Lupus Anticoagulant Testing in Patients Receiving Rivaroxaban or Apixaban for the Treatment of Venous Thromboembolism

Background. Lupus Anticoagulant (LA) testing is often performed in order to determine the cause of idiopathic venous thromboembolism (VTE) as well as the duration of therapy. The timing of the testing is often problematic. Acutely, many patients have received LMWH which often will interfere with test results. LA testing in patients on warfarin is technically feasible and current guidelines have established procedures for this situation. In contrast direct anti-Xa inhibitors such as apixaban and rivaroxaban can cause false positive results if residual anti-Xa inhibition is present. In general, prior to performing a thrombophilia screen, anticoagulants must be held in order to produce valid results. The duration of this varies with different anticoagulants. Some groups have advised that apixaban and rivaroxaban should be held for 2-3 days prior to testing. This overcomes the half-life of both agents. However, to date there have not been adequate studies to validate this approach, and no standardized approach has been proposed. At our centre we require patients to withhold apixaban or rivaroxaban on the day prior to and the day of LA testing. We aimed to determine the adequacy of this approach.

Methods. We reviewed consecutive patients with VTE treated with rivaroxaban or apixaban and who required LA screening. . LA testing was requested at least 3 months after the initial VTE diagnosis. Patients were asked to hold the anticoagulant the day prior to and the day of LA testing (last dose taken at least 48 hours prior to testing). Plasma was collected in 3.2% citrate tubes and LA testing was done using dilute Russell viper's venom time and LA-sensitive activated partial thromboplastin time, according to the guidelines of the International Society on Thrombosis and Haemostasis. Plasma aliquots were frozen at -20 Celsius for further testing and apixaban or rivaroxaban plasma levels were measured by liquid chromatography-tandem mass spectrometry.

Results. We included 21 patients (13 women). The mean age at VTE diagnosis was 57 years. Twelve patients had a pulmonary embolism (PE), 10 deep vein thrombosis (DVT), and 1 both a PE and DVT. Sixteen (76.2%) of the 21 patients received rivaroxaban, the rest apixaban. The mean apixaban level was 17.3 ng/ml (range 11.4 to 28.9). The mean rivaroxaban level was 11.7 ng/ml (range 8 to 27.8). All of these levels were consistent with being below trough levels for acute VTE treatment. All patients were negative for LA screening and there were no technical issues with performing the LA tests.

Conclusion. Our results suggest that holding rivaroxaban or apixaban both the day prior to and the day of testing allows for a valid assessment of LA. This is supported by the low measured levels of both rivaroxaban and apixaban and the lack of technical issues with the LA testing.