228. Factors Associated with Thrombosis in Behçet Syndrome: A Systematic Review and Meta-Analysis

Background: Behçet syndrome (BS) is a unique vasculitis that can affect arteries and veins of all sizes. Thrombosis is an important component of vascular involvement in BS. Although several studies were conducted to highlight the mechanism of thromboinflammation in BS, it is still not fully understood. We performed a systematic review and meta-analysis of studies investigating thrombotic, fibrinolytic, and endothelial factors in BS.

Methods: We searched PubMed and EMBASE with the keyword “Behcet*” in four languages (English, German, French and Turkish) from their inception up to April 2020. Titles and/or abstracts of all studies were screened independently by two reviewers (GGO and BY) and conflicts were solved by a third reviewer (GH). Studies comparing BS patients with and without thrombosis and studies comparing BS patients with thrombosis and patients with thrombosis due to other causes were analyzed separately. The pooled odds ratios (OR) with 95%CI were calculated for binary outcomes and standardized mean differences (MD) were calculated for continuous outcomes using RevMan 5.3.

Results: Of 15548 articles, 15052 were excluded due to duplication and inappropriate study design after reviewing titles and abstracts. Full text review of the remaining 388 articles yielded 106 papers meeting our predetermined inclusion criteria. Factors significantly associated with BS thrombosis compared to BS without thrombosis were high frequency of factor V Leiden mutation (15 studies, OR: 2.55, 95% CI 1.66, 3.93), high homocysteine levels (14 studies, MD: 4.27, 95% CI 2.31, 6.22), high protein C levels (5 studies, SMD: 0.80, 95% CI 0.15, 1.45), high VEGF levels (2 studies, SMD: 1.63, 95% CI 0.21, 3.05), high CEC concentrations (2 studies, SMD: 1.00, 95% CI 0.22, 1.77), and high factor 8 levels (4 studies, MD: 17.17, 95% CI 7.79, 26.55). There were no significant differences among the 18 factors assessed in at least 2 studies as shown in the table. Among the other factors assessed in 1 study each, ADMA level (MD: 0.16, 95% CI 0.08, 0.24), anti-C1q level (MD: 9.11, 95% CI 0.51, 17.71), thrombin level (MD:35.90, 95% CI 12.40, 59.40) and TAFI activity (MD:28, 95% CI 4.12, 51.88) were significantly high in patients with BS thrombosis compared to BS without thrombosis. Factors that were associated with BS thrombosis compared to thrombosis due to other causes including JAK-2 mutation, circulating endothelial cells, activated protein C resistance, tPA, and PAI were assessed in 1 study each. Among these, tPA levels (MD: -6.00, 95% CI -10.99, -1.01), APCR (OR: 0.09, 95% CI 0.01, 0.73) and JAK-2 mutations (OR: 0.01, 95% CI 0.00, 0.06) were significantly less in patients with BS thrombosis compared to patients with thrombosis due to other causes.

Conclusions: Several factors were identified that may potentially be associated with thrombosis in BS. However, the cut-offs used for defining the normal level for these factors, time of blood collection (during acute or chronic stage of thrombosis, use of anticoagulants) and the type of thrombosis (arterial, venous, or cerebral sinus) were not uniform across the studies. Studies investigating these factors together, in a large number of patients, and together with appropriate controls are needed to confirm these results.

Disclosures: SNE has received honorariums for presentations from UCB Pharma, Roche, Pfizer, and Merck Sharp Dohme. VH has received grant/research support from Celgene and has served as a speaker for AbbVie, Celgene, Novartis, and UCB Pharma. GH has received grant/research support from Celgene and has served as a speaker for AbbVie, Celgene, Novartis, and UCB Pharma.