Here’s a provocative question from Sacha N. Uljon, MD, PhD, Medical Director, Massachusetts General Brigham Special Coagulation Integrated Laboratory Service:
Hello, this post is about lab findings in apixaban overdose. We have now seen two suicide attempts involving apixaban. There was no clot at all on the PT/PTT (Werfen/Hemosil), so the anti-Xa level can’t be obtained. We can’t result it as “>” because there is no result. There is no HIL interference. How do I know it’s the DOAC? Offline treatment with DOAC-stop leaves some anti-Xa signal, but near-complete normalization of PT/PTT. In both cases, clots were not obtained for days after overdose.
Has anyone with Stago or Siemens seen this situation? I am interested to hear if this is a reagent-specific issue and whether others could get clots in such specimens. We ended up resulting the DOAC-stopped values with a huge disclaimer, but this is non-ideal from a medical-legal point of view. If it’s reagent specific, I’m thinking of bringing back the Stago PT/PTT offline for these cases. Sacha.
Here’s a 10-23-26 response from Paul Riley, PhD, MBA, Scientific Market Development Manager, Diagnostica Stago:
George spoke with a colleague and coagulation expert, Dave McGlasson, MS, MLS, who indicated that, regrettably, the DOAC-Dipstick, which accurately detects urine DOACs, is not FDA-approved and is not marketed in the USA.
Here is a response from Ali Sadeghi-Khomami, PhD, PBI: Hi George, Hope all is well with you and your family. How do I know it is a DOAC?
For medico-legal justification, the only definitive answer would be provided by LC-MS. There are, however, other indirect and less certain methods available:
- The DOAC Dipstick has a specificity of approximately 70%.
- Testing before and after DOAC-STOP, followed by an anti-Xa chromogenic assay or PT assay, is also not entirely specific but could indirectly support the case.
- Overall, apixaban has less impact on clot-based assays, and anti-Xa chromogenic assays are more appropriate for detecting apixaban in plasma samples.
It is well known that DOAC anti-Xa agents have a greater impact on PT prolongation than on PTT, and reagent sensitivity to them varies among commercial products (IL PT > Stago PT). So, if you need to mask the impact, you have a better chance with the Stago PT reagent. Click here to see an open-access article regarding the effect of apixaban on various PT and PTT reagents: Hillarp A, Gustafsson KM, Faxälv L, et al. Effects of the oral, direct factor Xa inhibitor apixaban on routine coagulation assays and anti-FXa assays. J Thromb Haemost. 2014;12(9):1545-53. doi: 10.1111/jth.12649. PMID: 24965851. Check Table 2 for the effects of apixaban on a series of PT thromboplastin reagents.
Summary
Introduction
Objectives
Materials and Methods
Results
Conclusions
Therapeutic concentrations of apixaban variably affect different assay groups, and even different reagents within an assay group. The effects were much smaller than with rivaroxaban. The use of APTT and/or PT assays to screen the anticoagulant activity of apixaban cannot be recommended. A chromogenic anti‐FXa assay can be used for reliable measurements of apixaban concentration.
10-27-26: In a chat with friend and colleague Dan Kaczor, Dan asked, ” Can we just prepare serial dilutions of the sample, run the anti-Xa assay, and locate the dilution that falls in the linear range?” This is a time-honored approach to many assays and enables us to estimate the analyte concentration, i. e., the level of DOAC overdose. Could we then employ this approach to manage DOAC levels?
You may wish to obtain this timely DOAC management review from your medical library: Reilly-Stitt C. Laboratory testing of direct oral anticoagulants. Handb Exp Pharmacol. 2026;291:123-133. doi: 10.1007/164_2025_783. PMID: 41398102.
Abstract
Direct oral anticoagulants (DOACs), also referred to as non-vitamin K oral anticoagulants (NOACs), have revolutionised anticoagulant therapy since their introduction in the late 2000s. These agents – dabigatran (a direct thrombin inhibitor) and the factor Xa inhibitors apixaban, edoxaban, and rivaroxaban – offer more predictable pharmacokinetics, fewer food and drug interactions, and do not typically require routine laboratory monitoring, unlike traditional anticoagulants such as warfarin and heparin. Despite these advantages, laboratory assessment of DOAC activity remains clinically important in specific circumstances, including bleeding, thrombosis during therapy, emergency surgery, renal or hepatic impairment, and suspected non-compliance.This chapter reviews the pharmacology, clinical applications, and laboratory evaluation of DOACs, outlining available assays and their principles. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the gold standard for quantification, though chromogenic anti-Xa and dilute thrombin time (DTT) or ecarin-based assays are more commonly used in clinical laboratories. The impact of DOACs on routine coagulation tests such as PT, APTT, and TT varies by reagent and is inconsistent, underscoring the need for drug-specific calibrators and assay validation. Quality assurance through both internal quality control (IQC) and external quality assessment (EQA) is essential to maintain assay accuracy and reproducibility, in accordance with ISO 15189:2022 standards. Furthermore, DOACs can interfere with other haemostasis assays – including factor assays, antithrombin, and lupus anticoagulant testing – leading to potential diagnostic errors. Recent studies demonstrate that activated charcoal-based reagents, such as DOAC Remove™ and DOAC Stop™, can effectively neutralise DOAC interference in such assays.In conclusion, while DOACs have largely supplanted warfarin in the management of non-valvular atrial fibrillation and venous thromboembolism due to their safety and convenience, laboratory testing retains a critical role in ensuring safe and effective patient management under specific clinical scenarios.
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