Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Aspirin Response Is Impaired in Patients with Systemic Lupus Erythematosus.
Kawai1, Vivian K., Avalos2, Ingrid B., Oeser5, Annette M., Oates4, John, Milne4, Ginger, Chung3, Cecilia P., Stein1, C. Michael
Patients with systemic lupus erythematosus (SLE) have an increased risk of myocardial infarction, stroke and other thrombotic events. Low-dose aspirin, used to prevent thrombotic events, irreversibly acetylates the platelet cyclooxygenase-1 (COX-1) enzyme and thus inhibits thromboxane A2 (TxA2) formation and platelet aggregation. However, some individuals do not respond adequately to aspirinsometimes termed "aspirin resistance". Although many lupus patients receive aspirin to prevent thrombosis, there is no information about platelet responses in this population. We examined the hypothesis that response to aspirin is impaired in SLE.
Material and Methods:
We prospectively studied 34 patients with SLE and 36 age and sex-matched controls who received immediate-release aspirin 81 mg /day for 7 days with monitoring of adherence. Subjects did not take NSAIDs for 7 days before the study. As a measure of aspirin's effect on its pharmacologic target, platelet COX-1, we measured concentrations of serum TxB2, the stable metabolite of TxA2, by mass spectrometry in whole blood allowed to clot at 37°C, before and after 7 days of aspirin treatment. We compared concentrations of serum TxB2 in patients and controls who were not receiving aspirin therapy at baseline, and after a week of aspirin therapy. Failure to suppress serumTxB2 below 10 ng/ml is widely reported as a threshold for defining aspirin resistance; we compared the proportion of patients and controls with aspirin resistance. Continuous variables were expressed as median and interquartile range [IQR]. McNemar and Wilcoxon rank sum tests were used to compare categorical and continuous data.
The demographic characteristics of patients with SLE (n = 34, 82% female, age 41 [2947 years] and controls (n = 36, 72% female, age 45 [3350 years]) were similar. At baseline, median serum TxB2 was similar in SLE (76.8 [39.0134.8 ng/ml]) and controls (103.3, [30.6130.3 ng/ml]) (P=0.84). Aspirin suppressed serum TxB2 production almost completely in controls to 1.5 [0.82.7 ng/ml] but had significantly less effect in SLE (3.1 [2.25.3 ng/ml]) (P=0.002) (Figure). Aspirin resistance was present in 5/34 (15%) SLE patients and 0/36 controls (P<0.001). Compared to those that were aspirin sensitive, the 5 aspirin resistant patients were more likely to have diabetes (P=0.034), hypertension (P=0.007), a history of smoking (P=0.056), and a higher BMI (p=0.055), but measures of disease activity (SLEDAI) (P=0.96) and damage (SLICC) (P=0.43) did not differ.
Patients with SLE are less responsive to aspirin than controls and resistance to the effect of aspirin on platelet COX-1 occurs. Obesity, diabetes, hypertension and a history of smoking were more common among lupus patients with aspirin resistance.
Figure. Serum Thromboxane B2 in patients with lupus and controls after aspirin treatment.
To cite this abstract, please use the following information:
Kawai, Vivian K., Avalos, Ingrid B., Oeser, Annette M., Oates, John, Milne, Ginger, Chung, Cecilia P., et al; Aspirin Response Is Impaired in Patients with Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2123