Letters to the Editor
The accuracy of the International Normalized Ratio and the American College of Chest Physicians recommendations on the use of vitamin K to reverse over-anticoagulation: a rebuttal
Version of Record online: 13 MAR 2013
© 2013 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 11, Issue 3, pages 566–567, March 2013
How to Cite
The accuracy of the International Normalized Ratio and the American College of Chest Physicians recommendations on the use of vitamin K to reverse over-anticoagulation: a rebuttal. J Thromb Haemost 2013; 11: 566–7., , .
- Issue online: 13 MAR 2013
- Version of Record online: 13 MAR 2013
- Accepted manuscript online: 29 DEC 2012 09:48AM EST
- Manuscript Accepted: 24 DEC 2012
- Manuscript Received: 17 DEC 2012
The comment of Tripodi and Moia regarding the inaccuracy of the International Normalized Ratio (INR) above 4.5 is correct, as calibration of thromboplastin is performed with plasmas from patients with mostly adequate anticoagulation (INR 1.5–4.5) . They are concerned that our suggestion in the latest edition of the American College of Chest Physicians clinical practice guidelines regarding reversal of asymptomatic high INR with vitamin K is misleading .
The basis for our suggestion to abstain from reversal with vitamin K of asymptomatic INRs between 4.5 and 10 is derived from four randomized controlled trials [3-6]. In three of those, the population studied had INRs of 4.5–10.0, whereas the smallest study included patients with INRs between 6.0 and 12.0 . The negative results are driven by the largest trial . One of the rules when authoring guidelines is to restrict the recommendations or suggestions to the population studied. Therefore, it is necessary that we, in our conclusion, address the population of patients with asymptomatic high INRs of 4.5–10. In addition, for the patients with very high INRs, we identified two cohort studies, both including patients with INRs above 10.0 [7, 8].
The second point to be made is that we ‘suggest’ rather than ‘recommend’, as the quality of the evidence in the randomized trials was only moderate. This was based on serious imprecision with wide confidence intervals for the risk of major bleeding, thromboembolism, or death. The implications of a 2B suggestion are as follows :
Best action may differ, depending on circumstances or patient or societal values. Higher-quality research may well have an important impact on our confidence in the estimate of effect, and may change the estimate.
The implications of a 2C suggestion are as follows :
Other alternatives may be equally reasonable. Higher-quality research is likely to have an important impact on our confidence in the estimate of effect, and may well change the estimate.
It is therefore clear that the treating physician should make an individual judgement in these cases on whether to treat or not.
It would be reasonable to add, in a future edition of the guidelines, the caution pronounced by Tripodi and Moia that high INRs are inherently inaccurate.
Disclosure of Conflict of Interests
The authors state that they have no conflict of interest.
- 9Methodology for the development of antithrombotic therapy and prevention of thrombosis guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: 53S–70S., , , , , , , , , , , , , .