Management of Warfarin therapy proved to be challenging, common
side-effects ranged from minor gum bleeding to severe intracranial
haemorrhages. Speculation had arising that supplementation daily with low levels
of vitamin K may advance anticoagulation control and be clinically beneficial. Hence available medical literature were studied,
specifically inspecting the effect of supplementation with low-dose vitamin K
in reducing adverse effects when taking vitamin K antagonist (VKA) and for
maintenance of the international normalized ratio (INR).
Many scientific studies and publications were
searched, looking at precise trials for effect of taking vitamin K
supplementation against placebos in patients taking a VKA. Examples include the
Cochrane Library, the U.S. National Institutes of Health clinical trials, Ovid
Medline database and International Pharmaceutical Abstracts. Further references
from applicable publications were also screened to recognise additional
clinical trials. All studies considered where in the English-language. Quality
of evidence in the abstract studies were rated by using the grading of the recommendations
assessment, development, and evaluation system. The data from these studies
were used to evaluate haemorrhage, thromboembolic events and the times when INR
was within the therapeutic range.
Studies issued between 1970 and 2012 that fitted the
search strategy. All studies identified were randomized and controlled. The
studies were checked for inclusion by two reviewers, who made sure the studies
met all necessary requirements.
Only published studies which included patients over
the age of eighteen were considered. All the patients were also receiving VKA
therapy at the time of their study.
A total of 624 studies were found and screened,
however only three studies (626 patients) was Included for the meta-analysis.
The reasons for this can be seen on the tables below:
Articles included (n=3)
§ Research question not fully addressed (n=475)
§ Not RCT (n=77)
§ Vitamin K dietary supplementation (n=4)
§ Irrelevant review article (n=18)
§ Single dose vitamin K (n=27)
Some of the limitations in this study includes:
Missing relevant studies due to
only using studies published in the English language.
Only used 3 studies in the
meta-analysis, therefore not very representative.
Lack of studies in groups with
poor INR control.
Publication bias may be present
as English studies have a higher chance of being published if a positive result
When Vitamin K supplementation
was taken daily at low doses (100-200 ?g), it was shown to cause a very
small increase of 0.7% in major bleeds, as well as a slight improvement of 0.3%
in thromboembolic events compared to a 0% change in group of participants
taking no supplements or a placebo. Furthermore, a rise of 3.5% was also seen
for the TTR in groups taking Vitamin K supplementation daily, although being
clinically insignificant. However, no conclusions can be drawn from this data
due to inaccuracies and potential bias, meaning the true results could be very
dissimilar to these assessments.
Ultimately due to the few number
of studies and unpolished quality of data, the results can not be concluded as
being comprehensively accurate. However, the study showed no correlation
between low doses of vitamin k (100 to 200 ?g)
supplementation and any benefits on lessening adverse effects in patients
taking VKAs. Conversely, a slight improvement was seen of the time in
therapeutic range, on average 3.5% better than a placebo. For patients with
unstable INRs, inadequate data collected meant no accurate deduction can be
Vandvik P,Qayyum F, Anne M. Holbrook (1997). Anticoagulation
control with daily low-dose vitamin K to reduce clinically adverse outcomes and
international normalized ratio variability.
Anticoagulation control with daily low-dose vitamin K
to decrease clinically adverse effects and international normalized ratio
A systematic review and meta-analysis.
Jason Lam, Sam Schulman, Daniel M. Witt, Per Olav
Vandvik, Fareeha Qayyum, Anne M. Holbrook