The influence of cyclo-oxygenase specificity of non-steroidal anti-inflammatory drugs on bleeding complications in concomitant coumarine users.

BACKGROUND: Concomitant use of coumarines and non-steroidal anti-inflammatory drugs (NSAIDs) may induce bleeding complications, due to the inhibition of both coagulant factors and platelet function. Unlike non-selective NSAIDs, cyclo-oxygenase-2 (COX-2)-selective NSAIDs interfere very little with platelet aggregation. AIM: To determine whether COX-2-selective NSAIDs are associated with less bleeding complications in coumarine users, compared with non-selective NSAIDs. DESIGN: Prospective, nested case-control study. METHODS: We studied concomitant coumarine and NSAID users over two years. Patients with bleeding (cases), and frequency-matched patients without bleeding (controls), were sent questionnaires regarding possible risk factors for bleeding. International normalized ratio (INR) values were recorded. Univariate and multivariate analyses were used to detect factors contributing to bleeding. RESULTS: There were 1491 reported bleeds. NSAIDs were involved in 14.8%; 3.9% involving COX-2-selective NSAIDs. In non-bleeders, 2601 prescriptions with a coumarine/NSAID combination were detected; 9.7% were COX-2-selective. Adjusted ORs (95% CI) for a bleeding complication were 3.07 (1.18-8.03) for non-selective NSAID use, 3.01 (1.42-6.37) for NSAID use > 1 month, and 1.89 (1.03-3.49) for INR > or = 4.0. DISCUSSION: In coumarine users, COX-2-selective NSAIDs are associated with less bleeding complications than non-selective NSAIDs are. Duration of NSAID use, as well as intensity of coumarine treatment, plays an important additional role. When the coumarine-NSAID combination is inevitable in an individual patient, a COX-2-selective NSAID may be preferred, with careful monitoring of the INR.

Elevated levels of platelet microparticles are associated with disease activity in rheumatoid arthritis.

OBJECTIVE: Platelets are involved in various thrombotic events, often by means of platelet-derived microparticles (PMPs). It is likely that platelets are also involved in inflammation. Because inflammatory processes play a central role in rheumatoid arthritis (RA), we sought to determine whether PMPs are present in this disease. METHODS: This descriptive, cross-sectional study included 19 RA patients and 10 healthy controls. Nine of the patients had active RA (erythrocyte sedimentation rate [ESR] > or =28 mm/hour and/or C-reactive protein [CRP] level > or =28 mg/liter, > or =9 painful joints, and > or =6 swollen joints), and 10 had inactive disease (ESR < or =27 mm/hour, CRP < or =27 mg/liter, no tender joints, and no swollen joints). Platelet counts and PMP numbers were determined using cell counter and flow cytometry, respectively. RESULTS: Platelet counts in the 3 groups were similar. However, levels of PMPs in RA patients were significantly higher than those in healthy controls (median 616 versus 118 x 10(6)/liter; P = 0.005). PMP levels were higher in patients with active RA than in those with inactive RA (median 2,104 versus 504 x 10(6)/liter; P > 0.05). Moreover, PMP levels correlated with disease activity (r = 0.67, P = 0.05). CONCLUSION: PMPs are associated with RA, and PMP levels are correlated with disease activity. Thus, platelets probably play a part in the inflammatory process of RA by means of PMPs. Given the importance of PMPs in cardiovascular diseases, this may be one reason for the enhanced cardiovascular morbidity and mortality in RA.

Platelet function is inhibited by non-selective non-steroidal anti-inflammatory drugs but not by cyclo-oxygenase-2-selective inhibitors in patients with rheumatoid arthritis.

BACKGROUND: Interaction with platelet function by non-steroidal anti-inflammatory drugs (NSAIDs) is related to the inhibition of cyclo-oxygenase-1 (COX-1). In patients with rheumatoid arthritis (RA), only one of the COX-2-selective NSAIDs (nabumetone) has been demonstrated to spare platelet function partially. OBJECTIVE: To compare the effects of the COX-2-selective inhibitor, meloxicam, with those of the non-selective NSAID, naproxen, on platelet function and thromboxane levels in RA patients. METHODS: In this randomized, controlled, cross-over trial, 10 RA patients used meloxicam 7.5 mg bid and naproxen 500 mg bid, each during a 2-week period. Washout periods were applied. Before and after each 2-week period of NSAID intake, laboratory studies were performed. RESULTS: Platelet aggregation was significantly less influenced, thromboxane levels were less inhibited (246 vs 117 pg/ml) and bleeding times were less prolonged with meloxicam than with naproxen (3.2 vs 2.3 min). Moreover, the results of all tests during meloxicam exposure were comparable with baseline values. CONCLUSION: In RA patients, meloxicam, a representative of the selective COX-2 inhibitors, does not interfere with platelet function and thromboxane levels, in contrast with naproxen (a non-selective COX inhibitor).