ACTIVATION OF BLOOD-COAGULATION AFTER ABRUPT OR STEPWISE WITHDRAWAL OF ORAL ANTICOAGULANTS - A PROSPECTIVE-STUDY

The occurrence of a ''rebound hypercoagulable state'' in patients afte r discontinuation of oral anticoagulants is still a matter of debate a nd no definite recommendation can be made on the best procedure for an ticoagulant withdrawal. The present study investigated the changes in the levels of markers of activated blood coagulation in 32 patients (p ts) in whom warfarin treatment (for venous thromboembolic disease) was randomly withdrawn abruptly (n = 17, group A) or gradually (n = 15, g roup B: 2/3 of initial dose the Ist week, 1/3 the 2nd weeks and nothin g from the 3rd week on). Blood was sampled at baseline, once a week fo r the first three weeks and after 2 months. At the Ist week group A ha d 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 diffe rent from those of group B. After baseline, higher than normal F1+2 le vels were recorded in 32/66 (48%) controls in group A vs 15/60 (25%) i n 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 air variables were not statistically different in the two groups; however, very high levels were observed in a few cases of group A. Thr ombotic events (one DVT recurrence and one thrombophlebitis in a varic ose vein) occurred in 2 pts of group A, both with high F1+2 and TAT AU C values. In conclusion, the present study shows that withdrawal of or al anticoagulants elicits low grade transient clotting activation, whi ch 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 complicat ions.