Reducing the use of allogenic blood transfusion in TKA is important for improving outcomes, mitigating risks to patients, and lowering healthcare costs [5, 6]. In the last decade, there have been impressive reductions in the rate of blood transfusions during TKA due to the use of TXA and the adoption of restrictive transfusion protocols [7, 18]. Currently, transfusion in elective TKA is uncommon in the absence of preoperative anemia. A low preoperative hematocrit or Hb level is the most important factor in blood transfusion after primary TKA. Baseline Hb level is a preoperative variable that can be modified using iron, folates, vitamin B12, and or EPO, but these pharmacologic agents are underused [19].

In the present patient series, no ACD patients received a blood transfusion during the first week. None had bleeding complications or reached the transfusion thresholds during the first perioperative week. To the best of our knowledge, this series is the first to show a blood transfusion rate of zero in a consecutive series of ACD patients undergoing primary TKA surgery. Importantly, cell savers and autotransfusion were not utilized during the study.

The most important finding of this study was that the BI-7 was lower in ACD + patients than in patients with no preoperative anemia. The present study is the first we are aware of to show a significantly lower blood loss in patients with baseline Hb levels < 12 g/dl than in those with baseline levels > 12 g/dl, all treated with the same PBM protocol. This contrasts with the results of a recent multicenter study that showed higher blood loss in preoperative anemic patients than in non-anemic patients, regardless of the use of a PBM [19]. Our finding has important clinical implications: preoperative Hb levels do not need to be highly optimized before TKA in ACD patients due to their low blood loss.

We believe that EPO therapy is indicated prior to the TK procedure in ACD patients without nutritional anemia who have a preoperative baseline Hb < 11 g/dl. Another important point is that a low dose of EPO is sufficient to raise Hb to 11 g/dl. This implies that the use of EPO has become more economical. Another overall positive finding is that optimization of preoperative Hb in contemporary TKA performed with blood conservation is not necessary in the overall population, only in patients with Hb baseline levels < 11 g/dl.

Current PBMs are multimodal, with variations in management common but under researched. For example, there is little agreement regarding the best preoperative diagnostic strategy and the use of erythropoiesis-stimulating biosimilar agents as a primary treatment. In addition, no consensus exists regarding the upper threshold level of baseline Hb to use EPO therapy. Pierson suggested using EPO in patients with Hb baseline levels < 12 g/Dl based on a mathematical formula that accounts for a restrictive transfusion threshold (7 g/dl) and a mean drop of 3.8 g/dl Hb (+ 1 SD) in TKA [20]. A few subsequent studies found that 12 g/dl was one point too low and that a threshold of 13 g/dl and above would be more appropriate. Currently, the mean drop in Hb in primary TKA is reduced to 3 g/dl with the use of TXA. However, a transfusion threshold of 8 g/dl remains the rule in patients with cardiovascular disease. Using Pierson’s formula [20] with updated parameters, including a BI-7 of 2.1 ± 1.1 g/dl and a transfusion threshold of 8 g/dl, the upper level for Hb optimization in ACD patients with cardiovascular disease is 11.2 g/dl. In the present series, all but one patient with baseline Hb levels < 11 g/dl received EPO, and none received a blood transfusion the first perioperative week.

In most hospitals, the risk of transfusion is evaluated at the preoperative anesthetic visit. Patients exposed to transfusion are submitted to an Hb optimization program whenever they are found to be anemic and can comply with the program, which requires time and sometimes postponement of planned surgery. In the present series, no surgery was delayed due to the implementation of EPO therapy, which was prescribed in line with the date of surgery.

The use of EPO in TKA is justified if it reduces complications; otherwise, it exacerbates costs, increase thrombotic risk, and has a carbon consequence [21]. In the present series, EPO was used before the surgical procedure since EPO therapy is considered more efficient when given prior to surgery. The EPO regimen was prescribed parsimoniously by the surgeon with a short course and a low dosage. Specifically, the regimen of two injections studied by Rosencher was employed, with a dose of 20,000 IU per injection [22]. This dose was supported by Feagan, who found no significant difference in the increase of preoperative Hb using either 20,000 IU or 40,000 IU of EPO alpha [23]. Patients receiving EPO were not given additional specific antithrombotic therapy since only a low dose of EPO was administered in a short course. Despite the prescription of a lower-than-average dose of EPO, we found that EPO therapy increased the preoperative Hb. The increased erythropoiesis that occurs early postoperatively has a direct effect on blood loss [24]. We found that the initial threshold Hb level of 12 g/dl for EPO implementation was too high in our practice.

The primary drawback of preoperative EPO therapy is its expense. However, the financial burden of EPO therapy must be weighed against the expenses of blood transfusions as well as the health and economic consequences of complications associated with postoperative anemia. Given that the costs and safety of EPO therapy are dose-dependent, we assert that our model is economical and safe. We used a lower Hb threshold, a lower dose, and a shorter duration of EPO therapy than reported in the literature [10]. In this study, most patients with preoperative Hb levels < l1 g/dl were treated with EPO therapy, while only a minority of patients with baseline Hb levels < 12 g/dl received EPO. The threshold we now consider for the use of EPO or EPO biosimilar medication is 11 g/dl.

Erythropoietin is a hormone produced by the kidneys, and its production is reduced in renal patients. Hence, EPO recombinant therapy is deemed to be more effective for patients with kidney issues. Notably, EPO therapy is considered safe when utilized at a low dose, particularly for individuals with renal problems. In the current series, more than 40% of ACD patients had a preoperative MDRD less than 60 ml/min/m2.

With the ubiquitous use of TXA and advancements in surgical techniques in recent years, the previous postoperative Hb drift of 3.8 g/dl (with a standard deviation of 1 g/dl) associated with total knee arthroplasty [20] has been mitigated to < 3 g/dl in modern TKA procedures. In the current study, a single infusion of TXA was given prior to the skin incision. No adverse effects were observed with TXA administration. Our approach involved a single adequately dosed shot to inhibit fibrinolysis during peak blood loss, without the need for repeated doses. Multiple trials have confirmed the efficacy of single-shot TXA compared to repeated-dose regimens [14, 25, 26]. The use of TXA plays a positive role in primary TKA, reducing the occurrence of hematomas [27], hidden blood loss, and the need for allogeneic blood transfusions. TXA reduces the transfusion rate from 23.3% to 9.1% in patients with renal impairment [28].

In the present series, all patients, except those with mechanical heart valves, received a 10 mg dose of direct-acting oral anticoagulant (DOAC) rivaroxaban once a day for a minimum of two weeks. We adopted rivaroxaban in 2009, as it reduces thrombotic events, bleeding risk, and drug monitoring requirements. No dose adjustment was implemented in relation to body weight or renal function. However, pauses were applied in cases of local or other nasal or urinary postoperative bleeding.

We did not use rivaroxaban in combination with other blood thinner agents to avoid provoking a marked prolongation of clotting time and to avoid increasing the risk of articular and periarticular bleeding and other complications related to excessive anticoagulation. Chronic anticoagulation was resumed once the risk of hemorrhage had mitigated |12.

One strength of the present study is that all data were collected prospectively as a part of regular clinical practice. The BI-7 data provided support for implementing EPO therapy. The efficiency and safety of the standardized PBM were evaluated over a long period (a decade) in a homogeneous study in terms of surgical technique and perioperative care protocols. A limitation of the study is that it only included a few patients with ACD. The group was too small to determine any differences in the rate of adverse drug reactions. All observational studies, i.e., studies without random group allocation of patients, are at risk of confounding due to unmeasured and/or unknown factors, which is another limitation of this study. The generalizability of our findings to other clinical settings needs to be determined. Further, given the monocentric nature of the current study and the fact that bleeding in orthopedic procedures varies between surgical teams, the reproducibility of our study needs to be confirmed by others. Another limitation is that the bleeding index is a confounded measure. The drop in Hb during the first week following TKA is influenced by several factors, including surgical and postoperative blood loss, hemodilution, transfusion (which is accounted for in the BI), and reduced erythropoiesis due to surgery-associated inflammation [29]. The effect of blood loss alone cannot be isolated, particularly not in the first few postoperative days. Nevertheless, in general, perioperative blood loss is the most significant factor.

Overall, this study shed light on clinical practice realities, provide clinical evidence, and support treatment recommendations. Observational studies have the potential to generate new hypotheses and identify specific patient groups, such as anemic patients, who may benefit significantly from a particular treatment. Thus, they contribute positively to our understanding of healthcare outcomes.