Lining up for low titer O whole blood in trauma care

Another study, reported in Transfusion in 2019, compared five type O positive whole blood units leukoreduced with platelet-sparing filters to five units leukoreduced with non-platelet sparing filters (Haddaway K, et al. Transfusion. 2019;59[5]:1809–1817). The authors measured four TEG-derived hemostatic variables: R time, K time, alpha-angle, and maximal amplitude. They found that in vitro hemostatic function of whole blood prepared with a platelet-sparing leukoreduction filter appears to be superior to whole blood prepared with a non-platelet sparing filter.

“What I take away from this is fairly obvious—platelets are important for hemostatic function,” Dr. Karp said. “And that’s what we’re after for our trauma patients.”

Haddaway, et al., also looked at how storage duration affects coagulation testing of whole blood leukoreduced with platelet-sparing and non-platelet sparing filters, measuring prothrombin time, activated partial thromboplastin time, factor V activity, and chromogenic factor VIII. For each day of storage over a two-week period, no significant difference was seen in PT and PTT between the units leukoreduced with a platelet-sparing filter and those leukoreduced with a non-platelet sparing filter. “And that makes sense because platelets generally don’t contribute to PT and PTT measurements,” Dr. Karp said. More important, she added, for each day of storage no significant difference was seen in PT and PTT. Coagulation factors other than labile factor VIII were preserved at 1° to 6°C for 14 days or more.

In sum, Dr. Karp said, these studies support the premise that LTOWB retains hemostatic function throughout storage, and that platelet-sparing filters, if leukoreduction is performed, are critical to maintaining that function. And leukoreduction may have some impact on hemostatic function, particularly early in storage, “but these changes are gradually superseded by the effects of storage itself.” What isn’t clear is whether these findings are clinically relevant. “Again, these are just laboratory in vitro studies.”

Finally, she said, “Treatment for trauma-induced coagulopathy, particularly soon after injury, can be accomplished with low titer O whole blood. We’ve seen that clinically, and we now have the laboratory testing to support the use of these products.”

The blood center will need information from customers interested in LTOWB about what the customer considers an acceptable titer, as well as massive transfusion protocol activations and component use, the makeup of the customer’s massive transfusion protocol coolers, and the leukoreduction preference, Dr. Cruz said in her talk on blood center perspectives. The trauma and transfusion services considering LTOWB use should ask their supplier if they already offer LTOWB. “If so, what are its attributes?”

And what is the available donor population? For LTOWB, donors must be group O, aspirin free, and transfusion-related acute lung injury (TRALI)-reduced risk. “Many centers don’t routinely test female whole blood donors who have ever been pregnant for human leukocyte antigen antibodies, so that population may be excluded from available donors,” said Dr. Cruz, a liaison to the CAP Transfusion, Apheresis, and Cellular Therapy Committee.

Rare units, antigen-negative units for treating patients with sickle cell disease, and pediatric units must be protected to ensure they’re available for patients who have no other options. And only Rh-positive units may be available if the blood center doesn’t have a consistent source of Rh-negative units. Many centers enroll a group of donors recruited specifically for LTOWB, but targeted recruitment is less efficient and more costly.

The anticoagulant or bag that is used will determine expiration, she noted, and whether leukoreduction is done can determine the bag. “You have to have a platelet-sparing filter, and there’s only one approved in-line leukoreduction filter available, so that determines the bag you’re using as well.” Logistically, if the collection bags are different than those used for routine donors, Dr. Cruz said, “you have to ensure the bags are available at the collection center when the appropriate donors are present.”

The blood center will discuss titer cutoff with the transfusion service, she said. “What are you requesting? What are your concerns? Can our donor population support a titer? The lower the titer you choose, the more donors you’re going to exclude.” Early studies used a titer cutoff of 50, but as evidence of safety has accumulated, isoagglutinin titer cutoffs of 200 or 256 are commonly selected. The method for determining the titer sometimes can also impact the level of donors excluded.

Whether donors will be titered serially is another question. Some evidence suggests it may be unnecessary to titer low-titer donors at every collection, Dr. Cruz said, noting that one study demonstrated anti-A or anti-B IgM and IgG titers for low-titer donors tend to stay low titer (Sprogøe U, et al. J Trauma Acute Care Surg. 2017:82[6S suppl 1]:S87–S90). This suggests that for these donors, she said, the titer could be verified at longer intervals such as annually. But that’s difficult to track, “so many centers continue to do it on every donation.”

Many suppliers are concerned about over-collecting LTOWB and then running short for non-trauma patients who need component therapy or single transfusions of red blood cells. Thus, supply potential must be assessed, she said, and that involves tracking the number of O-positive RBC units collected and distributed annually, the number of units imported, and the O-positive RBC apheresis to whole blood collection ratio. “Since we drive our collections toward apheresis, we can get two red cell products in one donation, and that maximizes our red cell supply,” she said, though those units are then not available as whole blood. The percentage of high-titer donors excluded due to the chosen titer and LTOWB expiration date also should be assessed.

The blood center’s logistical challenges include identifying appropriate units for the production lab and product loss. “You may collect from an inappropriate donor,” she said, one who is not TRALI-reduced, for example, or learn of positive infectious disease test results in downstream processing. Though these often are false-positives, she said, the unit still would be unavailable for distribution. More often it would be a new donor exceeding the low-titer cutoff or manufacturing problems for those that are leukoreducing. Ensuring supplies are at the collection sites when they’re needed is another challenge. “This is particularly the case for those who are collecting in a bag that is not their routine bag.” And “collecting on mobiles or a constraint around delivery of supplies,” she said, can be problems when trying unexpectedly to ramp up collection of LTOWB. Timing too is important: The only FDA-approved inline platelet-sparing filter bag requires that the product be filtered within eight hours of collection.

The most efficient way for the transfusion service to ensure regular delivery is to establish a fixed or standing order, Dr. Cruz said. With order changes or ad hoc ordering, lead time considerations come into effect. “I’ve got to be able to get that notice to the site, anticipate donors at the sites and mobiles, ensure that the supplies are in the right place, and potentially put the targeted recruitment machine into place.”

Communication between the blood center and transfusion service is key as production of LTOWB is increased to meet need, she said. “You want to ramp up to your comfort level, but also adjust down to account for seasonality or if you find you’re having wastage.”

So what is the best model for stewardship? Dr. Cruz asked. A blood center stock is possible but requires a critical level of demand and utilization to be reached. “Again, overstock will lead to outdating and wastage.” One option is to reclaim RBCs by spinning the product down at the 14-day mark, for example, and converting it to RBCs, but that product will have a shorter shelf life than regularly collected RBCs, she said. “So where are you in your ability to accept short dates? If your blood supplier is asking you to accept short-dated red cells, how often are you accepting and using those?” The other possibility, she said, and the one that’s preferred—at least from the blood center’s perspective—is just-in-time production.

Returns add cost and labor, and reclaimed red cells add labor and planning in the processing lab for units that can be difficult to place because of their short dates. Some transfusion services reclaim RBCs if they aren’t using and transfusing the blood out to the full 21 days. “Some report that they perform a reclamation at the center,” she said, and if they’re not able to do that, they may do separation via sedimentation. Others identify opportunities where expiring units might be appropriate, such as in the OR.

“Everything was looking good” for LTOWB, Dr. Cruz said of the ramping up of supply. “Then COVID. So we have more challenges than ever to collect donors in the blood supplier space.” Transfusion services too have “felt the pinch” of the severe blood shortage and especially of O-positive donors. And all have suffered supply chain and staffing problems. “In any case,” Dr. Cruz said, “we continue to move forward.”

Charna Albert is CAP TODAY associate contributing editor.