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Journal of Intensive Care Medicine Sep 2022New coronavirus disease (COVID-19) has become an international emergency. As many of the intensive care unit (ICU) patients with the disease also present multiple organ...
New coronavirus disease (COVID-19) has become an international emergency. As many of the intensive care unit (ICU) patients with the disease also present multiple organ failure, blood purification techniques might be a good choice in their treatment. In this study we aimed to investigate the role of cytokine removal in COVID-19 patients managed in ICUs. For this case-control study we have investigated the role of the cytokine removal by means of two resin membranes (HA330 and Mediasorb) in COVID-19 patients managed in ICUs. Particularly, we investigated the overtime variation in clinical severity scores, laboratory variables, and effects on hospital and ICU stay and mortality. Seventy-two patients have been evaluated, of which half constituted Cytokine Filtration (CF) Group, and other half the Case-Control (CC) Group. Mortality was 55.6% and 50% in CF and CC groups, respectively. In the CF Group, there was decrease in C-reactive protein (CRP) and fibrinogen levels measured at the end of cytokine adsorption; lymphocyte count and ratio were increased, whereas neutrophile ratio was decreased. There were no differences between the groups regarding other laboratory variables, SOFA scores and vasopressor uses. We have demonstrated decrease in CRP, fibrinogen and increase in lymphocyte count in the patients having cytokine adsorption, but there was no clinical reflection of these benefits, and no decrease in mortality as well. Even though there is physio-pathologic rationale to use cytokine adsorption techniques for immunomodulation in critically ill COVID-19 patients, it is early to make strong suggestions about their benefits.
Topics: Adsorption; COVID-19; Case-Control Studies; Critical Illness; Cytokines; Fibrinogen; Humans; Intensive Care Units; Retrospective Studies
PubMed: 35274999
DOI: 10.1177/08850666221085185 -
Interactive Cardiovascular and Thoracic... Mar 2014Fibrinogen concentrate is increasingly used in cardiac surgery when bleeding is anticipated or ongoing. Since randomized clinical studies to support this are lacking, it... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Fibrinogen concentrate is increasingly used in cardiac surgery when bleeding is anticipated or ongoing. Since randomized clinical studies to support this are lacking, it is relevant to know whether lower fibrinogen levels are associated with excessive bleeding. We performed a systematic review and meta-analysis to define the association between fibrinogen levels and blood loss after cardiac surgery.
METHODS
A database search (January 2013) was performed on publications assessing the association between pre- and postoperative fibrinogen levels and postoperative blood loss in adult patients undergoing cardiac surgery. Cohort studies and case-control studies were eligible for inclusion. The main outcome was the pooled correlation coefficient, calculated via Fisher's Z transformation scale, in a random-effects meta-analysis model stratified for the time point at which fibrinogen was measured.
RESULTS
A total of 20 studies were included. The pooled correlation coefficient of studies (n = 9) concerning preoperative fibrinogen levels and postoperative blood loss was -0.40 (95% confidence interval: -0.58, -0.18), pointing towards more blood loss in patients with lower preoperative fibrinogen levels. Among papers (n = 16) reporting on postoperative fibrinogen levels and postoperative blood loss, the pooled correlation coefficient was -0.23 (95% confidence interval: -0.29, -0.16).
CONCLUSIONS
Our meta-analysis indicated a significant but weak-to-moderate correlation between pre- and postoperative fibrinogen levels and postoperative blood loss in cardiac surgery. This moderate association calls for appropriate clinical studies on whether fibrinogen supplementation will decrease postoperative blood loss.
Topics: Biomarkers; Cardiac Surgical Procedures; Chi-Square Distribution; Coagulants; Fibrinogen; Humans; Postoperative Hemorrhage; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 24316606
DOI: 10.1093/icvts/ivt506 -
Journal of Thrombosis and Haemostasis :... Mar 2023Fibrinogen has an established, essential role in both coagulation and inflammatory pathways, and these processes are deeply intertwined in the development of thrombotic...
BACKGROUND
Fibrinogen has an established, essential role in both coagulation and inflammatory pathways, and these processes are deeply intertwined in the development of thrombotic and atherosclerotic diseases. Previous studies aimed to better understand the (patho) physiological actions of fibrinogen by characterizing the genomic contribution to circulating fibrinogen levels.
OBJECTIVES
Establish an in vitro approach to define functional roles between genes within these loci and fibrinogen synthesis.
METHODS
Candidate genes were selected on the basis of their proximity to genetic variants associated with fibrinogen levels and expression in hepatocytes and HepG2 cells. HepG2 cells were transfected with small interfering RNAs targeting candidate genes and cultured in the absence or presence of the proinflammatory cytokine interleukin-6. Effects on fibrinogen protein production, gene expression, and cell growth were assessed by immunoblotting, real-time polymerase chain reaction, and cell counts, respectively.
RESULTS
HepG2 cells secreted fibrinogen, and stimulation with interleukin-6 increased fibrinogen production by 3.4 ± 1.2 fold. In the absence of interleukin-6, small interfering RNA knockdown of FGA, IL6R, or EEPD1 decreased fibrinogen production, and knockdown of LEPR, PDIA5, PLEC, SHANK3, or CPS1 increased production. In the presence of interleukin-6, knockdown of FGA, IL6R, or ATXN2L decreased fibrinogen production. Knockdown of FGA, IL6R, EEPD1, LEPR, PDIA5, PLEC, or CPS1 altered transcription of one or more fibrinogen genes. Knocking down ATXN2L suppressed inducible but not basal fibrinogen production via a post-transcriptional mechanism.
CONCLUSIONS
We established an in vitro platform to define the impact of select gene products on fibrinogen production. Genes identified in our screen may reveal cellular mechanisms that drive fibrinogen production as well as fibrin(ogen)-mediated (patho)physiological mechanisms.
Topics: Humans; Fibrinogen; Interleukin-6; Gene Expression; Hepatocytes; Hep G2 Cells; Hemostatics
PubMed: 36696182
DOI: 10.1016/j.jtha.2022.10.027 -
Journal of Clinical Laboratory Analysis Feb 2019Heterophilic antibodies are still an important source of interference in immunoassays, but reports of interference with D-dimers are rare. Are D-dimer level...
BACKGROUND
Heterophilic antibodies are still an important source of interference in immunoassays, but reports of interference with D-dimers are rare. Are D-dimer level abnormalities, found in the clinic, caused by heterophilic antibodies as well, or are other mechanisms involved? We will elaborate on this issue through two different examples in this article.
METHODS
Serum from two patients with significantly elevated levels of D-dimers were measured and compared by different methods, diluted, and dealt with heterophilic antibody blockers. At the same time, to retrieve the interference, we focused on the cause of D-dimer false positives and made a systematic review of the literature.
RESULTS
The D-dimer values were normal (0.49 and 0.15 μg/mL) detected with different testing method and decreased after addition of heterophilic antibody blocking reagent. According to literature data, there were 66.7% (4/6) references showed the interference were heterophilic antibody.
CONCLUSIONS
The influence of heterophilic antibodies on the measurement of D-dimers remains a big challenge. Different measuring instruments and methods may have significant differences in the measurement of D-dimers. By using a combination of instrumental methods for measuring, incorporating heterophilic antibody blockers, and combining with clinical performance and imaging data, most of the interference can be eliminated.
Topics: Aged; Aged, 80 and over; Antibodies, Heterophile; Female; Fibrin Fibrinogen Degradation Products; Humans; Immunoassay; Reproducibility of Results
PubMed: 30320416
DOI: 10.1002/jcla.22687 -
Injury May 2023Fibrin stabilizing factor (FXIII) plays a crucial role in blood clotting, tissue repair, and immune defense. FXIII deficiency after trauma can lead to prolonged wound...
INTRODUCTION
Fibrin stabilizing factor (FXIII) plays a crucial role in blood clotting, tissue repair, and immune defense. FXIII deficiency after trauma can lead to prolonged wound healing due to persistent infections or coagulation disorders. The aim of this study was to describe the prevalence of acquired FXIII deficiency after trauma and to provide a description of the time-course changes of important coagulation parameters in relation to FXIII activity. In this context, patient characteristics, laboratory data, and treatment modalities were examined with respect to their influence on FXIII activity. Furthermore, the effects of in vitro administration of FXIII on clot firmness and outcomes in patients with severe traumatic brain injury were investigated.
PATIENTS AND METHODS
Two trauma cohorts (A and B) were examined prospectively in a two-center study, and another (cohort C) was examined retrospectively. In cohort A (trauma patients, n=880) routine laboratory tests were conducted, and FXIII activity was measured. In cohort B (polytrauma patients, n=26), additional clinical parameters were collected, and in-vitro FXIII administration and rotational thromboelastometry (ROTEM) analyses were performed. In cohort C (polytrauma patients with severe traumatic brain injury [sTBI], n=84), the impact of initially measured FXIII activity on clinical outcomes after sTBI was investigated using the modified Rankin Scale (mRS) at least 6 months after trauma.
RESULTS
The prevalence of FXIII activity <70% in cohort A was 12.4%, with significant differences in age, Hb, fibrinogen, and Hct levels, platelet count, aPTT, and INR (vs. prevalence of FXIII activity >70%). Cohort B showed a decrease in FXIII activity from 85% to 58% after 7 days. FXIII deficiency correlated with time after trauma, aPTT, and fibrinogen level, lactate, and Hb levels. In-vitro administration of FXIII showed a positive influence on clot firmness due to improved maximum clot firmness (MCF in FIBTEM) and reduced maximum lysis (ML in EXTEM). Finally, a significant difference in FXIII activity between patients after sTBI with good and poor clinical outcomes was observed 6 months after trauma.
CONCLUSION
We demonstrated that trauma-associated FXIII deficiency is a common coagulation disorder, with FXIII deficiency increasing further in the first 7 days after trauma, the period of early surgical care. In vitro administration of FXIII was able to demonstrate significant clot stabilizing effects. For trauma patients with sTBI, FXIII activity could serve as a prognostic parameter, as it differed significantly between patients with good and poor clinical outcomes.
Topics: Humans; Factor XIII Deficiency; Retrospective Studies; Blood Coagulation Disorders; Fibrinogen; Thrombelastography; Multiple Trauma; Brain Injuries, Traumatic
PubMed: 36577625
DOI: 10.1016/j.injury.2022.12.021 -
Vascular Health and Risk Management 2014TachoSil(®) is a medicated sponge coated with human fibrinogen and human thrombin. It is indicated as a support treatment in adult surgery to improve hemostasis,... (Review)
Review
BACKGROUND
TachoSil(®) is a medicated sponge coated with human fibrinogen and human thrombin. It is indicated as a support treatment in adult surgery to improve hemostasis, promote tissue sealing, and support sutures when standard surgical techniques are insufficient. This review systematically analyses the international scientific literature relating to the use of TachoSil in hemostasis and as a surgical sealant, from the point of view of its economic impact.
METHODS
We carried out a systematic review of the PubMed literature up to November 2013. Based on the selection criteria, papers were grouped according to the following outcomes: reduction of time to hemostasis; decrease in length of hospital stay; and decrease in postoperative complications.
RESULTS
Twenty-four scientific papers were screened, 13 (54%) of which were randomized controlled trials and included a total of 2,116 patients, 1,055 of whom were treated with TachoSil. In the clinical studies carried out in patients undergoing hepatic, cardiac, or renal surgery, the time to hemostasis obtained with TachoSil was lower (1-4 minutes) than the time measured with other techniques and hemostatic drugs, with statistically significant differences. Moreover, in 13 of 15 studies, TachoSil showed a statistically significant reduction in postoperative complications in comparison with the standard surgical procedure. The range of the observed decrease in the length of hospital stay for TachoSil patients was 2.01-3.58 days versus standard techniques, with a statistically significant difference in favor of TachoSil in eight of 15 studies.
CONCLUSION
This analysis shows that TachoSil has a role as a supportive treatment in surgery to improve hemostasis and promote tissue sealing when standard techniques are insufficient, with a consequent decrease in postoperative complications and hospital costs.
Topics: Blood Loss, Surgical; Cost-Benefit Analysis; Drug Combinations; Drug Costs; Fibrinogen; Hemostatic Techniques; Hemostatics; Hospital Costs; Humans; Length of Stay; Outcome and Process Assessment, Health Care; Postoperative Hemorrhage; Thrombin; Time Factors; Treatment Outcome
PubMed: 25246797
DOI: 10.2147/VHRM.S63199 -
Journal of Thrombosis and Haemostasis :... Dec 2022Fibrin, the main scaffold of thrombi, is susceptible to citrullination by PAD (peptidyl arginine deiminase) 4, secreted from neutrophils during the formation of...
BACKGROUND
Fibrin, the main scaffold of thrombi, is susceptible to citrullination by PAD (peptidyl arginine deiminase) 4, secreted from neutrophils during the formation of neutrophil extracellular traps. Citrullinated fibrinogen (citFg) has been detected in human plasma as well as in murine venous thrombi, and it decreases the lysability and mechanical resistance of fibrin clots.
OBJECTIVE
To investigate the effect of fibrinogen citrullination on the structure of fibrin clots.
METHODS
Fibrinogen was citrullinated with PAD4 and clotted with thrombin. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to measure fiber thickness, fiber height/width ratio, and fiber persistence length in clots containing citFg. Fiber density was measured with laser scanning microscopy (LSM) and permeability measurements were carried out to estimate the porosity of the clots. The intra-fiber structure of fibrin was analyzed with small-angle X-ray scattering (SAXS).
RESULTS
SEM images revealed a decrease in the median fiber diameter that correlated with the fraction of citFg in the clot, while the fiber width/length ratio remained unchanged according to AFM. With SAXS we observed that citrullination resulted in the formation of denser clots in line with increased fiber density shown by LSM. The permeability constant of citrullinated fibrin decreased more than 3-fold indicating significantly decreased porosity. SAXS also showed largely preserved periodicity in the longitudinal assembly of fibrin monomers.
CONCLUSION
The current observations of thin fibers combined with dense packing and low porosity in the presence of citFg can provide a structural framework for the mechanical fragility and lytic resistance of citrullinated fibrin.
Topics: Humans; Mice; Animals; Fibrinogen; Scattering, Small Angle; X-Ray Diffraction; Fibrin; Hemostatics; Thrombosis; Permeability; Microscopy, Electron, Scanning
PubMed: 36083779
DOI: 10.1111/jth.15875 -
Pharmacology 2023Autoimmune thyroiditis seems to be associated with increased cardiometabolic risk. Statins, the mainstay of cardiovascular risk reduction and prevention, were found to...
INTRODUCTION
Autoimmune thyroiditis seems to be associated with increased cardiometabolic risk. Statins, the mainstay of cardiovascular risk reduction and prevention, were found to reduce thyroid antibody titers. The aim of this study was to investigate plasma markers of cardiometabolic risk in statin-treated women with thyroid autoimmunity.
METHODS
We compared two matched groups of euthyroid women with hypercholesterolemia receiving atorvastatin treatment: subjects with autoimmune (Hashimoto's) thyroiditis (group A, n = 29) and subjects without thyroid pathology (group B, n = 29). Plasma lipids, glucose homeostasis markers, as well as circulating levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and 25-hydroxyvitamin D were measured before atorvastatin treatment and 6 months later.
RESULTS
At entry, both groups differed in antibody titers, insulin sensitivity, and plasma levels of uric acid, hsCRP, fibrinogen, homocysteine, and 25-hydroxyvitamin D. Atorvastatin-induced reduction in hsCRP and homocysteine, but not in total cholesterol and LDL-cholesterol, was more pronounced in group B than in group A. Only in group B, the drug decreased uric acid and fibrinogen and increased 25-hydroxyvitamin D. In group A, atorvastatin reduced insulin responsiveness.
CONCLUSION
The obtained results indicate that euthyroid women with Hashimoto's thyroiditis may benefit to a lesser degree from atorvastatin treatment than other populations of women with hypercholesterolemia.
Topics: Humans; Female; Atorvastatin; Hypercholesterolemia; Thyroiditis, Autoimmune; C-Reactive Protein; Cardiometabolic Risk Factors; Uric Acid; Risk Factors; Hashimoto Disease; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol; Fibrinogen; Cardiovascular Diseases
PubMed: 36878199
DOI: 10.1159/000529242 -
Interactive Cardiovascular and Thoracic... Sep 2022Air leakage after lung resection is a common morbidity that may lengthen hospital stay. Applying sealant to a lesion is an effective prophylaxis in clinical practice....
OBJECTIVES
Air leakage after lung resection is a common morbidity that may lengthen hospital stay. Applying sealant to a lesion is an effective prophylaxis in clinical practice. This study aimed to examine the effect of a combination of a bioabsorbable polyglycolic acid (PGA) fabric and fibrin glue (FG) on air sealing by measuring the in vitro mechanical strength and degradation of the fabric, and in vivo histological changes after implantation.
METHODS
A defect was created in the canine left upper lung lobe, and then filled with a fibrinogen solution and covered with a PGA sheet spray-coated with fibrinogen and thrombin. After 1 and 4 weeks, air leakage from the lesion was examined in vivo under airway pressure. Tissue samples were harvested for histological assessment.
RESULTS
The mechanical strength of the PGA fabric remained at 80-90% of the baseline level for 1 week in phosphate-buffered saline, and then rapidly decreased to zero thereafter. Air leakage from the lung defect was prevented by the combination of PGA fabric and FG at 1 and 4 weeks. Histological examinations showed that PGA bundles persisted with a non-specific inflammatory response for 2 weeks and then gradually broke into sparse yarns surrounded by collagen fibres and capillaries by 8 weeks. The lung defect was filled with FG at 1 week and by granulation tissue thereafter.
CONCLUSIONS
These results provide evidence for the efficacy of a combination of PGA fabric and FG for the prevention of air leakage in the critical period after lung surgery.
Topics: Animals; Dogs; Collagen; Fibrin Tissue Adhesive; Fibrinogen; Lung; Phosphates; Polyglycolic Acid; Postoperative Complications; Thrombin; Tissue Adhesives
PubMed: 35894665
DOI: 10.1093/icvts/ivac196 -
Journal of Thrombosis and Thrombolysis Jul 2021As patients with COVID-19 pneumonia admitted to intensive care unit (ICU) have high rates of thrombosis, high doses of thromboprophylaxis have been proposed. The...
As patients with COVID-19 pneumonia admitted to intensive care unit (ICU) have high rates of thrombosis, high doses of thromboprophylaxis have been proposed. The associated bleeding risk remains unknown. We investigated major bleeding complications in ICU COVID-19 patients and we examined their relationship with inflammation and thromboprophylaxis. Retrospective monocentric study of consecutive adult patients admitted in ICU for COVID-19 pneumonia requiring mechanical ventilation. Data collected included demographics, anticoagulation status, coagulation tests and outcomes including major bleeding and thrombotic events. Among 56 ICU COVID-19 patients, 10 (18%) patients had major bleeding and 16 (29%) thrombotic events. Major bleeding occurred later than thrombosis after ICU admission [17(14-23) days versus 9(3-11) days respectively (p = 0.005)]. Fibrinogen concentration always decreased several days [4(3-5) days] before bleeding; D-dimers followed the same trend. All bleeding patients were treated with anticoagulants and anticoagulation was overdosed for 6 (60%) patients on the day of bleeding or the day before. In the whole cohort, overdose was measured in 22 and 78% of patients receiving therapeutic anticoagulation during fibrinogen increase and decrease respectively (p < 0.05). Coagulation disorders had biphasic evolution during COVID-19: first thrombotic events during initial hyperinflammation, then bleeding events once inflammation reduced, as confirmed by fibrinogen and D-dimers decrease. Most bleeding events complicated heparin overdose, promoted by inflammation decrease, suggesting to carefully monitor heparin during COVID-19. Thromboprophylaxis may be adapted to this biphasic evolution, with initial high doses reduced to standard doses once the high thrombotic risk period ends and fibrinogen decreases, to prevent bleeding events.
Topics: Aged; Anticoagulants; Biomarkers; Blood Coagulation; COVID-19; Critical Illness; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hemorrhage; Humans; Inflammation Mediators; Male; Middle Aged; Respiration, Artificial; Retrospective Studies; Risk Assessment; Risk Factors; Thrombosis; Time Factors; Treatment Outcome
PubMed: 33646501
DOI: 10.1007/s11239-021-02403-9