TRAINING and EDUCATION

Each month in “ You Make the Call ,” we ’ ll pick a challenging clinical question submitted through the Consult-a-Colleague program and post the expert ’ s response . But , what would YOU do ? We ’ ll also pose a submitted question and ask you to send your responses . See how your answer matches up to the experts in the next print issue .

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

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 ?

Joel S . Bennett , MD Professor of Medicine Division of Hematology-Oncology Perelman School of Medicine University of Pennsylvania

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

References

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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34 ASH Clinical News April 2017