The Utility of International Normalized Ratio Monitoring in Antiphopholipid Syndrome and Lupus Anticoagulant

Abstract

INTRODUCTION: Antiphospholipid syndrome (APS) is an autoimmune condition characterized by recurrent thrombosis (1). Warfarin therapy is commonly given to preclude thrombotic events, with goal international normalized ratio (INR) between 2 and 3. However, a subset of patients with APS/Lupus anticoagulant (LA) positive status, are more prone to thrombotic events and may need higher INR levels (2). Additionally, end stage renal disease (ESRD) patients require 20% less warfarin to achieve the same INR (3). This index case further highlights the challenges of therapeutic anticoagulation with warfarin in patients with APS/ LA. CASE PRESENTATION: A 49 year old African American female with ESRD on hemodialysis, APS/LA antibodies, multiple thromboembolisms with IVC filter in-situ on lifelong warfarin, morbid obesity and atrial fibrillation presented to the emergency room. She was sent from the clinic for arteriovenous fistula (AVF) revision for concerns of ulcerations, bleeding and swelling at the fistula site. On presentation, her vitals were blood pressure 92/49, pulse 84, respiratory rate 20 with oxygen saturation of 100% on 3L of oxygen. On examination her left arm AVF had multiple small non-bleeding superficial ulcerations, with no palpable thrill. She was admitted for a non-functioning, possibly infected, AVF and subsequently bridged to unfractionated heparin in preparation for AVF repair. The procedure was successful, and attempts were made to recommence warfarin monotherapy. Despite incremental increases in warfarin while on heparin infusion, her INR was subtherapeutic. On day 23, she had hemoptysis with an INR of 2.20. There was no evidence of liver disease and no drug to drug interaction with warfarin. She was eventually discharged on warfarin 70 mg daily with an INR of 2.47 and no evidence of bleeding for outpatient follow-up. DISCUSSION: The use of INR to guide warfarin therapy is notoriously problematic in APS/LA patients. LA antibodies result in falsely elevated INR levels making it unreliable for warfarin monitoring, with no clear consensus of goal INR. Specific tests such as chromogenic factor X, which is more accurate than INR, are expensive and not readily available. Additionally, alternatives such as direct oral anticoagulants have not been adequately studied (1,4). Further confounding factors such as ESRD and hemoptysis at therapeutic INR make this case more challenging. CONCLUSIONS: The utility of monitoring INR while on warfarin therapy in APS/LA and ESRD patients can be unreliable. Further studies are needed to elucidate a protocolized approach for this specific patient cohort and to edify and guide their physicians.