Impact of Lupus Anticoagulant on INR Using Recombinant Prothrombin Time Reagent

Abstract

BACKGROUND Lupus anticoagulants (LA) can interfere with routine coagulation tests such as the activated partial thromboplastin time (aPTT) and prothrombin time (PT). The international normalized ratio (INR) is derived from PT and is used to monitor warfarin therapy. A positive LA result is one of the laboratory criteria of the 2023 ACR/EULAR antiphospholipid syndrome (APS) classification criteria. We report a case in which LA interfered with INR measurement in an APS patient. CASE REPORT Our patient was a 45-year-old man who had experienced multiple episodes of thromboembolism. His INR was consistently high, despite not being on any anticoagulant. Our laboratory used a recombinant PT reagent, Siemens Healthineers Dade® Innovin® on a fully automated coagulometer, the Sysmex CS-2500. PT measurements were repeated using 2 different analyzers, the Sysmex CA-104 and Werfen ACL Top 550 CTS. The PT results were 40.5 s (reference range (RR): 9.3-10.8 s) and 56 s, using Sysmex CS2500 and CS104, respectively. However, the PT was 13.4 s (RI: 10.3-12.7 s) using Werfen ACL Top 550 CTS. We retested the sample using Thromborel® S, a tissue-derived PT reagent, and PT was found to be within the reference range. The patient tested positive for LA, anti-cardiolipin, and anti-beta2 glycoprotein I antibodies. CONCLUSIONS LA can falsely prolong the PT when a recombinant PT reagent is used. When we retested the plasma using a tissue-derived PT reagent - Thromborel® S - PT was within normal limits. Thus, it is important to acknowledge that LA can react differently with different PT reagents.