Iron, vitamin B₁₂, and folate are integral to the development of red blood cells (RBCs), and deficiencies in these compounds have been associated with anemia.⁷ In particular, iron deficiency anemia has been reported to account for up to 50% of patients with hemoglobin levels below 12 g/dL.¹⁰ Patients with anemia due to nutritional causes, including iron deficiency anemia, can be treated with a healthy diet and nutritional supplementation with vitamin B₁₂, folate, and oral or intravenous (IV) iron, depending on the cause of anemia. A variety of treatment plans and algorithms are found in the literature. Cuenca et al demonstrated that preoperative supplementation with iron (256 mg/d), vitamin C (1000 mg/d), and folate (5 mg/d) 30 to 45 days prior to surgery significantly decreased the need for ABT when compared with patients who did not receive preoperative supplementation (5.8% and 32%, respectively).¹¹ This study demonstrates the importance of nutritional health prior to surgery and the impact of correction of nutritional deficiencies on perioperative outcomes.

With respect to iron deficiency anemia, both IV and oral administration can be beneficial in the appropriate setting.¹¹,¹²,¹³ However, IV administration appears to be superior to oral in terms of efficacy.¹⁴ In a prospective study, Theusinger et al demonstrated that administration of IV iron over a 3-week period prior to surgical intervention resulted in maximum increase in preoperative hemoglobin levels without adverse events related to oral iron treatments.¹⁵ Iron administration should be performed judiciously, as supplementation in the absence of iron deficiency has been associated with constipation, heartburn, and abdominal pain.¹⁶

Erythropoietin (EPO) is a naturally occurring glycoprotein produced from renal pericapillary cells in response to hypoxic conditions resulting from physiologic states such as anemia or chronic obstructive pulmonary disease.¹⁷ When produced, EPO acts on the bone marrow to increase RBC differentiation, maturation, and ultimately total RBC mass. The role of EPO in blood management is frequently discussed in arthroplasty literature, as its use leads to significant reductions in ABTs in patients receiving surgery.¹⁸,¹⁹ EPO in its recombinant form, epoetin-α, causes the same physiologic results and has been routinely used in chronic anemia patients with renal disease and those undergoing chemotherapy.⁷ Perioperative administration for arthroplasty procedures has been performed alone, in conjunction with preoperative autologous donation (PAD), and postoperatively.²⁰

A variety of dosing regimens have been described;²¹ however, three or four weekly preoperative subcutaneous injections (600 IU/kg) are most frequently used and may deliver the best results.²⁰,²²,²³ EPO supplementation leads to a mean rise in preoperative hemoglobin of 1.9 g/dL,²⁴ and multiple studies have demonstrated a significant benefit of preoperative EPO supplementation when compared to placebo, PAD, and reinfusion systems.²⁰,²⁴,²⁵

A major limitation to routine EPO use is cost, as the average price per patient is equivalent to two to three units of PAD or three to four units of allogenic blood.²⁶ Given this fact, it is not surprising that routine use of EPO as a blood management strategy was found to lack cost effectiveness.²⁶ Selective use of preoperative EPO is considered most appropriate in scenarios where significant amounts of blood loss are anticipated, such as complex primary TKA, simultaneous bilateral TKA, and revision TKA.²⁷ EPO supplementation should also be considered in patients diagnosed with preoperative anemia, those with low body weight (<50 kg), and in scenarios where ABT is especially undesirable such as in Jehovah’s Witnesses population.

The treatment team must appreciate the impact that outpatient medications have on blood management throughout a TKA episode of care. Cardiovascular disease is common among patients undergoing TKA, and antiplatelet therapies are routinely used to manage these conditions. Furthermore, a subset of patients with cardiovascular disease has previously undergone percutaneous coronary interventions (PCI) with stent placements. Dual antiplatelet therapies are common in this patient population and typically consist of aspirin and a P2Y₁₂ inhibitor (e.g., clopidogrel). Current guidelines for dual antiplatelet therapy in patients with coronary artery disease (CAD) vary and depend upon on a number of factors including the length of time since the PCI and the type of stent that was implanted.²⁸ From a surgical perspective, blood loss can be substantial when surgery is performed in a patient taking antiplatelet medications.²⁹ These patients can also be more challenging to the anesthesiologist, as excessive bleeding can occur when neuraxial anesthesia is attempted.³⁰

Increased perioperative bleeding may also result from nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs are widely used as an analgesic in the management of degenerative joint disease. NSAIDs reduce inflammation by impeding prostaglandin production via inhibition of cyclooxygenase enzymes. Nonselective NSAIDs (COX-1 and COX-2 inhibitors) are known to impair platelet aggregation and prolong bleeding time due to their blockade of the COX-1 enzyme. Alternatively, COX-2 selective medications such as celecoxib can relieve pain and reduce inflammation without impacting bleeding time or platelet aggregation and therefore can be safely used perioperatively.

Other common agents that may increase perioperative risk in patients planning elective TKA include warfarin, factor Xa inhibitors, and herbal supplements such as gingko biloba. As previously mentioned, a thorough accounting of all perioperative medications should be performed prior to elective TKA, including nonprescription medications and supplements. The benefit of stopping any medication should be weighed against its risks and should be done in collaboration with the prescribing physician. Ultimately, an individualized approach should be taken during the perioperative period with multidisciplinary input to maximize patient safety and surgical outcome.

Preoperative autologous blood donation (PAD) programs were developed in the late 1980s to combat the newly recognized risk of viral transmission of diseases such as HIV associated with ABT.³¹ The goal of PAD programs was to provide patients with a safe source of blood prior to major procedures such as TKA. PAD is performed 3 weeks prior to a planned surgery where major blood loss was expected. The ideal candidate is a patient who weighs more than 110 lbs and has hemoglobin greater than 11 g/dL.³² The technique involves procurement of one to two units of the patients own blood prior to
surgery. The procured blood is then processed, stored, and ultimately transfused back to the patient either intraoperatively or postoperatively. In 1992, PAD accounted for nearly 8.5% of all blood collected in the United States.³³ While the literature has demonstrated significant reductions in ABT when PAD programs were utilized,⁷ a consensus has yet to be reached with regard to its efficacy.

The logistics of PAD programs can be challenging and may present opportunities for complications to occur. Storage of donated blood requires advanced planning, storage, and preparation and as a result introduces the risk for clerical error, bacterial contamination, and infection.⁵,³² Additionally, mismanagement of donated blood may result in underutilization of product, with reports suggesting a >50% incidence of unused blood.⁵,³² PAD has also been associated with fluid overload.⁵,³² To be considered for PAD, patients must have a baseline hemoglobin level >11 g/dL; therefore, many of the patients most at risk for ABT (those with preoperative anemia) are excluded from consideration. Finally, cost is an additional factor which limits the use of PAD. For all of these reasons, routine use of PAD has fallen out of favor for primary TKA, especially with the routine use of tranexamic acid (TXA).

Acute normovolemic hemodilution (ANH) involves the removal of whole blood from a patient, while circulating blood volume is maintained with crystalloid fluid.³⁴,³⁵ Typically, two to three units of blood is collected from the patient 1 hour prior to the operation and total blood volume is maintained with IV fluids. Postoperatively, the stored blood units are reinfused to the patient. While some studies have shown that this technique can be efficacious in reducing the need for ABT,³⁴ other studies have demonstrated otherwise.³⁶,³⁷ Similar to PAD, logistical problems concerning the timing, storage, and usage of donated units of blood exist with this technique. However, ANH may be useful in the Jehovah’s Witnesses population when substantial blood loss is anticipated, but ABT is undesirable.

Tourniquets are commonly used in TKA as they allow for a technically easier surgery, with enhanced visualization through a bloodless field, improved cement interdigitation, and decrease in surgical time.³⁸ When utilized, tourniquets are typically inflated to a level 100 to 150 mm Hg greater than the patient’s systolic blood pressure. While the majority of surgeons commonly use tourniquets during TKA, their routine use is somewhat controversial. Within minutes of the applied pressure, local ischemia ensues, resulting in reactive hyperemia and the potential for local muscle damage, neurapraxia, thigh pain, delayed wound healing, thrombosis, increased joint swelling, and stiffness.³⁹

Thorey et al randomized knees in 20 patients undergoing simultaneous bilateral TKA to either have the tourniquet released prior to wound closure or after wound closure.⁴⁰ A significant reduction in surgical time was reported with delayed tourniquet release compared to release prior to wound closure (51 and 58 minutes, respectively). No differences were noted in perioperative blood loss or complications at 6 months follow-up. In a nonrandomized prospective cohort study of 90 patients undergoing TKA, Huang et al divided patients into three groups: tourniquet used the whole surgery until after wound closure, tourniquet deflated prior to wound closure, and tourniquet used only during cementation.⁴¹ They found that use of a tourniquet only during cementation resulted in lower levels of serum markers of inflammation and muscle damage. However, there were no observed differences between the groups with regard to Hospital for Special Surgery knee score, range of motion (ROM), estimated blood loss, swelling ratio, visual analog scale pain score, and hospital stay.

In 2011, Tai et al performed a meta-analysis of 8 randomized controlled trials (RCTs) and 3 high-quality prospective studies involving 634 knees, where clinical outcomes of TKA with and without tourniquet use were compared.³⁹ They found that TKA without tourniquet use had better clinical outcomes, fewer complications, and better ROM in the early postoperative period. Additionally, their results demonstrated that the true blood loss in TKA was not reduced with tourniquet use, as reactive hyperemia due to ischemic conditions may result in greater hidden blood loss during the postoperative period. It is important to point out that challenges associated with quantifying total blood loss and nonuniform indications for blood transfusion may limit the conclusions that can be drawn from these data.

At this time, the literature does not provide definitive guidance regarding the time and use of tourniquet use during TKA. Nevertheless, the treatment team should weigh the benefits of its use against the perceived
disadvantages. Additionally, patients with risk factors for arterial complications such as a history of vascular claudication, radiographic evidence of calcification, absent pedal pulses, or a history of vascular procedures should be screened and consultation with a vascular surgeon should be performed prior to consideration of tourniquet use. In most of the above scenarios, tourniquet use is typically avoided to prevent embolization of arterial plaque distally and potential vascular occlusion.

HEA is a technique introduced by Nigel Sharrock, whereby blood loss is reduced by maintaining a low mean arterial blood pressure (typically 50 to 55 mm Hg) throughout the surgical procedure.⁴² An epidural dermatome block at the T2 level results in a decrease in the conduction of the cardioacceleratory fibers of the sympathetic chain, ultimately leading to a reduction in arterial pressure. While HEA has been shown to limit intraoperative blood loss in the TKA,⁴³,⁴⁴ most of the literature has focused on its total hip arthroplasty applications. Additionally, concerns about tissue hypoperfusion, bradycardia, and other serious cardiopulmonary sequelae have been documented in the literature.⁴⁴,⁴⁵ However, studies suggest that HEA is safe even in high-risk patient populations, including patients with poor cardiac or renal function.⁴⁶ Ultimately, an interdisciplinary approach should be taken when deciding to use this approach.