PB0961 - Continued Suspected Direct Oral Anticoagulant Interference on Thrombophilia Testing: Experience of a Reference Laboratory

Background: Since approval of direct oral anticoagulants (DOACs) for anticoagulation, the diagnosis of thrombophilia risk factors has become challenging, especially when clot-based assays are utilized. Falsely elevated protein S and C activities and false-positive lupus anticoagulant results may occur with DOAC use. Little is known of the interference seen in subsequent years when educational efforts were undertaken to make licensed care providers aware of these interferences.

Aims: Examination of DOAC interference before and after DOACs were introduced to the US market.

Methods: Retrospective review of venous thrombophilia testing from January 2008 to December 2020 at a coagulation reference referral laboratory. To identify potential DOAC interference, we reviewed specimens submitted for both a protein C activity test and a dilute Russell viper venom test (dRVVT), which is a lupus anticoagulant test. DOAC interference was suspected when protein C activity was elevated (>200%) and dRVVT testing did not demonstrate an inhibitor pattern. DOAC interference was strongly suspected when protein C activity was elevated (>200%) and dRVVT testing demonstrated an inhibitor pattern. Annual percentages of thrombophilia tests with suspected and strongly suspected DOAC interference were compared.

Results: Percentage of suspected DOAC interference increased annually from 2008 to 2016, which corresponds to the introduction of DOACs to the US market. Strongly suspected DOAC interference increased from 0.21% in 2008, peaking at 5.07% (24.1-fold increase) in 2015; test results of elevated protein C activity without a dRVVT inhibitor pattern increased from 0.48% in 2008, peaking at 15.12% (31.5-fold increase) in 2014. Suspected interference of 7 - 9% has continued since 2016.

Conclusion(s): While strongly suspected DOAC interference has markedly decreased since the peak in 2015, suspected DOAC interference still affects a substantial percentage of thrombophilia test orders despite educational efforts by our laboratory and other investigators as evidenced by publications in the literature and choosing wisely recommendations by professional societies