OC 52.5 - ST-Genesia Thromboscreen following use of a direct oral anticoagulant neutraliser correlates with VTE recurrence in patients on direct oral anticoagulants.

Background: Direct oral anticoagulants (DOACs) interfere with predictive biomarker testing for recurrent venous thromboembolism (VTE). Compounds such as DOAC-stop may remove DOAC interference in-vitro and allow risk assessment during anticoagulation.

Aims: To remove the DOAC effect from plasma collected from therapeutically anticoagulated VTE patients, and assess thrombin generation using the ST-Genesia platform in correlation to risk of VTE recurrence.

Methods: Adult VTE patients receiving therapeutic anticoagulation with rivaroxaban or apixaban were recruited. Platelet poor-plasma was collected at around 3 months following VTE (while still therapeutically anticoagulated). Thrombin generation testing was performed using the ST-Genesia Thromboscreen, following the addition of DOAC-Stop.

Results: 260 patients were recruited (mean age 55.9 years, 55% male). 48.1% (n=125) proceeded to maintenance anticoagulation (MA) and were more likely to have had major and/or unprovoked VTE. Compared to patients with limited duration of anticoagulation (LD), the MA group showed higher endogenous thrombin potential (ETP) with (TM+, 783.9nM v 666.5nM.min, p=0.028) and without thrombomodulin (TM-, 1559.0nM v 1475.0nM, p=0.035) (Table 1), and a trend towards reduced ETP inhibition (49.6% v 55.4%, p=0.070).
Fewer recurrences occurred in the MA group (n=6). In the LD group, there were 15 VTE recurrences (11.1%) including 7 (46.7%) unprovoked episodes. With thrombomodulin, LD patients with unprovoked recurrence demonstrated the highest normalised peak height (p=0.026) and ETP (p=0.022) with reduced ETP inhibition (p=0.039) (Table 2).

Conclusion(s): This study found the MA group (deemed by the treating clinicians to have higher risk of VTE recurrence) and LD patients who later developed unprovoked recurrence to have more hypercoagulable thrombin generation parameters in the therapeutic anticoagulation period. These pilot findings support the use of DOAC-stop to enable testing during therapeutic anticoagulation for VTE, which can help to uncover underlying hypercoagulable tendency without having to interrupt anticoagulation for patients. Larger studies are required to confirm these findings.