Ordering Patterns, Cost, and Utility of Factor V Leiden Testing in an Academic Medical Center

Abstract

Factor V Leiden (FVL) is one of the most common inherited thrombophilias. It is an autosomal dominant condition, and 99% of individuals with FVL are heterozygous for the variant. Heterozygotes have a mildly increased risk of venous thromboembolism (VTE) compared to non-carriers, with an estimated lifetime risk of 10%. An association between FVL and arterial thromboembolism remains controversial and is likely to be relatively small if present. Although anticoagulation guidelines for VTE published by the American College of Chest Physicians are not affected by the presence or absence of thrombophilia, testing is commonly ordered. FVL in particular is one of the most frequently ordered molecular genetic tests. This testing is costly and may represent an unnecessary healthcare expenditure if it does not affect clinical decision making. This was a retrospective chart review of FVL testing performed at the University of Kansas Medical Center from 7/6/21-7/5/2022. The purpose of the study was to determine FVL testing patterns, cost, impact on clinical decision making, and potential opportunities for quality improvement. FVL screening was obtained in 192 patients during the study period; 21% of testing was obtained inpatient, and 79% outpatient. Hematology ordered testing most frequently overall (46% of the time), followed by cardiology (13%), neurology (12%), and internal medicine (8%). Nineteen (10%) tests were positive, all of which were heterozygous on subsequent gene testing. Additional thrombophilia testing was performed 89% of the time, which was positive in 6 patients (3 with lupus anticoagulant, 3 with heterozygous prothrombin G20210A mutation). Of the 41 tests performed inpatient, 88% were ordered by non-hematology services, and hematology was consulted only 11% of the time prior to testing. Inpatient testing was ordered most frequently by neurology (42%), internal medicine (20%), cardiology and intensive care units (7% each). The most frequent indications for inpatient testing were arterial thrombosis (56%), first venous thrombosis (24%), and recurrent venous thrombosis (10%). Neither anticoagulation type nor duration was change based on results in any of the patients. Regarding outpatient testing, hematology ordered the majority of tests (55%), followed by cardiology (15%), internal medicine, family medicine and surgery (5% each). The most frequent indications were first venous thrombosis (39%), recurrent venous thrombosis (15%), family history without any personal history of thrombosis (11%), and arterial thrombosis (9%). When provoked or unprovoked venous thrombosis was the testing indication, neither duration nor type of anticoagulation was changed in any of the 86 patients. The average charge for FVL testing from hospitals in the Kansas City Area is $119, totaling an estimated $22,848 in charges for the time period reviewed. Given the lack of impact test results had on the duration or type of anticoagulation, the utility of FVL testing appears to be limited in our sample. In particular, FVL testing of inpatients, most often performed for arterial thrombosis by non-hematology services, had no notable impact on patient care. These results suggest that a quality improvement project restricting testing to the outpatient setting and to indications where results would change clinical decision making, would result in significant cost savings. The additional thrombophilia work-up often performed with FVL screening is even more costly, with an average charge of $2500 for protein c, protein s, prothrombin, and anti-thrombin III testing. In addition, given only 3.5% of those tested for additional thrombophilias were found to be positive, investigation into the utility of these tests may also be warranted. This analysis is limited by its retrospective nature and limited follow-up. Future studies based on this data will include quality improvement measures with subsequent re-analysis to determine the effect on test reduction and cost savings.