Patterns of in vitro aspirin hydrolysis rates in rheumatoid arthritis and systemic lupus erythematosus.

In previous in vitro studies of normal human blood and in vivo canine studies an intracellular erythrocyte (RBC) esterase was identified which controlled the rate of aspirin (ASA) hydrolysis and thus modulated the duration of intact ASA survival and availability for transacetylations required for some therapeutic effects. In whole blood from 30 patients with systemic lupus erythematosus (SLE), 10 normal subjects, and 40 patients with active seropositive rheumatoid arthritis (RA), there were negative correlations between the hematocrit level and the ASA half-life in vitro: r = -0.50, -0.83, and -0.61, respectively. When ASA hydrolysis rates were normalized to approximate whole blood esterase content (k/Hb [min-1 X g-1 X dl] X 10(-4) the mean rate was most rapid in patients with RA (24.2 +/- 2.8) and lowest in patients with SLE (18.6 +/- 3.1), especially in those with recently active disease. To differentiate intracellular and extracellular factors, ASA hydrolysis rates were measured in washed RBC suspensions from similar groups. The mean ASA hydrolysis rate (k/10(6) RBC X 10(-3) was significantly lower in SLE RBC (7.72 +/- 0.81). In RBC from patients with RA the average rate (8.50 +/- 0.85) lay between the SLE group and controls (9.08 +/- 1.04). Thus, an erythrocyte esterase defect in SLE patients resulted in reduced ASA hydrolyzing capacity. In blood from patients with RA a small reduction in esterase activity was compensated by extracellular factors increasing ASA accessibility to the esterase.