Increased lipid peroxidation correlates with platelet activation but not with markers of endothelial cell and blood coagulation activation in patients with antiphospholipid antibodies

• Published in: British journal of haematology Vol. 114; no. 4; pp. 845 - 851
• Main Authors: Martinuzzo, Marta E., Forastiero, Ricardo R., Kordich, Lucía, Carreras, Luis O.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-09-2001; Blackwell
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Antiphospholipid - metabolism; antiphospholipid antibodies; antiphospholipid syndrome; Antiphospholipid Syndrome - metabolism; Antithrombins - analysis; Biological and medical sciences; Biomarkers - urine; Blood Coagulation; blood coagulation activation; Case-Control Studies; Chi-Square Distribution; Child; Child, Preschool; E-Selectin - blood; Endothelium, Vascular - metabolism; Female; Fibrin Fibrinogen Degradation Products - analysis; General aspects; Hematologic and hematopoietic diseases; Humans; Immunopathology; Isoprostanes - urine; Lipid Peroxidation; Lupus Erythematosus, Systemic - metabolism; Male; Medical sciences; Middle Aged; P-Selectin - blood; Platelet Activation; Platelet diseases and coagulopathies; Prothrombin - analysis; Statistics, Nonparametric; Thrombosis - metabolism; Thromboxane B2 - analogs & derivatives; Thromboxane B2 - urine; Vascular Cell Adhesion Molecule-1 - blood; Human; Immunopathology; Blood coagulation; Endothelial cell; Antiphospholipid antibody syndrome; Pathophysiology; Antibody; Cell adhesion molecule; Phospholipid; Cardiovascular disease; Autoimmune disease; Lipids; Hemopathy; Vascular disease; Platelet; Hemostasis; Platelet function; Peroxidation
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2001.03028.x

Recent studies have shown that patients with antiphospholipid antibodies (aPL) have increased lipid peroxidation. We evaluated the urinary excretion of 11‐dehydro thromboxane B2 (11‐DH‐TXB2) and isoprostane F2αIII (IPF2αIII), reflecting platelet activation and lipid peroxidation in vivo, and plasma soluble markers of endothelial cell, platelet and blood coagulation activation: soluble vascular cell adhesion molecule‐1 (sVCAM‐1), P‐ and E‐selectin (sPsel and sEsel), F1 + 2 fragment of prothrombin (F1 + 2), thrombin–antithrombin complexes (TAT) and D‐Dimer (DD). We studied 79 patients with aPL (47 with previous thrombosis), 45 healthy volunteers (normal controls, NC), 12 patients with systemic lupus erythematosus (SLE) without aPL and a thrombosis control group (TCG) without thrombophilia (n = 16). Urinary levels (mean, range) of eicosanoids and isoeicosanoids were significantly increased in 39 patients with aPL compared with 25 NC, 11‐DH‐TXB2 164·0 ng/mmol creatinine (9·5–1162·8) versus 43·4 ng/mmol creatinine (4·2–87·6), P < 0·001; IPF2αIII 56·9 pg/mg creatinine (5·5–388·7) versus 27·0 pg/mg creatinine (4·6–87·6), P = 0·03. Both metabolites were significantly correlated (ρ= 0·49, P = 0·014), but none correlated with any clinical manifestation or antibody profile. The aPL group presented increased levels of sPsel, sEsel, sVCAM‐1, TAT, F1 + 2 and DD, but any soluble marker correlated with IPF2αIII. Urinary 11‐DH‐TXB2 correlated with sPsel (ρ= 0·39, P = 0·04). Compared with SLE controls, the SLE group with aPL had higher levels of F1 + 2. Plasma levels of F1 + 2 and DD were significantly increased and a trend to higher sPsel was found in aPL patients with thrombosis compared with the TCG. Platelet activation, lipid peroxidation and blood coagulation activation seem to be important in the pathophysiology of antiphospholipid syndrome.