High Plasma Fibrinogen Levels Research Articles

High Plasma Fibrinogen Level Elevates the Risk of Cardiac Complications Following Spontaneous Intracerebral Hemorrhage

Cardiac complications are related to poor prognosis after spontaneous intracerebral hemorrhage (ICH). This study aims to predict the cardiac complications arising from small intracranial hematoma at ultraearly stage. The data of this work were derived from the Risk Stratification and Minimally Invasive Surgery in Acute ICH Patients study (ClinicalTrials.gov Identifier: NCT03862729). This work included patients with ICH but without brain herniation, as confirmed by a brain computed tomography scan within 48hours of symptom onset. Every Patient's information recorded at the emergent department, including clinical, laboratory, electrocardiogram, and medical records, was derived from the electronic data capture. Cardiac complications were defined as the occurrence of myocardial damage, arrhythmias, and ischemic electrocardiogram changes during hospitalization. Variables associated with cardiac complications were filtrated by univariate and multivariate regression analyses. Independent risk factors were used to form the early predictive model. The restricted cubic splines were employed to investigate the nonlinear associations in a more sophisticated and scholarly manner. A total of 587 ICH patients were enrolled in this work, including 72 patients who suffered from cardiac complications after ICH. Out of the 78 variables, 24 were found to be statistically significant in the univariate logistic regression analysis. These significant variables were then subjected to multivariate logistic regression analysis and utilized for constructing risk models. Multivariate logistic regression analysis showed high plasma fibrinogen (FIB) level [odds ratio (OR) per standard deviation (SD) 1.327, 95% confidence intervals (CI) 1.037-1.697; P=0. 024)] and older age (OR per SD 1.777, 95% CI 1.344-2.349; P ＜0.001) were associated with a higher incidence of cardiac complications after ICH. High admission pulse rate (OR 0.620, 95% CI 0.451-0.853; P=0. 003) was considered a protective factor for cardiac complications after ICH. In the restricted cubic spline regression model, FIB and cardiac complications following ICH were positively correlated and almost linearly (P for nonlinearity=0.073). The reference point for FIB in predicting cardiac complications after ICH was 2.64g/L. Emergent factors, including plasma FIB level, age, and pulse rate, might be independently associated with cardiac complications after ICH, which warrants attention in the context of treatment.

Prognostic value of neutrophil-to-lymphocyte ratio and fibrinogen levels in ovarian cancer

BACKGROUND High neutrophil-to-lymphocyte ratio (NLR) and fibrinogen levels have been associated with mortality in several malignancies. However, the studies on the association between NLR or fibrinogen levels and ovarian cancer prognosis are inconsistent. This study aimed to investigate the prognostic roles of NLR and fibrinogen in ovarian cancer.
 METHODS A systematic search of electronic databases was performed to analyze studies on the association of pre-treatment NLR and fibrinogen levels with overall survival (OS) and progression-free survival (PFS) among patients with ovarian cancer. The hazard ratio (HR) and corresponding 95% confidence intervals [CIs] were analyzed. All statistical analyses were done using RevMan version 5.4 (Cochrane, United Kingdom).
 RESULTS A total of 7,312 patients from 27 studies were included. The median cut-off for high NLR was 3.6 for OS among 17 studies and 3.23 for PFS among 11 studies reporting an NLR HR. The median cut-off for fibrinogen levels was 4.0 in 9 studies reporting fibrinogen levels HR. High NLR was associated with lower OS (HR 1.35, 95% CI 1.18 to 1.55, p<0.0001, I2 = 76%) and PFS (HR 1.35, 95% CI 1.14 to 1.60, p = 0.0005, I2 = 71%). High fibrinogen levels were associated with lower OS (HR 1.44, 95% CI 1.14 to 1.82, p = 0.002, I2 = 81%) and PFS (HR 1.34, 95% CI 1.17 to 1.55, p<0.0001, I2 = 15%). This association occurred in all ovarian cancer types.
 CONCLUSIONS High pre-treatment NLR and plasma fibrinogen levels were related to poor OS and PFS in ovarian cancer.

Pre-operative Plasma Fibrinogen Level as a Potential Predictor of Pathological T3 Upstaging in Clinically Localized Renal Cell Carcinoma.

We investigated pre-operative factors for predicting pathological T3 (pT3) upstaging in clinical T1 renal cell carcinoma (RCC). We evaluated 181 patients with renal tumors suspected to be clinical T1 RCC. All patients had undergone a partial or radical nephrectomy. Pre-operative parameters, including patient characteristics, RENAL nephrometry score and blood tests were analyzed to determine factors predicting pT3 upstaging. Eight (4.4%) tumors were diagnosed as pT3. Large tumor diameter, less than 4 mm distance between the tumor and the renal collecting system and a high level of preoperative plasma fibrinogen were associated with pT3 stage. Multivariate analysis showed that a preoperative plasma fibrinogen level >330 mg/dl was a significant independent factor predicting upstage (p=0.041). Furthermore, among patients diagnosed with RCC (n=162), a preoperative plasma fibrinogen level >330 mg/dl was related to poor overall survival (p<0.001) and poor recurrence-free survival (p=0.002). A high preoperative plasma fibrinogen level may be a predictor of pT3 upstaging and may suggest the need for radical nephrectomy rather than partial nephrectomy because of the associated poor oncological outcomes.

Can fibrinogen level be a criterion in choosing the treatment option in patients with acute cholecystitis?

We aimed to investigate whether there is a relationship between blood fibrinogen levels during hospitalization of patients hospitalized for conservative treatment due to acute cholecystitis (AC) in our clinic. Patients underwent surgery and were discharged with medical treatment. The files of 118 patients who were hospitalized due to the diagnosis of AC and planned for conservative medical treatment in our clinic between January 2018 and February 2020 were recorded, prospectively. The patients were divided into two groups as those who responded to conservative treatment (Group 1), and those who were operated urgently despite conservative treatment (Group 2). Increase in gallbladder wall thickness, presence of pericholecystic fluid and hydrops sac on ultrasound and computed tomography (CT) were considered significant for the diagnosis of acute cholecystitis. Blood fibrinogen levels were measured in all patients during hospitalization. The mean age of 118 patients included in the study was 58.32 (19-96) years. There were 77 patients in Group 1 and 41 patients in Group 2. Serum fibrinogen level was found to be 298.34±111.7 mg/dl in Group 1 and 637±124.5 mg/dl in Group 2, and a statistically significant difference was found (p<0.001). When the cut-off value for the fibrinogen level was taken as 564.50 mg/dl, the sensitivity and specificity of the test were found to be 75.6% and 61%, respectively in showing surgical treatment. As a result of our study, we concluded that when the data obtained are evaluated, it should be kept in mind that despite medical treatment, there is an urgent need for an operation in patients with acute cholecystitis, and in patients with high plasma fibrinogen level (cut-off) at first admission.

Plasma Fibrinogen and Echocardiography as Diagnostic Tool for Left Ventricular Hypertrophy among CKD Patients

Background: Left ventricular hypertrophy is the most common cardiac event associated with chronic kidney disease. Aim: To detect LVH by echocardiography among CKD patients and co-relationship between plasma fibrinogen and left ventricular mass index. Study Design: Observational study. Methodology: It was an observational study with total of 62 CKD patients enrolled through convenience sampling. Patient’s age ranged from 35-65 years. Almost 3ml of blood was taken for measuring serum creatinine and fibrinogen. Blood was centrifuged for plasma separation than stored at -20°C. ECG findings were confirmed by echo in all enrolled patients. Data was evaluated by SPSS v.24. The results were presented as counts (percentage), means and standard deviation as appropriate. Spearman correlation was applied to check the correlation of variables. Results: Echo confirmed that LVH was found in 41 (66.1%) patients with systolic dysfunction. There was a high level of plasma fibrinogen in 73% of enrolled participants. No correlation between plasma fibrinogen and LVMI was found. Practical Implication: Current project helped health providers to diagnose cardiac event at an early stage among patients of kidney fail¬ure on echo findings along-with plasma fibrinogen levels thus the adverse outcomes could be prevented or delayed. Conclusion: It was concluded that echocardiography is a helpful diagnostic tool as it confirms ECG abnormalities seen in hospitalized CKD patients. All CKD patients should have their echocardiography done. Plasma fibrinogen levels were raised with declining renal function. Thus combination of both echo and fibrinogen levels among CKD are handful investigations for LVH. Keywords: Echocardiography, Chronic Kidney Disease, Left Ventricular Hypertrophy and Plasma Fibrinogen.

Can plasma fibrinogen level predict bone marrow fibrosis?

Objective: We aimed to assess the possible relationship between plasma fibrinogen level and bone marrow fibrosis (BMF) grades in&#x0D; patients who had undergone bone marrow (BM) biopsy for any reason.&#x0D; Patients and Method: This retrospective cohort study included 106 participants aged 18 years and over who had undergone&#x0D; simultaneous BM biopsy and circulatory fibrinogen level measurement during 2020 and 2021 at our center. BMF grade was measured&#x0D; by the modified Bauermeister grading system (MBGS). Participants were divided into two groups according to MBGS as those without&#x0D; BMF and those with BMF.&#x0D; Results: Fifty-eight male were included in our study, and the median age of the patients was 63 (range: 19-97) years. Fibrinogen&#x0D; (p=0.004) and lactate dehydrogenase (LDH) (p=0.030) levels were significantly higher in the fibrosis group. Multiple regression&#x0D; revealed that high fibrinogen (≥359) and high LDH (≥238) were independently associated with a higher likelihood of fibrosis presence&#x0D; (adjusted for age and sex); however, diagnostic analyses revealed low accuracy.&#x0D; Conclusion: High plasma fibrinogen and LDH levels were found to be independently associated with the presence of BMF. However,&#x0D; it was also evident that neither of these parameters could be used for diagnostic purposes.

494 Low plasma fibrinogen levels are associated with poor prognosis in cutaneous angiosarcoma of the head and neck

Angiosarcomas are malignant vascular tumors that account for 2% of all soft-tissue sarcomas. Due to the rarity of angiosarcomas, the prognostic factors are seldom reported. Here, we investigated plasma fibrinogen levels as a prognostic factor for angiosarcoma of the head and neck (ASHN). This retrospective study reviewed a cohort of patients histologically diagnosed with ASHN at Nagoya University Hospital between April 2006 and July 2019. The 22 patients with ASHN included in the present study. The cutoff value of plasma fibrinogen levels was determined to be 257 mg/dL. The Kaplan–Meier curve showed the OS rate to be significantly higher in the high plasma fibrinogen group than in the low plasma fibrinogen group (p=0.0027). The univariable model showed that patients with low plasma fibrinogen levels had a significantly poor OS [hazard ratio 6.78, 95% confidence interval 1.63 to 28.2, p-value of 0.008503]. Recently, high plasma fibrinogen levels were reported to predict poor prognosis in several malignancies. Unexpectedly, the present study suggests that low plasma fibrinogen levels predict poor prognosis. ASHN is an extremely hemorrhagic tumor. From repeated microbleeds and blood coagulation in ASHN lesions, plasma fibrinogen is considered to be consumed and to decrease in patients with ASHN. Therefore, we speculate that the reduced plasma fibrinogen levels might reflect tumor burden indirectly. In conclusion, the present study suggests that pre-treatment plasma fibrinogen levels are a useful prognostic factor for ASHN that may reflect tumor burden.

Higher Plasma Fibrinogen Level at Admission Is Associated with Post-Stroke Depression at Discharge.

Background: Post-stroke depression (PSD) is a common complication of stroke, which seriously affects the functional outcome of patients. Systemic low-grade inflammation associated with PSD has been shown to occur at several months to years, however, whether these inflammatory markers predicted PSD at an acute stage of stroke is controversial. Method: A total of 625 patients with acute ischemic stroke (219 female, 35.40%) were included in this study. PSD was diagnosed using the 17-item Hamilton depression scale (HAMD) at 7 days following discharge (7–14 days after stroke onset). Multivariable logistic regression analysis was applied to build a prediction model for PSD at discharge. Discrimination and calibration of the model were assessed by C-index, calibration plot. Internal validation was conducted using bootstrapping validation. Results: At discharge of hospitalization, 95 patients (15.20%) were diagnosed with PSD. Multivariable logistic regression suggested that female gender (OR = 2.043, 95% CI = 1.287–3.245, p = 0.002), baseline NIHSS (OR = 1.108, 95% CI = 1.055–1.165, p < 0.001) and fibrinogen (OR = 1.388, 95% CI = 1.129–1.706, p = 0.002) were independent predictors for PSD at discharge. The cut-off of the fibrinogen plasma level was 3.08 g/L. These predictors were included in the nomogram. The model displayed good discrimination, with a C-index of 0.730 (95% CI = 0.683–0.777) and good calibration. Conclusion: Female gender, baseline stroke severity and a higher level of fibrinogen were independently associated with PSD at discharge. A nomogram based on these three predictors can be used to provide an individual, visual prediction of the risk probability of PSD.

An Agreement Study Between Point-of-Care and Laboratory Activated Partial Thromboplastin Time for Anticoagulation Monitoring During Extracorporeal Membrane Oxygenation.

BackgroundLaboratory activated partial thromboplastin time (LAB-aPTT) is a widely used laboratory assay for monitoring unfractionated heparin (UFH) therapy during extracorporeal membrane oxygenation (ECMO). But LAB-aPTT is confined to a central laboratory, and the procedure is time-consuming. In comparison, point-of-care aPTT (POC-aPTT) is a convenient and quick assay, which might be a promising method for anticoagulation monitoring in ECMO. This study was aimed to evaluate the agreement between POC-aPTT (hemochron Jr. Signature instruments) and LAB-aPTT for anticoagulation monitoring in adult ECMO patients.MethodsData of ECMO-supported adult patients anticoagulated with UFH in our institute from January 2017 to December 2020 was retrospectively reviewed. POC-aPTT and LAB-aPTT results measured simultaneously were paired and included in the analysis. The correlation between POC-aPTT and LAB-aPTT was assessed using Spearman’s correlation coefficient. Bias between POC-aPTT and LAB-aPTT were described with the Bland-Altman method. Influence factors for bias were identified using multinomial logistic regression analysis.ResultsA total 286 pairs of aPTT results from 63 patients were included in the analysis. POC-aPTT and LAB-aPTT correlated weakly (r = 0.385, P < 0.001). The overall bias between POC-aPTT and LAB-aPTT was 7.78 [95%CI (−32.49, 48.05)] s. The overall bias between POC-aPTT and LAB-aPTT ratio (to normal value) was 0.54 [95%CI (−0.68, 1.76)]. A higher plasma fibrinogen level [OR 1.353 (1.057, 1.733), P = 0.017] was associated with a higher chance of POC-aPTT underestimating LAB-aPTT. While a lower plasma fibrinogen level [OR 0.809 (0.679, 0.963), P = 0.017] and lower UFH rate [OR 0.928 (0.868, 0.992), P = 0.029] were associated with a higher chance of POC-aPTT overestimating LAB-aPTT.ConclusionThe present study showed poor agreement between POC-aPTT and LAB-aPTT. POC-aPTT was not suitable for anticoagulation monitoring in adult ECMO patients.

Association of Plasma Fibrinogen and Insulin Resistance in Women with Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is thought to be developed as a consequence of high insulin resistance (IR). It has been proposed that IR may involve in the pathogenesis of hyperfibrinogenemia in GDM. This study was aimed to evaluate the plasma fibrinogen levels and its association with insulin resistance in GDM. This cross sectional study was performed with 44 GDM women and 44 pregnant women with normal glucose tolerance (NGT) at or after 24 weeks of their gestation. Glucose was measured by glucose oxidase method, fasting insulin was measured by chemiluminescent immunoassay and plasma fibrinogen was measured by STA-fibrinogen kit with an automated coagulation analyzer. GDM women had significantly increased age and higher BMI than pregnant women with NGT (p=0.008). Plasma fibrinogen level was significantly higher in GDM (p<0.001). Fasting insulin level and Homeostasis Model Assessment of Insulin Resistance [HOMA-IR] were also significantly higher in GDM (p<0.001). Fibrinogen showed positive correlation with fasting insulin level (r=0.470, p<0.001) as well as with HOMA-IR (r=0.470, p<0.001) in GDM. Using HOMA-IR at cut-off value 2.89, it was observed that a significant number of GDM women had higher HOMA-IR values than pregnant women with NGT (p=0.002) and GDM women with HOMA-IR values ≥2.89 had significantly higher fibrinogen values (p=0.002). Gestational diabetes mellitus is associated with higher plasma fibrinogen level and increased insulin resistance, indicating a state of hypercoagulability than that of pregnant women with normal glucose tolerance. There is a clear association between hyperfibrinogenemia and insulin resistance.

Hyperfibrinogenemia and Reduced Plasma Protein C Levels in HIV-Infected Patients

Background: Heamatological problems have been associated with human immunodeficiency virus infection. Hypercoagulability, in particular, thrombosis is becoming more common in HIV-positive patients. Aim: The goals of this study were to determine levels of plasma fibrinogen, protein C, Hemoglobin, and ESR among Sudanese HIV-positive patients. Materials and Methods: This is a case-control study, for this investigation, a total of 100 participants were recruited for this study. Fifty people were diagnosed with HIV, 25 of whom were males (50 percent) and 25 of whom were females (50 percent), with an average age of 35.5 years. Further fifty healthy people, 26 (52%) of whom were men and 24 (48%) of whom were women, with a mean age of 37.1 years, matched the case group. Fresh Poor Plasma was obtained by centrifuging citrated venous blood samples at 3000 rpm for 15 minutes. The fibrinogen level was determined using an automated coagulation analyzer. Total protein C level was measured by a fully-automated blood coagulation analyzer (SYSMEX CA-500’JAPAN). The haemoglobin parameter was measured from EDTA anticoagulant samples using the Sysmex KX 21-N automated haematological analyzer. In one hour, the ESR was done using a Westergren tube. Data was collected using a structured direct questionnaire. SPSS version 21 was used to analyse the data. Results: The current study discovered that in Sudanese HIV infection, the mean and standard deviation of plasma fibrinogen levels were statistically substantially higher than in the normal control group (370.5 ± 67 vs 214.7 ± 21 with P value 0.001). Protein C levels were statistically significantly lower in HIV positive patients compared with control group (0.6 ± 0.1 vs 1.3 ± 0.2 with P value 0.001). In HIV positive patients, haemoglobin was statistically substantially lower than in healthy people (10.8 ± 1.8 vs 13.7 ± 1.9, P value 0.01). The erythrocyte sedimentation rate was statistically significantly higher in HIV positive patients than in the control group, with (58.00 ± 27 vs 7.68 ± 3 with P value 0.00). Conclusions: HIV infected patients had higher plasma fibrinogen levels and lower haemoglobin levels than normal healthy control groups. In 16 percent of HIV positive patients, protein C deficiency was discovered. HIV-positive patients had significantly greater ESR.

Are elevated plasma fibrinogen associated with lung function? An 8-year follow-up of the ELSA study.

Fibrinogen is an important biomarker of inflammation, but findings from longitudinal studies that correlated fibrinogen with lung function in older adults are inconsistent. To investigate the relationship between fibrinogen plasma levels and lung function impairment later in life. Longitudinal analysis of 2,150 participants of the English Longitudinal Study of Ageing (ELSA) aged 50 years and older. Associations between changes in plasma fibrinogen between waves 2 (2004-05) and 4 (2008-09) and lung function in wave 6 (2012-13) were performed using multiple linear regression adjusted by potential confounders. Regarding the fibrinogen profile, 18.5% of the participants presented higher levels in both waves. In the adjusted models, the maintenance of high fibrinogen levels was associated with a significant reduction of lung function only for men. FEV1 showed a reduction of 0.17L, FVC of 0.22L, and the percentages predicted were 5.16% for FEV1 and 6.21% for FVC compared to those that maintained normal levels of fibrinogen. To the best of our knowledge, this was the first study investigating the relationship between changes in fibrinogen levels over a long follow-up period and lung function in older adults without pre-existing chronic diseases. ELSA has information on critical demographic and clinical parameters, which allowed to adjust for potential confounding factors. It was found that the persistence of high levels of plasma fibrinogen in older English men, but not women, is associated with lung function decline. Therefore, plasma fibrinogen showed to be an important biomarker of pulmonary dysfunction in this population.

Low FXIII activity levels in intensive care unit hospitalized COVID-19 patients

BackgroundCOVID-19 infection is associated with a hypercoagulable state. Severe COVID-19 patients present with high plasma fibrinogen levels, continuous deposition of fibrin and the presence of microthrombi in their lungs, accompanied by significant fibrinolysis, resulting in high D-dimer levels. Due to the role of FXIII in fibrin crosslinking and clot stabilization, we analyzed its activity levels and dynamics in COVID-19 patients hospitalized in the intensive care unit (ICU).MethodsFXIII levels were measured in thirty four COVID-19 patients hospitalized in the ICU and in fourteen non-severe COVID-19 patients. FVIII levels were measured for comparison. Laboratory data and clinical variables were recorded.ResultsThe average FXIII activity level in 34 ICU hospitalized COVID-19 patients was 69.9±33 %, significantly lower compared to an average of 120±20.9 % FXIII activity in 14 non-severe COVID-19 patients. FXIII activity levels were below the low normal value (< 79 % FXIII activity) in 74 % of the ICU hospitalized COVID-19 patients. In contrast, high FVIII activity was measured among all severe COVID-19 patients. Consecutive measurements, performed in fourteen ICU hospitalized COVID-19 patients, pointed to a significant decrease in FXIII activity from the average of 85.7±28.2 %, (which is in the normal range), to an average of 68.0±20.4 %, below the low normal range, within 6.4±3.4 days of ICU hospitalization. Liver functions did not differentiate between patients with low and normal FXIII activity. No inhibitor to FXIII activity was found in the plasma of severe COVID-19 patients. Levels of FXIII-A antigen correlated with FXIII activity, and were low in severe COVID-19 patients.ConclusionsLow FXIII activity levels were found in COVID-19 patients hospitalized in the ICU, with gradual decline during their hospitalization. A mechanism of consumption may account for the low FXIII activity in these patients.

Plasma fibrinogen, d-dimer, and fibrin degradation product as biomarkers of rheumatoid arthritis

This study aimed to assess the association of coagulation-related indicators such as plasma fibrinogen (FIB), d-dimer, and fibrin degradation product (FDP) in rheumatoid arthritis (RA) with the disease activity. Data from 105 RA patients and 102 age- and gender-matched healthy controls were collected in the retrospective study. Disease activity score in 28 joints based on C-reactive protein (DAS28-CRP) was used to divide RA patients into low activity group (DAS28-CRP ≤ 2.7) and active group (DAS28-CRP > 2.7). Receiver operating characteristic (ROC) curve was applied to determine area under the curve (AUC). The association between plasma FIB, d-dimer, and FDP and DAS28-CRP was evaluated by spearman correlation. Logistical regression analysis was used to identify the independent variables associated with RA disease activity. RA patients showed higher levels of plasma FIB, d-dimer, and FDP than the controls (P < 0.01). Plasma FIB, d-dimer, and FDP were also increased in active groups of RA patients than those in inactive groups (P < 0.001). ROC curve analyses revealed that the AUC of d-dimer was higher than erythrocyte sedimentation rate (ESR) and rheumatoid factor (RF), and that of FDP was higher than RF in RA patients. In addition, the optimal cut-off value of plasma FIB, d-dimer, and FDP for RA diagnosis was 286 mg/dL, 470 μg/L, and 1.45 mg/L, respectively. Spearman analysis showed that plasma FIB, d-dimer, and FDP were positively related with DAS28-CRP (P < 0.001) in RA patients. Logistical regression analysis showed that d-dimer (odds ratio 2.862, 95% confidence interval 1.851–5.426, P < 0.001) was an independent variable associated with RA disease activity. FIB, d-dimer, and FDP were increased in RA patients and positively correlated with the disease activity of RA. d-dimer may act as a novel inflammatory indice for indicating disease activity in RA patients.

Low plasma fibrinogen levels are associated with poor prognosis in cutaneous angiosarcoma of the head and neck

Angiosarcoma of the head and neck (ASHN) is one of the most aggressive malignancies of the skin, but the prognostic factors are not well known because of its rarity. Recently, high plasma fibrinogen levels were reported to predict poor prognosis in several malignancies. In the present retrospective study, we suggest that low plasma fibrinogen levels predict poor prognosis for ASHN.

Role of fibrinogen–erythrocyte and erythrocyte–erythrocyte adhesion on cardiovascular pathologies

Cardiovascular pathologies are the major cause of death worldwide. Erythrocyte aggregation is an indicator of cardiovascular risk, which is influenced by high plasma fibrinogen levels. Our main goals were to understand how fibrinogen–erythrocyte binding influences erythrocyte aggregation and how it constitutes a cardiovascular risk factor in essential arterial hypertension (EAH) and chronic heart failure (CHF). Differences on cell stiffness, protein-cell interaction and cell–cell adhesion forces were evaluated by AFM-based force spectroscopy with cells from 31 EAH patients, 30 CHF patients and 15 healthy blood donors. The main procedures used were previously described by us [1–3]. Results were correlated with patients’ clinical profiles. From cell–cell adhesion studies, we concluded that, upon increasing fibrinogen concentration (from 0 to 1 mg/mL), there was an increase in the work and force necessary for erythrocyte–erythrocyte detachment on EAH patients and healthy donors. Nevertheless, higher values from both parameters were obtained for EAH patients, when comparing to healthy donors, at each fibrinogen concentration [4]. Fibrinogen-erythrocyte (un)binding forces were higher in EAH and in CHF patients, when compared with the control group, despite a lower binding frequency [5,6]. Ischaemic CHF patients showed increased binding forces compared to non-ischaemic patients. A 12-month clinical follow-up shows that CHF patients with higher fibrinogen–erythrocyte binding forces, probed by AFM at the beginning of the assessment, had a significantly higher probability of being hospitalised due to cardiovascular complications, pointing out the value of AFM for clinical prognosis [5]. Erythrocyte stiffness studies revealed differences between patients and healthy donors, in terms of erythrocyte elasticity (Young’s modulus) and AFM tip penetration depth into the cells [5,6]. Erythrocytes from non-ischaemic CHF patients presented a higher average stiffness than those from the other groups (ischaemic CHF and control). Nevertheless, a significantly higher cell penetration depth at the same applied force was observed for ischaemic CHF patients [5]. In conclusion, fibrinogen promotes erythrocyte adhesion, leading to its aggregation, probably by transient simultaneous binding of the protein to two cells, bridging them. Our results may be relevant for potential future drug interventions to reduce aggregation and enhance microcirculatory flow conditions in cardiovascular patients.

Fibrinogen is an Independent Risk Factor for White Matter Hyperintensities in CADASIL but not in Sporadic Cerebral Small Vessel Disease Patients.

The relationship between fibrinogen and white matter hyperintensities (WMHs) are inconsistent. Whether there are different relationships between WMHs and fibrinogen in disparate subtypes of cerebral small vessel disease (CSVD) remains unknown. Here, we investigated the roles of plasma fibrinogen in sporadic CSVD (sCSVD) and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) patients. We performed a cross-sectional study that included 74 CSVD patients (19 CADASIL and 55 sporadic) and 74 age- and gender-matched healthy controls (HCs). Plasma fibrinogen was determined, and the severity of WMHs in CSVD patients was rated according to Fazekas scales. Univariate analysis and ordinal logistic regression were performed to evaluate the relationship between fibrinogen and the severity of WMHs in CSVD. Both CADASIL and sCSVD patients showed significantly higher plasma fibrinogen levels than HCs. No significant difference in the plasma fibrinogen level was observed between CADASIL and sCSVD. Univariate analysis and ordinal logistic regression indicated that fibrinogen is an independent risk factor for the severity of WMHs in CADASIL patients (odds ratio [OR] =1.064; 95% Confidence interval (CI, 1.004-1.127); p =0.037). However, age (odds ratio [OR] =1.093; 95% CI (1.033-1.156); P = 0.002), but not fibrinogen (odds ratio [OR] =1.004; 95% CI (0.997-1.011); P=0.262), is an independent risk factor for the severity of WMHs in sCSVD patients. Our results suggest that high levels of plasma fibrinogen are associated with the severity of WMHs in CADASIL but not in sCSVD patients, indicating that the role of fibrinogen may be different in disparate subtypes of CSVD. A better understanding of fibrinogen may yield insights into the pathogenesis of CSVD.

Fibrinogen Levels and Cognitive Profile Differences in Patients with Mild Cognitive Impairment

Background: Fibrinogen is considered a marker of vascular pathology, indicating a weakened blood-brain barrier, and has a causative role in neuroinflammation and neurodegeneration. Little is known about the relationship between fibrinogen levels and cognitive function in patients with mild cognitive impairment (MCI). We aimed to investigate differences in cognitive profiles according to plasma fibrinogen levels in patients with MCI and the influence of plasma fibrinogen levels on cognitive decline. Methods: This retrospective cohort study included 643 patients with MCI: 323 patients in the high fibrinogen (high fib) group and 320 patients in the low fibrinogen (low fib) group. A multiple linear regression model was performed to compare cognitive test performance between groups. The Cox proportional hazard model was used to analyze the hazard ratio of fibrinogen level for disease progression. Results: The high fib group demonstrated poorer performance in attention, executive function, and confrontation naming than the low fib group. After adjustment for APOE genotype, the high fib group was associated with poor attention and executive function. After adjustment for vascular risk factors including body mass index, hypertension, diabetes mellitus, dyslipidemia, and smoking history, the high fib group showed declined attention and confrontation naming ability. High fibrinogen levels did not predict disease progression to CDR 1. Conclusion: High plasma fibrinogen levels were associated with poor performance in attention in patients with MCI, regardless of APOE genotype or vascular risk factors.

Plasma Fibrinogen Predicts the Prognosis of Bladder Cancer Patients After Radical Cystectomy.

BackgroundThis study aimed to determine the potential utility of plasma fibrinogen as a prognostic factor in patients with bladder cancer (BCa) after radical cystectomy (RC).MethodsPatients with BCa who underwent RC from 2014 to 2019 were analyzed retrospectively. The indexes of plasma coagulation and fibrinolysis system factors were collected. Kaplan–Meier survival curves were used to calculate the overall survival (OS) and disease-free survival (DFS). The prognostic value of plasma fibrinogen was analyzed by using Cox regression model, and a nomogram of BCa based on plasma fibrinogen was generated by R software.ResultsAmong 145 patients, the optimal cut-off value of plasma fibrinogen was 3.14g/L. High level of plasma fibrinogen was related to the poor prognosis of patients with BCa, and plasma fibrinogen has a more accurate prognostic ability than other plasma coagulation and fibrinolysis system factors. Multivariate Cox regression analysis showed that plasma fibrinogen was an independent predictor of OS (>3.14 vs ≤3.14 HR, 2.58, 95% CI = 1.28–5.23; p = 0.008) and DFS (>3.14 vs ≤3.14 HR, 2.60, 95% CI = 1.20–5.65; p = 0.016), and the nomogram based on plasma fibrinogen had better accuracy and discrimination (area under the curve (AUC): OS = 0.741, DFS = 0.733).ConclusionPlasma fibrinogen can be used as an independent predictor of OS and DFS for RC patients, and the nomogram based on plasma fibrinogen was a reliable model for predicting the prognosis after RC.

Inference from longitudinal laboratory tests characterizes temporal evolution of COVID-19-associated coagulopathy (CAC).

Temporal inference from laboratory testing results and triangulation with clinical outcomes extracted from unstructured electronic health record (EHR) provider notes is integral to advancing precision medicine. Here, we studied 246 SARS-CoV-2 PCR-positive (COVIDpos) patients and propensity-matched 2460 SARS-CoV-2 PCR-negative (COVIDneg) patients subjected to around 700,000 lab tests cumulatively across 194 assays. Compared to COVIDneg patients at the time of diagnostic testing, COVIDpos patients tended to have higher plasma fibrinogen levels and lower platelet counts. However, as the infection evolves, COVIDpos patients distinctively show declining fibrinogen, increasing platelet counts, and lower white blood cell counts. Augmented curation of EHRs suggests that only a minority of COVIDpos patients develop thromboembolism, and rarely, disseminated intravascular coagulopathy (DIC), with patients generally not displaying platelet reductions typical of consumptive coagulopathies. These temporal trends provide fine-grained resolution into COVID-19 associated coagulopathy (CAC) and set the stage for personalizing thromboprophylaxis.