Risk Of Venous Thromboembolism In Patients With Celiac Disease: A Systematic Review And Meta-Analysis

Abstract

Background/Purpose: Deep venous thrombosis (DVT) and pulmonary embolism (PE), collectively known as venous thromboembolism (VTE), are common medical conditions resulting in significant morbidity and mortality. Chronic inflammatory state has been increasingly recognized as a risk factor for VTE as several chronic inflammatory disorders, such as rheumatoid arthritis, inflammatory bowel disease and systemic lupus erythematosus have been shown to increase the risk of VTE in large epidemiological studies. However, the data on celiac disease, a chronic inflammatory disease affecting primarily the small bowel, remain unclear due to conflicting studies. Thus, to further investigate this possible association, we conducted a systematic review and meta-analysis of cohort and case-control studies that compared the risk of VTE in patients with celiac disease versus participants without it. Methods: Two investigators (P.U. and K.W.) independently searched published studies indexed in MEDLINE and EMBASE from inception to September 2015 using the terms for celiac disease in conjunction with the terms "venous thromboembolism", "pulmonary embolism" and "deep venous thrombosis". A manual search of references of selected retrieved articles was also performed. The inclusion criteria were as follows: (1) cohort or case-control studies evaluating the association between celiac disease and VTE and (2) odds ratios, relative risk, hazard ratio or standardized incidence ratio with 95% confidence intervals (CI) were provided. Study eligibility was independently determined by the two aforementioned investigators. Newcastle-Ottawa scale was used to assess the quality of the included studies. RevMan 5.3 software was used for the data analysis. Point estimates and standard errors were extracted from individual studies and were combined by the generic inverse variance method of DerSimonian and Laird. We used a random-effect model rather than a fixed-effect model in light of high likelihood of between study variance. Cochran's Q test and I2 statistics were used to determine the study's statistical heterogeneity. Results: Out of 210 potentially relevant articles, 5 studies (4 retrospective cohort studies and 1 case-control study) were identified and included in our data analysis. The pooled risk ratio of VTE in patients with AS was 1.36 (95% CI, 1.08 to 1.72). The statistical heterogeneity of this meta-analysis was high with an I2 of 83%. Conclusion: Our study demonstrated a statistically significant increased risk of VTE among patients with celiac disease with 36% excess risk.