Fibrinogen Levels Research Articles

Impact of extracorporeal hemadsorption on mortality in critically ill COVID-19 patients in the intensive care unit.

The consequences of COVID-19, such as respiratory failure and mortality, require the search for fast and effective solutions. The aim of this retrospective study is to determine the effect of extracorporeal hemadsorption on mortality in severe COVID-19 cases hospitalized in the intensive care unit (ICU). Our study is retrospective, single-center, and observational. The study included ICU patients diagnosed with COVID-19 who received extracorporeal hemadsorption treatment between March 2020 and December 2020. Effects on mortality were examined by comparing pre- and post-hemadsorption values. Seventeen patients were included in the study. The mortality rate in the study was 64.7%. After hemadsorption, an increase was observed in the lymphocyte numbers, APACHE-II, and SOFA values of the patients (p = 0.026, 0.043, and 0.033; respectively). A significant decrease was observed in CRP and fibrinogen levels (p = 0.003 and 0.005; respectively). In the non-surviving patient group, APACHE-II, SOFA, and procalcitonin values were found to be high before and after the procedure (p = 0.002, 0.048, and 0.06; respectively). In COVID-19 patients, APACHE-II and SOFA scores may be useful in predicting the effectiveness of extracorporeal hemadsorption. Our study found that patients with higher APACHE-II and SOFA scores at baseline had a higher mortality rate after hemadsorption. These findings show that the use of intensive care scoring systems may be useful in determining which patients should receive extracorporeal hemadsorption and that hemadsorption should be performed in the early stages of the disease.

Evaluation of tocilizumab-induced hypofibrinogenemia in rheumatology practice: a retrospective, real-life, single-center experience.

Tocilizumab (TCZ) which is a humanized interleukin (IL)-6 receptor antibody has been increasingly widespread used in rheumatology practice. TCZ-related hypofibrinogenemia is a not well-described side effect, but awareness seems to be incresing as publications on this topic are also becoming more frequent. Our aim in this study was to determine the frequency, timing, and approach to TCZ-related hypofibrinogenemia in rheumatic diseases. We retrospectively screened our patients who received TCZ for inflammatory rheumatic diseases and studied serum fibrinogen at least once before and/or after drug administration. We recorded and analyzed demographic features (age, gender, diagnosis), comorbidities, laboratory parameters, management, and outcome data. 30 patients who received TCZ due to rheumatological diseases and had at least one fibrinogen level were included in this study. 73.3% were female and median age was found to be 65 (42-82) years, with median disease duration of 148 (36-500) months. 90% of the patients received TCZ for RA and 10% for GCA. We examined the fibrogen levels at an average of 24 months (min 1 max 108) following the start of TCZ treatment. The study group was divided into those with normal fibrinogen levels (normal fibrinogen group) and those with low fibrinogen levels (lowfibrinogen group). In total, hypofibrinogenemia was found in 14 (46.6%) patients. Median serum fibrinogen level in the low fibrinogen group after TCZ was calculated to be 151.5mg/dl (min 92 max 171). Most patients were asymptomatic (71.4%). Ecchymoses were in seen 4 (28,6%) patients. No major bleeding were seen. TCZ was discontinued in 5 out of 14 patients (35.7%), while 9 out of 14 patients (64.3%) were closely followed. Outcomes regarding fibrinogen levels (11 out of 14) were as follows: increase in 4 and not checked in one after cessation of the drug, 3 spontaneous increases under the drug, and 3 persistently low levels on TCZ treatment. We found no difference in terms of gender (p = 0.417), platelets (p = 0.343), ESR (p = 0.448), and CRP (p = 0.660) at the time of TCZ initiation between groups. TCZ-related hypofibrinogenemia is more frequent than expected with occurence in both the early and late stages of treatment. Further research is required to determine whether to regularly measure fibrinogen levels in patients using TCZ and how to treat patients with hypofibrinogenemia.

Peculiarities of granulocyte-macrophage and macrophage colony-stimulating factors receptors expression in subpopulations of peripheral blood monocytes of patients with chronic obstructive pulmonary disease

Introduction. To analyze of the severity of respiratory symptoms in patients with chronic obstructive pulmonary disease (COPD), depending on the presence of an exacerbation or novel coronavirus infection (NCVI), taking into account the activity of acute phase blood parameters.Materials and methods. The medical documentation of 162 patients with COPD was studied, which were divided into 3 groups: group 1 (n=61) ‒ COPD and NCVI, group 2 (n=53) – stable COPD, group 3 (n=48) ‒ COPD exacerbation. The severity of respiratory symptoms was assessed using points. To assess the activity of inflammation the following biochemical indicators were used ‒ C-reactive protein (CRP) and fibrinogen (g/L).Results. According to the severity of cough and the intensity of dyspnea on the mMRC scale, the first, second and third groups did not differ statistically (p=0.07). Patients of the first group (82.5%) characterized by the absence of classical criteria for exacerbation of COPD. In terms of the severity of sputum production, the first, second and third groups are statistically different (p=0.0001). The first, second and third groups differ significantly in the level of serum CRP (p=0.0001) and fibrinogen (p=0.009). According to the results of the correlation analysis, some relationships found between respiratory symptoms and the level of CRP and fibrinogen.Conclusion. The clinical feature of the associated course of stable COPD and NCVI is the presence of severe dyspnea and the absence of classic criteria for exacerbation of COPD. Systemic inflammation in NCVI and stable COPD are more pronounced than in isolated stable COPD or exacerbation and correlates with cough and dyspnea. Practitioners for the differential diagnosis of NCVI in stable COPD can use the data obtained.

Do interleukin-17 and interleukin-23 inhibitors alter the coagulation parameters in psoriasis patients?: A retrospective study.

Psoriasis is a chronic inflammatory skin condition associated with systemic inflammation and a higher risk of cardiovascular comorbidities. This study retrospectively evaluates coagulation parameters in psoriasis vulgaris patients treated with IL-17 inhibitors (secukinumab, ixekizumab) and IL-23 inhibitors (risankizumab, guselkumab), compared to those untreated systemically. The study reviewed records from 177 patients treated between January 2019 and March 2023. Patients were grouped into control (n = 77), secukinumab (n = 36), ixekizumab (n = 19), guselkumab (n = 24), and risankizumab (n = 21). Coagulation parameters, including PT, aPTT, PLT, MPV, INR, fibrinogen, D-dimer, and B12 levels, were analyzed. The primary endpoint was the comparison of coagulation parameters between groups. Significant differences were found in PT, with secukinumab-treated patients showing a significantly shorter PT compared to controls (p = 0.002). No significant differences were observed in other coagulation parameters across the groups. The study highlights a potential effect of secukinumab on coagulation pathways, possibly related to IL-17's role in inflammation and endothelial function. Despite current literature suggest a risk of cerebrovascular events with risankizumab, this study did not show any significant changes in coagulation parameters with risankizumab, indicating no hypercoagulability risk associated with this IL-23 inhibitor. Our findings suggest IL-17 and IL-23 inhibitors are generally safe concerning coagulation parameters, but regular monitoring may be warranted for patients on secukinumab due to its effect on PT. Further long-term studies are needed to fully understand the cardiovascular risks associated with these therapies.

Association between fibrinogen and white matter lesions and cerebral atrophy in patients with acute ischemic stroke

BackgroundInflammation is a potential mechanism underlying the development of white matter lesions (WMLs) and cerebral atrophy. We aimed to investigate the relationship of fibrinogen levels with WMLs and cerebral atrophy in patients with acute ischemic stroke (AIS). MethodsA total of 701 AIS patients were enrolled. Participants were divided into four groups according to the quartiles of fibrinogen levels: Q1 < 2.58 g/L, Q2: 2.58-3.12 g/L, Q3: 3.12-3.67 g/L, Q4: ≥ 3.67 g/L. White matter hyperintensity (WMH), periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) were defined according to the Fazekas scale. Cerebral atrophy was defined according to global cortical atrophy scores. Univariate and multivariate logistic regression were used to explore the relationship of fibrinogen levels and WMHs, PVH, DWMH and cerebral atrophy. ResultsAmong 701 AIS patients, 498 (71.0 %), 425 (60.6 %), 442 (63.1 %), and 560 (79.9 %) had WMHs, PVH, DWMH and cerebral atrophy, respectively. After adjustment for potential covariates, the highest fibrinogen quartiles were significantly associated with increased risk of WMHs (odds ratio [OR] 1.97, 95 % confidence intervals [CI] 1.10-3.50), PVH (OR 1.85, 95 % CI 1.08-3.16) and cerebral atrophy (OR 2.53, 95 % CI 1.19-5.40) but not DWMH (OR 1.37 95 % CI 0.81-2.31) compared with the lowest fibrinogen quartile. Moreover, the association between elevated fibrinogen levels and the risk of WMLs and cerebral atrophy remained significant as continuous variables. ConclusionsIncreased baseline fibrinogen levels were independently associated with WMHs, PVH and cerebral atrophy in patients with ischemic stroke. Fibrinogen could be the potential blood biomarker of WMLs and cerebral atrophy.

Platelet Aggregation Alterations in Patients with Severe Viral Infection Treated at the Intensive Care Unit: Implications for Mortality Risk.

Severe viral infections often result in abnormal platelet function, affecting various stages of hemostasis. Activated platelets are often considered prothrombotic and more susceptible to further stimulation. However, emerging evidence suggests that initial hyperactivation is followed by platelet exhaustion and hypo-responsiveness, affecting platelet degranulation, activation, and aggregation. We examined early alterations in platelet aggregation among patients (N = 28) with acute respiratory distress syndrome and SARS-CoV-2 infection who were receiving mechanical ventilation and venovenous extracorporeal membrane oxygenation support. Blood samples were stimulated with four different activators: arachidonic acid, adenosine diphosphate, thrombin receptor-activating protein 6, and ristocetin. Our observations revealed that platelet aggregation was reduced in most patients upon admission (ranging from 61 to 89%, depending on the agonist used), and this trend intensified during the 5-day observation period. Concurrently, other coagulation parameters remained within normal ranges, except for elevated d-dimer and fibrinogen levels. Importantly, we found a significant association between platelet aggregation and patient mortality. Impaired platelet aggregation was more severe in patients who ultimately died, and reduced aggregation was associated with a significantly lower probability of survival, as confirmed by Kaplan-Meier analysis (p = 0.028). These findings underscore the potential of aggregometry as an early detection tool for identifying patients at higher risk of mortality within this specific cohort.

Acute exercise-induced inflammatory and thrombotic response in hypertensive patients.

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. 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. 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. All biomarkers increased with exercise, except PAI-1, which decreased (P < 0.05 for the change between resting and peak exercise for all biomarkers). Αfter adjusting for relevant confounders (duration of exercise, metabolic equivalents, systolic BP, and rate-pressure product achieved at peak exercise), the normotensive group had less marked (P < 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%). In conclusion, the acute exercise-induced inflammatory and thrombotic response seems to be more pronounced in non-treated hypertensive patients than in normotensive controls. Possible clinical implications of this finding merit further examination.

Neutrophil extracellular traps and citrullinated fibrinogen contribute to injury in a porcine model of limb ischemia and reperfusion.

Ischemia/reperfusion injury (IRI) is a complex pathological process, triggered by the restoration of blood flow following an interrupted blood supply. While restoring the blood flow is the only option to salvage the ischemic tissue, reperfusion after a prolonged period of ischemia initiates IRI, triggering a cascade of inflammatory responses ultimately leading to neutrophil recruitment to the inflamed tissue, where they release neutrophil extracellular traps (NETs). NETs are web-like structures of decondensed chromatin and neutrophilic proteins, including peptidyl-arginine deiminase 2 and 4 (PAD2, PAD4), that, once outside, can citrullinate plasma proteins, irreversibly changing their conformation and potentially their function. While the involvement of NETs in IRI is known mainly from rodent models, we aimed to determine the effect of NET formation and especially PADs-mediated extracellular protein citrullination in a porcine model of limb IRI. We conducted our study on amputated pig forelimbs exposed to 1h or 9h of ischemia and then reperfused in vivo for 12h. Limb weight, edema formation, compartmental pressure were measured, and skeletal muscle was analyzed by immunofluorescence (TUNEL assay and dystrophin staining) to evaluate tissue damage. Fibrin tissue deposition, complement deposition and NETs were investigated by immunofluorescence. Citrullinated plasma proteins were immunoprecipitated and citrullinated fibrinogen was identified in the plasma by Western blot and in the tissue by immunofluorescence and Western blot. Our data consolidate the involvement of NETs in a porcine model of limb IRI, correlating their contribution to damage extension with the duration of the ischemic time. We found a massive infiltration of NETs in the group subjected to 9h ischemia compared to the 1h and citrullinated fibrinogen levels, in plasma and tissue, were higher in 9h ischemia group. We propose fibrinogen citrullination as one of the mechanisms contributing to the worsening of IRI. NETs and protein citrullination represent a potential therapeutic target, but approaches are still a matter of debate. Here we introduce the idea of therapeutic approaches against citrullination to specifically inhibit PADs extracellularly, avoiding the downstream effects of hypercitrullination and keeping PADs' and NETs' intracellular regulatory functions.

Whole-genome analysis of plasma fibrinogen reveals population-differentiated genetic regulators with putative liver roles

AbstractGenetic studies have identified numerous regions associated with plasma fibrinogen levels in Europeans, yet missing heritability and limited inclusion of non-Europeans necessitates further studies with improved power and sensitivity. Compared with array-based genotyping, whole-genome sequencing (WGS) data provide better coverage of the genome and better representation of non-European variants. To better understand the genetic landscape regulating plasma fibrinogen levels, we meta-analyzed WGS data from the National Heart, Lung, and Blood Institute’s Trans-Omics for Precision Medicine (TOPMed) program (n = 32 572), with array-based genotype data from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n = 131 340) imputed to the TOPMed or Haplotype Reference Consortium panel. We identified 18 loci that have not been identified in prior genetic studies of fibrinogen. Of these, 4 are driven by common variants of small effect with reported minor allele frequency (MAF) at least 10 percentage points higher in African populations. Three signals (SERPINA1, ZFP36L2, and TLR10) contain predicted deleterious missense variants. Two loci, SOCS3 and HPN, each harbor 2 conditionally distinct, noncoding variants. The gene region encoding the fibrinogen protein chain subunits (FGG;FGB;FGA) contains 7 distinct signals, including 1 novel signal driven by rs28577061, a variant common in African ancestry populations but extremely rare in Europeans (MAFAFR = 0.180; MAFEUR = 0.008). Through phenome-wide association studies in the VA Million Veteran Program, we found associations between fibrinogen polygenic risk scores and thrombotic and inflammatory disease phenotypes, including an association with gout. Our findings demonstrate the utility of WGS to augment genetic discovery in diverse populations and offer new insights for putative mechanisms of fibrinogen regulation.

Menorrhagia in inherited bleeding disorders in Iraqi women

Abstract: BACKGROUND: Menorrhagia, or excessive menstrual bleeding, is a common symptom in women with inherited bleeding disorders; they are conditions where the blood ability to clot is impaired. Some of the common bleeding disorders include von Willebrand disease (VWD), clotting factor deficiencies, and platelet function disorders. OBJECTIVE: To assess different types of inherited bleeding disorders in women with menorrhagia referred to the National Center of Hematology/Mustansiriyah University in Baghdad/Iraq. PATIENTS AND METHODS: A prospective study was carried out on 193 women who had experienced menorrhagia for a duration of 3 years, from 2020 to 2023. These women sought consultation at the National Centre of Hematology/Mustansiriyah University. All participants were diagnosed through various laboratory tests, including complete blood count, blood film, blood group and Rh, bleeding time, prothrombin time, activated partial thromboplastin time, fibrinogen level, factor assay, von Willebrand factor antigen using ELISA technique, ristocetin cofactor, and platelet function test. RESULTS: Out of the 193 women with menorrhagia who participated in this study, the majority of whom had an unidentified cause (36.3%), followed by VWD (30.1%) and platelet function disorders (21.2%). Other bleeding disorders (thrombocytopenia and factors deficiencies) were 5.7% and 6.7%, respectively. Furthermore, the results showed that there was a significant difference in family history and consanguinity between patients with a hereditary bleeding disorder and nonhereditary bleeding disorder (P &lt; 0.001). CONCLUSIONS: Fifty eight percent of females with Menorrhagia in this study have inherited bleeding disorders(IBDs), VWD, and thrombasthenia account for 51.3% are the most common causes of inherit bleeding disorder (IBD). Consanguineous marriage should be discouraged in Iraqi society to reduce such inherited diseases.

The diagnostic value of neutrophil to lymphocyte ratio, albumin to fibrinogen ratio, and lymphocyte to monocyte ratio in Parkinson's disease: a retrospective study.

Parkinson's disease (PD) is a prevalent disorder of the central nervous system, marked by the degeneration of dopamine (DA) neurons in the ventral midbrain. In the pathogenesis of PD, inflammation hypothesis has been concerned. This study aims to investigate clinical indicators of peripheral inflammation in PD patients and to explore the diagnostic value of neutrophil-to-lymphocyte ratio (NLR), albumin-to-fibrinogen ratio (AFR), and lymphocyte-to-monocyte ratio (LMR) in assessing PD risk. This study included 186 patients with PD and 201 matched healthy controls (HC) with baseline data. Firstly, the differences of hematological indicators between PD group and healthy participants were compared and analyzed. Univariate and multivariate regression analyses were then conducted. Smooth curve fitting was applied to further validate the relationships between NLR, LMR, AFR, and PD. Subsequently, subgroup analysis was conducted in PD group according to different duration of disease and Hoehn and Yahr (H&Y) stage, comparing differences in clinical indicators. Finally, the receiver operating characteristic (ROC) curve was employed to assess the diagnostic value of NLR, LMR, and AFR in PD. Compared to the HC group, the PD group showed significantly higher levels of hypertension, diabetes, neutrophil count, monocyte count, CRP, homocysteine, fibrinogen, and NLR. Conversely, levels of LMR, AFR, lymphocyte count, HDL, LDL, TG, TC, uric acid, and albumin were significantly lower. The multivariate regression model indicated that NLR (OR = 1.79, 95% CI: 1.39-2.31, p < 0.001), LMR (OR = 0.75, 95% CI: 0.66-0.85, p < 0.001), and AFR (OR = 0.79, 95% CI: 0.73-0.85, p < 0.001) were significant factors associated with PD. Smooth curve fitting revealed that NLR was positively linked to PD risk, whereas AFR and LMR were inversely associated with it. In ROC curve analysis, the AUC of AFR was 0.7290, the sensitivity was 63.98%, and the specificity was 76.00%. The AUC of NLR was 0.6200, the sensitivity was 50.54%, and the specificity was 71.50%. The AUC of LMR was 0.6253, the sensitivity was 48.39%, and the specificity was 73.00%. The AUC of the combination was 0.7498, the sensitivity was 74.19%, and the specificity was 64.00%. Our findings indicate that NLR, LMR, and AFR are significantly associated with Parkinson's disease and may serve as diagnostic markers.

Assessment of health impacts in retired antisera-producing horses: Blood biochemistry and serum amyloid A analysis.

Horses used for antisera production are repeatedly hyperimmunized to produce high levels of specific antibodies. This prolonged process can lead to various health issues, including amyloidosis, which involves the accumulation of amyloid proteins in organs and tissues, potentially causing organ dysfunction and failure. These horses are often retired when they no longer produce adequate antibody levels. This study aimed to evaluate the impact of prolonged antisera production on the health of retired horses by examining their blood biochemistry and serum amyloid A (SAA) levels, which are indicators of systemic inflammation and organ damage. Blood samples were collected from 12 horses for this study. Nine horses were retired antisera-producing horses that had been discontinued for 2 years, while three healthy non-antisera-producing horses were used as controls. These twelve horses were divided into four groups based on the duration of their active period as antisera producers (never been used, 2-3 years, 4-5 years, and 6-7 years). We measured key blood biochemistry parameters and SAA levels to evaluate the health status of the horses. Total protein, fibrinogen, and globulin levels were elevated, whereas other parameters remained normal. The findings indicate that despite normal SAA levels, the horses exhibited signs of ongoing health issues related to their previous use in antisera production, such as increased total plasma protein, fibrinogen, and globulin levels, as well as the presence of amyloid deposits in vital organs such as the liver and kidneys, as observed in post-mortem examinations. Despite normal SAA levels, retired antisera-producing horses showed elevated total protein, fibrinogen, and globulin levels, indicating ongoing health issues.

Clinical features and predictors of early neurological deterioration in patients with Trousseau syndrome-related cerebral infarction

Objective: This study aimed to explore the clinical features of Trousseau syndrome (TS)-related cerebral infarction and determine predictors of early neurological deterioration (END). Methods: A retrospective study was conducted on patients with TS-related cerebral infarction admitted to the Zhongshan Hospital Affiliated with Xiamen University, from December 2015 to December 2023. Patients were categorized into groups with and without END. The laboratory findings and imaging data were compared, and receiver operating characteristic (ROC) curves were constructed to determine the best predictors of END. Results: The study included 30 patients with TS-related cerebral infarction, comprising 17 males and 13 females with an average age of 70.93 ± 8.7 years. Five patients experienced END. Lung cancer was the most common primary malignancy (n=13, 43.33%), with most patients (n=22, 73.33%) having stage IV disease with extensive metastasis. The primary neurological symptom was hemiplegia (n=17, 56.67%). The mean NIHSS score at admission was 9.33 ± 5.83. Imaging revealed varying stages of cerebral infarction in 10 patients (38.46%). Within three months, 25 patients (83.33%) died, 8 of whom (32%) succumbed to tumor-related complications. The incidence of END in TS-related cerebral infarction patients was 16.67% (5/30). Patients in the END group had significantly greater D-dimer levels and lower fibrinogen (Fib) levels upon admission (P &lt; 0.001, P = 0.042). Comparisons of ROC curves revealed that D-dimer (AUC 0.916, optimal cutoff 17.86, sensitivity 1.000, specificity 0.840) and Fib (AUC 0.788, optimal cutoff 2.54, sensitivity 1.000, specificity 0.740) significantly predicted END (P = 0.004, P = 0.045). The combined use of these markers improved the AUC to 0.952, with a sensitivity of 1.00 and specificity of 0.920, surpassing those of the individual markers (P = 0.002). Conclusion: TS-related cerebral infarction most commonly occurs in patients with advanced-stage lung cancer with widespread metastasis and is associated with poor long-term prognosis. Elevated D-dimer and decreased fibrinogen levels are significant predictors of END in patients with TS-related cerebral infarction.

Maternal and Fetal Outcomes in Disseminated Intravascular Coagulation Cases Associated with Pregnancy Complications.

The relationship between the pregnancy modified DIC score, which is applied in obstetric conditions where the risk of disseminated intravascular coagulation is high, and underlying disease, as well as its effect on the prognosis, was investigated. Those with a DIC score ≥ 26 from obstetric conditions, such as obstetric bleeding, placental abruption, or preeclampsia/HELLP syndrome, which are at high risk of developing DIC, were included in the study. These patients were compared in terms of laboratory results, maternal morbidity/mortality, and neonatal outcomes, according to the underlying disease. The DIC score was ≥ 26 in 224 of 154,233 deliveries in our center, and the incidence was 0.14%. In the preeclampsia/HELLP syndrome group, the platelet count and prothrombin time were lower, and the fibrinogen level was higher than those of the obstetric hemorrhage and placental abruption groups. In addition, the rates of blood transfusion and hysterectomy were lower in women who developed DIC due to pre-eclampsia/HELLP syndrome than in those with obstetric hemorrhage. Considering the underlying disease is an important factor in predicting prognosis, when using the new pregnancy modified diagnostic scores for DIC diagnosis.

Bivariate genome-wide association study of circulating fibrinogen and C-reactive protein levels

BackgroundFibrinogen and C-reactive protein (CRP) play an important role in inflammatory pathways and share multiple genetic loci reported in previously published genome-wide association studies (GWAS), highlighting their common genetic background. Leveraging the shared biology may identify further loci pleiotropically associated with both fibrinogen and CRP. ObjectivesTo identify novel genetic variants that are pleiotropic and associated with both fibrinogen and CRP, by integrating both phenotypes in a bivariate GWAS by using a multitrait GWAS. MethodsWe performed a bivariate GWAS to identify further pleiotropic genetic loci, using summary statistics of previously published GWAS on fibrinogen (n = 120 246) from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium, consisting of European ancestry samples and CRP (n = 363 228) from UK Biobank, including 5 different population groups. The main analysis was performed using metaUSAT and N-GWAMA. We conducted replication for novel CRP associations to test the robustness of the findings using an independent GWAS for CRP (n = 148 164). We also performed colocalization analysis to compare the associations in identified loci for the 2 traits and Genotype-Tissue Expression data. ResultsWe identified 87 pleiotropic loci that overlapped between metaUSAT and N-GWAMA, including 23 previously known for either fibrinogen or CRP, 58 novel loci for fibrinogen, and 6 novel loci for both fibrinogen and CRP. Overall, there were 30 pleiotropic and novel loci for both traits, and 7 of these showed evidence of colocalization, located in or near ZZZ3, NR1I2, RP11-72L22.1, MICU1, ARL14EP, SOCS2, and PGM5. Among these 30 loci, 13 replicated for CRP in an independent CRP GWAS. ConclusionBivariate GWAS identified additional associated loci for fibrinogen and CRP. This analysis suggests fibrinogen and CRP share a common genetic architecture with many pleiotropic loci.

The hemostatic activity and Mechanistic roles of glucosyloxybenzyl 2-isobutylmalate extract (BSCE) from Bletilla striata (Thunb.) Rchb.f. in Inhibiting pulmonary hemorrhage

BackgroundHemorrhagic events cause numerous deaths annually worldwide, highlighting the urgent need for effective hemostatic drugs. The glucosyloxybenzyl 2-isobutylmalates Control Extract (BSCE) from the orchid plant Bletilla striata (Thunb.) Rchb.f. has demonstrated significant hemostatic activity in both in vitro and in vivo studies. However, the effect and mechanism of BSCE on non-traumatic bleeding remain unclear. MethodsPulmonary hemorrhage was induced in 40 Sprague-Dawley rats by administering Zingiber officinale Roscoe. for 14 days. These rats were then randomly divided into five groups: model (Mod), positive control (YNBY), and BSCE low, medium, and high-dose groups. An additional 8 rats served as the control group (Con). The BSCE groups received different doses of BSCE for 10 days, while the YNBY group received Yunnan Baiyao suspension. The effects on body weight, food and water intake, red blood cell count (RBC), hemoglobin concentration (HGB), lung tissue pathology, platelet count, coagulation parameters, and fibrinolytic system markers were evaluated. Network pharmacology and molecular docking analyses were also conducted to identify potential targets and pathways involved in BSCE's effects. ResultsBSCE treatment significantly improved body weight, food intake, and water consumption in rats with pulmonary hemorrhage. RBC and HGB levels increased significantly in the BSCE medium and high-dose groups compared to the Mod group (P < 0.05). Pathological examination revealed that BSCE reduced lung tissue hemorrhage and inflammation, with improvements in alveolar structure. BSCE also positively affected platelet count, thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (FIB) levels, and fibrinolytic markers (D-dimer, PAI-1, and t-PA). Network pharmacology and molecular docking identified key targets such as MMPs, CASPs, and pathways including IL-17 and TNF signaling, suggesting BSCE's involvement in hemostasis and anti-inflammatory processes. ConclusionsBSCE exhibits significant hemostatic and protective effects on Z.officinale-induced pulmonary hemorrhage in rats by improving hematological parameters, reducing lung tissue damage, and modulating the coagulation and fibrinolytic systems. The study provides evidence supporting the potential of BSCE as a therapeutic agent for hemorrhagic diseases, with its efficacy linked to multi-target and multi-pathway interactions.

Whether coagulation dysfunction influences the onset and progression of diabetic peripheral neuropathy: A multicenter study in middle-aged and aged patients with type 2 diabetes.

Nearly half of patients with diabetes experience diabetic peripheral neuropathy (DPN), resulting in a mere 53% survival rate within 3 years. Aberrations in coagulation function have been implicated in the pathogenesis of microvascular complications, prompting the need for a thorough investigation into its role as a contributing factor in the development and progression of DPN. Data were gathered from 1211 type 2 diabetes patients admitted to five centers from September 2018 to October 2022 in China. DPN was evaluated by symptoms and electromyography. Motor and sensory nerve conduction velocity (NCV) was appraised and the NCV sum score was calculated for the median, ulnar, and peroneal motor or sensory nerves. Patients with DPN exhibited alterations in coagulation function. (i) Specifically, they exhibited prolonged thrombin time (p = 0.012), elevated fibrinogen (p < 0.001), and shortened activated partial thromboplastin time (APTT; p = 0.026) when compared to the control group. (ii) After accounting for potential confounders in linear regression, fibrinogen, and D-dimer were negatively related to the motor NCV, motor amplitude values, and mean velocity and amplitude. Also, fibrinogen was associated with higher Michigan neuropathy screening instrument (MNSI) scores (β 0.140; p = 0.001). This result of fibrinogen can be validated in the validation cohort with 317 diabetic patients. (iii) Fibrinogen was independently associated with the risk of DPN (OR 1.172; p = 0.035). In the total age group, DPN occurred at a slower rate until the predicted fibrinogen level reached around 3.75 g/L, after which the risk sharply escalated. Coagulation function is warranted to be concerned in patients with type 2 diabetes to predict and prevent the occurrence of DPN in clinical practice.

Temporal Association Between COVID-19 Immunoglobulin-G Antibody Induced Focal Cerebral Arteriopathy and New-Onset Acute Ischemic Stroke in a Pediatric: Is it Causal or Coincidental?

ABSTRACT Focal cerebral arteriopathies, vasculitis, microangiopathies, coagulopathies, and in-situ microthrombi leading to territorial infarction of neural tissues are some of the most recent instances which are reported as a consequence of the infection caused by the novel coronavirus (SARS-CoV-2). Acute ischemic stroke (AIS) is one of the major neurological manifestations that have been linked with COVID-19. We describe a case of a 5-year-old boy who had an acute-onset of bilateral arm and leg weakness due to a posterior circulatory ischemic stroke that was temporally associated with COVID-19 Immunoglobulin-G antibody-induced cerebral arteriopathies and vasculitis. Laboratory examination was suggestive of elevated D-dimer levels to 3302 ng/ml, elevated C-reactive protein to 10 mg/dl, and elevated fibrinogen levels to 433 mg/dl. He had a negative COVID-19 nasopharyngeal polymerase chain reaction and positive COVID-19 serologies. Focal cerebral arteriopathy and AIS were managed by administering early antithrombotics, steroids, and multivitamins. On routine follow-ups, the patient remained free from new neurological and functional deficits. Although many hypotheses are proposed to explain the causal relationship between the two, it could as well be sheer coincidence.

A hypothesis on treatment strategy of severe multicentric Castleman disease with continuous renal replacement therapy.

Castleman disease (CD) is a rare lymphoproliferative disorder, with non-specific clinical manifestations, often delayed diagnosis and treatment, which pose a significant challenge in the present times. Patients diagnosed with this disease have poor prognosis due to the limited treatment options. Multicentric CD occurs at multiple lymph node stations and is associated with a proinflammatory response that leads to the development of the so-called 'B symptoms'. IL-6 seems to be a key cytokine involved in various manifestations such as lymphadenopathies, hepatosplenomegaly, and polyclonal hypergammaglobulinemia. Its levels correlate with the activity of the disease. Other consequences of MCD include increased fibrinogen levels leading to deep vein thrombosis and thromboembolic disorders, high hepcidin levels causing anaemia, elevated VEGF levels promoting angiogenesis and vascular permeability, which, along with hypoalbuminemia, induce oedema, ascites, pleural and pericardial effusions, and in severe cases, generalized anasarca. In extreme cases multiple organ failure can occur, often resulting in death. We propose the use of continuous renal replacement therapy (CRRT) in managing severe multicentric CD. Our arguments are based on the principles that CRRT is able to remove IL-6 from circulation thus attenuating the cytokine storm, can influence hepcidin levels, and reduction in oedema, and is often used in multiple organ failure to regain homeostasis control. Therefore, it could be used as a therapy or bridge therapy in severe cases. To sustain our hypothesis with evidence, we have gathered several studies from the literature confirming the successful removal of cytokines, especially IL-6 from circulation, which can be used as a starting point.

Optimizing Coagulation Profile E-Reporting: A Design Thinking Perspective on Healthcare and Technological Integration

The coagulation profile report is crucial for assessing blood clots and diagnosing various bleeding disorders. Key metrics in these reports include the international normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, and fibrinogen levels. Traditionally, these reports have been delivered through paper-based methods, which often face significant challenges such as human errors, delays in distribution, and limited accessibility. To address these issues, this preliminary investigation explores integrating technology into the reporting process for coagulation profiles. By leveraging a design-thinking approach, the study aims to understand the needs and preferences of stakeholders and users. This approach includes creating personas to represent different user types, mapping their experiences through empathy and journey maps, and generating and testing ideas through ideation and prototyping. The core objective of the study is to develop a mobile application that simplifies and enhances the reporting process of coagulation profiles. This application is designed to integrate seamlessly with Electronic Medical Record (EMR) systems, providing real-time notifications to healthcare providers when laboratory results are available. The proposed solution aims to improve the timeliness and accuracy of reporting, facilitating better patient care and more efficient workflows. The paper details the components of this solution, including the prototype design and the validation procedures used to ensure its effectiveness. The study seeks to revolutionize how coagulation profiles are documented and communicated in healthcare by adopting a digital reporting system.