Control of surgical bleeding and directed resuscitation remains a critical component of intraoperative patient care. When necessary, blood components play a vital role in stabilizing the hemorrhaging patient. As surgical techniques have evolved over the past several decades, there has been increasing focus on the appropriate use of blood components. It is important to understand how perioperative transfusion medicine has evolved in the setting of changing surgical practices, such as laparoscopy, robotic surgery, improved surgical hemostatic techniques, and hemostatic agents for perioperative care. In addition, novel pretransfusion practices are making transfusion safer and more efficient. (Table 1 lists commonly used terms, abbreviations, and definitions.)
We searched the following databases: PubMed, EMBASE, Google Scholar, and the Cochrane Library from January 1970 through March 2014 for keywords “Electronic Crossmatch,” “Computer Crossmatch,” “Virtual Blood Bank,” “Maximum Surgical Blood Ordering Schedule,” and “Electronic Remote Blood Issue.” Subsequent reference searches of retrieved articles were also evaluated. All article types (including case series and case reports) were included.
Patient Blood Management
The majority of transfusions for surgical patients are due to (1) preoperative anemia, (2) perioperative blood loss, or (3) using liberal transfusion thresholds in the postoperative period.1 However, there are concerns that red blood cell (RBC) transfusions are associated with higher mortality, increased hospital length of stay, and a higher incidence of organ dysfunction.2–5 Patient blood management programs have subsequently tried to reduce RBC transfusions6 and comprise 3 basic tenets:
1. Optimizing preoperative hematopoiesis: A thorough patient history of bleeding disorders and possible coagulopathies (either congenital or acquired, including medication induced) should be obtained from the patient or the family to screen for increased risk of intraoperative bleeding. Preoperative anemia is best managed by first determining the etiology of the anemia and then treating the underlying cause. The Network of Advanced Transfusion Alternatives recommends all patients scheduled for elective orthopedic procedures be screened for anemia 4 weeks before surgery.7 The timeline for this remains a matter of debate. One study showed that initiation of erythropoiesis-stimulating agents and IV iron even 2 days before surgery reduces RBC transfusions.8
2. Minimize intraoperative blood loss: Improving hemostasis can be achieved in several ways. Systemic infusions of antifibrinolytic drugs such as tranexamic acid have been shown to reduce blood loss in both trauma and surgical patients.9,10 Topical hemostatic agents such as fibrin, collagen, and thrombin are commercially available and have been shown to achieve hemostasis at both raw surfaces and anastomotic sites.11 Autologous blood salvage has been shown to be effective in reducing the number of allogeneic transfusions.12 Concerns have been expressed as to the reintroduction of unwanted cells (mainly tumor cells) or material (fat, amniotic fluid, etc.) into the patient as a source of harm. The data suggest that these risks are low in appropriately selected patients.13 Surgical approach can also affect intraoperative blood loss. Studies have demonstrated benefits of laparoscopy and robotic surgery over open surgery. For example, we reported that only 1 in 1000 patients undergoing robotic prostate, kidney, or adrenal surgeries were transfused intraoperatively.14 Similarly, when compared with open distal pancreatectomy, the laparoscopic approach had less blood loss and reduced hospital length of stay.15
3. Optimize tolerance to anemia: Patient blood management requires assessment of anemia and early identification of the causes of reduced oxygen delivery. Transfusions are only performed when absolutely necessary. The AABB (formerly the American Association of Blood Banks) endorses a restrictive transfusion strategy (7–8 g/dL) in stable hospitalized patients.16a The Society of Critical Care Medicine and the Eastern Association for the Surgery of Trauma Practice Management both promote transfusion only when hemoglobin (Hb) is less than 7 g/dL as opposed to a “liberal” transfusion strategy (when Hb is <10 g/dL) in critically ill patients who are hemodynamically stable. The exception to this recommendation is in patients with acute myocardial ischemia at which point transfusion should be considered when Hb levels decrease <8 g/dL.16 The American College of Physicians recommends using a restrictive RBC transfusion strategy (Hb threshold of 7–8 g/dL) in hospitalized patients with coronary heart disease.17
Evaluating the Surgical Patient
One of the most critical factors influencing perioperative blood loss is the patient’s coagulation system. Other factors include type of surgery, underlying tissue injury, and previous operations at the same site.18 A common practice is to perform indiscriminant coagulation testing (most commonly activated partial thromboplastin time and prothrombin time) in patients with no known risk factors or history of excessive bleeding in an attempt to predict bleeding risk.19,20 This practice has been the subject of multiple prospective and retrospective studies and several systematic reviews. The overall conclusion of these studies is that coagulation testing of unselected patients does not have a significant positive predictive value for bleeding risk.21–23 Furthermore, activated partial thromboplastin time and prothrombin time have a high rate of false-positive and false-negative rates that can lead to unnecessary surgical delays and more costly testing.24 In 2008, the British Committee for Standards in Haematology released guidelines on the assessment of bleeding risk before surgery. Their recommendations focused on a detailed history to include excessive bleeding during previous surgery or trauma, family history of bleeding, and a review of antithrombotic medications. They concluded that if the bleeding history is negative, no further coagulation testing is indicated.21
In addition to a careful bleeding history, one should inquire about previous transfusions including adverse reactions and awareness of antibodies to RBC antigens that developed from previous transfusions or pregnancies (Fig. 1). History of adverse reactions or alloantibodies can extend the normal pretransfusion workup performed by the blood bank. For example, the presence of alloantibodies will prompt the blood bank to perform a manual serologic crossmatch (as opposed to an electronic crossmatch). A history of adverse reactions may require manipulation of blood components, such as the washing of RBCs to reduce the risk of recurrent severe allergic transfusion reactions. Unfortunately, however, these required manipulations can potentially lead to delays in obtaining blood components and consequently the surgical start time. In cases where there are multiple alloantibodies, there may even be difficulties in obtaining the appropriate RBCs.25 However, if this information is not obtained, patients are at risk for recurrent adverse transfusion reactions or hemolysis of subsequently transfused RBCs. Awareness of these special circumstances ensures that the patient receives appropriate blood components and reduces the potential for adverse transfusion reactions.
The preoperative transfusion assessment should also consider the posted surgical procedure. Most notably, liver transplants and thoracoabdominal aortic surgical procedures have been reported to have an estimated blood loss of at least 15 units.14 The experience and seniority of the surgeon should also be considered. When performed in a timely fashion, a thorough preoperative transfusion assessment can ensure that appropriate blood components are available and provided to patients in a timely and safe fashion.
There are clinical situations when RBCs are emergently needed for a hemodynamically unstable patient, and there is insufficient time for complete pretransfusion evaluation by the clinical staff or pretransfusion testing by the blood bank. In these urgent settings, uncrossmatched group O emergency release RBCs should be readily available. In nonemergent settings, blood products provided by the blood bank are ABO and Rh compatible. In addition, alloimmunized patients have units serologically crossmatched before transfusion to prevent immune-mediated hemolysis. The safety of group O RBCs (“universal donor”) in emergency transfusions is due to the lack of A and B surface antigens. Although considered safe, uncrossmatched group O emergency release RBCs are still associated with a small risk of hemolytic transfusion reactions due to the presence of recipient alloantibodies to donor non-ABO blood group antigens.26 In a series of 265 episodes of emergency release RBC transfusions at a level 1 trauma center, the risk of non-ABO alloantibody-mediated hemolytic transfusion reactions to emergency release RBCs was described as 0.4% per emergency release episode, with a 2.6% risk of antigen-incompatible transfusion per emergency release episode.27 No acute hemolytic transfusion reactions were observed in a smaller series of 161 patients who received 581 units of uncrossmatched group O emergency release RBC transfusions.28 These data demonstrate that the benefits of transfusing emergency release group O RBCs in hemodynamically unstable patients far outweigh the risks of delaying transfusion for the completion of the blood bank pretransfusion testing.
Maximum Surgical Blood Ordering Schedule
After assessing the patient, it is important to determine whether the patient may need RBCs during the surgical procedure. In the 1960s and 1970s, transfusion practices varied widely both within and across various surgical specialties.29,30 As an example, before starting a surgical procedure if the anesthesiologist or surgeon saw fit, the patient would have a type and crossmatch for a variable number of RBC units. This type and crossmatch would result in RBC units crossmatched with serologic techniques to confirm compatibility between the patient and donor RBCs. These units would then be set aside in the blood bank for the patient’s use for up to 72 hours.31 (Pretransfusion samples must be no more than 3 days old at the time of transfusion because recent transfusions or pregnancy may stimulate the production of unexpected antibodies.) If unused, the RBC units would be released after 3 days and made available for another patient. This process was repeated until the unit was eventually transfused. However, these RBC units would often remain reserved for a patient and would expire before being transfused, increasing wastage and costs of RBCs. The process of crossmatching and holding units for patients was most problematic in surgical specialties, where patients were crossmatched with at least 1 unit of RBCs even though the transfusion expectations were either low or absent. The lack of evidence-based recommendations for the optimal number of RBC units required for a surgical patient led to great variability in the number of units crossmatched and increased wastage of RBC units.
Noting the major differences in the number of crossmatched units requested for similar procedures, Friedman et al.33 in the early 1970s proposed and subsequently implemented a maximum surgical blood ordering schedule (MSBOS) to standardize blood product ordering according to surgical procedure. This schedule suggested limits on presurgical RBC crossmatching based on data from prior surgical procedure-specific blood usage.
To create the MSBOS, Friedman et al.33 compiled surgical transfusion data from the University of Michigan in 1973 and determined the mean number of units crossmatched and transfused over a 3-month period. He then used these data to suggest the appropriate RBC orders to the surgical and anesthesiology staff who reviewed and approved the schedule. Friedman et al. focused on elective procedures and noted that elective cholecystectomies were most commonly crossmatched for 2 units of RBCs, when on average, the number of units required intraoperatively was only 0.5.32 Friedman et al.33 argued that an MSBOS would actually improve patient safety by providing a “gentle barrier” to blood transfusion, thereby decreasing the morbidity and mortality associated with unnecessary blood transfusions.
The first MSBOS had positive outcomes. Between 1972 and 1976, the University of Michigan noted a decrease in blood unit expiration from 6.5% to 4.5%.33 Friedman33 further improved the MSBOS by analyzing data from the Commission on Professional and Hospital Activities sample file (multi-institutional data) from 1974 and suggested surgical blood orders and type and screen recommendations for 63 common elective surgical procedures. This system became widely accepted as a standard of transfusion practices with replicated reductions in the crossmatch to transfusion ratios and has become the basis for blood ordering.34
Despite these initial improvements in transfusion practices, changes in patient management and surgical techniques, including laparoscopic and minimally invasive procedures, have developed rapidly, making the initial MSBOS less applicable to today’s surgical procedures. In many cases, institutions adopted the early Friedman et al. recommendations without collected data from their own practices or failed to update these data over time. In 2013, Frank et al.14 demonstrated the continuing utility of MSBOS. The study by Frank et al. used anesthesia information systems to determine the blood use for 53,526 patients who underwent 1632 different surgical procedures to provide an updated, institution-specific MSBOS. This MSBOS categorized patients as requiring a type and crossmatch, type and screen, or no sample required. After implementing the revised MSBOS, there was a 38% decrease in the number of type and screen samples ordered. During this time, they noted a statistically significant increase in the number of emergency release RBC units issued, from 2.2 patients per 1000 to 3.1 patients per 1000.35 However, within the category of “no sample needed,” the use of emergency release blood components only increased from 0.4 to 1.0 per 1000 patients, suggesting that the increase in emergency release blood components cannot be entirely attributed to patients with no sample. These findings further support that type and screen and no samples are safe alternatives to type and crossmatch when transfusion is unlikely. Of course anemic patients may need preoperative blood orders, despite the MSBOS recommendations.
Type and Screen/Type and Crossmatch Orders
It is important to order a type and screen or type and crossmatch after assessing the patient’s risk of bleeding and the potential need for RBC transfusion.36 The type and screen order, which typically requires 1 hour to perform, involves determining the patient’s ABO group and RhD type and screening the patient’s plasma for clinically significant antibodies. When antibodies are detected, the additional testing required to identify the antibodies and locate appropriate antigen-negative RBC units may take hours (or days, in rare cases) to complete. The type and crossmatch order involves determining the patient’s ABO group and RhD types, screening the patient’s plasma for clinically significant antibodies (i.e., a type and screen), and crossmatching the blood (i.e., ensuring the donor RBCs are compatible with the patient).37 Historically, all RBC units were crossmatched, using a manual serologic test (i.e., incubating donor RBCs with patient plasma and subsequently adding an additional reagent producing visible agglutination when antibodies are present) to confirm compatibility between the donor and the recipient.38 This manual procedure, currently required for alloimmunized patients only, typically requires at least 1 additional hour to perform and thus, requires an increased amount of time and effort in the blood bank.39
One of the most significant risks for surgical patients is failure to send a type and screen or type and crossmatch sample to the blood bank before the day of surgery. A College of American Pathologist Q-Probe in 2003 sought to specifically determine the incidence of avoidable problems with unavailable type and screen samples, identify practices and procedures associated with improved rates of pretransfusion testing, and determine the likelihood of antibody detection problems that affect the availability of RBCs.40 The results showed that 9% of type and screen samples were not completed before the start of surgery and that 2% of all patients had positive antibody screens. Of those 2% with positive screen, 33% required special and prolonged efforts to obtain blood. Ultimately, the Q-Probe made several recommendations to ensure that preoperative testing can be completed before the start of an elective surgery. These recommendations include open communication between blood banks and the anesthesiologists, and strict policies regarding the timing of type and screen sample collection and completion of testing. If a sample has not been sent to the blood bank before initiation of surgery, and alloantibodies are detected, there is a significant risk that compatible RBCs may not be available. In addition, incomplete preoperative transfusion testing has been shown to increase turnaround time of blood delivery from the blood bank to the operating room (OR).41 Thus, anesthesiologists and surgeons need to ensure that patient samples are obtained and tested before start of the case by communicating with patients and placing blood orders before the day of surgery. Timely pretransfusion testing remains problematic, including delaying surgery, and remains an area in need of improvement. Many centers have extended the expiration time to 30 days, for type and screen samples for patients undergoing elective surgeries who have not been transfused or pregnant in the past 3 months, and thus at no risk for developing new RBC antibodies.42
When obtaining the pretransfusion sample, it is also important to ensure proper patient identification and specimen labeling. Misidentification of type and screen or type and crossmatch samples is the primary etiology of ABO-incompatible hemolytic transfusion reactions. Transfusion services have strict requirements for proper labeling of the samples, including the use of 2 unique identifiers (i.e., full first and last name, identification number, and date of birth) and a complete match of the unique identifiers to the request for transfusion. Lumadue et al.43 have shown that specimens that failed to meet these acceptable criteria were 40 times more likely to have a blood grouping discrepancy. Barcode technology may help reduce identification errors during sample collection.44
The Electronic (Computer) Crossmatch
Historically, all potential recipients of blood transfusions were serologically crossmatched. In a study of 16,000 patients (28,000 antibody screens total) at a tertiary care hospital in Australia, only 1.9% of the recipients had a positive screen caused by a clinically significant antibody. A majority of the antibodies detected were directed against RhD and Kell antigens, and the highest rates of alloimmunization were among previously pregnant women or individuals with hematologic or oncologic diseases.45 However, overall, patients with previous exposure to allogeneic RBCs had a low incidence of developing clinically significant antibodies. In 1995, Heddle et al.46 examined 2490 patients who were transfused 11,218 units of RBCs. Blood samples were collected within 7 days of the transfusion and screened for serologic evidence of alloimmunization. The study demonstrated that 96.5% of the transfused patients had a negative antibody screen.46 In a more recent study, Tormey et al.47 retrospectively reviewed the transfusion records of 18,750 military veterans at a Department of Veterans Affairs Medical Center and demonstrated a 2.4% alloimmunization rate.
As the sensitivity of antibody screening methods has improved, the need for serologic crossmatching to detect incompatibility of donor and recipients has become less important. In 1994, Butch et al.48 developed and used the electronic or computer crossmatch at the University of Michigan Medical Center to replace the serologic crossmatch with electronic verification of the patients and donor ABO/RhD types. The electronic crossmatch uses software to determine the compatibility of donor and recipient blood based on current ABO/Rh typing in patients with no current or previously detected antibodies. The software validates 2 concordant ABO/Rh typing results from both the donor and the recipient. Based on the rules set forth by the Food and Drug Administration, the software prevents incompatible RBC units from being issued. This method removes the need to test donor RBCs and recipient plasma, thereby reducing the amount of time required to crossmatch a unit of RBCs to <1 minute, resulting in more rapid availability of compatible blood to assist anesthesiologists and surgeons with bleeding patients.
Despite the reported low rates of alloimmunization of patients, potential concerns with the safety of the electronic crossmatch have been voiced regarding the system’s inability to detect antibodies to low-frequency antigens, which are readily detected by serologic crossmatch.49 However, in the late 1970s, Boral and Henry50 published an important study demonstrating that the type and screen was a safe alternative to the serologic type and crossmatch. These authors determined that screening reagents were able to detect 96.11% of 283 antibodies present in 247 patients. After this demonstration that the type and screen was a safe alternative to type and crossmatch, the question arose about which patients should have a type and screen performed. Saxena et al.51 created a checklist for patients seen in a preoperative clinic. After introduction of this checklist, 99% of surgical patients had at least a type and screen sample ordered and received in the laboratory at least 1 day before the surgery. This experience is in contrast to Ghirardo et al.52 who do not recommend universal type and screen testing for all patients. Overall, the electronic crossmatch is as safe as the serologic crossmatch and works well for the large majority of surgical patients.53,54
From Electronic Crossmatch to the “Virtual Blood Bank”
In addition to the electronic crossmatch, further advances in technology enabling access to compatible RBCs in clinical areas such as ORs and emergency rooms have significantly decreased the time required for compatible RBCs to be delivered to the patient. The concept of a “self service blood bank” was introduced in Hong Kong in 1997 by Wong et al.55 The system began with a computer-generated list of group-compatible RBCs (determined by electronic crossmatch) placed in a refrigerator outside the ORs. This storage system allowed the OR staff to have access to all blood group-identical units in the OR refrigerator (i.e., individual units were not assigned to a specific patient). This concept of “shared inventory” eliminates the need to set units aside for a given patient, reducing the chances of wasted blood due to outdating. Once the RBC unit has been transfused to a patient, the nurse from the OR communicates the unit number to the blood bank staff to be manually entered into the patient’s chart and removed from the subsequently generated lists. A series of advancements ultimately has led to refrigerated and networked systems to dispense blood within close proximity to operating suites. These systems are capable of confirming recipient eligibility for electronic crossmatch from computer records and are able to dispense electronically crossmatched units to OR staff. This capability allows almost complete independence from the physical blood bank after ABO/RhD typing and antibody determination (by type and screen) have been completed. It also obviates the need for nurses, physicians, and technicians to leave the operating area to retrieve RBCs in urgent situations.
In 2008, Staves et al. studied the potential benefits of electronic remote blood issue for cardiac surgery patients.56 Before electronic remote blood issue, the clinical time for staff dedicated to prelabeling RBCs and packaging units for patients (which had to be transported to refrigerators outside the cardiothoracic ORs and returned to the blood bank if not used) was on average 58 minutes per day. After initiation of electronic remote blood issue, the time spent by staff was 17 minutes. This same study assessed time efficiency (for patients who already had crossmatched blood in the blood bank) and found an average time of 24 minutes from an “urgent” call to the blood bank until the blood arrived in the OR. After initiation of electronic remote blood issue, this time was decreased to a median time of 59 seconds.
At our institution, we observed a 27% decrease in the crossmatch to transfusion ratio after implementing an electronic remote blood issue system (Hemosafe, Haemonetics Corp, Braintree, MA).35 We specifically measured the time required to dispatch an electronically crossmatched unit from our electronic remote blood issue system, which was 1 minute and 2 seconds; however, only 42 seconds were required to dispatch a type-O emergency release RBC unit. By decreasing the time it takes to obtain RBCs, the electronic remote blood issue reduces unnecessary laboratory tests and decreases wastage of RBCs. During a 30-day time period that was studied, the number of crossmatch requests decreased from 151 (1.3 per patient) to 91 (0.7 per patient). The total number of matched units decreased from 407 to 197 (52% reduction), equating to a decrease in the mean number of RBC units crossmatched per patient from 3.5 to 1.6. The reduction was attributed to the change in practice of the cardiothoracic service where it was no longer standard practice to reserve RBC units before surgery. The system also demonstrated reduction in blood wastage. Part of this waste can be attributed to the shorter time required to move blood to the bedside. According to the AABB Technical Manual, blood products must be continually maintained within a specified temperature range due to the concerns for bacterial overgrowth or metabolic changes.57 In 1997, Cox et al.58 showed that by instituting an electronic remote blood issue system in their hospital, they were able to improve blood bank inventory management and subsequently reduce the number of outdated RBC units by 30%.
There have been exciting changes in the world of transfusion medicine over the past 20 years. Just as refinements in anesthesia and surgical techniques have led to improved outcomes, so too have advancements in transfusion medicine. Two innovations, in particular, have drastically changed the way RBCs are ordered, inventoried, and the speed in which they are delivered. Since its inception in 1976, the MSBOS has served as a guideline for surgical services regarding preoperative blood testing and ordering. A much-needed update published in 2013 accounts for modern surgical techniques derived from institution-specific anesthesia information system data that further supports the safety of a type and screen or no sample for procedures that are unlikely to require blood.14 The electronic or computer crossmatch can replace the serologic crossmatch with electronic verification of the patients ABO/RhD type.39 In conjunction with networked remote storage and delivery systems, the electronic crossmatch can reduce the time it takes for compatible blood to arrive to the OR from 30 minutes to <60 seconds. In addition, initiation of a remote electronic blood release system can lead to a 25% reduction in the number of units requested, a 30% reduction in the number of outdated RBC units, and a reduction in laboratory workload.56 These innovations have led to more timely, efficient, and safer use of this life-saving therapy.
These technologic advancements can enhance transfusion support in surgical cases but remain dependent on the performance of a presurgical transfusion assessment, the availability of a correctly labeled blood specimen before the morning of elective surgery, and continuing communication of departments of surgery, anesthesia, and transfusion medicine to provide safe transfusion support.
Name: Marissa J. White, MD.
Contribution: This author helped design the review and prepare the manuscript.
Attestation: Marissa J. White approved the final manuscript.
Name: Sprague W. Hazard III, MD.
Contribution: This author helped design the review and prepare the manuscript.
Attestation: Sprague W. Hazard III approved the final manuscript.
Name: Steven M. Frank, MD.
Contribution: This author helped design the review and prepare the manuscript.
Attestation: Steven M. Frank approved the final manuscript.
Name: Joan S. Boyd, MT(ASCP)SBB.
Contribution: This author helped prepare the manuscript.
Attestation: Joan S. Boyd approved the final manuscript.
Name: Elizabeth C. Wick, MD.
Contribution: This author helped prepare the manuscript.
Attestation: Elizabeth C. Wick approved the final manuscript.
Name: Paul M. Ness, MD.
Contribution: This author helped design the review and prepare the manuscript.
Attestation: Paul M. Ness approved the final manuscript.
Name: Aaron A. R. Tobian, MD, PhD.
Contribution: This author helped design the review and prepare the manuscript.
Attestation: Aaron A. R. Tobian approved the final manuscript.
This manuscript was handled by: Steven L. Shafer, MD.
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