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Testing for Inherited Thrombophilias Provides Limited Benefit

December 30, 2021

Inherited thrombophilias are associated with an increased risk of initial and recurrent venous thromboembolism (VTE), but testing for these conditions in the setting of an acute venous or arterial thrombotic event offers little benefit, according to research presented at the 2020 ASH Annual Meeting.

Other risk factors, such as cancer, hypertension, or smoking, may be more clinically useful for making decisions about use and duration of anticoagulation, said study author Ruben Rhoades, MD, from Thomas Jefferson University in Philadelphia, Pennsylvania.

To determine the utility of this type of testing, Dr. Rhoades reviewed all instances of inpatient inherited thrombophilia testing in 2019 at Thomas Jefferson University Hospitals, including three primary hospitals in Philadelphia. The types of tests included tests for the following conditions: factor V Leiden (FVL); prothrombin G20210A mutation; protein C, S, and antithrombin deficiency; hyperhomocysteinemia; and plasminogen activator inhibitor-1 (PAI-1) elevation.

In total, 231 patients underwent 872 tests for inherited thrombophilias. The patients' median age was 50.8 years, and 129 (55.8%) were female.

Tests were ordered most commonly after a thrombosis/arterial ischemic event (n=126; 54.5%), the most common of which was stroke or transient ischemic attack (n=94; 40.7%). Approximately one-quarter of patients had a VTE that prompted thrombophilias testing (n=60; 26%). However, in 14.7% of patients, there was no documented thrombosis, ischemic event, or pregnancy complication that led to testing.

In the group of patients who experienced an arterial ischemic/thrombotic event, more than three-quarters of patients had at least one documented risk factor for this type of event.

The most frequently observed risk factors included:

  • hypertension (n=61; 45.9%)
  • smoking (n=32; 24.1%)
  • hyperlipidemia (n=28; 21.1%)
  • diabetes mellitus (n=25; 18.8%)

In those who experienced VTE that led to thrombophilia testing, one-third, or 32.8%, had an underlying risk factor. The two most common risk factors were pregnancy/hormones (n=7; 10.4%) and cancer (n=6; 9%).

Of the 872 tests ordered, 5 of every 6 tests ordered, or 83.3%, were negative for inherited thrombophilias, Dr. Rhoades reported. Testing for specific genetic mutations was negative in most cases, including in 98% of tests evaluating prothrombin and 89% of tests evaluating FVL mutation. Positive tests were most often seen in tests that evaluated MTHFR mutation (76.0%), antithrombin (36.0%), protein C antigen (40.0%), PAI-1 (33.3%), and total protein S (22.2%). Many of the abnormal test results – especially for antithrombin and protein C/S testing – were below the range of normal, but not in a clinically relevant range, suggesting the presence of false positives due to being ordered in the acute setting.

As seen in the TABLE, the likelihood of an abnormal result was not significantly different among patients with or without an underlying risk factor. Also, after reviewing charts and inpatient and outpatient notes, "In all but three instances, covering just two patients, there were clearly no changes made in clinical management as a result of a positive test," Dr. Rhoades noted. "And, in those two patients, based on the available documentation, it was unclear whether anticoagulation was started because of FVL or other reasons."

Despite their limited clinical utility, the costs of these tests are high, he added, and were associated with $398,912 in total charges to the hospitals. "These data justify education and pathway implementation aimed at decreasing inpatient utilization of thrombophilia tests."

However, the implications of this study are limited by the single-center, retrospective design.

The authors report no relevant conflicts of interest.


Rhoades R. Inpatient inherited thrombophilia testing at an academic health center: high cost, low value. Abstract #1625. Presented at the 2020 American Society of Hematology Annual Meeting, December 5, 2020.


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