Risk of Venous Thromboembolism/Pulmonary Embolism with Intravenous Immunoglobulin Administration across Various Diseases: NIS Database Analysis 2016-2020
Authors: Sanjeevi Aditya , Vijay Rao Aniket , Jose Domench Daniel Idoate , Shah Purva , Orakzai Abdullah , Bhandari Samikchhya Keshary , Kharel Himal 
Published: December 2024

Objectives: IVIG administration has been indicated for the treatment of various autoimmune and hematologic disorders. Its use has been implicated in the development of venous thromboembolism (VTE) /pulmonary embolism (PE). Our study evaluates the effect of IVIG on the incidence of VTE/PE in systemic lupus erythematosus (SLE), autoimmune hemolytic anemia (AIHA), heparin-induced thrombocytopenia (HIT), Guillain-Barré syndrome (GBS), Kawasaki disease, lymphoma, chronic lymphocytic leukemia (CLL), and immune thrombocytopenic purpura (ITP).

Methods: We used the National Inpatient Sample (NIS) provided by HCUP for the years 2016-2020 to conduct a retrospective analysis. ICD-10 code were used to code for IVIG administration, VTE/PE and other disease conditions mentioned. As the NIS files contain de-identified data, IRB exemption was not required. We applied the discharge weight DISCWT provided in the database to obtain the national estimates. ICD-10 codes were used to code for patients receiving IVIG, VTE/PE, other disease conditions and comorbidities. Categorical variables were compared by Pearson Chi-square test, and the Student's t-tests/one-way ANOVA was used for continuous variables to compare baseline demographics and hospital characteristics between the two groups. Multivariate logistic regression analysis after adjusting for demographic variables and comorbidities was done to obtain adjusted odds ratio (aOR) of development of VTE/PE with IVIG administration in specific disease conditions.

Results: Of the total cohort, 40,670 patients received IVIG. Of these, 895 patients (2.20%) developed VTE. The median age for the VTE patients was significantly higher at 57 years (IQR: 41-69), in contrast to the median age of those without VTE-31 years (IQR: 5-60), at a p-value less than 0.001. The sex distribution in both groups remained roughly the same, with 46.93% females in both VTE/PE and no VTE/PE groups (p = 0.9977). Compared with those patients without VTE/PE, the patients who developed VTE/PE had higher rates for a variety of comorbid conditions like chronic lung disease, diabetes mellitus, hypothyroidism, hypertension, obesity, congestive heart failure, alcohol abuse, liver disease, neurological disorders, and pulmonary circulation disorders. There was a variation in the incidence of VTE/PE in patients treated with IVIG due to various underlying diseases. In SLE, 40 of 510 patients developed VTE/PE (aOR 1.33, 95% CI 0.86-2.04, p=0.194). In HIT, 30 of 35 had a co-existing diagnosis VTE/PE (85.71%), for APS, 20 of 45 had a coexisting diagnosis of VTE/PE. We did not calculate aOR in these patients since VTE/PE might have been the indication for IVIG use and likely occurred before the use of IVIG. In AIHA, there were 80 VTE/PE cases against 1050 patients, accounting for 7.62%, with an aOR of 2.62 and a 95% CI of 1.95-3.51, with p &lt; 0.001-a significantly increased risk. Lymphomas-65 of 845 patients developed VTE/PE, accounting for 7.69%, with an aOR of 0.83 and a 95% CI of 0.58 to 1.19, with p = 0.324. For GBS, there were 375 VTE/PE cases in 13,115 patients, for an adjusted OR of 1.36 with a 95% CI 1.12 to 1.66. In CLL, there were 35 VTE/PE cases in 435 patients, for a prevalence of 8.05%, with an adjusted OR of 0.95 and 95% CI 0.58 to 1.57, indicating a non-statistically significant risk reduction. In Kawasaki disease, 5 of 8,705 patients developed VTE/PE 0.06% and we could not calculate aOR. For ITP, 245 of 17,685 patients experienced VTE/PE 1.38%, with an aOR of 0.86 95% CI: 0.66-1.22, p=0.087, which represents a decrease in the risk of VTE/PE that was not statistically significant

Conclusion: There is a variation in the incidence of VTE/PE among patients receiving IVIG across different disease conditions. Noticeably, in AIHA and GBS, there was a significantly increased risk of VTE/PE, while in other conditions such as SLE, lymphoma, CLL, and ITP, the associated risk was not significant. Kawasaki disease had the lowest incidence of VTE following the administration of IVIG. Specifically, the study finds that assessment of the safety profile of IVIG therapy must be based on a disease-specific risk model, while also demonstrating the appropriateness of individually tailored preventive measures in populations at risk.