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What are the prescribing options in the case of anticoagulation failure in deep vein thrombosis?

December 30, 2021
Joel S. Bennett, MD
Professor of Medicine, Division of Hematology-Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

This month, Joel S. Bennett, MD, discusses the possibility of novel oral anticoagulant failure in a patient with deep vein thrombosis.

And don’t forget to check out next month’s clinical dilemma – send in your responses for a chance to win an ASH Clinical News-themed prize!


I have a 53-year-old patient who works as a consultant with frequent travel in the United States. There is no significant past medical history, and the patient is very active. There is a family history of thrombophilia in the fifth decade. The patient presented with proximal deep vein thrombosis (DVT) and was discharged home on apixaban 10 mg twice daily. The patient presented to the emergency room 3 days later with sudden onset shortness of breath. The computed tomography angiography was positive for pulmonary embolism (PE). The patient is compliant with taking the prescribed dose of apixaban. The patient is currently on intravenous heparin. Is this failure of novel oral anticoagulant (NOAC)? Is there any data to suggest switching to another NOAC? What are the prescribing options?


The issue of anticoagulation failure is often challenging. Whether a new thrombotic event is really new and, if so, whether the patient was adequately anticoagulated when the event occurred are often difficult to determine. This is even more difficult when a patient is treated with an NOAC, since dosing is not based on laboratory measurements that confirm the patient is actually adequately anticoagulated.

It is my opinion that the PE the patient suffered was not the result of anticoagulant failure for the following reasons: First, anticoagulation is given after a venous thromboembolic event (VTE) to prevent further thrombosis. It does not cause the lysis or organization of the existing thrombi. Thus, it would seem intuitively possible that for a period of time, a piece of an existing clot could "break off" and embolize until either endogenous clot lysis or organization occurs.

Second, reviews of the natural history of VTE have shown that asymptomatic clot extension is common during the initial phase of therapy when patients are treated with low-molecular-weight heparin (LMWH) or unfractionated heparin.1,2 Further, the resolution of DVT in anticoagulated patients can be slow. Lastly, a sub-analysis of patients in the AMPLIFY trial who were initially treated for 7 days with apixaban revealed a recurrence rate of 0.68 percent by day 7, indicating that early recurrence is an uncommon event.3

Based on all of the above, I would put this patient back on apixiban, since it is at least as effective as warfarin (with less bleeding) and it is certainly more convenient than LMWH. However, if the patient is not achieving "on-therapy range" apixaban blood levels (i.e., >5th percentile trough levels) despite taking the recommended apixaban doses, there are anti–factor Xa activity assays specifically calibrated for apixaban that could settle this concern.4,5


  1. Kearon C. Natural history of venous thromboembolism. Circulation. 2003;107(23 Suppl 1):I22-30.
  2. Basu D, Gallus A, Hirsh J, Cade J. A prospective study of the value of monitoring heparin treatment with the activated partial thromboplastin time. N Engl J Med. 1972;287(7):324-27.
  3. Raskob GE, Gallus AS, Sanders P, et al. Early time courses of recurrent thromboembolism and bleeding during apixaban or enoxaparin/warfarin therapy. A sub-analysis of the AMPLIFY trial. Thromb Haemost. 2016;115(4):809-16.
  4. Ward C, Conner G, Donnan G, Gallus A, McRae S. Practical management of patients on apixaban: a consensus guide. Thromb J. 2013;11(1):27.
  5. Samuelson BT, Cuker A. Measurement and reversal of the direct oral anticoagulants. Blood Rev. 2017;31(1):77-84.

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Disclaimer: ASH does not recommend or endorse any specific tests, physicians, products, procedures, or opinions, and disclaims any representation, warranty, or guaranty as to the same. Reliance on any information provided in this article is solely at your own risk.


I have a pregnant 38-year-old female patient who was noted to have factor XI (FXI) deficiency when an assay was ordered because of her Jewish heritage. She has never had any heavy menstrual complaints, had genitourinary (GU) surgery for repair of reflux at age 8 with no bleeding, and had her wisdom teeth removed with no excess bleeding. No one in her family has bleeding problems or is known to have FXI deficiency. FXI runs 39-55 percent so far. I was thinking of observation and reserving fresh frozen plasma (FFP) for bleeding. Thoughts?

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