Strategies for Blood Conservation in Joint Replacement Surgery
A proactive approach to blood management will have a positive effect on early- and long-term outcomes and greater success in the management of total joint arthroplasty patients.
David Liu, FRACS; Michael Dan, MBBS; and Natalie Adivi, BN
The authors have no disclosures relevant to this article.
Editor’s Note: This article has been adapted from “Blood Conservation Strategies in Total Hip and Knee Arthroplasty,” published in the December 2014 issue of Reconstructive Review.
A strategy for blood management is one of a number of critical components for successful patient care in joint arthroplasty. Hip and knee arthroplasty can result in substantial perioperative blood loss, putting the patient at risk for a blood transfusion [1,2]. In fact, total joint arthroplasty and fracture surgery are top reasons for transfusion in patients undergoing surgery, accounting for 9.8% of all transfused red blood cell units .
Transfusion is not without risks, with complications of allogenic blood transfusion including: 
- Risk of disease transmission
- Hemolytic reactions
- Fluid and haemodymanic overload
- Acute lung injury
- Allergic reactions
- Febrile non-hemolytic reactions
There is evidence that allogenic transfusions are associated with immunomodulation, and an increased incidence of infection . Bierbaum reported transfusion rates of 57% for total hip arthroplasty (THA) and 39% for total knee arthroplasty (TKA), with an increased risk of fluid overload, infection rate, and duration of hospitalization in the patients who received allogenic transfusion .
Several studies have highlighted the disadvantages of allogenic blood, including a negative effect on postoperative complications, length of hospital stay, cost and mortality [7,8,9].
The fundamental aim of a blood management strategy is to eliminate the need for allogenic blood while at the same time preventing anemia. Thereby the risks of transfusion are removed and hemoglobin status is maximized, leading a positive effect on the patient’s recovery and early- and long-term outcomes.
Such a strategy should be individualized and based on patient-specific risk factors, including preoperative hemoglobin level, anticipated difficulty of the procedure and blood loss, and associated medical co-morbidities. Hemoglobin loss in routine primary THA has been calculated to be 4.0 g/dL and in TKA, 3.8 g/dL . The ultimate transfusion trigger should also be individualized based on the risks and benefits for each patient.
Multiple strategies, used either in isolation or combination, are available to reduce the need for allogeneic blood in joint arthroplasty patients. Available strategies can be broadly divided into 3 stages: 
- Preoperative assessment and optimization
- Intraoperative protocols
- Postoperative protocols
These are summarized in Table 1.
Table 1. Summary of blood management interventions available to reduce allogenic transfusion rates in THA and TKA patients.
Predicting the risk and need for transfusion preoperatively has been shown to be an important element of an effective blood management program in joint arthroplasty surgery. Several studies have highlighted the significant influence of preoperative hemoglobin on the requirement for transfusion in total joint arthroplasty [10,12].
Salido et al demonstrated that few patients with a preoperative hemoglobin level greater than 150 g/L need allogenic blood, while patients with preoperative hemoglobin level less than 110 g/L had a 100% transfusion rate . Similarly, Pierson et al showed that an algorithm-based strategy aimed at improving the preoperative hemoglobin level was effective in reducing transfusion rate .
Other risk factors associated with an increased need for transfusion include weight, age greater than 75 years, male gender, hypertension, and body mass index less than 27 . Although many of these factors are non-modifiable, Pola showed that having more than 1 risk factor has a compounding effect on transfusion rate . Therefore, in patients with multiple risk factors, it is vitally important to correct anemia and maximize the preoperative hemoglobin.
Correcting anemia not only reduces the risk of allogenic transfusion, but it also has a positive impact on the patient’s rehabilitation and functional recovery. A postoperative hemoglobin level of between 80 and 100 g/dL may not be low enough to warrant transfusion, but these patients often feel lethargic and have a higher risk of syncopal episodes, impairing their ability to mobilize and participate in rehabilitation.
The cause of preoperative anemia needs to be fully investigated and corrected as necessary. A common reason, especially in older arthroplasty patients, is iron deficiency due to a combination of poor dietary intake and peptic disease secondary to the use of non-steroidal anti-inflammatory drugs.
The typical pattern seen in these patients is low hemoglobin and low ferritin. In our institution, patients are screened 3 months prior to surgery with a full blood count, proceeding to iron studies if the preoperative hemoglobin is less than 120 g/dL.
The parameters measured to investigate preoperative anemia are listed in Table 2, with the minimum cut-off values. Any patient who is identified as anemic is referred to the hematology unit for further investigation and management.
Table 2. Preoperative iron studies and critical values used at the authors’ institution for patients with preoperative anemia requiring correction prior to THA and TKA.
The options for maximizing hemoglobin in preparation for surgery include iron supplements or erythropoietin. Iron supplements can either be given orally or intravenously. Both routes have been shown to be effective; however, oral iron may not be efficacious in patients with malabsorption such as celiac disease.
Another disadvantage of oral iron supplements is their slow effect; therefore, they need to be given well in advance of surgery to treat anemia. In a cohort study, 156 patients were given 256 mg / day of ferrous sulfate in combination with vitamin C, which enhances iron absorption, for 1 month preoperatively, resulting in a reduced transfusion rate for the non-anemic patients .
For our patients with iron deficiency, the hematologists administer 500 mg to 1000 mg of ferritin carboxymaltose as an intravenous infusion over 15 minutes. The dosage depends on the duration and severity of iron deficiency. The infusion needs to be given a minimum of 3 weeks before surgery to enable enough time for red blood cells to regenerate.
Erythropoietin is a synthetic hormone that stimulates progenitor cells in the bone marrow to differentiate into red blood cells and, thereby, stimulate hematopoiesis. As a powerful agent in correcting anemia, erythropoietin is extremely effective in reducing allogenic blood requirement in joint replacement surgery.
In a systematic review, Spahn  showed erythropoietin to be successful in improving mean preoperative and post operative hemoglobin levels with reduced transfusion rates when combined with iron therapy in patients undergoing orthopedic procedures, including hip fracture surgery, THA and TKA.
A large part of blood conservation in surgery is aimed at limiting blood loss. Patients undergoing THA and TKA frequently take antiplatelet and anticoagulant medications that affect the risk of bleeding. The decision and timing of cessation of antiplatelelet and anticoagulant therapy needs to take into consideration the risks of thrombosis versus the risk of bleeding.
Platelet activation occurs with non-cardiac surgery, making myocardial infarction the most common major vascular complication after surgery. Under usual circumstances, warfarin should be discontinued 5 days prior to arthroplasty surgery  and restarted postoperatively when the risks of acute bleeding are believed to be stable.
Bridging anticoagulation therapy is commonly used in the interim period with agents such as low molecular heparin that have a shorter half-life . There are no clear guidelines or consensus on the optimal bridging therapy for patients on warfarin for conditions such as atrial fibrillation, previous embolic cerebrovascular events, or mechanical valve replacement. Further clinical trials are required to clarify the optimal regime.
Cessation of aspirin and antiplatelet therapy before surgery is believed to result in an increased risk of cardiovascular complications and major cardiac events [19,20]. However, a recent large randomized controlled trial of 10,010 patients – 39% of whom underwent orthopaedic procedures – found conflicting results: There was no difference between the aspirin and placebo groups in the primary outcome of death or myocardial infarction 30 days following surgery, regardless of whether the patient was taking aspirin prior to surgery . Aspirin increased the risk of major bleeding compared with placebo in the study. The most commonly reported bleeding sites were the surgical site (78.3%) and gastrointestinal tract (9.3%).
The authors concluded that aspirin administration before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or non-fatal myocardial infarction, but it increased the risk of major bleeding . We now ask our patients to stop aspirin prior to THA and TKA.
Preoperative autologous donation was once popular in elective joint replacement surgery, as it has been demonstrated to be effective in reducing allogenic blood requirements. Three cohort studies showed reduction in allogeneic transfusion rates from 40%, 52%, and 91% in their control groups to 3%, 18%, and 9%, respectively, in their autologous donor groups [22-24].
However preoperative autologous donation is associated with a high rate of wasted blood units and is no longer deemed to be cost effective. There remains the potential for the wrong blood being returned to the patient due to clerical errors [25,26]. The process itself necessitates the inconvenience of having to donate blood in advance of scheduled surgery. The use of preoperative autologous blood donation has, therefore, fallen out of favor.
A major element of intraoperative blood management is limiting the amount of blood loss. The risk of bleeding depends on the difficulty of the procedure and patient risk factors such as obesity, co-morbidities, and bleeding disorders.
Maintaining steady blood pressure and normothermia are recommended in reducing blood loss. Crucial to blood loss management is meticulous and efficient surgical technique, with careful dissection, soft tissue handling, and bleeding control.
The technique of acute normovolemic hemodilution attempts to achieve a similar effect to preoperative autologous blood donation, but without the inconvenience. Blood is collected from the patient in the immediate preoperative period and volume is replaced with colloid or crystalloid fluid. The rationale behind the technique is that surgical blood loss will have a lower hematocrit. The preoperatively collected whole blood is transfused in the immediate postoperative period, negating the downsides of blood storage.
The effectiveness of acute normovolemic hemodilution in reducing transfusion need is debatable, however . Its use may be appropriate in selected cases in which cross matching blood is difficult due to the presence of antibodies.
Perioperative red cell salvage is another strategy available to minimize the effects of blood loss following total hip and knee arthroplasty. Blood lost during the operative procedure and immediate postoperative period can be salvaged and returned to the patient.
This technique has several advantages over the previously described methods of preoperative autologous donation and acute normovolemic hemodilution.
Perioperative red cell salvage reinfuses fresh blood and avoids the problems with storage of red blood cells seen with autologous pre-donation and allogeneic red blood cells. This translates to more efficacious oxygen-carrying red blood cells with a higher mean erythrocyte viability  and increased preservation of 2-3 diphosphoglycerate . Perioperative red cell salvage also incorporates washing the blood loss volume. Washing the blood removes biochemical, cellular, and non-cellular debris . Unwashed cell salvage has been associated with adverse postoperative effects due to the presence of cytokines, including hypotension, hyperthermia, increased postoperative bleeding, and non-cardiogenic pulmonary edema. [30, 31]
We have been using intraoperative red cell salvage in our unit for the past 4 years for primary and revision hip and knee replacement. An audit of our transfusion rates in comparison with other studies in the literature is listed in Table 3 for THA [32-34] and Table 4 for TKA [35-37].
Table 3. Effects on allogenic transfusion rates of autologous retransfusion of salvaged blood cells in randomized controlled trials and cohort studies for THA compared to historical rate reported by Bierbaum without intervention.
Table 4. Effects on allogenic transfusion rates of autologous retransfusion of salvaged blood cells in randomized controlled trials and cohort studies for TKA compared with historical rate reported by Bierbaum without intervention.
Perioperative red cell salvage reduces but does not eliminate the need for allogenic blood, especially in patients who have a low baseline hemaglobin preoperatively.
The routine use of intraarticular wound drainage in THA and TKA has been shown to increase blood transfusion requirement . This needs to be balanced with the reported increased risk of persistent ooze, bruising, and hematoma formation . The evidence for use of an intraarticular drain, therefore, remains inconclusive and very much an individual decision based on surgeon preference.
Postoperative reinfusion drains are also commonly used in orthopaedic practice, and reported results suggest it reduces allogeneic transfusion rates. A meta-analysis by Huet et al  showed a relative risk reduction of 0.35 in the need for allogeneic transfusion with the use of reinfusion drains.
Zacharopoulos performed a prospective randomized controlled trial with reinfusion drains, showing to a decrease in allogenic blood transfusion . In contrast, Hazarika showed reinfusion drains had no significant benefit, with the downside of additional costs .
Reinfusion drains carry the potential for transfusion reactions, as the unwashed blood contains fibrin degradation products and other potential contaminants [42,43]. The drained blood needs to be reinfused within 6 hours to avoid the potential for hemolysis.
A logical strategy in blood conservation is to enhance hemostasis during the perioperative period. Recently, a multitude of publications have highlighted the use and benefits of antifibrinolytic agents. Tranexamic acid (TXA), a synthetic plasminogen-activator inhibitor, is one such agent demonstrating clinical efficacy and an acceptable safety profile.
Tranexamic acid inhibits the activation of plasminogen to plasmin by blocking the lysine binding sites of plasminogen to fibrin. This results in a decrease in proteolytic action on fibrin monomers and fibrinogen, leading to clot stabilization . The use of TXA in primary THA and TKA patients has been associated with reduced transfusion rates, increase discharge rate to home, and reduced costs .
Tranexamic acid has the desirable features of ease of administration, minimal effect on operative procedure flow, and extremely low cost as a generic medicine. In multiple studies involving THA and TKA patients, intravenous TXA has been shown to significantly reduce the amount of blood loss and blood transfusion requirements without an increase in venous thromboembolic risk [46,47,48]. Oral TXA has also shown similar effectiveness in orthopadic surgery .
Several contraindications preclude the use of intravenous TXA at the time of surgery, including renal insufficiency, history of previous deep venous thrombosis, and cerebrovascular and cardiac disease. In 1 study, intravenous TXA was contraindicated in 28% of patients . Topical administration of TXA may be more appropriate in patients with contraindications due to the delay in systemic absorption after application into a joint.
Intraarticular application limits systemic exposure and maximizes drug concentration and activity directly at the site of bleeding. Wong et al proved the efficacy of intraarticular TXA in a double-blind, placebo-controlled, randomized trial in TKA . The authors demonstrated a significant difference in hemoglobin reduction and blood loss using 3.0 g of TXA in 100 mL of normal saline compared with placebo, with no difference in thromboembolic complications. Plasma levels of TXA following topical administration were 70% less than an equivalent dose of intravenous injection.
More recently, a retrospective study found intraarticular and pericapsular injection of TXA after capsular closure resulted in a transfusion rate reduction from 17.5% to 5.5%, as well as a significantly higher postoperative hemoglobin in the TXA group .
Alshryda et al performed a systematic review and meta-analysis showing topical TXA to be safe and to significantly reduce the rate of blood transfusion in patients undergoing THA or TKA . Indirect comparison of placebo-controlled trials indicated topical administration to be superior to the intravenous route.
There is, however, no clear consensus on ideal dosage, timing, frequency, and route of administration for use of TXA in joint arthroplasty surgery. Additionally, there may be differences in the efficacy and response of different regimes between THA and TKA patients.
A number of studies comparing intravenous TXA with topical TXA have demonstrated the efficacy and safety of topical administration in TKA [53,54,55]. Patel at al , using a single intravenous dose, and Soni et al , using a 3-dose intravenous regimen, concluded topical TXA had similar efficacy to intravenous TXA in terms of perioperative change in hemaglobin, lowest postoperative hemoglobin, total drain output, and transfusion rate.
In a study comparing 3 methods of administration in TKA, single-dose intravenous TXA was more effective in reducing the drop in hemoglobin that occurs during surgery than topical and intraarticular TXA injected via the drain . Local administration through the drain yielded the least blood drainage postoperatively compared with intravenous and topical application, with 80% reduction in drainage volume compared with 45% and 18%, respectively.
In contrast, Maniar et al found that a single intravenous dose did not give effective results . A 3-dose regimen of pre-, intra- and postoperative doses of 10 mg/kg produced maximum effective reduction of drain loss and total blood loss in TKA. The authors concluded a preoperative dose prior to tourniquet inflation was important to inhibit the activation of the fibrinolysis cascade.
Fewer studies have examined the utility of topical TXA in THA. Wind et al showed a significant reduction in transfusion rate with intravenous TXA in THA, but not with topical TXA . In contrast, Alshryda et al found a significant reduction in the rate of transfusion with topical TXA in THA, comparable to that achieved with TKA . Studies from Konig et al and Tuttle et al revealed topical TXA to be efficacious in THA as well [45,61].
Another form of pharmacotherapy used to reduce blood loss is topical fibrin sealants. These agents are composed of fibrinogen and thrombin, which, when mixed together during the application process, mimic the final step of the coagulation cascade.
Randelli performed a randomized trial of topical fibrin versus a control group but found no difference in hemoglobin levels, postoperative decrease in hemoglobin, drainage, or mean total blood loss . In particular, the transfusion rate was 32.3% in the control group compared with 25.8% in the fibrin group, which was not significantly different. The authors concluded the topical application of fibrin sealant was not effective in reducing perioperative blood loss in TKA.
Another randomized study comparing topical fibrin spray to intravenous TXA demonstrated comparable reduction in blood loss, but the cost of the fibrin spray was significantly greater .
A blood management strategy in total joint arthroplasty aims to reduce the need for allogenic blood and avoid the risks of transfusion, while at the same time maximizing the hemaglobin level and preventing anaemia in the acute postoperative period. Effective blood conservation (Figure 1) encompasses:
- Identifying patients at high risk for transfusion preoperatively
- Correcting preoperative anemia with hemopoietic agents
- Salvaging blood lost during the perioperative period
- Limiting postoperative blood loss with hemostatic measuresIndividualizing the transfusion trigger according to the patient’s symptoms and medical co-morbidities
- A proactive approach to blood management will have a positive effect on early- and long-term outcomes and greater success in the management of total joint arthroplasty patients.
Figure 1. Blood conservation algorithm used at the authors’ institution for total hip and knee arthroplasty patients.
David Liu, FRACS, and Natalie Adivi, BN, are from Gold Coast Centre for Bone and Joint Surgery, Queensland, Australia. Michael Dan, MBBS, is from John Hunter Hospital, New South Wales, Australia, and Bond University, Queensland, Australia.
Liu D, Dan M, Adivi N. Blood conservation strategies in total hip and knee arthroplasty. Reconstructive Review 2014;4(4):39-45. Copyright 2015. All articles published are the shared property of the authors and Reconstructive Review. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. JISRF gives permission for reproduction of articles as long as notification and recognition is provided.
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