Measurement of Prothrombin Fragment 1+2 for the Assessment of Anticoagulant Activity in Patients Treated with Warfarin or Non-vitamin K Antagonist Oral Anticoagulant

Abstract

[Background and purpose] Prothrombin fragment 1+2 (PF1+2) is a sensitive marker for blood coagulation system. In order to evaluate anticoagulant activity in patients treated with warfarin or non-vitamin K antagonist oral anticoagulant (NOAC), we measured plasma levels of PF1+2 and evaluated anticoagulant activity by each anticoagulant agent. [Methods] Subjects were 28 patients, 17 men and 11 women, 77±6 year old, with oral anticoagulant therapy for secondary prevention of stroke. We measured plasma levels of PF1+2 in 70 times in 7 patients treated with warfarin, and 154 times in 27 patients treated with NOAC. PT-INR was simultaneously measured in patients treated with warfarin. [Results] In warfarin treatment groups, PT-INR values were median 1.96 (IQR 1.8-2.1) and PF1+2 levels were median 111 pmol/l (IQR 95-141). All PF1+2 levels were below the upper limit of normal range, but 12 values (17%) of them in 5 patients were below the lower limit of normal range. 8 of the 12 values were at PT-INR below 2.5, and 1 of whom developed intracerebral hemorrhage. Plasma levels of PF1+2 in patients treated with dabigatran 150mg BID, dabigatran 110mg BID, rivaroxaban 15mg QD, rivaroxaban 10mg QD, apixaban 5mg BID, apixaban 2.5mg BID, and edxaban 30mg QD were median 116 pmol/l (IQR 99-136), 132 pmol/l (IQR 99-162), 109 pmol/l (IQR 100-125), 133 pmol/l (IQR 100-177), 88 pmol/l (IQR 76-102), 148 pmol/l (IQR 93-167), 221 pmol/l (IQR 208-234). They were all above the lower limit of the normal range, 3 of which were above the upper limit of the normal range. Excessive suppression of thrombin production was more frequently seen in warfarin treatment than in NOAC treatment (p<0.05). [Conclusion] In warfarin treatment, thrombin production was suppressed excessively in 17%, although it was not in NOAC treatment. (Received September 21, 2016; Accepted December 26, 2016; Published May 1, 2017).