High Mortality and Risk of Severe Sepsis in in-Hospital Cardiac Arrest Patients with Antithrombin Deficiency: Analysis of National Inpatient Sample Database
Authors: Hsieh Tien-Chan , Zou Guangchen , Lee Gin Yi , Rajapakse Pramuditha , Yeo Yee Hui 
Published: November 2021

Abstract
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.