CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Anne Paxton
October 2014—When it comes to the blood supply, the tradeoffs between safety and availability are a tightrope that blood centers walk with extreme care.
For several years now, TRALI (transfusion-related acute lung injury) has topped the list of causes of transfusion-related mortality in the U.S. Defined as acute lung injury that occurs during or within six hours of transfusion of a blood product, TRALI is fatal to six to 10 percent of the patients it strikes.
As with all quality and safety initiatives in blood banking, risk reduction on behalf of patient safety can bring new risks in the area of availability. The trick is how to screen out the sources of TRALI without creating shortages of blood products for transfusion.
In 2006, the AABB recommended that its members adopt measures to address TRALI in plasma by November 2007, and TRALI in platelets by November 2008. The specific steps to take were left up to the blood centers, but large numbers opted for predominantly male plasma (meaning males plus never-pregnant females), though AB plasma was often excepted from this policy. Soon, TRALI cases showed a significant decline. But since 2009, reports by the Food and Drug Administration show, the number of TRALI deaths from all blood products has stopped dropping and leveled off.
This year, spurred by its TRALI task force, the AABB turned up the pressure in its campaign against TRALI. The AABB’s new standard 5.4.1.2 includes screening of women plasma donors who have had one or more pregnancies for the presence of human leukocyte antigen (HLA) antibodies, or anti-HLA, the major known TRALI risk factor. People develop anti-HLA antibodies because they’re exposed to foreign antigens, and exposure is usually due to pregnancy, transplant, or transfusion. Less common are human neutrophil antigen (HNA) antibodies, or anti-HNA. They are also a risk factor and are more commonly associated with fatal TRALI.
As of this April, the AABB started requiring that blood centers it accredits manufacture transfusable plasma from whole blood donations only if the donations are from males, never-pregnant females, or screened by an HLA antibody test and found negative. Blood centers are not required to be accredited by the AABB, but the large majority are.
Most blood centers had already been producing male-predominant plasma, with one significant exception: Donations from women with type AB blood sometimes continued to be used for transfusable plasma because it was thought there would be severe shortages of crucial AB plasma if half of the potential donor population could not be used for this purpose.
Under standard 5.4.1.2, the exception for AB plasma will be ended. So the new standard is likely to have significant effects on blood centers, hospitals, and possibly the nation’s plasma supply.
Although TRALI was first described in 1985, most people did not really know what TRALI was until early 2000, says Manish J. Gandhi, MD, associate professor of laboratory medicine and pathology and consultant in the Mayo Clinic’s Division of Transfusion Medicine.
“Unfortunately, a lot of patients needing blood transfusion may have an acute lung injury. And it was not being picked up that this could be associated with transfusion. The 2004 consensus conference, where experts agreed on a definition of TRALI, made it easier for people to recognize these sorts of transfusion reaction,” Dr. Gandhi says.
A four-year prospective study, which began in 2005 and was led by Pearl Toy, MD, provided further information about anti-HLA’s role in TRALI. Funded by the National Heart, Lung, and Blood Institute, the study was conducted at two surveillance sites, the Mayo Clinic and the University of California, San Francisco (Toy P, et al. Blood. 2012;119[7]:1757–1767).
Dr. Gandhi was a coauthor of the study. “The whole idea of it was to have clinicians who would prospectively monitor patients who received transfusion within a window of six hours. If there were any symptoms, then all the vital signs and other patient data would be looked at by a panel of three physicians who were completely blinded to what they were looking at, and they would make the diagnosis of whether it was TRALI or not on the clinical side,” Dr. Gandhi says.
The study tested for several factors implicated in TRALI. “We would test for everything that was available,” including anti-HLA, anti-HNA, and some bioactive substances, Dr. Gandhi says. The study established that reducing exposure to plasma from female donors was concurrent with a decrease in TRALI incidence, which dropped, after risk reduction, from one in 4,000 blood component exposures to about one in 12,000 blood component exposures.
Dr. Kopko
In 2007—in fact, in the middle of the UCSF/Mayo study—the weight of evidence from available research and from a successful male plasma mandate in the U.K. led the AABB to issue a recommendation that all plasma come from males and never-pregnant females. “For the most part, blood centers had done that, but some had not done it for AB plasma,” says Patricia Kopko, MD, professor of pathology and director of transfusion medicine at the University of California, San Diego, and a member of the AABB’s TRALI task force.
Since AB type plasma is universal plasma, there is high demand for it. But while hospitals need about 11 percent AB plasma, only about four percent of blood donors are AB. So switching to all male plasma would essentially double blood centers’ problems on the supply side, Dr. Kopko explains.
After looking at the data, however, the TRALI task force saw a distinct pattern. “Most TRALI cases from plasma were from AB plasma,” Dr. Kopko says. So the task force decided it was time for a standard; it would argue for a requirement that all plasma, regardless of blood group, come from male donors.
According to studies, about 20 percent of multiparous women have anti-HLA antibodies—the more pregnancies they had had, the higher the HLA antibodies, Dr. Gandhi says. This finding had the most implications for plasma. “When we talk about blood products, we tend to refer to the ‘red product’ and the ‘yellow product,’ because when we split whole blood into its components, the red cells would have very little plasma, and fresh frozen plasma and platelets would have a lot of plasma. So the yellow products would have much higher antibody levels, even though studies show red cells may also cause TRALI.”
In the AABB’s guideline, male-predominant plasma was recommended. “Most of the centers did go down that path, and some donor centers stopped taking female donors as plasma apheresis, with the exception of AB plasma because it was difficult to meet the needs,” Dr. Gandhi adds.
Meanwhile, improvement started becoming apparent; statistics on incidence of TRALI show that the screening measures were having an impact after 2006. “We could actually show the number of TRALI cases decreased substantially when the policy was put in place,” says Steven Kleinman, MD, senior medical advisor for the AABB and chair of the TRALI task force.
When the American Red Cross looked at its numbers for plasma, the risk was significantly decreased with implementation of predominantly male plasma. The ARC is still implementing the policy in AB plasma and a lot of the TRALI they had was AB females, Dr. Kopko says. “That data was part of what led the AABB TRALI task force to say there was enough evidence to go forward with the new standard.”
Coincidentally, and unfortunately, these new restrictions on plasma for transfusion have been happening at the same time that use of group AB plasma has increased dramatically because of “massive transfusion” protocols, practiced by the military and extended to the civilian population.