Fibrinogen Levels Research Articles

Association of clonal haematopoiesis with recurrent venous thromboembolism: A case-control study.

Venous thromboembolism (VTE) is the third most common cardiovascular disease. Clonal haematopoiesis (CH) is linked to cardiovascular disease risk, but its potential association with VTE remains poorly understood. We assessed the prevalence of CH in patients with recurrent VTE (n = 107; median age [IQR] 57 [48-63] years, 44.9% female) and matched healthy controls (n = 127; median age [IQR] 53 [45-60] years, 51.2% female) to investigate a putative association of CH with VTE risk. We detected 12 CH-associated mutations in 11 (10.3%) VTE cases and six mutations in 5 (3.9%) controls. Thus, patients with recurrent VTE tended to have higher odds of presenting with CH compared to controls (OR: 2.74, 95% CI: 0.95-9.16). Moreover, the odds of detecting CH were significantly higher in VTE cases in the subgroup of individuals without thrombophilia (OR: 4.58, 95% CI: 1.48-15.99). VTE cases with CH showed elevated platelet counts compared to cases and controls without CH (median [IQR]: 292 [254-298], 223 [198-260] and 220 [185-259] × 109/L; both p < 0.01). Fibrinogen, sP-selectin, D-dimer and hsCRP levels did not differ according to CH status. Overall, we identified a trend for an association between CH and recurrent VTE, particularly in individuals without underlying thrombophilia, warranting further research in this patient group.

Biological Variation of Hemostasis Analytes in Atrial Fibrillation Patients Using Dabigatran.

Analytical criteria for laboratory analysis based on biological variation are considered state-of-the-art. While biological variance should ideally be measured in patient populations for whom the tests are relevant, data are mostly only available from healthy individuals. We determined the biological variance of activated partial thromboplasmin time (APTT), prothrombin time (PT), fibrinogen, and trough dabigatran levels in patients with atrial fibrillation (AF) who were treated with dabigatran. Between 2019 and 2022, patients with AF treated >3 months with dabigatran were included. Blood was collected monthly up to 10 times for the measurement of APTT, PT, fibrinogen, and trough dabigatran levels. Between-subject variance (CVG), within-subject variance (CVI), and analytical variance (CVA) were calculated. Eighteen participants (median age 65.8 years, 22.2% women) were included, with 130 samples in total. For APTT, the CVG was 11.5%, the CVI 8.8%, and the CVA 1.1%. For PT, these values were 5.2%, 4.0%, and 1.0% and for fibrinogen 13.6%, 11.8%, and 1.6%, respectively. For the dabigatran levels, the percentages were 37.9%, 33.0%, and 3.4%, respectively. We assessed the biological variance of APTT, PT, fibrinogen, and dabigatran in a patient population with long-term dabigatran use. The analytical performances of coagulation laboratory tests in patients with AF treated with dabigatran were comparable to those in healthy volunteers.CCMO Registration Number: NL67304.078.18.

The Impact of Inflammatory Markers and Obesity in Chronic Venous Disease.

Background: Chronic venous disease (CVD) represents a significant health challenge, particularly in obese individuals. This study focuses on the interplay between inflammation, obesity, and CVD, by analyzing the role of inflammatory markers in the disease progression. Methods: Clinical and paraclinical data of 619 patients hospitalized and treated in the Phlebology Department (1stSurgical Department, "Pius Brînzeu" Emergency County Hospital Timișoara, Romania) between 2018 and 2024 were analyzed. Results: The statistical analysis revealed that age, C-reactive protein (CRP), fibrinogen, and absolute neutrophil count (ANC) were key predictors of CVD progression. Specifically, elevated CRP and fibrinogen levels correlated strongly with increased CVD severity, particularly in patients with higher body-mass index (BMI). BMI, while not an independent predictor, contributed indirectly to the disease severity through its association with these inflammatory markers. The logistic regression model incorporating age, BMI, CRP, fibrinogen, and ANC demonstrated a high predictive accuracy, with an area under the curve (AUC) of 0.902, highlighting the models reliability in stratifying patients at risk for severe CVD. Conclusions: This predictive model not only aids in identifying high-risk patients but also reinforces inflammation as a critical therapeutic target in CVD management.

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.

Clinical and Epidemiological Features of Pediatric COVID-19: A Retrospective Study.

There is a demand for additional data regarding the impact of coronavirus disease 2019 (COVID-19) on the pediatric population. This study sought to determine the clinical and epidemiological features of pediatric COVID-19 in Iran. A retrospective study was performed to assess medical records of children with COVID-19 admitted to Abuzar Hospital in Ahvaz (Iran). Their clinical and demographic data were recorded. In this study, 600 medical records of pediatric COVID-19 patients were evaluated. Over 50% of them were boys. Mild, moderate, and severe manifestations of COVID-19 were identified in 250, 200, and 150 children, respectively. Patients with severe or moderate COVID-19 had substantially higher levels of various inflammatory markers (C-reactive protein (CRP), fibrinogen, and d-dimer), alanine transaminase (ALT), creatine kinase (CPK), blood urea nitrogen (BUN), neutrophils, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatinine (Cr), bilirubin, and gamma-glutamyl transferase (GGT) compared to children with mild COVID-19 (p < 0.001); they also had lower levels of lymphocytes, hemoglobin (Hb), and vitamin D than patients with mild COVID-19 (p < 0.001). In addition, children with severe or moderate COVID-19 had a notably higher incidence of fever or dry cough and longer hospital stays than those with mild COVID-19 (p < 0.001). The prevalence of malnutrition and anemia in patients was 50.6% and 31.5%, respectively. A significant proportion of children who were underweight and stunted experienced moderate to severe COVID-19. Furthermore, there was a considerably higher prevalence of malnutrition, anemia, and vitamin D insufficiency, or deficiency in children with moderate-to-severe COVID-19 compared to patients with mild COVID-19 (p < 0.001). The outcomes of this study revealed a significantly higher prevalence of malnutrition, anemia, vitamin D insufficiency or deficiency, elevated liver and kidney function test results, and increased inflammatory markers in children with moderate to severe COVID-19 compared to those with mild COVID-19.

High-dose atorvastatin and rosuvastatin reduce the levels of neutrophil extracellular trap-related proteins in coronary artery disease: association with prothrombotic state.

Neutrophil extracellular trap (NET) formation is involved in atherothrombosis. We sought to investigate whether statins affect neutrophil extracellular traps activation and release (NETosis) in coronary artery disease (CAD), and whether such changes show associations with statin‑induced additional effects. We studied 130 patients with advanced CAD before and at least 6 months after initiation of high‑dose statin therapy with rosuvastatin 40 mg/d or atorvastatin 80 mg/d. The levels of circulating citrullinated histone H3 (H3cit), myeloperoxidase (MPO), and neutrophil elastase (NE) were assessed as proteins associated with NETosis along with thrombin generation, plasma clot permeability (Ks), clot lysis time (CLT), and fibrinolysis inhibitors. Following statin therapy intensification, we observed reduced accumulation of H3cit (-30.4%), MPO (-28.1%), and NE (-25.5%; all P <0.001), all not associated with low‑density lipoprotein cholesterol (LDL‑C) lowering (-25%). However, H3cit level was lower in 50 patients (38.5%) who achieved the target LDL‑C below 1.8 mmol/l (-16.5%; P = 0.004), and in 19 patients (14.6%) with LDL‑C below 1.4 mmol/l (-25.5%; P = 0.001), as compared with the remaining individuals. The reductions in H3cit and MPO levels were associated with a 42.9% decrease in C‑reactive protein (CRP) level on high‑dose statins (R = 0.855; P <0.001 and R = 0.25; P = 0.004, respectively), along with increases in Ks and reduction in thrombin activatable fibrinolysis inhibitor (TAFI) activity, but not with CLT or thrombin generation (all |R|, 0.24-0.4; P <0.01). In multivariable analysis, changes in CRP (β = 0.771; P <0.001), TAFI activity (β = 0.125; P = 0.013), and fibrinogen level (β = 0.106; P = 0.034) were independently associated with a decrease in H3cit concentration. We showed for the first time that high‑dose statins can reduce the level of NET‑related proteins in association with anti‑inflammatory and antithrombotic actions in CAD patients.

Identification of fibrinogen as a plasma protein binding partner for lecanemab biosimilar IgG.

Recombinant monoclonal therapeutic antibodies like lecanemab, which target amyloid beta in Alzheimer's disease, offer a promising approach for modifying the disease progression. Due to its relatively short half-life, lecanemab administered as a bi-monthly infusion (typically 10 mg/kg) has a relatively brief half-life. Interaction with abundant plasma proteins binder in the bloodstream can affect pharmacokinetics of drugs, including their half-life. In this study, we investigated potential plasma protein binding (PPB) interaction to lecanemab using lecanemab biosimilar. Lecanemab biosimilar used in this study was based on publicly available sequences. ELISA and western blotting were used to assess lecanemab biosimilar immunoreactivity in the fractions of human plasma obtained through size exclusion chromatography. The binding of lecanemab biosimilar to candidate plasma binders was confirmed by western blotting, ELISA, and surface plasmon resonance analysis. Using a combination of equilibrium dialysis, ELISA, and western blotting in human plasma, we first describe the presence of likely PPB partners to lecanemab biosimilar and then identify fibrinogen as one of them. Utilizing surface plasmon resonance, we confirmed that lecanemab biosimilar does bind to fibrinogen, although with lower affinity than to monomeric amyloid beta. In the context of lecanemab therapy, these results imply that fibrinogen levels could impact the levels of free antibodies in the bloodstream and that fibrinogen might serve as a reservoir for lecanemab. More broadly, these results indicate that PPB may be an important consideration when clinically utilizing therapeutic antibodies in neurodegenerative disease.

Dual guided heparin monitoring with anti-Xa and APTT during micro-axial flow pump support for cardiogenic shock

Abstract Background Precise management of unfractionated heparin (UFH) is key to avoid coagulopathic complications in patients on percutaneous mechanical circulatory support (pMCS) for cardiogenic shock (CS). While the activated partial thromboplastin time (APTT) is commonly used for this purpose, it can be affected by various laboratory factors during critical illness. Alternatively, the anti-Xa test directly measures UFH activity. We proposed a parallel anti-Xa/APTT-based protocol for UFH titration during pMCS. (1) Purpose We aimed to investigate the correlation between parallel anti-Xa/APTT measurements in a CS population on pMCS. We also evaluated mortality correlation in samples exhibiting prolonged APTT and in-range anti-Xa levels, based on fibrinogen levels and INR. Methods We assessed all CS patients with isolated left-sided ImpellaTM-support (&amp;gt;24h) and UFH anticoagulation monitoring per protocol at two pMCS-institutions from April-2017 to June-2022. Overall correlation between parallel anti-Xa/APTT samples was assessed by Pearson correlation coefficient (with ≤0.7 considered to confer a weak correlation). Anti-Xa levels were defined as 0.20-0.30IU/mL or 0.31-0.50IU/mL, with corresponding APTT values of 40-55s and 55-80s, respectively. Samples with prolonged APTT as compared to the in-range anti-Xa were stratified based on fibrinogen (&amp;lt;1.5g/dL or ≥ 1.5g/dL) and INR (&amp;lt;1.5 or ≥1.5) on the same day as the index sample. Mortality of patients with normal fibrinogen ànd INR was then compared to those with abnormal fibrinogen and/or INR via a Chi² test. Results Ninety-three ImpellaTM-runs (77 men, 83%) with a median age of 56 years (IQR 46-66) were analyzed. Median support was 6 days (IQR 4-12). In 2447 parallel anti-Xa/APTT samples, the Pearson correlation coefficient was 0.50 (p&amp;lt;0.001). Among the 1914 in-range anti-Xa samples, APPT was shortened in 460 (24%), in-range in 986 (52%) and prolonged in 468 (24%) samples. In the 59 patients with samples with prolonged APTT, two patients (with 80 samples) were excluded due to absence of fibrinogen and/or INR measurements on the same day. The mortality in patients with prolonged APTT but normal fibrinogen levels and normal INR (N=29; APTT prolongation due to FXI/FXII-consumption) was significantly lower compared to the remaining 28 patients who showed samples with reduced fibrinogen levels and/or prolonged INR (suffering from concomitant conditions) (10% vs. 32%; p=0.043). Conclusion We highlight a weak correlation between anti-Xa and APTT in an anti-Xa guided UFH anticoagulated CS population during left-sided ImpellaTM support. Patients with APTT-prolongation due to concomitant conditions with INR prolongation and/or fibrinogen shortage are at highest mortality risk. The APTT/Anti-Xa coefficient can serve as an independent risk factor whilst managing critically CS patients.

Thrombin generation, fibrin clot permeation and lysis in patients with severe mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair: mitral fibrin study

Abstract Background/Introduction The management of heart failure (HF), particularly in the context of reduced ejection fraction, is further complicated by an increased risk of thromboembolic events. Structural alterations of both left ventricle and mitral valve contribute to mitral regurgitation (MR). However, the body of evidence provides inconclusive insights into the relationship between MR and thromboembolic risk. Purpose This study aimed to investigate the impact of transcatheter edge-to-edge repair (TEER) on thrombin generation, clot permeation and clot lysis time in HF patients with severe MR eligible for mitral TEER. Methods A cohort of 31 HF patients with severe MR undergoing TEER underwent systematic evaluation at three time points. Coagulation parameters, including fibrinogen concentration, thrombin generation, fibrin clot permeability (Ks), and clot lysis time (CLT), were assessed. Comprehensive evaluations also covered echocardiographic, laboratory, and clinical parameters. Results TEER induced changes in fibrinogen levels (p=0.009, visit 3 vs. visit 2) and improved fibrin clot properties over a 50-day follow-up (Ks, p=0.005, visit 3 vs. visit 2). No significant differences were observed among time points in analyzed blood clot parameters. Linear regression, incorporating thrombin generation variables, Ks, and CLT for delta NT-proBNP, highlighted CLT as the sole predictor of NT-proBNP change between visit 2 and visit 1 (p=0.03; R2=0.18). Conclusions MR reduction through TEER led to transient alterations in fibrinogen concentration and improved fibrin clot characteristics. Additionally, baseline CLT emerged as a significant predictor of early NT-proBNP reduction, emphasizing its role as a key indicator of the hemodynamic response to TEER.

Clinical characteristics and outcomes of patients presenting with acute coronary syndromes and suspected plaque erosion

Abstract Background Plaque erosion (PE) is the second most common pathology of acute coronary events after plaque rupture. PE is characterized by endothelial denudation and formation of neutrophil extracellular traps. Patients with PE may have a different prognosis as compared to those with plaque rupture. Specific clinical and laboratory predictors were validated to suspect PE among acute coronary syndrome (ACS) patients. Purpose The objectives of this study were to compare both clinical and laboratory findings, and outcomes of ACS patients with high probability of PE and those with less likely PE. Methods Six hundred ninety-six ACS patients were divided into two groups (suspected PE vs less likely PE) based on 5 reported predictors of PE. The predictors were: age &amp;lt;68, anterior ischemia, no diabetes mellitus, hemoglobin &amp;gt;15 g/dL and normal renal function (eGFR&amp;gt; 60 ml/min) as assessed at hospital admission. Patients with 4 or 5 of these 5 predictors were included in the suspected PE group, while patients with 0 or 1 entered less likely PE group. Baseline clinical features and laboratory analyses at hospital admission were compared between the two groups. Major adverse cardiac events (MACE), defined as death from any cause, non-fatal myocardial infarction or unplanned revascularization, were compared between the two groups at 20 months after hospital discharge. Results Among 696 patients, 283 (41%) composed the suspected PE group, while 413 (59%) entered into less likely PE group. The suspected PE group had a higher prevalence of current smokers and had a higher BMI. They showed higher values of both LDL cholesterol and triglycerides, while C-reactive protein and fibrinogen levels were significantly lower. The suspected PE group showed a higher frequency of single vessel disease (Table). The suspected PE group showed a significantly lower rate of MACEs at 20 months (7.4% vs 28.8%, p=0.0001) as well as death from any cause was significantly lower (2.1% vs 24.9%, p=0.0001). The median time from the index ACS episode to recurrent myocardial infarction or unplanned coronary revascularization tended to be longer in the suspected PE group as compared to the less likely PE group (15 months [9-20] vs 9 months [6-13], p=0.062) (Figure). Conclusions In a cohort of ACS population, the suspected PE group showed distinctive clinical characteristics with less coronary plaque burden and low grade of systemic inflammation. The suspected PE group had a better prognosis at 20-month follow-up time with a significantly lower rate of death from any cause, and non-fatal coronary events tended to occur later.Table.Baseline characteristicsFigure.Non fatal coronary events

Exercise-induced inflammatory and thrombotic acute phase response in hypertensive patients

Abstract Background/Introduction Vigorous physical activity may acutely trigger the onset of an acute coronary syndrome especially in sedentary persons with established cardiovascular risk factors such as arterial hypertension. The rupture of an inflamed coronary plaque and the activation of the coagulation cascade are the main underlying mechanisms. Purpose The present study aimed to determine the effect of acute exercise on the inflammatory and thrombotic response in patients with arterial hypertension as compared to normotensive peers. Methods After excluding patients with any inflammatory or/and coronary artery disease, a total of 60 non-treated hypertensive patients and 65 normotensive individuals underwent a maximal treadmill exercise testing. Βlood samples were drawn at rest and immediately after peak exercise. High-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), white blood cell (WBC), interleukin-6 (IL-6), and total fibrinogen (TF) levels, as well as plasminogen activator inhibitor-1 (PAI-1) activity were measured. Results All biomarkers increased with exercise, except PAI-1, which decreased (P&amp;lt;0.05 for the change between resting and peak exercise for all biomarkers). The normotensive group had less marked (P&amp;lt;0.05) exercise-induced changes than the hypertensive group in hsCRP (7.7 vs. 8.6%), SAA (5.6 vs. 11.9%), WBC (45.0 vs. 51.7%), and PAI-1 (-17.3 vs. -20.1%) and a similar (P=NS) change in IL-6 (23.8 vs. 23.0%) and TF (8.5 vs. 8.5%) (see also Figure). Conclusion(s) In conclusion, the exercise-induced inflammatory and thrombotic acute phase response seems to be more pronounced in non-treated hypertensive patients than in normotensive controls. The effect of blood-pressure lowering treatment on the exercise-induced acute phase response remains to be elucidated.Figure

Markers of coagulation and early coronary stent thrombosis

Abstract Background Acute stent thrombosis is a rare but deleterious event after percutaneous coronary intervention (PCI). Hemostatic factors such as D-Dimer, fibrinogen, and platelet count have emerged as potential indicators of increased thrombotic risk. However, data regarding the association with early stent thrombosis (ST) is sparse. Purpose The aim of this study was to investigate whether markers of coagulation are associated with increased risk of early (&amp;lt; 30 days after PCI) ST. Methods Within a prospective single-center registry, we retrospectively analyzed the association between pre-procedural platelet count, plasma levels of fibrinogen and D-Dimer with the occurrence of early ST within 30 days after PCI. Results We included 10,714 consecutive patients who underwent percutaneous coronary intervention (PCI) with implantation of drug-eluting stents (DES). Pre-procedural measurements of platelet count, fibrinogen and D-Dimer was available in 6,337, 6,155 and 956 patients, respectively. The number of definite early ST within 30 days was 58 (0.92 %). Pre-procedural platelet count (p&amp;lt;0.05) and plasma levels of fibrinogen (p&amp;lt;0.05) were significantly higher in patients with early ST as compared to patients without ST. Whereas D-Dimer was not associated with early ST, patients in the fifth quintile of platelet count had a significant increased risk for early ST (HR 2.43; 95% CI 1.43 - 4.14; p=0.001) as compared to patients in the lower four quintiles and patients in the fifth quintile of fibrinogen had a significant increased risk for early ST (HR 1.86; 95% CI 1.07 – 3.26; p&amp;lt;0.05) as compared to patients in the lower four quintiles. These associations were independent of clinical risk factors, the presence of acute coronary syndromes and the number of stents. Conclusions Pre-procedural platelet count and plasma levels of fibrinogen are associated with the risk of early ST in patients after implantation of DES. Device-level risk factors like stent-type or size and procedure-level risk factors like peri-interventional medication and complications during stent apposition are associated with ST. Platelet count and plasma levels of fibrinogen may be additional patient-level risk factors that have to be taken in account in the development of future personalized strategies to prevent these rare but deleterious complications.

Pre-diagnostic trajectory of pediatric hemophagocytic lymphohistiocytosis: observations from hematological and hepatic parameters.

Understanding the early features and characteristics of hemophagocytic lymphohistiocytosis (HLH) is essential for identifying high-risk individuals and also providing valuable pathological insights. This study aims to investigate the characteristics and trends of blood and hepatic parameters before an HLH diagnosis was established. Longitudinal hematological and hepatic test results from pediatric patients with HLH and an age- and sex-matched control group were analyzed. According to the length of time between hospital admission and the establishment of the HLH diagnosis, the HLH cases were divided into early-onset (≤ 7 days) and late-onset (> 7days) groups. Among the 229 pediatric HLH patients, the length of time between hospital admission and the establishment of an HLH diagnosis ranged from 0 to 41 days (median = 4 days). Over 80% of pediatric HLH patients presented abnormal laboratory results for aspartate aminotransferase (AST), triglycerides, lactate dehydrogenase (LDH), and hemoglobin at admission. The abnormal rates in the initial platelet count, neutrophil count, and fibrinogen tests were 67.3%, 48.3%, and 52.2%, respectively. The initial test results for AST, alanine aminotransferase (ALT), LDH, serum sodium, and albumin showed AUCs > 80% for discriminating early-onset HLH. For the discrimination of late-onset HLH, the performance of initial test results was poor. To conclude, abnormalities in AST, triglycerides, LDH, and hemoglobin are early presentations of pediatric HLH; platelet, neutrophil, and fibrinogen levels may become abnormal at a relatively late stage of the HLH disease trajectory; and the initial test results for AST, ALT, LDH, serum sodium, and albumin can be used to identify suspected early-onset HLH.

. Predictive Value of Pre-delivery Serum β-human Chorionic Gonadotropin, Fibrinogen, and Homocysteine for Hypertensive Disorders of Pregnancy

Introduction: it was to investigate the relationship between pre-delivery serumβ-human chorionic gonadotropin (β-HCG), fibrinogen (FIB), and homocysteine (HCY) with hypertensive disorder complicating pregnancy (HDCP). Materials and Methods: 200 HDCP patients and 150 normal pregnant women were selected as study subjects. Fasting cubital venous blood samples were collected to measure serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL), as well as β-HCG, FIB, and HCY levels. Pearson correlation analysis examined relationship between β-HCG, FIB, HCY, and HDCP. Receiver operating characteristic (ROC) curve analysis evaluated the predictive value of these indicators for HDCP. Multiple logistic regression analysis identified risk factors (RFs) for HDCP.Results: serum TG, TC, HDL, LDL, FIB,β-HCG, and HCY were greatly elevated in the HDCP group versus control group (CG) (P&lt;0.05). Serumβ-HCG, FIB, and HCY showed notable positive correlations with HDCP (r = 0.935, 0.547, 0.811; P&lt;0.05), and the areas under the ROC curve (AUC) for predicting HDCP based on serum β-HCG, FIB, HCY, and their combination were 0.743, 0.659, 0.801, and 0.886, respectively (P&lt;0.05). Lipid indicators and serum levels of FIB, β-HCG, and HCY were RFs for HDCP.Conclusion:pregnant women with HDCP exhibited markedly elevated serum lipid levels and FIB, β-HCG, and HCY levels before delivery, which can serve as predictive indicators for HDCP.

Plasma Fibrinogen Level’s: A Comparative Study Between Newly Diagnosed Diabetics and Healthy Individuals

The study examines the plasma fibrinogen levels in patients with newly diagnosed Type 2 Diabetes Mellitus (T2DM) compared to healthy individuals at Aarupadai Veedu Medical College in Puducherry. Plasma fibrinogen, an essential protein involved in the process of blood clotting, also functions as a biomarker for cardiovascular and inflammatory illnesses. Employing a comparative cross-sectional approach, we assessed the levels of fibrinogen in a group of 57 patients with newly diagnosed type 2 diabetes mellitus (T2DM) and a group of 57 healthy individuals who were in non-diabetic. The findings indicate a substantial increase in fibrinogen levels among individuals with newly diagnosed type 2 diabetes mellitus (T2DM) at 384.66 mg/dL, in contrast to the control group at 287.24 mg/dL, with a p-value of less than 0.0001. The age distribution discrepancies were found to be statistically significant (p=0.007), indicating that age may be a confounding factor. The gender distribution was balanced, suggesting the absence of any gender-related prejudice. The results of our study emphasise the increased levels of fibrinogen in patients with newly diagnosed type 2 diabetes mellitus (T2DM) and emphasise the necessity for additional investigation into its clinical significance and potential as a target for therapy.

Effect of Selected Crystalloid and Colloid Solutions on Coagulation Status Evaluated by Rotational Thromboelastometry and Platelet Function Analyser: An in vitro Study

Introduction: Crystalloid and colloid solutions commonly used in intensive and perioperative care can affect haemocoagulation status. This in vitro study assessed the impact of Plasma-Lyte, albunorm 5%, and Gelaspan 4% solutions on primary and secondary haemostasis using rotational thromboelastometry and platelet function analyser. Methods: In this prospective study, we examined blood samples from 20 healthy volunteers using rotational thromboelastometry and platelet function analyser. Simultaneously, we analysed the blood samples subjected to 10% dilution using Plasma-Lyte, albunorm 5%, and Gelaspan 4% solutions. Results: Compared to controls, Plasma-Lyte shortened EXTEM-CT (p = 0.005) and reduced FIBTEM-MCF (p = 0.017). albunorm 5% prolonged EXTEM-CFT (p = 0.001), decreased EXTEM-alpha (p < 0.001) and MCF in EXTEM, INTEM, and FIBTEM tests (p < 0.001, p = 0.038, p = 0.001, respectively), along with MCE in the PLTEM test (p < 0.001). Gelaspan 4% also prolonged EXTEM-CFT (p < 0.001), decreased EXTEM-alpha (p < 0.001) and MCF in EXTEM, INTEM, and FIBTEM tests (p < 0.001, p < 0.001, p = 0.009, respectively), along with MCE in the PLTEM test (p < 0.001). Gelaspan 4% also reduced EXTEM-CT (p = 0.021). All solution prolonged CT in PFA Col/ADP (p = 0.003 for Plasma-Lyte, p < 0.001 for albunorm and Gelaspan) and albunorm 5% also prolonged CT in Col/Epi (p = 0.003). Conclusion: Plasma-Lyte had the least effect on secondary haemostasis, whereas albunorm 5% had the least effect among colloids. Gelaspan 4% adversely affected the propagation phase of coagulation, maximal strength and elasticity of the coagulum, and the level of functional fibrinogen. All solutions adversely affected platelet function in primary haemostasis, with Plasma-Lyte showing the least effect.

Effect of Trichosanthes cucumerina Methanol Extract on CRP and Fibrinogen Levels in Diabetic Ulcer Rat Models

Diabetic ulcers can be fatal for people with long-term diabetes. This is caused by the spread of diabetic ulcers and inadequate care for the wound, which can induce an infection and even death. This study aims to determine inflammatory markers, specifically fibrinogen and C-Reactive Protein (CRP), as indicators of healing, particularly in a rat model of diabetic ulcers treated with Trichosanthes cucumerina methanol extract. The methods used were making extracts, measuring blood glucose levels, measuring CRP, and measuring fibrinogen levels in 25 male Wistar rats. Based on the results of glucose and fibrinogen examinations in all groups before treatment and after treatment, it showed a decrease in glucose and fibrinogen levels. Meanwhile, the results of CRP examinations, before and after treatment did not show any differences. The results of statistical analysis showed that there was a significant difference of p&lt;0.05 in pre and post glucose, as well as pre and post fibrinogen.The extract that reduced fibrinogen levels the most was group 3 with 500 mg/KgBW. Meanwhile, CRP levels before and after treatment did not show a decrease.

Time-Dependent Association of Preinjury Anticoagulation on Traumatic Brain Injury-Induced Coagulopathy: A Retrospective, Multicenter Cohort Study

BACKGROUND AND OBJECTIVES: The impact of preinjury anticoagulation on coagulation parameters over time after traumatic brain injury (TBI) has remained unclear. Based on the hypothesis that preinjury anticoagulation significantly influences the progression and persistence of TBI-induced coagulopathy, we retrospectively examined the association of preinjury anticoagulation with various coagulation parameters during the first 24 hours postinjury in 5 periods. METHODS: Data from the Japanese registry of patients with TBI aged ≥65 years admitted between 2019 and 2021 were used. Time since injury was classified into 5 categories through a graphical analysis of coagulation parameters. We examined the association between preinjury anticoagulation and the platelet count, prothrombin time-international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), D-dimer level, and fibrinogen level during each period by analysis of covariance using 10 clinical factors as confounding factors. RESULTS: Data from 545 patients and 795 blood tests were analyzed. The patients' mean age was 78.9 years, and 87 (16%) received anticoagulation therapy. The preinjury anticoagulation group had significantly greater Rotterdam computed tomography scores and poorer outcomes at discharge than the control group, with significantly lower D-dimer levels and higher fibrinogen levels. Analysis of covariance revealed significant associations between the D-dimer level and preinjury anticoagulation within 2 to 24 hours postinjury, APTT and preinjury anticoagulation within 1 to 24 hours, and PT-INR and preinjury anticoagulation throughout all periods up to 24 hours postinjury. CONCLUSION: Despite more severe TBI signs and poorer outcomes, the preinjury anticoagulation group had significantly lower D-dimer levels, especially within 2 to 24 hours postinjury. Thus, D-dimer levels during this period may not reliably represent TBI severity in patients receiving anticoagulation therapy before injury. Preinjury anticoagulation was also associated with an elevated PT-INR and prolonged APTT from early to 24 hours postinjury, highlighting the importance of aggressive anticoagulant reversal early after injury.

A novel γ-chain mutation p.Asp318His in a Chinese family with dysfibrinogenemia.

Congenital dysfibrinogenemia is characterized by reduced fibrinogen activity, but normal immunoreactive fibrinogen levels. Here, we present a novel case with an elevated risk of thrombosis. Coagulation assays, gene analysis, in silico tools, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), fibrin polymerization, thrombin generation assay, and electron microscopy scanning were utilized to elucidate the pathogenic mechanism. The proband manifested with a normal immunologic fibrinogen (2.13 g/l) but reduced functional fibrinogen (0.39 g/l). Subsequent genetic analysis unveiled a novel heterozygous mutation, c.1030G>C (p.Asp318His), in the γ-chain D domain of fibrinogen, which was highly conserved in homologous species and led to enhanced thrombin generation capability. The ability of the proband's fibrinogen to polymerize was significantly impaired, with decreased final turbidity. Scanning electron microscopy indicated that the fibers of the proband were thinner than normal, with smaller pores. Thromboelastography (TEG) results demonstrated prolonged K time, decreased angle value, and a normal confidence interval value in the proband. We present a novel case displaying the γAsp318His mutation, which resulted in dysfibrinogenemia.

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.