Sarcoidosis is Associated With Increased Risk of Venous Thromboembolism: A Population-Based Study

Background/Purpose: Chronic inflammation has been increasingly recognized as a risk factor of venous thromboembolism (VTE). Several epidemiologic studies have demonstrated an increased incidence of VTE among patients with chronic inflammatory disorders such as rheumatoid arthritis, inflammatory myositis and vasculitis. However, data on sarcoidosis, another relatively common immune-mediated chronic inflammatory disorder, are still limited.

Methods: 345 patients (50% female; 90% Caucasian, 5% African-American; mean age 45.6 years) with incident sarcoidosis in 1976-2013 in a geographically well-defined population were identified based on comprehensive individual medical record review. Inclusion required physician diagnosis supported by histopathology, compatible clinical presentation, and exclusion of other granulomatous diseases. 345 sex and age-matched comparators (50% female; 95% Caucasian, 1% African-American; mean age 45.4 years) were also identified from the same underlying population. Medical records of both cases and comparators were individually reviewed for both subtypes of VTE including deep venous thrombosis (DVT) and pulmonary embolism (PE). The prevalence of VTE, DVT and PE prior to index date was compared between the 2 groups using Fisher’s exact test. The cumulative incidence of VTE adjusted for the competing risk of death was estimated. Cox proportional hazards models with adjustment for age, sex, calendar year, current smoking, diabetes mellitus, hypertension, dyslipidemia and obesity were used to compare the rate of development of VTE between the 2 groups.

Results: The mean length of follow-up was 15.1 years and 16.8 years for cases and comparators, respectively. The prevalence of VTE prior to index date was not significantly different between cases and comparators (1.4% and 1.4%, p-value = 1.0).  After index date, 27 VTE events were observed among cases and 10 VTE events were observed among comparators. After adjusting for age, sex and calendar year,  the risk of incident VTE after index date was significantly elevated among patients with sarcoidosis with adjusted hazard ratio (HR) of 3.04 (95% CI, 1.47 – 6.29). Increased risk was observed in both DVT (HR 3.14; 95% CI 1.32 – 7.48) and PE (HR 4.29; 95% CI 1.21 – 15.23). Further adjustment for current smoking, diabetes mellitus, hypertension, dyslipidemia and obesity yielded adjusted HR of 3.04 (95% CI 1.25 – 7.39) for VTE, adjusted HR of 3.00 (95% CI 1.05 – 8.58) for DVT and adjusted HR of 4.24 (95% CI 1.11 – 16.18) for PE.  Sensitivity analysis including only VTE that occurred at least 6 months after index date to reduce the likelihood of detection bias was also performed.  The adjusted HR for VTE slightly decreased to 2.73 and remained statistically significant (95% 1.30 – 5.72). The adjusted HR for DVT and PE decreased to 3.00 (95% CI; 1.25 – 7.20) and 3.58 (95% CI; 0.98 – 13.03), respectively.

Conclusion: Patients with sarcoidosis have a higher risk of VTE. It is possible that this risk is related to the systemic inflammatory nature of the disease, however further investigations are required to address this increased risk in clinical practice.