Differences In Fibrinogen Levels Research Articles

Study of clinical profile of patients with acute coronary syndrome and the correlation of serum fibrinogen and grace score as a prognostic marker for predicting 3-month mortality

Introduction. Acute coronary syndrome (ACS), encompassing unstable angina, non-ST-segment eleva­tion myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI), is a major global health concern due to its high morbidity and mortality. Research highlights a link between ACS and elevated acute phase reactants like C-reactive protein, emphasizing the role of inflammation and atherosclerosis. Serum fibrinogen, crucial in thrombus formation and an inflammatory marker, is significant in the coagu­lation process. This study investigates the predictive value of serum fibrinogen levels and the GRACE score for 3-month mortality in ACS patients. Aim. To examine the clinical profile of ACS patients and evaluate serum fibrinogen and GRACE score as prognostic markers for 3-month mortality. Methodology. A prospective observational study was conducted on 50 patients diagnosed with ACS at Saveetha Medical College Hospital. The study included adults over 18 with ACS, excluding those with severe comorbid conditions like end-stage liver disease or malignancy. Serum fibrinogen levels were measured at presentation and at 3 months using an automated coagulation analyzer. GRACE scores were calculated, and clinical assessments including ECG, cardiac markers, and ECHO were conducted. Data analysis involved IBM SPSS Statistics, utilizing descriptive statistics, t-tests, ANOVA, and Pearson's Correlation. Results. The study group had diverse demographics and a high prevalence of cardiovascular symptoms and comorbidities. The clinical profile of ACS showed a higher incidence of STEMI. Serum fibrinogen levels varied significantly across different Killip classes at presentation and at 3 months, with the highest levels in the more severe classes. Higher serum fibrinogen was linked to recurrent heart failure admissions and higher KILIPS class. However, there was no significant difference in fibrinogen levels between patients with and without interventions. The GRACE score was higher in STEMI patients, those with LV dysfunction, and correlated with higher serum fibrinogen. Lower FACIT F scores, indicating higher fatigue, were associated with higher fibrinogen levels and readmissions for heart failure. Conclusion. Higher serum fibrinogen levels and GRACE scores at presentation and at three months are indicators of severe myocardial infarction, increased heart failure readmission rates, and greater fatigue in ACS patients. These markers are valuable for evaluating morbidity in ACS and can aid in enhancing patient management strategies.

Reusing Plasma Filters in Resource-Poor Settings: Experience From a Tertiary Care Hospital.

Therapeutic plasma exchange (TPE) is used to manage various life-threatening illnesses. It is widely performed by nephrologists, intensivists, pathologists, or experts in transfusion medicine worldwide. However, the costs of TPE sessions are exceedingly high, and they have a huge impact on patients' financial burden. Herein, we investigated the outcomes of the reuse of plasma filters in TPE on several occasions. This is a retrospective analysis of patients receiving TPE from January 1, 2020, to April 30, 2023, in the Department of Nephrology. A formulation of 4.5% peracetic acid and 24% hydrogen peroxide acid with RO water dilution was used for reprocessing. Clinical outcomes, risks, and cost-benefit were evaluated and compared between the plasma filter reuse group (GP-1) and the no-reuse group (GP-2). A total of 70 patients were included in this study. 200 and 112 TPE sessions were performed in GP-1 and GP-2, respectively. The most common indication for TPE in both groups was neurological. The clinical efficacy of TPE was similar in both groups. There was no difference in the clotting of the plasma filter, any allergic reaction, infection, or bleeding in the group. However, there was a significant difference in levels of fibrinogen (p=0.03) pre and post-procedure in both groups. The incidence of hypotension was found to be higher in GP-1 (26%) compared to GP-2 (15.6%), p = 0.05. The cost of overall treatment was 38% less in GP-1. The reuse of plasma filters is a safe and effective method for cost minimization in patients requiring TPE. This method can be effectively utilized in resource-poor settings without any increased risk of adverse effects.

Impact of early and empirical cryoprecipitate administration on the transfusion requirements in trauma patients with hemorrhagic shock

Abstract BACKGROUND: Fibrinogen is the earliest coagulation factor falling to the critical levels in severely bleeding trauma patients. Early fibrinogen supplementation in these patients has been recommended to improve the patient outcomes. However, its role in reducing the overall transfusion requirement remains equivocal. AIMS: This study aimed to evaluate the effect of early cryoprecipitate (CRYO) administration on the transfusion requirement and the coagulation assays in trauma patients with hemorrhagic shock. SETTINGS AND DESIGN: An interventional study was conducted in two phases at level I trauma center. During the 1st phase (Group I), patients received blood components in accordance with current practices, whereas in the 2nd phase (Group II), patients received an additional CRYO (pool of 6 units) empirically within 90 min of admission. METHODS: Demographics, clinical, injury characteristics, transfusion requirements, blood counts, and coagulation assays were assessed for both the study groups. STATISTICAL ANALYSIS: The comparative analysis was done for blood component utilization and coagulations assays (prothrombin time, activated partial thromboplastin time, and fibrinogen levels) in both study groups. RESULTS AND CONCLUSIONS: A total of 50 patients in Group I and 51 patients in Group II were recruited. Demographics, clinical, injury characteristics, and laboratory investigations were comparable, except for heart rate, blood pressure, and injury scores. Significant reductions in red blood cell and platelet transfusions were observed, whereas the fresh-frozen plasma transfusions remained unaffected. The results of coagulation assays at 18–24 h were similar for both groups. Although no significant differences in fibrinogen levels were observed despite CRYO administration, decreased requirement for transfusions indicated an improved hemostasis in CRYO group.

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.

Effectiveness of Administration of Fibrinogen Concentrate as Prevention of Hypofibrinogenemia in Patients with Traumatic Brain Injury with a Higher Risk for Severe Hyperfibrinolysis: Single Center Before-and-After Study.

Coagulopathy is often observed in severe traumatic brain injury (sTBI), and hyperfibrinolysis (HF) is associated with a poor prognosis. Although the efficacy of fibrinogen concentrate (FC) in multiple trauma has been reported, its efficacy in sTBI is unclear. Therefore, we delineated severe HF risk factors despite fresh frozen plasma transfusion. Using these risk factors, we defined high-risk patients and determined whether FC administration to this group improved fibrinogen level. In the first part of this study, successive adults with sTBI treated at our hospital between April 2016 and March 2019 were reviewed. Patients underwent transfusion as per our conventional protocol and were divided into two groups based on whether fibrinogen levels of ≥ 150mg/dL were maintained 3-6h after arrival to delineate the risk factors of severe HF. In the second part of the study, we conducted a before-and-after study in patients with sTBI who were at a higher risk for severe HF (presence of at least one of the risk factors identified in the first part of the study), comparing those treated with FC between April 2019 and March 2021 (FC group) with those treated with conventional transfusion before FC between April 2016 and March 2019. The primary outcome was maintenance of fibrinogen levels, and the secondary outcome was 30-day mortality. In the first part of the study, 78 patients were included. Twenty-three patients did not maintain fibrinogen levels ≥ 150mg/dL. A D-dimer level on arrival > 50μg/mL, a fibrinogen level on arrival < 200mg/dL, depressed skull fracture, and multiple trauma were severe HF risk factors. In the second part, compared with 46 patients who were identified as being at high risk for severe HF but were not administered FC (non-FC group), fibrinogen levels ≥ 150mg/dL 3-6h after arrival were maintained in 14 of 15 patients in the FC group (odds ratio: 0.07; 95% confidence interval: 0.01-0.59). Although there were significant differences in fibrinogen levels, no significant differences were observed in terms of 30-day mortality between the groups. Coagulation abnormalities on arrival, severe skull fracture, and multiple trauma are severe HF risk factors. FC administration may contribute to rapid correction of developing hypofibrinogenemia.

Valproic acid during hypotensive resuscitation in pigs with trauma and hemorrhagic shock does not improve survival.

Valproic acid (VPA) has been extensively used for treatment of anxiety and seizure. Recent studies have shown that VPA has cellular protective effects in preclinical models following severe hemorrhage. This study investigated the effects of VPA on coagulation and survival in pigs after traumatic hemorrhage and hypotensive resuscitation. Following baseline measurements, femur fracture was performed in 20 anesthetized and instrumented pigs (41 ± 2 kg), followed by hemorrhage of 55% of the estimated blood volume and a 10-minute shock period. Pigs were then resuscitated for 30 minutes with normal saline (NS) alone (NS group, n = 10, 4 mL/kg) or VPA solution (VPA group, n = 10, 90 mg/kg, 2 mL/kg of 45 mg VPA/mL, plus 2 mL NS/kg). All pigs were then monitored for 2 hours or until death. Hemodynamics were recorded, and blood samples were taken for blood and coagulation analysis (Rotem) at baseline, after hemorrhage, resuscitation, and 2 hours or death. Femur fracture and hemorrhage caused similar reductions in mean arterial pressure and cardiac output, and increase in heart rate in both groups. Resuscitation with NS or VPA did not return these measurements to baseline. No differences were observed in hematocrit, pH, lactate, base excess, or total protein between the groups. Compared with NS, resuscitation with VPA decreased platelet counts and prolonged activated partial thromboplastin time, with no differences in fibrinogen levels, prothrombin time, or any of the Rotem measurements between the two groups. Neither survival rates (NS, 7 of 10 pigs; VPA, 7 of 10 pigs) nor survival times after resuscitation (NS, 97 ± 40 minutes; VPA, 98 ± 43 minutes) differed between the groups. Following traumatic hemorrhage and hypotensive resuscitation in pigs, VPA provides no benefit toward improving coagulation function or survival times.

The Difference Of PT, aPTT, Fibrinogen, D-Dimer Activities In HIV Patients With CD4 Count Of &lt;200 uL And &gt;200 uL

ABSTRACT&#x0D; Introduction: HIV is a developing disease that has been a global problem. The progress of HIV infection is characterized by decreased CD4 count. Hemostasis disorder is often found in patients with HIV, where the formed virus-antibody complex can activate the coagulation system, beginning from the activation of the Hageman factor (Factor XII) into the active form (Factor XIIa). This factor will activate the fibrinolysis process. Fibrin polymer is broken down into fragments X and Y. Fragment Y is further broken down into Fragment D and E, which is known as D-dimer.&#x0D; Objective: To determine the difference of PT, aPTT, Fibrinogen, and D-Dimer in HIV patients with a CD4 lymphocyte count of &lt; 200/µL and &gt; 200/µL in H. Adam Malik General Hospital Medan.&#x0D; Hypothesis: There is a difference of PT and aPTT activities in HIV patients with a CD4 count of &lt; 200 cells/µL and ≥ 200 cells/µL and a difference of D-dimer and fibrinogen levels in HIV patients with a CD4 count of &lt; 200/µL and &gt; 200/µL in H. Adam Malik General Hospital Medan.&#x0D; Methods: This study was conducted in the Clinical Pathology Laboratory, Department of Internal Medicine, H. Adam Malik General Hospital. Samples were collected with a consecutive sampling method which included patients diagnosed with HIV in H. Adam Malik General Hospital Medan from September 2019 to July 2020 who fulfilled the inclusion and exclusion criteria. Thirty-eight patients were divided into two groups, i.e., HIV patients with a CD4 count of &lt; 200/µL and HIV patients with a CD4 lymphocyte count of &gt; 200/ µL.&#x0D; Results: Mann-Whitney test was used to assess the comparison of PT and aPTT values between HIV patients with a CD4 count of &lt; 200 cells/µL and ≥ 200 cells/µL. The result was significant with a p-value = 0.002, which means that there is a significant difference in PT and aPTT values between HIV patients with a CD4 count of &lt; 200 cells/µL and ≥ 200 cells/µL. An Independent T-test was used to assess the difference in fibrinogen level between HIV patients with a CD4 count of &lt; 200/µL and &gt; 200/µL, which resulted in p-value = 0.032. This means that there is a significant difference in fibrinogen levels between HIV patients with a CD4 count of &lt; 200/µL and &gt; 200/µL. Mann-Whitney test was used to determine the comparison in D-dimer level between HIV patients with a CD4 count of &lt; 200/µL and &gt; 200/µL, which showed a p-value = 0.002. This indicated a significant difference in D-dimer level between HIV patients with a CD4 count of &lt; 200/µL and &gt; 200/µL.&#x0D; Conclusion: The lower the CD4 lymphocyte count, the higher the activities of PT, aPTT, fibrinogen, and D-dimer in HIV patients.&#x0D; &#x0D; Keywords: HIV, PT, aPTT, D-Dimer, Fibrinogen, Hemostasis

An application of machine learning based on real-world data: Mining features of fibrinogen in clinical stages of lung cancer between sexes.

BackgroundLung cancer is the most threatening malignant tumor to human health and life. Using a variety of machine learning algorithms and statistical analyses, this paper explores, discovers and demonstrates new indicators for the early diagnosis of lung cancer and their diagnostic performance from large samples of clinical data in the real world.MethodsBy applying machine learning methods, including minimum description length (MDL), naive Bayesian (NB), K-means (KM), nonnegative matrix factorization (NMF), and decision tree (DT), based on large sample data of 2,502 patients, we built a classification model and systematically explored differences in fibrinogen levels in different clinical stages of lung cancer between the sexes. We also validated the reliability of the model by testing it on a validation cohort of 447 patients. This report adheres to the “Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis” (TRIPOD) statement for the reporting of prediction models.ResultsThe analysis revealed significant differences in fibrinogen levels, pleural effusion, chlorine levels, A-G ratio, glutamic-oxaloacetic transaminase and alkaline phosphatase levels as well as in sex composition between the early-stage lung cancer group and the middle-late-stage lung cancer group. The classification model created by the combination of fibrinogen, alkaline phosphatase and sex demonstrated good performance with an AUC of 73.5%. In addition, in males, a fibrinogen level of 2.94 g/L could initially serve as the upper limit for determining the early-stage lung cancer group, but a level of 3.91 g/L could be preliminarily used as a reference threshold for the lower limit for middle- to late-stage lung cancer. This latter level could also serve as the upper limit of the critical value for early-stage lung cancer in females.ConclusionsAn integrated application based on supervised and unsupervised machine learning algorithms could effectively explore the potential links contained in the clinical data and reveal the differences in fibrinogen levels in different clinical stages of lung cancer between the sexes, which could provide a new reference basis for lung cancer staging.

Clinical significance of blood platelets and mean platelet volume in patients with ulcerative colitis

ObjectivesThis retrospective study aimed to investigate and analyze the clinical significance of blood platelets (PLTs) and mean platelet volume (MPV) in patients with ulcerative colitis (UC).MethodsA total of 132 patients with UC and 208 healthy subjects were enrolled. PLTs, MPV, platelet-large cell rate (P-LCR), C-reactive protein (CRP), fibrinogen (FIB) and D-dimer were analyzed. Correlations were calculated between disease activity/extent of disease and MPV, PLT, and CRP levels in patients with UC.ResultsPLT levels were significantly higher while MPV and P-LCR were lower in patients with UC compared with controls. Disease activity was positive correlated with CRP (r = 0.564) and PLT (r = 0.307) but negatively correlated with MPV (r = −0.351). Extent of disease was positively correlated with CRP (r = 0.312) but showed no correlation with PLTs and MPV. FIB and D-dimer were higher in patients with UC, but the difference in FIB levels was not statistically significant.ConclusionsPLTs and MPV are potential biomarkers for UC disease activity. These data may help clinicians to attain a more comprehensive judgment of the general condition of patients with UC.

Accuracy of Fibrinogen/D-dimer Ratio in Predicting the Occurrence of Coronary Slow Flow Phenomenon

BACKGROUND: Fibrinogen is a risk factor for coronary heart disease (CHD), which is an acute-phase protein that is released when inflammation occurs. Fibrinogen is an essential component in the coagulation cascade and affects hemostasis, hemorheology, platelet aggregation, and endothelial function. D-dimers are inevitable products of fibrin degradation that results from thrombin activation; XIII activated factors and plasmin.&#x0D; AIM: This study was aimed to explore the accuracy of the fibrinogen/D-dimer ratio in predicting the slow flow phenomenon in CHD.&#x0D; METHODS: The study design is a diagnostic test with a cross-sectional design to assess the accuracy of the fibrinogen/d-dimer ratio in predicting coronary slow flow phenomenon (CSFP) in CHD. The study was conducted at the Department of Internal Medicine, Faculty of Medicine, Dr. Moh Hoesin Hospital, Palembang, Indonesia. The independent variables in this study were serum fibrinogen and D-dimer levels. Meanwhile, the dependent variable is sufferers of CHD with CSFP and regular flow. All data obtained from this study were analyzed using the SPSS version 20.0 for Windows program with a 95% confidence limit.&#x0D; RESULTS: This study showed that there was no difference in levels of fibrinogen and D-dimer in groups with CSFP and regular flow. Fibrinogen and D-dimer do not play a significant role in the CSFP process. The various etiological parts of this possible disorder still need further exploration and detail, ranging from the role of the renin-angiotensin-aldosterone system, the function of the autonomic nervous system, to the position of other endothelial factors.&#x0D; CONCLUSION: This study proves that fibrinogen has specific but not sensitive predictors of CSFP. The d-dimer value is also not accurate as a CSFP predictor. This study demonstrates that the fibrinogen / d-dimer ratio is not precise as a predictor of CSFP events.

Thromboelastography as a tool to evaluate blood of healthy volunteers and blood component quality: a review.

Thromboelastography is a technique to evaluate the overall coagulation behaviour of blood and blood components. First, we evaluated the literature concerning the use of thromboelastography for characterizing coagulation behaviour of healthy volunteers, such as blood donors. Overall coagulation is sensitive to gender, most likely caused by the difference in haematocrit and plasma content of male versus female blood. Smaller and less pronounced effects in thromboelastographic response are caused by differences in fibrinogen level or by use of oral contraceptives. Short-term hypercoagulable effects are observed after smoking or blood donation, while small effects of non-steroidal anti-inflammatory drugs on platelets are also present. Second, in whole blood donations, the thromboelastographic variables are also sensitive to storage time and temperature, but are less sensitive to levels of clotting factors. Platelet count and quality have little influence on thromboelastographic variables, and differences are mainly observed at counts <100x109 /l, after extended storage time of platelet concentrates or storage under specific conditions, including freezing. Thromboelastographic profiles of plasma samples are mainly affected by residual cell counts, microparticles and fibrinogen levels, and less by levels of clotting factors. Taken together, publications have shown that as an overall clotting test, thromboelastography may support optimization of blood component preparation and storage with regard to temperature, time and secondary and tertiary treatments. Minimal deviations of in vitro quality are most reliable demonstrated when an appropriate assay is chosen.

The correlation between plasma fibrinogen level and different types of sudden sensorineural hearing loss

Objective: To investigate the correlation between plasma fibrinogen level and the incidence of sudden hearing loss. Method: A total of 225 patients (age ranging from 18 to 70 years) with sudden sensorineural hearing loss(SSNHL) were selected. The disease onset was within 2 weeks. No patient received previous medical intervention. Depending on the types of auditory threshold curve, SSNHL was divided into low frequency descending type, high frequency descending type, flat desending type and total deafness type. Two hundred and twenty-nine cases with normal hearing and no inflammatory diseases in the same period was selected as control group. Fibrinogen level and Blood Routine Indexes were detected for the purpose of retrospective cohort study.Result: The levels of fibrinogen in SSNHL group(2.98±0.59) g/L were significantly higher than that in control group(2.66±0.36) g/L (P<0.01). According to the types of auditory threshold curve, SSNHL groups were divided into group A(55 cases, 24.44%), Group B(36 cases, 16.00%), Group C(43 cases,19.11%) and Group D(91 cases, 40.44%). The average fibrinogen levels before treatment were at(2.75±0.46)g/L, (3.16±0.61) g/L, (3.02±0.63) g/L and(3.03±0.63) g/L respectively. There was no significant difference in fibrinogen level(P=0.286) between group A and the control group. Fibrinogen levels of group B, group C and group D were significantly elevated compared to control group (P<0.01). Conclusion: The level of fibrinogen is not significantly correlated with development of sudden deafness of low frequency descending type. The incidence of high frequency descending type, flat descending type and profound deafness type are all correlated with the level of high fibrinogen at the onset of sudden deafness. The classification of sudden deafness based on audiogram curves could be of great significance for analysis of possible causes and selection of treatment options.

Association Between Perioperative Fibrinogen Levels and the Midterm Outcome in Patients Undergoing Elective Endovascular Repair of Abdominal Aortic Aneurysms

We investigated the potential association between perioperative fibrinogen levels and outcome in patients undergoing elective endovascular abdominal aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs). Consecutive patients with an intact AAA undergoing elective EVAR with a specific bifurcated endograft (Endurant, Medtronic) were recruited between December 2012 and October 2016. Preoperative and 24-hr postoperative fibrinogen levels were recorded, and potential associations with outcome were tested. Primary outcome measures included endoleaks, lower limb ischemic complications, including endograft limb occlusion, and aneurysm-related reinterventions. Ninety-four patients (91 male, mean age 71.8±8.0years) with an intact AAA were enrolled in the study. The technical success was 98% (2 failures: 1 type Ia endoleak on completion angiography, 1 lower limb ischemia immediately postoperatively requiring femoral endarterectomy). There was 1 death during the first 30days due to myocardial infarction (1%). Another patient died 15months after the procedure from cardiac causes. During the existing follow-up (mean 14.8±14.3months), 14 patients (15%) developed an endoleak (4, type Ia endoleak and 10, type II endoleak), 6 patients (6.3%) had lower limb ischemia/endograft limb occlusion, and 10 patients (10.6%) required reintervention. Compared with the preoperative values, no significant change occurred with regard to the fibrinogen levels 24hr after procedure (mean preoperative fibrinogen 360±101mg/dl vs 24-hr postoperative fibrinogen 349±105mg/dl, P=0.1). Neither preoperative nor 24-hr postoperative fibrinogen levels were significantly associated with the development of endoleaks, lower limb ischemia, or reinterventions. However, the difference in fibrinogen levels (baseline to 24hr after procedure) was significantly higher in patients with endoleaks (median -65mg/dl vs. 15mg/dl, P=0.04). Perioperative fibrinogen levels may play a role in predicting midterm outcomes in patients undergoing elective EVAR and appears to be associated, directly or indirectly, with the development of endoleaks. Further studies are needed to investigate these findings and explore future therapeutic implications.

Changes of plasma fibrinogen level in postoperative bleeding patients undergoing cardiac surgery with cardiopulmonary bypass

Objective To evaluate perioperative fibrinogen levels as a predictor of postoperative bleeding in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Methods In this single-center, observational cohort study of 623 patients following cardiac surgery with CPB, excessive bleeding group was defined as patients with a 24 h chest tube output (CTO) exceeding the 90th percentile of distribution. According to the occurrence of excessive bleeding, the patients were divided into 2 groups: excessive bleeding group and control group. A total of 63 patients were identified as having excessive bleeding (10.1%), and the rest were classed as control group. The possible risk factors associated with excessive bleeding were retrospectively analyzed. Hemoglobin, platelet count, prothrombin time, activated partial thrombolastin time, and fibrinogen level were measured before the surgery (T0), and at admission to the intensive care (T1). Results At T1, there was significant difference in fibrinogen levels (t=3.763, P=0.001) between the two groups. The fibrinogen level at T1 was significantly correlated with the 24 h CTO (r=-0.114, P=0.000). Multivariate analysis demonstrated that the fibrinogen level [P=0.001, odds ratio (OR)=0.590, 95% confidence interval (CI): 0.463-0.771] at T1 was the best perioperative standard laboratory test to predict excessive bleeding, whereas preoperative fibrinogen level was not a predictor. Body mass index (P=0.045, OR=0.814, 95%CI: 0.991-1.010), asprin treatment (P=0.012, OR=1.248, 95%CI: 1.050-1.484), previous cardiac surgery (P=0.027, OR=2.771, 95%CI: 1.469-3.142), CPB time (P=0.002, OR=1.614, 95%CI: 1.196-2.179), the hemoglobin level (P=0.014, OR=0.857, 95%CI: 0.758-0.969), the prothrombin time (P=0.005, OR=1.212, 95%CI: 1.124-1.323) at T1 were the other common predictors. The receiver operating characteristics curve analyses revealed at T1 the best fibrinogen level cutoff to predict postoperative bleeding was 2.2 g/L. Conclusion In this study, the fibrinogen level upon admission to the intensive care unit after CPB predicted the risk of postoperative bleeding. Our data add to the concern regarding the fibrinogen level threshold that might require fibrinogen concentration infusion to reduce postoperative blood loss. Key words: Fibrinogen; Postoperative blood loss; Cardiopulmonary bypass

Impact of plasma fibrinogen levels in benign and malignant soft tissue tumors.

Fibrinogen, a 340 kDa glycoprotein synthesized in the liver, is known to be involved in tumor angiogenesis, enlargement, and metastasis. Elevated plasma fibrinogen levels are associated with tumor progression in many cancer patients. However, there are no reports about differences in fibrinogen levels between benign and malignant soft tissue tumors. The purpose of this study was to clarify whether preoperative plasma fibrinogen levels can be used for differential diagnosis of benign or malignant soft tissue tumors. The plasma fibrinogen levels from 102 primary soft tissue tumor patients were measured before biopsy or treatment. Fibrinogen levels were analyzed and compared to various clinical parameters. According to receiver operating characteristic (ROC) curve analysis, a threshold of serum fibrinogen of 315 mg/dL identified malignant patients with 60.9% sensitivity and 87.5% specificity. The diagnostic accuracy was evaluated by area under the curve (AUC: 0.805). Over 315 mg/dL of fibrinogen was associated with a significantly increased risk of malignancy by multiple logistic regression analysis (OR: 6.452, p= 0.0004). We demonstrated that plasma fibrinogen levels have a relationship with tumor malignancy of soft tissue tumors. High fibrinogen levels can be a helpful subsidiary tool for the prediction of malignant soft tissue tumors with other diagnostic tools.

Effect of Serum Fibrinogen, Total Stent Length, and Type of Acute Coronary Syndrome on 6-Month Major Adverse Cardiovascular Events and Bleeding After Percutaneous Coronary Intervention

This study evaluated the relation between baseline fibrinogen and 6-month major adverse cardiovascular events (MACE) and bleeding after percutaneous coronary intervention (PCI). Three hundred eighty-seven subjects (65.6 ± 16.1years, 69.5% men, 26.9% acute coronary syndrome [ACS]) who underwent PCI with baseline fibrinogen and platelet reactivity (VerifyNow P2Y12 assay, Accumetrics, San Diego, California) measured were enrolled. Fibrinogen (368.8 ± 144.1 vs 316.8 ± 114.3mg/dl; p= 0.001), total stent length (TSL; 44.5 ± 25.0 vs 32.2 ± 20.1mm; p <0.001), and ACS presentation (40.6% vs 23.9%; p= 0.005) were independently associated with 6-month MACE rates (17.8%: myocardial infarction 9.8%, rehospitalization for ACS 3.6%, urgent revascularization 3.6%, stroke 0.5%, and death 0.3%). Measures of platelet reactivity were not associated with 6-month MACE. After multivariate analysis, fibrinogen ≥280mg/dl (odds ratio [OR] 2.60, 95% CI 1.33 to 5.11, p= 0.005), TSL ≥32mm (OR 3.21, 95% CI 1.82 to 5.64, p <0.001), and ACS presentation (OR 2.58, 95% CI 1.45 to 4.61, p= 0.001) were associated with higher 6-month MACE. In 271 subjects receiving chronic P2Y12 inhibitor therapy, 6-month Thrombolysis In Myocardial Infarction bleeding after PCI was 7.0%, but no difference in fibrinogen level (338.3 ± 109.7 vs 324.3 ± 113.8mg/dl, p= 0.60) stratified by Thrombolysis In Myocardial Infarction bleeding was observed. In conclusion, elevated serum fibrinogen, ACS presentation, and longer TSL are independently associated with higher 6-month MACE after PCI, whereas no association with on-thienopyridine platelet reactivity and 6-month MACE was observed. Post-PCI bleeding was not associated with lower fibrinogen level.

Use of human fibrinogen concentrate during proximal aortic reconstruction with deep hypothermic circulatory arrest

ObjectiveHuman fibrinogen concentrate (HFC) is approved by the Food and Drug Administration for use at 70 mg/kg to treat congenital afibrinogenemia. We sought to determine whether this dose of HFC increases fibrinogen levels in the setting of high-risk bleeding associated with aortic reconstruction and deep hypothermic circulatory arrest (DHCA). MethodsThis was a prospective, pilot, off-label study in which 22 patients undergoing elective proximal aortic reconstruction with DHCA were administered 70 mg/kg HFC upon separation from cardiopulmonary bypass (CPB). Fibrinogen levels were measured at baseline, just before, and 10 minutes after HFC administration, on skin closure, and the day after surgery. The primary study outcome was the difference in fibrinogen level immediately after separation from CPB, when HFC was administered, and the fibrinogen level 10 minutes following HFC administration. Additionally, postoperative thromboembolic events were assessed as a safety analysis. ResultsThe mean baseline fibrinogen level was 317 ± 49 mg/dL and fell to 235 ± 39 mg/dL just before separation from CPB. After HFC administration, the fibrinogen level rose to 331 ± 41 mg/dL (P < .001) and averaged 372 ± 45 mg/dL the next day. No postoperative thromboembolic complications occurred. ConclusionsAdministration of 70 mg/kg HFC upon separation from CPB raises fibrinogen levels by approximately 100 mg/dL without an apparent increase in thrombotic complications during proximal aortic reconstruction with DHCA. Further prospective study in a larger cohort of patients will be needed to definitively determine the safety and evaluate the efficacy of HFC as a hemostatic adjunct during these procedures.

Severity of obstructive sleep apnea is associated with elevated plasma fibrinogen in otherwise healthy patients

Obstructive sleep apnea (OSA) has been implicated in both cardiovascular and cerebrovascular diseases. Systemic inflammation and coagulation may be related to cardiovascular pathophysiology in patients with OSA. Fibrinogen is a major coagulation protein associated with inflammation, and long-term elevated plasma fibrinogen is associated with an increased risk of major cardiovascular diseases. We assessed whether severity of OSA is associated with levels of fibrinogen in newly diagnosed, untreated, and otherwise healthy OSA patients. We studied 36 men with OSA and 18 male control subjects (apnea-hypopnea index [AHI]<5 events/h). OSA patients were divided into mild (AHI≥5<15 events/h) and severe (AHI≥15 events/h) OSA groups. Morning fibrinogen levels in OSA patients were compared to those in control subjects of similar age, body mass index, blood pressure, smoking habits, and alcohol consumption. Fibrinogen levels were significantly elevated in patients with severe OSA compared to both control (P=0.003) and mild OSA (P=0.02) subjects after adjustment for covariates. However, there were no significant differences in fibrinogen levels between mild OSA and control subjects. Fibrinogen levels were directly related to AHI and arousal index and inversely related to mean and lowest oxygen saturation during sleep. Severity of OSA was associated with increased fibrinogen level independent of other factors, suggesting that apneic events and oxygen desaturation during sleep are mechanisms for increased fibrinogen levels in patients with OSA.

Characteristics of Fibrin Formation and Clot Stability in Individuals with Congenital Type IIb Protein C Deficiency

Many studies have shown that unregulated or excessive thrombin formation is potentially a cause of thrombosis; however, studies examining processes that contribute to fibrin stabilization in individuals predisposed to thrombosis are limited. In this study, we investigate a family with familial thrombosis via type IIb protein C (PC) deficiency. Using contact pathway inhibited whole blood, thrombin generation, fibrin clot formation and factor (f)XIII activation were monitored over time in control (n=5) and PC deficient (n=4, 34 – 69% PC by activity) subjects. The dynamics of thrombin generation varied significantly with the time required to reach the maximal rate of thrombin-antithrombin formation being much shorter in PC deficiency (5.8±0.4 minutes) than in controls (9.7±0.4 minutes; p<0.001). PC deficient clots were significantly heavier than control clots (p<0.001) and this difference could not be contributed exclusively to differences in fibrinogen levels between groups. FXIII was consumed faster in PC deficient subjects (23.7±2.0 nM/minute) than in controls (5.1±1.5 nM/minute; p<0.0001) suggesting increased fXIII activation and incorporation of fXIIIa substrates into the clot. In plasma, the clot lysis time was increased in PC deficiency by both TAFIa dependent and independent mechanisms. Since PC deficient clots are both denser and show a greater degree of resistance to fibrinolysis, these clots would likely resist fibrinolysis and potentiate fibrin deposition observed in thrombosis.

Fibrinogen and cardiovascular disease: Genetics and biomarkers

Several prospective epidemiological studies and clinical observations provided evidence regarding fibrinogen and coronary artery disease (CAD). Many of these studies firmly correlate fibrinogen with CAD. However, it is uncertain whether this relation is causal or reflects genetic variability and residual confounding by other risk factors. Several polymorphisms on fibrinogen chain genes affect its levels, however only few of the genetic variants are associated with increased cardiovascular risk. As regards the role of fibrinogen in myocardial infarction (MI) studies indicate that genetic variations have at best a modest impact on the process resulting in MI. Therefore, the screening of fibrinogen genes might not be useful for the assessment of the risk of MI. However, the findings that specific genotypes lead to specific differences in fibrinogen levels, but may not be linked to cardiovascular risk, complicates the hypothesis of causality of fibrinogen in the pathogenesis of cardiovascular disease.