Unfavorable Outcomes Associated with Antithrombin Deficiency in Patients Required Mechanical Ventilation: A Nationwide Database Study

Background:

Mechanical ventilation (MV) is associated with increased risk of venous thromboembolism (VTE). Together with other thrombosis risk factors such as hereditary thrombophilia (HT), VTE can lead to unfavorable outcomes. We aim to investigate the outcomes in various types of HT patients required mechanical ventilation (MV), which is relatively unknown.

Methods:

This was a retrospective study using National Inpatient Sample from the year 2016 to 2018. International Classification of Diseases 10 ^th Revision was used to identify various types of HT (antithrombin III deficiency [ATIII deficiency), Factor V Leiden, congenital protein C or S deficiency, prothrombin gene mutation, other congenital hyper-coagulopathy), VTE, MV, and other conditions or procedures. The cohort of interest was MV-associated adults (age at least 18-year-old). Primary outcome was mortality. Comorbidities were evaluated with Charlson Comorbidity Index (CCI). Continuous variables were compared using Welch two sample T-test. Categorical variables were analyzed with Pearson's Chi-squared test. The possible associated variables and confounders were adjusted with the generalized linear model.

Results:

Among 616,717 adult MV hospitalizations, 5,024 cases had at least one HT diagnosis. In HT subgroup, the patients were significantly younger (mean age 59.4 vs 61.7, p value <0.0001). The portion of female and Caucasian were higher in the HT subgroup (46.7% vs 44.5%, p value <0.002; 66.0% vs 63.3%, p value <0.0001). CCI was slightly higher in HT group (5.09 vs 4.94, p value <0.005). HT was independently associated with higher mortality (adjusted odds ratio [aOR]: 1.16; p value<0.000005) even after adjusted for VTE, myocardial infarction, ischemic stroke, and other comorbidities. HT patients had significantly higher risk of developing pulmonary embolism (PE) and deep vein thrombosis (DVT) (aOR: 2.86 and 2.09 respectively; both p value <0.0001). Among various types of HT, subgroup analysis revealed that only ATIII deficiency was associated with significantly higher mortality (aOR: 1.67, p value <0.0001). The odd of mortality in ATIII deficiency was higher in young adults and less prominent among older population (<40-year-old aOR: 2.81, p value <0.0001; >=65-year-old aOR: 1.53, p value <0.0001). ATIII deficiency patients also had higher risk of developing severe sepsis (aOR: 1.52, p value <0.0001).

Conclusion:

Among HT, only ATIII deficiency significantly increased the risk of mortality. The mortality odd was higher especially among young adults with ATIII deficiency. ATIII deficiency group also had higher odd of developing severe sepsis and VTE. Even though the other types of HT also had increased risk of VTE, they were not found to be associated with mortality in MV. It was unclear why only ATIII deficiency was associated with poor prognosis. Additional research needs to be done to fully investigate the underlying mechanism.