Thrombosis Risk and Immunosuppressants in Behçet Disease

Kevin Deane, MD


October 04, 2012

Immunosuppressants Reduce Venous Thrombosis Relapse in Behçet's Disease

Desbois AC, Wechsler B, Resche-Rigon M, et al
Arthritis Rheum. 2012;64:2753-2760

Thrombosis in Behçet Disease

Vascular thrombosis is known to be associated with Behçet disease and has been reported in nearly 40% of patients.[1] Furthermore, thrombosis (especially pulmonary embolism and Budd-Chiari syndrome) has been reported to account for up to 17% of the mortality seen with Behçet disease.[2] Although vascular inflammation is thought to be a major factor in the etiology of thrombosis in Behçet disease, the optimal methods to treat and prevent it are unknown.

Study Summary

Desbois and colleagues evaluated factors associated with relapse of thrombosis and mortality in patients with Behçet disease by performing chart reviews of 807 patients, 296 (37%) of whom had a total of 586 venous thrombotic events.

They found that most events were cases of lower-extremity thrombosis, approximately 10% were Budd-Chiari syndrome, and another 10% were cases of pulmonary embolism. Death directly related to thrombosis was significantly associated with Budd-Chiari syndrome.

The investigators also found that the use of immunosuppressive agents (methotrexate, azathioprine, cyclosporine, chlorambucil, and cyclophosphamide) was associated with a significantly lower rate of relapse of venous thrombosis (hazard ratio, 0.27; P < .01) and that glucocorticoid use was associated with a trend toward prevention of relapse.

Almost all patients in this study (99%) were treated with anticoagulation (typically heparin followed by warfarin for a median duration of 10 months), limiting the ability to analyze the effect of anticoagulation on recurrent disease. Therefore, Desbois and colleagues did not report the effect of anticoagulation on recurrent thrombosis. However, they mention that only 2% of patients had hemorrhagic complications -- a concern in patients with Behçet disease, who may have arterial aneurysms. These investigators reported that approximately 15% of their patients had such aneurysms.

Procoagulant factors, such as genetic mutations and anticardiolipin antibodies, were evaluated in only 93 of 296 (31%) patients; however, of these 93 patients, 42 (45%) had prothrombotic factors, including 12% who had anticardiolipin antibodies.

The investigators concluded that immunosuppressive agents significantly reduce recurrent relapse of venous thrombosis in Behçet disease, perhaps because venous inflammation plays a primary role in the etiology of these clots.


These findings, although limited by the uncontrolled nature of the study, suggest that immunosuppression can be beneficial in preventing relapse of thrombosis in patients with Behçet disease. Therefore, the use of immunosuppression may be an important component of thrombosis management in this disease.

Hopefully, these findings will set the stage for randomized, controlled trials that will provide clinically meaningful data regarding immunosuppressive drugs (eg, methotrexate vs cyclophosphamide) and duration of therapy, as well as anticoagulation approaches, that might improve outcomes related to thrombosis in Behçet disease.

Such studies should also formally evaluate the role that testing for prothrombotic factors (such as antiphospholipid antibodies) should play in long-term management of thrombosis in patients with Behçet disease. For example, should someone with Behçet disease and thrombosis who has elevated antiphospholipid antibodies be treated differently from someone with Behçet disease and thrombosis, but who lacks such antibodies?