In elective surgery, a preadmission assessment of patient’s clinical conditions is generally performed some 30 days before surgery. Potential benefits include increased patient safety, reduced cancellation or delay of surgery, reduced LOS, and increased quality of patient experience. Pillars of preanesthesia evaluation are medical records, patient interview, and physical examination and tests, where indicated (NICE 2003; ASA 2012): major surgery schedule for adults includes a complete blood cell count and blood typing (T&S).

In a PBM program, such schedule is to be further integrated with the ultimate aim of optimizing patient’s medical health prior to surgery, ultimately avoiding unnecessary transfusions. For the weight that anemia has as a prognostic factor of unfavorable outcome, its diagnosis is central to subsequent correction. Etiology is heterogeneous, and unexpected diseases such as chronic kidney failure or occult malignancy are to be considered. In these cases, referral to appropriate specialist is necessary, before planning any elective surgery. Overall, iron-restricted erythropoiesis as the most relevant abnormal condition in elderly and chronic inflammation are common in candidates for lower limb arthroplasty (Spahn 2010). Consequently, the “iron status” must be assessed, by measuring blood ferritin and TSAT, together with an inflammation index (CRP). These tests can be ordered contemporaneously to full blood cell count or later, only for anemic patients, depending on organizational constrains (Goodnough et al. 2011; Royal Cornwall Hospitals 2013).

All the collected data will lead to discriminate among three possible conditions:

In elderly population, also vitamin B12 and folate deficiency are relatively common (Bisbe et al. 2008; Saleh et al. 2007). We suggest to order their dosage (as a reflex test) when defects are suspected, i.e., when macrocytosis is present.

In order to minimize blood loss during surgery, the assessment of hemorrhagic risk constitutes a priority. Algorithms for scoring the risk are available (Tosetto et al. 2007; Nichols et al. 2008). Fundamental is the interview, where any personal and family history of bleeding disorders must be uncovered, as well as the use of medicaments, both prescribed or not. Besides anticoagulant or antiplatelet drugs, agents that are able to interfere with hemostasis include NSAIDs, serotonin reuptake inhibitor antidepressants, and herbal remedies such as garlic, ginkgo biloba, ginseng, and others (Ang-Lee et al. 2001).

Preoperative evaluation must also assess a transfusion strategy, beginning with the prediction of the need for ABT. Apposite algorithms have been elaborated (Mercuriali and Inghilleri 1996; Noticewala et al. 2012; Park et al. 2013), taking into account surgical technique, procedure duration, hemostatic measures, and patient’s features. On the basis of that, alternatives to transfusion are to be planned, including the use of autologous blood and/or pharmacological treatments.

For major surgery, a preadmission ABO/Rh typing should be ordered. Instead, the usefulness of a red cell antibody screening depends on patient’s history (previous transfusions) and on organizational peculiarities, i.e., it is advisable if pre-transfusion tests and cross-matched blood may be not available because of time constraints, when surgery occurs shortly after admission.

Nutritional deficiencies should be treated by proper vitamin and/or mineral medicament, besides a correct diet. Treatment of iron-restricted erythropoiesis is particularly important for the prevalence of preoperative anemia and for its unfavorable consequences. It is based on the availability of two classes of agents: iron, in oral and IV formulations, and erythropoiesis-stimulating agents (ESAs).

In brief, oral iron therapy, when tolerated, will work appropriately in most iron-deficient patients, unless an absorption defect is present. When a diagnosis is made of functional iron deficiency, iron sequestration, or mixed anemia, IV iron therapy may be necessary, particularly in the presence of a systemic inflammatory response, because of inhibition of gastrointestinal absorption caused by increased hepcidin levels. At present, IV iron is included in guidelines as a recommended pharmacological measure aimed to reduce transfusion rate (Leal-Noval et al. 2013). Several formulations are available for IV use, currently for different anemic conditions. High-molecular-weight iron dextran (HMWD) should be abandoned in favor of low-molecular-weight iron dextran (LMWD), for a lower rate of adverse reactions. Ferric gluconate and iron sucrose are formulations widely used in chronic kidney disease, but adverse effects are not rare. The recently introduced ferumoxytol does not require dilution for slow IV use, in contrast to iron sucrose and sodium ferric gluconate. Ferric carboxymaltose and iron isomaltoside, still in the course of study for some applications, are proposed, as well as ferumoxytol, for total dose infusion, that is, a slow infusion of 1–1.5 g. The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP; 2013) has emanated new recommendations to manage risk of allergic reactions with intravenous iron-containing medicines indicating that IV iron medicines are used when iron supplements given by mouth cannot be used or do not work and staff trained to evaluate and manage anaphylactic and anaphylactoid reactions must be immediately available, as well as resuscitation facilities. Moreover, the utility of test dose is underscored, and a 30-min period of observation after infusion is prescribed.

In the late 1980s, ESAs were first approved for use in chronic kidney disease patients, who mostly continue to benefit of this therapy. Later on, ESAs have also been approved for oncology patients suffering from chemotherapy-induced anemia and for patients candidate for elective surgery, even though not universally. In particular, in many European countries, ESA preoperative use is not approved, unless preoperative autologous blood donation (PABD) is scheduled. More recently, following post-approval clinical trials, targeting risk of thrombotic adverse effects of ESAs, and overall increased rate of morbidity and mortality, limits for their use have been indicated, in respect to Hb levels and an appropriate antithrombotic prophylaxis, by regulatory agencies.

Used preoperatively, ESAs are able to increase Hb levels, being the equivalent of 1 RBC unit produced by day 7 of treatment. In the course of a PABD program, 5 units can be produced with a timing compatible with storage and use during surgery (Goodnough et al. 1992). Most effective dosage and timing of administration are debated, and diverse schedules are used. Low doses of erythropoietin (400 U/kg over a 2-week period) are sufficient to exert a significant stimulus on erythropoiesis (Sans et al. 1996). Even a single administration of erythropoietin plus iron, 1 day before surgery, has been found to be effective in reducing the need in ABT in cardiac surgery (Yoo et al. 2011). Aggressive schedules are employed in the course of a PABD program, when the RBC mass produced on a 3-week period, directly related to erythropoietin dosage, can be anticipated: RBC volume (ml per kg) = 6.34 + 0.0013X, where X equals the total units of erythropoietin administered, per kg body weight (Goodnough et al. 1994). Throughout the course of ESA treatment, iron supplementation is necessary to maximize the RBC production stimulated by ESAs.

In order to prevent severe blood loss, withdrawal of anticoagulant or antiplatelet drugs is recommended, unless critical for patient’s safety. Under usual circumstances, warfarin and aspirin should be discontinued, 5 days before surgery, but at least 7 days of withdrawal are necessary for clopidogrel. Stopping aspirin and/or clopidogrel for secondary prevention should be carefully weighted case by case, after discussion with the prescribing cardiologist, but maintaining low-dose aspirin is mostly recommended (Korte et al. 2011; Royal Cornwall Hospitals 2013). Experiences of urgent orthopedic surgery in patients on antiplatelet drugs should relieve general concerns about excessive perioperative bleeding (Collinge et al. 2012; Feely et al. 2013). The BRIDGE trial, targeting bridging for anticoagulation, is still ongoing.

The use of other, nonprescribed drugs and herbal remedies possibly interfering with the hemostatic process is to be discouraged. Classical NSAIDs, because of their short half-life, usually do not raise concern of intraoperative bleeding; also, there is no indication for withdrawal of COX-2 inhibitors, provided adverse cardiac effects are taken into account. Serotonin reuptake inhibitor antidepressants have been imputed to enhance perioperative bleeding, but so far a clear evidence of increased risk of ABT is lacking; it is advisable to avoid coadministration with aspirin (Movig et al. 2003; van Haelst et al. 2010). For recommended behavior regarding perioperative use of drugs, see a list in Royal Cornwall Hospitals (2013).

Preoperative autologous blood donation (PABD), consisting of collecting and storing the patient’s own blood prior to surgery, has been widely practiced in different surgical settings, offered to patients as a main alternative to ABT. Indeed, PABD programs in major orthopedic surgery have caused a reduction in risk of ABT (Rosencher et al. 2003; Carless et al. 2004). Greater effectiveness is obtained when a PABD program is integrated with treatment with an ESA. Yet, the overall risk of transfusion is increased, entailing an increased risk of clerical errors as well as some kind of complication also presented by PABD (TACO, fever and chills, infections, possibly immunomodulation). These and other disadvantages (over-collection, outdating, wasting) are to be taken into account in order to evaluate PABD cost/benefit ratio. The British Committee for Standards in Hematology (2007) emanated internationally recognized guidelines that do not recommend PABD unless specific conditions are present. In particular, patients still considerable candidate for PABD are children with scoliosis, patients who refuse transfusion but would consent to PABD, bearers of rare blood groups, or who are poly-immunized. A PABD program, in combination with blood salvage, may be beneficial in bilateral TKA (Boettner et al. 2009).