State of the Art

Blood management in total knee arthroplasty: state-

J ISAKOS: first published as 10.1136/jisakos-2017-000168 on 21 September 2018. Downloaded from http://jisakos.bmj.com/ on June 22, 2020 by guest. Protected by copyright.
of-the-art review
Antony Palmer,1 Antonia Chen,2 Tomoyuki Matsumoto,3 Mike Murphy,4,5
Andrew Price1
1
Nuffield Department of Abstract Total knee arthroplasty (TKA) represents major
Orthopaedics, Rheumatology, Total blood loss from primary total knee arthroplasty surgery that is performed on an ageing population.
and Musculoskeletal Sciences,
University of Oxford, Oxford, UK may exceed 2 L with greater blood loss during revision Over 35% of patients undergoing lower limb arthro-
2
Department of Orthopaedic procedures. Blood loss and allogeneic transfusion are plasty are anaemic preoperatively4 5 and over 85%
Surgery, Brigham and Women’s strongly associated with adverse outcomes from surgery are anaemic after knee arthroplasty surgery, defined
Hospital, Harvard Medical including postoperative mortality, thromboembolic by the WHO as a haemoglobin (Hb) concentration
School, Boston, Massachusetts, below 120 g/L for women and 130 g/L for men.6 7
USA
events and infection. Strategies to reduce blood loss
3
Department of Orthopaedic and transfusion rates improve patient outcomes and The strongest risk factor for transfusion is preop-
Surgery, Kobe University, Kobe, reduce healthcare costs. Interventions are employed erative anaemia and preoperative patient optimisa-
Japan preoperatively, intraoperatively and postoperatively. tion is essential.8 9
4
NHS Blood and Transplant, Studies report a large variation in blood loss
Oxford, UK
The strongest predictor for allogeneic blood transfusion
5
Department of Haematology, is preoperative anaemia. Over 35% of patients are during knee arthroplasty surgery, in part due to
Oxford University Hospitals NHS anaemic when scheduled for primary and revision heterogeneous patient cohorts, surgical and anaes-
Foundation Trust, Oxford, UK knee arthroplasty, defined as haemoglobin <130 thetic techniques and methods of calculating the
g/L for men and women, and the majority of cases volume of blood loss.6 A study of 4769 patients
Correspondence to are secondary to iron deficiency. Early identification who underwent primary TKA had a calculated
Mr Antony Palmer, Nuffield mean total blood loss of 2181 mL (SD 931) with a
Department of Orthopaedics, and treatment of anaemia can reduce postoperative
Rheumatology, and transfusions and complications. Anticoagulation must mean postoperative drop in Hb concentration of
Musculoskeletal Sciences, be carefully managed perioperatively to balance 3.0 g/L (SD 1.2) and 14.6% of patients received
Botnar Research Centre, the risk of thromboembolic event versus the risk an allogeneic blood transfusion.5 Blood loss is
University of Oxford, Oxford higher for revision procedures, although diffi-
OX3 7LD, UK;
of haemorrhage. Intraoperatively, tranexamic acid
reduces blood loss and is recommended for all knee cult to quantify due to the heterogeneity of these
​antony.​palmer@n​ dorms.​ox.​
ac.​uk arthroplasty surgery; however, the optimal route, dose procedures.
or timing of administration remains uncertain. Cell This review article discusses preoperative, intra-
Received 13 February 2018
salvage is a valuable adjunct to surgery with significant operative and postoperative measures that can be
Revised 17 July 2018 used to deliver optimal blood management and
Accepted 25 August 2018 expected blood loss, such as revision knee arthroplasty.
Published Online First Autologous blood donation is not recommended in improved patient outcomes after knee arthroplasty. 
21 September 2018 routine care, sealants may be beneficial in select cases
but further evidence of benefit is required, and the Preoperative
use of a tourniquet remains at the discretion of the
Preoperative anaemia
surgeon. Postoperatively, restrictive transfusion protocols
The strongest risk factor for allogeneic blood trans-
should be followed with a transfusion threshold fusion after primary and revision TKA is preop-
haemoglobin of 70 g/L, except in the presence of acute erative anaemia.4 6 The WHO defines anaemia as
coronary syndrome. Recent studies report no allogeneic an Hb concentration below 120 g/L in women and
transfusions after primary knee arthroplasty surgery after 130 g/L in men. However, a recent consensus state-
employing blood conservation strategies. The current ment outlines key limitations of sex-specific thresh-
challenge is to select and integrate different blood olds when optimising patients for surgery. The same
conserving interventions to deliver an optimal patient surgical procedure will result in comparable blood
pathway with a multidisciplinary approach. loss for both sexes, and therefore a higher blood
loss in women relative to their circulating volume
may result in higher transfusion rates.6 9 The recom-
mended target preoperative Hb is therefore 130 g/L
Introduction for both sexes.9
The number of primary and revision knee arthro- Preoperative anaemia is prevalent among ortho-
plasty procedures continues to increase,1 and blood paedic patients but varies between patient popula-
management strategies form a key intervention to tion and depends on the Hb threshold used to define
© International Society of
Arthroscopy, Knee Surgery and
improve outcomes and reduce costs.2 The primary anaemia. Adopting a threshold of 130 g/L, Jans et al
Orthopaedic Sports Medicine goal is to reduce the severity of postoperative report an anaemia prevalence of 31% of patients
2018. No commercial re-use. anaemia through preoperative optimisation and undergoing primary TKA in Denmark,12 and the
See rights and permissions. minimising intraoperative and postoperative blood same prevalence has been reported in Spain.13
Published by BMJ.
loss through patient-specific approaches. Strategies Anaemia is more prevalent in patients undergoing
To cite: Palmer A, Chen A, to reduce blood loss may have secondary bene- revision surgery in association with increasing age
Matsumoto T, et al. JISAKOS fits to improve postoperative pain and functional and comorbidities. Adopting the WHO thresholds
2018;3:358–366. outcomes.3 for anaemia, the prevalence of anaemia has been
358 Palmer A, et al. JISAKOS 2018;3:358–366. doi:10.1136/jisakos-2017-000168. Copyright © 2018 ISAKOS
 State of the Art
Absolute iron deficiency describes reduced or absent total body

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Box 1  Measuring blood loss iron stores, whereas functional iron deficiency usually describes
a reduced ability to mobilise iron from these stores due to
Research in this field is frequently limited by different measures
chronic inflammation.9 A large number of protocols have been
of blood loss, making it difficult to interpret and compare studies.
proposed to treat preoperative iron deficiency, which typically
A key distinction is between visible and hidden blood loss.10
consist of oral iron supplementation for absolute deficiency, and
Visible blood loss is that from the operative field and in drains,
intravenous iron for functional iron deficiency or where oral
whereas hidden loss includes blood lost through extravasation
iron proves ineffective.9 Lower oral iron doses can increase effi-
into tissues and residual haemarthrosis. Hidden blood loss may
cacy and reduce gastrointestinal side effects.16 Patients diagnosed
account for 49% of calculated total blood loss.10 Total blood
with iron deficiency anaemia must also be screened for gastroin-
loss is the sum of visible and hidden losses and is calculated
testinal malignancy and other causes of chronic blood loss.
using a number of available formulas.11 Many formulas require
The diagnosis and treatment of iron deficiency anaemia
calculation of the total blood volume, typically estimated using
increases Hb concentrations, reduces transfusion rates and
Moore or Nadler’s formula.
improves outcomes from surgery. Evidence is limited to cohort
studies, but the introduction of a preoperative anaemia algo-
Blood loss outcome measures:
rithm reduces rates of hospital readmission and admission to
►► Change in haemoglobin (Hb) concentration.
critical care, length of stay2 17 and possibly infection.18 Increased
►► Estimated intraoperative loss.
Hb concentrations also prevent transfusion-related complica-
►► Drain output.
tions.19 Health economic analysis reveals significant savings
►► Transfusion rate.
from preoperative anaemia screening and management.2 The
►► Number of units transfused.
benefits of treating anaemia may not purely reflect increased Hb
►► Calculated total blood loss.
concentrations, as iron is important for cellular processes such as
oxygen transport and cellular immunity.20
Calculated total blood loss
Many different formulas have been proposed for calculating total
blood loss and those described by Gross and Mercuriali are used Other causes of anaemia
most frequently.11 Formulas to calculate total blood loss require When anaemia is not secondary to iron deficiency, alternative
an estimate of circulating blood volume using either the Moore causes must be sought and addressed. Vitamin B12 and folate
or Nadler formulas.11 deficiency account for 15% of preoperative anaemia,21 while
anaemia may also result from renal, haematological and endo-
Gross formula crine disorders. Anaemia management may therefore require
Estimated total blood loss (mL)=estimated blood input from multiple medical specialties to address the under-
volume×(Hct0−Hct1)/HctAv, where Hct0 is preoperative lying cause. Besides iron supplementation, additional strategies
haematocrit, Hct1 is postoperative haematocrit and to increase Hb concentration include administration of recom-
HctAv is average of preoperative and postoperative haematocrit. binant human erythropoietin to stimulate eropoiesis. Erythro-
poietin increases preoperative and postoperative Hb in patients
Mercuriali formula with TKA,22 but it is expensive and may not be approved for
Estimated total blood loss (mL of RBC)=estimated blood patient use. Erythropoietin is only recommended in specific
volume×(Hct0−Hct5)+mL transfused RBC, where circumstances, including anaemia secondary to chronic renal
Hct0 is preoperative haematocrit and Hct5 is haematocrit failure or when blood products are not available or acceptable
postoperative day 5. to patients.23

Preoperative autologous blood donation

reported as 13%14 and 19%15 for primary TKA compared with Preoperative autologous blood donation, where blood is donated
42%4 for revision TKA. and stored preoperatively and then administered if required
postoperatively, was used widely prior to elective surgery, partic-
Iron-deficiency anaemia ularly in the USA. However, disadvantages include the potential
The most frequent aetiology of preoperative anaemia is iron defi- exacerbation of preoperative anaemia and risks associated with
ciency,9 which can be classified as absolute or functional (table 1). interval reinfusion. There is also significant cost and wastage,
since less than half of the preoperative blood collected is used.24
The technique is now rarely used, but may be indicated in select
cases, such as patients with multiple red cell antibodies where
Table 1  Classification of preoperative anaemia8
compatible donor blood may not be available.
Blood results Classification
Ferritin <30 mcg/L Absolute iron deficiency
Optimising patients for surgery
Ferritin 30-100 mcg/L and CRP >5 mg/L Iron deficiency in presence of
inflammation Preoperative optimisation of anaemia requires early identifi-
Ferritin 30-100 mcg/L and CRP ≤5 mg/L Probable iron deficiency
cation and treatment. A full (complete) blood count should be
and transferrin saturation <20% requested at the time patients are scheduled for knee arthroplasty,
Ferritin 30-100 mcg/L and CRP ≤5 mg/L Restricted iron stores for significant with renal function and group and save (type and screen).25 Iron
and transferrin saturation ≥20% blood loss studies and markers of inflammation, such as C-reactive protein,
Ferritin >100 mcg/L and CRP ≤5 mg/L Non-iron deficiency anaemia should also be included if Hb measurements are below 130 g/L
Management algorithm for preoperative anaemia should be agreed locally with in both men and women. If iron studies are normal, preoper-
engagement of multidisciplinary team. ative anaemia requires further investigation, and interventions
CRP, C-reactive protein. to optimise anaemia should commence at diagnosis. Significant
Palmer A, et al. JISAKOS 2018;3:358–366. doi:10.1136/jisakos-2017-000168 359
 State of the Art
increases in Hb can be obtained within 4 weeks, and there is no Warfarin

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required minimum time between commencing iron or other Warfarin inhibits the synthesis of vitamin K dependent proco-
therapy, and surgery.18 agulation factors and has a half-life of approximately 36 hours.
An additional scenario to consider is when patients have In the acute setting, warfarin can be reversed with intravenous
adequate iron stores to support erythropoiesis and are there- phytomenadione or prothrombin complex, and in the elec-
fore not anaemic preoperatively but have low iron stores that tive setting, warfarin must be stopped 5 days before surgery to
restrict the ability to restore Hb concentration after surgical normalise laboratory tests of coagulation.29 Treatment options
blood losses (table 1). Patients with low iron stores may there- include stopping warfarin 5 days prior to surgery with or without
fore benefit from iron supplementation prior to surgery in the treatment dose bridging heparin.
absence of anaemia, and iron studies may be appropriate for all Evidence to support bridging therapy with heparin is limited
preoperative patients.9 and studies reveal a similar risk of thromboembolic events but an
There is no agreed Hb threshold to proceed with surgery increased risk of bleeding when using bridging heparin compared
and decisions must take into account the clinical urgency of a with no anticoagulation.32 Bridging anticoagulation is no longer
procedure, particularly in the case of periprosthetic fractures or indicated in most patients receiving warfarin for atrial fibrilli-
infection. The lower the preoperative Hb, the higher the risk ation.33 However, it may be appropriate in patients at partic-
of perioperative transfusion.8 The goal is to correct reversible ularly high risk of thromboembolic events such as those who
causes of anaemia prior to elective surgery, acknowledging that experienced a venous thromboembolic event or stroke within
it may not be possible to achieve a preoperative Hb greater the past 3 months, or patients with a mechanical heart valve.29
than 130 g/L in all patients. Correcting anaemia with preopera- It is best practice to measure the international normalised ratio
tive transfusion is not recommended and can be detrimental to on the day preceding surgery to ensure there is no residual
outcomes.9 anticoagulation.29
Small studies report no difference in complication or transfu-
sion rates between individuals continuing therapeutic warfarin
Preoperative management of antiplatelet agents and
dose throughout surgery compared with individuals who stop
anticoagulants
warfarin and commence bridging low-molecular weight heparin
A significant proportion of patients who undergo knee arthro-
(LMWH) for primary and revision knee arthroplasty.34 35 Further
plasty may take antiplatelet agents to modify cardiovascular and
evidence is required before recommending this practice, which
cerebrovascular risk, and anticoagulant agents to modify throm-
prevents the use of neuroaxial anaesthesia.
boembolic risk where indications include atrial fibrillation,
Complications after TKA are more frequent in patients
previous thromboembolic events and prosthetic heart valves.
taking warfarin preoperatively compared with patients not
Perioperative management of these agents is patient specific and
must balance the risk of haemorrhage with the risk of thrombo- taking anticoagulants, including prolonged wound discharge,
embolic events. Management decisions may require input from superficial and deep infection, and further surgery.36 However,
the patient, surgeon, physician and anaesthetist. this may reflect comorbidity rather than the anticoagulation
itself.

Antiplatelet agents
Antiplatelet agents inhibit platelet aggregation and thrombus Direct oral anticoagulants
formation. Most agents irreversibly bind platelet receptors, Direct oral anticoagulants (DOAC) either inhibit thrombin
which means their action lasts the lifetime of a platelet, typically (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban).
up to 10 days. It therefore takes approximately 7 days after drug They have several advantages over warfarin, including more
cessation before platelet function is restored. predictable pharmacokinetics resulting in no requirement to
Aspirin withdrawal precedes up to 10% of acute cardiovas- monitor laboratory tests of coagulation. When it is desirable to
cular events,26 and stopping aspirin 7 days prior to surgery in monitor laboratory tests, patients require an assay of thrombin
patients with high cardiovascular risk significantly increases time for dabigatran and factor Xa for rivaroxaban, apixaban
the 30-day risk of major cardiovascular event from 1.8% to and edoxaban. Normal prothrombin time and activated partial
9%.27 Individual studies have not identified differences in the thromboplastin times do not exclude residual action of DOACs.
rate of thromboembolic or bleeding events when comparing A disadvantage of DOACs over warfarin is the lack of reversal
preoperative aspirin cessation or continuation.28 However, agents; however, these are under development. Idarucizumab is
a meta-analysis concluded that continuing aspirin results in a now available as a reversal agent for dabigatran, although this is
1.5 times increase in the risk of bleeding complications, but usually only used in emergency settings.
does not increase the number of bleeding complications that The shorter half-life of DOACs compared with warfarin
require medical intervention.26 Consensus guidelines recom- means they can be stopped closer to the date of surgery, leaving
mend continuing aspirin monotherapy for knee arthroplasty patients non-anticoagulated for a shorter period of time. In
surgery,29 30 and this strategy still allows for the use of neuro- the presence of normal renal and hepatic function, guidelines
axial anaesthesia.31 There is currently insufficient evidence to recommend stopping DOACs 48 hours prior to surgery.29 30
guide management of ADP receptor antagonist monotherapy, Stopping dabigatran 48 hours prior to surgery does not result
such as clopidogrel.29 in any significant difference in perioperative bleeding events
An increasing number of patients are prescribed dual anti- compared with stopping warfarin 5 days previously.37 As with
platelet therapy after a cardiac event or coronary revasculari- warfarin, the role of bridging anticoagulation is debated and a
sation. Dual antiplatelet therapy consists of aspirin and an study has shown higher rates of major bleeding and no differ-
ADP receptor antagonist. Current guidance is to stop the ADP ence in the rate of thromboembolic events when comparing no
receptor antagonist 7 days preoperatively and to continue aspirin anticoagulation with bridging anticoagulation in patients with
monotherapy.29 30 atrial fibrillation.38
360 Palmer A, et al. JISAKOS 2018;3:358–366. doi:10.1136/jisakos-2017-000168
 State of the Art
Normovolaemic haemodilution is a technique where blood

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Box 2  Tips and tricks
is collected in the immediate preoperative period with fluid
replacement to reduce the haematocrit of blood lost during
1. Obtain laboratory tests for full (complete) blood count and
surgery. Surgery is followed by autologous reinfusion of the
renal function at the time patients are scheduled for surgery.
preoperative collected blood; however, the benefits remain
2. Investigate the aetiology of preoperative anaemia and
uncertain.22
commence treatment at the earliest opportunity (target
haemoglobin (Hb) >130 g/L for men and women).
3. Use topical, intravenous, oral or combined routes of Tourniquet
tranexamic acid administration for all knee arthroplasty Tourniquet application is used by most surgeons during knee
procedures. arthroplasty procedures with the goal of reducing blood loss
4. Do not use conventional suction drains. Consider cell salvage and creating a bloodless field to improve visualisation of tissues.
for revision knee arthroplasty when significant blood loss is Proposed potential benefits also include improving cement
expected. integration with bone, which has not been supported by recent
5. Follow postoperative restrictive transfusion regimen with imaging studies.46 Patients also experience increased pain with
Hb threshold <70 g/L except in patients with acute coronary compromised quadriceps function47 48 and a higher incidence of
syndrome. thrombotic events49 with the use of a tourniquet.
Studies report conflicting outcomes with respect to the effect
of tourniquet use on blood loss. Meta-analyses suggest that
Intraoperative
while a tourniquet decreases intraoperative blood loss, there is
Surgical technique
no difference in total blood loss.49 50 Tourniquet use may even
Surgical technique varies significantly between surgeons and
increase total blood loss through the release of inflammatory
may influence blood loss. An alternative to the traditional
mediators secondary to limb ischaemia.51 Surgeons may elect to
medial parapatellar surgical approach for TKA is the mid-vastus
have the tourniquet inflated for different portions of the proce-
or subvastus approach, which can be used as part of a minimally
dure, and overall, the effects on blood loss do not appear to be
invasive procedure. These techniques may improve early pain and
clinically significant.52 The decision of whether to use a tourni-
range of movement, but do not reduce blood loss.39 40 A comput-
quet may be guided by factors other than blood management.
er-navigated mid-vastus approach may even increase blood
loss compared with a computer-navigated medial parapatellar
approach, potentially secondary to increased operating times.41 Tranexamic acid
Retrospective cohort studies demonstrate that increased opera- Tranexamic acid is a synthetic lysine analogue that competitively
tive time is associated with increased rates of allogeneic trans- inhibits plasminogen activation to provide antifibrinolytic action
fusion; however, confounding factors including the indication and clot stabilisation. It is recommended for all TKA surgery in
for surgery may contribute to this observation. Computer navi- the UK,23 but it is not approved by the Food and Drug Admin-
gation may reduce total blood loss during surgery by negating istration for this purpose. Tranexamic acid has been shown to
the need for entering the intramedullary canal; however, gains reduce the need for transfusion by 69%53 without increased risk
may be offset by increased operating times.42 The same obser- of thromboembolic complications.54 A vast number of studies
vation may also be found for patient-specific knee prostheses. investigate the efficacy of tranexamic acid, and while they invari-
Retrospective studies demonstrate that unicompartmental knee ably demonstrate that tranexamic acid reduces blood loss and
arthroplasty results in less blood loss than TKA,43 and that there the need for transfusion, the optimal route, dose and timing of
is less blood loss with a cruciate retaining implant than a poste- administration remain undetermined. A further uncertainty is
rior stabilised implant.44 Implant selection may therefore affect whether the risk of thromboembolic events has been adequately
expected blood loss from arthroplasty procedures. addressed in high-risk subgroups.
Tranexamic acid administration can be intravenous, intra-ar-
Anaesthesia ticular or oral, or in combination. Combined intra-articular and
Anaesthetic factors to reduce intraoperative blood loss include intravenous delivery has been shown to result in a greater reduc-
maintaining patient normothermia and reducing blood pres- tion in blood loss than intravenous delivery alone for primary
sure. Spinal anaesthesia produces a blockage of preganglionic TKA,55 or intra-articular delivery alone for revision TKA.56
sympathetic nerves that reduces peripheral vascular resistance Intra-articular delivery alone may be as efficacious as intrave-
and blood pressure. During total hip arthroplasty, regional nous57 or combined intra-articular and intravenous delivery58
anaesthesia results in lower blood loss than general anaesthesia; for primary TKA; however, the use of different tranexamic
however, this finding is not reliably reproduced for knee surgery, doses between studies limits the interpretation. No differences
perhaps due to the use of tourniquets.5 45 The choice of anaes- in rate of thromboembolic complications have been observed
thetic modality should be driven by other factors such as lumbar with different routes of administration.55 58 There is emerging
spine pathology and recent anticoagulation. evidence that tranexamic acid reduces postoperative swelling,
and improves range of movement and patient-reported outcomes
after TKA.48 59
Box 3  Major pitfalls
Current evidence supports the use of topical tranexamic acid
with or without intravenous delivery. Oral tranexamic acid also
1. Late diagnosis or failure to address preoperative anaemia.
reduces blood loss after primary TKA and requires further explo-
2. Failure to discuss blood conservation strategies with the
ration due to lower costs.60 Potential advantages of intra-artic-
anaesthetic team.
ular delivery are that it may overcome systemic contraindications
3. Transfusion of allogeneic blood with inappropriate clinical
such as renal insufficiency due to lower plasma levels.61 Concerns
indication.
over tranexamic acid chondrotoxicity may prevent topical use in
Palmer A, et al. JISAKOS 2018;3:358–366. doi:10.1136/jisakos-2017-000168 361
 State of the Art
Fibrin sealant

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Box 4  Ten key publications
Topical application of fibrin sealants (fibrinogen and thrombin)
to bleeding tissues is another haemostatic strategy that can be
1. Jans Ø, Jørgensen C, Kehlet H, Johansson PI. Role
used during TKA. Meta-analyses offer contradictory conclusions
of preoperative anemia for risk of transfusion and
as to whether fibrin sealant reduces total blood loss; however,
postoperative morbidity in fast-track hip and knee
there may be a reduction in drain output and transfusion rate
arthroplasty. Transfusion 2014;54:717–26.
without an increased risk of complications.70 Fibrin sealant is not
2. Muñoz M, Acheson AG, Auerbach M, et al. International
as effective as tranexamic acid at reducing blood loss71 and given
consensus statement on the perioperative management of
the high additional cost, the role of fibrin sealant in a multi-
anaemia and iron deficiency. Anaesthesia 2017;72:233–47.
modal blood management algorithm is uncertain.
3. Pujol-Nicolas A, Morrison R, Casson C, et al. Preoperative
screening and intervention for mild anemia with low iron
stores in elective hip and knee arthroplasty. Transfusion Diathermy
2017;0:1–9. Monopolar radiofrequency electrocautery is a valuable tool to
4. Keeling D, Tait RC, Watson H, British Committee of achieve intraoperative haemostasis. An alternative is a bipolar
Standards for Haematology. Perioperative management of sealer system that works at lower temperatures to denature
anticoagulation and antiplatelet therapy. Br J Haematol collagen and seal blood vessels, which is thought to cause less
2016;175:602–13. damage to adjacent healthy tissues.72 73 It is challenging to quan-
5. Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative tify the effects of cautery due to variation in technique among
bridging anticoagulation in patients with atrial fibrillation. N surgeons. At present, there is insufficient evidence to recommend
Engl J Med 2015;373:823–33. routine use of bipolar sealer systems to reduce blood loss, which
6. Poeran J, Rasul R, Suzuki S, et al. Tranexamic acid use and carry a significant cost. Bipolar sealer systems do not appear to
postoperative outcomes in patients undergoing total hip or confer benefits in the presence or absence of tranexamic acid for
knee arthroplasty in the United States: retrospective analysis primary TKA,72 or in the absence of a tourniquet during revision
of effectiveness and safety. BMJ 2014;349:1–10. TKA.73
7. Franchini M, Mengoli C, Marietta M, et al. Safety of
intravenous tranexamic acid in patients undergoing
Cell salvage and drains
major orthopaedic surgery: a meta-analysis of randomised
Cell salvage describes the recovery of blood from the surgical
controlled trials. Blood Transfus 2018;16:36–43.
field, and it is recommended for major orthopaedic procedures
8. Carless PA, Henry DA, Moxey AJ, O’Connell D, Brown T,
where blood loss exceeds 20% of estimated blood volume.23 74
Fergusson DA. Cell salvage for minimising perioperative
Cell salvage reduces the risk of exposure to allogeneic blood by
allogeneic blood transfusion. Cochrane Database Syst Rev
54%75 76 and can be performed intraoperatively by collecting
2010.
blood though a suction system or postoperatively using an autol-
9. Docherty AB, O’Donnell R, Brunskill S, et al. Effect of
ogous reinfusion drain that is inserted at the time of surgery.
restrictive versus liberal transfusion strategies on outcomes
Collected blood is anticoagulated and filtered (40 μm or leuco-
in patients with cardiovascular disease in a non-cardiac
cyte depletion filter) and can then be reinfused directly, or the
surgery setting: systematic review and meta-analysis. BMJ
red blood cells can be washed and resuspended in normal saline
2016;352. doi:10.1136/bmj.i1351.
prior to reinfusion. Blood from intraoperative cell salvage is
10. Gibon E, Courpied JP, Hamadouche M. Total joint
typically washed, whereas blood from reinfusion drains is typi-
replacement and blood loss: what is the best equation? Int
cally unwashed, but either technique can be used in each setting.
Orthop 2013;37:735–9.
Concerns over unwashed blood include low Hb concentration,
and the presence of anticoagulant and inflammatory mediators
in the reinfused blood. Both washed and unwashed blood results
unicompartmental knee arthroplasty, but studies investigating in a hypocoagulable state, although less so with washed blood,77
the effect on chondrocytes are limited to in vitro experiments.62 but no difference in clinical outcomes has been identified.75
Intraoperative cell salvage is less widely used than postoper-
A limitation to comparing routes of delivery is that different
ative drain collection during knee arthroplasty surgery due to
doses and timing of delivery are used in each study, and deter-
the frequent use of a tourniquet. In the absence of a tourniquet,
mining the optimal regimen is a research priority. Some studies
cell salvage may be a valuable adjunct to blood conversation,
suggest reduced blood loss with higher doses of tranexamic acid
particularly during revision surgery where there is greater blood
(>25 mg/kg) with combined routes of administration63 or as a
loss.23 Previous contraindications to cell salvage have included
single preoperative dose.64 There are conflicting studies as to
bacterial infection and malignancy; however, these guidelines are
whether multiple doses of intravenous tranexamic acid confer a now debated.78 When a leucocyte depletion filter is used and the
greater reduction in blood loss or allogeneic transfusion rates.65 66 collected blood is washed, there is a 99% reduction in bacte-
Continuous intravenous infusions of tranexamic do not appear rial contamination.79 Thus, while there is a theoretical increased
superior to a single bolus.67 Standardisation of tranexamic acid risk of adverse events with reinfusion of blood with bacterial
regimens would greatly aid future clinical practice in this field. contamination, there is a definite risk of bacterial contamina-
Haemostasis after TKA may be enhanced when topical tion from allogeneic blood transfusion. No association has been
tranexamic acid is supplemented with topical epinephrine.68 An identified between the use of call salvage and development of
alternative antifibrinolytic agent to tranexamic acid is ꞓ-ami- metastases in cancer surgery.78
nocaproic acid and has demonstrated equivalent efficacy to Conventional suction drains were widely adopted with the
tranexamic acid at lower cost.69 In the USA, the approximate aim of reducing haemarthrosis and may reduce the need for
cost per surgery for ꞓ-aminocaproic acid is US$2, compared dressing reinforcement, but can increase postoperative blood
with US$40 for tranexamic acid.69 loss.80 Temporary clamping of conventional suction drains
362 Palmer A, et al. JISAKOS 2018;3:358–366. doi:10.1136/jisakos-2017-000168
 State of the Art
postoperatively only serves to reduce drain output and not total Allogeneic blood transfusion carries a number of risks,

J ISAKOS: first published as 10.1136/jisakos-2017-000168 on 21 September 2018. Downloaded from http://jisakos.bmj.com/ on June 22, 2020 by guest. Protected by copyright.
blood loss.81 Drains have not been shown to increase infection including haemolytic and allergic reactions, transfusion-related
rates, despite concerns over leaving a tract into the joint, but may acute lung injury and circulatory overload, graft-versus-host
interfere with mobilisation after surgery, and the optimal time disease and transmission of bloodborne infection.19 Transfusion
for drain removal has not been established. is an independent predictor of in-hospital mortality.92 There are
Autologous reinfusion drains can half the proportion of concerns that transfusion may increase the risk of venous throm-
patients requiring allogeneic blood compared with conventional boembolism,93 and immunomodulation also increases suscepti-
suction drains.82 83 However, this is not true in more recent bility to postoperative infection including the lower respiratory
studies with restrictive transfusion thresholds (Hb  ≤80 g/L).83 tract, urinary tract and surgical site.74 Increased infection rates
In addition, autologous reinfusion drains result in a smaller are observed with allogeneic but not autologous blood19 and
reduction in allogeneic transfusion rates when compared with leucocyte depletion decreases postoperative infection rates.94
no conventional suction drain.83 It therefore remains unclear Leucodepletion of all blood products was introduced in the UK
whether autologous reinfusion drains provide clinical benefit or in 1998 but is not used globally. Whether transfusion specifically
cost-effectiveness when used alongside other blood conservation increases the risk of bone and joint infection after arthroplasty
strategies and restrictive transfusion thresholds.84 surgery remains uncertain.95

Postoperative Postoperative management of antiplatelet agents and

Cryotherapy anticoagulants
Patients who regularly take antiplatelet agents and anticoagu-
A number of compression dressings and cryotherapy strategies
lant medication prior to surgery require these postoperatively. In
have been adopted to reduce blood loss; however, their role in
addition, it is recommended that physical and chemical measures
routine clinical practice remains uncertain.85 Most studies do not
are used to prevent venous thromboembolic events during the
demonstrate a reduction in blood loss using cryotherapy devices
postoperative period.96 The drug, time of initiation and duration
for knee arthroplasty.86 Assessment of new devices should take
of administration, and dose of thromboprophylactic agents may
into account combined benefits in terms of blood loss, pain and
influence postoperative bleeding.
functional outcomes.
When recommencing anticoagulation, the long half-life of
warfarin means it can be restarted within 24 hours of surgery29
Transfusion with a mean time to reach therapeutic levels in 8 days.26 Dosing
There is a large variation in transfusion rates after TKA. A study warfarin can prove challenging after surgery due to the metabolic
of arthroplasty surgeons in the USA revealed transfusion rates response to surgery, and an interesting development is geno-
ranging from 3.8% to 63.8% for primary TKA,87 rising to 84% type-guided dosing after hip or knee arthroplasty to reduce the
for bilateral TKA.88 Studies in the UK reported transfusion rates risk of bleeding, venous thromboembolism and death.97 When
of 2.7% for primary TKA2 and 29.1% for revision TKA.4 bridging anticoagulation is indicated, the last dose of LMWH
Transfusion rates are dictated by a number of factors, including should be given 24 hours prior to the procedure and restarted
the adoption of blood conversation strategies and different 48 hours after the procedure.33 Antiplatelet agents and DOACs
patient cohorts. Transfusion thresholds also play a role. A number should be restarted once haemostasis is achieved and typically
of studies compared outcomes after restrictive transfusion regi- reaching full dose 48–72 hours after surgery.98
mens (transfusion threshold Hb 70 g/L and post-transfusion The optimal agent for chemical venous thromboprophylaxis
target 70–90 g/L) and liberal transfusion regimens (transfusion after knee surgery is a source of great controversy, and there is
threshold Hb 80 g/L and post-transfusion target 80–100 g/L) for significant regional variation in practice. In the UK, LWMH is
non-cardiac surgery.89 In the absence of cardiovascular disease, most widely employed, although aspirin and prophylactic dose
there is no difference between liberal regimens and restrictive DOACs are recommended alternatives.96 In the USA, warfarin
in terms of functional recovery, mortality or medical complica- and aspirin are widely used. Prophylactic dose DOACs are also
tions.89 The exception is patients with ischaemic heart disease, increasingly used for thromboprophylaxis.
where the risk of acute coronary syndrome may be increased The choice of agent for venous thromboprophylaxis and
with restrictive regimens.89 Recent guidelines recommend timing of administration may significantly influence blood loss.
lowering the threshold for transfusion from 80 to 70 g/L in all In the UK, thromboprophylaxis LMWH is typically commenced
patients except those with acute coronary syndrome.23 74 90 between 6 and 12 hours after surgery,96 whereas in the USA, it
Restrictive transfusion regimens reduce the use of allogenic is typically commenced between 12 and 48 hours after surgery.99
blood, and if all liberal regimens were replaced by restrictive In elective hip surgery, the administration of LMWH within
regimens, patient exposure to blood transfusion would decrease 4 hours of surgery increased the risk of major bleeding to 6.3%
by 43%.90 Adoption of a restrictive transfusion regimen reduces compared with 2.5% when administered between 12 and
overall infection rates after orthopaedic surgery.91 In the USA, 48 hours after surgery, but with a possible decrease in risk of
venous thromboembolic event.99
allogeneic blood transfusions after arthroplasty surgery increased
over a 19-year period, although this may be secondary to reduced
rates of autologous blood transfusion.92 A recent study evalu- Future developments
ating blood conserving protocols in 376 patients undergoing A large number of interventions demonstrate the potential to
primary TKA reported no autologous or allogeneic blood trans- reduce blood loss during knee arthroplasty surgery. The current
fusions.58 Such low transfusion rates question whether a preop- challenge is to determine how to combine these interventions
erative group and save (type and screen) is required, particularly to deliver an optimal patient pathway. Heterogeneity of studies
for unicompartmental knee arthroplasty where blood loss is to date with respect to interventions and outcome measures
lower than TKA.43 Given the variation in transfusion rates, such severely limits the ability to compare the efficacy of different
decisions should be made after local departmental audits. interventions. A consensus agreement to develop a core set of
Palmer A, et al. JISAKOS 2018;3:358–366. doi:10.1136/jisakos-2017-000168 363
 State of the Art
outcome measures and to recommend standardised treatments 8 Salido JA, Marín LA, Gómez LA, et al. Preoperative hemoglobin levels and the need

J ISAKOS: first published as 10.1136/jisakos-2017-000168 on 21 September 2018. Downloaded from http://jisakos.bmj.com/ on June 22, 2020 by guest. Protected by copyright.
in future studies may facilitate progress. Collaborative trials for transfusion after prosthetic hip and knee surgery: analysis of predictive factors. J
Bone Joint Surg Am 2002;84-A:216–20.
may also overcome the small patient numbers observed in most 9 Muñoz M, Acheson AG, Auerbach M, et al. International consensus statement
studies published in this field, allowing adequate power to assess on the peri-operative management of anaemia and iron deficiency. Anaesthesia
outcomes in patient subgroups, such as those at high cardiovas- 2017;72:233–47.
cular risk. The most effective strategies to date are optimisation 10 Sehat KR, Evans R, Newman JH. How much blood is really lost in total knee
arthroplasty? Correct blood loss management should take hidden loss into account.
of anaemia, tranexamic acid delivery and restrictive transfusion
Knee 2000;7:151–5.
strategies. It may be that further gains from additional blood 11 Gibon E, Courpied JP, Hamadouche M. Total joint replacement and blood loss: what is
conversation strategies are not clinically important or cost-effec- the best equation? Int Orthop 2013;37:735–9.
tive. Nevertheless, strategies must be patient specific, and small 12 Jans Ø, Bandholm T, Kurbegovic S, et al. Postoperative anemia and early functional
gains may become clinically significant in select groups, such as outcomes after fast-track hip arthroplasty: a prospective cohort study. Transfusion
2016;56:917–25.
patients with haemophilia or Jehovah's witnesses. In addition, 13 Muñoz M, Laso-Morales MJ, Gómez-Ramírez S, et al. Pre-operative haemoglobin
different algorithms will be needed for successful and cost-ef- levels and iron status in a large multicentre cohort of patients undergoing major
fective blood conservation strategies for unicompartmental knee elective surgery. Anaesthesia 2017;72:826–34.
arthroplasty, and primary and revision TKA. 14 Jans Ø, Jørgensen C, Kehlet H, et al. Role of preoperative anemia for risk of
transfusion and postoperative morbidity in fast-track hip and knee arthroplasty.
Transfusion 2014;54:717–26.
Conclusions 15 Viola J, Gomez MM, Restrepo C, et al. Preoperative anemia increases postoperative
complications and mortality following total joint arthroplasty. J Arthroplasty
Implementing strategies to reduce blood loss can improve 2015;30:846–8.
patient outcomes and reduce healthcare costs. Such interven- 16 Moretti D, Goede JS, Zeder C, et al. Oral iron supplements increase hepcidin and
tions in patients undergoing knee arthroplasty are employed decrease iron absorption from daily or twice-daily doses in iron-depleted young
preoperatively, intraoperatively and postoperatively. The stron- women. Blood 2015;126:1981–9.
17 Loftus TJ, Spratling L, Stone BA, et al. A patient blood management program
gest predictor for allogeneic blood transfusion is preoperative
in prosthetic joint arthroplasty decreases blood use and improves outcomes. J
anaemia, and early identification and treatment reduces the rates Arthroplasty 2016;31:11–14.
of transfusion and complications. Intraoperatively, tranexamic 18 Muñoz M, Gómez-Ramírez S, Cuenca J, et al. Very-short-term perioperative
acid reduces blood loss. The optimal route, dose or timing of intravenous iron administration and postoperative outcome in major orthopedic
administration remains uncertain. Postoperatively, cell salvage surgery: a pooled analysis of observational data from 2547 patients. Transfusion
2014;54:289–99.
is a valuable adjunct for cases with significant expected blood 19 Ponnusamy KE, Kim TJ, Khanuja HS. Perioperative blood transfusions in orthopaedic
loss. Autologous blood donation is not recommended, sealants surgery. J Bone Joint Surg Am 2014;96:1836–44.
require further evidence of benefit but may play a role in select 20 Camaschella C. Iron-Deficiency Anemia. N Engl J Med Overseas Ed
cases, and the use of a tourniquet remains at the discretion of the 2015;372:1832–43.
21 Bisbe E, Castillo J, SÁEz M, et al. Prevalence of preoperative anemia and hematinic
surgeon. Restrictive transfusion protocols should be followed,
deficiencies in patients scheduled for elective major orthopedic surgery. Transfusion
and more current studies report no allogeneic transfusions after Alternatives in Transfusion Medicine 2008;10:166–73.
primary knee arthroplasty surgery. 22 Spahn DR. Anemia and patient blood management in hip and knee surgery: a
systematic review of the literature. Anesthesiology 2010;113:482–95.
Contributors  AJRP drafted the initial manuscript. All authors performed critical 23 NICE Guideline[NG24]. Blood Transfusion, 2015.
revision and approved the final manuscript. 24 Muñoz M, García-Erce JA. Preoperative autologous blood donation in lower
limb arthroplasty surgery: has the time come for its retirement? Blood Transfus
Funding  Outside of the submitted work, AFC received grant funding from the 2013;11:333–6.
Orthopaedic Research and Education Foundation; consultancy fees from Heraeus, 25 NICE Guideline [NG45]. Routine Preoperative Tests for Elective Surgery, 2016.
Zimmer, 3M, Convatec, Irrisept, Haylard, Pfizer, DJO, ACI, bOne and Stryker; royalties 26 Burger W, Chemnitius JM, Kneissl GD, et al. Low-dose aspirin for secondary
from SLACK Publishing; and holds equity in Joint Purification Systems, Sonoran cardiovascular prevention - cardiovascular risks after its perioperative withdrawal
Biosciences, Graftworx, and sits on the advisory board for Recro. AJP receives grant versus bleeding risks with its continuation - review and meta-analysis. J Intern Med
funding from Arthritis Research UK and the National Institute for Health Research, 2005;257:399–414.
and personal fees from Zimmer Biomet, DePuy, and Smith and Nephew. 27 Oscarsson A, Gupta A, Fredrikson M, et al. To continue or discontinue aspirin
Competing interests  None declared. in the perioperative period: a randomized, controlled clinical trial. Br J Anaesth
2010;104:305–12.
Patient consent  Not required.
28 Mantz J, Samama CM, Tubach F, et al. Stratagem Study Group. Impact of preoperative
Provenance and peer review  Commissioned; externally peer reviewed. maintenance or interruption of aspirin on thrombotic and bleeding events after
elective non-cardiac surgery: the multicentre, randomized, blinded, placebo-controlled,
STRATAGEM trial. Br J Anaesth 2011;107:899–910.
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Erik T. Newman, MD, et al.: "Impact of perioperative allogeneic and autologous blood 99 Strebel N, Prins M, Agnelli G, et al. Preoperative or postoperative start of prophylaxis
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