Post-operative blood salvage in patient blood management: is it really cost-effective and safe?

Knee replacement surgery can result in significant peri-operative bleeding and expose patients to an increased risk of receiving transfusion therapy. Allogeneic blood transfusion, though increasingly and constantly safer than ever, is not devoid of risks¹. In addition, as recently shown by Shander et al. through an activity-based cost analysis², red blood cell transfusion is an expensive treatment whose costs, largely underestimated and several fold the red blood cell production costs, absorb a consistent part of total health care financial resources.

Transfusion-related risks and costs together with a growing awareness of the possible future shortage of the blood supply^3–5 have stimulated the interest of the scientific community in the concept of “blood management”⁶.

Patient blood management (PBM) has been defined as “the timely application of evidence-based medical and surgical concepts designed to maintain haemoglobin concentration, optimise haemostasis and minimize blood loss in an effort to improve patient outcome”⁷. PBM is a multiprofessional, multidisciplinary, multimodal, “hospital-wide and patient-centred” approach to managing anaemia, perioperative blood conservation, surgical haemostasis, and blood use that can be applied also to medical patients⁸. It relies “on a patient’s own blood rather than on donor blood” and “goes beyond the concept of appropriate use of blood products, because it pre-empts and significantly reduces the resort to transfusions by addressing modifiable risk factors that may result in transfusion long before a transfusion may even be considered”⁹. The objectives of PBM programmes, namely better outcomes for patients and cost reduction, are pursued through a new standard of care based on the so-called three pillars of PBM: optimising the patient’s erythropoiesis, minimising bleeding and blood losses, and harnessing and optimising the patient-specific physiological reserve of anaemia⁹. In 2010, the World Health Organisation identified the need for PBM and urged all the 189 member states of the United Nations to implement various transfusion-related strategies including PBM with its three-pillar approach¹⁰.

In the United States of America (USA), PBM has attracted the attention of the Association for Advancing Transfusions and Cellular Therapies (formerly known as the American Association of Blood Banks - AABB), the Society for the Advancement of Blood Management (SABM) and the Joint Commission^11,12; the Joint Commission published seven PBM performance measures and placed them in the organisation’s reserve library¹³. The number of PBM programmes in the USA has grown considerably so that from fewer than 10 in 1994, there are currently around 100¹¹. This new standard of care is now adopted in several centres in Australia where national and state-wide initiatives are underway to implement PBM broadly as a new and cost-effective standard of care in the public health system¹⁴. Currently, despite the initiatives of the Network for Advancement of Transfusion Alternatives (NATA), the implementation of PBM in Europe¹⁵, except for Austria and the Netherlands, is limited¹⁶.

According to the second pillar of PBM, autologous blood salvage is one of the tools to minimise blood loss in the intra-operative and post-operative periods¹⁷.

In this issue of Blood Transfusion, Manuel Muñoz and colleagues present a comprehensive and elegant cost analysis of post-operative cell salvage after total knee arthroplasty¹⁸. The authors retrospectively reviewed data from 1,093 consecutive primary total knee replacements. They compared outcomes and costs in two groups of patients for whom a transfusion protocol had been defined and managed with reinfusion of unwashed shed blood recovered with two different devices (reinfusion group, 763 patients) or without reinfusion of shed blood (control group, 330 patients). The patients treated with shed blood had a significantly lower allogeneic transfusion rate and spent a shorter time in hospital. Both reinfusion systems were able to provide variable savings in different cost scenarios incorporating the costs of extra days of hospitalisation. The aforementioned blood management cost scenarios were also analysed after stratifying patients according to their pre-operative haemoglobin and varying the rate of allogeneic blood transfusion support in both groups. The authors concluded that the reinfusion of unwashed shed blood can reduce allogeneic transfusion rate and blood management costs in patients with pre-operative haemoglobin levels between 120 g/L and 150 g/L.

However, as no transfusion trigger was adopted in the reinfusion group for the infusion of shed blood, despite a lower allogeneic transfusion rate, the overall transfusion index was significantly higher than in the control group; unfortunately, only 139 out of 488 re-infused patients (28.5%) received a dose of shed blood equivalent to one or more units of packed red blood cells and, hence, a therapeutic dose. This study confirmed that reinfusion devices rarely yield more than the equivalent of one unit of red blood cells. Moreover, it also showed that the real challenge lies in identifying those patients at risk of significant early post-operative blood loss and those who, being anaemic, would really benefit from shed blood transfusion therapy. A low haemoglobin transfusion trigger is a key element to reduce the transfusion rate and should also be applied to transfusions of shed blood in the post-operative period in patients who have undergone knee replacement surgery. In fact, the existing evidence supports the use of restrictive strategies adopting transfusion thresholds lower than 70 g/L of haemoglobin in haemodynamically stable patients^19,20 and, though with a lower strength of recommendation, lower than 80 g/L in elderly high-risk patients^20,21. In addition, if only the anaemic patients could be treated more efficiently with doses of recovered blood that are really therapeutic and do not, therefore, fall within the category of unnecessary transfusions²², the cost-effectiveness of post-operative cell salvage after total knee arthroplasty would be further increased.

As correctly pointed out by Muñoz et al., another controversial issue is the quality and safety of unwashed shed blood. While intuitively, it makes sense that washing would reduce the presence of contaminants in shed blood and the risk of the possible associated complications²³, it is important to recognise that no direct comparisons between an unwashed and a washed product have been published. We, therefore, thoroughly agree with the Australian National Blood Authority that considers “the evidence for the use of washed rather than unwashed blood is unclear; as no direct comparisons between an unwashed and a washed product have been published so far, further studies are needed to evaluate the safety of postoperative cell salvage using unwashed blood”²⁴. For this reason transfusion therapy with washed blood, when necessary and really feasible with therapeutic doses of red blood cells, should be preferred²⁵ at least until a similar degree of safety between washed and unwashed blood shed blood is proven (by randomised controlled trials) rather than postulated (based on observations).

Previous reports to the Serious Hazards of Transfusion (SHOT) Group on side effects due to unwashed shed blood have been sporadic but in the 2009 SHOT report there are descriptions of five adverse reactions related to post-operative, unwashed autologous transfusion²⁶. In 2011, a higher number of adverse events or reactions (n =25) associated with the autologous transfusion of post-operative cell salvaged (washed or unwashed) blood was submitted to SHOT and it is also worth mentioning that in no case was it known where the transfusion had taken place²⁷. Therefore, if we want to combine cost-effectiveness, appropriate use of shed blood and safety we need to bring this practice back to the transfusion world and expand the surveillance of our haemovigilance systems to both intra-operative and post-operative cell salvage.

In the meanwhile, it is prudent and safe to establish procedures for assessing the quality and safety of blood products deriving from peri-operative blood salvage procedures (e.g. excessive coagulation factor activation, excessive haemolysis, contamination from the surgical field) as required by the Italian Standards of Transfusion Medicine, recently translated into English and freely available at the Italian Society of Transfusion Medicine and Immunohaematology (SIMTI) website ²⁸.

In addition, we deem that in the quest for accountable (and sustainable) care, namely the creation and development of a model that can constrain health care costs while improving quality and the health of patients²⁹, when substantial blood loss is anticipated, transfusion medicine specialists adopting PBM should also take into consideration the use of pharmacological therapies to minimise peri-operative bleeding in joint replacement surgery^8,30–32, especially if, in addition to being of proven safety and efficacy, they also are cheap such as tranexamic acid. In fact, three very recent meta-analyses showed that the use of this antifibrinolytic agent in total knee arthroplasty is effective and safe and significantly reduces the amount of blood loss, the number of blood transfusion units per patient and the proportion of patients requiring transfusion therapy^33–35.