Plasma Fibrinogen Concentration Research Articles

Characteristics of fibrin/fibrinogen degradation products in multiple sclerosis following SARS-CoV-2 infection

Background. The purpose of this study was to investigate plasma levels of fibrinogen and products of its degradation in patients with multiple sclerosis (MS) with and without a history of coronavirus disease 2019 (COVID-19). Materials and methods. We examined 97 patients with MS. Based on the presence of COVID-19, all cases were divided into two groups. MS group included 56 patients who did not suffer from COVID-19 previously. MS + COVID group consisted of 41 cases who had a laboratory-verified diagnosis of COVID-19. The group of healthy controls included 30 healthy volunteers. Spectrophotometric techniques were used to measure the concentrations of fibrinogen, D-dimer, and soluble fibrin monomer complexes (SFMCs). Size-exclusion chromatography was applied to analyze the composition of SFMC fractions. Results. We found that concentrations of fibrinogen, D-dimer, and SFMCs were remarkably increased in plasma of all MS patients compared with healthy controls. The levels of D-dimer, and SFMCs did not differ between two MS groups, while plasma fibrinogen concentration was significantly increased in MS + COVID patients compared to MS group. Moreover, the development of MS was accompanied by the changes in both quantity and quality of SFMC composition compared to that of healthy controls. Our results demonstrated accumulation of high-molecular-weight SFMCs in plasma of MS patients. Conclusions. The findings indicated that MS patients had changed hemostasis characteristics; however, more research is required to determine the connection between particular hemostatic factors, namely fibrinogen, D-dimer, and SFMCs, and the pathophysiology of MS.

The factors influencing the occurrence of post-ischemic stroke depression and its relationship with the burden score of cerebral small vessel disease.

This study explored the determinants of post-stroke depression (PSD) in ischemic stroke (AIS) patients and its association with the burden score of cerebral small vessel disease (CSVD). We analyzed 374 AIS patients treated between January 2020 and January 2022. Patients were categorized into 90 with PSD and 284 without PSD, enabling an investigation into PSD risk factors and the CSVD-PSD relationship. There was no significant difference in health factors between PSD and non-PSD patients (p>0.05). However, significant disparities were noted in age, gender, initial Barthel Index (BI), Mini-Mental State Examination (MMSE) score, plasma fibrinogen, homocysteine, red cell distribution width, National Institutes of Health Stroke Scale (NIHSS) score, and CSVD burden score (p<0.05). Regression analysis indicated that these variables were pivotal PSD predictors (OR>1, p<0.05). Surprisingly, a positive correlation with PSD occurrence was found for age, NIHSS score, plasma fibrinogen, homocysteine levels, red cell distribution width, CSVD burden score (r=0.565, 0.615, 0.482, 0.514, 0.572, 0.608, respectively; p<0.05). Meanwhile, the MMSE score and BI index were inversely related to PSD onset (r=-0.604, -0.590; p<0.05). The ROC curve analysis of the combination model based on MMSE, NIHSS and CSVD score revealed an AUC of 0.926 and Youden's index of 0.744. Age, MMSE score, BI index, NIHSS score, plasma fibrinogen concentration, homocysteine level, red blood cell distribution width, and CSVD burden score are all major influencing factors in the occurrence of PSD. The combination model based on MMSE, NIHSS, and CSVD scores presented a valuable approach to predicting PSD.

Effect of increasing the number of repeated measurements on the accuracy of determining factor VIII activity and fibrinogen concentrations in blood plasma

Effect of increasing the number of repeated measurements on the accuracy of determining factor VIII activity and fibrinogen concentrations in blood plasma

Preoperative plasma fibrinogen and C-reactive protein/albumin ratio as prognostic biomarkers for pancreatic carcinoma.

Pancreatic carcinoma is characterised by high aggressiveness and a bleak prognosis; optimising related treatment decisions depends on the availability of reliable prognostic markers. This study was designed to compare various blood biomarkers, such as neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), platelet/lymphocyte ratio (PLR), C-reactive protein (CRP), albumin (Alb), plasma fibrinogen (PF), and CRP/Alb in patients with pancreatic carcinoma. Our study retrospectively reviewed 250 patients with pancreatic carcinoma diagnosed between July 2007 and December 2018. The Cutoff Finder application was used to calculate the optimal values of CRP/Alb and PF. The Chi-square test or Fisher's exact test was used to analyse the correlation of CRP/Alb and PF with other clinicopathological factors. Conducting univariate and multivariate analyses allowed further survival analysis of these prognostic factors. Multivariate analysis revealed that, in a cohort of 232 patients with pancreatic ductal adenocarcinoma (PDAC), the PF level exhibited statistical significance for overall survival (hazard ratio (HR) = 0.464; p = 0.023); however, this correlation was not found in the entire group of 250 patients with pancreatic carcinoma. Contrastingly, the CRP/Alb ratio was demonstrated statistical significance in both the entire pancreatic carcinoma cohort (HR = 0.471; p = 0.026) and the PDAC subgroup (HR = 0.484; p = 0.034). CRP/Alb and PF demonstrated a positive association (r=0.489, p<0.001) as indicated by Spearman's rank correlation analysis. Additionally, in 232 PDAC patients, the combination of the CRP/Alb ratio and PF had synergistic effects on prognosis when compared with either the CRP/Alb ratio or the PF concentration alone. PF concentration is a convenient, rapid, and noninvasive biomarker, and its combination with the CRP/Alb ratio could significantly enhance the accuracy of prognosis prediction in pancreatic carcinoma patients, especially those with the most common histological subtype of PDAC.

Association of clinical respiratory disease signs and lower respiratory tract bacterial pathogens with systemic inflammatory response in pre-weaned dairy calves

This study investigated the potential associations between 3 acute phase proteins (APPs) haptoglobin, serum amyloid A, and fibrinogen, clinical signs of respiratory disease, and the presence of bacterial pathogens in the lower respiratory tract (LRT) of pre-weaned dairy calves. This cross-sectional study included 150 pre-weaned calves (2-86 d old) from 15 large dairy herds in Estonia. Tracheobronchial lavage, blood, and fecal samples were collected from 5 calves showing clinical signs indicative of LRT disease, and samples from 5 calves without clinical signs of LRT disease per herd. All samples collected from these calves were analyzed for concentrations of systemic APPs, LRT bacteria, and intestinal pathogens. Heifer blood and bulk tank milk samples were collected for the detection of disease-specific antibodies against bovine herpesvirus 1, bovine viral diarrhea virus, bovine respiratory syncytial virus, and Mycoplasma bovis. Mixed-effects linear regression models were used to analyze the associations of clinical respiratory disease signs and LRT bacteria with APPs. Increased plasma fibrinogen concentrations in calves were associated with higher rectal temperature (>39.5°C), increased respiratory rate (>50 breaths/min), and coughing. Increased serum amyloid A concentrations were associated with higher rectal temperature (>39.5°C) and respiratory rate between 40 and 50 breaths/min. Calves with the presence of fecal Cryptosporidium spp. and rectal temperature of 39°C and above had increased serum haptoglobin concentrations. Increased fibrinogen concentrations were associated with the presence of Pasteurella multocida in the calf LRT, whereas increased concentrations of fibrinogen and serum amyloid A were associated with the presence of Trueperella pyogenes. In conclusion, APPs showed variable associations with clinical signs of respiratory disease and LRT bacteria. Plasma fibrinogen concentration could be used as a complementary calf-side test to assess systemic inflammation caused by LRT bacteria such as P. multocida and T. pyogenes in pre-weaned dairy calves.

Point-of-care and traditional erythrocyte sedimentation rate, point-of-care rheometry, and cell-free DNA concentration in dogs with or without systemic inflammation.

RBC aggregation and deformability characteristics are altered by inflammatory, microcirculatory, and hemorheologic disease. These changes can be indirectly evaluated using the erythrocyte sedimentation rate (ESR). Newer point-of-care devices employ syllectometry to evaluate RBC rheology, which can give information beyond the ESR. We evaluated 2 point-of-care rheometers (iSED and MIZAR; Alcor Scientific) in 52 dogs presented to a university teaching hospital. Whole blood samples were analyzed for correlation between the ESR using the Westergren (ESRw) method (measured at 1 h and 24 h) and the predicted ESR using iSED. Plasma fibrinogen and cell-free DNA concentrations were also measured as probable markers of inflammation. The iSED-predicted ESR was positively correlated to the ESRw method at 1 h (r = 0.74; p < 0.001) and 24 h (r = 0.62; p < 0.001). Comparing dogs with or without inflammation (defined as plasma fibrinogen concentration >3.5 g/L [350 mg/dL]), significant differences were seen in the MIZAR parameters of base point, amplitude, integral, and half-time. Median cell-free DNA concentrations were higher in the group of dogs with inflammation (117 [range: 51-266] ng/mL vs. 82.7 [range: 19-206] ng/mL; p = 0.024). The iSED-predicted ESR is a good predictor of the ESRw and was obtained more rapidly. Rheometric parameters measured by MIZAR may be useful in detecting inflammation and monitoring secondary morphologic and functional changes in canine RBCs.

In silico study of combination thrombolytic therapy with alteplase and mutant pro-urokinase for fibrinolysis in ischemic stroke

The synergistic advantage of combining tissue plasminogen activator (tPA) with pro-urokinase (proUK) for thrombolysis has been demonstrated in several in vitro experiments, and a single site proUK mutant (m-proUK) has been developed for better stability in plasma. Based on these studies, combination thrombolytic therapy with intravenous tPA and m-proUK has been suggested as a promising treatment for patients with ischemic stroke. This paper evaluates the efficacy and safety of the dual therapy by computational simulations of pharmacokinetics and pharmacodynamics coupled with a local fibrinolysis model. Seven dose regimens are simulated and compared with the standard intravenous tPA monotherapy. Our simulation results provide more insights into the complementary reaction mechanisms of tPA and m-proUK during clot lysis and demonstrate that the dual therapy can achieve a similar recanalization time (about 50 min) to tPA monotherapy, while keeping the circulating fibrinogen level within a normal range. Specifically, our results show that for all dual therapies with a 5 mg tPA bolus, the plasma concentration of fibrinogen remains stable at around 7.5 μM after a slow depletion over 50 min, whereas a rapid depletion of circulating fibrinogen (to 5 μM) is observed with the standard tPA therapy, indicating the potential advantage of dual therapy in reducing the risk of intracranial hemorrhage. Through simulations of varying dose combinations, it has been found that increasing tPA bolus can significantly affect fibrinogen level but only moderately improves recanalization time. Conversely, m-proUK doses and infusion duration exhibit a mild impact on fibrinogen level but significantly affect recanalization time. Therefore, future optimization of dose regimen should focus on limiting the tPA bolus while adjusting m-proUK dosage and infusion rate. Such adjustments could potentially maximize the therapeutic advantages of this combination therapy for ischemic stroke treatment.

Evaluation of Clotting Parameters in Pregnant Women with Placental Blood Clots: Impact of Patient Characteristics and Assessment of Clexane Efficacy

Background: Clexane is used in pregnant women (PW) to minimize placental blood clotting (PBC) and fetal danger. Standard coagulation tests such as prothrombin time (PT), activated partial thromboplastin time (APTT), and international normalized ratio (INR) are critical for anticoagulant medication optimization. As a result, the study's goal was to evaluate the efficacy of clexane as well as adherence to the American Heart Association's recommended limits for routine coagulation tests. Methods: The study included forty normal PW as controls and forty PW with PBC as patients from Al-Mafraq Hospital in Jordan. Patients were administered daily subcutaneous injections of 40 mg of clexane as an anticoagulant, in conjunction with a daily 75 mg aspirin regimen. During the first trimester, 5 ml of venous blood were drawn from each participant. The PT, INR and APTT were measured. This assessment also considered variables including plasma fibrinogen concentration (PFC), age, body mass index (BMI), blood type, and fetal gender. Results: The mean age \(\pm\) SD were 29.6 \(\pm\) 6.2 for the patient group and 28.3 \(\pm\) 5.9 years for the control group. The changes in PT, INR, APTT and PFC between the control and patient groups were statistically significant independent of mother's age, BMI, baby gender, or blood type. Patients displayed inadequate anticoagulation with an INR of 0.8, falling below the recommended therapeutic range of 2-3 for anticoagulant treatment. Surprisingly, by the end of the clinical study, all patients under investigation had safely delivered their babies without difficulties. Conclusion: The observed rise in fibrinogen levels among patients may contribute to PBC formation, necessitating further investigation. Evaluation of the safety and efficacy of a combined 40 mg Clexane and 75 mg aspirin regimen in PW from the Al-Mafraq region, Jordan, is warranted.

Prophylaxis and Treatment of Bleeding or Thrombosis with Fibrinogen Concentrate (Fibryga) in Patients with Congenital Hypofibrinogenemia or Dysfibrinogenemia

Congenital fibrinogen disorders (CFDs) are rare and make up approximately 0.6% of all inherited bleeding disorders. Two subtypes include a quantitative deficiency of fibrinogen, congenital afibrinogenemia (CA), congenital hypofibrinogenemia (CH), and qualitative defect of the fibrinogen molecule, congenital dysfibrinogenemia (CD). Patients with CD may have a thrombotic as well as a hemorrhagic disease phenotype. In the past, fresh frozen plasma or cryoprecipitate were the only options available for treatment and prevention of bleeding in patients with CFD. Today in the US, human plasma-derived concentrates (FIBRYGA, Octapharma, Lachlen, Switzerland, and RiaSTAP, CSL, Melbourne, Australia) are available and considered safe and effective treatment options for CD and CH. Guidelines for the treatment and prevention of bleeding is not established for CFDs, and especially for CD. We present eight clinical cases of patients with hypo- or dysfibrinogenemia that were effectively treated with a pooled, plasma-derived fibrinogen concentrate (FIBRYGA) either prophylactically for elective or urgent surgery, or post-traumatic injury. The mean age of patients treated was 34 years (min-max 8-70 years). Three patients were male and five, female. Four patients had CH and four, CD. FIBRYGA was used to prophylactically treat a total of ten surgical procedures and two post-traumatic events in these patients. Dosing of FIBRYGA was based on the goal peak plasma fibrinogen concentration and the manufacturer's prescribing information, but modified to align with local laboratory reference ranges for the functional fibrinogen test. No acute or delayed infusion reactions (nausea, fever, rigors, headache) and no hypersensitivity reactions were noted. One patient developed two adverse events, one thrombotic and one hemorrhagic. This patient underwent left, above the knee amputation (AKA) and had a complicated postoperative period due to her multiple comorbidities including type 2 diabetes, hypertension, and long standing, poorly-controlled, severe peripheral arterial disease. She presented nineteen days after receiving FIBRGYA with a PE and multiple DVTs. Fifty-nine days later she presented with wound dehiscence and underwent an extensive excisional debridement with postoperative bleeding deemed to be secondary to her strap sliding during surgery and acting as a tourniquet for venous blood flow. For the majority (86%) of our patients described here with CH and CD, FIBRYGA was well tolerated and effective in preventing post procedural or post traumatic bleeding complications. The post procedural bleeding noted in one patient may have been due to inadequate fibrinogen concentration or other comorbid conditions. Further clinical studies are needed to determine the role of FIBRGYA and other HFC in the treatment of patients with CFD, especially those with CD.

Coagulation factor XIII is a critical driver of liver regeneration after partial hepatectomy

BackgroundActivation of coagulation and fibrin deposition in the regenerating liver appears to promote adequate liver regeneration in mice. In humans, perioperative hepatic fibrin deposition is reduced in patients who develop liver dysfunction after partial hepatectomy (PHx), but the mechanism underlying reduced fibrin deposition in these patients is unclear. Methods and ResultsHepatic deposition of cross-linked (ie, stabilized) fibrin was evident in livers of mice after two-thirds PHx. Interestingly, hepatic fibrin cross-linking was dramatically reduced in mice after 90% PHx, an experimental setting of failed liver regeneration, despite similar activation of coagulation after two-thirds or 90% PHx. Likewise, intraoperative activation of coagulation was not reduced in patients who developed liver dysfunction after PHx. Preoperative fibrinogen plasma concentration was not connected to liver dysfunction after PHx in patients. Rather, preoperative and postoperative plasma activity of the transglutaminase coagulation factor (F)XIII, which cross-links fibrin, was lower in patients who developed liver dysfunction than in those who did not. PHx-induced hepatic fibrin cross-linking and hepatic platelet accumulation were significantly reduced in mice lacking the catalytic subunit of FXIII (FXIII−/− mice) after two-thirds PHx. This was coupled with a reduction in both hepatocyte proliferation and liver–to–body weight ratio as well as an apparent reduction in survival after two-thirds PHx in FXIII−/− mice. ConclusionThe results indicate that FXIII is a critical driver of liver regeneration after PHx and suggest that perioperative plasma FXIII activity may predict posthepatectomy liver dysfunction. The results may inform strategies to stabilize proregenerative fibrin during liver resection.

The state of hemostasis system in patients after mild coronavirus infection

Introduction. One of the complications of the new coronavirus infection (COVID-19) is the development of venous thromboembolic complications. In this regard, changes in the hemostasis system that persist in the process of recovery in patients who have had a mild form of the disease are of interest.Aim. To evaluate plasma hemostasis in patients after mild coronavirus infection Materials and methods. 39 patients after mild coronavirus infection were examined. The following parameters were assessed: APTT, PT, fibrinogen, factor VIII, von Willebrand factor, D-dimer, proteins C and S, and thrombin generation. Results. In patients who underwent COVID-19, in comparison with healthy individuals, an increase in the plasma concentration of fibrinogen, von Willebrand factor antigen, and D-dimer was detected. Furthermore, increased activity of antithrombin III, decreased sensitivity to thrombomodulin, and an increase in the coagulation index were detected. Conclusion. Patients who have undergone COVID-19 are characterized by a procoagulant orientation of changes in plasma hemostasis that persist up to 3 months after the disease. It is necessary to take into account the state of the hemostasis system even in patients who have undergone COVID-19 in mild form.

The impact of aging and atrial fibrillation on thrombus formation in-silico

Abstract Background Atrial fibrillation (AF) is an age-related cardiac arrythmia that underlies one third of all strokes, with thromboemboli commonly originating from the left atrial appendage (LAA). Personalised in-silico modelling of Virchow’s triad (blood stasis, hypercoagulability and endothelial damage) can improve stroke risk assessment metrics, such as the CHA2DS2-VASc score, by providing quantitative mechanistic information [1]. The ability to quantify the impact of aging may play a critical role in patient stratification and therapy selection to reduce the risk of AF-related stroke. Aim We aim to perform in-silico modelling to quantify the effect of aging and AF on thrombus formation in the LAA by using advanced computational tools to capture blood flow, clotting mechanisms and endothelial damage [2]. Methods A virtual physiological LA model was derived from cardiac Cine MRI from an adult AF patient imaged during sinus rhythm (SR). Biomarkers for a geriatric patient were obtained from literature and applied as: i) elevated plasma fibrinogen concentration and ii) longer thrombin time-to-peak (ttP) [3]. Blood flow was simulated in SR and AF conditions for 5 cardiac cycles in the LA for both ages (totalling 4 test cases). The catalytic conversion of fibrinogen to a fibrin clot by thrombin was modelled to mimic hypercoagulability [2]. The site of endothelial injury was prescribed in the middle of the LAA. The area under curve for the fibrin concentration (Fn AUC) was measured to quantify thrombus formation. Results In the two SR cases, LA blood flow velocity increased to a maximum of 1.8 m/s after 0.6 s with a mean of 0.63 m/s during the cardiac cycle, while the two AF cases showed 1.3 m/s and 0.39 m/s, respectively, corresponding to a 38% decrease in AF. Peak velocity in the LAA was 0.35 m/s during SR and 0.18 m/s in AF. The fibrin concentration in the adult-SR case rose to 1.1 mmol/m³ over the first cardiac cycle, but both thrombin and fibrin were washed out of the LA after 1.5 s, with a Fn AUC of 0.045mmol s/m³ (Fig. 1a). The geriatric-SR case sustained fibrin generation throughout the 5 cardiac cycles reaching 3.1 mmol/m³, an Fn AUC of 2.4 mmol s/m³, and the formation of an LAA thrombus (Fig. 1b). Similarly, the adult-AF and geriatric-AF cases also saw continuous growth to 5.0 and 7.4 mmol/m³, with Fn AUCs of 6.4 and 12.6 mmol s/m³, respectively, with formation of a thrombus in the LAA in both (Fig. 1c and d). The thrombus formed in the adult-AF case was 25% larger than the geriatric-SR case, while thrombus in the geriatric-AF case was 80% larger. Conclusions This investigation quantifies the increased risk of LAA thrombus formation in older patients, with an Fn AUC increase of 55% between adult and geriatric in SR and a 100% increase when combining geriatric biomarkers with AF conditions. With further validation on larger patient cohorts, this novel in-silico tool may improve our understanding of the risks in AF-related stroke.

GRSF1 antagonizes age-associated hypercoagulability via modulation of fibrinogen mRNA stability

Age-associated hypercoagulability is accompanied by the increase of plasma levels of some coagulation factors including fibrinogen which may contribute to the increased risk of cardiovascular, cerebrovascular, and thrombotic diseases in elderly people. However, the underlying mechanism of increased plasma fibrinogen concentration during aging is still elusive. GRSF1 belongs to the heterogeneous nuclear ribonucleoproteins F/H (hnRNP F/H) subfamily. Here, we report that GRSF1 attenuates hypercoagulability via negative modulation of fibrinogen expression. We demonstrated that GRSF1 negatively regulated fibrinogen expression at both mRNA and protein levels. GRSF1 directly interacted with the coding region (CDS) of FGA, FGB, and FGG mRNAs, and decreased their stability thus mitigating fibrinogen expression. We further identified that only a few G-tracts within the Fib C domain of FGA, FGB, and FGG CDS and the qRRM2 domain of GRSF1 were required for their interaction. Moreover, we confirmed hypercoagulability and the decrease of GRSF1 expression level during mice aging. Functionally, GRSF1 overexpression in old mice liver decreased fibrinogen plasma level, reduced hypercoagulability, and mitigated blood coagulation activity, whereas GRSF1 knockdown in young mice liver increased fibrinogen plasma level and promoted blood coagulation activity. Collectively, our findings unveil a novel posttranscriptional regulation of fibrinogen by GRSF1 and uncover a critical role of GRSF1 in regulating blood coagulation activity.

Prospective, Randomized Study of Fibrinogen Concentrate Versus Cryoprecipitate for Correcting Hypofibrinogenemia in Cardiac Surgery Patients

Objective: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with hypofibrinogenemia and severe bleeding requiring transfusion. Guidelines recommend cryoprecipitate or fibrinogen concentrate (FC) for treatment of acquired hypofibrinogenemia. This study compares cryoprecipitate and FC for correction of acquired hypofibrinogenemia, and the associated costs.Design: A single-center, prospective, randomized study evaluating patients with hypofibrinogenemia after cardiac surgery. The primary endpoint was direct treatment cost. Secondary endpoints included change in fibrinogen level following FC/cryoprecipitate dosing.Setting: Single center study in Astana, Kazakhstan.Participants: Participants who underwent CPB in 2021–2022 and developed clinically significant bleeding and hypofibrinogenemia.Interventions: Patients were randomized to receive cryoprecipitate or FC.Main Results: Eighty-eight adult patients with acquired hypofibrinogenemia (<2.0 g/L) following CPB were randomized to receive cryoprecipitate (N=40) or FC (N=48) with similar demographics between groups. Overall, mean±SD 9.33±0.94 U (range, 8–10) cryoprecipitate or 1.40±0.49 g (1–2) FC were administered to the two groups. From before administration to 24 hours following, mean plasma fibrinogen increased by a mean±SD of 125±65 and 96±65 mg/dL in the cryoprecipitate and FC group, respectively. At 48 hours following administration, there was no significant difference in fibrinogen levels between groups. The mean direct cost of treatment with FC was significantly lower than with cryoprecipitate (p<0.0001): 1505.06±152.40 USD and 631.75±223.67 USD per patient for cryoprecipitate and FC, respectively.Conclusion: Analysis of plasma fibrinogen concentration showed that cryoprecipitate and FC had comparable effectiveness. However, FC is advantageous over cryoprecipitate due to its ease of handling, lower cost, and high purity.

Alterations of Body Composition, Blood Morphology and Fibrinogen Concentration after Vibration Therapy in Older Adult Women: A Randomized Controlled Trial.

Vibrotherapy is one of the methods of physical therapy. Vibration, like various forms of physical activity, affects metabolic processes and health. The aim of this study was to assess the influence of thirty vibration sessions on body composition, hematologic and rheological indexes of blood, and protein and fibrinogen concentration in elderly women's blood. The study included 69 women, aged 60-70 years (mean age 64.6 ± 2.9), who were randomly and parallel assigned into: the vibrotherapy group 1 (G1) that took part in vibrotherapy on the Knees module, the vibrotherapy group 2 (G2) that took part in vibrotherapy on the Metabolism module, and the control group (CG) without interventions. In all patients, the following assessments were performed twice-baseline and after thirty vibrotherapy sessions: an assessment of body composition, a complete blood count with a hematology analyzer and erythrocyte aggregation by a laser-optical rotational red cell analyzer; total plasma protein and fibrinogen concentrations were established, respectively, by biuret and spectrophotometric methods. Intergroup (between groups) and intragroup (within each group) changes were statistically evaluated. After applying thirty vibration sessions, a decrease in body composition parameters (BM, body mass G1, p < 0.05; G2, p < 0.001 and FFM, fat free mass G1, p < 0.05; G2, p < 0.05) was confirmed in both intervention groups and BMI, body mass index in G2 (p < 0.05). It was found that, in G2, changes in erythrocyte aggregation indexes (T ½, half time kinetics of aggregation, p < 0.05 and AI, aggregation index, p < 0.05) and decrease of fibrinogen concentration (p < 0.05) took place. A series of thirty vibration sessions did not cause significant alterations in blood morphological parameters; therefore, vibrotherapy did not disturb hematological balance. Vibration sessions had a positive effect on BM, BMI, AG and fibrinogen concentration in the studied women, indicating the usefulness of this form of activation in older adults. Due to a decrease in FFM observed in the study, vibrotherapy should be employed in conjunction with physical exercise and other forms of physical activity in the group of older adults.

Serum Fibrinogen and Renal Dysfunction as Important Predictors of Left Atrial Thrombosis in Patients with Atrial Fibrillation.

As has been shown previously, patients with atrial fibrillation (AF) who have left atrial thrombus (LAT) also have elevated plasma concentrations of fibrinogen. In this study, we tried to determine if this is the consequence of a genetic trait and whether elevated concentrations of fibrinogen could be used to predict LAT in patients with AF. We recruited 181 consecutive patients scheduled for pulmonary vein isolation (PVI) or direct current cardioversion. The primary endpoint was the presence of LAT on transesophageal echocardiography (TOE). We recorded routine clinical and biochemical data as well as the polymorphism type of the fibrinogen gene for the β chain. To control potentially interfering variables, we performed propensity score matching (PSM). Multivariable and univariable logistic regression models (LRM) were computed using the CHA2DS2-Vasc score, the fibrinogen concentration and creatinine clearance as estimated by the Cockcroft-Gault equation. 60 of 181 patients had LAT as detected by TOE. As expected, patients with LAT had significantly higher concentrations of fibrinogen (3.9 vs. 3.6 g/L); p = 0.01 in the unadjusted analysis. After performing PSM, there were no statistically significant differences between the groups, except for creatinine clearance (79.9 vs. 96.8 mL/min); p = 0.01. There were also no differences regarding the -455 G/A βfibrinogen polymorphism distribution between the two groups. After constructing the LRM, we found no performance enhancement for the CHA2DS2-Vasc score by adding the fibrinogen concentration or creatinine clearance alone, but when all three variables were put together, there was a significant improvement in LAT prediction (AUC 0.64 vs. 0.72), p = 0.026. Our study found no evidence of elevated levels of circulating fibrinogen in patients with LAT or a connection between those levels and the A/A and A positive polymorphism. When used together with renal function markers such as creatinine clearance, plasma fibrinogen concentrations can provide additional power to the CHA2DS2-Vasc score for predicting LAT.

Blood and liver telomere length, mitochondrial DNA copy number, and hepatic gene expression of mitochondrial dynamics in mid-lactation cows supplemented with l-carnitine under systemic inflammation

The current study was conducted to examine the effect of l-carnitine (LC) supplementation on telomere length and mitochondrial DNA copy number (mtDNAcn) per cell in mid-lactation cows challenged by lipopolysaccharide (LPS) in blood and liver. The mRNA abundance of 31 genes related to inflammation, oxidative stress, and the corresponding stress response mechanisms, the mitochondrial quality control and the protein import system, as well as the phosphatidylinositol 3-kinase/protein kinase B pathway, were assessed using microfluidics integrated fluidic circuit chips (96.96 dynamic arrays). In addition to comparing the responses in cows with or without LC, our objectives were to characterize the oxidative and inflammatory status by assessing the circulating concentration of lactoferrin (Lf), haptoglobin (Hp), fibrinogen, derivates of reactive oxygen metabolites (dROM), and arylesterase activity (AEA), and to extend the measurement of Lf and Hp to milk. Pluriparous Holstein cows were assigned to either a control group (CON, n = 26) or an LC-supplemented group (CAR; 25 g LC/cow per day; d 42 ante partum to d 126 postpartum (PP), n = 27). On d 111 PP, each cow was injected intravenously with LPS (Escherichia coli O111:B4, 0.5 µg/kg). The mRNA abundance was examined in liver biopsies of d -11 and +1 relative to LPS administration. Plasma and milk samples were frequently collected before and after the challenge. After LPS administration, circulating plasma fibrinogen and serum dROM concentrations increased, whereas AEA decreased. Moreover, serum P4 initially increased by 3 h after LPS administration and declined thereafter irrespective of grouping. The Lf concentrations increased in both groups after LPS administration, with the CAR group showing greater concentrations in serum and milk than the CON group. After LPS administration, telomere length in blood increased, whereas mtDNAcn per cell decreased; however, both remained unaffected in liver. For mitochondrial protein import genes, the hepatic mRNA abundance of the translocase of the mitochondrial inner membrane (TIM)-17B was increased in CAR cows. Moreover, TIM23 increased in both groups after LPS administration. Regarding the mRNA abundance of genes related to stress response mechanisms, 7 out of 14 genes showed group × time interactions, indicating a (local) protective effect due to the dietary LC supplementation against oxidative stress in mid-lactating dairy cows. For mtDNAcn and telomere length, the effects of the LPS-induced inflammation were more pronounced than the dietary supplementation of LC. Dietary LC supplementation affected the response to LPS primarily by altering mitochondrial dynamics. Regarding mRNA abundance of genes related to the mitochondrial protein import system, the inner mitochondrial membrane translocase (TIM complex) seemed to be more sensitive to dietary LC than the outer mitochondrial membrane translocase (TOM complex).

Utility of serum amyloid A in monitoring clinical response to antimicrobial treatment in horses with bacterial pneumonia.

Serum amyloid A (SAA) is a major acute phase protein in horses which could be a useful tool for assessing clinical response to treatment of bacterial pneumonia in adult horses. To monitor SAA concentration in response to treatment and identify associations among SAA concentration, WBC and neutrophil counts, and fibrinogen in bacterial pneumonia in adult horses. Eighteen adult horses with bacterial pneumonia. Prospective clinical study. Horses hospitalized with bacterial pneumonia were enrolled and SAA concentration and vital signs were assessed daily. SAA concentration was measured by a handheld meter. CBC and plasma fibrinogen were assessed on days 0, 1, and 2, then every 3 days until discharge. Data were not normally distributed and therefore were log transformed. Log-transformed data were analyzed and comparisons were performed on LSMeans by the 2-sided Student's t-test at the 5% level of significance. Geometric mean SAA concentration on day 0 was 537 μg/mL (SE 383 μg/mL). Geometric mean SAA concentration decreased significantly over time (P = .0001), peaking at day 2 (geomean 1038 μg/mL, SE 261.7 μg/mL) and decreasing until discharge. Plasma concentration of fibrinogen (P = .06), neutrophil count (P = .48), and WBC count (P = .07) did not change significantly over time. SAA concentration decreased significantly over the course of treatment and correlated with clinical improvement of pneumonia whereas fibrinogen, neutrophil, and WBC counts did not.

Association between FGA gene polymorphisms and coronary artery lesion in Kawasaki disease.

To investigate the correlation between FGA gene polymorphisms and coronary artery lesion in Kawasaki disease. Two hundred and thirty four children with Kawasaki disease (KD group), 200 healthy children (normal group) and 208 children with non-KD fever (fever group) were enrolled. General clinical indicators, the concentration of serum MMPs, TIMP-1, FG-α,fibrinogen level, molecular function (FMPV/ODmax) and FGA Thr312Ala polymorphism were detected individually by testing peripheral venous blood after fasting in the morning. There was no significant difference in average age among the three groups, which were 3.03 ± 1.22 years, 3.17 ± 1.30 years, and 3.21 ± 1.31 years, respectively. Compared with those in the fever group, the levels of white blood cell count (WBC), platelet count (PLT), procalcitonin (PCT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and fibrinogen (Fg) levels were significantly increased in the KD group. Red blood cell count (RBC) and hemoglobin (Hb) levels were significantly decreased (p < 0.05).The concentration of serum MMPs, TIMP-1, and FG-α in the KD and fever groups were significantly higher than those in the normal group (p < 0.05). The concentration of MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1, and FG-α in the KD group were significantly higher than those in the fever group (p < 0.05).The KD group was divided into two subgroups,55 patients with combined CAL and 179 patients without combined CAL. The plasma fibrinogen concentration in the combined CAL group was significantly higher than that in the non-combined CAL and normal groups (p < 0.01). There was no statistically significant difference in FMPV/ODmax among the three groups (p > 0.05). Compared with normal group, the FGA GG, GA, and AA genotype and G, A allele frequency of the FGA gene polymorphism in the KD group showed no significant difference (p > 0.05). In the KD group, the most common type in children with CAL was GA, while the most common type in children without CAL was GG. MMPs and FG-α were significantly upregulated in KD patients. The proportion of FGA genotype GA in children with CAL was significantly higher than that in children without CAL, suggesting that FGA gene polymorphisms affect coronary artery lesion in children with KD.

Full blood count and some haemorheologic variables of vendors exposed to liquefied petroleum (cooking) gas: a comparative study

Introduction: Cooking gas in the form of liquefied petroleum gas is sold in gas stations and outlets by vendors who do not use personal protective equipment despite working in a high-risk environment hence they have a high exposure to inhalation of the chemicals in the gas. This study assessed the full blood count and haemorheologic variables of vendors exposed to liquefied petroleum gas. Methods: Forty gas vendors were enrolled from four gas stations in Calabar while forty apparently healthy individuals who do not work in gas-related jobs were recruited as control. Ethical approval was granted by the Cross River State Ministry of Health, Calabar. Permission to enroll workers was obtained from the management of gas stations while study subjects gave informed consent. A structured questionnaire was used to obtain demographic information and health history while blood pressure, weight and height were measured using standard instruments; the body mass index was calculated. The full blood count and haemorheologic variables were determined by standard methods. Data analysis was done using a student t-test on SPSS version 21 and a P value ≤0.05 was considered significant. Results: The mean age was 25.9±3.2 years and 26.5±6.5 years for the test and control groups with gas vendors being predominantly males (97.5%). Work duration of 97.5% of gas vendors was ≤5 years. Sixty percent of the control and 42.5% of the gas vendors engaged in regular exercise while 40% and 57.5% do not. Sixty-seven-point five percent (67.5%) of the control rarely go for medical checks and 27.5% had never had a medical check with only 2% who check often. For the gas vendors, 55% have never had a medical check while 45% of them rarely check. Also, 42.5% of the control have never or rarely checked their blood pressure while 15% check often; 62.5% of the gas vendors have never checked their blood pressure while 37.5% rarely check. There was a family history of hypertension for 2 (5%) of the control and none for the test group. Also, 1 (2.5%) of the gas vendors had a history of fainting episodes while 39 of them and the control did not. Only 10% and 20% of the gas vendors use nose mask and hand gloves with the use of overalls and safety boots being 40% for each. The body mass index of the control group (25.15kg/m2) was not different (P&gt;0.05) from that of the test group (24.53kg/m2). Whereas the systolic blood pressure was higher for the gas vendors than the control (126.47mmHg and 120.32mmHg), the diastolic blood pressures were comparable (74.60mmHg versus 72.92mmHg). The full blood count shows the red blood cell count, haematocrit and haemoglobin of the gas vendors were significantly higher (P&lt;0.05) than the control value while the mean corpuscular volume and mean corpuscular haemoglobin were comparable (P&gt;0.05). Again, the mean corpuscular haemoglobin concentration and red cell distribution width standard deviation of the gas vendors were significantly higher (P&lt;0.05) versus the control while the red cell distribution width coefficient of variation was comparable (P&gt;0.05). The total white blood cell count and the absolute granulocyte and lymphocyte counts of the gas vendors were significantly higher (P&lt;0.05) than the control value while the mixed leucocyte count was not different (P&gt;0.05) between the two groups. The platelet count, mean platelet volume, platelet distribution width, plateletcrit, platelet large cell ratio and platelet large cell count were significantly higher (P&lt;0.05) for the gas vendors when compared to the control. Relative plasma viscosity and fibrinogen concentration were significantly higher (P=0.030) when the test group was compared to the control. Conclusions: This study has demonstrated an increase in red cell, white cell and platelet parameters of vendors exposed to cooking gas as a probable response to an induced state of chronic inflammation. There is also impaired haemorheology as expressed by an increase in relative plasma viscosity and fibrinogen concentration with possible pre-disposition to cardiovascular disease as a consequence. Management of cooking gas stations and the vendors should be educated on the need to use personal protective equipment in order to reduce exposure to the components of cooking gas.