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International Journal of Molecular... Aug 2023Severe hemostatic disturbances and impaired fibrinolysis occur in sepsis. In the most serious cases, the dysregulation of fibrinolysis contributes to septic shock,... (Review)
Review
Severe hemostatic disturbances and impaired fibrinolysis occur in sepsis. In the most serious cases, the dysregulation of fibrinolysis contributes to septic shock, disseminated intravascular coagulation (DIC), and death. Therefore, an analysis of circulating concentrations of pro- and anti-fibrinolytic mediators could be a winning strategy in both the diagnosis and the treatment of sepsis. However, the optimal cutoff value, the timing of the measurements, and their combination with coagulation indicators should be further investigated. The purpose of this review is to summarize all relevant publications regarding the role of the main components of the plasminogen activation system (PAS) in the pathophysiology of sepsis. In addition, the clinical value of PAS-associated biomarkers in the diagnosis and the outcomes of patients with septic syndrome will be explored. In particular, experimental and clinical trials performed in emergency departments highlight the validity of soluble urokinase plasminogen activator receptor (suPAR) as a predictive and prognostic biomarker in patients with sepsis. The measurements of PAI-I may also be useful, as its increase is an early manifestation of sepsis and may precede the development of thrombocytopenia. The upcoming years will undoubtedly see progress in the use of PAS-associated laboratory parameters.
Topics: Humans; Plasminogen; Sepsis; Shock, Septic; Fibrinolysis; Serine Proteases; Biomarkers
PubMed: 37569751
DOI: 10.3390/ijms241512376 -
Breathe (Sheffield, England) Dec 2023Pleural infection remains a medical challenge. Although closed tube drainage revolutionised treatment in the 19th century, pleural infection still poses a significant... (Review)
Review
Pleural infection remains a medical challenge. Although closed tube drainage revolutionised treatment in the 19th century, pleural infection still poses a significant health burden with increasing incidence. Diagnosis presents challenges due to non-specific clinical presenting features. Imaging techniques such as chest radiographs, thoracic ultrasound and computed tomography scans aid diagnosis. Pleural fluid analysis, the gold standard, involves assessing gross appearance, biochemical markers and microbiology. Novel biomarkers such as suPAR (soluble urokinase plasminogen activator receptor) and PAI-1 (plasminogen activator inhibitor-1) show promise in diagnosis and prognosis, and microbiology demonstrates complex microbial diversity and is associated with outcomes. The management of pleural infection involves antibiotic therapy, chest drain insertion, intrapleural fibrinolytic therapy and surgery. Antibiotic therapy relies on empirical broad-spectrum antibiotics based on local policies, infection setting and resistance patterns. Chest drain insertion is the mainstay of management, and use of intrapleural fibrinolytics facilitates effective drainage. Surgical interventions such as video-assisted thoracoscopic surgery and decortication are considered in cases not responding to medical therapy. Risk stratification tools such as the RAPID (renal, age, purulence, infection source and dietary factors) score may help guide tailored management. The roles of other modalities such as local anaesthetic medical thoracoscopy and intrapleural antibiotics are debated. Ongoing research aims to improve outcomes by matching interventions with risk profile and to better understand the development of disease.
PubMed: 38229682
DOI: 10.1183/20734735.0146-2023 -
Research and Practice in Thrombosis and... Mar 2024A State of the Art lecture entitled "Connecting Fibrinolysis and Dyslipidemia" was presented at the International Society on Thrombosis and Haemostasis Congress 2023....
A State of the Art lecture entitled "Connecting Fibrinolysis and Dyslipidemia" was presented at the International Society on Thrombosis and Haemostasis Congress 2023. Hemostasis balances the consequences of blood clotting and bleeding. This balance relies on the proper formation of blood clots, as well as the breakdown of blood clots. The primary mechanism that breaks down blood clots is fibrinolysis, where the fibrin net becomes lysed and the blood clot dissolves. Dyslipidemia is a condition where blood lipid and lipoprotein levels are abnormal. Here, we review studies that observed connections between impaired fibrinolysis and dyslipidemia. We also summarize the different correlations between thrombosis and dyslipidemia in different racial and ethnic groups. Finally, we summarize relevant and new findings on this topic presented during the 2023 International Society on Thrombosis and Haemostasis Congress. More studies are needed to investigate the mechanistic connections between impaired fibrinolysis and dyslipidemia and whether these mechanisms differ in racially and ethnically diverse populations.
PubMed: 38706781
DOI: 10.1016/j.rpth.2024.102394 -
Biomedicines Jan 2024The existing literature highlights the presence of numerous coagulation factors and markers. Elevated levels of coagulation factors are associated with both existing and... (Review)
Review
The existing literature highlights the presence of numerous coagulation factors and markers. Elevated levels of coagulation factors are associated with both existing and newly diagnosed cases of atrial fibrillation (AF). However, this article summarizes the role of coagulation in the pathogenesis of AF, which includes fibrinogen and fibrin, prothrombin, thrombomodulin, soluble urokinase plasminogen activator receptor, von Willebrand factor, P-selectin, D-dimer, plasminogen activator inhibitor-1, and platelet activation. Coagulation irregularities play a significant role in the pathogenesis of AF.
PubMed: 38397876
DOI: 10.3390/biomedicines12020274 -
Journal of Inflammation Research 2023Venous thromboembolism is a condition that includes deep vein thrombosis and pulmonary embolism. It is the third most common cardiovascular disease behind acute coronary... (Review)
Review
Venous thromboembolism is a condition that includes deep vein thrombosis and pulmonary embolism. It is the third most common cardiovascular disease behind acute coronary heart disease and stroke. Over the past few years, growing research suggests that venous thrombosis is also related to the immune system and inflammatory factors have been confirmed to be involved in venous thrombosis. The role of inflammation and inflammation-related biomarkers in cerebrovascular thrombotic disease is the subject of ongoing debate. P-selectin leads to platelet-monocyte aggregation and stimulates vascular inflammation and thrombosis. The dysregulation of miRNAs has also been reported in venous thrombosis, suggesting the involvement of miRNAs in the progression of venous thrombosis. Plasminogen activator inhibitor-1 (PAI-1) is a crucial component of the plasminogen-plasmin system, and elevated levels of PAI-1 in conjunction with advanced age are significant risk factors for thrombosis. In addition, it has been showed that one of the ways that neutrophils promote venous thrombosis is the formation of neutrophil extracellular traps (NETs). In recent years, the role of extracellular vesicles (EVs) in the occurrence and development of VTE has been continuously revealed. With the advancement of research technology, the complex regulatory role of EVs on the coagulation process has been gradually discovered. However, our understanding of the causes and consequences of these changes in venous thrombosis is still limited. Therefore, we review our current understanding the molecular mechanisms of venous thrombosis and the related clinical trials, which is crucial for the future treatment of venous thrombosis.
PubMed: 38111686
DOI: 10.2147/JIR.S439205 -
Research and Practice in Thrombosis and... Aug 2023Patients with COVID-19 have a higher risk of thrombosis and thromboembolism, but the underlying mechanism(s) remain to be fully elucidated. In patients with COVID-19,...
BACKGROUND
Patients with COVID-19 have a higher risk of thrombosis and thromboembolism, but the underlying mechanism(s) remain to be fully elucidated. In patients with COVID-19, high lipoprotein(a) (Lp(a)) is positively associated with the risk of ischemic heart disease. Lp(a), composed of an apoB-containing particle and apolipoprotein(a) (apo(a)), inhibits the key fibrinolytic enzyme, tissue-type plasminogen activator (tPA). However, whether the higher Lp(a) associates with lower tPA activity, the longitudinal changes of these parameters in hospitalized patients with COVID-19, and their correlation with clinical outcomes are unknown.
OBJECTIVES
To assess if Lp(a) associates with lower tPA activity in COVID-19 patients, and how in COVID-19 populations Lp(a) and tPA change post infection.
METHODS
Endogenous tPA enzymatic activity, tPA or Lp(a) concentration were measured in plasma from hospitalized patients with and without COVID-19. The association between plasma tPA and adverse clinical outcomes was assessed.
RESULTS
In hospitalized patients with COVID-19, we found lower tPA enzymatic activity and higher plasma Lp(a) than that in non-COVID-19 controls. During hospitalization, Lp(a) increased and tPA activity decreased, which associates with mortality. Among those who survived, Lp(a) decreased and tPA enzymatic activity increased during recovery. In patients with COVID-19, tPA activity is inversely correlated with tPA concentrations, thus, in another larger COVID-19 cohort, we utilized plasma tPA concentration as a surrogate to inversely reflect tPA activity. The tPA concentration was positively associated with death, disease severity, plasma inflammatory, and prothrombotic markers, and with length of hospitalization among those who were discharged.
CONCLUSION
High Lp(a) concentration provides a possible explanation for low endogenous tPA enzymatic activity, and poor clinical outcomes in patients with COVID-19.
PubMed: 37680312
DOI: 10.1016/j.rpth.2023.102164 -
World Journal of Critical Care Medicine Sep 2023Sepsis is defined as a life-threatening organ dysfunction caused by the dysregulated host response to infection. It is a complex syndrome and is characterized by... (Review)
Review
Sepsis is defined as a life-threatening organ dysfunction caused by the dysregulated host response to infection. It is a complex syndrome and is characterized by physiologic, pathologic and biochemical abnormalities in response to an infection. Diagnosis of sepsis is based on history, physical examination and other investigations (including biomarkers) which may help to increase the certainty of diagnosis. Biomarkers have been evaluated in the past for many diseases and have been evaluated for sepsis as well. Biomarkers may find a possible role in diagnosis, prognostication, therapeutic monitoring and anti-microbial stewardship in sepsis. Since the pathophysiology of sepsis is quite complex and is incompletely understood, a single biomarker that may be robust enough to provide all information has not been found as of yet. However, many biomarkers have been studied and some of them have applications at the bedside and guide clinical decision-making. We evaluated the PubMed database to search for sepsis biomarkers for diagnosis, prognosis and possible role in antibiotic escalation and de-escalation. Clinical trials, meta-analyses, systematic reviews and randomized controlled trials were included. Commonly studied biomarkers such as procalcitonin, Soluble urokinase-type plasminogen activator (Supar), presepsin, soluble triggering receptor expressed on myeloid cells 1, interleukin 6, C-reactive protein, ., have been described for their possible applications as biomarkers in septic patients. The sepsis biomarkers are still an area of active research with newer evidence adding to the knowledge base continuously. For patients presenting with sepsis, early diagnosis and prompt resuscitation and early administration of anti-microbials (preferably within 1 h) and source control are desired goals. Biomarkers may help us in the diagnosis, prognosis and therapeutic monitoring of septic patients. The marker redefining our view on sepsis is yet a mirage that clinicians and researchers continue to chase.
PubMed: 37745257
DOI: 10.5492/wjccm.v12.i4.188 -
Pharmaceuticals (Basel, Switzerland) Jan 2024Fibrinolysis is the process of the fibrin-platelet clot dissolution initiated after bleeding has been stopped. It is regulated by a cascade of proteolytic enzymes with...
Fibrinolysis is the process of the fibrin-platelet clot dissolution initiated after bleeding has been stopped. It is regulated by a cascade of proteolytic enzymes with plasmin at its core. In pathological cases, the balance of normal clot formation and dissolution is replaced by a too rapid lysis, leading to bleeding, or an insufficient one, leading to an increased thrombotic risk. The only approved therapy for emergency thrombus lysis in ischemic stroke is recombinant tissue plasminogen activator, though streptokinase or urokinase-type plasminogen activators could be used for other conditions. Low molecular weight compounds are of great interest for long-term correction of fibrinolysis dysfunctions. Their areas of application might go beyond the hematology field because the regulation of fibrinolysis could be important in many conditions, such as fibrosis. They enhance or weaken fibrinolysis without significant effects on other components of hemostasis. Here we will describe and discuss the main classes of these substances and their mechanisms of action. We will also explore avenues of research for the development of new drugs, with a focus on the use of computational models in this field.
PubMed: 38256925
DOI: 10.3390/ph17010092 -
The Journal of Innovations in Cardiac... Nov 2023Obesity is a major risk factor for heart failure (HF). The relationship between adipokines and HF has been implicated in many previous studies and reviews. However, this... (Review)
Review
Obesity is a major risk factor for heart failure (HF). The relationship between adipokines and HF has been implicated in many previous studies and reviews. However, this review article summarizes the basic role of major adipokines, such as apelin, adiponectin, chemerin, resistin, retinol-binding protein 4 (RBP4), vaspin, visfatin, plasminogen activator inhibitor-1, monocyte chemotactic protein-1, nesfatin-1, progranulin, leptin, omentin-1, lipocalin-2, and follistatin-like 1 (FSTL1), in the pathogenesis of HF. Apelin is reduced in patients with HF and upregulated following favorable left ventricular (LV) remodeling. Higher levels of adiponectin have been found in patients with HF compared to in control patients. Also, high plasma chemerin levels are linked to a higher risk of HF. Serum resistin is related to the severity of HF and associated with a high risk for adverse cardiac events. Evidence indicates that RBP4 can contribute to inflammation and damage heart muscle cells, potentially leading to HF. Vaspin might stop the progression of cardiac degeneration, fibrosis, and HF according to experiments on rats with experimental isoproterenol-induced chronic HF. The serum concentrations of visfatin are significantly lower in patients with systolic HF. Leptin levels were found to be correlated with low LV mass and myocardial stiffness, both of which are significant risk factors for the development of HF with preserved ejection fraction (HFpEF). Measuring serum omentin-1 levels appears to be a novel prognostic indicator for risk stratification in HF patients. Increased expression of neutrophil gelatinase-associated lipocalin in both systemic circulation and myocardium in clinical and experimental HF suggests that innate immune responses may contribute to the development of HF. FSTL1 was elevated in patients with HF with reduced ejection fraction and associated with an increase in the size of the left ventricle of the heart. However, other adipokines, such as plasminogen activator inhibitor-1, monocyte chemotactic protein-1, nesfatin-1, and progranulin, have not yet been studied for HF.
PubMed: 38058391
DOI: 10.19102/icrm.2023.14111 -
Revista Da Associacao Medica Brasileira... 2023The aim of this study was to analyze the second-trimester levels of vitronectin and plasminogen activator inhibitor-1 in gestational diabetes mellitus.
OBJECTIVE
The aim of this study was to analyze the second-trimester levels of vitronectin and plasminogen activator inhibitor-1 in gestational diabetes mellitus.
METHODS
This study was conducted between September 2020 and December 2020 at the University of Health Sciences, Bursa Yuksek Ihtisas Research and Training Hospital, Department of Obstetrics and Gynecology. A total of 30 pregnant women with gestational diabetes mellitus and 60 healthy controls between 24 and 27/6 weeks of gestation were included. The inclusion criteria were as follows: being between 18 and 45 years old and 24-27/6 gestational weeks, having singleton pregnancy, diagnosed with gestational diabetes mellitus by using a two-step challenge test. The exclusion criteria of this study were as follows: chronic inflammatory or infectious disease, fasting blood glucose>126 mg/dL, intolerance to glucose tolerance testing, abnormal liver or kidney function tests, as well as pregnancy with pre-gestational diabetes history of adverse perinatal outcomes. Serum vitronectin and plasminogen activator inhibitor-1 levels were measured using the enzyme-linked immunosorbent assay method.
RESULTS
Vitronectin and plasminogen activator inhibitor-1 levels were higher in the gestational diabetes mellitus group compared with controls [91.85 (23.08) vs. 80.10 (39.18) ng/mL, for vitronectin and 6.50 (1.05) vs. 4.35(1.0) ng/mL, for plasminogen activator inhibitor-1 (for both p<0.001)]. vitronectin >84.7 ng/mL was found to predict gestational diabetes mellitus with a sensitivity of 70% and specificity of 63.3%. Moreover, vitronectin had a significant positive correlation with fasting blood glucose (r=0.476, p<0.001), postprandial blood glucose (r=0.489, p<0.001), HbA1c (r=0.713, p<0.001), and plasminogen activator inhibitor-1 (r=0.586, p<0.001).
CONCLUSION
This study revealed that second-trimester vitronectin and plasminogen activator inhibitor-1 are increased in gestational diabetes mellitus and vitronectin could be a candidate for the prediction of gestational diabetes mellitus.
Topics: Pregnancy; Humans; Female; Adolescent; Young Adult; Adult; Middle Aged; Diabetes, Gestational; Vitronectin; Blood Glucose; Enzyme-Linked Immunosorbent Assay; Exercise Test
PubMed: 37729377
DOI: 10.1590/1806-9282.20230563