Abstract
Thrombophilia is responsible for a majority of unprovoked vascular thrombotic events, with a positivity rate of approximately 65 percent. Thrombophilia is diagnosed by a combination of genetic, activity-based, antigenic, and serologic tests. These evaluations incur significant costs and frequently require unnecessary consultation with specialists. Many of the tests also require follow-up to exclude transient alterations. In order to improve diagnostic yield, screening guidelines for inherited and acquired thrombophilia have been published by the College of American Pathologists and the International Society of Thrombosis and Haemostasis. This study evaluates diagnostic yield and adherence to clinical guidelines for thrombophilia screening at a major university teaching hospital.
We performed a retrospective review of laboratory Results for thrombophilia screening tests ordered between August 2010 and June 2013. A thrombophilia workup panel was defined as a group of 2 or more thrombophilia tests, including but not limited to protein C (PC), protein S (PS), and antithrombin (AT) activity. For activity-based and PS free antigen testing, the appropriate confirmatory period was defined as at least 30 days from the initial testing date. For LA and/or serologic evidence of anti-phospholipid antibodies, the appropriate confirmatory period was defined as at least 12 weeks from the initial testing date.
Subsequently, approximately 10 percent of the charts were randomly selected for complete chart review. Chart histories were evaluated to assess compliance with the screening guidelines published by the College of American Pathologists and the International Society of Thrombosis and Hemostasis. Patients younger than 18 years of age and charts with inadequate documentation were excluded from full review.
We identified a total of 2081 patients who had thrombophilia screening, representing 4630 unique thrombophilia panels. First time panel orders had an 18% positivity rate, which was significantly lower than the expected positivity rate if guidelines were followed (p<0.01). Appropriate confirmatory testing of PC, PS, and AT deficiencies was performed in 6.0%, 13%, and 4.6% of cases, respectively. Verification of lupus anticoagulant (LA) and/or serologic anti-phospholipid antibodies (aPLs) was performed in 17% of cases. Overall, only 12% of abnormal Results had appropriate follow-up. When repeated, 40% of AT, 46% of PC, 50% of PS, and 39% of LA remained abnormal.
Of the 213 charts reviewed, 113 were excluded due to insufficient documentation. Of the remaining 100 charts, only 27% followed the guidelines for both inherited and acquired thrombophilia screening. Inherited thrombophilia screening was more frequently ordered incorrectly (65%) than acquired thrombophilia screening (44%). Overall, 14% of incorrectly ordered panels were due to medication interactions, 95% due to incorrect indications, and 8% due to both reasons. We further evaluated appropriateness of thrombophilia screening by clinical service. Hematologists and oncologists most frequently followed screening guidelines (61%), followed by internists (40%), transplant surgeons (19%), and obstetrics/gynecologist (15%). Neurologists and nephrologists both had 0% percent adherence to screening guidelines.
The majority of thrombophilia screening is ordered in the absence of adequate clinical indications and confirmatory testing is inconsistently performed. This leads to significantly increases in costs associated with improper testing and inadequate diagnosis of thrombophilia due to insufficient follow-up. Our study demonstrates an urgent need for educating health care professionals on the appropriate ordering of thrombophilia screening tests and for implementing laboratory intervention for incorrectly ordered tests.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
