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Therapeutische Umschau. Revue... 2016
Review
Topics: Antithrombin III Deficiency; Blood Coagulation Tests; Contraceptives, Oral, Hormonal; Estrogen Replacement Therapy; Female; Genetic Testing; Guideline Adherence; Humans; Male; Pregnancy; Risk Factors; Thrombophilia; Venous Thromboembolism; Young Adult
PubMed: 28045363
DOI: 10.1024/0040-5930/a000843 -
Clinical and Applied... Nov 2014The increased risk of cardiovascular and cerebrovascular events in patients with migraine remains unexplained. Prothrombotic states are thought to contribute to this...
The increased risk of cardiovascular and cerebrovascular events in patients with migraine remains unexplained. Prothrombotic states are thought to contribute to this increased risk. The present study aimed to compare the prevalence of prothrombotic states in patients with migraine and headache-free controls. We conducted a case-control study to screen for prothrombotic states protein C, protein S (PS), antithrombin III, factor V Leiden, lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein 1 antibodies in 101 consecutive patients with migraine and 148 controls. An underlying prothrombotic state was encountered in 11.8% of the patients with migraine, PS deficiency being the most common (4.0%). There was no significant difference in the prevalence of prothrombotic states in patients with migraine compared to controls. Traditional prothrombotic states do not seem to have a higher prevalence in patients with migraine compared to controls.
Topics: Adolescent; Adult; Antibodies, Anticardiolipin; Antithrombin III; Blood Coagulation Disorders; Case-Control Studies; Factor V; Female; Humans; Male; Middle Aged; Migraine Disorders; Protein C; Protein S; beta 2-Glycoprotein I
PubMed: 23637003
DOI: 10.1177/1076029613486538 -
EBioMedicine Mar 2017We previously reported that insufficiency of antithrombin III (ATIII), the major anti-coagulation molecule in vivo, exacerbated renal ischemia-reperfusion injury in...
We previously reported that insufficiency of antithrombin III (ATIII), the major anti-coagulation molecule in vivo, exacerbated renal ischemia-reperfusion injury in animal models and possibly humans. In the present study, we investigated the relationship between ATIII level and contrast induced nephropathy (CIN) in patients and examined therapeutic effect of ATIII on CIN in Sprague-Dawley rats. Patients with low ATIII activity presented a higher incidence of acute kidney injury (AKI) following coronary angiography. ATIII (500μg/kg) was intravenously injected before or after the induction of AKI in rats. Our data demonstrated ATIII significantly attenuated the elevation of serum creatinine, blood urea nitrogen, and renal histological injury. The beneficial effects of ATIII were accompanied by diminished renal inflammatory response, oxidative stress, cell apoptosis and improved renal blood flow in rats. In conclusion, ATIII appears to attenuate CIN through inhibiting inflammation, oxidative stress, apoptosis and improving renal blood flow. ATIII administration may represent a promising strategy for the prevention and treatment of contrast-induced AKI.
Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Animals; Antithrombin III; Contrast Media; Coronary Angiography; Female; Humans; Injections, Intravenous; Iodine; Male; Middle Aged; Rats; Rats, Sprague-Dawley
PubMed: 28219627
DOI: 10.1016/j.ebiom.2017.02.009 -
Yonago Acta Medica May 2021As antithrombin III (AT-III) is produced in the hepatocytes, its serum activity decreases at the time of liver failure, in addition to ischemia reperfusion injury,...
BACKGROUND
As antithrombin III (AT-III) is produced in the hepatocytes, its serum activity decreases at the time of liver failure, in addition to ischemia reperfusion injury, vascular endothelial dysfunction, and disseminated intravascular coagulation (DIC). Here, we examined whether the serum AT-III value after hepatectomy could be a prognostic factor for hepatocellular carcinoma (HCC).
METHODS
Of 141 patients who underwent hepatectomy for HCC, data for 101 patients in whom serum AT-III activity was measured on the first postoperative day were extracted. Patients with serum AT-III activity > 50% and ≤ 50% were assigned to high value (72 cases) and low value (29 cases) groups, respectively. We examined the clinical and prognostic differences between these two groups.
RESULTS
The average age of enrolled patients (83 men and 18 women) was 68.0 years. The 5-year overall survival rate was 88% and 60% in the high and low value groups, respectively ( < 0.01). Furthermore, the 2-year relapse-free survival rate was 71% and 54% in the high and low value groups, respectively ( = 0.03).
CONCLUSION
This is the first study to demonstrate that serum AT-III levels on the first postoperative day may serve as a prognostic factor in HCC patients.
PubMed: 34025191
DOI: 10.33160/yam.2021.05.007 -
The Journal of Extra-corporeal... Jun 2022Pediatric patients undergoing cardiopulmonary bypass (CPB) require adequate anticoagulation to combat hemostatic activation. Heparin is used to bind and catalyze... (Review)
Review
Pediatric patients undergoing cardiopulmonary bypass (CPB) require adequate anticoagulation to combat hemostatic activation. Heparin is used to bind and catalyze antithrombin III (ATIII) that works to inhibit clot formation. To dose heparin, a weight-based (WB) or patient-specific concentration-based (PSCB) method can be used. The WB protocol calculates the dose based on the patients' weight and uses an activated clotting time (ACT) test to ensure anticoagulation. The ACT has limitations during CPB especially for pediatric patients who have immature hemostatic systems. The PSCB method predicts the patients' response to heparin by projecting a heparin dose-response (HDR) curve. Some investigators have found benefit to using the PSCB method but further investigation into how well the HDR predicts the heparin response is needed. A literature review was conducted for studies that looked at heparin management strategies in pediatric CPB patients between 1992 and 2020. Articles that focused on pediatric physiology, heparin management strategies, and anticoagulation were included. Articles older than 1990 were excluded. The literature review highlights that utilizing the PSCB approach more adequately anticoagulated patients. The WB protocol was found to have several flaws due to its reliance on the ACT, especially in infants. The results show that further investigation is needed to understand why there is benefit to using the PSCB approach. Observing the association between the HDR curve and subsequent heparin concentrations could determine how accurately it predicts the patients' response to heparin and why there is benefit to using this method.
Topics: Anticoagulants; Blood Coagulation; Cardiopulmonary Bypass; Child; Hemostatics; Heparin; Humans; Infant; Whole Blood Coagulation Time
PubMed: 35928334
DOI: 10.1182/ject-153-160 -
Anatolian Journal of Cardiology Apr 2017
Topics: Antithrombin III Deficiency; Humans
PubMed: 28466834
DOI: No ID Found -
The Journal of Pediatric Pharmacology... 2022The purpose was to characterize antimicrobial and anticoagulation therapies used in health systems with children receiving extracorporeal membrane oxygenation (ECMO).
OBJECTIVE
The purpose was to characterize antimicrobial and anticoagulation therapies used in health systems with children receiving extracorporeal membrane oxygenation (ECMO).
METHODS
An anonymous electronic survey assessing health system demographics and antimicrobial and anticoagulation therapies during ECMO was distributed to the American College of Clinical Pharmacy Pediatric Practice and Research Network and the Pediatric Pharmacy Association Critical Care Special Interest Group. The primary objective was to identify the number of respondents using antimicrobial prophylaxis for ECMO cannulation and ECMO runs. Secondary objectives included the first- and second-line anticoagulants and anticoagulation laboratory parameters. Additionally, the antimicrobial regimens and the dosing and administration of antithrombin III (AT III) with systemic anticoagulation were collected. Descriptive statistics were employed.
RESULTS
The questionnaire was completed by 38 respondents from 33 health systems; respondents practiced in the pediatric ICU (n = 20; 52.6%), cardiovascular ICU (n = 14; 36.8%), and neonatal ICU (n = 4; 10.5%). Twenty-eight (73.6%) respondents use antimicrobial prophylaxis during ECMO cannulation or ECMO runs, with most units using cefazolin monotherapy. Thirty-five (92.1%) respondents use heparin as the first-line anticoagulant and used a variety of laboratory tests including anti-factor Xa, activated clotting time, and activated partial thromboplastin time. The most common second-line anticoagulant was bivalirudin (n = 24; 63.2%). Thirty-six (94.7%) respondents use AT III with heparin, with most patients receiving AT III dosing calculated based on a formula for the desired AT III concentration.
CONCLUSIONS
The majority of respondents use antimicrobial prophylaxis, but variations in the regimens were noted. Heparin was the most common anticoagulant, but variations in laboratory monitoring and concomitant use of AT III were found.
PubMed: 35002562
DOI: 10.5863/1551-6776-27.1.72 -
British Journal of Haematology Sep 2022Individuals with sickle cell disease (SCD) have persistently elevated thrombin generation that results in a state of systemic hypercoagulability. Antithrombin-III...
Individuals with sickle cell disease (SCD) have persistently elevated thrombin generation that results in a state of systemic hypercoagulability. Antithrombin-III (ATIII), an endogenous serine protease inhibitor, inhibits several enzymes in the coagulation cascade, including thrombin. Here, we utilize a biomimetic microfluidic device to model the morphology and adhesive properties of endothelial cells (ECs) activated by thrombin and examine the efficacy of ATIII in mitigating the adhesion of SCD patient-derived red blood cells (RBCs) and EC retraction. Microfluidic devices were fabricated, seeded with ECs, and incubated under physiological shear stress. Cells were then activated with thrombin with or without an ATIII pretreatment. Blood samples from subjects with normal haemoglobin (HbAA) and subjects with homozygous SCD (HbSS) were used to examine RBC adhesion to ECs. Endothelial cell surface adhesion molecule expression and confluency in response to thrombin and ATIII treatments were also evaluated. We found that ATIII pretreatment of ECs reduced HbSS RBC adhesion to thrombin-activated endothelium. Furthermore, ATIII mitigated cellular contraction and reduced surface expression of von Willebrand factor and vascular cell adhesion molecule-1 (VCAM-1) mediated by thrombin. Our findings suggest that, by attenuating thrombin-mediated EC damage and RBC adhesion to endothelium, ATIII may alleviate the thromboinflammatory manifestations of SCD.
Topics: Anemia, Sickle Cell; Anticoagulants; Antithrombins; Cell Adhesion; Endothelial Cells; Endothelium, Vascular; Erythrocytes; Humans; Thrombin
PubMed: 35822297
DOI: 10.1111/bjh.18328 -
Pediatrics and Neonatology Oct 2017Regular blood transfusion and compliance with iron chelation therapy has markedly improved life expectancy in thalassemia; however, this improvement is accompanied by...
BACKGROUND
Regular blood transfusion and compliance with iron chelation therapy has markedly improved life expectancy in thalassemia; however, this improvement is accompanied by several complications of this chronic disease including thromboembolic disorders. The objective of this work is to study natural coagulation inhibition as well as the fibrinolysis processes in thalassemic children who are otherwise in a steady state with no overt clinical manifestations of thromboembolism.
METHODS
In a case-control study design conducted at Sohag University Hospital, Sohag, Egypt, 50 thalassemic children and 20 age- and sex-matched healthy controls were compared as regards prothrombin concentration, international normalized ratio, partial thromboplastin time, protein C, protein S, antithrombin III, D-dimers, and thrombin activatable fibrinolysis inhibitor (TAFI).
RESULTS
When compared to healthy controls, natural coagulation inhibitors (protein C, protein S, and antithrombin-III) were significantly lower in thalassemic children (p < 0.0001). While D-dimers showed a significant increase in thalassemic children, TAFI was significantly lower (p < 0.0001). Splenectomized thalassemic children showed significantly lower levels of protein C, protein S and TAFI (p < 0.001, p < 0.0001, p < 0.0001, respectively) when compared to nonsplenectomized thalassemic children.
CONCLUSION
Significant changes in natural coagulation inhibition and fibrinolysis processes favoring thromboembolism can be detected in otherwise healthy thalassemic children. Because these changes are more pronounced in splenectomized patients, study of primary prophylactic strategies in this subgroup is warranted.
Topics: Adolescent; Blood Coagulation Disorders; Blood Proteins; Case-Control Studies; Child; Child, Preschool; Female; Fibrin Fibrinogen Degradation Products; Humans; Infant; Male; Protein S; beta-Thalassemia
PubMed: 28351558
DOI: 10.1016/j.pedneo.2016.07.009 -
The Cochrane Database of Systematic... Feb 2016Critical illness is associated with uncontrolled inflammation and vascular damage which can result in multiple organ failure and death. Antithrombin III (AT III) is an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Critical illness is associated with uncontrolled inflammation and vascular damage which can result in multiple organ failure and death. Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties but the efficacy and any harmful effects of AT III supplementation in critically ill patients are unknown. This review was published in 2008 and updated in 2015.
OBJECTIVES
To examine:1. The effect of AT III on mortality in critically ill participants.2. The benefits and harms of AT III.We investigated complications specific and not specific to the trial intervention, bleeding events, the effect on sepsis and disseminated intravascular coagulation (DIC) and the length of stay in the intensive care unit (ICU) and in hospital in general.
SEARCH METHODS
We searched the following databases from inception to 27 August 2015: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid SP), EMBASE (Ovid SP,), CAB, BIOSIS and CINAHL. We contacted the main authors of trials to ask for any missed, unreported or ongoing trials.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published, or language. We contacted the investigators and the trial authors in order to retrieve missing data. In this updated review we include trials only published as abstracts.
DATA COLLECTION AND ANALYSIS
Our primary outcome measure was mortality. Two authors each independently abstracted data and resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as risk ratios (RR) with 95% confidence intervals (CI). We performed subgroup analyses to assess risk of bias, the effect of AT III in different populations (sepsis, trauma, obstetrics, and paediatrics), and the effect of AT III in patients with or without the use of concomitant heparin. We assessed the adequacy of the available number of participants and performed trial sequential analysis (TSA) to establish the implications for further research.
MAIN RESULTS
We included 30 RCTs with a total of 3933 participants (3882 in the primary outcome analyses).Combining all trials, regardless of bias, showed no statistically significant effect of AT III on mortality with a RR of 0.95 (95% CI 0.88 to 1.03), I² statistic = 0%, fixed-effect model, 29 trials, 3882 participants, moderate quality of evidence). For trials with low risk of bias the RR was 0.96 (95% Cl 0.88 to 1.04, I² statistic = 0%, fixed-effect model, 9 trials, 2915 participants) and for high risk of bias RR 0.94 (95% Cl 0.77 to 1.14, I² statistic = 0%, fixed-effect model, 20 trials, 967 participants).For participants with severe sepsis and DIC the RR for mortality was non-significant, 0.95 (95% Cl 0.88 to 1.03, I² statistic = 0%, fixed-effect model, 12 trials, 2858 participants, moderate quality of evidence).We conducted 14 subgroup and sensitivity analyses with respect to the different domains of risk of bias, but detected no statistically significant benefit in any subgroup analyses.Our secondary objective was to assess the benefits and harms of AT III. For complications specific to the trial intervention the RR was 1.26 (95% Cl 0.83 to 1.92, I² statistic = 0%, random-effect model, 3 trials, 2454 participants, very low quality of evidence). For complications not specific to the trial intervention, the RR was 0.71 (95% Cl 0.08 to 6.11, I² statistic = 28%, random-effects model, 2 trials, 65 participants, very low quality of evidence). For complications other than bleeding, the RR was 0.72 ( 95% Cl 0.42 to 1.25, I² statistic = 0%, fixed-effect model, 3 trials, 187 participants, very low quality of evidence). Eleven trials investigated bleeding events and we found a statistically significant increase, RR 1.58 (95% CI 1.35 to 1.84, I² statistic = 0%, fixed-effect model, 11 trials, 3019 participants, moderate quality of evidence) in the AT III group. The amount of red blood cells administered had a mean difference (MD) of 138.49 (95% Cl -391.35 to 668.34, I² statistic = 84%, random-effect model, 4 trials, 137 participants, very low quality of evidence). The effect of AT III in patients with multiple organ failure (MOF) was a MD of -1.24 (95% Cl -2.18 to -0.29, I² statistic = 48%, random-effects model, 3 trials, 156 participants, very low quality of evidence) and for patients with an Acute Physiology and Chronic Health Evaluation score (APACHE) at II and III the MD was -2.18 (95% Cl -4.36 to -0.00, I² statistic = 0%, fixed-effect model, 3 trials, 102 participants, very low quality of evidence). The incidence of respiratory failure had a RR of 0.93 (95% Cl 0.76 to 1.14, I² statistic = 32%, random-effects model, 6 trials, 2591 participants, moderate quality of evidence). AT III had no statistically significant impact on the duration of mechanical ventilation (MD 2.20 days, 95% Cl -1.21 to 5.60, I² statistic = 0%, fixed-effect model, 3 trials, 190 participants, very low quality of evidence); on the length of stay in the ICU (MD 0.24, 95% Cl -1.34 to 1.83, I² statistic = 0%, fixed-effect model, 7 trials, 376 participants, very low quality of evidence) or on the length of stay in hospital in general (MD 1.10, 95% Cl -7.16 to 9.36), I² statistic = 74%, 4 trials, 202 participants, very low quality of evidence).
AUTHORS' CONCLUSIONS
There is insufficient evidence to support AT III substitution in any category of critically ill participants including the subset of patients with sepsis and DIC. We did not find a statistically significant effect of AT III on mortality, but AT III increased the risk of bleeding events. Subgroup analyses performed according to duration of intervention, length of follow-up, different patient groups, and use of adjuvant heparin did not show differences in the estimates of intervention effects. The majority of included trials were at high risk of bias (GRADE; very low quality of evidence for most of the analyses). Hence a large RCT of AT III is needed, without adjuvant heparin among critically ill patients such as those with severe sepsis and DIC, with prespecified inclusion criteria and good bias protection.
Topics: Anti-Inflammatory Agents; Anticoagulants; Antithrombin III; Critical Illness; Humans; Randomized Controlled Trials as Topic
PubMed: 26858174
DOI: 10.1002/14651858.CD005370.pub3