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

Abstract

have been approved for the treatment of osteoarthritis and rheumatoid arthritis. Unlike nonsteroidal antiinflammatory 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 A 2 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.Prostaglandins (PG) and thromboxane (TX) are regulators of platelet and endothelial cell function. Activated platelets synthesize TXA 2 , which is a potent platelet aggregant and vasoconstrictor. PGI 2 , which is synthesized primarily by endothelial cells, inhibits platelet activation by elevating platelet cyclic AMP and induces vasodilation. There is evidence that endogenous PGI 2 has antithrombotic properties. Infusion of PGI 2 and enhancement of endogenous PGI 2 also provide antiplatelet activity (1).A multienzyme pathway that includes the cyclooxygenase (COX)

Anti-inflammatory Activity of Gumiganghwaltang through the Inhibition of Nuclear Factor-κB Activation in Peritoneal Macrophages

“…26,27) The present study showed that GMGHT effectively inhibited the mRNA and protein expression of COX-2 in a dose dependent manner. It suggests that GMGHT may provide its beneficial effect on anti-inflammation.…”

Bradykinin B2 receptor knockout mice are protected from thrombosis by increased nitric oxide and prostacyclin

“…Since clinical thrombosis is the summation of risk factors, small changes in prostacyclin levels, as the result of treatment with cyclooxygenase 2 antagonists in systemic lupus erythematosis patients with other risk factors for thrombosis, result in increased risk for clinical thrombosis. 45 Thus, the present investigations indicate that components of the plasma kallikrein/kinin system indirectly influence one's risk for thrombosis through its interaction with components of the renin angiotensin pathway. These findings broaden our notion of factors that modify thrombosis risk and suggest new targets for antithrombotic therapy.…”

Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function

“…Neither disruption of PGHS-2 nor IP deletion results in spontaneous thrombosis, but, rather, both augment the response to thrombogenic stimuli. Thus, an unrelated predisposition to thrombosis would facilitate detection of a cardiovascular hazard from PGHS-2 inhibitors, as has been observed in patients (29)(30)(31).…”