Plasma Fibrinogen Levels Research Articles

A novel ex vivo approach for measuring plasminogen activation upon established plasma clots

BackgroundThe fibrinolytic system plays a critical role in maintaining hemostasis. Central to fibrinolysis is the degradation of fibrin by plasmin, produced in the circulation following the activation of plasminogen by plasminogen activators (PAs). Accurately measuring the plasminogen activation rate is vital for the understanding of fibrinolytic processes, particularly in the context of thrombolysis. Yet, due to the insoluble nature of fibrin, in vitro and ex vivo investigations of PA‐mediated plasminogen activation have proven challenging. As researchers frequently adopt soluble fibrinogen fragments and/or alter the experimental system beyond what is physiologically relevant, they limit the validation and interpretation of their findings. Here, we present a novel, high‐throughput assay for measuring plasminogen activation rates on natural, plasma‐derived fibrin that optimally simulates in vivo conditions. MethodHuman plasma was used as the source of plasmin(ogen) and fibrin(ogen). “Halo‐shaped” plasma clots were produced in a 96‐well plate using a thrombin‐containing clotting mixture, ensuring that an optically compatible and plasma‐free center is maintained in each well. Subsequent additions of a plasmin chromogenic substrate and different PAs were followed by absorbance measurements over time to extract the corresponding enzyme kinetics information. Results and DiscussionValidation experiments demonstrated the capability of our approach to accurately model fibrin‐dependent and ‐independent plasminogen activation as well as sensitively detect variations in plasminogen and fibrinogen plasma levels. ConclusionThis assay allows a straightforward, yet powerful, measurement of plasminogen activation rates on established plasma clots, with the capability of properly assessing fibrin‐ and non–fibrin‐dependent plasminogen activation by various therapeutic PAs.

Роль фибриногена в коагуляционном статусе, методы его коррекции. Обзор литературы и клинический случай

Fibrinogen is an important protein of hemostasis. In blood plasma, its concentration is the highest of all coagulation proteins - clotting factors. When coagulation cascade activated, thrombin splits fibrinogen and triggers fibrin polymerization to the form required for efficient clot formation. In acute blood loss, dilutional coagulopathy may develop, causing decreasing fibrinogen levels, which is critical for clot formation. Recently, there has been emerged and rapidly increased the interest in fibrinogen replacement during acute bleeding as a point of the bleeding treatment and prevention, especially in the perioperative patients. This study reviews current data on relevant plasma fibrinogen levels and dosing in various clinical settings, as well as clinical experience with the use of fibrinogen concentrate in patients with dilutional coagulopathy and disseminated Intravascular coagulation syndrome is described.

An Agreement Study Between Point-of-Care and Laboratory Activated Partial Thromboplastin Time for Anticoagulation Monitoring During Extracorporeal Membrane Oxygenation.

BackgroundLaboratory activated partial thromboplastin time (LAB-aPTT) is a widely used laboratory assay for monitoring unfractionated heparin (UFH) therapy during extracorporeal membrane oxygenation (ECMO). But LAB-aPTT is confined to a central laboratory, and the procedure is time-consuming. In comparison, point-of-care aPTT (POC-aPTT) is a convenient and quick assay, which might be a promising method for anticoagulation monitoring in ECMO. This study was aimed to evaluate the agreement between POC-aPTT (hemochron Jr. Signature instruments) and LAB-aPTT for anticoagulation monitoring in adult ECMO patients.MethodsData of ECMO-supported adult patients anticoagulated with UFH in our institute from January 2017 to December 2020 was retrospectively reviewed. POC-aPTT and LAB-aPTT results measured simultaneously were paired and included in the analysis. The correlation between POC-aPTT and LAB-aPTT was assessed using Spearman’s correlation coefficient. Bias between POC-aPTT and LAB-aPTT were described with the Bland-Altman method. Influence factors for bias were identified using multinomial logistic regression analysis.ResultsA total 286 pairs of aPTT results from 63 patients were included in the analysis. POC-aPTT and LAB-aPTT correlated weakly (r = 0.385, P < 0.001). The overall bias between POC-aPTT and LAB-aPTT was 7.78 [95%CI (−32.49, 48.05)] s. The overall bias between POC-aPTT and LAB-aPTT ratio (to normal value) was 0.54 [95%CI (−0.68, 1.76)]. A higher plasma fibrinogen level [OR 1.353 (1.057, 1.733), P = 0.017] was associated with a higher chance of POC-aPTT underestimating LAB-aPTT. While a lower plasma fibrinogen level [OR 0.809 (0.679, 0.963), P = 0.017] and lower UFH rate [OR 0.928 (0.868, 0.992), P = 0.029] were associated with a higher chance of POC-aPTT overestimating LAB-aPTT.ConclusionThe present study showed poor agreement between POC-aPTT and LAB-aPTT. POC-aPTT was not suitable for anticoagulation monitoring in adult ECMO patients.

Combining ultra-high-performance liquid chromatography quadruple exactive orbitrap mass spectrometry with chemometrics to identify and verify the blood-activating components of hawthorn.

Hawthorn, one of the widely-used Chinese herbal medicines, has been used to treat blood stasis syndrome in the clinic, but its blood-activating components are unclear. This study combined the ultra-high-performance liquid chromatography-quadruple exactive-orbitrap mass spectrometry with chemometrics to identify the blood-activating components of hawthorn. Different polar fractions of hawthorn aqueous extracts were extracted and mixed to prepare 14 samples. The contents of 25 chemical components for 14 samples were determined by the proposed quantitative method which was validated in terms of linearity, precision, stability, repeatability, and recovery, while the blood-activating effect was evaluated by measuring the whole blood viscosity, plasma viscosity, and plasma fibrinogen levels. Then the partial least squares model was established on the spectrum-effect relationship. The result showed that vitexin-2″-O-rhamnoside, rutin, citric acid, malic acid, gallic acid, and fumaric acid could reduce the whole blood viscosity, plasma viscosity, and plasma fibrinogen levels in blood stasis model rats, and these components were the blood-activating components of hawthorn. This study provided a scientific basis for clarifying the blood-activating components of hawthorn, and the spectrum-effect approach proved to be an effective approach to discovering the bioactive components of Chinese herbal medicines.

ASO Author Reflections: Does Elevation of the Prognostic Factor Plasma Fibrinogen Level Reflect the Tumor Microenvironment at the Primary Site?

ASO Author Reflections: Does Elevation of the Prognostic Factor Plasma Fibrinogen Level Reflect the Tumor Microenvironment at the Primary Site?

Elevation of the Prognostic Factor Plasma Fibrinogen Reflects the Immunosuppressive Tumor Microenvironment in Esophageal Squamous Cell Carcinoma.

Despite previous reports on the clinical significance of plasma fibrinogen (FNG) levels as a prognostic indicator of ESCC, its underlying mechanism remains unclear. This study aimed to validate the prognostic impact of plasma FNG levels and clarify its relationship with primary tumors in patients with esophageal squamous cell carcinoma (ESCC). The prognostic impact of FNG was evaluated in patients with ESCC who underwent esophagectomy between 2000 and 2019. The RNA sequencing of the primary ESCC site, which was from pre-operative biopsy, was performed, followed by immune profile characterization using an immunogram. Those profiles were assessed via the immunohistochemical staining of tumor-associated macrophages (TAMs) and clinical response to nivolumab. Multivariate analysis identified FNG as a significant prognostic factor in ESCC. The immunogram suggested an immunosuppressive tumor environment in the high-FNG group. Immunostaining with the TAM markers CD163 and CD204, revealed that the high-FNG group had significantly higher number of TAMs compared with the low-FNG group. The immunosuppressive characteristics were clinically validated in patients with metastatic ESCC;thosewho had elevated FNG levelsshowed poor responseto nivolumab. This study successfully validated the prognostic impact of plasma FNG levels in an expanded cohort with ESCC. Accordingly, our findings showed that increased plasma FNG reflects an immunosuppressive tumor microenvironment that facilitates tumor progression and poor responses to nivolumab.

ASO Visual Abstract: Prognostic Impact of Using Combined Plasma Fibrinogen Level and Neutrophil-to-Lymphocyte Ratio in Resectable Non-small Cell Lung Cancer

ASO Visual Abstract: Prognostic Impact of Using Combined Plasma Fibrinogen Level and Neutrophil-to-Lymphocyte Ratio in Resectable Non-small Cell Lung Cancer

Prognostic Impact of Using Combined Plasma Fibrinogen Level and Neutrophil-to-Lymphocyte Ratio in Resectable Non-small Cell Lung Cancer.

Both plasma fibrinogen level and neutrophil-to-lymphocyte ratio (NLR) are associated with malignant potential in different cancer types. The current study evaluated the use of combined plasma fibrinogen level and NLR (F-NLR) as a prognostic predictor in patients with non-small cell lung cancer (NSCLC). Data collected from 279 patients with resectable NSCLC were retrospectively reviewed. Patients were divided into three groups based on the F-NLR score: score 2, high fibrinogen level (≥350 mg/dL) and high NLR (≥2.5); score 1, either high fibrinogen level or high NLR; and score 0, neither abnormal. Overall survival (OS) and relapse-free survival (RFS) were evaluated using the Kaplan-Meier method and log-rank test. Cox proportional hazard model was used to assess prognostic factors. Numbers of patients with F-NLR score of 0, 1, and 2 were 122 (43.7%), 105 (37.6%), and 52 (18.6%), respectively. The F-NLR was found to be significantly associated with age, male sex, heavy smoking history, high pT status and pathological stage, and nonadenocarcinoma. Moreover, the OS and RFS significantly differed according to the F-NLR score (P < 0.001, P = 0.003). A multivariate analysis revealed that a high F-NLR score (≥1) was an independent poor prognostic factor for OS (P = 0.027). In subgroup analyses, an adverse prognostic impact of the F-NLR score on OS was identified regardless of nodal involvement or pathological stage. The F-NLR score, which is based on histological inflammation and coagulability, could be a potential prognostic indicator in patients with resectable NSCLC.

Baseline Plasma Fibrinogen and Glycated Haemoglobin (HbA1c) Levels in Normoglycaemic Offspring of Adults with Type 2 Diabetes Mellitus

Background: Type 2 Diabetes mellitus (T2DM) is known to be preceded by a long pre-diabetic stage. Family studies have confirmed that the incidence of T2DM in the first-degree offspring of T2DM patients is higher than in the non-diabetic population. The levels of plasma fibrinogen and HbA1c in offspring of T2DM patients may be markers of the development of T2DM later in life.&#x0D; Objectives: To determine the plasma fibrinogen and HbA1c levels of normoglycaemic offspring of T2DM patients. &#x0D; Methods: This study involved randomly selected 100 offspring of T2DM patients (ODP) and 100 offspring of non-diabetic parents (ONDP) aged between 16 and 40 years. Fasting Blood Glucose (FBG), plasma fibrinogen and HbA1c and height and body weight were measured using standard methods. &#x0D; Results: The mean age of the ODP and ONDP were similar: 23.3±0.44 years and 23.44 ±0.40 years, respectively. The mean BMI was 23.83±0.42kg/m2 for ODP and 23.20±0.29kg/m2 for ONDP. The prevalence of overweight was 13.0% and 25.0% among the ODP and ONDP, respectively. The mean plasma fibrinogen was significantly higher in ODP (322.85 ± 5.15g/l vs 303.11 ±4.92 g/l; p = 0.006). The mean plasma HbA1c was also significantly higher among OND (5.13±0.03% vs 4.76±0.05; p = 0.000).&#x0D; Conclusions: The plasma fibrinogen and HbA1c levels are higher among ODP than ONDP. This pattern of variations may serve as a reason for instituting precautionary measures since it predates the development of T2DM.

Hyperfibrinogenemia as a Poor Prognostic Indicator in Myelodysplastic Syndrome.

BackgroundMyelodysplastic syndrome (MDS) is a group of heterogeneous myeloid clonal diseases originating from hematopoietic stem cells. It has been demonstrated that fibrinogen (FIB) is associated with disease risk in several cancer types. Coagulation and fibrinolysis problems are widespread in MDS patients. Therefore, FIB might be one of these indicators. We thus examined the role of FIB levels in the prognosis of MDS.MethodsA cohort of 198 MDS patients were retrospectively analyzed to explore the prognostic value of the plasma FIB levels at diagnosis. Patients were divided into the high FIB group and low FIB group. The prognostic significance of FIB was determined by univariate and multivariate Cox hazard models.ResultsIn our cohort, the FIB levels in 198 MDS patients were higher than those in 100 healthy donors (3.9 g/L vs 2.9 g/L, P < 0.0001). MDS patients with high FIB levels had significantly shorter overall survival (OS; P = 0.001) and decreased leukemia-free survival (LFS; P = 0.036). Multivariate cox proportional hazards regression analysis indicated that, in addition to older age, gender, lower HB, poorer karyotype for OS, lower NE, and higher bone marrow blast percentage for OS and LFS, elevated FIB level was also an independent adverse prognostic factor for OS (P = 0.045) but not for LFS (P = 0.188).ConclusionElevated FIB levels may be associated with mortality risk among MDS patients and could predict disease progress and patient prognosis. Thus, assessment of FIB levels may promote the determination of the prognosis of MDS patients.

Subgaleal Hematoma with Bilateral Proptosis as a Manifestation of Fibrinogen and Factor X Deficiency - A Case Report

Subgaleal hematomas are usually seen after high-velocity head trauma; however, their presence following trivial injury should raise suspicion regarding an associated clotting disorder. Here we describe an interesting patient who presented to us with bilateral proptosis associated with a subgaleal hematoma due to fibrinogen and factor X deficiency. This condition can result in serious bleeding diathesis often necessitating multiple surgeries to control haemorrhage.&#x0D; Our patient, an 11-year-old male child presented to us 4 weeks after a minor head injury. He had a gradually progressive soft swelling on his forehead with proptosis of both eyes. Aspiration of the swelling at a nearby private hospital had revealed blood. The swelling recurred over a span of 2 weeks.&#x0D; On neurological examination, there were no positive findings. On local examination, he had a large, non-tender subgaleal hematoma over the bilateral fronto-temporo-parieto-occipital region of his head extending to both eyes. There was associated bilateral subconjunctival haemorrhage, periorbital ecchymosis and gross proptosis. The vision was affected on the right side, finger counting at 1 foot. Left side vision was intact. Extraocular movements were restricted in both eyes in all planes. CT scan of the brain showed subgaleal hematoma over the bilateral fronto-temporo-parieto-occipital region with an extension over the supraorbital ridge into the bilateral orbit beneath the orbital roof, there were bilateral relatively symmetrical areas of subperiosteal haemorrhages involving superior aspect of orbit causing proptosis and inferior displacement of the globes. On haematological examination, his haemoglobin was 5 gm/dl. Platelet count was 240,000/cumm. On coagulation profile, prothrombin time was 45 seconds (normal range 11.1–14.5 seconds) with an activated partial thromboplastin time of 39.5 seconds (normal range 28.1–39.7 seconds), and thrombin time was 58 seconds. The plasma fibrinogen levels were &lt; 100 mg/dl (normal range- 200-400 mg/dl). D-dimer was strongly positive. The patient also had factor X deficiency. The peripheral blood smear had a normocytic normochromic picture.

Efficacy and safety of fibrinogen administration in acute post-traumatic hypofibrinogenemia in isolated severe traumatic brain injury: A randomized clinical trial

AimThis study was conducted to evaluate clinical outcomes after fibrinogen administration in hypofibrinogenemia following severe traumatic brain injury. BackgroundPost traumatic coagulopathy (PTC) is a common but devastating medical condition in patients with severe head injury. Hypofibrinogenemia is considered as an indicator for poor clinical outcomes in traumatic brain injury (TBI). MethodsIn this randomized clinical trial (RCT), primarily 137 patients with severe traumatic brain injury (Glasgow coma scale score: GCS < 9) were enrolled. Thereafter, their plasma fibrinogen level was measured. The patients with primary hypofibrinogenemia (<200 mg/dL) with no concurrent coagulopathy were randomly allocated into fibrinogen-receiving (n = 50) and control (n = 54) groups. P-value < 0.05 was considered as statistically significant. ResultsSeventy-one patients were analyzed in the final step of the study. The mean value for age in fibrinogen and control groups was 25.64 ± 10.71 and 28.91 ± 12.25 years old, respectively. Male – female patients in both groups were equally distributed. In the fibrinogen receiving group, GCS scores were significantly higher after 24, 48, and 72 h compared to the control group (p = 0.000). Hematoma expansion was better controlled in the fibrinogen receiving group (p = 0.000). Notably, the number needed to treat (NNT) for fibrinogen infusion and hematoma expansion control was 2.3. Glasgow outcome scale-extended (GOSE) was significantly better in the fibrinogen group (p = 0.25). Multiple regression tests showed intracerebral hematoma (ICH) and severe brain edema had the most detrimental effect on GOSE outcomes. The need for cranial surgery, hospital stay duration, mechanical ventilator dependency, in hospital and 90-day post discharge mortality rates were similar in both study groups. ConclusionIn severe TBI, hypofibrinogenemia correction (>200 mg/dL) could improve GOSE, GCS score progression within 3 days after primary head injury and hematoma expansion controllability.

Lower-leg injury and knee arthroscopy have distinct effects on coagulation

AbstractIt is unknown how lower-leg injury and knee arthroscopy, both associated with venous thromboembolism (VTE), affect coagulation. To study the effect of (1) lower-leg trauma and (2) knee arthroscopy on coagulation, plasma samples of the Prevention of Thrombosis following CAST immobilization (POT-CAST, #NCT01542762) and Prevention of Thrombosis following Knee Arthroscopy (POT-KAST, #NCT01542723) trials were used, which were collected shortly after lower-leg trauma and before/after (<4 hours) knee arthroscopy. For aim 1, 1204 lower-leg injury patients were compared with preoperative samples of 1001 controls. Mean differences/ratios (if ln-retransformed because of skewedness) were adjusted for sex, age, body mass index, comorbidity, malignancy, and oral contraceptives using linear regression. For aim 2, perioperative mean changes of 715 arthroscopy patients were calculated. Plasma levels of fibrinogen, factor (F)VIII, FIX, FXI, von Willebrand Factor (VWF), and D-dimer were measured in all individuals. Parameters of underlying mechanisms (tissue factor, interleukin-6 [IL-6], myeloperoxidase DNA, cell-free DNA) were measured in random subsets. In lower-leg injury patients, coagulation parameter levels increased, especially FVIII, VWF, and D-dimer, that is, adjusted mean differences: FVIII 26.8% (95% confidence interval [CI], 23.7-29.9), FIX 13.8% (95% CI, 11.9-15.6), FXI 5.1% (95% CI, 3.3-7.0), VWF 29.8% (95% CI, 26.0-33.6), fibrinogen 32.5 mg/dL (95% CI, 25.8-39.2), and D-dimer (mean ratio) 3.3 (95% CI, 3.1-3.6). Remaining parameters were unchanged, except for increased IL-6 levels. After arthroscopy, all parameters decreased. Lower-leg trauma is associated with increased procoagulant factor levels in contrast to knee arthroscopy. This suggests that, in both situations, different pathways are involved in development of VTE.

ASO Author Reflections: Clinical Significance of Combined Plasma Fibrinogen Level and Neutrophil-to-Lymphocyte Ratio in Non-small Cell Lung Cancer.

ASO Author Reflections: Clinical Significance of Combined Plasma Fibrinogen Level and Neutrophil-to-Lymphocyte Ratio in Non-small Cell Lung Cancer.

Effect of Early Electroacupuncture Combined with Enhanced Recovery after Surgery (ERAS) on Pain Perception and Dysfunction in Patients after Total Knee Arthroplasty (TKA).

Objective A retrospective case-control study was performed to observe the effect and clinical significance of early electroacupuncture combined with enhanced recovery after surgery (ERAS) on pain perception and dysfunction after total knee arthroplasty (TKA). Methods About 100 patients who diagnosed with TKA from February 2019 to April 2021 were enrolled in our hospital. The patients were arbitrarily assigned into control group and study group. The former group was cured with electroacupuncture in the early stage, and the latter group was intervened on the basis of early electroacupuncture combined with the concept of ERAS. The curative effect, the time of getting out of bed for the first time after operation, the time of postoperative rehabilitation, postoperative rehabilitation cost, pain score and knee joint function score, range of motion (ROM) of knee joint, low shear of whole blood viscosity, plasma viscosity, fibrinogen level, and postoperative complications were compared. Results There exhibited no statistical difference in clinical data. In terms of the treatment effects, there were 27 cases of markedly effective, 22 cases of effective, and 1 case of ineffective in the study group, and the total effective rate was 98.00%; in the control group, 15 cases were markedly effective, 28 cases were effective, and 13 cases were ineffective, and the total effective rate was 86.00%. Compared to the control group, the total effective rate of the study group was higher (P < 0.05). And the first time to get out of bed and the postoperative rehabilitation time in the study group were lower. Compared to the control group (10113.42 ± 524.83) yuan, the postoperative rehabilitation cost in the study group (12401.71 ± 530.77) yuan was higher. In terms of the scores of VAS and HSS, there exhibited no remarkable difference before treatment (P > 0.05). After treatment, the VAS score lessened and the HSS score augmented the study group VAS score (1.76 ± 0.28); the score in the control group was lower compared to the control group (3.45 ± 0.36), and HSS scoring (83.48 ± 11.23) points higher compared to the control group (65.82 ± 10.44) points (P < 0.05). The ROM of knee joint augmented successively at the 1st, 2nd, 4th, and 8th week after treatment comparison between groups, the ROM of the knee joint in the study group at the 1st, 2nd, 4th, and 8th week was (49.47 ± 3.60)°, (64.38 ± 5.32)°, (86.93 ± 6.72)°, and (104.20 ± 9.11)°, is higher compared to the control group (46.53 ± 3.41)°, (61.52 ± 5.20)°, (78.42 ± 6.45)°, and (98.77 ± 8.67)° (P < 0.05). One day after operation, there exhibited no remarkable difference in whole blood viscosity low shear, plasma viscosity, and fibrinogen level (P > 0.05). However, there exhibited no remarkable difference in plasma viscosity and fibrinogen level at 1 day and 7 days after operation (P > 0.05). Seven days after operation, the whole blood viscosity, plasma viscosity, and fibrinogen in the study group were lower (P < 0.05). The probability of postoperative complications was compared. In the study group, there were 2 cases of limb swelling and pain, 1 case of joint stiffness, and no swelling and pain complicated with deep venous thrombosis, and the total incidence was 6.00%. In the control group, there were 5 cases of limb swelling and pain, 3 cases of joint stiffness, and 3 cases of swelling and pain complicated with deep venous thrombosis, with a total incidence of 22.00%. The incidence of adverse reactions in the study group was lower (χ2 = 5.317 P < 0.05). Conclusion Early electroacupuncture combined with ERAS is of positive significance to the patients after TKA, which can reduce the pain, enhance the function of the knee joint, and promote the ROM of the knee joint, and can effectively shorten the first time out of bed and postoperative rehabilitation time and reduce whole blood viscosity low shear, plasma viscosity, and fibrinogen level, but the overall rehabilitation cost is high, and clinical application should be combined with the actual situation of patients.

The effect of cigarette smoking in plasma fibrinogen level and platelet count in male Smokers in Nnewi, Anambra State, Nigeria

Cigarette Smoking has been shown to induce hypercoagulability and a hyper thrombotic state, possibly by increased platelet aggregation and adhesiveness as a result of its nicotine content. During tissue and vascular injury, Fibrinogen (factor I) is converted enzymatically by thrombin to fibrin and subsequently to a fibrin-based blood clot. This study was aimed to determine the effect of cigarette smoking in plasma fibrinogen and platelet levels in male smoker in Nnewi, Anambra state. Apparently healthy 80 male cigarette smokers and 80 male non cigarette smokers, aged between 18 and 40 years, resident in Nnewi were recruited for this study. Four milliliters of blood were collected from each participants (test and control samples), 2ml in trisodium citrate anticoagulated tubes and 2ml in EDTA for the estimation of plasma fibrinogen levels and platelets count respectively. Fibrinogen was estimated using the method described by Clauss. Platelets were estimated using Mythic 22 Automated Hematological Analyzers. The results showed a significant difference between the mean plasma Fibrinogen level in cigarette smokers and non-cigarette smokers (365.90±66.79 vs 203.02±47.40; p= 0.001). There was no significant difference observed in the mean platelets count of cigarette smokers when compared to the mean values of non-cigarette smokers (242.80±94.70 VS 202.84±76.31; p = 0.564). The study concluded that cigarettes smoking elicits an increase in the plasma fibrinogen level.

Correlations of Plasma Thyroxine with Activated Partial Thromboplastin Time and Fibrinogen Levels in Hyperthyroid Patients

Background: A complex pattern of hypercoagulability is associated with hyperthyroidism which is attributed to the actions mediated by boosting up of platelet activation, release of pro-coagulatory cytokines and chemokines, and probable interactions of activated platelets and endothelial cells that may lead to increased risk for intravascular thrombosis. Hyperthyroidism is linked to higher levels of fibrinogen, vWF and factor VIII, lower levels of plasminogen and plasminogen activator, decrease in PT and activated partial thromboplastin time (aPTT) levels and non-significant changes in PAI and antiplasmin levels. Aim: To assess the hypercoagulability and determine the correlation of plasma T4 with aPTT and fibrinogen levels in hyperthyroid patients. Methods: It was an observational prospective study carried out at Niazi Medical College and teaching hospital, Sargodha from January to November 2021. 118 patients with diagnosed hyperthyroidism and above 15 years were recruited in the study that did not have history of coagulability of blood such as hemophilia, immune disorders, cancers, pregnancy, clinically known hypercoagulable state, and on any type of anticoagulant therapy. Levels of thyroid hormones (TSH, T3 and T4), aPTT and fibrinogen were measured in the laboratory. Data was analyzed using SPSS version 20. Frequencies, percentages and range were calculated for categorical variables. Spearman’s correlation was used to determine the correlation between plasma T4 levels and aPTT and plasma T4 and fibrinogen in all patients. Results: Cumulative results showed that 34 (29%) patients had T4 level between 11– 16µg/dl, 45(38%) between 17- 21µg/dl and 39(33%) had T4 levels &gt; 21 µg/dl. Spearman’s correlation’s results to determine association between plasma T4 and aPTT revealed that a strong negative correlation (rs= -.67, p&lt; .001) exists between plasma levels of Thyroxine (M = 18.49, SD= 3.78) and aPTT (M=23.70, SD=1.70). A moderate positive correlation (rs= .37, p &lt; .001) is evident between plasma thyroxine (M = 18.49, SD = 3.78) and fibrinogen (M = 4.27, SD = 0.43) levels. Conclusion: High levels of thyroxine (T4) lead to a hypercoagulable state due to shortened aPTT and higher fibrinogen levels and there is a strong negative correlation between plasma thyroxine (T4) and aPTT and fibrinogen levels in hyperthyroid patients. Keywords: Hyperthyroidism, hypercoagulability, thyroxine (T4), activated partial thromboplastin time (aPTT).

Ammonia exposure by intratracheal instillation causes severe and deteriorating lung injury and vascular effects in mice

Objective Ammonia (NH3) is a corrosive alkaline gas that can cause life-threatening injuries by inhalation. The aim was to establish a disease model for NH3-induced injuries similar to acute lung injury (ALI) described in exposed humans and investigate the progression of lung damage, respiratory dysfunction and evaluate biomarkers for ALI and inflammation over time. Methods Female BALB/c mice were exposed to an NH3 dose of 91.0 mg/kg·bw using intratracheal instillation and the pathological changes were followed for up to 7 days. Results NH3 instillation resulted in the loss of body weight along with a significant increase in pro-inflammatory mediators in both bronchoalveolar lavage fluid (e.g. IL-1β, IL-6, KC, MMP-9, SP-D) and blood (e.g. IL-6, Fibrinogen, PAI-1, PF4/CXCL4, SP-D), neutrophilic lung inflammation, alveolar damage, increased peripheral airway resistance and methacholine-induced airway hyperresponsiveness compared to controls at 20 h. On day 7 after exposure, deteriorating pathological changes such as increased macrophage lung infiltration, heart weights, lung hemorrhages and coagulation abnormalities (elevated plasma levels of PAI-1, fibrinogen, endothelin and thrombomodulin) were observed but no increase in lung collagen. Some of the analyzed blood biomarkers (e.g. RAGE, IL-1β) were unaffected despite severe ALI and may not be significant for NH3-induced damages. Conclusions NH3 induces severe acute lung injuries that deteriorate over time and biomarkers in lungs and blood that are similar to those found in humans. Therefore, this model has potential use for developing diagnostic tools for NH3-induced ALI and for finding new therapeutic treatments, since no specific antidote has been identified yet.

Prognostic value of preoperative plasma fibrinogen levels in resected stage I non-small cell lung cancer.

BackgroundThe number of surgical procedures has increased among patients with early‐stage lung cancer. If the poor prognostic factors for stage I non‐small cell lung cancer (NSCLC) can be simply validated preoperatively, appropriate treatment will be provided. The current study aimed to evaluate the prognostic value of preoperative plasma fibrinogen levels in patients with resected stage I NSCLC.MethodsWe retrospectively analyzed the clinicopathological information of patients (n = 149) who underwent lobectomy for stage I NSCLC between May 2014 and July 2016. Data about peripheral blood analysis, histopathological finding, and follow‐up assessment results were collected from the databases. Patients were divided into the low and high fibrinogen groups. Univariate and multivariate analyses were performed to evaluate the predictors of recurrence and survival.ResultsCompared with the low fibrinogen group (<377 mg/dl), the high fibrinogen group (≥377 mg/dl) had a significantly greater number of male participants (p = 0.04), smokers (p < 0.001), and those with elevated cytokeratin antigen levels (p = 0.04), lymphatic invasion (p = 0.007), and squamous cell carcinoma (p < 0.001). Plasma fibrinogen level was considered a significant independent factor for recurrence and overall survival on both the univariate and multivariate analyses (p < 0.001 and p = 0.010) and the multivariate analysis alone (p = 0.020 and p < 0.012).ConclusionPreoperative plasma fibrinogen level might be a useful predictor of recurrence and survival in patients with stage I NSCLC. The treatment strategy for patients with high fibrinogen levels could be cautiously considered preoperatively.

Association of Preoperative Plasma D-Dimer and Fibrinogen and Osteosarcoma Outcome.

ObjectiveWe aimed to evaluate the utility of preoperative D-dimer and plasma fibrinogen (PF) levels as useful markers for predicting the clinical value of patients with osteosarcoma.Methods145 enrolled patients with osteosarcoma were studied retrospectively. We determined the critical values of D-dimer and PF by receiver operating characteristic curve analysis. Cox regression analysis was used to assess prognostic role of the D-dimer and PF levels among osteosarcoma patients.ResultsThe critical values of D-dimer and PF were calculated to be 0.46 µg/mL and 3.34 mg/mL, respectively. Upregulation of D-dimer and PF showed positive correlations with a higher clinical stage, tumour metastasis and recurrence. Survival curve results confirmed that osteosarcoma patients with higher levels of D-dimer and PF predicted worse overall survival (OS) and progression-free survival (PFS). Moreover, only a high D-dimer level was associated with a shorter OS (P = 0.013) and PFS (P = 0.042) in both the univariate and multivariate analysis.ConclusionElevated preoperative D-dimer levels are correlated with aggressive clinicopathological features and poor survival outcomes, which indicates that assessment of the D-dimer could be a useful prognostic marker in osteosarcoma.