title: Acquired activated protein C resistance associated with anti-protein S antibody as a strong risk factor for DVT in non-SLE patients.
abstract: Anti-phospholipid (aPL) antibodies (Abs) are well known to be associated with thromboembolic events in patients with systemic lupus erythematosus (SLE). However, the clinical relevance of a PL Abs in patients without SLE (non-SLE) who have venous thromboembolism remains unclear. We evaluated 143 non-SLE patients with a first episode of clinically suspected deep vein thrombosis (DVT) by using objective tests for diagnosing DVT and laboratory tests including the activated protein C resistance (APC-R) test, the factor V Leiden test, and various aPL Abs. The prevalence of acquired APC-R, in which case there was no factor V Leiden mutation, was significantly higher in patients with DVT (15/58 cases, 25.9%, p < 0.0001) than in those without DVT (3/80 cases, 3.7%), and confirmed that acquired APC-R was a strong risk factor for DVT (odds ratio [OR], 8.95; 95% confidence intervals [CI], 2.45-32.7; p < 0.001). Multivariate logistic analysis revealed that the presence of LA, aCL, anti-beta2-glycoprotein I, anti-prothrombin and anti-protein C Abs was not reliable as a risk factor for DVT in non-SLE patients, and that the presence of anti-protein S Abs was the most significant risk factor for DVT (OR, 5.88; 95% CI, 1.96-17.7; p < 0.002). Furthermore, the presence of anti-protein S Abs was strongly associated with acquired APC-R (OR, 57.8; 95% CI, 8.53-391; p < 0.0001). These results suggest that acquired APC-R may reflect functional interference by anti-protein S Abs of the protein C pathway, which action may represent an important mechanism for the development DVT in non-SLE patients.
authors.affiliation: Laboratory for Clinical Investigation, Osaka University Hospital, 2-15 Yamadaoka, Suita, Osaka 565-0871, Japan. nojima@hp-lab.med.osaka-u.ac.jp
authors.forename: Junzo
authors.initials: J
authors.lastname: Nojima
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Kuratsune
authors.forename: Etsuji
authors.initials: E
authors.lastname: Suehisa
authors.forename: Tomio
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Machii
authors.forename: Teruo
authors.initials: T
authors.lastname: Kitani
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Iwatani
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kanakura
mesh_terms: D020016:Activated Protein C Resistance / Q000150:complications* / Q000175:diagnosis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017152:Antibodies, Antiphospholipid / Q000032:analysis; D001323:Autoantibodies / Q000097:blood / Q000502:physiology*; D005165:Factor V / Q000032:analysis; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011486:Protein C / Q000276:immunology; D017293:Protein S / Q000276:immunology*; D011516:Prothrombin / Q000276:immunology; D012307:Risk Factors; D020246:Venous Thrombosis / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D053482:beta 2-Glycoprotein I
chemical_list: D017152:Antibodies, Antiphospholipid; D001323:Autoantibodies; D006023:Glycoproteins; D011486:Protein C; D017293:Protein S; D053482:beta 2-Glycoprotein I; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin