Implementation of an anaemia walk‐in clinic: Feasibility and preliminary data from the Orthopedic University Hospital

Approximately one in three patients suffers from preoperative anaemia. Even though haemoglobin is measured before surgery, anaemia management is not implemented in every hospital.


| INTRODUCTION
Preoperative anaemia is common in surgical patients scheduled for major surgery. 1 Within orthopaedic surgery, preoperative anaemia prevalence ranges from 14% for hip or knee endoprosthesis to 45% for duoprosthesis implantation. 2,3 Anaemia is associated with increased morbidity and mortality, prolonged hospital length of stay (LOS), intensive care admissions and red blood cell (RBC) transfusions. 1,[4][5][6][7] Anaemia-related postoperative complications are associated with increased medical costs, thus putting enormous pressure on health-care facilities. 8 Iron deficiency (ID) accounts for~60% of all anaemia cases. 9 The effectiveness of iron supplementation in iron-deficient patients has been demonstrated in many studies. 10 For example, supplementation of intravenous (IV) iron in orthopaedic patients 1-3 days before surgery was associated with a reduction of RBC transfusion rate from 37% to 24% and LOS from 11.7 to 10.7 days. 11 In order to minimise risks associated with anaemia in surgical patients, a patient blood management (PBM) programme has evolved within the last decade. 12 PBM is an evidence-based, patientcentred, multidisciplinary approach to reduce anaemia (pillar 1), minimise iatrogenic blood loss (pillar 2) and optimise patient-specific tolerance of anaemia (pillar 3) in order to maintain the patient's own blood volume. 13 So far, more than 100 individual PBM measures have been defined based on the broad interdisciplinary fields and temporal application. 14 In this context, an anaemia walk-in clinic was established in 2014 at the University Hospital in Frankfurt. 15,16 Overall, IV iron supplementation in iron-deficient anaemia (IDA) patients undergoing major non-orthopaedic surgery was associated with a decreased transfusion rate and LOS. 16 Even though the effectiveness of an anaemia walk-in clinics has been demonstrated, 10,[15][16][17][18] anaemia walk-in clinics have only been implemented in a few hospitals so far. Reasons might be the lack of knowledge and/or resources. In addition, there is only limited information available for assistance in implementation of an anaemia walk-in clinic. For the detection of ID, most hospitals measure ferritin or transferrin saturation (TSAT). 19 It is worth noting that ferritin is an acutephase protein, and therefore, false-positive increased serum ferritin levels may be observed in patients with increased inflammation values. 20 Recently, a reticulocyte haemoglobin equivalent (Ret-He) has been proposed as an additional marker to detect ID. 21 Reticulocytes are immature RBCs and exist for up to 2 days in the peripheral blood. Thus, Ret-He provides information of shortly produced RBCs. 22 In addition, Ret-He is not affected by inflammation compared to ferritin. 20 14 Here, we report the implementation of an anaemia walk-in clinic at another hospital, the OUF.

| Overall requirements for anaemia management in an anaemia walk-in clinic
Our anaemia walk-in clinic was individualised according to local conditions, infrastructure, staff and economic resources. At the OUF, an anaemia coordinator was in charge of the hospital's anaemia management.
The anaemia coordinator played a central role in communication and multidisciplinary organisation. The cooperation of further key stakeholders, like hospital administration, chief medical staff, nursing staff, anaesthesiologists and surgeons, was established. Support by the hospital pharmacy department (to facilitate access to IV iron formulas), financial department (to manage costs associated with anaemia management), information technology (IT) department and central clinical laboratory was required. To ensure awareness of the importance of anaemia management, medical education to health-care personnel was provided in order to extend or refresh knowledge on different forms of anaemia, anaemia management, blood transfusion and alternatives (Table 1).
T A B L E 1 Overall requirements for anaemia management in an anaemia walk-in clinic

| Everyday clinical requirements of an anaemia walk-in clinic
To identify potential eligible patients, surgical timetables and schedules of the pre-hospital admission unit of patients undergoing major elective orthopaedic surgery were screened. Lists of major surgeries for the assessment of preoperative anaemia management were available to the staff at any time. Blood samples were drawn either at the pre-hospital admission unit or by the staff on the ward from non-mobile patients. As demonstrated in Figure 1, a defined pathway, including screening process, diagnostic algorithm and treatment protocol, was used to ensure consistency and sustainability. IV iron supplementation was adminis-

| Classification of iron deficiency anaemia
According to the World Health Organization (WHO), anaemia is defined as a Hb concentration of <12 g/dl in women and <13 g/dl for F I G U R E 1 Diagnostic algorithm of the anaemia walk-in clinic. ID, iron deficiency; IDA, iron deficiency anaemia; IV, intravenous; RBC, red blood cell; TSAT, transferrin saturation men. Iron deficiency was defined by laboratory results according to Munoz 24 and Anker et al. 25 Briefly, ID was defined as serum ferritin level < 100 ng/ml and TSAT <20%, 24 and in case of chronic kidney disease or heart failure, a serum ferritin level < 300 ng/ml was used. 25 In addition, full medical history of the patient was taken into account.

| Data collection
Data were extracted from the electronic hospital information system.
Patient-specific observation periods ranged from pre-hospital admission to hospital discharge.

| Endpoints
The primary endpoint was the prevalence of preoperative anaemia in patients undergoing major orthopaedic surgery. Secondary endpoints were Ret-He level, RBC transfusion rate, LOS and prevalence of anaemia at hospital discharge.

| Statistical analysis
Descriptive statistical methods such as mean ± SD, median and interquartile range (IQR) (25%; 75%) were used to analyse the data. The  infections (n = 2) or alcohol withdrawal therapy (n = 1). The remaining 97 patients were included in analysis ( Figure S1). Overall, 20 of 97 (20.6%) patients were anaemic. No difference was found between age and gender in both groups. The prevalence of existing comorbidities differed significantly between the groups regarding respiratory (p = 0.008) and chronic renal disease (p = 0.017). No significant difference was found in type of surgery between the two groups (Table 3).

| Hb levels, RBC transfusions and LOS in the anaemia and non-anaemia groups
The preoperative Hb level of patients in the anaemia group was lower (11.6 [10.8-11.8] g/dl) compared to the non-anaemia group (13.3

T A B L E 2 Everyday clinical requirements of an anaemia walk-in clinic
Step

| Comparison of RBC indices and iron parameters between the anaemia and non-anaemia groups
We compared RBC indices between the anaemia and non-anaemia  (Table 4).

| Treatment of iron deficiency
Overall, IV iron was supplemented in 23 patients. There were no con-

| DISCUSSION
In many surgical patients, anaemia is present and associated with an impaired erythropoiesis due to ID. 26 Even though Hb values are measured before surgery, preoperative anaemia management is not performed in every hospital. In this study, we present the results of the implementation of an anaemia walk-in clinic at the OUF based on the example of the University Hospital in Frankfurt. 15,16 In addition, the usefulness of Ret-He in preoperative anaemia management was evaluated.
For implementation of the anaemia walk-in clinic, multidisciplinary consensus between hospital administration, leading professionals and medical staff at the OUF was established. Potential barriers such as lack of interest or underestimation of the impact of preoperative anaemia management were mostly eliminated by medical anaemia education in forms of written information material and lectures. Anaemia management was included in routing slips and electronic medical records, obvious to all health-care workers. For adherence and to ensure daily routine, a treatment algorithm for preoperative anaemia management was provided. Scheduling patients for anaemia management a few weeks prior to surgery was challenging. IV iron supplementation up to 21 days before surgery significantly increased Hb levels 4 weeks after surgery. 18 However, Spahn and colleagues revealed that ultra-short IV iron administration in combination with erythropoietin alpha, vitamin B12 and folic acid on the day before surgery can also be effective. 17 In our anaemia walk-in clinic, IV iron was administered until the day of surgery and up to 3 days after surgery.
In our analysis, anaemia was present in 20 of 97 (20.6%) patients; therefore, 12 of 20 anaemic patients (60.0%) presented with IDA. Iron T A B L E 4 RBC indices, iron status parameters and CRP for the anaemia and non-anaemia groups and for all patients before surgery Anaemia n = 20 Non-anaemia n = 77 p value All n = 97 Hb (g/dl) 11.6 (10.  Our results are in accordance with a study by Theusinger et al, where a preoperative anaemia rate of 20.0% was revealed in patients undergoing major orthopaedic surgery. 10 Besides ID being the most common form of preoperative anaemia, one-third of the patients suffer from anaemia of chronic inflammation, and another 30% suffer from anaemia of mixed cause or unexplained origin. 27 In the anaemia group, we observed a higher median age compared to the non-anaemia group. In addition, comorbidities, such as chronic kidney diseases, were significantly higher in the anaemia group. Reasons for anaemia in elderly orthopaedic patients may be caused by changes in stem cell physiology associated with inflammation, renal diseases or the use of multiple drugs. 27 Possible causes of ID in elderly patients may also include malnutrition, dysfunctional enteral iron absorption or chronic blood loss. 3  Of all investigated parameters, iron parameters like ferritin and TSAT showed no significant differences between the anaemia and non-anaemia groups. Ret-He was significantly lower in the anaemia group compared to the non-anaemia group. An analysis of subgroups revealed that Ret-He was significantly lower in patients in the IDA subgroup compared to the ID subgroup and control subgroup. Ret-He is an early marker of iron-deficient erythropoiesis. Changes in MCV (21 days) and Hb value (60 days) occur when IDA has already taken place. 20 Furthermore, the effect of iron supplementation can be monitored closely with Ret-He as its effect can already be detected after 2 days, whereas ferritin levels increase only after 2 weeks. 20 In clinical practice, serum ferritin plays a major role in the diagnosis of IDA. However, ferritin as an acute-phase protein may increase false positively in the presence of inflammation, whereas Ret-He is not affected by inflammation. 28 Thus, with increased levels of Ret-He and ferritin in the presence of inflammation, IDA can be ruled out, and iron supplementation is not indicated. However, high levels of ferritin and a low Ret-He count indicate that ID and iron supplementation is recommended. 28 Therefore, we have included the Ret-He as a standard parameter to assess the presence of ID at the OUF and also at the University Hospital of Frankfurt and to enable effective preoperative anaemia management.

| Limitations
Our study has some limitations. First, we used an observational design; therefore, confounding factors cannot be excluded.

| Conclusion
In conclusion, our study provides detailed information for the implementation of an anaemia walk-in clinic. Preoperative anaemia is common in orthopaedic patients and was associated with a relevant increase in RBC concentrate consumption. In addition, our analysis supports the use of Ret-He as an additional parameter for diagnosis of ID and the decision for iron supplementation in orthopaedic patients. However, further studies are needed to investigate and validate its feasible utility and cost-saving effect in this clinical setting of preoperative anaemia management.

ACKNOWLEDGEMENTS
We thank Sabine Isik for her support. We also acknowledge the help of hospital managers, health-care personnel (nurses, surgeons and anaesthesiologist) from the OUF for their invaluable support during the implementation of the anaemia walk-in clinic.