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International Journal of Molecular... Oct 2023Antithrombin III is an important anticoagulant factor with anti-inflammatory properties. However, few studies have explored its anti-inflammatory actions in...
Antithrombin III is an important anticoagulant factor with anti-inflammatory properties. However, few studies have explored its anti-inflammatory actions in overexpressed transgenic animals. In this study, the dairy goats with mammary overexpression of were used to investigate their general health, milk quality and particularly their response to inflammatory challenge. The results showed that transgenic goats have a normal phenotype regarding their physiological and biochemical parameters, including whole blood cells, serum protein levels, total cholesterol, urea nitrogen, uric acid, and total bilirubin, compared to the WT. In addition, the quality of milk also improved in transgenic animals compared to the WT, as indicated by the increased milk fat and dry matter content and the reduced somatic cell numbers. Under the stimulation of an LPS injection, the transgenic goats had elevated contents of IGA, IGM and superoxide dismutase SOD, and had reduced proinflammatory cytokine release, including IL-6, TNF-α and IFN-β. A 16S rDNA sequencing analysis also showed that the transgenic animals had a similar compositions of gut microbiota to the WT goats under the stimulation of LPS injections. Mammary gland overexpression in dairy goats is a safe process, and it did not jeopardize the general health of the transgenic animals; moreover, the compositions of their gut microbiota also improved with the milk quality. The LPS stimulation study suggests that the increased expression may directly or indirectly suppress the inflammatory response to increase the resistance of transgenic animals to pathogen invasion. This will be explored in future studies.
Topics: Animals; Female; Lipopolysaccharides; Antithrombin III; Milk; Animals, Genetically Modified; Anticoagulants; Goats; Health Status; Mammary Glands, Animal; Lactation
PubMed: 37894983
DOI: 10.3390/ijms242015303 -
Diseases (Basel, Switzerland) Oct 2023The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has generated an unprecedented challenge for healthcare systems worldwide. Currently, the...
UNLABELLED
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has generated an unprecedented challenge for healthcare systems worldwide. Currently, the scientific community wonders if liver injury in patients suffering from severe forms is a direct consequence of the virus or secondary manifestations of systemic inflammation. The liver plays an essential role in the development of the inflammatory storm typical of this disease, and its involvement is associated with worse clinical outcomes and a higher risk of morbidity and mortality from Coronavirus disease 2019 (COVID-19).
METHODS
Ten patients suffering from severe COVID-19 disease who died between January 2020 and December 2021 were included in the present analysis. These subjects underwent a post mortem examination with a focused evaluation of the hepatic injury. Also, several laboratory parameters have been evaluated, with a primary focus on prothrombin time, partial thromboplastin time, fibrinogen, antithrombin III, and D-dimers to detect coagulative changes.
RESULTS
The main cause of death was represented by pulmonary thromboembolism events (50%). The analysis of coagulation laboratory parameters and liver biomarkers revealed a statistically significant rise in aPTT and ALP, and a decrease in albumin, when comparing the blood value at admission and death. We also found high levels of D-dimers in most of the subjects at the time of hospitalization. Interestingly, the post mortem analysis of the liver showed ample morphologic variability, with several disease features. In detail, the liver histology revealed the following: the presence of a variable degree of micro- and macrovacuolar steatosis, inflammation (also, hepato-cholangitis), and variable fibrosis. Of mention, we were also able to detect organized fibrinous material.
CONCLUSIONS
Our results indicate that in subjects with a severe form of COVID-19, liver disease is related to changes in coagulative and fibrinolytic pathways. In particular, we noted low fibrinogen levels and high D-dimer levels with histological liver findings. Our data suggest that fibrinogen and D-dimers may be used as prognostic markers to detect the severity of liver disease in patients with COVID-19. Finally, we underline the crucial role of coagulation balance in subjects with severe forms of COVID-19.
PubMed: 37873785
DOI: 10.3390/diseases11040141 -
Frontiers in Genetics 2023Hereditary antithrombin-III deficiency can significantly increase the risk for thrombosis, which is common in limb deep vein and pulmonary cases. However, thrombotic...
Hereditary antithrombin-III deficiency can significantly increase the risk for thrombosis, which is common in limb deep vein and pulmonary cases. However, thrombotic microangiopathy (TMA) caused by hereditary antithrombin deficiency is rare. We reported the case of a 32-year-old Chinese female patient with TMA with renal injury caused by decreased antithrombin-III activity due to a new mutation (chr1-173884049 c.50A>G) in , which encodes antithrombin-III. In this case, the patient had no history of relevant drug use, diabetes, or monoclonal plasma cells in the bone marrow puncture. Consequently, TMA of the kidney was considered secondary to hereditary antithrombin-III deficiency. Gene detection was the only clue that led us to suspect that TMA was caused by hereditary antithrombin deficiency. Our findings indicated that for patients with repeated findings of antithrombin-III activity less than 50%, the possibility of antithrombin-III deficiency and complete gene detection must be considered immediately after excluding the use of anticoagulants and lack of availability to facilitate early detection, diagnosis, and intervention.
PubMed: 37829283
DOI: 10.3389/fgene.2023.1278511 -
Clinical and Applied... 2023Antithrombin (AT) is a natural anticoagulant pivotal in inactivating serine protease enzymes in the coagulation cascade, making it a potent inhibitor of blood clot...
Antithrombin (AT) is a natural anticoagulant pivotal in inactivating serine protease enzymes in the coagulation cascade, making it a potent inhibitor of blood clot formation. AT also possesses anti-inflammatory properties by influencing anticoagulation and directly interacting with endothelial cells. Hereditary AT deficiency is one of the most severe inherited thrombophilias, with up to 85% lifetime risk of venous thromboembolism. Acquired AT deficiency arises during heparin therapy or states of hypercoagulability like sepsis and premature infancy. Optimization of AT levels in individuals with AT deficiency is an important treatment consideration, particularly during high-risk situations such as surgery, trauma, pregnancy, and postpartum. Here, we integrate the existing evidence surrounding the approved uses of AT therapy, as well as potential additional patient populations where AT therapy has been considered by the medical community, including any available consensus statements and guidelines. We also describe current knowledge regarding cost-effectiveness of AT concentrate in different contexts. Future work should seek to identify specific patient populations for whom targeted AT therapy is likely to provide the strongest clinical benefit.
Topics: Pregnancy; Female; Humans; Antithrombins; Endothelial Cells; Anticoagulants; Antithrombin III; Blood Coagulation; Antithrombin III Deficiency
PubMed: 37822179
DOI: 10.1177/10760296231205279 -
Scientific Reports Oct 2023Antithrombin (AT) deficiency increases the risk for venous thromboembolism, therefore, a highly sensitive assay to identify this condition is crucial. The aim of this... (Meta-Analysis)
Meta-Analysis
Antithrombin (AT) deficiency increases the risk for venous thromboembolism, therefore, a highly sensitive assay to identify this condition is crucial. The aim of this paper was to perform a meta-analysis comparing AT activities measured by different AT activity assays in patients with heparin binding site AT deficiency. In addition, the diagnostic sensitivity of selected assays was compared depending on the available data. An extensive literature search was performed considering results with publication date up to July 10, 2021. Seven relevant English-language observational studies, comparing AT activity measured by different AT activity assays in Caucasian Europeans with either the AT Budapest III or AT Padua I mutation were included in meta-analyses. There was no significant difference in AT activity between Labexpert and Innovance in patients with AT Budapest III (P = 0.567) and AT Padua I (P = 0.265), while AT activity determined by HemosIL was significantly higher compared to Innovance for both mutations (AT Budapest III: P < 0.001; AT Padua I: P < 0.001). These results are in line with the results of comparison of diagnostic sensitivity. In patients with AT Budapest III, the AT activity was also higher when measured with Berichrom compared to Innovance (P = 0.002), however, the results of comparison of diagnostic sensitivity across studies were variable. No significant difference (P = 0.117) in AT activity as well as diagnostic sensitivity was observed between Sta-Stachrom and Innovance. The results of our study suggest that Innovance, Labexpert and Sta-Stachrom are the most sensitive activity assays for detection of AT Budapest III and AT Padua I, whereas HemosIL showed considerably lower sensitivity for these two variants. As revealed in our study, the diagnostic sensitivity of AT activity assays to type II heparin binding site AT deficiency is different, and in some assays mutation dependent.
Topics: Humans; Heparin; Anticoagulants; Blood Coagulation Tests; Antithrombin III Deficiency; Binding Sites; Antithrombins
PubMed: 37794095
DOI: 10.1038/s41598-023-43941-x -
Clinical and Applied... 2023Preeclampsia (PE) is associated with endothelial injury and hemostatic abnormalities. However, the diagnostic role of coagulation parameters and natural anticoagulants...
Preeclampsia (PE) is associated with endothelial injury and hemostatic abnormalities. However, the diagnostic role of coagulation parameters and natural anticoagulants in predicting PE has not been explored in Ghana. This study assessed plasma levels of these factors as surrogate markers of PE and its subtypes. This case-control study included 90 women with PE (cases) and 90 normotensive pregnant women (controls). Blood samples were drawn for the estimation of complete blood count and coagulation tests. The prothrombin time (PT), activated partial thromboplastin time (APTT), and the calculation of the international normalized ratio (INR) were determined by an ACL elite coagulometer while the levels of protein C (PC), protein S (PS), antithrombin III (ATIII), and D-dimers were also measured using the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA) method. All statistical analyses were performed using the R Language for Statistical Computing. Results showed significantly (< .05) shortened APTT (28.25 s) and higher D-dimer levels (1219.00 ng/mL) among PE women, as well as low levels of PC (1.02 µg/mL), PS (6.58 µg/mL), and ATIII (3.99 ng/mL). No significant difference was found in terms of PT and INR. From the receiver operating characteristic analysis, PC, PS, and ATIII could significantly predict PE and its subtypes at certain cutoffs with high accuracies (area under the curve [AUC] ≥0.70). Most women with PE are in a hypercoagulable state with lower natural anticoagulants. PC, PS, and ATIII are good predictive and diagnostic markers of PE and its subtypes (early-onset PE [EO-PE] and late-onset PE [LO-PE]) and should be explored in future studies.
Topics: Female; Humans; Pregnancy; Anticoagulants; Ghana; Pre-Eclampsia; Case-Control Studies; Blood Coagulation Factors; Protein C; Biomarkers
PubMed: 37787124
DOI: 10.1177/10760296231204604 -
Cureus Aug 2023Andexanet alfa is an analog of activated factor X and is used as an antagonist of anti-activated factor X agents. Andexanet alfa is useful for hemostasis in emergent...
Andexanet alfa is an analog of activated factor X and is used as an antagonist of anti-activated factor X agents. Andexanet alfa is useful for hemostasis in emergent bleeding during direct oral anticoagulant administration, which contributes to safety. In patients undergoing surgery with cardiopulmonary bypass because of heparin resistance, anesthesiologists are faced with a choice of anticoagulants. Herein, we experienced anesthesia for vascular prostheses with cardiopulmonary bypass for acute aortic dissection in a patient who had received andexanet alfa preoperatively. Heparin was initially used as the anticoagulant during cardiopulmonary bypass; however, despite the administration of large doses and antithrombin III preparations, anticoagulation was insufficient. Therefore, nafamostat mesilate was administered and sufficient anticoagulation was attained. The patient completed surgery under cardiopulmonary bypass, coagulation function was recovered shortly after withdrawal, and no obvious adverse effects were observed.
PubMed: 37746371
DOI: 10.7759/cureus.44003 -
Frontiers in Immunology 2023To evaluate the usefulness of urine SERPINC1 and ORM1 as biomarkers for early detection of lupus nephritis (LN).
BACKGROUND
To evaluate the usefulness of urine SERPINC1 and ORM1 as biomarkers for early detection of lupus nephritis (LN).
METHODS
Using proteomics, we screened for potential urine biomarkers that differentiate LN from systemic lupus erythematosus (SLE) patients without nephritis. In addition, urine levels of target biomarkers were measured by ELISA in 13- and 23-week-old MRL-lpr (murine model for LN) and MRL/MpJ mice. Histological analysis was also performed on the kidneys of 23-week-old mice.
RESULTS
Urine SERPINC1 and ORM1 were elevated in SLE patients with newly diagnosed LN compared with SLE patients without LN (SERPINC1, AUC=.892, P<.001; ORM1, AUC=.886, P<.001). Levels of urine SERPINC1 and ORM1 were also significantly higher in MRL-lpr mice than in MRL/MpJ mice at 13 and 23 weeks (SERPINC1: p<.01 and p<.001 at 13 and 23 weeks, respectively; ORM1: p<.01 at 13 and 23 weeks). In contrast, a significant difference in urine albumin between the two groups was only observed at 23 weeks (p<.001) not at 13 weeks (p=.83). Regarding the kidney pathology of MPL-lpr mice, urine ORM1 and urine albumin, but not urine SERPINC1, were positively correlated with the activity index (ORM1, rho =.879, p<.001; albumin, rho =.807, p=.003) and chronicity index (ORM1, rho =.947, p<.001; albumin, rho =.869, p<.001).
CONCLUSION
We propose that urine SERPINC1 and ORM1 are novel biomarkers for early LN.
Topics: Humans; Animals; Mice; Lupus Nephritis; Mice, Inbred MRL lpr; Lupus Erythematosus, Systemic; Albumins; Biomarkers; Antithrombin III
PubMed: 37744355
DOI: 10.3389/fimmu.2023.1148574 -
BMC Surgery Sep 2023As an emerging standard of care for portal vein cavernous transformation (PVCT), Meso-Rex bypass (MRB) has been complicated and variated. The study aim was to propose a...
BACKGROUND
As an emerging standard of care for portal vein cavernous transformation (PVCT), Meso-Rex bypass (MRB) has been complicated and variated. The study aim was to propose a new classification of PVCT to guide MRB operations.
METHODS
Demographic data, the extent of extrahepatic PVCT, surgical methods for visceral side revascularization, intraoperative blood loss, operating time, changes in visceral venous pressure before and after MRB, postoperative complications and the condition of bypass vessels after MRB were extracted retrospectively from the medical records of 19 patients.
RESULTS
The median age of the patients (13 males and 6 females) was 32.5 years, while two patients were underage. Causes of PVCT can be summarized as follows: thrombophilia such as dysfunction of antithrombin III or proteins C; secondary to abdominal surgeries; secondary to abdominal infection or traumatic intestinal obstruction, and unknown causes. Intraoperatively, the median operation time was 9.5 h (7-13 h), and the intraoperative blood loss was 300 mL (100-1,600 mL). Ten cases used autologous blood vessels while 10 used allogeneic blood vessels. The vascular anastomosis was divided into the following types according to the site and approach: Type (T) 1-PV pedicel type, T2-confluence type, T3-major visceral vascular type; and T4-collateral visceral vascular type. Furthermore, the visceral venous pressure before and after MRB dropped significantly from 36 cmHO (28-44) to 24.5 cmHO (15-31) (P < 0.01). Postoperatively, one patient had delayed wound healing, two developed biochemical pancreatic fistulae, one experienced lymphatic leakage, the former caused by heat damage of the pancreatic tissues, the latter by cutting lymphatic vessels in the mesentery or removing the local lymph nodes during the process of separating the superior mesenteric vein, and one was re-operated on for an intervening intestinal fistulae. Postoperative enhanced CT scans revealed a significant improvement in abdominal varix in the patients with patent bypass, and at the 1-year postoperative follow-up, enhanced CT scans of six patients showed that the long axis of the spleen was reduced by ≥ 2 cm.
CONCLUSIONS
MRB can effectively reduce visceral venous pressure in patients with PVCT. It is feasible to determine the PVCT type according to the extent of involvement and to choose individualized visceral side revascularization performances.
Topics: Female; Male; Humans; Adult; Portal Vein; Blood Loss, Surgical; Retrospective Studies; Vascular Surgical Procedures; Spleen
PubMed: 37705015
DOI: 10.1186/s12893-023-02168-3 -
Journal of Clinical Medicine Sep 2023Knowledge of the natural history and management of hepatic hemangiomas is lacking. The aim of this study was to investigate the natural history of hemangiomas and to...
BACKGROUND
Knowledge of the natural history and management of hepatic hemangiomas is lacking. The aim of this study was to investigate the natural history of hemangiomas and to elucidate the factors that determine tumor growth and optimal management.
METHODS
A total of 211 adult patients were enrolled, with follow-up for more than three years. Follow-up was performed with repeated ultrasonography (US) and laboratory tests for liver function and coagulation factors (platelets, prothrombin time (PT), fibrinogen, thrombin-antithrombin III complex (TAT), D-dimer, and fibrin and fibrinogen degradation products (FDP)).
RESULTS
Tumor size decreased in 38.9% of patients, showed no change in 31.3%, and increased in 29.8%. The incidence of a size increase was very high in patients under 40 years of age and decreased gradually with age, whereas the incidence of a size decrease increased with age and increased markedly over 60 years of age. The incidence of an increase in size decreased gradually with size enlargement, whereas the incidence of a decrease in size increased markedly with tumor size and further increased rapidly when hemangiomas became larger than 60 mm. Values of TAT, D-dimer, FDP, and Mac-2 binding protein glycosylation isomer (M2BPGi) were closely related to the change in size of hemangiomas.
CONCLUSIONS
Hemangiomas in older patients (>60 years of age) and larger tumors (>60 mm in size) had a tendency to decrease in size, resulting from the reduction in coagulation disorders and the progression of liver fibrosis. Therefore, the majority of patients with hemangiomas can be safely managed by clinical observation.
PubMed: 37685768
DOI: 10.3390/jcm12175703