Optimal therapeutic range for oral anticoagulants in Japanese patients with prosthetic heart valves: a preliminary report from a single institution using conversion from thrombotest to PT-INR

Abstract

The thrombotest (TT) technique has been widely used in Japan for monitoring oral anticoagulant therapy (OAT). The therapeutic range was originally recommended to be 10%-25%. However, the International Committee for Standardization in Hematology/International Committee on Thrombosis and Hemostasis (ICSH/ICTH) recommended using the international normalized ratio of prothrombin time (PT-INR) for monitoring OAT. It is necessarv to use a universal standard measure for monitoring OAT in accordance with the ICSH/ISTH recommendation. We simultaneously measured TT and PT in blood samples from 1,157 patients on long-term warfarin therapy, and studied the correlation between TT and PT-INR. An excellent linear correlation was obtained between TT-INR and PT-INR with the regression equation PT-INR = 1.0420 TT-INR - 0.0987 (r = 0.905, P < 0.001). We also examined the correlation between the incidence of thromboembolism in 170 patients receiving warfarin therapy after prosthetic valve replacement; 50.5% received concomitant antiplatelet therapy. Thromboembolism occurred in 9 of 170 patients during a mean follow-up period of 2.44 years. The average TT values in patients with and without thromboembolism were 26.4% (PT-INR: 1.53) and 21.1% (1.73), respectively (P < 0.01). The incidence of thromboembolism did not differ significantly between patients on warfarin alone (average TT: 22.2%) and those on warfarin and antiplatelet agent (average TT: 20.9%). Our results suggest that the incidence of thromboembolism is low in Japan despite a less intensive regimen having been adopted.

The effects of a low international normalized ratio on thromboembolic and bleeding complications in patients with mechanical mitral valve replacement

“…Mori et al [6] studied 102 Japanese patients with mechanical heart valve prosthesis and found a significant increase in morbidity from bleeding with an INR >2.5. Uetsuka et al [7] studied 1,157 Japanese patients receiving warfarin therapy after prosthetic valve replacement during a mean follow-up period of 2.44 years and found that the incidence of TEs did not increase with a lower INR of 1.5. Therefore, they suggested that the incidence of TEs is lower in Japan, despite a less intensive regimen.…”

Japanese Society for Dialysis Therapy Guidelines for Management of Cardiovascular Diseases in Patients on Chronic Hemodialysis

“…Since there are racial differences in warfarin control after mechanical valve replacement, careful evaluation of the results in Japanese patients must be considered (3–5). Also, careful monitoring according to the prothrombin time‐international normalized ratio (PT‐INR) by integrating conflicting risks of bleeding and thromboembolism is necessary.…”

Obstruction of St. Jude Medical Valves in the Aortic Position: Plasma Transforming Growth Factor Type Beta 1 in Patients With Pannus Overgrowth

“…PT‐INR levels as indices of anticoagulation therapy for patients with prosthetic valves are maintained in a lower range in Japan than in North America and Europe because of particular concerns about bleeding complications, but good results free from thromboembolic complications have been reported (24,25). Our target INR level is slightly lower than that of the guideline set by the Japanese Circulation Society in 2004 (ranging from 2.0 to 3.0) because higher incidence of serious bleeding complications in Japanese patients is reported (24,25,30). However, the follow‐up for these patients was excellent because 80% of them ranged in the optimal therapeutic value of the PT‐INR (31).…”

“…Their postoperative anticoagulation level was maintained at the PT‐INR ranging from 1.6 to 2.5 in relation to the control level, using warfarin and an antiplatelet agent administered every month by family doctors (24,25). For double valve replacement and atrial fibrillation, a higher intensity of PT‐INR (2.0–3.0) was maintained.…”