Antithrombin III infusion improves anticoagulation in congenital diaphragmatic hernia patients on extracorporeal membrane oxygenation

Purpose Achieving effective anticoagulation during neonatal extracorporeal membrane oxygenation (ECMO) without increasing the risk of hemorrhage remains challenging. The use of antithrombin III (AT-III) for this purpose has been examined, but studies have been limited to intermittent bolus dosing. We aimed to evaluate the efficacy and safety of an institutionally developed AT-III continuous infusion protocol in neonates receiving ECMO for the treatment of congenital diaphragmatic hernia (CDH). Methods In this single center, retrospective study, all neonates with a CDH who received ECMO support during the study period were included. Data on anticoagulation labs and therapy, life-threatening bleeding, and circuit changes were analyzed. Results Eleven patients were divided into two groups: patients with AT-III continuous infusion ( n = 5) and without ( n = 6). There were no differences in the gestational age ( p = 0.29), sex ( p = 1.00), ECMO duration ( p = 0.59), or initial AT-III levels ( p = 0.76) between groups. Patients in the AT-III infusion group had on average 18.5% higher AT-III levels ( p < 0.0001). Patients receiving continuous AT-III infusions spent a significantly higher percentage of ECMO time within the therapeutic range, measured using anti-Factor Xa levels (64.9±4.2% vs. 29.1±8.57%, p = 0.008), and required fewer changes to the heparin infusion rate (6.48±0.88 vs 2.38±0.36 changes/day changes/day, p = 0.005). Multivariate analysis revealed continuous infusion of AT-III did not increase the rate of intracranial or surgical bleeding ( p = 0.27). Conclusion AT-III as a continuous infusion in CDH neonates on ECMO provides a decreased need to modify heparin infusion and more consistent therapeutic anticoagulation without increasing the risk of life-threatening bleeding.

The rise of factor X level in blood plasma of patients at severe burn injuries

This work is dedicated to the detection of imbalance between the pro- and anti-coagulant branches of hemostasis at severe burn injuries by evaluating the content or activity of individual clotting factors. To select the targets for accurate diagnostics we measured the concentrations of soluble fibrin monomeric complexes and fibrinogen, levels of total prothrombin, factor X, protein C and antithrombin III, and recorded the time of clotting in activated partial thromboplastin time and prothrombin time tests. Factor X level was increased in 26 % of patients on the first day after the burn and it rose further in 62 % patients on the 14 th day of recovery. Increasing factor X level is assumed to be a risk factor of thrombotic complications. We propose to use it as a marker of predisposition to thrombosis at severe burn injury.

Antithrombin III Supplementation in a Premature Infant: Is There a Target Antithrombin Level?

The optimal antithrombin (AT) activity for low-molecular-weight heparin efficacy and the benefits of antithrombin III (ATIII) supplementation in premature infants diagnosed with venous thromboembolism are unknown. Currently, there are no neonatal-specific guidelines directing the appropriate target AT activity during supplementation. This case report describes a critically ill premature infant with a progressive, occlusive inferior vena cava thrombus who received supplemental ATIII during enoxaparin treatment. The patient did not achieve therapeutic anti-Xa levels despite increasing enoxaparin dosing to 3 mg/kg every 12 hours. ATIII supplementation sufficient to attain an AT activity of &gt;40%, in combination with an enoxaparin dosing of &gt;2 mg/kg every 12 hours, was needed to achieve therapeutic anti-Xa levels. Future large studies are needed to determine if there is an optimal target AT activity for critically ill premature infants.

High Mortality and Risk of Severe Sepsis in in-Hospital Cardiac Arrest Patients with Antithrombin Deficiency: Analysis of National Inpatient Sample Database

Background: Previous studies found the association between hereditary thrombophilia (HT) and increased risk of inpatient arterial thromboembolism, such as myocardial infarction and ischemic stroke. Nevertheless, the outcomes of hospitalized HT patients with cardiac arrest remains unclear. We aim to investigate the outcomes of inherited thrombophilia after in-hospital cardiac arrest (IHCA). Methods: This is a retrospective analysis of National Inpatient Sample database with 2016-2018 data years. We included adult (age above 18 years old) who had IHCA. IHCA, various types of HT (Factor V Leiden/activated protein C resistance, prothrombin mutation, deficiencies of antithrombin [AT] III, protein C or S deficiencies, other inherited thrombophilia), and other comorbidities were identified with International Classification of Diseases, 10th Revision, Clinical Modification Procedure Codes and Diagnosis Codes. Charlson Comorbidity Index (CCI) was used to adjust for comorbidities. Age distribution was analyzed with unpaired two-samples t-test. Gender and racial group distribution were compared with Chi-square test. Primary outcome was mortality. All independent factors associated with IHCA in inherited thrombophilia were determined by weighted multivariable logistic regression. SAS and R were used for statistical analysis. Results: Among 67,351 adult patients with IHCA, 620 patients had at least one diagnosis of HT (Factor V Leiden: 86; antithrombin III deficiency: 235; protein C/S deficiencies: 301; prothrombin gene mutation: 6; 5 cases have both factor V Leiden and protein C/S deficiencies; 3 cases have both antithrombin III and protein C/S deficiencies). Patients with HT were significant younger (mean age: 60.6 vs 65.9, p value &lt; 0.0001) with fewer comorbidities (mean CCI: 5.32 vs 5.81, p value &lt;0.0005). There was no significant difference in gender and racial groups distribution. HT was not associated with risk of mortality after IHCA (adjusted odds ratio (aOR): 0.98, Confidence interval (CI): 0.82 - 1.16, p value = 0.75). Nevertheless, subgroup analysis with different types of HT revealed increased mortality in AT III deficiency group (aOR: 1.40, CI: 1.02 - 1.91 p value &lt; 0.05). On the contrary, factor V Leiden and protein C/S deficiencies had a weak association of lower mortality (aOR: 0.70, p value &lt; 0.1; aOR: 0.80, p value = 0.06). AT III deficiency was also associated with higher risk of developing severe sepsis (aOR: 1.56, p &lt; 0.005). Myocardial infarction, ischemic stroke, pulmonary embolism, and deep venous thrombosis were not significantly associated with HT after adjusted for other potential confounders. Conclusion: HT patients who developed IHCA were younger with fewer underlying comorbidities. Only AT III deficiency subgroup was associated with higher odds of mortality and severe sepsis. Factor V Leiden and protein C/S deficiencies had a tendency of favorable outcomes. The unfavorable outcome of AT III deficiency subgroup couldn't be attributed to either arterial or venous thromboembolism. Disclosures No relevant conflicts of interest to declare.

Potential of Antithrombin III as a Biomarker of Antidepressive Effect in Major Depressive Disorder

Background: The evaluation of treatment response to antidepressant therapy commonly depends on neuropsychologic assessments, as there are currently no suitable biomarkers. Previous research has identified a panel of increased proteins in patients with major depressive disorder (MDD), including antithrombin III (ATIII), as potential biomarkers of depression.Methods: A total of 90 MDD patients were recruited. Of these, 74 patients received occipital repetitive transcranial magnetic stimulation (rTMS) as individualized, standard, or sham treatment for 5 days, and underwent the complete procedure, including clinical assessments, blood collection, and protein measurement.Results: After treatment, ATIII was significantly decreased in both the individualized and standard groups (both p &lt; 0.001) relative to the sham group. In the individualized group, reduction in ATIII was associated with improvements in several neuropsychological assessments. Furthermore, ATIII at baseline in the standard group and after individualized rTMS showed good performance for evaluating or predicting the response to five-day treatment (AUC = 0.771, 95% CI, 0.571–0.971; AUC = 0.875, 95% CI, 0.714–1.000, respectively) and remission at follow-up (AUC = 0.736, 95% CI, 0.529–0.943; AUC = 0.828, 95% CI, 0.656–1.000, respectively). Lastly, both baseline ATIII and change in ATIII showed good predictive value for the 24-item Hamilton Depression Rating Scale at follow-up (p = 0.024 and 0.023, respectively).Conclusion: Our study revealed a reduction in ATIII after occipital rTMS in MDD patients and a relationship between change in ATIII and therapeutic response. Taken together, these findings provide evidence for the potential of ATIII as a biomarker for the evaluation and prediction of antidepressive effects.