The effect of aspirin and indomethacin on prostacyclin and thromboxone production by placental tissue incubated with immunoglobulin G fractions from patients with lupus anticoagulant

OBJECTIVE: We investigated the hypothesis that nonsteroidal antiinflammatory agents can influence the abnormal prostanoid production associated with antiphospholipid antibodies. We specifically assessed whether aspirin or indomethacin could eliminate the increased placental thromboxane production previously observed with immunoglobulin G fractions from patients with lupus anticoagulant without adversely affecting prostacyclin production. STUDY DESIGN: Immunoglobulin G fractions were prepared from the plasma of eight nonpregnant patients with antiphospholipid antibody syndrome and demonstrable lupus anticoagulant. Samples from each patient were then placed in incubation wells containing explains from normal term pregnancies and 10−4 mol/L aspirin, 10−7 mol/L indomethacin, or no added drug. Aliquots were removed all intervals up to 48 hours of incubation and assessed for placental prostacyclin and thromboxane production by radioimmunoassay of the stable metabolites prostaglandin F1α and thromboxane B2. RESULTS: The addition of aspirin to wells contaiing immunoglobulin G from patients with lupus anticoagulant was associated with a significant decrease in thromboxane production compared with wells without added drug, but prostacyclin production was unaffected. In contrast, the addition of indomethacin also decreased thromboxane production significantly, but prostacyclin production was also diminished, so the ratio of thromboxane to prostacyclin was unaffected. CONCLUSION: These results support a role for the use of aspirin for antiphospholipid antibody-related pregnancy loss through a mechanism similar to that postulated for preeclampsia, namely, selective inhibition of thromboxane production.