Background
Total knee arthroplasty (TKA), as one of the most common surgeries in orthopaedics, is routinely applied to treat end-stage knee diseases. It has been proven to be tolerable in correctly selected patients and can effectively alleviate pain, ameliorate function, and improve the quality of life of patients (1). As the proportion of aging adults increases in the general population so does the demand for TKA. It is estimated that the demand for primary TKA will grow to 3.48 million procedures by 2030 in the United States (2). Although the procedure has potential in facilitating the patient’s functional recovery, substantial intraoperative and postoperative blood loss and consequential acute anaemia and transfusion are major concerns for orthopaedic surgeons. The TKA procedure is associated with substantial blood loss, leading to a high prevalence (82.5% in males and 84.3% in females) of postoperative anaemia (3), which may therefore cause the relatively high rate (nearly 45%) of postoperative allogeneic blood transfusion (4). In addition, most patients undergoing TKA are elderly and have a high prevalence (25.3-30.2%) of preoperative anaemia, which is widely accepted as a predictive factor of postoperative allogeneic transfusion. Allogeneic transfusion carries a substantial risk of transfusion-associated complications requiring additional treatment and increased length of stay (5).
To reduce blood loss and allogeneic blood transfusion requirements while accelerating haemoglobin and function recovery, many blood-saving strategies have been reported, of which recombinant human erythropoietin (rhEPO) has demonstrated effectiveness in perioperative autologous blood donation, reducing haemoglobin (Hb) level drop and blood transfusion requirements according to numerous randomized controlled trials (6-10). Currently, there are two main plans for the perioperative application of rhEPO in patients who are scheduled for total joint arthroplasty (TJA). One is the weekly administration of large-dose rhEPO for 2-4 weeks before surgery, which is called the long-term dosing schedule (10). The other is the daily administration of small-dose rhEPO from 0-5 days preoperatively to a few days (less than a week) postoperatively, which is called the short-term dosing schedule (6-9). However, the weekly dosing schedule has some known drawbacks; for instance, patients receiving the long-term dosing schedule and who had not undergone TKA are not allowed to visit the hospital for weekly injections, which is very inconvenient to the patients and will increase the preoperative waiting time and medical costs. The implementation of the dosing schedule is difficult in patients with poor compliance. In addition, initial high peak levels of erythropoietin caused by high weekly doses are likely considered to be wasteful, as erythropoietin receptors on progenitor cells in bone marrow may become saturated; when these receptors are again free for binding, the level of serum erythropoietin will fall (11). Compared with the weekly protocol, the short-term daily dosing schedule with small amounts of rhEPO could maintain a more constant low but relatively more effective level of serum erythropoietin without causing inconvenience or other potential risk to the patient (11). In addition, previous studies also reported that repeated administration of rhEPO is more effective in stimulating the reticulocyte response than the weekly large dose of the same total amount of rhEPO (12).
It has been reported that one daily dose (150 IU/kg) of rhEPO, starting from 3 days before arthroplasty, is more effective in increasing Hb levels and reducing blood loss without causing additional complications than starting on the day of surgery. In the same study, researchers also concluded that the initial application of rhEPO on the surgery day neither significantly reduced blood loss nor increased Hb level after arthroplasty when compared with the blank control group (7). In contrast, Na et al (9) administered 3000 IU of rhEPO subcutaneously to patients, starting on the surgery day through the postoperative period, and found that compared with the placebo group, starting rhEPO on the surgery day could effectively attenuate anaemia and decrease transfusion requirements in patients undergoing arthroplasty, which was comparable with the conclusion of a study by Bernabeu-Wittel et al (6) with a similar rhEPO dosing schedule. Moreover, in another study (8), researchers suggested that each patient undergoing arthroplasty receive a dosing schedule involving 10,000 IU of rhEPO daily subcutaneously from preoperative day 5 to postoperative day 3, which is also the same dosing schedule as our centre. Under this dosing schedule of rhEPO, researchers found a significant reduction of 94% in the need for allogeneic blood transfusion in patients.
As a result, the optimal short-term daily dosing schedule of rhEPO for TKA patients still needs to be investigated. This prospective double-blinded randomized placebo-controlled trial was conducted to compare three different types of short-term rhEPO-based treatment plans for perioperative autologous blood donation in TKA.