Activation of Blood Coagulation after Abrupt or Stepwise Withdrawal of Oral Anticoagulants - A Prospective Study

Abstract

SummaryThe occurrence of a “rebound hypercoagulable state” in patients after discontinuation of oral anticoagulants is still a matter of debate and no definite recommendation can be made on the best procedure for anticoagulant withdrawal. The present study investigated the changes in the levels of markers of activated blood coagulation in 32 patients (pts) in whom warfarin treatment (for venous thromboembolic disease) was randomly withdrawn abruptly (n = 17, group A) or gradually (n = 15, group B: ⅔ of initial dose the 1st week, ⅓ the 2nd weeks and nothing from the 3rd week on). Blood was sampled at baseline, once a week for the first three weeks and after 2 months. At the 1st week group A had significantly higher F1+2 and TAT values (p <0.001); at the 2nd week F1 + 2 levels remained higher (p <0.05) though INR values were not different from those of group B. After baseline, higher than normal F1+2 levels were recorded in 32/66 (48%) controls in group A vs 15/60 (25%) in group B (p <0.01); at the 2nd week, 10/17 (59%) patients in group A vs 1/15 (7%) in group B still had higher than normal F1+2 levels (p <0.01 ). The values of areas under curve (AUC) and maximum concentrations of all variables were not statistically different in the two groups; however, very high levels were observed in a few cases of group A. Thrombotic events (one DVT recurrence and one thrombophlebitis in a varicose vein) occurred in 2 pts of group A, both with high F1+2 and TAT AUC values. In conclusion, the present study shows that withdrawal of oral anticoagulants elicits low grade transient clotting activation, which is more intense and longer lasting after abrupt discontinuation. In single cases, however, such activation is particularly intense. It is possible that these cases are at greater risk of thrombotic complications.

Perioperative Complications of Endoscopic Submucosal Dissection for Early Gastric Cancer in Elderly Japanese Patients 75 Years of Age or Older

“…For example, it is known that the onset of cardiovascular events or cerebral infarction increases approximately three times by stopping antiplatelet therapy (27,28), and the development of serious thromboembolism following the discontinuation of anticoagulant therapy has been reported in several conditions (29)(30)(31). A recent report showed that significant risk factors for delayed bleeding include a reduced platelet count, extended prothrombin time, large extent of resection and positive/indeterminate lateral margin (32).…”

Evidence-Based Management of Anticoagulant Therapy

“…143 Five small controlled trials (total n 5 217) have addressed this issue. [144][145][146][147] The primary outcomes of four of the studies were laboratory results suggestive of a hypercoaguable state 144,145,147,148 and produced inconsistent results. Elevations tended to persist for 8 to 9 weeks, regardless of discontinuation strategy, suggesting an unmasked prothrombotic state in the absence of anticoagulant protection rather than a rebound phenomenon associated with abrupt discontinuation.…”

“…[144][145][146][147][148] The only major hemorrhage occurred in the gradual withdrawal group. Gradual discontinuation of VKA is likely to be more confusing and inconvenient for the patient.…”

“…Unclear whether allocation was concealed in Tardy, de Groot, and Ascani; it was not concealed in Michaels. Clinicians and patients were not blinded in de Groot, Michaels, Palareti et al, 147 or Ascani. c Very small patient groups and few events.…”

A Call to Reduce the Use of Bridging Anticoagulation

“…There is longstanding controversy over the phenomenon of rebound hypercoagulability after the cessation of anticoagulation. 1 Although some studies do seem to confirm that there is activation of the coagulation system shortly after interruption of therapy, [2][3][4] it is unclear if this phenomenon is clinically meaningful, or how important it would be in the context of a brief periprocedural interruption. For example, a meta-analysis of studies of patients with venous thromboembolism (VTE) found that there is a transient increase of 2% in the rate of recurrent VTE during the 2 months after cessation of anticoagulant therapy.…”