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The growing use of group AB plasma in the United States in recent years poses unique challenges to blood centers and transfusion services. Blood centers must collect sufficient plasma components from a limited pool of group AB donors while taking steps to improve transfusion safety that further restricts the available supply. Transfusion services, on the other hand, must use the finite resource in the most conscientious and medically appropriate manner. Recently, many investigations have challenged long-held beliefs about transfusion practice and appropriate indications for blood components across a variety of specialties. Balancing supply and demand of group AB plasma requires collaboration between blood suppliers and transfusion services, and opportunities for improvement exist on both sides of the equation.
plasma frozen within 24 hours after phlebotomy held at room temperature up to 24 hours after phlebotomy
The increased demand for group AB plasma in the United States in recent years poses unique challenges to blood centers and transfusion services. Blood centers must collect sufficient plasma components from a limited pool of group AB donors while taking steps to improve transfusion safety that further restricts the available supply. Transfusion services, on the other hand, must use the finite resource in the most conscientious and medically appropriate manner. Recently, many investigations have challenged long-held beliefs about transfusion practice and appropriate indications for blood components across a variety of specialties. In addition, the United States does not currently have licensed four-factor prothrombin complex concentrates, which may be contributing to the strain on the AB plasma inventory. Balancing supply and demand of group AB plasma requires collaboration between blood suppliers and transfusion services, and opportunities for improvement exist on both sides of the equation.
Approximately 4.8 million plasma transfusions and 14.8 million allogeneic red blood cell (RBC) transfusions were administered in the United States in 2008, according to the National Blood Collection and Utilization Survey. The growth in plasma use has outpaced that observed for RBCs: the absolute number of plasma units transfused in the United States increased by 474,000 units (11.8%) in 2008 compared to 2006, whereas transfusion of RBCs only increased by 5.8% during the same period. A survey of 10 large US blood centers in March 2012 confirmed the increasing plasma demand reported in the National Blood Collection and Utilization Survey, but revealed a turning point in 2008. At the blood centers in this survey, the total number of plasma units distributed for transfusion decreased by approximately 4% each year, but the total number of distributed group AB plasma units increased by approximately 6% each year between 2008 and 2010, leveling off in 2011 (Fig. 1). Overall, this survey revealed a 27% increase in group AB plasma or 52,278 more units distributed by the 10 US blood centers in 2011 compared to 2006. Furthermore, the disproportionate use of group AB plasma relative to the other blood groups has continued on its upward trend in recent years. The proportion of group AB plasma distributed in 2011 for transfusion by the 10 blood centers surveyed ranged from 7% to as much as 25% of total plasma components (Fig. 1B); in contrast, only approximately 3% of the donor population is group AB. The factors contributing to the observed increase in group AB plasma usage are not immediately apparent, but the trend that started in 2006 may have been spurred by the publication of the manuscript by Borgman et al. in 2007 on plasma ratios in massive transfusion protocols.
Blood Center Perspective
Universally, blood centers must overrecruit group AB donors from a limited donor pool to ensure an adequate supply of plasma and platelet (PLT) components to meet patients' needs and hospitals' increasing demand. Blood centers now face additional pressure on the supply of group AB plasma because of their efforts to reduce the risk of transfusion-related acute lung injury (TRALI), which remains the leading cause of transfusion-related deaths reported to the Food and Drug Administration (FDA). Plasma more than any other blood component has been implicated in TRALI cases, and many, but not all, of the cases are likely caused by white blood cell antibodies, which are more prevalent in women than men. Limiting patient exposure to plasma from female donors effectively reduced the risk of TRALI and was a feasible first step toward TRALI mitigation for many blood centers.
The American Red Cross demonstrated that a male donor–predominant plasma strategy effectively reduced the overall risk of TRALI from plasma transfusion by approximately 80% overall, but was not uniformly successful for all blood types (Fig. 2). For groups A, B, and O, considerably more plasma is collected through whole blood donation than is needed for transfusion; consequently, plasma for transfusion could be obtained almost exclusively (>99%) from male donors and the units collected from women were diverted for further manufacture into plasma derivatives. In contrast, no such surfeit exists for group AB plasma, and the proportion of group AB plasma from male donors remained relatively constant at 60% over the study period despite selective recruitment efforts. While a significant reduction in TRALI was observed for group A, B, and O plasma, there was no change in the risk from group AB plasma (Fig. 2). Less than 4% of all plasma units distributed in 2008 to 2011 by the American Red Cross were from group AB female donors; however, half of the TRALI cases in this series involved plasma from group AB female donors with HLA or HNA antibodies.
Several US blood centers have successfully compensated for the effect of TRALI mitigation strategies on their available supply of group AB plasma and have increased collection or production of group AB plasma while eliminating the distribution of plasma from donors who have or are at risk of having HLA antibodies. If screened group AB plasma is not available, one blood center in the informal 2012 survey reported a process to quarantine such plasma units for release only in a medical emergency, after discussion with the medical service. Reducing the number of group AB plasma units transfused to non–group AB patients would reduce the recipient's exposure to these unscreened units (see below).
A recent regulatory change now enables blood centers to increase the collection and distribution of group AB plasma from apheresis procedures. In 2012, the US FDA recognized two new licensed plasma components and approved language describing the changes for the Circular of Information (available at http://www.aabb.org/resources/bct/Pages/aabb_coi.aspx). The change to an existing product plasma frozen within 24 hours after phlebotomy (PF24) allows preparation of licensed PF24 from apheresis collections as well as whole blood collections. A newly licensed plasma component is descriptively called plasma frozen within 24 hours after phlebotomy held at room temperature up to 24 hours after phlebotomy (PF24RT24). The indications stated in the Circular of Information for PF24 and PF24RT24 are the same as for fresh-frozen plasma, based on evidence of comparable levels of clotting factors. This change alleviates logistic constraints in the manufacturing process and will greatly facilitate collection of concurrent plasma during other apheresis procedures. Some blood centers also collect and distribute apheresis PLTs with PLT additive solutions, which provides another opportunity to recover additional group AB plasma units.
Finally, Octaplas, a pooled, sterile plasma (human) blood product for the replacement of clotting proteins, was recently approved by the FDA and will soon become available as an alternative pharmaceutical source of group AB plasma, albeit likely at additional expense.
Transfusion Service Perspective
AB plasma hospital use
There are a number of uses of the hospital's AB plasma inventory. Other than transfusing it to group AB recipients for whom no other plasma is compatible, the service that transfuses the largest number of AB plasma units to non-AB recipients is the trauma or emergency service. Plasma is currently an important component in treating certain patients—either in the reversal of warfarin in a patient who is bleeding or requires urgent surgery or in the initial resuscitation of a severely bleeding trauma patient, perhaps as part of a massive transfusion protocol. As plasma is often required on an urgent basis before patient identification can occur, much less the completion of pretransfusion testing, group AB plasma is often used in these situations. As stated earlier, four-factor prothrombin complex concentrates are not yet approved for use in the United States, but have been used “off-label” in Europe to support trauma patients; however, its effectiveness in this clinical setting is uncertain.
There are two interrelated processes whereby trauma patients can pose a challenge to the AB plasma inventory. As stated, the current standard of care is to provide AB plasma to recipients who do not have a valid type and screen at the time the plasma is required. Many trauma patients are in this situation, and the longer it takes a properly labeled sample to be sent to the blood bank and tested, the longer only AB plasma can be issued. At the same time, although based mainly on retrospective or observational literature, there is a trend toward earlier and increased quantities of plasma transfusion to severely injured trauma patients as part of fixed ratio transfusion resuscitation protocols, especially before point-of-care hemostasis tests can be obtained. The suggestion that the early administration of plasma in trauma resuscitation is beneficial has likely resulted in having prethawed plasma increasingly available at most institutions that care for these patients. Studies such as PROPPR, expected to be completed in mid to late 2013, may provide additional insight into appropriate plasma usage.
Similarly, patients who are taken to the operating room for elective, nonurgent surgery and require plasma before a type and screen can be completed will receive group AB plasma. With an increased plasma demand for patients on whom even the short time required to perform pretransfusion testing before ABO identical plasma can be issued is life-threatening, it is not surprising that many transfusion services find it difficult to meet the demands for AB plasma. Other demands on the AB plasma inventory include the preferential use of group AB plasma over other ABO types in a thawed plasma inventory, use of simplified transfusion service protocols whereby universal donor products are preferred to group-specific products to reduce complexity for generalist or cross-trained staff, and possibly an increased number of ABO-incompatible stem cell transplants, which would require the provision of group AB plasma products.
While some of the situations in which emergency-issued group AB plasma is used in the operating room cannot be avoided due to the unexpected complexity or urgency of the case, the use of group AB plasma in this manner could likely have been avoided if the clinical team had adhered to the recommendations for pretransfusion testing in the institution's type-and-screen protocol and/or maximum surgical blood ordering schedule (MSBOS). Observational data from two of the authors (KJL and MHY) of hospitals served by their blood centers suggests that, unfortunately, the usage of formalized type-and-screen protocols and MSBOS to reduce unnecessary blood component orders may not be as prevalent as perceived in some regions of the United States. The emerging trend of extending preadmission samples for elective surgeries beyond the traditional three days to up to or beyond 30 days, assuming that the patient has not been transfused or pregnant in the prior 3 months, can streamline the surgical preadmission process, reduce same day blood typing stat tests, and reduce avoidable delays in providing compatible blood components.
Another potential strain on the AB plasma inventory is the check type sample (CTS). A CTS is a specimen collected on a patient who does not have a historical ABO group on file at the hospital where they are to be transfused and it is used to confirm the findings of the initial ABO group and is mainly used for RBCs. The CTS is an important method of detecting wrong-blood-in-tube errors and preventing mistransfusions but is not currently a requirement for pretransfusion testing by the AABB; however, it is one of the possible steps to be taken to meet College of American Pathologists expectations regarding reducing the risk of mistransfusion and is “recommended” by the FDA in their guidance on use of the electronic cross-match. CTS implementation is a significant sample collection process change and requires a widespread and ongoing educational effort to ensure compliance. In most instances of the CTS, only un–cross-matched or emergency-issued products can be released until the ABO group performed on the CTS specimen confirms that from the first collection. Thus, if there is a delay in collecting and testing the CTS specimen then a hemorrhaging patient can put the AB plasma inventory in jeopardy. If the CTS is drawn promptly and delivered to the blood bank immediately, it can be expedited in 10 minutes or less, before the antibody screen has completed its incubation. Although CTS is the best practice, another acceptable option that can be used in the blood bank during emergency protocols is to require a second ABO and Rh typing performed by a second technologist on (ideally) a new suspension from the original specimen. Note that unlike the CTS in which the ABO and Rh typings are performed on completely different samples, the above option would not detect a wrong-blood-in-tube error. Another option is to issue group-specific plasma based only on the patient's forward type and not require a CTS sample.
Special considerations for infants under 4 months allow the release of ABO-identical blood products after initial pretransfusion testing given their immature immunologic status and use of a maternal sample to screen for unexpected RBC antibodies. Many large pediatric centers routinely issue type-specific or -compatible RBC plasma to infants under 4 months of age, after appropriate pretransfusion testing for the presence of passively transferred maternal anti-A or anti-B or unexpected RBC antibodies. Some hospitals, however, still issue only group AB plasma to infants under 4 months for the sake of simplicity or to allow 1 unit to be used for multiple neonates, but such practice is an unwarranted and unnecessary use of group AB plasma. Some hospitals, to reduce unnecessary AB usage in infants, have implemented handheld bedside labeling devices so that a single sample that has been tested twice can be used for infants while still attempting to address wrong-blood-in-tube concerns. As in other clinical settings, studies have shown that the implementation of and compliance with transfusion guidelines can reduce the number of transfusions, including plasma transfusions, without adversely affecting clinical outcomes.[12-14]
A call to action: What can be done to ensure an adequate supply of AB plasma in the future?
On the donor center side, efforts should continue to maximize group AB donor recruitment and retention. New opportunities for increasing concurrent collections of plasma from apheresis procedures are now possible after the revision to the Circular of Information and the newly licensed plasma components, PF24 and PF24RT24 from apheresis procedures. Collaboration among blood centers may identify additional donor recruiting and manufacturing strategies to further augment the community supply of group AB plasma. Even with these efforts, however, the supply of plasma may still be insufficient if the demand for group AB plasma continues to grow.
Regularly scheduled meetings between blood center and hospital to evaluate supply, delivery, and usage patterns of blood components, and especially AB plasma, as a process improvement process to understand the impact of changes in donor and patient populations, collection and ordering practices should occur. Active participation by both the blood center and the hospital will provide ample educational content and action items for each institution's process improvement efforts (Fig. 3).
On the hospital side, the first step in reducing AB plasma utilization is to ensure that all plasma units, regardless of ABO group, are being transfused in an evidence-based manner.[15-18] This entails both establishing institutional guidelines for plasma transfusion and ensuring that the guidelines are being followed. The latter task is achieved by retrospective or concurrent audits of plasma transfusion and by using automated decision support tools or even simple automated audit reports in the computerized physician order entry system to help alert clinicians when plasma is being ordered on patients whose laboratory values do not suggest that the transfusion is indicated. When nonconformances are noted through the audits or an excessive number of alerts are generated by a particular physician or service, focused educational campaigns can be conducted to educate the prescribers and align their practice with the current evidence. Tracking the final disposition of the thawed AB plasma inventory, including wastage, with feedback to the trauma teams might inform everyone on the inventory impact of prethawed plasma and potentially lead to refinements in the number and perhaps ABO type of thawed plasma units provided. Prudent usage of FDA-approved rapid thawing devices (i.e., microwaves) and early communication of incoming trauma with a high probability of activating a massive transfusion protocol could reduce the need for maintaining large (four plus) inventories of prethawed plasma. Establishing a policy and accompanying performance metric to target no more than 2 units of AB plasma going to a patient before switching to group specific component therapy would help reinforce solid communication, early lab draws, and active team cooperation.
Another simple action is to review or revise transfusion operating procedures, job aids, and current practice to reduce any barriers that prevent the rapid switch from emergency-issued AB plasma to type-specific plasma, in particular, in trauma situations. This may be difficult in some institutions that maintain thawed AB plasma, presumably as part of their readiness to serve Level II or III trauma centers, which will eventually use most of that plasma on non–group AB patients in nonurgent situations to reduce wastage. Some institutions, however, are beginning to question the need to keep only prethawed AB plasma on hand due to ongoing concerns about reserving AB plasma for those who need it and are exploring using low-titer group A plasma.[21, 22] Additionally, others have suggested that, due to the formation of A and B immune complexes, the utilization of non–type-specific plasma might not be ideal especially for group O patients who receive AB plasma.[23, 24] Further studies are needed to understand how much AB plasma intended for trauma patients is either discarded or used in nonurgent cases. Moreover, specific randomized trials should address the cost versus benefit of a prethawed plasma inventory compared to other methods of providing early “on-demand” plasma.
From the discussion herein, it would seem that the way to reduce the amount of emergency-issued AB plasma to patients who are later determined to be non-AB is through education and a systemwide view of the entire patient population, instead of focusing on the needs of one patient type at the potential expense of other types. In particular, the need to impress the importance of obtaining a sample for pretransfusion testing (and a CTS where indicated) upon the clinical team early in the management of the patient cannot be understated. Ideally this message should be made to nurses, physicians, and housestaff before an emergency situation arises through clearly written nursing protocols, rounds-style sessions, and intrahospital electronic or printed communications. However, in the midst of a resuscitation, the transfusion service can be helpful in this regard by reminding the clinicians about the need to supply at least one sample for pretransfusion testing when the clinical team calls the blood bank to order products or when a member of the team picks up the emergency-issued products. If the blood bank's policy is to notify their medical director when un–cross-matched or emergently-issued blood products are issued, then they too can champion the need for sending appropriate samples quickly when they speak with the clinical team to assess the situation and help plan the blood bank's strategy for the patient. Type-specific plasma should be issued as soon as possible to preserve the AB inventory. The routine use of AB plasma in neonates less than 4 months of age is not necessary.
Establishing protocols to manage complex processes is associated with improved patient outcomes,[25, 26] because they help to reduce the communication chaos that can occur between departments and the shortening of turnaround times for product delivery when patient treatment regimens are standardized and based on the best medical evidence, especially for those who present with coagulopathy. An example of a published massive transfusion protocol is provided by Nunez and colleagues.
In addition, as alluded to, having an up-to-date and easily accessible MSBOS can reduce the incidence of having to transfuse emergency-issued group AB plasma to a patient in the operating room. The need and availability of an in-date type and screen should be included in all presurgery “time-out” checklists so if pretransfusion testing is not complete, a sample can be sent before the start of surgery for elective cases. By the time the patient bleeds, the sample will be completed. At one of the author's institutions (MHY), a new initiative is being phased in whereby at the time that a surgeon's office schedules an elective procedure using computerized operating room scheduling software, the MSBOS' recommendation on the extent of pretransfusion testing that is required for that procedure automatically populates an order field on the screen. It is hoped that this automatic recognition and ordering of the appropriate pretransfusion testing will ensure that a valid type and screen has been obtained on patients scheduled for surgery where blood loss is anticipated and reduce the number of times that group AB plasma is emergently issued to elective surgery patients who are already in the operating room.
In summary, AB plasma is a scarce community resource, and both the collection center and the hospital are its stewards. Centers must overrecruit AB donors relative to their presence in the population and adopt manufacturing processes to maximize collection. Similarly, hospitals should reduce unnecessary blood transfusions and eliminate overreliance on group AB plasma in certain clinical situations. Current evidence-based guidelines, audits, education, and a recurrent, systematic review of the literature and individual hospital policies and practices focusing on their impact on the entire patient population are all necessary parts of a hospital's strategy to use the right product at the right dose at the right time for the right patient and for the right reasons. Ideally as partners, collection centers and hospitals will work together such that supply and demand of group AB plasma will again converge.
The authors acknowledge the individuals from 10 US blood centers who participated in the AB plasma survey: James AuBuchon, Puget Sound Blood Center; Richard Benjamin, American Red Cross; Jerry Gottschall, Blood Center of Wisconsin; Louis Katz, Mississippi Valley Regional Blood Center; Tuan Le, Bonfils Blood Center; Susan Rossmann, Gulf Coast Regional Blood Center; Merlyn Sayers, Carter BloodCare; Beth Shaz, New York Blood Center; Peter Tomasulo, Blood Systems, Inc.; and Darrell Triulzi, The Institute for Transfusion Medicine.
Conflict of Interest
The authors declare that they have no conflicts of interest relevant to the manuscript submitted to TRANSFUSION.