ENDOTHELIUM-DERIVED HAEMOSTATIC FACTORS AND THE ANTIPHOSPHOLIPID SYNDROME

• Published in: British journal of rheumatology Vol. 34; no. 3; pp. 201 - 206
• Main Authors: MACKWORTH-YOUNG, C. G., ANDREOTTI, F., HARMER, I., LOIZOU, S., POTTINGER, B. E., PEARSON, J. D., DAVIES, G. J., MASERI, A., WALPORT, M. J.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.03.1995; Oxford Publishing Limited (England)
• Subjects: Adult; Anti-endothelial cell antibodies; Antibodies, Antiphospholipid - blood; Anticardiolipin antibody; Antiphospholipid syndrome; Antiphospholipid Syndrome - blood; Antiphospholipid Syndrome - immunology; Autoantibodies - blood; Biomarkers - blood; Female; Humans; Lupus anticoagulant; Male; Middle Aged; Periodicity; Plasminogen Activator Inhibitor 1 - blood; Plasminogen activator type 1; Platelet; Statistics as Topic; Systemic lupus erythematosus; Thrombosis; Tissue Plasminogen Activator - blood; Tissue-type plasminogen activator; Von Willebrand factor; von Willebrand Factor - analysis
• ISSN: 1462-0324; 0263-7103; 1462-0332
• DOI: 10.1093/rheumatology/34.3.201

The cause of thrombosis in the antiphospholipid syndrome (APS) is unknown. There have been reports of abnormalities in the antigenic levels or activity of endothelium-derived haemostatic factors, such as tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1); however the data from these studies are conflicting. We studied plasma from nine patients with APS; seven of them had a history of thrombosis, and three had systemic lupus erythematosus (SLE). We also studied nine matched control patients who had SLE without APS, and 14 healthy individuals. We measured t-PA, von Willebrand factor (vWF), anticardiolipin antibody (ACA) and anti-endothelial cell antibody (AECA) levels by enzyme-linked immunoassay (ELISA), PAI-1 activity by a parabolic-rate chromogenic assay, and lupus anticoagulant (LA) activity by a standard mixing test. For t-PA and PAI-1, measurements were made on morning and evening plasma samples. The two groups of patients did not differ significantly with respect to age, sex, plasma lipids or anti-inflammatory drugs. Most APS patients (7/9) but none of the controls were taking warfarin. Between the APS and the control patients no significant differences were detected in t-PA, PAI-1, vWF or AECA levels. When APS patients were considered alone, vWF levels correlated positively with IgG ACA levels (r = 0.81, P <0.01) and negatively with platelet count (r = −0.68, P <0.05). There was no correlation between levels of ACA or LA activity and t-PA, PAI-1 or AECA. Compared with healthy volunteers, the diurnal variation of t-PA and PAI-1 was blunted in the two patient groups. The data suggest that ACA do not alter plasma t-PA or PAI-1 levels. However, compared with normal subjects, patients with APS or SLE have an altered diurnal rhythm of t-PA and PAI-1 which may reflect an abnormality of endothelial function unrelated to ACA. The results do indicate that raised IgG ACA levels may be associated with increased release of vWF by the endothelium. This may lead to enhanced vascular platelet adhesion and reduced circulating platelet number.