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Thrombosis Research Mar 2024Markers of hemostasis such as procoagulant factors and peak thrombin generation are associated with cardiovascular outcomes, but their associations with dementia risk...
INTRODUCTION
Markers of hemostasis such as procoagulant factors and peak thrombin generation are associated with cardiovascular outcomes, but their associations with dementia risk are unclear. We aimed to evaluate prospective associations of selected procoagulant factors and peak thrombin generation with dementia risk.
METHODS
We measured levels of 7 hemostatic factors (fibrinogen, factor VII coagulant activity [FVIIc], activated factor VII [FVIIa], factor VIIa-antithrombin [FVIIa-AT], factor XI antigen [FXI], peak thrombin generation, and platelet count) among participants in the Cardiovascular Health Study, a cohort of older adults free of dementia in 1992/1993 (n = 3185). Dementia was adjudicated and classified by DSM-IV criteria through 1998/1999. Cox proportional hazards models estimated hazard ratios (HRs) for any dementia associated with 1-standard deviation (SD) differences, adjusting for sociodemographic and clinical factors and APOE genotype. Secondary analyses separately evaluated the risk of vascular dementia, Alzheimer's disease, and mixed dementia.
RESULTS
At baseline, participants had a median age of 73 years. Over 5.4 years of follow-up, we identified 448 dementia cases. There was no evidence of linear associations between levels of these hemostatic factors with any dementia risk (HRs per 1-SD difference ranged from 1.0 to 1.1; 95 % confidence intervals included 1.0). Results of secondary analyses by dementia subtype were similar.
CONCLUSIONS
In this prospective study, there was no strong evidence of linear associations between levels of fibrinogen, FVIIc, FVIIa, FVIIa-AT, FXI, peak thrombin generation, or platelet count with dementia risk. Despite their associations with cardiovascular disease, higher levels of these biomarkers measured among older adults may not reflect dementia risk.
Topics: Humans; Aged; Thrombin; Prospective Studies; Factor VIIa; Antithrombins; Anticoagulants; Antithrombin III; Fibrinogen; Hemostatics; Dementia
PubMed: 38340522
DOI: 10.1016/j.thromres.2024.01.024 -
International Journal of Molecular... Feb 2024Serine proteases are members of a large family of hydrolytic enzymes in which a particular serine residue in the active site performs an essential role as a nucleophile,... (Review)
Review
Serine proteases are members of a large family of hydrolytic enzymes in which a particular serine residue in the active site performs an essential role as a nucleophile, which is required for their proteolytic cleavage function. The array of functions performed by serine proteases is vast and includes, among others, the following: the ability to fight infections; the activation of blood coagulation or blood clot lysis systems; the activation of digestive enzymes; and reproduction. Serine protease activity is highly regulated by multiple families of protease inhibitors, known collectively as the SERine Protease INhibitor (SERPIN). The serpins use a conformational change mechanism to inhibit proteases in an irreversible way. The unusual conformational change required for serpin function provides an elegant opportunity for allosteric regulation by the binding of cofactors, of which the most well-studied is heparin. The goal of this review is to discuss some of the clinically relevant serine protease-serpin interactions that may be enhanced by heparin or other negatively charged polysaccharides. The paired serine protease-serpin in the framework of heparin that we review includes the following: thrombin-antithrombin III, plasmin-anti-plasmin, C1 esterase/kallikrein-C1 esterase inhibitor, and furin/TMPRSS2 (serine protease Transmembrane Protease 2)-alpha-1-antitrypsin, with the latter in the context of COVID-19 and prostate cancer.
Topics: Serpins; Heparin; Serine Proteases; Serine Proteinase Inhibitors; Anticoagulants; Thrombin
PubMed: 38339082
DOI: 10.3390/ijms25031804 -
Nutrients Jan 2024Blood coagulation is a complex physiological process critical for maintaining hemostasis, and disruptions in this system can lead to various health complications. Since...
Blood coagulation is a complex physiological process critical for maintaining hemostasis, and disruptions in this system can lead to various health complications. Since the effects of specific food groups on a series of circulating coagulation parameters in the population are not well established, this study examines such associations in the population-based KORA-Fit study. A total of 595 subjects (263 men and 332 women) born between 1945 and 1964 and living in the study region of Augsburg were included in the study. Habitual food intake was estimated based on a combination of repeated 24-h food lists (24HFLs) and a food frequency questionnaire (FFQ). Antithrombin III, D-dimers, factor VIII, fibrinogen, protein C, protein S, aPTT, Quick value and INR were measured in citrate plasma. Multivariable linear regression models were applied to investigate associations between the consumption of specific foods of plant or animal origin and hemostatic factors. We found that the consumption of plant-based food groups, including green leafy vegetables (rich in vitamin K1), were hardly associated with coagulation parameters. Surprisingly, a high consumption of dairy products and especially butter were associated with higher D-dimer concentrations. These findings need further evaluation in prospective studies.
Topics: Male; Animals; Humans; Female; Prospective Studies; Eating; Vegetables; Dairy Products; Hemostatics; Diet
PubMed: 38337715
DOI: 10.3390/nu16030432 -
Cureus Jan 2024Antithrombin (AT) deficiency and antiphospholipid syndrome (APS) are distinct but potentially overlapping disorders with significant implications for thrombosis. We...
Antithrombin (AT) deficiency and antiphospholipid syndrome (APS) are distinct but potentially overlapping disorders with significant implications for thrombosis. We present a case of a 28-year-old male with hereditary AT deficiency who subsequently developed primary APS. Despite the challenges of overlapping symptoms and anticoagulation therapy, a careful diagnostic approach revealed the coexistence of these rare conditions. The patient was successfully managed with long-term anticoagulation, hydroxychloroquine, and other supportive measures. This case underscores the importance of comprehensive laboratory testing, especially when managing patients with pre-existing anticoagulation needs.
PubMed: 38314001
DOI: 10.7759/cureus.51555 -
Research and Practice in Thrombosis and... Jan 2024Several studies have examined parameters of increased thrombogenicity in COVID-19, but studies examining their association with long-term outcome and potential effects...
BACKGROUND
Several studies have examined parameters of increased thrombogenicity in COVID-19, but studies examining their association with long-term outcome and potential effects of antiviral agents in hospitalized patients with COVID-19 are scarce.
OBJECTIVES
To evaluate plasma levels of hemostatic proteins during hospitalization in relation to disease severity, treatment modalities, and persistent pulmonary pathology after 3 months.
METHODS
In 165 patients with COVID-19 recruited into the NOR-Solidarity trial (NCT04321616) and randomized to treatment with hydroxychloroquine, remdesivir, or standard of care, we analyzed plasma levels of hemostatic proteins during the first 10 days of hospitalization ( = 160) and at 3 months of follow-up ( = 100) by enzyme immunoassay.
RESULTS
Our main findings were as follows: (i) tissue plasminogen activator (tPA) and tissue factor pathway inhibitor (TFPI) were increased in patients with severe disease (ie, the combined endpoint of respiratory failure [Po-to-FiO ratio, <26.6 kPa] or need for treatment at an intensive care unit) during hospitalization. Compared to patients without severe disease, tPA levels were a median of 42% ( < .001), 29% ( = .002), and 36% ( = .015) higher at baseline, 3 to 5 days, and 7 to 10 days, respectively. For TFPI, median levels were 37% ( = .003), 25% ( < .001), and 10% ( = .13) higher in patients with severe disease at these time points, respectively. No changes in thrombin-antithrombin complex; alpha 2-antiplasmin; a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; or antithrombin were observed in relation to severe disease. (ii) Patients treated with remdesivir had lower levels of TFPI than those in patients treated with standard of care alone. (iii) TFPI levels during hospitalization, but not at 3 months of follow-up, were higher in those with persistent pathology on chest computed tomography imaging 3 months after hospital admission than in those without such pathology. No consistent changes in thrombin-antithrombin complex, alpha 2-antiplasmin, ADAMTS-13, tPA, or antithrombin were observed in relation to pulmonary pathology at 3 months of follow-up.
CONCLUSION
TFPI and tPA are associated with severe disease in hospitalized patients with COVID-19. For TFPI, high levels measured during the first 10 days of hospitalization were also associated with persistent pulmonary pathology even 3 months after hospital admittance.
PubMed: 38292350
DOI: 10.1016/j.rpth.2023.102289 -
Journal of Thrombosis and Thrombolysis Mar 2024Patients with ovarian cancer have a high risk of developing thrombosis. We aimed to investigate pre and post operative biomarkers associated with thrombosis including...
Patients with ovarian cancer have a high risk of developing thrombosis. We aimed to investigate pre and post operative biomarkers associated with thrombosis including deep vein thrombosis and pulmonary thromboembolism in patients treated for ovarian cancer. We collected pre and post operative blood samples from 133 patients undergoing surgery for ovarian cancer between December 2021 and August 2022. The measured parameters were white blood cell count, hemoglobin, platelets, monocytes, serum glucose, CA125, D-dimer, fibrinogen, prothrombin time, activated partial thromboplastin time, fibrinogen degradation products, antithrombin III, protein C, protein S, plasminogen, plasminogen activator inhibitor 1, homocysteine, N-terminal pro-brain natriuretic peptide, interleukin 6, thrombopoietin, soluble P-selectin and granulocyte stimulating factor. Body mass index of patients were collected. Differences between patients who developed thrombosis and those without were compared with Wilcoxon rank-sum test and we analyzed the continuous variables using logistic regression. Twenty-one (15.8%) patients developed thrombosis ranging from 6 to 146 days (median 15 days) after surgery. Pre operative values of homocysteine (p = 0.033) and IL-6 (p = 0.043) were significantly increased and post operative aPTT (p = 0.022) was prolonged and plasminogen (p = 0.041) was decreased in patients with thrombosis. It is important to find novel biomarkers for thrombosis to carefully manage patients who are prone to develop thrombosis despite preventive measures were applied.
Topics: Humans; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Thrombosis; Ovarian Neoplasms; Plasminogen; Biomarkers; Homocysteine
PubMed: 38281230
DOI: 10.1007/s11239-023-02944-1 -
Cureus Dec 2023Andexanet alfa (AnAl) is utilized for the urgent reversal of direct oral anticoagulants (DOACs) in cases of severe bleeding. While the guidelines from the Society of...
Andexanet alfa (AnAl) is utilized for the urgent reversal of direct oral anticoagulants (DOACs) in cases of severe bleeding. While the guidelines from the Society of Thoracic Surgeons recommend AnAl for urgent cardiac surgery in patients treated with DOACs, concerns persist regarding the potential of AnAl to induce heparin resistance. This report details the case of an 85-year-old woman diagnosed with acute type A aortic dissection, who received AnAl due to prior edoxaban use. During the emergent aortic surgery, she exhibited heparin resistance following the administration of unfractionated heparin (UFH). The administration of antithrombin III (ATIII) significantly influenced activated clotting times, facilitating successful surgery while maintaining adequate anticoagulation. This case underscores the importance of cautious management of AnAl-induced heparin resistance during critical surgeries, emphasizing the role of ATIII supplementation for effective anticoagulation.
PubMed: 38249168
DOI: 10.7759/cureus.50856 -
Journal of Cancer Research and Clinical... Jan 2024Hepatic sinusoidal obstruction syndrome (SOS) is a serious complication following hematopoietic stem cell transplantation (HSCT) in which early diagnosis improves...
Analysis of laboratory parameters before the occurrence of hepatic sinusoidal obstruction syndrome in children, adolescents, and young adults after hematopoietic stem cell transplantation.
PURPOSE
Hepatic sinusoidal obstruction syndrome (SOS) is a serious complication following hematopoietic stem cell transplantation (HSCT) in which early diagnosis improves patient outcome. The aim of our study was to detect laboratory parameters following HSCT that can predict the occurrence of SOS.
METHODS
This retrospective study included 182 children, adolescents, and young adults who underwent allogeneic or autologous HSCT for the first time (median age 7.2 years). The diagnosis of SOS was based on the pediatric criteria of European Society for Blood and Marrow Transplantation (EBMT). We investigated 15 laboratory parameters after HSCT before the onset of SOS.
RESULTS
The overall incidence of SOS was 14.8%. SOS developed in 24 of 126 allogeneic (19.1%) and in 3 of 56 autologous (5.4%) HSCT patients at a median time of 13 days after HSCT. We observed a low SOS mortality rate of 11.1% within 100 days after HSCT. International normalized ratio (INR) ≥ 1.3, activated partial thromboplastin time (aPTT) ≥ 40 s, reptilase time ≥ 18.3 s, factor VIII ≤ 80%, antithrombin III ≤ 75%, protein C ≤ 48%, D-dimer ≥ 315 µg/L, bilirubin ≥ 9 µmol/L, and ferritin ≥ 3100 µg/L showed significant associations with the onset of SOS in the univariate analyses. In the multivariate analysis, INR ≥ 1.3 [odds ratio (OR) = 8.104, p = 0.006], aPTT ≥ 40 s (OR = 10.174, p = 0.001), protein C ≤ 48% (OR = 5.215, p = 0.014), and ferritin ≥ 3100 µg/L (OR = 7.472, p = 0.004) could be confirmed as independent risk factors after HSCT before SOS. If three of the four significant cut-off values were present, the probability of developing SOS was more than 70%. The probability of SOS was 96%, if all four laboratory parameters were changed according to the cut-off values. The values of factor XIII, von Willebrand factor (vWF), von Willebrand factor activity (vWF activity), protein S, fibrinogen, and alanine aminotransferase (ALT) were not relevant for the occurrence of SOS.
CONCLUSION
In summary, the laboratory parameters INR, aPTT, protein C, and ferritin were very useful to predict the occurrence of SOS. In addition, this is the first report on a significant association between SOS and high values of INR and aPTT after HSCT before SOS.
Topics: Humans; Adolescent; Young Adult; Child; Hepatic Veno-Occlusive Disease; Protein C; von Willebrand Factor; Retrospective Studies; Ferritins; Hematopoietic Stem Cell Transplantation
PubMed: 38206490
DOI: 10.1007/s00432-023-05561-w -
Endocrine Jun 2024The study aimed to investigate the potential effect of Antithrombin III (ATIII) between chronic renal insufficiency and chronic coronary artery disease (chronic CAD) in...
PURPOSE
The study aimed to investigate the potential effect of Antithrombin III (ATIII) between chronic renal insufficiency and chronic coronary artery disease (chronic CAD) in type 2 diabetes mellitus (T2DM) patients.
METHODS
T2DM patients hospitalized in ZhongDa Hospital from 2013 to 2018 were enrolled. Relationships between renal function, ATIII, and chronic CAD risk were explored using multivariate regression models. Multiplicative and additive interactions were investigated between ATIII and renal function for CAD risk, and the role of ATIII was determined by bootstrap mediation analysis in patients with chronic renal dysfunction.
RESULTS
A total of 4197 patients were included in the study, with a chronic CAD prevalence of 23.02%. Low ATIII level was statistically associated with chronic renal insufficiency and elevated CAD risk even after adjustments (P < 0.05). A positive correlation between renal function and ATIII was demonstrated, and each 1 SD increase in renal function, ATIII increased by 2.947% (2.406-3.488%, P < 0.001) and 0.969% (0.297-1.642%, P < 0.001) in crude and adjusted models respectively. Patients with decreased renal function and ATIII were at the highest chronic CAD risk (OR = 1.51, 95%CI:1.15-1.98, P < 0.05), while no multiplicative and additive interaction effects were significant. Bootstrap mediation analysis estimated that ATIII mediated approximately 4.27% of the effect of chronic renal insufficiency on chronic CAD risk.
CONCLUSION
ATIII may serve as a mediator between chronic renal insufficiency and chronic CAD, providing mechanistic clues for renal-heart association and new insight into clinical therapies.
Topics: Humans; Male; Female; Middle Aged; Antithrombin III; Renal Insufficiency, Chronic; Coronary Artery Disease; Diabetes Mellitus, Type 2; Aged; Risk Factors
PubMed: 38190026
DOI: 10.1007/s12020-023-03669-0 -
Blood Coagulation & Fibrinolysis : An... Mar 2024Antithrombin is an essential protein that acts as a natural anticoagulant in the human body. It is synthesized by the liver and belongs to the serine protease... (Review)
Review
Antithrombin is an essential protein that acts as a natural anticoagulant in the human body. It is synthesized by the liver and belongs to the serine protease inhibitors, which are commonly referred to as the SERPINS superfamily. The antithrombin molecule comprises 432 amino acids and has a molecular weight of approximately 58 200 D. It consists of three domains, including an amino-terminal domain, a carbohydrate-rich domain, and a carboxyl-terminal domain. The amino-terminal domain binds with heparin, whereas the carboxyl-terminal domain binds with serine protease. Antithrombin is a crucial natural anticoagulant that contributes approximately 60-80% of plasma anticoagulant activities in the human body. Moreover, antithrombin has anti-inflammatory effects that can be divided into coagulation-dependent and coagulation-independent effects. Furthermore, it exhibits antitumor activity and possesses a broad range of antiviral properties. Inherited type I antithrombin deficiency is a quantitative disorder that is characterized by low antithrombin activity due to low plasma levels. On the other hand, inherited type II antithrombin deficiency is a qualitative disorder that is characterized by defects in the antithrombin molecule. Acquired antithrombin deficiencies are more common than hereditary deficiencies and are associated with various clinical conditions due to reduced synthesis, increased loss, or enhanced consumption. The purpose of this review was to provide an update on the structure, functions, clinical implications, and methods of detection of antithrombin.
Topics: Humans; Antithrombins; Antithrombin III; Anticoagulants; Heparin; Blood Coagulation; Antithrombin III Deficiency
PubMed: 38179715
DOI: 10.1097/MBC.0000000000001271