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Biologicals : Journal of the... Jun 2024Convalescent plasma was proposed for passive immunization against COVID-19; but so far there are conflicting results and still open questions. However, besides...
Convalescent plasma was proposed for passive immunization against COVID-19; but so far there are conflicting results and still open questions. However, besides antibodies, other plasma proteins may be good candidates for further research and application. Thromboinflammation frequently complicates severe COVID-19, and classical anticoagulants like heparins seem to have limited effect. The natural protease inhibitors antithrombin III (ATIII), α-antitrypsin (α-AT) and α-macroglobulin (α-M), which are found decreased in severe COVD-19, play a crucial role in prothrombotic and inflammatory pathways. While ATIII and α-AT are licensed as commercially prepared therapeutic concentrates, there is no preparation of α-M available. The diagnostic, prognostic, and even therapeutic potential of plasma protease inhibitors should be further explored.
PubMed: 38924809
DOI: 10.1016/j.biologicals.2024.101781 -
Journal of Neurointerventional Surgery Jun 2024Flow diverting stents (FDS) have transformed the treatment of intracranial aneurysms; however, their metallic structure associated with their intra-luminal positioning...
BACKGROUND
Flow diverting stents (FDS) have transformed the treatment of intracranial aneurysms; however, their metallic structure associated with their intra-luminal positioning hamper angiographic and clinical outcomes. Therefore, there is a need to develop FDS with optimized surfaces that reduce thrombogenicity while promoting the healing process and endothelialization.
METHODS
P8RI, a peptide mimicking the CD31 protein, was previously developed and grafted onto Silk Vista (SV) FDS. P8RI-SV and bare-SV were used in vitro in a blood loop model to test their hemocompatibility using human whole blood and in vivo using the rabbit elastase model for optical coherence tomography (OCT) comparisons of neointimal formation at day 5 and day 28.
RESULTS
After blood loop incubation, P8RI-SV showed significant reduction in fibrin binding (p=0.004) and platelet adhesion (p=0.041) compared with bare-SV. Similarly, derivative markers measured in blood, thromboxane B2 (platelet activation) and Thrombin-Antithrombin III complexes (coagulation activation), were also significantly reduced in the P8RI-SV group (both p=0.002). In vivo, complete or near-complete occlusion was reached in all aneurysms (n=6) at day 28. Excellent rate of stent-coverage ratio was obtained at day 5 (89.3% (79.1%-98.7%)) comparable to the observation at day 28 (91.8% (79.1%-100%); p=0.44). These rates were significantly higher compared with bare-SV at day 5 (77.8% (58.3%-86.8%); p<0.001) and at day 28 (67.7% (52.6%-88.9%); p<0.0001).
CONCLUSION
In vitro results confirm enhanced hemocompatibility with a significant anti-thrombotic effect of the P8RI-SV. In vivo results provide evidence of rapid neo-intimal growth reaching near-complete tissue healing as early as day 5 in a rabbit model.
PubMed: 38914459
DOI: 10.1136/jnis-2024-021694 -
Bulletin of Experimental Biology and... Jun 2024We studied the effectiveness of Xe/O mixture inhalation (30% Xe and 70% O, 20 min for 5 days) in a model of experimental thromboplastin pneumonitis. Inhalation of the...
We studied the effectiveness of Xe/O mixture inhalation (30% Xe and 70% O, 20 min for 5 days) in a model of experimental thromboplastin pneumonitis. Inhalation of the studied mixture decreased the intensity of the inflammatory process in the lung tissue assessed by the temperature response of animals, changed lung weight and lung weight coefficient. At acute stage of pneumonitis, an increase in xenon consumption was recorded due to its retention in the gas exchange zone and a natural decrease in oxygen consumption due to partial alveolar/capillary block. The formation of pneumonitis was accompanied by a pronounced procoagulant shift in the regulation system of the aggregate state of blood. The Xe/O inhalations ensured physiologically optimal levels of prothrombin and activated partial thromboplastin time against the background of a moderate decrease in fibrinogen level throughout the experiment. At the same time, the activity of the natural anticoagulant antithrombin III increased from day 5 to day 14.
PubMed: 38904932
DOI: 10.1007/s10517-024-06098-9 -
Early diagnosis of occult pulmonary embolism secondary to lower limb fractures: summary of 18 cases.Frontiers in Medicine 2024Pulmonary thromboembolism is a severe but probably underdiagnosed disorder. Patients with lower limb fractures are at high risk for pulmonary thromboembolism. This study...
OBJECTIVES
Pulmonary thromboembolism is a severe but probably underdiagnosed disorder. Patients with lower limb fractures are at high risk for pulmonary thromboembolism. This study aimed to demonstrate the early identification strategies for occult pulmonary thromboembolism.
METHODS
From January to December 2022, 18 patients diagnosed with pulmonary thromboembolism were reviewed for this study. Data on patients' demographics, laboratory test results, and radiographic findings were collected. Finally, the data was analyzed.
RESULTS
Eighteen patients with lower limb fractures were included in this study. All of them present different symptoms, including 12 cases (12/18, 66%) of unexplained decrease in oxygen saturation; 16 patients had deep vein thrombosis in the lower limbs, with nine cases involving proximal veins and seven involving distal veins. One patient had an antithrombin III level of 35%. Thirteen cases were diagnosed with pulmonary embolism using CT pulmonary angiography. Four patients had pulmonary embolisms incidentally detected during coronary CT angiography, and one patient during aortic CT angiography.
CONCLUSION
Patients with lower limb fractures showing chest tightness and unexplained decrease in finger pulse oxygen levels should be assessed for pulmonary thromboembolism. Simultaneously, selecting appropriate diagnostic tools is essential to guaranteeing quick and accurate diagnosis.
PubMed: 38873198
DOI: 10.3389/fmed.2024.1355030 -
Cureus May 2024The onset of cardiovascular complications has increased the mortality rate in rheumatoid arthritis (RA) patients. Presently, there is a need to diagnose cardiovascular...
BACKGROUND
The onset of cardiovascular complications has increased the mortality rate in rheumatoid arthritis (RA) patients. Presently, there is a need to diagnose cardiovascular co-morbidity in rheumatic disease. While biomarkers such as P-selectin glycoprotein ligand-1 (PSGL-1), fibrinogen, anti-thrombin III (AT-III), hsCRP, lipoprotein (a) (lp(a)), leptin, adiponectin, and asymmetric dimethyl arginine (ADMA) are already established as independent risk factors for the development of atherosclerosis, the association of these biomarkers with disease activity in RA patients is unclear.
METHODS
The case-control study comprised 40 cases along with age- and gender-matched controls recruited from a tertiary care hospital in southern India. Platelet activation in plasma was analyzed by flow cytometry using CD41 per CPCY 5.5 (platelet marker) and human CD62P FITC monoclonal antibody (P-selectin marker). Other parameters were quantified through nephelometry and ELISA. The association between the risk factors and RA disease severity, as per the disease activity score (DAS/DAS28), was analyzed. Furthermore, an ROC analysis was done to assess the utility of these biomarkers in the diagnosis of RA.
RESULTS
With the exception of leptin, adiponectin, and ADMA, there was a significant increase in the levels of PSGL-1, fibrinogen, AT-III, hsCRP, and lp(a) when compared to healthy controls. Conventional risk factors contributing to dyslipidemia were also assessed, in which the low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio was found to be significantly higher in RA patients compared to controls. Moreover, a significant positive correlation was identified between DAS score and activated platelets, fibrinogen, and hsCRP. ROC analysis identified that fibrinogen could predict the RA disease status with 95% accuracy, followed by activated platelets and hsCRP.
CONCLUSION
Several of the studied atherothrombotic risk factors were significantly altered in patients with RA. Activated platelets, fibrinogen, and hsCRP were associated with disease activity and also served as good diagnostic predictors for RA. Based on our findings, further studies could explore the potential of introducing anti-thrombotic agents in the treatment regimen of patients with RA.
PubMed: 38846255
DOI: 10.7759/cureus.59818 -
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue May 2024The incidence and mortality of venous thromboembolism (VTE) are high in critically ill patients, and there is still a risk of VTE and bleeding after the use of... (Review)
Review
The incidence and mortality of venous thromboembolism (VTE) are high in critically ill patients, and there is still a risk of VTE and bleeding after the use of fixed-dose low molecular weight heparin (LMWH) for prophylaxis. The level of anti-factor Xa is not up to standard after LMWH prophylaxis in patients with surgery or trauma. The condition of critically ill patients is complicated, and the proportion of patients with low antithrombin III is high, which can affect the prophylactic efficacy of LMWH and contribute to VTE occurrence. There is currently no consensus on whether adjusting LMWH dose according to anti-factor Xa levels can reduce VTE occurrence in critically ill patients. High-quality multicenter randomized controlled studies are needed in the future to establish new approaches for precise prevention of VTE in critically ill patients.
Topics: Humans; Venous Thromboembolism; Heparin, Low-Molecular-Weight; Critical Illness; Anticoagulants; Factor Xa Inhibitors; Factor Xa
PubMed: 38845490
DOI: 10.3760/cma.j.cn121430-20231103-00937 -
Frontiers in Endocrinology 2024A prothrombotic state was demonstrated in patients with Cushing's syndrome and is involved in the development and progression of cardiovascular and renal damage in...
BACKGROUND AND AIMS
A prothrombotic state was demonstrated in patients with Cushing's syndrome and is involved in the development and progression of cardiovascular and renal damage in hypertensive patients. This study was designed to examine the relationships between cortisol secretion and the hemostatic and fibrinolytic systems in hypertension.
METHODS
In 149 middle-aged, nondiabetic, essential hypertensive patients free of cardiovascular and renal complications, we measured hemostatic markers that express the spontaneous activation of the coagulation and fibrinolytic systems and assessed daily cortisol levels (8 AM, 3 PM, 12 AM; area under the curve, AUC-cortisol) together with the cortisol response to dexamethasone overnight suppression (DST-cortisol).
RESULTS
Plasma levels of D-dimer (D-dim), prothrombin fragment 1 + 2 (F1 + 2), and von Willebrand factor (vWF) were progressively and significantly higher across tertiles of AUC-cortisol and DST-cortisol, whereas no differences were observed in fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor-1, antithrombin III, protein C, and protein S. D-dim, F1 + 2, and vWF were significantly and directly correlated with age and both AUC-cortisol and DST-cortisol. Multivariate regression analysis showed that both AUC-cortisol and DST-cortisol were related to plasma D-dim, F1 + 2, and vWF independently of age, body mass index, blood pressure, and renal function.
CONCLUSION
Greater daily cortisol profile and cortisol response to overnight suppression are independently associated with a prothrombotic state in hypertensive patients and might contribute to the development of organ damage and higher risk of cardiovascular complications.
Topics: Humans; Male; Middle Aged; Female; Hydrocortisone; Dexamethasone; Hypertension; Adult; Thrombosis; von Willebrand Factor; Circadian Rhythm; Aged; Biomarkers
PubMed: 38836224
DOI: 10.3389/fendo.2024.1397062 -
Respirology Case Reports Jun 2024The Coronavirus Disease 2019 (COVID-19), caused by the virus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a global public health problem in...
The Coronavirus Disease 2019 (COVID-19), caused by the virus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a global public health problem in which atypical findings other than the usual fever and respiratory symptoms render early diagnosis and treatment difficult. Cases with atypical clinical and laboratory presentations continue to pose a challenge in the treatment and control of the disease. This case report aims to share our follow-up and treatment experience in a patient considered to have antithrombin III (ATIII) deficiency based on activated clotting time (ACT) levels unresponsive to heparin who was admitted to intensive care unit due to COVID-19-induced cytokine storm associated with extreme D-dimer elevation (>65,000 μg/L).
PubMed: 38827641
DOI: 10.1002/rcr2.1394 -
Journal of Gastroenterology and... Jun 2024The development of acute pancreatitis (AP) is strongly linked to blood clotting and fibrinolysis issues. Modern clinical practices now utilize advanced blood markers...
Predictive value of thrombin-antithrombin III complex and tissue plasminogen activator-inhibitor complex biomarkers in assessing the severity of early-stage acute pancreatitis.
BACKGROUND AND AIM
The development of acute pancreatitis (AP) is strongly linked to blood clotting and fibrinolysis issues. Modern clinical practices now utilize advanced blood markers like thrombin-antithrombin III complex (TAT), plasmin-α2-plasmin inhibitor complex, thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) to assess thrombosis risk. Our study used a highly sensitive chemiluminescence technique to measure these markers in AP patients, aiming to determine their early predictive value for AP severity.
METHODS
There were 173 patients with AP, all of whom developed symptoms within 72 h; 102 individuals had onset symptoms within 48 h. The biomarkers were measured upon admission before determining the severity of AP.
RESULTS
The levels of TAT, plasmin-α2-plasmin inhibitor complex, TM, and t-PAIC were significantly higher in the severe acute pancreatitis (SAP) group compared with the mild acute pancreatitis and moderate severe acute pancreatitis groups. For the patients within 72 h of onset, TAT, TM, and t-PAIC predicted the occurrence of SAP. For the patients within 48 h of onset, TAT and t-PAIC predicted the occurrence of SAP. The area under the curve (AUC) of prediction models is similar to Bedside Index for Severity in Acute Pancreatitis (BISAP) but significantly higher than C-reactive protein (P < 0.05). Notably, t-PAIC had a larger AUC than TAT, BISAP, and C-reactive protein.
CONCLUSION
In the initial 48 h, plasma TAT and t-PAIC levels may predict the development of SAP. Within 72 h, plasma levels of TAT, TM, and t-PAIC may predict the development of SAP, and the TAT + TM + t-PAIC prediction model achieved a maximum AUC of 0.915, comparable to BISAP.
PubMed: 38822643
DOI: 10.1111/jgh.16641 -
Frontiers in Nutrition 2024Nattokinase (NK) and red yeast rice (RYR) are both indicated for their potential in cardiovascular disease prevention and management, but their combined effects...
Lipid-lowering, antihypertensive, and antithrombotic effects of nattokinase combined with red yeast rice in patients with stable coronary artery disease: a randomized, double-blinded, placebo-controlled trial.
Nattokinase (NK) and red yeast rice (RYR) are both indicated for their potential in cardiovascular disease prevention and management, but their combined effects especially in coronary artery disease (CAD) are scarcely examined. This 90-day randomized, double-blind trial aims to investigate the effect of NK and RYR supplementations on cardiometabolic parameters in patients with stable CAD. 178 CAD patients were randomized to four groups: NK + RYR, NK, RYR, and placebo. No adverse effects due to the interventions were reported. In comparisons across groups, NK + RYR showed the maximum effect in reducing triglyceride (-0.39 mmol), total cholesterol (-0.66 mmol/L), diastolic blood pressure (-7.39 mmHg), and increase in high-density lipoprotein cholesterol (0.195 mmol/L) than other groups (all p for multiple groups comparison<0.01). Both NK + RYR and NK groups had significantly better-improved lactate dehydrogenase than the others (-29.1 U/L and - 26.4 U/L). NK + RYR group also showed more potent reductions in thromboxane B2 and increases in antithrombin III compared to placebo (both < 0.01). These improved markers suggest that combined NK and RYR may preferably alter antithrombin and COX-1 pathways, potentially reducing thrombosis risks in CAD patients. Overall, the combined NK and RYR supplementation is safe and more effective than separately in improving cardiometabolic markers among CAD patients with multiple heart medications use.
PubMed: 38812930
DOI: 10.3389/fnut.2024.1380727