Evaluating the Incidence and Risk Factors Associated with Deep Venous Thrombosis and Pulmonary Embolism in Patients with Multiple Sclerosis

Background

Numerous studies have shown that multiple sclerosis (MS) is a known risk factor for the development of deep venous thrombosis or pulmonary embolism (VTE), which is possibly related to a combination of chronic inflammation and hypomobility, among other factors. To the practicing hematologist, it may be difficult to determine when or if it is reasonable to prescribe prophylactic anticoagulation to mitigate the occurrence of VTE. There has been limited investigation thus far into alternate risk factors that may further increase the risk of VTE in patients with MS, which may ultimately aid in making this decision. We present an analysis of several possible risk factors that may be associated with the development of VTE among patients with MS.

Methods

De-identified patient data was extracted from the TriNetX database, a composite of electronic health records from 86 healthcare organizations, yielding 192,379 patients with MS as well as an additional 192,379 patients without MS that were matched based on age, sex, and race using propensity score matching. A separate group of 234,647 patients with MS was analyzed to evaluate differences between MS patients who develop VTE and those who do not develop VTE. Patients who were diagnosed with atrial fibrillation or any type of malignancy were excluded, in addition to patients who were on anticoagulation therapy prior to the diagnosis of MS. Risk factors that were evaluated included age, sex, race, body mass index (BMI), hypertension, diabetes, coronary artery disease (CAD), factor V Leiden (FVL) and prothrombin gene mutations, type of MS medication used (monoclonal antibodies, oral therapies, platform injection therapies), and the presence of common complications of MS such as pneumonia and urinary tract infection (UTI). Categorical variables were analyzed using Pearson’s chi-squared test of association or Fisher’s exact test, whereas continuous variables were analyzed using Welch’s t-test. Possible predictors of VTE were evaluated using logistic regression. All statistical analyses were conducted using R version 4.3.2. A p-value of less than 0.05 was considered statistically significant.

Results

Patients with MS experienced a higher rate VTE, as 1,664 of 192,379 (0.86%) patients with MS had VTE compared to 68 of 192,379 (0.04%) patients without MS (p-value < 0.001). Additionally, MS was a significant predictor of VTE (Odds Ratio 17.00, 95% Confidence Interval: 13.43, 21.91, p-value < 0.001). When comparing patients with MS and VTE to those with MS and without VTE, there was a significant association between age, hypertension, diabetes, CAD, either FVL or prothrombin gene mutations, pneumonia, UTI, and BMI with the development of VTE (all p-values < 0.001). Specifically, compared to patient with MS and without VTE, those with MS and VTE were older (59.3 vs. 54.3 years) had higher rates of hypertension (53.2% vs. 24.5%), diabetes (22.1% vs. 8.6%), CAD (14.5% vs. 4.2%), either FVL or prothrombin gene mutations (2.3% vs. 0.25%), pneumonia (29.1% vs. 5.1%), UTI (38.2% vs. 14.8%) and had higher BMI (29.4 vs. 28.27 kg/m²). There was a significant association between the use of oral MS therapies and VTE (p-value <0.001), with a lower percentage of patients in the MS and VTE group utilizing oral MS therapy (8.2% vs. 11.4%). There was not a significant association between the use of monoclonal antibodies or platform injection therapies and the development of VTE among patients with MS.

Conclusion

MS is associated with a significantly increased risk for VTE. Among patients with MS, those with co-morbid conditions such as hypertension, CAD, and diabetes as well as common complications of MS such as pneumonia or UTI appear to be at greater risk of developing VTE. Incorporating these additional risk factors when deciding to initiate prophylactic anticoagulation in patients with MS warrants further investigation.