Choosing Wisely in Thrombophilia: Hematologist Required

Background: Selection for thrombophilia testing among patients with venous thromboembolism (VTE) is controversial. Choosing Wisely guidelines published by the American Society of Hematology (ASH) recommend against testing patients with VTE provoked by the major transient risk factors of major surgery, immobility and trauma. Testing is most often considered in patients with recurrent VTE, unprovoked VTE, VTE occurring in an unusual site, and a significant family history of VTE. The purpose of this study was to review the practices in thrombophilia testing at Jersey Shore University Medical Center (JSUMC) and Ocean Medical Center (OMC) with respect to these recent recommendations.

Methods: A retrospective review at JSUMC and OMC was performed of all adult in-patients who received thrombophilia testing for VTE from November 5, 2014 to May 26, 2015. Baseline characteristics, clinical data, VTE risk factors, and test results were collected. Data were analyzed using Fisher exact tests.

Results: Sixty patients were included in this review. Inherited thrombophilias were identified in 16 (26.7%), and acquired thrombophilias were identified in 11 (18.3%). Thrombophilia testing was ordered for 23 patients with provoked VTE, 16 of which had the major transient risk factors of major surgery, immobility and trauma. Testing in these patients would have been excluded by the Choosing Wisely recommendations. The other seven patients whose VTE was provoked had risk factors of oral contraceptives, central venous catheters, malignancy, prolonged travel and active smoking. In this group of 23 VTE provoked patients, positive hypercoagulation tests were seen in eight patients. Hereditary hypercoagulation tests were positive in six patients and positive acquired hypercoagulation tests (unconfirmed by repeat testing in 12 weeks) were seen in two patients. In the remaining 37 patients in whom hypercoagulability testing is often considered (vide supra), 16 patients were found to have positive tests. Testing only for hereditary thrombophilias was positive in seven patients, and testing only for acquired thrombophilia tests was positive (but unconfirmed) in six patients. Testing done for hereditary and acquired thrombophilias was positive in three patients. In our total group of 60 patients, thrombophilias were seen in both provoked and non-provoked cases. There was no significant difference in the number of thrombophilias seen in patients with provoked VTE (again, many of whom would have been excluded by Choosing Wisely) as opposed to the often considered group consisting of those with recurrent VTE, unprovoked VTE, VTE in an unusual site, or a family history of VTE.

Unnecessary, incomplete, and inappropriate testing was noted in various scenarios. Inadequate medical history led to six unnecessary duplicate orders for genetic mutation analysis in four patients. In seven patients identified with the lupus anticoagulant confirmation testing was not, to our knowledge, repeated at the required three month interval. Inappropriate testing, as defined by tests that were uninterpretable due to confounding factors such as acute thrombosis and active anticoagulation treatments, were ordered for 41 patients (68.3%). Unwarranted tests, as defined by tests that did not contribute to thrombosis risk assessment (such as MTHFR, JAK2 mutation studies, and coagulation factor assays), were ordered for 32 patients (53.3%). The incidences of inappropriate tests and unwarranted tests decreased when a hematology consultant ordered the diagnostic studies (p=0.04, p=0.01, respectively).

Conclusions: Thrombophilias in patients with recurrent VTE, unprovoked VTE, VTE occurring in an unusual site, or a family history of VTE occurred at an equal incidence as in those patients with provoked VTE. Choosing Wisely may limit the selection criteria in testing for the hypercoagulable state. Exclusion criteria for testing needs to be further refined. Inappropriate or unwarranted testing can be avoided by consultation with a hematologist, which should be strongly considered prior to obtaining a thrombophilia evaluation.