Incidence, Predictors, and Outcome of Venous Thromboembolism/Pulmonary Embolism in Patients Receiving Intravenous Immunoglobulin - an NIS Database Study from 2016-2020
Authors: Sanjeevi Aditya , Jose Domench Daniel Idoate , Vijay Rao Aniket , Shah Purva , Bhandari Samikchhya Keshary , Kharel Himal 
Published: December 2024

Background: Intravenous immunoglobulin (IVIG) is a major therapeutic modality in several autoimmune, hematologic, and inflammatory neurologic disorders. Intravenous immunoglobulins use has been said to be associated with the development of VTE/PE. This study evaluates the incidence, predictors, and outcomes of VTE/PE in patients treated with intravenous immunoglobulin and helps in the optimization of VTE/PE management and outcome in such patients.

Methods: A retrospective analysis using ICD 10 codes for IVIG administration, VTE/PE and comorbidities. We used the National Inpatient Sample (NIS) databases as provided by the HCUP for the years 2016-2020. Because the NIS uses de-identified data, no Institutional Review Board (IRB) approval was required. Since the data are provided with discharge weight (DISCWT), we used that to get the national estimates. We used Pearson Chi-square tests for categorical variables and Student's t-tests/one-way ANOVA for continuous variables to compare both baseline demographics and hospital characteristics between the two groups. Multivariate logistic regression analysis was carried after adjusting for demographic variables and comorbidities to obtain adjusted odds ratio (aOR) for predictors and hospitalization outcomes of VTE/PE in patients receiving IVIG.

Results: In total, 40,670 patients received IVIG therapy. Of these, 2.20% developed VTE/PE, which is equal to 895 patients versus 39,775 patients (97.80%) who did not. The median age of the patients in the VTE/PE group was 57 years (IQR: 41 to 69), which was significantly higher compared to the median age group of 31 years, (IQR: 5 to 60) in the no VTE/PE group (p &lt; 0.001). In this group of patients, predictors of VTE/PE included obesity (aOR 1.74, 95% CI 1.44-2.10; p&lt;0.001), presence of neurological disorder (aOR 1.47, 95% CI 1.17-1.85, p=0.0007); history of alcohol abuse also increased risk although not statistically significant (aOR 1.15 with 95% CI 0.79-1.67 and p=0.449), while the history of chronic lung disease, congestive heart failure, liver disease, hypertension and diabetes mellitus appeared to have a lower risk of VTE/PE being a factor. Race and gender came into play among the risk factors for VTE/PE. African American and Hispanic patients receiving IVIG showed lower risk in comparison with white patients. Of the patients who reported VTE/PE incidence, IVIG was associated with hospital-related factors. Patients treated in larger hospitals were at increased risk of VTE/PE, aOR of 1.59, 95% CI 1.24 to 2.05 ; p&lt;0.001./OR Patients at increased risk were treated in urban teaching hospitals with an aOR of 2.28, a 95% CI 1.09 to 4.77 ; p=0.0009. This result is potentially because sick, complex patients are treated in larger teaching centers. Outcome-wise, patients who developed VTE/PE had significantly worse in-hospital outcomes compared to patients who did not. There was a significant difference in median LOS for VTE/PE patients for 13 days (IQR of 6-31 days) compared to 4 days (IQR of 2-7 days) for non-VTE/PE patients. The hospital stays significantly varied in VTE/PE patients, where the median cost for inpatient care summed to $63,627.48 compared to $19,359.81 for non-VTE/PE patients. The in-hospital mortality rate significantly differed in VTE/PE patients, which was at 6.70% compared to a value of 1.14%, with an aOR of 6.199 (95% CI 4.693-8.187, p&lt;0.001)

Conclusions: In patients receiving IVIG, this study has described some of the most important predictors and effects of VTE/PE. The significant predictors were obesity and a neurological disorder, and the incidence of VTE/PE was affected by hospital size and teaching status. Patients experiencing VTE/PE were much worse off in terms of extended stay, higher costs, and higher mortality. The results suggest VTE/PE patients have 6.2 times higher adjusted odds of in-hospital death than those without VTE/PE. These results emphasize the importance of continuing close monitoring of VTE/PE in the setting of IVIG therapy, along with tailored management strategies intended to minimize adverse outcomes and improve overall care.