Volume 200 - Issue 2
An update of consensus guidelines for warfarin reversal
Author: Krishna G Badami
Med J Aust 2014; 200 (2): 80-82. || doi: 10.5694/mja13.10271
Published online: 3 February 2014
Published online: 3 February 2014
To the Editor: The recently updated warfarin reversal guideline recommends prothrombin complex concentrate (PCC) dosing based on international normalised ratios (INRs), rather than fixed dosing.1 While achieving a target INR may
be made more likely, this may be inconsequential clinically.2
The reasons are these. The relationship between vitamin K-dependent clotting factor levels and INR or bleeding is uncertain. As INR increases above 5.0, these levels decline ...
To the Editor: The recently updated warfarin reversal guideline recommends prothrombin complex concentrate (PCC) dosing based on international normalised ratios (INRs), rather than fixed dosing.1 While achieving a target INR may be made more likely, this may be inconsequential clinically.2
The reasons are these. The relationship between vitamin K-dependent clotting factor levels and INR or bleeding is uncertain. As INR increases above 5.0, these levels decline little;3 and thrombin generation does not decline as INR increases above 4.0.4 Thromboplastins are sensitive to clinically insignificant reductions in factor VII.3,4 Furthermore, the significance of an INR greater than 4.5 is doubtful, as calibrations were never performed beyond this point.5 Therefore, fixed, lower PCC doses may be as effective as INR-linked, higher ones.2
Second, all patients with high INR may not be similar. Individual variations may determine which vitamin K-dependent clotting factors are low and, hence, bleeding risk. Low factor II and X levels may predispose patients more to bleeding than low factor VII or IX levels.3 Like fresh frozen plasma in this setting, even PCC — while providing all, or most, ostensibly equally important vitamin K-dependent clotting factors — may be insufficiently specific for warfarin reversal. While PCC is clearly superior to fresh frozen plasma for warfarin reversal, randomised trials comparing three-factor and four-factor PCC using clinical end points are lacking.2 Three-factor PCC may have little factor VII, but does this matter clinically? Determining vitamin K-dependent clotting factor levels in bleeding or non-bleeding warfarinised patients with in-range or high INRs may help to determine which cause bleeding and which merely cause high INR.
Finally, with all guidelines, including warfarin reversal guidelines, compliance is a problem.6 Might the complexity of this updated warfarin reversal guideline add to the problem?
Competing interests
No relevant disclosures.
References
- Tran HA, Chunilal SD, Harper PL, et al. An update of consensus guidelines for warfarin reversal. Med J Aust 2013; 198: 198-199. 0_CHDICJHD
- Leissinger CA, Blatt PM, Hoots WK, Ewenstein B. Role of prothrombin complex concentrates in reversing warfarin anticoagulation: a review of the literature. Am J Hematol 2008; 83: 137-143. 0_CBBHEIFC
- Sarode R, Rawal A, Lee R, et al. Poor correlation of supratherapeutic international normalised ratio and vitamin K-dependent procoagulant factor levels during warfarin therapy. Br J Haematol 2006; 132: 604-607. 0_CBBFDAFH
- Gatt A, Riddell A, van Veen JJ, et al. Optimizing warfarin reversal – an ex vivo study. J Thromb Haemost 2009; 7: 1123-1127. 0_CBBFIIIB
- Poller L. International normalised ratios (INR): the first 20 years. J Thromb Haemost 2004; 2: 849-860. 0_i1142891
- Le-Kim L, Kerr D, Kelly A. Are patients on warfarin with high INR treated according to published guidelines? The Internet Journal of Hematology 2009; 5. doi: 10.5580/24f2. http://ispub.com/IJHE/5/1/12484 (accessed Mar 2013).