Effects of non-vitamin K antagonist oral anticoagulants on fibrin clot and whole blood clot formation, integrity and thrombolysis in patients with atrial fibrillation.

Yee Cheng Lau,Eduard Shantsila,Gregory Y H Lip,Qinmei Xiong,Andrew D Blann

doi:10.1007/s11239-016-1399-3

Abstract

Non-vitamin K antagonist oral anticoagulants (NOACs) are replacing warfarin and heparins in several clinical situations. With varying modes of action, the effects of NOACs on thrombus formation, integrity, and lysis is unknown. To determine whether two techniques of thrombelastography (TEG) and a micro-plate assay (MPA) provide novel data on thrombus formation, integrity and lysis in those taking a NOACs compared to warfarin and a control group taking aspirin. We assessed thrombogenesis, clot integrity and fibrinolysis in blood (TEG) and plasma (MPA) from 182 atrial fibrillation patients—50 on aspirin, 50 on warfarin, and 82 on a NOAC (17 apixaban, 19 dabigatran and 46 rivaroxaban). Eleven of 16 TEG indices and 4 of 5 MPA indices differed (p ≤ 0.01) between those on aspirin, warfarin or a NOAC. Three TEG indices and 4 MPA indices differed (p < 0.01) between the NOACs. Time to initiation of clot formation was most rapid on apixaban, then rivaroxaban and slowest on dabigatran. The rate of clot formation was most rapid on dabigatran, then apixaban, and slowest on rivaroxaban. Clot density was greatest on rivaroxaban, then apixaban, but weakest on dabigatran. The rate of clot dissolution was most rapid in apixaban, then dabigatran, and slowest on rivaroxaban. The TEG and MPA identify major differences in thrombogenesis and fibrinolysis in different NOACs. These techniques may have value in investigating the effects of these drugs on haemostasis in a clinical setting, and in identifying those in need of targeted therapy.

Highlights

The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) has fundamentally changed clinical practice in the use of oral and parenteral anticoagulation therapy in the prevention of stroke in atrial fibrillation (AF), and in the prevention and treatment of venous thromboembolism, including after orthopaedic surgery
Clot integrity and fibrinolysis in blood (TEG) and plasma (MPA) from 182 atrial fibrillation patients—50 on aspirin, 50 on warfarin, and 82 on a Non-vitamin K antagonist oral anticoagulants (NOACs) (17 apixaban, 19 dabigatran and 46 rivaroxaban)
NOACs may in exceptional circumstances be assessed by standard laboratory tests, lack of sensitivity and specificity of these tests calls for other assays [4,5,6]

Summary

Introduction

The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) has fundamentally changed clinical practice in the use of oral and parenteral anticoagulation therapy in the prevention of stroke in atrial fibrillation (AF), and in the prevention and treatment of venous thromboembolism, including after orthopaedic surgery. Unlike vitamin K antagonists (VKAs, such as warfarin), which non- suppress hepatic production of functional coagulation factors II, VII, IX and X by inhibiting vitamin K metabolism, NOACs target specific molecules of the coagulation cascade: dabigatran is a direct thrombin inhibitor whilst apixaban and rivaroxaban both target factor Xa [1,2,3,4]. NOACs may in exceptional (emergency) circumstances be assessed by standard laboratory tests (such as the prothrombin time and the activated partial thromboplastin time), lack of sensitivity and specificity of these tests calls for other assays (such as ecarin clotting time and anti-Factor Xa activity) [4,5,6]. A further feature of NOACs use is that renal function must be assessed as use of these drugs require caution in those with severe renal failure [7]

Methods

Results

Conclusion