Background
The World Health Organisation (WHO) originally defined anaemia based on
haemoglobin (Hb) levels as < 130 g L-1 for men and <
120 g L-1 for non-pregnant women[6]. Based on this definition being
widely used within protocols across the National Health Service (NHS),
there have been large variations of the reported prevalence of anaemia
within communities. Unfortunately, this definition does not account for
other factors that may have important contributions to the effects of
anaemia such as age, gender, ethnicity, symptoms of fatigue and the
presence of cardiovascular disease, to name a few.
Two particular studies quote the prevalence of anaemia to be 20-25% of
the population cohort presenting for major lower limb surgeries[7,
8]. The relationship and impact of anaemia on surgical outcomes has
been widely investigated to understand if improvements in the
peri-operative period can lead to better results for patients.
Historically, the initial studies began within cardiac surgery. From
there, further studies were published looking into other specialities.
Specifically delving into major lower limb orthopaedic surgery, a couple
of studies suggested that allogenic blood transfusions in this cohort
accounted for 8-10% of the total donated blood transfusions within the
UK[9, 10]. In addition to this, Kotze et al demonstrated that a
patient’s preoperative Hb concentration predicted the likelihood of the
need to receive allogenic blood transfusions, as well as the hospital
length of stay[7]. There is evidence to suggest that both anaemia
and allogenic blood transfusions contribute in an accumulative method to
risk factors for poor post-operative outcomes[11]. A retrospective
study looking at 300,000 patients undergoing non-cardiac surgery
identified that a preoperative haematocrit of less than 39% had a
statistically significant increase in mortality at 30 days[12].
With an understanding of the impact of pre-operative anaemia the Network
for Advancement of Transfusion Alternatives (NATA), constituted of a
multidisciplinary panel of physicians, developed guidelines for
identifying, evaluating and managing pre-operative anaemia in patients
undergoing elective orthopaedic surgery[13]. These guidelines have
been widely adapted across the UK as well as the implementation of
enhanced recovery programmes to assist patients in achieving a
satisfactory and better surgical outcome.
However, to best understand the management options, we must firstly
understand the cause of the anaemia. A publication released through the
AAGBI in 2015 suggested that the cause of anaemia could be categorised
into 3 broad groups: nutrient deficiency anaemia, anaemia of chronic
inflammation, and unexplained anaemia[14]. Nutrient deficiency
anaemia includes deficiencies in iron (accounting for the largest cause
of all anaemias at 16.6%[14]), B12 and folate.
Anaemia of chronic inflammation (or chronic disease) incorporates
conditions such as chronic kidney disease, autoimmune disorders,
malignancy and inflammatory conditions. These are typically seen as
normocytic and normochromic anaemia. There is often a crossover between
these 2 groups of anaemias, typically identified by low iron stores due
to the pathophysiology within the chronic inflammatory conditions.
Hepcidin, a protein secreted by the liver, is key to regulating iron
levels within the plasma. It inhibits iron absorption from the gut, as
well as causing iron trapping within macrophages and liver cells. In
chronic infection and inflammatory conditions, Hepcidin production is
significantly increased which can lead to a ‘functional’ iron deficient
anaemia[15]. The second mechanism by which anaemia of chronic
inflammation occurs is by the reduction of erythropoiesis mediated by
various cytokine pathways, including interleukin (IL)-6, as well as
TNFα, IL-1α and IL-1β. There is also a third and final pathway to
consider, in which cytokines cause a decrease in red cell survival and
cell death. These mechanisms are also important to understand in the
post-operative period because surgery will often blunt the body’s
response to anaemia through release of these inflammatory
cytokines[16], and therefore, it could be expected that blood loss
and intra-operative haemodilution could prolong the extent of
post-operative anaemia.
The third category of unexplained anaemia includes those conditions that
did not meet the criteria for the previous 2 groups based on detection
and tests, and those who’s conditions may not have been identified
without further specialist tests (such as myeloma). Nevertheless, these
patients can still be treated in spite of an exact cause not known.
Having understood the pathophysiology of anaemia, the NATA guidelines
for the management of pre-operative anaemia (following detection and
evaluation) concentrate on the correction of nutrient deficiency anaemia
and anaemia of chronic inflammation. In the first instance, NATA
recommends that nutritional deficiencies be treated, in particular,
attempting to correct iron deficiency as it is the most common cause of
anaemia. Traditionally, this has been through oral iron supplements.
However, we know that these are not always well tolerated by patients as
they can lead to gastrointestinal disturbances[17]. As an
alternative, intravenous (IV) iron therapy has been recommended within
the guidelines depending on the time scale as well as the intolerance of
oral iron supplements. There have been studies in which IV iron
supplementation reduced the requirements for allogenic blood
transfusions in gynaecological cancer patients[18, 19].
The alternative stage recommended by NATA is the suggestion to stimulate
erythropoiesis by erythropoiesis-stimulating agents (ESA). The
guidelines published first performed a meta-analysis of 41 studies
looking into the use of ESA before recommending their concomitant use
with iron therapy[13], which correlates in theory with the crossover
in mechanism for the cause of anaemia in this group of patients.