RELATIONSHIP BETWEEN PROTHROMBIN ACTIVATION FRAGMENT F1.2 AND INTERNATIONAL NORMALIZED RATIO IN PATIENTS WITH ATRIAL-FIBRILLATION

Background and Purpose The prothrombin time (expressed as the internat ional normalized ratio [INR]) is the standard method of monitoring war farin therapy in patients with atrial fibrillation. Prothrombin activa tion fragment F1.2 provides an index of in vivo thrombin generation an d might provide a better index of the effective intensity of anticoagu lation. We examined the relationship between F1.2 and INR in patients with atrial fibrillation. Methods We measured INR and F1.2 levels in 8 46 patients with atrial fibrillation participating in the Stroke Preve ntion in Atrial Fibrillation III study. Two hundred nineteen (26%) wer e taking aspirin alone, 326 (39%) were taking adjusted-dose warfarin, and 301 (36%) were taking a low fixed dose of warfarin (1 to 3 mg) plu s aspirin (combination therapy). F1.2 levels were measured with an enz yme-linked immunosorbent assay. Results Patients receiving adjusted-do se warfarin or combination therapy had significantly higher INR and si gnificantly lower F1.2 values than those on aspirin alone (P less than or equal to .0001 for each of the four comparisons). F1.2 values (nan omolar) were inversely correlated with INR (F1.2 = -0.1 + 2.3[1/INR]; R-2 = .37; P <.0001; simple linear regression). However, significant v ariability remained. Among patients receiving warfarin, older patients had higher F1.2 values than younger patients after adjustment for INR intensity (P < .001) in the model. There was no difference in the rel ationship between F1.2 and INR between men and women. Conclusions Incr easing intensity of anticoagulation, as measured by the INR, is associ ated with decreasing thrombin generation as measured by the F1.2 level , but significant variability exists in this relationship. Older antic oagulated patients have higher F1.2 values than younger patients at eq uivalent INR values. The clinical significance of these differences is not clear. F1.2 measurement might provide information regarding antic oagulation intensity in addition to that reflected by the INR.