title: Thrombosis in patients with connective tissue diseases treated with specific cyclooxygenase 2 inhibitors. A report of four cases.
abstract: Specific inhibitors of cyclooxygenase 2 (COX-2) have been approved for the treatment of osteoarthritis and rheumatoid arthritis. Unlike nonsteroidal anti-inflammatory drugs, specific COX-2 inhibitors do not inhibit platelet activation. However, these agents significantly reduce systemic production of prostacyclin. As a result, theoretical concerns have been raised that specific COX-2 inhibitors could shift the hemostatic balance toward a prothrombotic state. Patients with connective tissue diseases (CTD), who may be predisposed to vasculopathy and thrombosis, often have arthritis or pain syndromes requiring treatment with antiinflammatory agents. Herein we describe 4 patients with CTD who developed ischemic complications after receiving celecoxib. All patients had a history of Raynaud's phenomenon, as well as elevated anticardiolipin antibodies, lupus anticoagulant, or a history compatible with antiphospholipid syndrome. It was possible to measure a urinary metabolite of thromboxane A2 in 2 of the patients as an indicator of in vivo platelet activation, and this was markedly elevated in both. In addition, the patients had evidence of ongoing inflammation as indicated by elevated erythrocyte sedimentation rate, hypocomplementemia, and/or elevated levels of anti-DNA antibodies. The findings in these 4 patients suggest that COX-2 inhibitor-treated patients with diseases that predispose to thrombosis should be monitored carefully for this complication.
authors.affiliation: University of Michigan, Ann Arbor, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Crofford
authors.forename: J C
authors.initials: JC
authors.lastname: Oates
authors.forename: W J
authors.initials: WJ
authors.lastname: McCune
authors.forename: S
authors.initials: S
authors.lastname: Gupta
authors.forename: M J
authors.initials: MJ
authors.lastname: Kaplan
authors.forename: F
authors.initials: F
authors.lastname: Catella-Lawson
authors.forename: J D
authors.initials: JD
authors.lastname: Morrow
authors.forename: K T
authors.initials: KT
authors.lastname: McDonagh
authors.forename: A H
authors.initials: AH
authors.lastname: Schmaier
mesh_terms: D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000097:blood; D000068579:Celecoxib; D003240:Connective Tissue Diseases / Q000150:complications* / Q000188:drug therapy*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013927:Thrombosis / Q000139:chemically induced / Q000150:complications* / Q000209:etiology*
chemical_list: D017153:Antibodies, Anticardiolipin; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib