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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 -
EXCLI Journal 2021One of the key difficulties in glioma treatment is our limited ability to consistently assess cancer response or progression either by neuroimaging or specific blood...
One of the key difficulties in glioma treatment is our limited ability to consistently assess cancer response or progression either by neuroimaging or specific blood biomarkers. An ideal biomarker could be measured through non-invasive methods such as blood-based biomarkers, aiding both early diagnosis and monitoring disease evolution. This is a single-center, case-control, 10-year retrospective, longitudinal study. We evaluated routine coagulation factors in 138 glioma patients (45 Females/93 Males; median [range] age, 56.4 [27-82] years; 64 non-recurrent/74 recurrent) and, for comparison, in 56 relapsing-remitting MS patients (41 Females/15 Males; 40.8 [25-62] years, 35 stable/21 active) and 23 controls (16 Females/7 Males; 41.7 [24-62] years) as well as Neutrophil-to-lymphocyte ratio (NLR) in subgroups of 127 glioma patients, 33 MS patients and 23 healthy controls. Secondly, we assessed whether these indicators could be predictive of overall (OS) and progression-free survival (PFS) in glioma patients. NLR, d-dimer, Antithrombin III and Factor VIII were significantly higher in glioma patients compared to both MS patients and controls (p<0.0001 for all). ROC curves confirmed that either NLR, Antithrombin III or Factor VIII were moderately accurate biomarkers (0.7
Antithrombin III, Factor VIII, or d-dimer in glioma patients compared to MS patients and controls, where the first three represented moderately accurate biomarkers for this cancer. Among these markers, only NLR was found to be predictive for OS along with severe disability and steroid therapy. PubMed: 34345234
DOI: 10.17179/excli2021-3831 -
Indian Journal of Hematology & Blood... Sep 2014This report describes a 4 year old female child who presented with fever, pain and swelling of left leg following a trivial trauma. She was diagnosed as a case of deep...
This report describes a 4 year old female child who presented with fever, pain and swelling of left leg following a trivial trauma. She was diagnosed as a case of deep vein thrombosis and subsequently found to be due to protein C deficiency.
PubMed: 25332562
DOI: 10.1007/s12288-013-0298-4 -
Hamostaseologie Oct 2022Antithrombin (AT) deficiency is a high-risk thrombophilia and a rare condition. The risk of venous thromboembolism (VTE) is increased in AT-deficient women during...
Antithrombin (AT) deficiency is a high-risk thrombophilia and a rare condition. The risk of venous thromboembolism (VTE) is increased in AT-deficient women during pregnancy and the postpartum period and is especially high in women with a prior history of VTE. A thorough assessment of VTE risk is recommended in pregnant AT-deficient women, comprising the degree and type of AT deficiency, genetic mutations, personal and family history, and additional preexisting or pregnancy-specific risk factors. Due to a lack of adequate study data, there is limited guidance on the management of AT deficiency in pregnancy, including the need for prophylactic anticoagulation, the appropriate dose of low-molecular-weight heparin (LMWH), and the role of AT substitution. LMWH is the medication of choice for the pharmacological prophylaxis and treatment of VTE in pregnancy. Patients with a history of VTE should receive full-dose LMWH during pregnancy and the postpartum period. AT concentrates are a treatment option when anticoagulation is withheld in potentially high-risk events such as childbirth, bleeding, or surgery and in cases of acute VTE despite the use of therapeutic dose anticoagulation. Women with AT deficiency should be counseled at specialized centers for coagulation disorders or vascular medicine, and close cooperation between obstetricians and anesthesiologists is warranted before delivery and during the peripartum period.
Topics: Pregnancy; Humans; Female; Heparin, Low-Molecular-Weight; Venous Thromboembolism; Antithrombin III Deficiency; Anticoagulants; Antithrombins; Risk Factors
PubMed: 36323279
DOI: 10.1055/a-1841-0399 -
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 -
Lakartidningen May 2016The inner side of the endothelium is covered by a thin layer of glycosylated proteins called the glycocalyx, which binds plasma to its surface up to a total thickness of... (Review)
Review
The inner side of the endothelium is covered by a thin layer of glycosylated proteins called the glycocalyx, which binds plasma to its surface up to a total thickness of 1-3 µm. The glycocalyx governs the endothelial permeability for macromolecules and has a key role in the regulation of microvascular perfusion. The glycocalyx also prevents adhesion of thrombocytes to the endothelial surface and counteracts microthrombosis by harbouring antithrombin III and thrombomodulin in its plasma layer. Knowledge about the ultrastructure of the glycocalyx has resulted in a revision of the Starling equation, which currently takes little notice of the oncotic pressure of the interstitial fluid space. The glycocalyx is involved in the initiation of the inflammatory response and is easily broken down (shedded) in response to sepsis, trauma, surgery, and cardiovascular disease. A shedded glycocalyx layer seems to impair the prognosis of heart failure and kidney disease. Its role as a mediator of cardiovascular complications to chronic disease is currently an important research topic.
Topics: Albuminuria; Capillary Permeability; Cardiovascular Diseases; Endothelial Cells; Endothelium, Vascular; Glycocalyx; Humans; Microcirculation
PubMed: 27187696
DOI: No ID Found -
Journal of Thrombosis and Haemostasis :... Jun 2023Venous thromboembolism (VTE) is associated with excessive coagulation activity, which in part can be attributed to activation of contact system. However, the knowledge...
BACKGROUND
Venous thromboembolism (VTE) is associated with excessive coagulation activity, which in part can be attributed to activation of contact system. However, the knowledge regarding the impact of contact activation in acute VTE is limited.
OBJECTIVE
To unravel the involvement of contact activation in acute VTE.
METHODS
Contact activation was investigated in patients with acute VTE (n = 321) and population controls without a history of VTE (n = 300). For comparison, Factor XI(a) levels, activity, and plasma kallikrein (PKa) activity were determined in plasma samples with an activated partial thromboplastin time- or thrombin generation-based assay (free FXI concentration [FXI:c] and calibrated automated thrombogram:FXIa, respectively) and with enzyme-linked immunosorbent assays for enzyme-inhibitor complexes (FXIa:alpha-1-antitrypsin [α1AT], FXIa:antithrombin [AT], FXIa:C1-inhibitor [C1Inh], and PKa:C1-inh).
RESULTS
In patients with VTE, higher FXI:c levels (124 ± 37% vs 114 ± 28%), but lower calibrated automated thrombogram:FXIa levels were apparent. This was accompanied by increased FXIa:α1AT, FXIa:AT, and PKa:C1-inh levels in patients compared with controls (312pM [238-424] vs 203pM [144-288]; 29pM [23-38] vs 23pM [20-30]; 1.9nM [1.2-4.7] vs 1.4nM [0.7-3.5], respectively), whereas FXIa:C1-inh levels did not differ. Logistic regression models showed good discriminatory values for FXI:c and FXIa:α1AT (area under the curve = 0.64 [0.6/0.69] and 0.73 [0.69/0.77], respectively). After a 2-year follow-up, 81 recurrent VTE events or deaths occurred in the patient cohort, for which the baseline levels of FXIa:α1AT and FXIa:C1Inh had a significant prognostic value (Hazard ratios per SD [95% CI], 1.26 [1.10-1.45]; p =.0012 and 1.19 [1.05-1.36]; p =.0082, respectively).
CONCLUSION
Our study revealed elevated FXIa levels and activity in acute VTE, which was also associated with recurrent VTE, suggesting an important risk contribution of FXI activation to VTE. The evidence provided by this study supports the utility of FXIa inhibition in the setting of acute VTE.
Topics: Humans; Factor XIa; Venous Thromboembolism; Factor XI; Venous Thrombosis; Blood Coagulation; Plasma Kallikrein; Anticoagulants; Antithrombin III
PubMed: 37003466
DOI: 10.1016/j.jtha.2023.02.031 -
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 -
Open Access Macedonian Journal of... Mar 2019Sepsis is a significant cause of morbidity and mortality in children. The diagnosis of sepsis remains continuing to develop which determines treatment and prognostic....
BACKGROUND
Sepsis is a significant cause of morbidity and mortality in children. The diagnosis of sepsis remains continuing to develop which determines treatment and prognostic. Antithrombin III is one of the coagulation markers to evaluate the prognosis of sepsis.
AIM
To determine the association between the level of antithrombin III and mortality in children with sepsis in the Pediatric Intensive Care Unit, Haji Adam Malik General Hospital, Medan.
METHODS
A cross-sectional study was conducted in Haji Adam Malik General Hospital, Medan from April until June 2015. There were 41 children with sepsis. Sepsis was diagnosed from clinical and laboratory findings. Complete blood count, antithrombin III level, C-reactive protein and procalcitonin were an indicator of unproven sepsis that performed in the laboratory. Meanwhile blood culture was performed in the microbiology laboratory. The association between the level of antithrombin III and mortality was analysed by using chi-square test.
RESULTS
Of the 41 participants, the low antithrombin III level was 13 of 41 children (31.7%) meanwhile the normal antithrombin III level was 28 of 41 children (68.3%). There was 8 of 13 (42.1%) and 11 of 28 (57.9%) children in death cases of low and normal antithrombin III level, respectively. Samples with low antithrombin III level had 2.473 higher risk mortality than normal antithrombin III level (P = 0.184; 95% CI 0.641 to 9.5421; PR = 2.473).
CONCLUSION
There was no statistically significant association between levels of antithrombin III and mortality in children with sepsis.
PubMed: 30976340
DOI: 10.3889/oamjms.2019.211 -
Annals of Palliative Medicine May 2024Antithrombin is a small plasma glycoprotein synthesized in the liver that belongs to the serpin family of serine protease inhibitors and inactivates several enzymes in...
Clinical outcomes of antithrombin III supplementation in an overt disseminated intravascular coagulation: a longitudinal single-institutional experience and retrospective analysis.
BACKGROUND
Antithrombin is a small plasma glycoprotein synthesized in the liver that belongs to the serpin family of serine protease inhibitors and inactivates several enzymes in the coagulation pathway. It plays a leading major factor on coagulation pathway, therefore administration of antithrombin is essential to treat serious clinical conditions such as disseminated intravascular coagulation (DIC). Despite the theoretical benefits of antithrombin supplementation, the optimal antithrombin activity for heparin efficacy and the benefits of antithrombin supplementation in various disease entities are not yet fully understood.
METHODS
The strict administration guidelines on antithrombin III in cases of DIC by the National Health Insurance Service and the Ministry of Food and Drug Safety complied as follows: antithrombin levels below 20 mg/dL in adults; antithrombin activity below 70% of normal in adults; total administration period of antithrombin must be carefully limited to within maximum 3 days, and the total administration dose must be below 7,000 international unit (IU), (loading dose, 1,000 IU in 1 hour: maintenance dose, 500 IU every 6 hours for 3 days).
RESULTS
We identified 76 eligible for analysis according to the above-mentioned criteria in our institution (male/female, 59/17). Forty-four were identified to the non-survivor group and 32 patients were recognized as the survivor group. The baseline parameters in the non-survivor and survivor groups were comparable with no significant differences in age (66.5±18.1 vs. 66.0±16.2 years, P=0.90), sex (32/12 vs. 27/5, P=0.35), hospital length of stay (31.1±34.5 vs. 31.2±26.1 days, P=0.99), sequential organ failure assessment (SOFA) (7.3±2.5 vs. 6.6±2.0, P=0.22), simplified acute physiology score II (SAPS II) (46.0±8.8 vs. 43.5±9.2, P=0.23), cause for DIC (P=0.95), and underlying disease (P=0.38). The levels of antithrombin III on the day just before the administration significantly lower in the non-survivor groups than in the survivor groups (50.1%±13.6% vs. 57.6%±12.5%, P=0.01). The hemoglobin level in the 2nd day and 7th day after antithrombin III administration was significantly different between the non-survivor and survivor groups (9.9±1.9 vs. 11.0±2.0 g/dL, P=0.01, and 9.4±1.8 vs. 10.5±1.6 g/dL, P=0.006). The antithrombin III levels on the day of administration [area under the curve (AUC) =0.672] demonstrated significantly better prediction of mortality than the A antithrombin III levels on 1st day (AUC =0.552), the 2nd day (AUC =0.624), and 7th day (AUC =0.593).
CONCLUSIONS
Our study suggests that the antithrombin administration may be effective tools for DIC treatment, and may be more positively considered, especially in the cases of DIC, which is a frequent complication of septic shock, sepsis, and other critical disease entities and which is associated with a high level of mortality. Furthermore, our study also suggests that the total doses and periods of antithrombin administration, which recommended by national guidelines, may be insufficient, therefore prolongation of period and increase of total dose of antithrombin supplement might be necessary.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Antithrombin III; Disseminated Intravascular Coagulation; Longitudinal Studies; Retrospective Studies; Treatment Outcome
PubMed: 38735696
DOI: 10.21037/apm-23-535