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Optimizing diagnostic testing for venous thromboembolism

Cleveland Clinic Journal of Medicine. 2017 July;84(7):545-554 | 10.3949/ccjm.84a.16049
July 1, 2017|Cleveland Clinic Journal of Medicine
Patrick Rendon, MD;Allison E. Burnett, PharmD, PhD, CACP;Jessica Zimmerberg-Helms, MD;Taylor Goot, MD;Michael B. Streiff, MD
Author and Disclosure Information

Patrick Rendon, MD
Assistant Professor, Department of Internal Medicine, University of New Mexico Hospital, Albuquerque, NM

Allison E. Burnett, PharmD, PhD, CACP
Clinical Assistant Professor, University of New Mexico College of Pharmacy, Inpatient Antithrombosis Service, University of New Mexico Hospital, Albuquerque, NM

Jessica Zimmerberg-Helms, MD
Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM

Taylor Goot, MD
Assistant Professor, Department of Internal Medicine, The University of New Mexico Health Sciences Center, Albuquerque, NM

Michael B. Streiff, MD
Associate Professor, Department of Medicine, Division of Hematology, Johns Hopkins School of Medicine, Baltimore, MD

Address: Patrick Rendon, MD, Department of Internal Medicine, University of New Mexico Hospital, MSC 10 5550 – 1 University of New Mexico, Albuquerque, NM 87131-0001; prendon@salud.unm.edu

Dr. Streiff has disclosed that he is an independent contractor or consultant for Boehringer Ingelheim, Janssen Research & Development, Portola Pharmaceuticals, and Roche Diagnostics.

ABSTRACT

Diagnostic algorithms for venous thromboembolism exist, but most do not provide detailed guidance as to which patients, if any, may benefit from screening for thrombophilia. This article provides an overview of the optimized diagnosis of venous thromboembolism, with a focus on the appropriate use of thrombophilia screening.

KEY POINTS

  • A pretest clinical prediction tool such as the Wells score can help in deciding whether a patient with suspected venous thromboembolism warrants further workup.
  • A clinical prediction tool should be used in concert with additional laboratory testing (eg, D-dimer) and imaging in patients at risk.
  • In many cases, screening for thrombophilia to determine the cause of a venous thromboembolic event may be unwarranted.
  • Testing for thrombophilia should be based on whether a venous thromboembolic event was provoked or unprovoked.

WHAT IF VENOUS THROMBOEMBOLISM IS DISCOVERED INCIDENTALLY?

Thrombophilia testing should be approached the same regardless of whether the venous thromboembolism was diagnosed intentionally or incidentally. First, determine whether the thrombosis was provoked or unprovoked, then order additional tests only if indicated, as recommended. Alternative approaches such as forgoing anticoagulation (but performing serial imaging, if indicated) may be reasonable if the thrombus is deemed clinically irrelevant (eg, nonocclusive, asymptomatic, subsegmental pulmonary embolism in the absence of proximal deep vein thrombosis; isolated distal deep vein thrombosis).25,27

It is still debatable whether the increasing incidence of asymptomatic pulmonary embolism due to enhanced sensitivity of noninvasive diagnostic imaging warrants a change in diagnostic approach.28

FACTORS TO CONSIDER BEFORE THROMBOPHILIA TESTING

Important factors to consider before testing for thrombophilia are29:

  • How will the results affect the anticoagulation plan?
  • How may the patient’s clinical status and medications influence the results?
  • Has the patient expressed a desire to understand why venous thromboembolism occurred?
  • Will the results have a potential impact on the patient’s family members?

Tests for thrombophilia
If testing is to be done (Table 4), it is important that patients first have a full course of anticoagulation for the index event and then be off anticoagulation for an appropriate interval before the test.

How will the results of thrombophilia testing affect anticoagulation management?

Because the goal of any diagnostic test is to find out what type of care the patient needs, clinicians must determine whether knowledge of an underlying thrombophilia will alter the short-term or long-term anticoagulation therapy the patient is receiving for an acute venous thromboembolic event.

As most acute episodes of venous thromboembolism require an initial 3 months of anticoagulation (with the exception of some nonclinically relevant events such as isolated distal deep vein thrombosis without extension on reimaging), testing in the acute setting does not change the short-term management of anticoagulation. Many hospitals have advocated for outpatient-only thrombophilia testing (if testing does occur), as testing in the acute setting may render test results uninterpretable (see What factors can influence thrombophilia testing? below) and can inappropriately affect the long-term management of anticoagulation. We recommend against testing in the inpatient setting.

To determine the duration of anticoagulation, clinicians must balance the risk of recurrent venous thromboembolism and the risk of bleeding. If a patient is at significant risk of bleeding or does not tolerate anticoagulation, clinicians may consider stopping therapy instead of evaluating for thrombophilia. For patients with provoked venous thromboembolism, anticoagulation should generally be limited to 3 months, as the risk of recurrence does not outweigh the risk of bleeding with continued anticoagulation therapy.

Patients with unprovoked venous thromboembolism have a risk of recurrence twice as high as those with provoked venous thromboembolism and generally need a longer duration of anticoagulation.30,31 Once a patient with an unprovoked venous thromboembolic event has completed the initial 3 months of anticoagulation, a formal risk-benefit evaluation should be performed to determine whether to continue it.

Up to 42% of patients with unprovoked venous thromboembolism may have 1 or more thrombotic disorders, and some clinicians believe that detecting an underlying thrombophilia will aid in decisions regarding duration of therapy.32 However, the risk of recurrent venous thromboembolism in these patients does not differ significantly from that in patients without an underlying thrombophilia.33–35 As such, it has been suggested that the unprovoked character of the thrombotic event, rather than an underlying thrombophilia, determines the risk of future recurrence and should be used instead of testing to guide the duration of anticoagulation therapy.32

For more information, see the 2016 ACCP guideline update on antithrombotic therapy for venous thromboembolism.27

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