Platelet transfusions: safety, cost, and workflow

With culturing, there are concerns about false-positives as well as false-negatives. “There may not be sufficient bacterial load when 8 mLs of the platelet unit are used to inoculate the culture bottle,” Dr. Ziman says. “So a residual risk with the culture strategies remains when bacterial loads do not reach a critical mass in the unit until day four or day five. When considering a strategy that uses the point-of-issue test, there are concerns with false-positives and the resulting impact on the platelet supply, as well as the fact that this testing requires technologist time.”

A recent paper reported that about 80 percent of positives found by culture are false-positives and about 20 percent are true positives (Corean J, et al. Transfus Med Rev. 2021;35[3]:44–52).

Amid staffing shortages, additional testing becomes problematic, Dr. Ziman notes. “Blood bank staff would not only have to perform blood typing and antibody screen tests, but they’d also have to do this other test to get the platelet unit to the patient.” When her laboratory at UCLA considered this testing several years ago, “We talked about performing point-of-issue testing in batches once a day rather than at point of issue in order to not delay patient care. This would result in testing our entire inventory on day four and day five.”

“While this ties up staff to test the entire inventory, it ensures there are no delays when platelets are needed emergently or for patients who are getting an outpatient platelet transfusion.” These are all reasons why she believes pathogen reduction provides the safest product for patients and the most efficient product from a workflow and staffing standpoint. Even accounting for the savings in staff time needed for other methods, “pathogen-reduced platelets are still a more expensive product. But I believe it’s the best product available for our hospitals and our patients.”

Contamination of a platelet product during collection is rare. But “another source we’re increasingly recognizing” is “there are opportunistic environmental bacteria that may sneak in through tears in the bag,” Dr. Vassallo says (Gammon RR, et al. Transfusion. 2021;62[3]:641–650).

Within the past year, “the FDA issued a warning about a few cases of pathogen-reduced platelets that were actually growing bacteria” because of such tears, says Glenn E. Ramsey, MD, chair of the CAP Transfusion, Apheresis, and Cellular Therapy Committee and medical director of the blood bank, Northwestern Memorial Hospital, Chicago, and professor of pathology, Northwestern’s Feinberg School of Medicine.

“The vendor for the pathogen-reduced platelets issued more information to blood centers and hospitals about how to store these products to avoid damage to the platelet bags,” he says. “So there’s still a small chance of contamination. I don’t know to what extent that result has helped resolve the problem, but that was the first time I was aware there could be still some issue with contamination of a treated product.” While he hasn’t seen that at Northwestern, the hospital is aware of it. “In some cases when we get a patient with an unusually severe febrile reaction, we continue to culture the products to make sure there is no bacteria in them. We’re still doing that sometimes with pathogen-reduced platelets just to make sure.”

A December 2021 FDA memorandum said “it is important for blood establishments and transfusion services to recognize the residual risk of bacterial contamination of platelets, including pathogen-reduced platelet components.” Since 2018, the FDA said in the memo, the seven cases of reported platelet septic transfusion reactions are “associated with Acinetobacter species and certain other bacterial species seen in combination, and where additional genetic testing indicates relatedness of the organisms.” No source has been identified, it said, and the FDA and CDC continue to investigate.

Those residual risks aside, the availability of PRPs has increased the discussion of possibly using paid platelet donations, Dr. Vassallo says, noting there are several proposals on the horizon to extend platelet shelf life as well as find new donors. “Paid donations have historically been a little less safe. We have very good testing, but there’s still a window period and a pathogen-reduced platelet from paid donors would probably be a very, very safe product.” It’s one more way to deal with shortages.

Cold storage of platelets immediately after donation would produce a 14-day product, Dr. Vassallo explains. “It’s generally out within two days so it has about 12 days’ shelf life. The problem is that when you put platelets in the cold, they express ‘eat me’ signals to the immune system, which quickly removes them from circulation. Nature never meant us to put platelets in the refrigerator. But these more active platelets should be very good at stopping bleeding in a person who is actively bleeding,” he says, though they would not be effective for prophylaxis.

Transitioning room-temperature–stored platelets to cold storage after five days—then refrigerating them for the next nine—would also extend platelet availability for certain patients. “The problem is during those five days you have to have some mechanism to prevent bacteria from growing, and that is either pathogen reduction or a retest on day five to make sure bacteria haven’t grown in those five days.”

Frozen platelets could become available in the next five years or so, he says. “In an emergency when someone has an accident, half of the frozen platelets rush to the wound and the other half circulate. So frozen platelets will be a game changer for patients as well,” Dr. Vassallo says. “If hospitals stock a frozen platelet, we don’t need to collect as many platelets to have just-in-case stock.”

Under the FDA’s guideline for mitigating bacteria in platelets, Dr. Ramsey says, “the two most common pathways are delayed sampling, where the platelets are held for 48 hours and then sampled and cultured. Then they could be stored up to seven days. With pathogen reduction, the platelets are treated up front and they wouldn’t need to be cultured.” At Northwestern, about half of the platelets are pathogen-reduced and half are culture. “It depends on the supplier to some extent, but there’s still a fair mixture of both in the blood supply,” he says.

PRPs are still a five-day product at this point, he notes, while some of the large-volume blood sampling protocols can go up to seven days. “The pathogen-reduced platelets do have a slightly reduced response and the patients do not get quite as good a post-transfusion platelet count increment compared with untreated platelets.” Moreover, the circulation time of those platelets is a little shorter than that of untreated platelets.

“There’s been conflicting data on whether that leads to more usage of platelets,” he says. “Some studies found more usage at hospitals that were converting to pathogen-reduced platelets, and in other studies in other countries there was not such a difference. But there is at least a small effect on the platelet quality from treating the product.”

The academic medical centers have led the way in adopting PRP in California, says Patricia Kopko, MD, professor of pathology and director of transfusion medicine, University of California San Diego Medical Center. “The California experience has been that a large group of the centers, including the UCs, Stanford, and Cedars-Sinai, switched to pathogen-reduced platelets. Then the bigger community hospitals began switching.”

Alongside this trend, “The American Red Cross decided to go to pathogen-reduced platelets entirely over the next year or two, because when you’re talking about manufacturing, two streams is much more costly than putting everything into the same workflow.”

But there should be little debate, she says, about whether the added assurance of safety justifies the use of PRP, because risks of a septic transfusion reaction are still high. Without intervention, the rate of contamination occurrence—at least one in 10,000 and possibly higher—remains a shocking number, Dr. Kopko says.

“We transfuse over 10,000 platelets a year here, so that means once a year we would be giving somebody a reaction. If you’re on the receiving end, would it seem reasonable to you or your family that the hospital saved $75 on your platelet unit but your wife, daughter, mother, or whomever, died of a septic transfusion reaction?” Using PRP to avoid such outcomes, she says, is well worth the cost to hospitals.

Anne Paxton is a writer and attorney in Seattle.