THE EFFECT OF ASPIRIN AND INDOMETHACIN ON PROSTACYCLIN AND THROMBOXANE PRODUCTION BY PLACENTAL TISSUE INCUBATED WITH IMMUNOGLOBULIN-G FRACTIONS FROM PATIENTS WITH LUPUS ANTICOAGULANT

OBJECTIVE: We investigated the hypothesis that nonsteroidal antiinflam matory agents can influence the abnormal prostanoid production associa ted with antiphospholipid antibodies. We specifically assessed whether aspirin or indomethacin could eliminate the increased placental throm boxane production previously observed with immunoglobulin G fractions from patients with lupus anticoagulant without adversely affecting pro stacyclin production. STUDY DESIGN: Immunoglobulin G fractions were pr epared from the plasma of eight nonpregnant patients with antiphosphol ipid antibody syndrome and demonstrable lupus anticoagulant. Samples f rom each patient were then placed in incubation wells containing expla nts from normal term pregnancies and 10(-4) mol/L aspirin, 10(-7) mol/ L indomethacin, or no added drug. Aliquots were removed at intervals u p to 48 hours of incubation and assessed for placental prostacyclin an d thromboxane production by radioimmunoassay of the stable metabolites prostaglandin F-1 alpha and thromboxane B-2. RESULTS: The addition of aspirin to wells containing immunoglobulin G from patients with lupus anticoagulant was associated with a significant decrease in thromboxa ne 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 prostac yclin was unaffected. CONCLUSION: These results support a role for the use of aspirin for antiphospholipid antibody-related pregnancy loss t hrough a mechanism similar to that postulated for preeclampsia, namely , selective inhibition of thromboxane production.