Unwashed shed blood: should we transfuse it?

While increasing the blood oxygen carrying capacity, transfusion of red blood cells also carries inherent risks and complications¹. As the risks of transmission of viruses through allogeneic blood transfusion have been reduced to exceedingly low levels, transfusion-related acute lung injury, haemolytic transfusion reactions, and transfusion-associated sepsis have emerged as the leading causes of allogeneic blood transfusion-related deaths. In addition, an association between the transfusion of non-leucoreduced red cells and mortality has been detected in cardiac surgery².

At a time when the increased demand for blood coincides with a significant reduction in blood donations, conservative transfusion guidelines and the use of drugs and techniques to contain the need for peri-operative homologous blood components are being given growing attention by anaesthetists, surgeons and transfusion medicine specialists^3,4. The increasing focus on peri-operative blood management has led to the use of many techniques, several of which require the involvement of the laboratory, to decrease the exposure to allogeneic blood⁵.

Recovery and reinfusion of blood from surgical drains is a commonly used technique to avoid transfusion of allogeneic blood. In 2005, approximately 320,000 post-operative collection devices were sold in the United States, thus showing an extensive use of these systems⁶. To the knowledge of the authors, similar data are not available for Italy. The primary function of these devices is to act as a reservoir for the shed blood. When adequate amounts of blood are collected, the system is flipped over and plugged into an intravenous line⁷. This procedure has earned these devices the nickname of “flip-n-drip” systems. They dominate the market primarily because of their simplicity and low cost and because they are user-friendly. They are composed of an inlet which is connected to the wound drain, gross filtration (typically between 100 and 200 microns), a collection reservoir, and an access port for an intravenous administration set. The more sophisticated of these devices add vacuum control, fat-specific filtration, a label, an anti-air embolism valve, a check valve and a port for the possible addition of an anticoagulant. Typically, the blood is collected, filtered and reinfused without washing. The stated potential benefits of utilising these devices is the reduction of allogeneic transfusion and its associated risks, and cost. Because of the absence of washing, significant controversy exists about the technique.

Unwashed salvaged blood is laden with various inflammatory mediators^8-11, fibrin split products^12-14, complement fractions^8,9,15, interleukins^16-18, tumour necrosis factor α¹⁰, and fat particles¹⁹, present at concentrations significantly higher than circulating levels. Most of these mediators are constituents of cascade systems and, once generated, they induce and amplify further reactions in the blood resulting in even more activation products^20,21. It is easy to believe that there is significant risk associated with re-administration of this unwashed blood as some of these “biochemical debris” (fibrin(ogen) degradation products and D-dimers, tissue plasminogen activator, activated fibrinolytic products, activated complement, cytokines, proteolytic enzymes, marker enzymes, red cell stroma, activated leukocytes, free haemoglobin, bacteria and endotoxins, fats, anticoagulants, metal ions and debris from orthopaedic prostheses) have been identified as the main mediators of coagulopathy, disseminated intravascular coagulation, acute respiratory distress syndrome, systemic inflammatory response syndrome and multiorgan failure. This being said, the reported risks appear to be minimal. The most commonly reported complication after re-administration of this blood is febrile reaction. Fever is reported to occur in 4% to 12% of patients following postoperative recovery of blood and its re-administration^22-25, which is more frequent than with allogeneic transfusions. In most reports on the use of unwashed blood salvage, this is generally the only reported complication; however, one needs to be careful in coming to this conclusion because all of these reports are small case series⁷.

In a recently updated Cochrane systematic review, Carless et al. reviewed the complications of all available studies on peri-operative blood recovery²⁶. They evaluated the total blood loss, the adverse events and other outcomes such as mortality, re-operation for bleeding, any infection, wound complications, any thrombosis, stroke, non-fatal myocardial infarction, deep vein thrombosis and duration of stay in hospital. The use of cell salvage did not appear to affect clinical outcomes adversely except for a slight decrease in the rate of any infection; however, they mixed studies of washed with unwashed recovery and studies in cardiac surgery were preponderant.

In a recent retrospective study comparing the strategy of unwashed salvaged blood to no salvage, the reinfusion of unwashed salvaged blood after total knee arthroplasty in patients with rheumatoid arthritis was shown to be useful for avoiding allogeneic blood transfusion, but the total post-operative drainage volume was significantly greater (even after unilateral total knee arthroplasty) compared with that in patients receiving only allogeneic transfusion²⁷. The post-operative drainage volume was proportional to the autotransfusion volume, suggesting that autotransfusion with unwashed blood influences coagulation and fibrinolysis in some way. In a subsequent, prospective study, the same authors showed that autotransfusion with a large volume of unwashed shed blood results in an increase of post-operative drainage due to the activation of fibrinolysis²⁸. They confirmed previous reports showing that unwashed blood has a very low fibrin level, an increase of fibrin split products and tends to promote excessive fibrinolysis and activation of blood coagulation^12,25,29.

The autologous reinfusion of the content of drains was shown to reduce the rate of post-operative allogeneic blood transfusion significantly in a small, prospective, non-randomised study by Singh et al. published in this issue of Blood Transfusion³⁰. However, 24-48 hours after surgery a larger mean total drain output was recorded by the authors in the group of patients to whom unwashed shed blood was reinfused [517.4 mL (range: 150-1,110)] in comparison to the control group [416.2 mL (range: 60-950)] where it was discarded, although the difference was not statistically significant (p = 0.06). This occurred despite the fact that, as the maximum drain output recorded after 24-48 hours was 1,110 mL, the volume of the blood collected within 6 hours of surgery and re-infused back into the patients was well below the arbitrary upper safety limit of 1,000 mL³¹ which is recommended by many of the manufacturers of these devices.

Furthermore, the platelets and leucocytes in salvaged blood are markedly activated and their re-infusion causes a decrease in platelet count in the recipient and a possible increase in thrombin generation which could potentially favour thrombosis³². One of the most feared complications of orthopaedic surgery is that of venous thromboembolism. No adequately powered studies have been performed to show whether reinfusion of this blood leads to more significant complications, such as thrombotic events. The previously mentioned Cochrane systematic review²⁶ included only five reports of unwashed shed blood in orthopaedic surgery in which this adverse event was evaluated^33-37. The number of patients in these studies ranged from 20 to 92; no cases of deep venous thrombosis were found in three studies^34-36; both control and study groups had two patients with deep vein thromboses in one study³³, and one patient in the unwashed blood group versus two in the control group were diagnosed with the same adverse event in the more recent study³⁷. In general, the rates of deep venous thrombosis are reported to be 2.27% in hip arthroplasty and 1.79% in knee arthroplasty with the rate of fatal pulmonary embolism being 0.22%³⁸. To detect changes in the incidence of this complication related to blood salvage, much larger sample sizes would be needed than those included in the aforementioned studies. A prospective, randomised study in knee surgery with a power of 80% to show that unwashed blood salvage is likely to increase this incidence by 50% (from 1.79% to 2.7%) would require a population of 700 patients; 920 patients would be needed if the power of the designed trial were to be set at 90%. Similarly, in hip surgery these figures would be 530 and 700, respectively, in order to raise the incidence from 2.27% to 3.4%.

It is easy to imagine that there is a marked underreporting of side effects after transfusion of post-operative shed blood. In fact, nurses most commonly perform this procedure, with no quality overview being mandated. Thus, the paucity of reports of serious sequelae in the literature may simply be due to a lack of observation and auditing of more serious untoward effects of unwashed blood which could be effectively prevented by simply washing the blood⁶.

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 five adverse reactions were described relating to the transfusion of post-operative, unwashed autologous blood. These reports included pyrexia, rigor and bradycardia and it is envisaged that, with the advent of the online reporting system, these may be a feature of future reports¹.

A simple solution to the hazards of the contaminants of unwashed, postoperative cell recovery would be to wash the blood properly with saline to eliminate the “biochemical debris”, as suggested by Muñoz in this issue of Blood Transfusion³⁹. Improved safety and quality management can be achieved using a processing device that concentrates the red cells and washes out contaminants. This processing can occur with a traditional blood salvage device or a device specifically designed for washing post-operative wound drainage blood⁵. While intuitively it makes sense that washing would reduce the risk of these complications, it is important to recognise that no direct comparisons between an unwashed and a washed product have been published.

A second controversy concerning unwashed shed blood is related to the volume of red cells returned to the patient and whether this small volume warrants the perceived risk associated with reinfusion of the unwashed blood⁵. After cardiac surgery, an average of approximately 500 mL of blood is returned to the patient^40-42, whereas the variability in orthopaedic procedures is greater, with reported blood loss ranging from 166 to 750 mL^22,25,43. Typically, this shed blood has a haemoglobin level ranging from 20% to 30%^12,44. What this means is that less than 100 mL of red blood cells is being given back to the average patient, amounting to approximately half a unit of allogeneic red cells, and that, even in optimum circumstances, little more than a single packed red blood cell equivalent is returned to the patient. Many clinicians suggest that if only one unit of allogeneic blood is given, it is probably not needed, so half a unit would also fall into a category of unnecessary transfusion⁴⁵, being “clearly inadequate to cause any impact on the postoperative haemoglobin”, as stated by a recent retrospective study of patients undergoing primary total knee replacement⁴⁶. Since these devices will rarely yield more than the equivalent of one red cell unit, a careful cost analysis should be made prior to universal adoption.

Furthermore, the use of unwashed cell salvage merely as a means of obtaining an autologous volume replacement due to the relatively low haemoglobin concentration in unwashed blood, though recommended by Munoz et al.³⁹, seems unjustified; in fact, as there are other volume expanders with a greater level of proven safety and a better cost-benefit ratio, the administration of a clinically insignificant red cell mass with incorporated contaminants represents an unreasonable risk⁴⁷. In addition, any transfusion needs a clear indication and volume replacement is not an accepted one⁴⁸.

Finally, though there are no official European quality standards for autologous blood obtained during peri-operative cell salvage, in the guidance document published in this issue of Blood Transfusion, the Italian Society of Transfusion Medicine and Immunohaematology (SIMTI) recommends the use of washed blood in orthopaedic surgery and in other possible surgical settings⁴⁹. One approach to meeting the safety and quality expectations of patients is to follow the transfusion medicine standards issued by SIMTI and assess “both the quality and safety of blood products deriving from the peri-operative cell salvage procedures (e.g. excess activation of coagulation factors, excess haemolysis, contaminants from the surgical field)⁵⁰. In North America the suggested approach to providing quality management to postoperative blood recovery is to follow the AABB (formerly known as the American Association of Blood Banks) Standards for Perioperative Autologous Blood Collection and Administration and monitor unprocessed blood for haematocrit, volume, and expiration time^7,51; blood processed at the point of care or with an intra-operative device should be checked for concentration and wash effectiveness both before and after processing and the devices should also be subjected to observational measurement of quality.

In conclusion, quality surveillance of cell salvage procedures, although not currently mandatory, can represent a strategic tool both for patients’ safety and for understanding and monitoring serious adverse reactions and events, especially with the use of unwashed blood. We agree with Muñoz that the adoption of voluntary standards and good practice guidelines for peri-operative cell salvage procedures are a priority step in order to comply with European Directives on transfusion safety³⁹, quality and haemovigilance. In this regard, in Europe the SHOT Group is continuing to record all adverse events related to autologous transfusion, including cell salvage incidents. These data are being collected in collaboration with the UK Cell Salvage Action Group¹. The haemovigilance data will provide us with a definitive solution to the dilemma of whether to use unwashed shed blood or not.