June 2026

STOPPING THE DOACs – NEWS ON NEUTRALISERS

Whatever happened to andexanet.alfa? The withdrawal of Andexanet alfa (Andexxa, Astra Zeneca), until recently the only approved reversal agent for factor Xa direct oral anticoagulants, has reopened an important clinical and commercial gap in urgent bleeding management. In a December 2025 safety communication, the FDA said postmarketing data showed serious and fatal thromboembolic events and concluded that the product’s risks outweighed its benefits. That safety signal is not entirely surprising. Earlier concern about procoagulant activity by Saddiqui and others (2019) has been supported by mechanistic work from Hoornstra et al. (2025), which suggests Andexanet alfa can promote clotting not only by reversing anti factor Xa DOACs but also by suppressing natural antithrombotic pathways, including tissue factor pathway inhibitor. Against this backdrop, VMX-C001 from VarmX (Netherlands, project funded by CSL) is emerging as a potentially important alternative. Described recently as a novel recombinant modified factor X protein designed to bypass anti factor Xa DOAC activity, it appears remarkably similar to Andexanet alfa as a DOAC absorber. Nagy M, Gomes T, van Oerle R, Hacking TM, Magdelijns FJH, Henskens YMC, Reitsma P, Short G, Spronk HMH, Verhoef D. Coagulation assays for assessing the bypassing of factor Xa direct oral anticoagulants using VMX-C001. Res Pract Thromb Haemost. 2026 Feb 2;10(2):103375.PMC13053743. The binding site for DOACs has been modified by some 16 amino acids but it retains the phospholipid binding domain deleted in Andexxa.  Laboratory comparisons of Andexxa and VMX-C001 have been carried out using dilute PT and dRVVT clotting tests at VARMX and these show equivalent neutralization of apixaban and rivaroxaban. It remains to be seen if clinical trials can confirm effective reversal without reproducing the thrombotic liabilities that undermined Andexxa.  

Antibodies to the task

In another major development researchers at the Synapse Institute in Maastricht (owned by Diagnostica Stago) have developed monoclonal antibodies specific for neutralizing apixaban, rivaroxaban and edoxaban. “These low-cost reversal agents work directly on plasma or whole blood without incubation or preanalytical steps and may enable rapid, reliable baseline coagulation testing in patients treated with these DOACs”. Zhao J, Hoornstra I, Huskens D, Swieringa F, Stroobants AK, Rijpma S, Heylen R, de Laat B, Roest M. Single-domain antibodies to reverse the effects of factor Xa inhibitors on coagulation tests. J Thromb Haemost. 2026 Apr 20:S1538-7836(26)00264-3.  

DOAC-Stop™ stands the test of time

In comparison with these direct-acting products DOAC StopTM offers a more general adsorbent for all DOACs and related compounds, including the FXIa inhibitors and bivalirudin. It does require a mix-spin but has an advantage of a proven history of 7 years of use without problems. Exner T, Ahuja M, Ellwood L. Effect of an activated charcoal product (DOAC Stop™) intended for extracting DOACs on various other APTT-prolonging anticoagulants. Clin Chem Lab Med. 2019 Apr 24;57(5):690-696.

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