ASH Clinical News April 2017 New | Page 5

2017 ; 31 ( 1 ): 77-84 .

You Made the Call

TRAINING and EDUCATION

You Make the Call

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 .

Clinical Dilemma :

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 ?

Experts Make the Call

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

The issue of anticoagulation failure is AMPLIFY trial who were initially treated for 7 days with often challenging . Whether a new thrombotic event is apixaban revealed a recurrence rate of 0.68 percent by day 7 , really new and , if so , whether the patient was adequately indicating that early recurrence is an uncommon event . 3 anticoagulated when the event occurred are often difficult Based on all of the above , I would put this patient back on to determine . This is even more difficult when a patient is apixiban , since it is at least as effective as warfarin ( with less treated with an NOAC , since dosing is not based on laboratory measurements that confirm the patient is actually However , if the patient is not achieving “ on-therapy range ”

bleeding ) and it is certainly more convenient than LMWH . adequately anticoagulated . apixaban blood levels ( i . e ., > 5th percentile trough levels ) despite taking the recommended apixaban doses , there are anti –

It is my opinion that the PE the patient suffered was not the result of anticoagulant failure for the following reasons : First , factor Xa activity assays specifically calibrated for apixaban anticoagulation is given after a venous thromboembolic event that could settle this concern . 4 , 5 ( 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

Next Month ’ s Clinical Dilemma :

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 .

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 .

A pregnant 38-year-old female was strual complaints , had genitourinary noted to have factor XI ( FXI ) deficiency surgery for repair of reflux at 8 years when the assay was ordered because of of age with no bleeding . No one in her her Jewish heritage . family has bleeding problems or is

She has never had any heavy men- known to have FXI deficiency .

She is pregnant again , with FXI levels of 39-55 percent so far . Should I follow her with observation , reserving fresh frozen plasma for bleeding events ?

Consult-a-Colleague Through ASH

Consult-a-Colleague is a service for ASH members that helps facilitate the exchange of information between hematologists and their peers . ASH members can seek consultation on clinical cases from qualified experts in 11 categories :

• Anemias

• Hematopoietic cell transplantation

• Hemoglobinopathies

• Hemostasis / thrombosis

• Lymphomas

• Lymphoproliferative disorders

• Leukemias

• Multiple myeloma & Waldenström macroglobulinemia

• Myeloproliferative disorders

• Myelodysplastic syndromes

• Thrombocytopenias

Assigned volunteers (“ colleagues ”) will respond to inquiries within two business days ( either by email or phone ).

Have a puzzling clinical dilemma ? Submit a question , and read more about Consult-a-Colleague volunteers at hematology . org / Clinicians / Consult . aspx or scan the QR code .

* If you have a request related to a hematologic disorder not listed here , please email your recommendation to ashconsult @ hematology . org so it can be considered for addition in the future .

How would you respond ? Email us at ashclinicalnews @ hematology . org or scan the QR code on your mobile device to generate an email .

34 ASH Clinical News April 2017

nosis of deep vein thrombosis ( DVT ). In this case , I would switch to therapeutic LMWH for one week , and then return to a DOAC thereafter , assuming that the patient is not on any medications that interact with a DOAC that would lower the effectiveness of apixaban , and that his body weight is less than 120 kg .

Dimitri Scarvelis , MD Ontario , Canada

First of all , there is no data to support changing to a NOAC . The underlying question is whether there is failure of the NOAC . The dyspnea may be related to pain . There was no mention of hypoxia , which would be more concerning . Heparin is not a good idea because it is difficult to get patients into the therapeutic range . LMWH would have been a better idea ; it is more reliable and a readily bioavailable drug . The only reason to use heparin would be if you thought this patient would benefit from thrombolysis and needed to stop the heparin . I would consider a month of lovenox , and would go back to a NOAC .

Lorinda A Coombs , PhDc , RN University of California San Francisco

San Francisco , CA

We asked , and you answered ! Here are a few responses from this month ’ s “ You Make the Call .”

For the full description of the clinical dilemma , and to see how the expert responded , turn to page 34 .

Clinical Dilemma :

A 53-year-old patient presented with proximal deep vein thrombosis and was discharged home on apixaban 10 mg twice daily . The patient presented to the emergency room three days later with sudden-onset shortness of breath . The computed tomography angiography was positive for pulmonary embolism . Is this failure of novel oral anticoagulant ( NOAC )? Is there any data to suggest switching to another NOAC ?

It is clearly a failure of apixaban . As in any other rare case of failure of anticoagulant therapy , provided the chosen drug was effectively administrated , my main concern is to diagnose the condition that leads to recurrence . Given the age of this patient , I would try to disclose an occult neoplasm and antiphospholipid syndrome . If the patient is stable , I would switch to enoxaparin 1 mg / kg three times a day until the workup is complete . Lupus anticoagulant can be a problem to study while on unfractionated heparin , but enzymelinked immunosorbent assays can be of value in this situation .

Jorge David Korin , MD Buenos Aires , Argentina

Is this failure of novel oral anticoagulant ( NOAC )? Yes . Is there any data to suggest switching to another NOAC ? No . What are the prescribing options ? Warfarin with international normalized ratio ( INR ) control or low-molecularweight heparin ( LMWH ).

Giuseppe Avvisati , MD , PhD Rome , Italy

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are not attained or bleeding is not controlled with appropriate dose , perform an assay to measure Factor IX inhibitor concentration . Factor IX activity assay results may vary with the type of activated partial thromboplastin time reagent used .

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* In well-controlled patients 12 years and older , defined as 1 month without spontaneous bleeding on a weekly dose of ≤40 IU / kg .

†

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I would not classify this as a failure of direct oral anticoagulant ( DOAC ) as the pulmonary embolism ( PE ) occurred within only three days of diag-

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