Rebound after cessation of oral anticoagulant therapy: the biochemical evidence

Abstract

The existence of a phenomenon of rebound hypercoagulability after cessation of oral anticoagulant therapy is controversial. The sensitive procoagulant markers for in vivo thrombin and fibrin formation are potential tools for the reassessment of the presence of each a phenomenon. We examined 19 patients anticoagulated for 6 +/- 2 months (SD, range 3-12) because of venous thromboembolism or myocardial infarction as follows: twice during stable, oral anticoagulation (INR 3.1-3.7) and then on days 1, 2, 3, 4, 5, 7, 9, 11, 13, 15, and > 30 after cessation of oral anticoagulation. Thrombin-antithrombin III complexes (TAT) and fibrinopeptide A (FPA) were measured in addition to the prothrombin times and factors II, V, VII, and X. None of the 19 patients developed clinically manifest thromboembolism within the following 9-18 months. However, the patients' TAT levels increased transiently: rising from 1.5 +/- 0.1 ng/ml (SEM) to 3.0 +/- 0.2 ng/ml on day 4 (P < 0.001), and returned to 1.7 +/- 0.1 ng/ml after day 30 (normals 1.8 +/- 0.33). 17/19 patients showed TAT peak levels above the upper limit of normal between days 3 and 11 (average: day 4), which normalized again after 30 d. 8/19 patients also had transient FPA levels above the upper normal limits ( < 1.81). We conclude that our patients increased their thrombin and fibrin formation transiently and that a subpopulation reached values consistent with a prethrombotic state.

2008 Focused Update Incorporated Into the ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease

“…There are theoretical concerns that stopping the drug and then reinstituting it might result in hypercoagulability or that there might be a thrombotic "rebound." An increase in markers for activation of thrombosis with abrupt discontinuation of warfarin therapy has been observed, 964 but it is not clear whether the clinical risk of thromboembolism increases. 965 In addition, when warfarin therapy is reinstituted, there are theoretical concerns about a hypercoagulable state caused by suppression of protein C and protein S before the drug affects the thrombotic factors.…”

Persistence and Discontinuation of Oral Anticoagulant: Remaining Issues Not Addressed by Phase III Clinical Trials

“…A warning regarding “rebound increases in thrombogenicity” after discontinuation of warfarin has been indicated because of a potential imbalance between coagulant and anticoagulant activities related to the reduction of the vitamin K–dependent coagulant and coagulation regulatory proteins (such as Protein C and Protein S) 6, 7. Despite theoretical cautions, there is no clear clinical evidence concerning increased thrombotic events after warfarin discontinuation 8, 9…”

Dental management of patients receiving anticoagulation or antiplatelet treatment

“…Besides this, independent of the intensity of anticoagulation, the perioperative risk of thromboembolism may be increased due to other factors, in particular a rebound hypercoagulable state caused by the discontinuation of warfarin and the prothrombotic effect of the surgery itself (16). Consequently, for patients whose INR returns to normal shortly after stopping warfarin therapy, it can be assumed that the risk of preoperative arterial thromboembolism, postoperative arterial thromboembolism, and preoperative venous thromboembolism will be similar to that which is expected in the absence of anticoagulation (7).…”