This study aimed to test whether RDW can predict
the risk of amputation in the early postoperative
or midterm period in patients who underwent
embolectomy for acute lower limb ischemia. The
mean RDW in the amputation group was within
the normal range but was significantly higher than
that of the patients in the limb salvage group. In
the univariate analysis, RDW was found to be a
significant predictor of major amputation but not
that of minor amputation. In the multivariate analysis
adjusted for age and sex, this significant association
was absent. The overall amputation (major and minor
amputations or early and midterm amputations)
sensitivity and specificity of RDW as a laboratory
indicator was unsatisfactory.
It is controversial whether the ideal interventional
treatment in acute lower limb ischemia is the use
of evolving endovascular methods or the traditional
surgical approach. Lukasiewicz,[9] in a recent study
comparing the results of endovascular procedures
and surgery/hybrid therapy in acute limb ischemia,
reported that amputation and complication rates
were comparable, six-month mortality was higher
in those who underwent surgery, and the rate of
reintervention was higher in those who underwent
endovascular treatment. This study concludes that both
modalities have an effective role in the contemporary
management of acute lower limb ischemia, with
two-thirds of all patients having arterial thrombus in
the etiology (half underwent surgery) and embolism
(86% underwent surgery) in the remaining. Surgery
has been our routine approach in cases with arterial
embolism from a distal source to the lower limb, and
in the present study, we wanted to determine the prognostic role of RDW in this patient subgroup; our
early amputation rate (n=26, 10.6%) was close to the
rate reported after surgery in the above study (8.9%).
Several studies have addressed clinical and
demographic risk factors for amputation following
acute lower limb ischemia, but the parameters reported
were varied. In a recent epidemiological study, the
one-year amputation rate was as high as 46%, and
high-grade ischemia, the female sex, age, and anemia
were associated with a higher risk of amputation. In
addition, this study reported that the amputation rate
in individuals living at a nursing home was 100%.[1]
There were also studies reporting that delayed surgical
intervention after admission significantly increased
the risk of amputation.[7,14] In our study, recurrent
embolism in the related limb and urea level appeared
to be significant predictors of both major and minor
amputations, even when adjusted for age and sex.
Red cell distribution width reflects the erythrocyte
size distribution and is routinely calculated in the total
blood count. Although it is used in the differential
diagnosis of anemia, it has been shown to be correlated
with fragility and vulnerability in individuals with
systemic disease. Therefore, its usefulness in calculating
cardiovascular risk has recently been the focus of
research.[15] Talarico et al.,[10] in a retrospective study,
found that the highest RDW tertile was independently
associated with increased risk of all-cause death
(hazard ratio [HR]=2.73, 95% CI: 1.63-4.5) and
composite end point (adjusted HR=2.23, 95% CI:
1.53-3.24), (Cox regression, median follow-up: 3.78
years), proposing that RDW is a good prognostic
marker for cardiovascular mortality. Others reported
that the increased values of RDW were significantly
associated with several cardiovascular outcomes,
including coronary calcium score and related
cardiovascular risk,[11] periprocedural myocardial
infarct in patients receiving elective percutaneous
coronary intervention,[16] mortality due to carotid
atherosclerosis,[17] and stroke risk.[18]
A survey study demonstrated that RDW is an
independent predictor of the risk of developing
peripheral artery disease. The study determined that
even when multiconfounding adjustment was made,
each unit increase in the RDW increased the risk of
peripheral arterial disease. Finding Odd’s ratio 1.9
was a numerical indicator of this. In fact, the high
quartile RDW was found to significantly improve
the predictive accuracy of peripheric arterial disease screening criteria.[14] Ye et al.,[19] in a study in which
they followed 13,039 patients with peripheral artery
disease, showed that patients in the highest quartile of
RDW had a 66% higher overall mortality than those
in the lowest quartile (after adjustment for age, sex,
cardiovascular risk factors, and comorbidities). Another
more recent study suggested that an RDW level above
the 75th percentile (>14.1%) is an independent predictor
of peripheral artery disease presence and complexity
(TASC [TransAtlantic InterSociety Consensus] C
and D).[20] Although these studies reliably indicate
that RDW levels are indicative of the presence and
prognosis of lower extremity ischemic artery disease,
none of them have addressed whether RDW levels
are associated with limb salvage after acute lower limb
ischemia.
Since the cut-off value we found (13.85%) for the
prediction of overall (major and minor) amputation
is in the normal range, it may not have prognostic
significance alone in patients presenting with acute
lower limb ischemia. Red cell distribution width is
used in routine clinical practice in the differential
diagnosis of vitamin B12 deficiency, folic acid
deficiency, and other megaloblastic anemias with
macrocytosis. Therefore, RDW can be affected by
the level of these substances. Moreover, although the
upper limit of RDW is reported as 14.0%, this value is
an instrument-specific value and may vary according
to the standards of each laboratory. In addition to
these, considering that RDW is affected by acute
inflammation, white blood cell count, and even lipid
profile, it can only aid other prominent risk factors
in calculating the risk of amputation after acute limb
ischemia.[21]
The main limitation of the present study was its
retrospective design. In a prospective and matchcontrolled
study, the deviation of RDW from the
normal value could be calculated, and a more accurate
effect size could be obtained. Another limitation of
the study was that the operations were performed
by different surgeons, which may have affected the
patency. The inability to include amputation-free
survival rates in the risk calculation due to the short
follow-up period is one of the limitations that should
be noted. Because of the heterogeneity in our patient
group, RDW levels may not have accurately predicted
the risk of amputation in our study. A larger study in a
more homogeneous group is required.
In conclusion, RDW may have a role in the
prediction of adverse outcomes in patients treated for acute lower limb ischemia; however, since amputation
is associated with many confounders and RDW levels
are affected by certain clinical parameters, it cannot be
used as a stand-alone predictive marker. Future studies
on risk assessment in amputation are needed, in which
the confounders are adjusted and the RDW values are
calibrated with a control group sampled at the same
health center, to determine the optimal cut-off value
or percentile of RDW.
Ethics Committee Approval: The study protocol
was approved by the Türkiye Yüksek Ihtisas Education
and Research Hospital Education Planning Board (date:
23.09.2014, no: 12631). The study was conducted in
accordance with the principles of the Declaration of Helsinki.
Patient Consent for Publication: A written informed
consent was obtained from each patient.
Data Sharing Statement: The data that support the
findings of this study are available from the corresponding
author upon reasonable request.
Author Contributions: Data collection and/or processing,
analysis and/or interpretation, literature review, writing the
article, critical review, references and fundings: S.S.; Idea/
concept, design: I.T.
Conflict of Interest: The authors declared no conflicts
of interest with respect to the authorship and/or publication
of this article.
Funding: The authors received no financial support for
the research and/or authorship of this article.