Thrombosis in patients with connective tissue diseases treated with specific cyclooxygenase 2 inhibitors - A report of four cases

Specific inhibitors of cyclooxygenase 2 (COX-2) have been approved for the treatment of osteoarthritis and rheumatoid arthritis. Unlike nonsteroidal a ntiinflammatory drugs, specific COX-2 inhibitors do not inhibit platelet ac tivation. However, these agents significantly reduce systemic production of prostacyclin, As a result, theoretical concerns have been raised that spec ific COX 2 inhibitors could shift the hemostatic balance toward a prothromb otic state. Patients,vith connective tissue diseases (CTD), who may be pred isposed to vasculopathy and thrombosis, often have arthritis or pain syndro mes requiring treatment with antiinflammatory agents. Herein we describe 4 patients with CTD who developed ischemic complications after receiving cele coxib. All patients had a history of Raynaud's phenomenon, as well as eleva ted anticardiolipin antibodies, lupus anticoagulant, or a history compatibl e with antiphospholipid syndrome. It was possible to measure a urinary meta bolite of thromboxane A(2) in 2 of the patients as an indicator of in vivo platelet activation, and this was markedly elevated in both. In addition, t he patients had evidence of ongoing inflammation as indicated by elevated e rythrocyte sedimentation rate, hypocomplementemia, and/or elevated levels o f anti-DNA antibodies. The findings in these 4 patients suggest that COX-2 inhibitor-treated patients with diseases that predispose to thrombosis shou ld be monitored carefully for this complication.