bearing mice, was also not affected by antithrombin silencing. While elevated fibrin deposition in the liver upon Serpinc1 targeting was not significantly affected by the presence of breast cancer, knockdown of antithrombin did significantly increase intratumoral fibrin deposition and inflammation. Surprisingly, in the presence of an aggressive tumor, a protective outcome with less clinical features coinciding with venous thrombosis were observed in mice with antithrombin knockdown. ConclusionWe conclude that the presence of a breast tumor protects hypercoagulant mice from severe consumption of coagulation factors after lowering hepatic antithrombin levels, possibly due to elevated platelet counts. However, the consequences on cancer-associated thrombosis remained inconclusive.

A-172 Feasibility of PT, aPTT, and Fibrinogen on a Multifunctional Digital Microfluidic Cartridge

Abstract Background Excessive bleeding is prevalent in severe trauma patients, and measurement of multiple coagulation parameters is vital to correcting coagulopathy and improving outcomes. There are no rapid, near-patient technologies that can perform multiple coagulation assays simultaneously on a single consumable. We are developing a point-of-care digital microfluidic (DMF) platform to test three critical coagulation markers: prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen. Methods Five proficiency testing plasma samples were obtained from the College of American Pathologists (CAP) with normal, intermediate, and prolonged response of PT and aPTT, and normal and elevated fibrinogen levels. After loading 10 μL of sample onto the cartridge, autonomous digital microfluidic operations divided the sample into three droplets, which were then combined with reagents for PT, aPTT or fibrinogen. The viscosity of these droplets, measured from the electrical impedance on a toaster-sized instrument, changes at a rate proportional to the amount of coagulation precursors present from which time/activity was calculated. Results Classification of samples into normal, intermediate or prolonged categories along with the respective times obtained from the DMF cartridges matched those obtained on the Stago Compact Max instrument (Figure). We also demonstrated separation of plasma from whole blood within the DMF cartridge using agglutinating reagents, enabling an easy-to-use workflow without the need for centrifugation. Conclusions Our preliminary results demonstrate that PT, aPTT and fibrinogen can be measured on a single cartridge with performance similar to comparator methods, with a time to result of &amp;lt;15 minutes. To our knowledge, this is the first time these 3 assays have been performed simultaneously on a single consumable and furthermore, this is the first time viscoelastic tests have been performed on a multifunctional instrument that also performs chemistry and molecular tests. Studies are underway to evaluate analytical and clinical performance.