title: Lupus anticoagulant inhibition of in vitro prostacyclin release is associated with a thrombosis-prone subset of patients.
abstract: OBJECTIVE
  The effect of lupus anticoagulant-containing sera on endothelial prostacyclin generation (both basal and after thrombin stimulation) was determined. Subsets of patients who had experienced arterial, venous, or no thrombosis were compared with respect to the quantitation of antiphospholipid antibody and effects on prostacyclin production.
  
  
  METHODS
  Serum antiphospholipid antibodies were detected in 26 patients by immunologic (enzyme-linked immunosorbent assay) and kinetic (anticoagulant) assays. Cultured human endothelial cells were exposed to patient or normal serum, and the release of prostacyclin was determined by radioimmunoassay of supernatants. Release was determined in the absence and presence of the secretagogue, thrombin (1 U/mL), corrected for interassay variation, and correlated with other clinical and laboratory variables.
  
  
  RESULTS
  The normal prostacyclin response was a 2.5-fold increase after thrombin (1 U/mL) compared to basal production. Patients with a history of arterial thrombosis (Group 1, n = 10) had the highest IgG anticardiolipin antibody titers (449 +/- 115 [OD x 1,000]), most prolonged kaolin clotting times (140 +/- 15 seconds), and the least prostacyclin response to thrombin (1.36-fold). Patients with venous thrombosis (Group 2, n = 6) had lower titers (329 +/- 120), intermediate clotting times (125 +/- 19 seconds), and slightly impaired prostacyclin responses (2.18-fold). Patients with no history of thrombosis (Group 3, n = 10) had low antibody titers (220 +/- 20), mildly prolonged clotting times (108 +/- 6 seconds), and normal prostacyclin responses (2.33-fold). Patient serum did not alter basal or arachidonate-induced prostacyclin production. Group 1 had significantly lower platelet counts (99 +/- 19) compared to Group 2 (167 +/- 35) or Group 3 (167 +/- 34), but were similar in age and associated diagnoses.
  
  
  CONCLUSIONS
  Inhibition of prostacyclin responses is commonly found in serum from patients with lupus anticoagulants, and is likely to be present in patients with high IgG anticardiolipin antibodies, strong lupus anticoagulants, low platelet counts, and a recent arterial thrombosis.
authors.affiliation: Minneapolis Veterans Administration Medical Center, Minnesota 55417.
authors.forename: K V
authors.initials: KV
authors.lastname: Watson
authors.forename: A E
authors.initials: AE
authors.lastname: Schorer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis*; D001778:Blood Coagulation Disorders / Q000150:complications / Q000276:immunology; D001779:Blood Coagulation Factors / Q000276:immunology*; D002478:Cells, Cultured; D015331:Cohort Studies; D004727:Endothelium / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016682:Lupus Coagulation Inhibitor; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000276:immunology*; D013927:Thrombosis / Q000150:complications / Q000276:immunology*; D013997:Time Factors
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001779:Blood Coagulation Factors; D016682:Lupus Coagulation Inhibitor; D010743:Phospholipids; D011464:Epoprostenol