ORIGINAL ARTICLESCorrelation between the potency of a beta2-glycoprotein I-dependent lupus anticoagulant and the level of resistance to activated protein Cde Laat, Basa,b; Eckmann, Carel Ma; van Schagen, Marliesa; Meijer, Alexander Bb; Mertens, Koenb,c; van Mourik, Jan Aa,b,dAuthor Information aDepartment of Blood Coagulation, Diagnostic Services Sanquin, The Netherlands bDepartment of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands cDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands dDepartment of Vascular Medicine, Amsterdam Medical Center, Amsterdam, The Netherlands Received 22 January, 2008 Revised 6 May, 2008 Accepted 17 May, 2008 Correspondence to Dr B. de Laat, PhD, Sanquin Blood Supply Foundation, Department of Plasma Proteins, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands Tel: +31 20 5123120; fax: +31 20 5123680; e-mail: email@example.com Blood Coagulation & Fibrinolysis: December 2008 - Volume 19 - Issue 8 - p 757-764 doi: 10.1097/MBC.0b013e32830f1b85 Buy Metrics Abstract The antiphospholipid syndrome is characterized by the occurrence of vascular thrombosis combined with the presence of antiphospholipid antibodies in plasma of patients. It has been published that antibeta2-glycoprotein I (beta2-GPI) antibodies, with lupus anticoagulant activity (LAC), highly correlate with thrombosis. Resistance related to antiphospholipid antibodies against activated protein C (APC) is one of the proposed mechanisms responsible for thrombosis. We investigated a possible correlation between a beta2-GPI-dependent LAC (titration of cardiolipin into an activated partial thromboplastin time-based assay) and increased APC resistance in a population of 22 plasma samples with LAC activity. Eleven plasma samples that displayed a beta2-GPI-dependent LAC also showed increased APC resistance. In contrast, only one of the 11 plasma samples with a beta2-GPI-independent LAC displayed increased APC resistance. In addition, a monoclonal antibeta2-GPI antibody and patient-purified immunoglobulin G (both with LAC activity) were diluted in plasma with/without protein C. Both antibodies only displayed a beta2-GPI-dependent LAC in plasma in the presence of protein C. This indicates that the principle of the beta2-GPI LAC-assay was based on increased resistance against protein C. Surface plasmon resonance analysis was used to investigate binding between APC and beta2-GPI. We observed that beta2-GPI was able to bind APC directly, especially in the presence of a monoclonal antibeta2-GPI antibody. In conclusion, our observations show a direct correlation between a major clinical symptom of antiphospholipid syndrome (thrombosis), a diagnostic assay (beta2-GPI-dependent LAC) and a potential mechanism responsible for thrombosis in the antiphospholipid syndrome (increased APC resistance). © 2008 Lippincott Williams & Wilkins, Inc.