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Monitoring "mini-intensity" anticoagulation with warfarin: comparison of
the prothrombin time using a sensitive thromboplastin with prothrombin
fragment F1+2 levels
MM Millenson, KA Bauer, JP Kistler, S Barzegar, L Tulin and RD Rosenberg
Department of Medicine, Beth Israel Hospital, Boston, MA 02215.
Treatment with warfarin using a target International Normalized Ratio (INR)
range of 1.7 to 2.5 is efficacious for many clinical indications, but the
minimal intensity of anticoagulation required for antithrombotic protection
has yet to be determined. To evaluate whether patients could be reliably
monitored with a less intense regimen, we anticoagulated patients with
warfarin for several months using a target INR range of 1.3 to 1.6 as
determined by prothrombin time (PT) using a sensitive thromboplastin (Dade
IS, International Sensitivity Index [ISI] = 1.3). Plasma measurements of
F1+2, a marker of factor Xa action on prothrombin in vivo, were also
obtained to determine the suppressive effect of warfarin on hemostatic
system activity. Overall, 20 of 21 patients with a history of
cerebrovascular events (mean age, 61 years) could be reliably regulated
with warfarin in the target INR range. F1+2 levels were significantly
suppressed from baseline in all patients, with a mean reduction of 49%
(range, 28% to 78%). We found a significant relationship between the extent
of suppression of prothrombin activation levels and the baseline
measurements. A mean reduction of 65% was observed for those patients with
baseline F1+2 greater than or equal to 1.5 nmol/L, but only 38% for
baseline F1+2 less than or equal to 0.5 nmol/L. Overall, 68% of plasma
samples obtained during stable anticoagulation were within the target INR
range. PTs were also determined on all plasma samples with two
thromboplastins of lower sensitivity (C+, ISI = 2.09; and automated
simplastin, ISI = 2.10). Only 47% and 35% of PT determinations,
respectively, were within the target range with these reagents. We conclude
that prothrombin activation can be significantly suppressed in vivo with
use of warfarin in an INR range of 1.3 to 1.6. This level of
anticoagulation can be reliably achieved by monitoring PTs with a
thromboplastin of high sensitivity.
Volume 79,
Issue 8,
pp. 2034-2038,
04/15/1992
Copyright © 1992 by The American Society of Hematology
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