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Artificial Organs Dec 2023Bleeding and thrombosis are common extracorporeal membrane oxygenation (ECMO) complications associated with increased mortality. Heparin is the most commonly used ECMO...
BACKGROUND
Bleeding and thrombosis are common extracorporeal membrane oxygenation (ECMO) complications associated with increased mortality. Heparin is the most commonly used ECMO anticoagulant, employed in 94% of cases. Reduced antithrombin III (AT3) levels could decrease heparin effectiveness. Neonates have inherently lower levels of AT3 than adults, and pediatric patients on ECMO can develop AT3 deficiency. One potential approach for patients on ECMO with AT3 deficiency is exogenous AT3 supplementation. However, there is conflicting data concerning the use of AT3 for pediatric and neonatal patients on ECMO.
METHODS
We analyzed the Bleeding and Thrombosis during ECMO database of 514 neonatal and pediatric patients on ECMO. We constructed daily regression models to determine the association between AT3 supplementation and rates of bleeding and thrombosis. Given the physiological differences between pediatric patients and neonates, we constructed separate models for each.
RESULTS
AT3 administration was associated with increased rates of daily bleeding among pediatric (adjusted odds ratio [aOR] 1.59, p < 0.01) and neonatal (aOR 1.37, p = 0.04) patients. AT3 supplementation did not reduce the rate of thrombosis for either pediatric or neonatal patients.
CONCLUSION
AT3 administration was associated with increased rates of daily bleeding, a hypothesized potential complication of AT3 supplementation. In addition, AT3 supplementation did not result in lower rates of thrombosis. We recommend clinicians utilize caution when considering supplementing patients on ECMO with exogenous AT3.
Topics: Infant, Newborn; Adult; Humans; Child; Antithrombin III; Extracorporeal Membrane Oxygenation; Retrospective Studies; Anticoagulants; Heparin; Thrombosis; Hemorrhage; Dietary Supplements
PubMed: 37658611
DOI: 10.1111/aor.14639 -
Antithrombin Activity and Association with Risk of Thrombosis and Mortality in Patients with Cancer.International Journal of Molecular... Dec 2022Venous and arterial thromboembolism (VTE/ATE) are common complications in cancer patients. Antithrombin deficiency is a risk factor for thrombosis in the general... (Observational Study)
Observational Study
Venous and arterial thromboembolism (VTE/ATE) are common complications in cancer patients. Antithrombin deficiency is a risk factor for thrombosis in the general population, but its connection to risk of cancer-associated thrombosis is unclear. We investigated the association of antithrombin activity levels with risk of cancer-associated VTE/ATE and all-cause mortality in an observational cohort study including patients with cancer, the Vienna Cancer and Thrombosis Study. In total, 1127 patients were included (45% female, median age: 62 years). Amongst these subjects, 110 (9.7%) patients were diagnosed with VTE, 32 (2.8%) with ATE, and 563 (49.9%) died. Antithrombin was not associated with a risk of VTE (subdistribution hazard ratio (SHR): 1.00 per 1% increase in antithrombin level; 95% CI: 0.99-1.01) or ATE (SHR: 1.00; 95% CI: 0.98-1.03). However, antithrombin showed a u-shaped association with the risk of all-cause death, i.e., patients with very low but also very high levels had poorer overall survival. In the subgroup of patients with brain tumors, higher antithrombin levels were associated with ATE risk (SHR: 1.02 per 1% increase; 95% CI: 1.00-1.04) and mortality (HR: 1.01 per 1% increase; 95% CI: 1.00-1.02). Both high and low antithrombin activity was associated with the risk of death. However, no association with cancer-associated VTE and ATE across all cancer types was found, with the exception of in brain tumors.
Topics: Humans; Female; Middle Aged; Male; Antithrombins; Venous Thromboembolism; Antithrombin III; Thrombosis; Risk Factors; Brain Neoplasms
PubMed: 36555414
DOI: 10.3390/ijms232415770 -
Intensive Care Medicine Apr 2016Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties. We assessed the benefits and harms of AT III in critically ill patients. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties. We assessed the benefits and harms of AT III in critically ill patients.
METHODS
We searched from inception to 27 August 2015 in CENTRAL, MEDLINE, EMBASE, CAB, BIOSIS and CINAHL. We included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published or language.
RESULTS
We included 30 RCTs with a total of 3933 participants. The majority of included trials were at high risk of bias. Combining all trials, regardless of bias, showed no statistically significant effect of AT III on mortality (RR 0.95, 95% CI 0.88-1.03, I (2) = 0%, fixed-effect model, 29 trials, 3882 participants). Among those with severe sepsis and disseminated intravascular coagulation (DIC), AT III showed no impact on mortality (RR 0.95, 95% Cl 0.88-1.03, I (2) = 0%, fixed-effect model, 12 trials, 2858 participants). We carried out multiple subgroup and sensitivity analyses to assess the benefits and harms of AT III and to examine the impact of risk of bias. AT III significantly increased bleeding events (RR 1.58, 95% CI 1.35-1.84, I (2) = 0%, fixed-effect model, 11 trials, 3019 participants). However, for all other outcome measures and analyses, the results did not reach statistical significance.
CONCLUSIONS
There is insufficient evidence to support AT III substitution in any category of critically ill participants including those with sepsis and DIC. AT III did not show an impact on mortality, but increased the risk of bleeding.
Topics: Antithrombin III; Antithrombins; Critical Illness; Disseminated Intravascular Coagulation; Humans; Randomized Controlled Trials as Topic; Sepsis
PubMed: 26862016
DOI: 10.1007/s00134-016-4225-7 -
Scientific Reports Dec 2023Disseminated intravascular coagulation (DIC) is a frequent complication in patients with sepsis and is associated with increased mortality. Anticoagulant therapy may be...
Risk stratification utilizing sequential organ failure assessment (SOFA) score, antithrombin activity, and demographic data in sepsis-associated disseminated intravascular coagulation (DIC).
Disseminated intravascular coagulation (DIC) is a frequent complication in patients with sepsis and is associated with increased mortality. Anticoagulant therapy may be appropriate for certain patients with DIC, particularly those with increased disease severity and deficiency in the physiologic anticoagulant antithrombin. We retrospectively analyzed post-marketing survey data from 1562 patients with sepsis-associated DIC and antithrombin activity of 70% or less. All the patients were treated with antithrombin concentrates. Baseline sequential organ failure assessment (SOFA) score, DIC score, and antithrombin activity were assessed. Cox multivariate regression analysis, Kaplan-Meier curve analysis, and receiver operating characteristic (ROC) curve analysis were performed to evaluate the performance of variables used to assess mortality. Furthermore, a decision tree was constructed to classify the risk of 28-day mortality. COX multivariate regression analysis demonstrated a significant association of age, sex, baseline SOFA score, baseline antithrombin activity, and the presence of pneumonia or skin/soft tissue infection with increased mortality. The area under the curve of SOFA score or antithrombin activity for mortality was 0.700 and 0.614, respectively. Kaplan-Meier analysis demonstrated that mortality was significantly higher in patients with SOFA score ≥ 12 and antithrombin activity < 47%. The decision tree analysis accurately classified the risk of death into high (> 40%), medium (40%-20%), and low (< 20%) categories in 86.1% of the cohort. Twenty eight-day mortality can be strongly predicted using baseline SOFA score, antithrombin activity, infection site, age, and sex as variables in the clinical decision tree for patients with sepsis-associated disseminated intravascular coagulation (DIC).
Topics: Humans; Antithrombins; Organ Dysfunction Scores; Disseminated Intravascular Coagulation; Retrospective Studies; Anticoagulants; Antithrombin III; Sepsis; Risk Assessment; Demography
PubMed: 38110515
DOI: 10.1038/s41598-023-49855-y -
Critical Care Clinics Apr 2020The pathobiology of the septic process includes a complex interrelationship between inflammation and the coagulations system. Antithrombin (AT) and tissue factor are... (Review)
Review
The pathobiology of the septic process includes a complex interrelationship between inflammation and the coagulations system. Antithrombin (AT) and tissue factor are important components of the coagulation system and have potential roles in the production and amplification of sepsis. Sepsis is associated with a decrease in AT levels, and low levels are also associated with the development of multiple organ failure and death. Treatment strategies incorporating AT replacement therapy in sepsis and septic shock have not resulted in an improvement in survival or reversal of disseminated intravascular coagulation.
Topics: Antithrombin III; Critical Illness; Humans; Multiple Organ Failure; Sepsis; Shock, Septic; Thromboplastin
PubMed: 32172812
DOI: 10.1016/j.ccc.2019.12.002 -
Thrombosis and Haemostasis Nov 2015
Topics: Antithrombin III; Blood Proteins; Fibrinolysis; Genetic Association Studies; Genetic Predisposition to Disease; Hematopoiesis; Humans; Mutation; Pedigree; Polymorphism, Genetic; Protein C; Protein S; Risk Factors; Thrombophilia
PubMed: 26467566
DOI: 10.1160/TH15-10-0774 -
Pharmacological Research Oct 2017Tibolone is a synthetic steroid with estrogenic, androgenic and progestogenic activity, but the evidence regarding its effects on fibrinogen and antithrombin III (ATIII)... (Meta-Analysis)
Meta-Analysis Review
Tibolone is a synthetic steroid with estrogenic, androgenic and progestogenic activity, but the evidence regarding its effects on fibrinogen and antithrombin III (ATIII) has not been conclusive. We assessed the impact of tibolone on fibrinogen and ATIII through a systematic review and meta-analysis of available randomized controlled trials (RCTs). The search included PUBMED, Web of Science, Scopus, and Google Scholar (up to January 31st, 2016) to identify controlled clinical studies investigating the effects of oral tibolone treatment on fibrinogen and ATIII. Overall, the impact of tibolone on plasma fibrinogen concentrations was reported in 10 trials comprising 11 treatment arms. Meta-analysis did not suggest a significant reduction of fibrinogen levels following treatment with tibolone (WMD: -5.38%, 95% CI: -11.92, +1.16, p=0.107). This result was robust in the sensitivity analysis and not influenced after omitting each of the included studies from meta-analysis. When the studies were categorized according to the duration of treatment, there was no effect in the subsets of trials lasting either <12months (WMD: -7.64%, 95% CI: -16.58, +1.29, p=0.094) or ≥12months (WMD: -0.62%, 95% CI: -8.40, +7.17, p=0.876). With regard to ATIII, there was no change following treatment with tibolone (WMD: +0.74%, 95% CI: -1.44, +2.93, p=0.505) and this effect was robust in sensitivity analysis. There was no differential effect of tibolone on plasma ATIII concentrations in trials with either <12months (WMD: +2.26%, 95% CI: -3.14, +7.66, p=0.411) or≥12months (WMD: +0.06%, 95% CI: -1.16, +1.28, p=0.926) duration. Consistent with the results of subgroup analysis, meta-regression did not suggest any significant association between the changes in plasma concentrations of fibrinogen (slope: +0.40; 95% CI: -0.39, +1.19; p=0.317) and ATIII (slope: -0.17; 95% CI: -0.54, +0.20; p=0.374) with duration of treatment. In conclusion, meta-analysis did not suggest a significant reduction of fibrinogen and ATIII levels following treatment with tibolone.
Topics: Antithrombin III; Controlled Clinical Trials as Topic; Estrogen Receptor Modulators; Fibrinogen; Humans; Norpregnenes
PubMed: 28760491
DOI: 10.1016/j.phrs.2017.07.024 -
Lipids in Health and Disease Jun 2023Population-based studies investigating the association between blood coagulation markers and non-alcoholic fatty liver disease (NAFLD) are rare. Thus, we aimed to...
BACKGROUND
Population-based studies investigating the association between blood coagulation markers and non-alcoholic fatty liver disease (NAFLD) are rare. Thus, we aimed to investigate the relationship between the Fatty Liver Index (FLI) as a measure of hepatic steatosis and plasma concentrations of antithrombin III, D-dimer, fibrinogen D, protein C, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value and international thromboplastin time (INR) in the general population.
METHODS
After the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men, aged 54-74 years) of the population-based KORA Fit study with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the associations between FLI and hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the history of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol levels, and diabetes status. In addition, analyses were stratified by diabetes status.
RESULTS
In the multivariable models (with or without health conditions), significantly positive associations with FLI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein C, protein S, and quick value, while INR and antithrombin III were inversely associated. These associations were weaker in pre-diabetic subjects and largely disappeared in diabetic patients.
CONCLUSION
In this population-based study, an increased FLI is clearly related to changes in the blood coagulation system, possibly increasing the risk of thrombotic events. Due to a generally more pro-coagulative profile of hemostatic factors, such an association is not visible in diabetic subjects.
Topics: Male; Humans; Female; Factor VIII; Antithrombin III; Protein S; Protein C; Blood Coagulation; Hemostatics; Anticoagulants; Fibrinogen
PubMed: 37386502
DOI: 10.1186/s12944-023-01854-8 -
Vascular Pharmacology May 2017The implications of altered coagulation-fibrinolytic system in the pathophysiology of several vascular disorders, such as stroke and myocardial infarction, have been... (Review)
Review
The implications of altered coagulation-fibrinolytic system in the pathophysiology of several vascular disorders, such as stroke and myocardial infarction, have been well researched upon and established. However, its role in the progression of diabetic retinopathy has not been explored much. Since a decade, it is known that hyperglycemia is associated with a hypercoagulated state and the various impairments it causes are well acknowledged as independent risk factors for the development of cardiovascular diseases. But recent studies suggest that the hypercoagulative state and diminished fibrinolytic responses might also alter retinal homeostasis and induce several deleterious molecular changes in retinal cells which aggravate the already existing hyperglycemia-induced pathological conditions and thereby lead to the progression of diabetic retinopathy. The major mediators of coagulation-fibrinolytic system whose concentration or activity get altered during hyperglycemia include fibrinogen, antithrombin-III (AT-III), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF). Inhibiting the pathways by which these altered mediators get involved in the pathophysiology of diabetic retinopathy can serve as potential targets for the development of an adjuvant novel alternative therapy for diabetic retinopathy.
Topics: Angiogenesis Inhibitors; Animals; Anticoagulants; Antithrombin III; Blood Coagulation; Blood Glucose; Diabetic Retinopathy; Fibrinogen; Fibrinolysis; Humans; Neovascularization, Pathologic; Plasminogen Activator Inhibitor 1; Retinal Neovascularization; Signal Transduction; von Willebrand Factor
PubMed: 28366840
DOI: 10.1016/j.vph.2017.03.005 -
Renal Failure Dec 2022Coagulation factors participates in the inflammatory cascade, known to play a crucial role in the development of acute kidney injury (AKI). Thus, it's likely that some...
OBJECTIVES
Coagulation factors participates in the inflammatory cascade, known to play a crucial role in the development of acute kidney injury (AKI). Thus, it's likely that some factors may be associated with AKI. Among them, low levels of fibrinogen and antithrombin III (ATIII) activity have been proved to increase mortality in patients with sepsis. Moreover, they are also reported to be associated with higher incidence of AKI. However, the association between coagulation parameters, especially fibrinogen and ATIII, and prognosis of AKI has not been examined.
METHODS
Data were acquired from Multiparameter Intelligent Monitoring in Intensive Care Database IV (MIMIC-IV) version 1.0. Cox proportional hazards regression model was used to estimate the relationship between coagulation parameters and in-hospital mortality in critically ill patients with AKI. Subgroup analysis was also conducted to assess the robustness of the association. Restricted cubic spline (RCS) curve was utilized to examine the nonlinear relationships between fibrinogen or ATIII and in-hospital mortality. Kaplan-Meier method was used to estimate cumulative incidence of mortality by fibrinogen or ATIII levels. Receiver-operating characteristic (ROC) curve was plotted and area under curve was calculated to evaluate predictive ability of fibrinogen or ATIII.
RESULTS
A total of 5914 eligible patients were enrolled in fibrinogen cohort study and 115 patients were eligible for ATIII cohort study. The baseline of low fibrinogen (<150 mg/dL) or ATIII (<80%) activity was associated with significantly higher in-hospital mortality (fibrinogen HR [95% CIs] 2.01 [1.79, 2.27]; ATIII 3.73 [1.11, 12.54]). The HR [95% CIs] of low fibrinogen remained significant 1.29 (1.13, 1.48) in multivariate analysis. The RCS curve showed nearly linear relationship. Subgroup analysis also proved the robustness of the association between fibrinogen and in-hospital mortality. Kaplan-Meier survival curve and ROC demonstrated the predictive capability of fibrinogen and ATIII.
CONCLUSION
Low fibrinogen is an independent predictor of in-hospital mortality in critically ill patients with AKI. Low ATIII activity is also likely to impact the risk of in-hospital death.
Topics: Humans; Critical Illness; Hospital Mortality; Antithrombin III; Fibrinogen; Cohort Studies; Acute Kidney Injury; Prognosis; Anticoagulants; Retrospective Studies
PubMed: 36354059
DOI: 10.1080/0886022X.2022.2142138