Abstract Number: PB2428
Meeting: ISTH 2020 Congress
Theme: Venous Thromboembolism and Cardioembolism » VTE Treatment
Background: Current coagulation assays measure only the start of the clotting process, and do not reflect the in-vivo anticoagulant effect of direct oral anticoagulants (DOACs). Global coagulation assays such as the calibrated automated thrombogram (CAT) and overall haemostatic potential (OHP) may provide a better assessment.
Aims: As part of a larger prospective VTE biomarker study, we provide an interim analysis to explore the role of CAT and OHP in VTE patients receiving therapeutic anticoagulation.
Methods: Patients with symptomatic VTE were prospectively consented between Jan 2018 and Dec 2019. Blood was sampled whilst patients were receiving therapeutic anticoagulation and measured for rivaroxaban and apixaban specific anti-Xa, as well as CAT and OHP assays using manufacturer specifications.
Results: 193 (105 M, 88 F) patients with median age 57 years were recruited. Unprovoked events comprised 51.8% (n=100) and major VTE were 67.4% (n=130). Of patients who had been sampled, there were 65 on rivaroxaban, 58 on apixaban, 31 on warfarin and 13 on clexane. CAT assays demonstrated a reduction of thrombin generation parameters consistent with anticoagulation effect. Thrombin peak provided the best correlation displaying a logarithmic relationship between thrombin peak and rivaroxaban (R2= 0.55) or apixaban anti-Xa (R2= 0.45) (Fig 1) with significant variation noted at low anti-Xa levels. Fibrin generation was not affected by anticoagulation (Table 1) and appeared significantly increased compared to normal controls.
Normal controls n=135 | VTE patients n=138 | Rivaroxaban n=63 | Apixaban n=39 | Warfarin n=27 | |
OCP, mean (95%CI) | 57.83 (55.84-59.82) | 67.41 (65.32-69.5) p<0.001 | 65.1 (62.12-68.07) p<0.001 | 65.83 (62.33-69.33) p<0.001 | 74.51 (69.95-79.06) p<0.001 |
OHP, mean (95%CI) | 28.52 (27.33-29.7) | 35.81 (34.16-37.47) p<0.001 | 35.4 (32.89-37.92) p<0.001 | 34.85 (31.95-37.75) p<0.001 | 38.09 (34.27-41.91) p<0.001 |
OFP%, mean (95%CI) | 49.93 (48.54-51.32) | 47.06 (45.65-48.47) P=0.005 | 45.86 (43.72-48) P=0.002 | 47.05 (44.00-50.1) P=0.07 | 49.39 (46.75-52.04) P=0.75 |
[Table 1 – OHP results (available at time of interim analysis) for study patients compared to normal controls]
Conclusions: The anticoagulant effect of rivaroxaban and apixaban can be measured using CAT, with significant individual variation particularly at low anti-Xa levels. Fibrin generation capacity is not affected by anticoagulation due to the addition of excess thrombin. However all fibrin generation parameters are significantly increased compared to normal controls, suggesting a hypercoagulable tendency in VTE patients. Further analysis of the fibrinolytic pathways in VTE as well as correlation with clinical outcome is suggested and is ongoing.
[Figure 1 – relationship between thrombin peak and available anti-Xa levels (A) Rivaroxaban (n=31) and (B) Apixaban (n=10)]
To cite this abstract in AMA style:
Wang J, Lim HY, Brook R, Aswapanyawongse O, Ho P. Evaluation of Thrombin and Fibrin Generation in Venous Thromboembolism (VTE) Patients Receiving Anticoagulation [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/evaluation-of-thrombin-and-fibrin-generation-in-venous-thromboembolism-vte-patients-receiving-anticoagulation/. Accessed April 26, 2024.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/evaluation-of-thrombin-and-fibrin-generation-in-venous-thromboembolism-vte-patients-receiving-anticoagulation/