Recombinant Thromboplastin Reagents and High Titer Antiphospholipid Antibodies

Introduction The determination of prothrombin time (PT) is increasingly performed using recombinant tissue factor preparations, like Innovin or PT Rec. The phospholipid composition of these reagents is especially sensitive to antiphospholipid antibodies, leading, in some cases, to artificially prolonged clotting times. As thromboprophylaxis for such patients is basically restricted to vitamin K antagonists, therapy monitoring is negatively impacted. Also, a significant portion of patients with highly volatile prothrombin time results, that are referred to our outpatient clinic, are found to have antiphospholipid antibodies. PT reagents from native sources, like placenta or rabbit brain, may improve testing. Finally, in many cases, sample dilution like in the Hepato Prest assay is required for reliable monitoring. Method This study includes 30 patients with high-titer antiphospholipid antibodies. PT was assessed using PT Rec (Roche Diagnostics), Innovin and Thromborel S (Siemens Healthineers) and Hepato Prest (Stago). Lupus Anticoagulant was determined using LA1/LA2 (Siemens Healthineers), aPTT HS (Stago). Anti-cardiolipin and anti-ß2-glycoprotein I antibodies were quantified on the BioFlash analyzer (Werfen), anti-prothrombin and anti-phosphatidylserine antibodies were assessed by ELISA (Orgentec). Results In 15 patients (50%) we observed significantly prolonged PT results with recombinant reagents compared to the Hepato Prest assay, with Innovin being slightly less sensitive than PT Rec . In some cases Thromborel S is sufficient for PT measurement, although we often observed INR values somewhere between the recombinant reagents and the Hepato Prest assay. LA1/LA2 is sensitive for most antiphosphoslipid antibodies, but in four cases (13%) showed no abnormality. The direct determination of coagulation factors can be impacted by antiphospholipid antibodies. In some cases factors II, V, VIII and X have to be assessed using reagents less sensitive to antiphospholipid antibodies. Conclusion The determination of prothrombin time may be significantly impacted by antiphospholipid antibodies. Generally, a very heterogeneous pattern is observed that requires sophisticated interpretation of laboratory findings. Antiphospholipid antibodies may lead to a significant overestimation of the therapeutic effect. Special attention has to be given to patients with highly volatile PT result under vitamin K antagonist therapy. Antiphospholipid antibodies are found in a substantial proportion in this patient group. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany