Platelet transfusions: safety, cost, and workflow

Anne Paxton

October 2022—The jury may no longer be out on whether pathogen reduction of platelet units reduces the risk of a septic transfusion reaction enough to replace culturing of platelet units. Nor is there doubt that pathogen-reduced platelets have a shorter hold time before they can be released for transfusion and the potential for a longer shelf life. These merits have helped convince the American Red Cross to switch, over the next year or two, to supplying only pathogen-reduced platelets to its client institutions that need platelets.

“There’s nothing that’s all good or all bad, though,” says Ralph Vassallo, MD, chief medical and scientific officer of blood supplier Vitalant, Scottsdale, Ariz. “We use pathogen inactivation technology and most blood centers have an option to provide pathogen-reduced platelets.” However, the expense of such platelets—commonly an additional $150 for each unit—can’t be ignored.

“The great thing about platelet pathogen reduction is that bacteria present at collection are not going to grow in that unit. As many as one in 2,000 units have bacteria in them, but only one in 10,000 grow to levels high enough to hurt someone. But one in 10,000 when there are 2.2 million transfusions a year is a lot. So pathogen reduction significantly enhances bacterial safety,” Dr. Vassallo says.

The FDA approved the use of Cerus’ Intercept pathogen-reduced platelets (PRP) in the United States in 2014.

Nonbacterial pathogens are also proactively inactivated by pathogen reduction, which Cerus estimates has proven efficacy against more than 40 clinically relevant pathogens. That means unknown, emerging viruses may be caught in many cases. “We didn’t recognize West Nile or dengue and chikungunya viruses and other potential pathogens that have emerged,” Dr. Vassallo says. “So if something’s in your blood supply and you’re not aware of it yet, pathogen reduction may take care of that.”

Since pathogen inactivation also acts like radiation, “you don’t have to irradiate to prevent transfusion-associated graft-versus-host disease.” Pathogen inactivation also eliminates the need for a cytomegalovirus test as well as some tests for other infectious diseases, although, he adds, “the FDA hasn’t yet gotten to the point where we can cease doing many of them.”

“But the cons are significant,” Dr. Vassallo says. “Pathogen reduction is twice the additional cost of units that we culture more aggressively for bacteria,” so to replace culturing with pathogen inactivation would cost an additional $165 million a year across the United States. “However, we’re talking about 220 people who were harmed each year from bacterial transmissions before enhancement of culturing techniques.”

In addition, pathogen reduction is an exacting process, Dr. Vassallo says. “You can’t have too many platelets. You can’t have too much suspension medium, which is generally plasma or an additive solution, because if you do that, the UV light doesn’t penetrate well enough. So what you end up doing is setting your collection device in a way that you collect fewer platelets. Worse, you may collect in too little volume and have to throw the entire collection away.”

The American Red Cross has opted to focus on Intercept pathogen reduction for a number of reasons, says Pampee Young, MD, PhD, chief medical officer, biomedical services, American Red Cross. “While it gives the second longest shelf life, it is the earliest available product so that hospitals have the freshest platelet possible. The other products can only be tested at 36 hours or 48 hours, and the hospital can’t get them until 12 hours after that at the earliest, whereas a Cerus product is available 24 hours after collection.”

By safeguarding against so many pathogens, pathogen inactivation technology gives PRPs a great safety profile, Dr. Young says. “But the main reason we like pathogen reduction exclusively is that it increases availability of products for hospitals. What happens when a blood center produces 30 percent non-PR and 70 percent PR, or some other mix? When you’re trying to deal with a mixed inventory, it invariably results in inefficiency and discard and ultimately fewer units available to patients. Our data showed the greatest efficiency can be achieved by having a single technology that provides a safe product with a good shelf life.”

Clinical studies have shown that patients’ platelet counts rise less with PRP, on the whole, than with non-PRP, she says. But clinically, this difference is not significant. “There’s no increase in platelet use or increased risk of bleeding,” as a result of using PRPs. So in terms of efficacy, “We feel comfortable that this is a noninferior product, and that’s the basis on which the FDA approved this product in this country.”

The expense of the PRP technology does not discourage smaller hospitals from wanting to take advantage of it, says Claudia Cohn, MD, PhD, chief medical officer of the Association for the Advancement of Blood and Biotherapies (AABB) and director of the blood bank laboratory, associate director of clinical laboratories, and professor of laboratory medicine and pathology, University of Minnesota.

“The smaller the hospital, the more they want to be taken care of,” she says. Non-specialists don’t want to deal with the complications and nuances that are part of transfusion medicine, Dr. Cohn says. “The American Red Cross will hand you this pathogen-reduced platelet that is super-safe and super-easy to use and it takes care of your needs.”

“It’s the largest centers”—the biggest users of platelets—“that have the greatest concerns about the choices that blood centers have made to satisfy the FDA requirements, and about how heavy-handed some blood centers can be in terms of providing only one kind of platelet,” she says.

Dr. Cohn’s own contracts specify that her laboratory is not allowed to go to another blood center to seek blood if there’s a shortage. “It is up to my blood center to seek that blood for me. That’s fine with me and it works.” But other hospitals have contracts that are more open, and they may not be able to rely on predesignated blood units. She says she has heard horror stories that reveal what can happen to midsize hospitals without a primary contract with a blood center. “If there’s a shortage, they can call the blood center and say we need 10 units and the blood center will say, ‘Sorry, we don’t have it for you’—because the blood center is holding it for its larger clients.”

That can aggravate the tendency of hospitals, in a time of shortage, to hoard. “A lot of hospitals take in more than they need so they have enough for their patients in case the blood center says no to them. Of course, the more they hoard, the more waste there is. And that’s unfortunate, but that is the environment in which we function.”

AABB Bulletin No. 21-02 (June 2, 2021) says “blood center decision drivers should include the preferences of their hospital partners although the logistics and cost of providing multiple mitigation strategies may also be a factor.”

The smaller hospital will prefer a platelet product that doesn’t require subsequent testing, agrees Alyssa Ziman, MD, medical director for Ronald Reagan UCLA Medical Center clinical laboratories and medical director of transfusion medicine and professor of pathology and laboratory medicine at UCLA. “Non-pathogen–reduced units may require a secondary culture or a point-of-issue test. The responsibility of additional testing falls on the blood bank, and [in the smaller hospitals] they lack the expertise or staff to manage the inventory like that.”

At UCLA, 95 percent of platelets are pathogen-reduced, she says. “To me, pathogen reduction provides the safest product as it further minimizes the risk of transfusion-transmitted infections when coupled with standard donor infectious disease testing. In addition, our hospital-based donor center can release the platelet units to our blood banks at day two or as soon as standard donor test results are available.” This is important for patient care, she says, especially during times of shortage.

That process contrasts with platelet culture at the time of collection or shortly after, which is another of the bacterial risk control strategies the FDA approved in its 2019 Guidance for Industry, along with testing before transfusion. The FDA guidance required blood centers and transfusion services to implement one of the three strategies by October 2021.