Lupus anticoagulant, warfarin, and alternative laboratory monitoring of anticoagulation

Abstract

A 53 year old woman was evaluated for recurrent native and prosthetic mitral valve thromboembolism in the setting of antiphospholipid antibody syndrome. In 1989, at age 30 years, she suffered a thromboembolic stroke and was diagnosed with antiphospholipid antibody syndrome for which long-term warfarin therapy was prescribed. She was subsequently assigned a goal international normalized ratio (INR) of 2.5–3.5. In 2008, at age 49 years, she was diagnosed with mitral valve stenosis and underwent mitral valve replacement (29 mm Carbomedics prosthesis). Pathology was consistent with nonbacterial thrombotic endocarditis involving a fibrotic and focally calcified mitral valve. After valve replacement, the target INR range was increased to 3.0–4.0. Nine months later, she developed thrombosis of the prosthetic mitral valve and required redo valve replacement surgery (27 mm St. Jude Biocor). Postoperatively, she developed heparin induced thrombocytopenia (HIT) for which she received argatroban while transitioning to warfarin. Her target INR range was subsequently increased to 3.5–4.5. In 2012, she developed recurrent prosthetic mitral valve thrombosis despite being mostly therapeutic(INR 3.5–4.5) and at times supra-therapeutic with INR monitoring. Transesophageal echocardiogram confirmed an 8 mm thick layer of organized thrombus encasing each of the prosthetic mitral valve leaflets with severe valvular stenosis. Laboratory testing upon admission revealed a prothrombin time (PT) of 101.7s (INR 11.1). Simultaneously measured chromogenic factor X activity was 20 % (therapeutic range 20–35 %) and factor II activity was 14 % (normal reference range 75–145 %), confirming adequate anticoagulation at that time. A third mitral valve replacement procedure was pursued (27 mm Hancock II bioprosthesis) and she was yet again restarted on warfarin postoperatively. Initial special coagulation testing done at our institution in 1989 established the presence of a lupus anticoagulant (LAC). This diagnosis was subsequently confirmed on four occasions (1995–2012). Prior to 2004, the LAC assays were performed using the dilute Russel viper venom time (DRVVT) assay kit from American Diagnostica (Stamford, CT). After 2004, the DRVVT assay was performed using the kit from Precision Biologics (Dartmouth, NS, Canada) following the manufacturer’s instructions. She had a persistently high titer of anticardiolipin antibodies (IgG and IgM) as well. Her baseline prothrombin PT (11.3s) and INR (1.1), were normal and remained so until 2012, when measured during brief interruptions of warfarin anticoagulation (six occasions; 1995–2011). Prior to 2009, the PT assay was performed with Innovin (Siemens, New York, NY formerly Dade Behring, Deerfield, IL). Beginning in 2009, the PT was performed with Recombiplastin 2G (Instrumentation Laboratories, Bedford, MA). The temporal trends in INR and chromogenic factor X activity are shown in Fig. 1. Since INR differences are much larger at low factor activities than at high activities, we compared the log INR with the factor activities. Log INR did not correlate well with chromogenic factor X activity (Fig. 2a, r = 0.32) and factor II (Fig. 2b, S. S. Ketha (&) R. D. McBane W. E. Wysokinski Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Gonda 4-130 (VM), 200 First St. SW, Rochester, MN 55905, USA e-mail: Ketha.Siva@mayo.edu