ORIGINAL ARTICLE Monitoring anticoagulant therapy with vitamin K antagonists in patients with antiphospholipid syndrome Mecki Isert 1 & Wolfgang Miesbach 2 & Gundolf Schüttfort 1 & Yvonne Weil 1 & Vanessa Tirneci 1 & Alexander Kasper 1 & Adele Weber 1 & Edelgard Lindhoff-Last 1 & Eva Herrmann 3 & Birgit Linnemann 1 Received: 28 December 2014 /Accepted: 30 March 2015 # Springer-Verlag Berlin Heidelberg 2015 Abstract Because of the possible interference of antiphospholipid antibodies (APL) with the phospholipid component of thromboplastin reagents, concerns have been raised about the validity of international normalized ratio (INR) testing to monitor anticoagulant therapy with vitamin K antagonists in patients with antiphospholipid syndrome (APS). To investigate the reliability of the INR, we determined the INR using various prothrombin time (PT) assays and com- pared the results with those of a chromogenic factor X (CFX) assay. The study cohort consisted of 40 APS patients and 100 APL-negative patients who were on anticoagulant therapy for reasons other than APS. The agreement (i.e. the percentage of patients with a difference ≤0.5 INR units) between the PT- derived INR and CFX-derived INR equivalents was only moderate in both patient groups. The best agreement with CFX-derived INR equivalents was observed for the Thromborel S reagent in APS patients (69.1 %) and for Neoplastin Plus in APL-negative patients (72.0 %). Regarding the results for the point-of-care system CoaguChek XS, an agreement between the INR and the CFX-derived INR equiv- alent was less frequently observed in the APS patients (55.6 vs. 67.8 %; p =0.050). When considering all 3058 pairs of INR tests within the international sensitivity index (ISI)- calibrated range of 1.5 to 4.5 s, we did not observe a higher variability of INR values in either the APS patient group or the subgroup of APS patients positive for lupus coagulants com- pared with the APL-negative controls. In conclusion, moni- toring vitamin K antagonists (VKA) therapy with laboratory INR measurements seems to be suitable for the majority of APS patients. Keywords Antiphospholipid syndrome . Lupus anticoagulants . International normalized ratio . Chromogenic factor X assay . Anticoagulant therapy Introduction Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the occurrence of vascular thrombosis or pregnancy complications [1, 2]. Anticoagulant therapy has been shown to be highly effective in preventing recurrent thrombotic events. Despite the advantages of anticoagulant therapy, APS patients remain at high risk of developing future thromboembolic events. Pengo et al. followed 160 patients with APS who were triple-positive (i.e. the presence of lupus anticoagulant, anticardiolipin and anti-beta-2-glycoprotein-I antibodies) and reported a cumulative incidence of 29 % for subsequent thromboembolism among APS patients during long-term oral anticoagulant treatment [3]. Vitamin K antagonists (VKA) are the therapy of choice for a long-term anticoagulant therapy, but adequate dosing re- quires rigid laboratory monitoring. VKA therapy is monitored using the international normalized ratio (INR), which is de- rived from the prothrombin time (PT) and the appropriate international sensitivity index (ISI) of the thromboplastin used in the PT test system [4, 5]. However, some PT assays have been demonstrated to be sensitive to the effects of lupus * Birgit Linnemann Birgit.Linnemann@kgu.de 1 Division of Vascular Medicine, Department of Internal Medicine, Goethe University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt/ Main, Germany 2 Frankfurt Haemophilia Center, Institute of Transfusion Medicine, Goethe University Hospital, Frankfurt/Main, Germany 3 Institute of Biostatistics and Math, Modelling, Faculty of Medicine, Goethe University Hospital, Frankfurt/Main, Germany Ann Hematol DOI 10.1007/s00277-015-2374-3