Every blood center knows that summer brings a significant drop in the number of donations. The problem is especially acute with platelets. Platelets have a very short shelf life (5-7 days post collection, vs 35 days for red blood cells and 6 months for frozen plasma) Inventory is thus very tightly coupled with recent donor activity. Summer typically sees decreased donor visits as college students disperse and families spend more time traveling.
Compounding this seasonal pattern, however, are several long-term demographic trends. For one, year-over-year demand for platelets is increasing as America’s population ages and grows. At the same time, the donor population is shrinking. Younger people are increasingly pressed for time and are less able to commit the 2-3 hours required for platelet apheresis.
Beyond the demographic trends, AABB[i]and the FDA have recommended that blood centers defer platelet collection from multiparous female donors in order to mitigate the risk of Transfusion Associated Lung Injury (TRALI). Although a definitive causative link has not been established, the condition appears to arise when antibodies against Human Leukocyte Antigen (HLA) in transfused plasma indirectly results in pulmonary edema.[ii] Single donor platelet units are considered a high risk due to the platelets being stored in the donor’s own plasma. Until recently, TRALI was the leading transfusion-associated cause of death in the US.
Elevated levels of anti-HLA antibodies are most likely to occur in women who have borne at least one child. Each additional child raises both the likelihood and the titer of anti-HLA antibodies. As such, many blood centers collect platelets and plasma exclusively from male donors. Some are willing to bear the additional cost of screening female donors for anti-HLA antibodies, especially for universal AB plasma donors. The net effect, however, has been a dramatic decrease in the pool of potential platelet and plasma donors.
The next challenge will be an eventual FDA guidance requiring additional testing of platelets for bacterial contamination. A previous Hemoblogin column covered this issue in some detail. The guidance discussed in that column is currently on hold, according to industry insiders. It is likely to be revised in some form within the next few years. Even without the guidance, however, there is growing awareness that bacterial contamination of platelets needs to be addressed in units stored longer than four days.
Meeting the need
The RAND Corporation report, released in 2016, addresses many of these concerns by advocating for increased technological innovation, regulatory reform, greater investment in blood centers as a public health resource, and a more fluid distribution network.
In the short term, however, there are several promising avenues for expanding platelet resources available: pre-storage pooled platelets (Acrodose), single donor platelets suspended in Platelet Additive Solution (PAS), units with 7 days of post-collection viability, and expanding the geographical area from which units can be procured.
Pre-storage pooled platelets were approved for use in the US in 2005. In many European countries, pooled platelets derived from whole blood donation are the norm. In the US, however, adoption has been slow and sporadic.
As this archived story from a 2010 edition of the College of American Pathologists newsletter indicates[iii], pooled platelets were once sidelined by concerns over bacterial contamination. Prior to the development of Acrodose, whole blood derived pooled platelets could be stored for only 4 hours before transfusion, making culture-based testing of platelets impractical. With the approval of pre-storage pools, however, the entire pooled platelet product can be tested for bacterial contamination. Pooled products are also eligible for the rapid test developed by Verax, provided they have undergone the initial, post-manufacture culture-based test.
There are several potential advantages to using Acrodose platelets. The most immediate is that they are an untapped resource in a time of scarcity. Like single donor platelets, Acrodose platelets are viable for 5 days post collection, and are tested for bacterial and viral contamination using FDA-approved methods.
Significantly, Acrodose units are not considered “high plasma volume” components, and studies show[iv] no increase in the risk of TRALI relative to SDP units derived from male donors. Not only is it easier to recruit whole blood donors than apheresis, but the potential pool of donors is significantly larger. As a result, the per unit cost for Acrodose is typically much less than for SDP units.
The objection to more widespread use of Acrodose is partly due to concerns about increased viral exposure. A mathematical model, Vamvakis et al[v], suggested that switching to 100% pooled platelets in the US could result in an increase in exposure to viral pathogens. The central argument is that pooling platelets from 5 donors results in a 5-fold increase in risk that the unit contains undetected pathogens. It is worth noting, however, that the risk of undetected viral contaminants is much higher when relying on anti-body based tests than on nucleic acid tests (NAT). As Haemonetics is keen to point out, NAT for HIV and HCV were approved by the FDA for blood product screening in 2014, specifically with pre-storage pooled platelet products in mind. Additional perspective can be found in conversations with Drs. Rachel Beddard, MD and Chistopher Clark, MD, as posted on Hemoblogin. Both consider Acrodose clinically equivalent to SDP for nearly all uses.
Another barrier to increased adoption of Acrodose is the seemingly inexplicable omission of pooled platelets from recent FDA guidances. Pooled platelets are not currently eligible for use in conjunction with Pathogen Reduction Technology, for example. Combining PRT and Acrodose technologies could simultaneously solve several vexing issues. PRT has been shown to render most viruses inert, neatly solving the concerns regarding increased risk of exposure from multi-donor units. From the perspective of PRT, being able to pool multiple small aliquots would be one way of addressing concerns that PRT loses too much product to be widely applicable to SDP platelets. Cerus and Fenwal have announced a collaboration to seek approval for PRT treatment of Acrodose platelets. Also, the lower cost of Acrodose platelets could make the expense of PRT more manageable. Terumo and Cerus have independently been seeking FDA approval of PRT technologies to treat whole blood, too, which could create phenomenal efficiency in ensuring safe and available blood supply.
Another means of expanding the pool of platelets is to use platelets suspended in platelet additive solution (PAS). There are a number of vendors and approved protocols for creating PAS units. The central theme, however, is that 65% - 80% of the plasma component of the platelet unit is replaced with a sterile nutrient-saline solution.
The key benefit of PAS is the reduction in anti-HLA antibody titer relative to units suspended in 100% donor plasma. Lower titer appears to correlate with lower incidence of TRALI. As a further benefit, allergic reactions to transfusions are reduced as well.
With PAS, blood centers can have access to a wider pool of apheresis platelet donors. Unfortunately, this does not necessarily translate to lower per unit costs. On the contrary, the additional processing combined needed to add PAS, along with the lengthier apheresis collection process, means that PAS units are typically more costly than standard SDP. As supplies become more constrained, however, it may be worth exploring options for PAS platelets.
PAS has been shown to maintain therapeutic viability of platelets beyond 10 days.[vi] Platelets with 10+ days are still a long way from FDA approval, but the possibility is tantalizing. Combined with the near-zero incidence of bacterial contamination observed in units treated with Pathogen Reduction Technology, such technology could revolutionize platelet therapy. The RAND report called specifically for increased government funding for research into just such innovation.
7-day platelets are another option for increasing access to this precious resource. At present, the only eligible conditions for 7-day storage are SDP platelets suspended in plasma and manufactured with Fenwal or Terumo equipment and stored in containers approved by the FDA. Additionally, platelets must be screened with a bacterial contamination test approved by the FDA as a “safety measure”. Currently, Verax is the only such approved test. Unfortunately, Acrodose platelets are not currently eligible for 7-day dating, regardless of container or secondary testing. Addressing this oversight could provide an additional resource for expanding platelet supply.
Despite these hurdles, having two extra days of viability allows for greater flexibility in inventory management. Additionally, facilities equipped to implement Verax testing have the option of securing still-viable platelets that would otherwise be discarded after 5 days. Not only does this process preserve precious donated resources, but it expands a transfusion center’s pool of potential supplies. The key is that 7-day platelets have been shown therapeutically equivalent to fresh platelets.[vii]
The final option for expanding short term supply is to increase a geographic reach. Seasonal shortages affect all areas of the US to some extent, but there is always a mismatch between supply and demand. Blood centers have been forming such relationships for some time now. The goal, however, has been to ensure their ability to fulfill contractual obligations to transfusion centers.
Transfusion centers, however, can take initiative to ensure a steady supply of blood products. Blood banks and blood centers can be partners working together to ensure fair and even distribution of blood. Bloodbuy can be a part of that solution by connecting providers and producers who might otherwise never communicate.
In the long term, increased donor recruitment, technological innovation, and regulatory reform will all be needed to meet America’s growing need for platelets. We can meet that challenge by working together to ensure the future of America’s blood supply.
[ii] Triulzi, D. J. (2009). Transfusion-Related Acute Lung Injury: Current Concepts for the Clinician. Anesthesia & Analgesia,108(3), 770-776. doi:10.1213/ane.0b013e31819029b2
[iv] Gerber, D. (2012). Transfusion-related acute lung injury: reports to the French Hemovigilance Network 2007 through 2008. Yearbook of Critical Care Medicine,2012, 178-179. doi:10.1016/j.yccm.2011.12.011
[v] Vamvakas, E. C. (2009). COMMENTARY: Relative safety of pooled whole blood-derived versus single-donor (apheresis) platelets in the United States: a systematic review of disparate risks. Transfusion,49(12), 2743-2758. doi:10.1111/j.1537-2995.2009.02338.x
[vi] Slichter, S. J., Corson, J., Jones, M. K., Christoffel, T., Pellham, E., Bailey, S. L., & Bolgiano, D. (2013). Exploratory studies of extended storage of apheresis platelets in a platelet additive solution (PAS). Blood,123(2), 271-280. doi:10.1182/blood-2013-05-501247
[vii] Rogers, T. S., DO. (2016, July 25). A Brief Overview of 7-day Platelets. Retrieved June 23, 2017, from https://labmedicineblog.com/2016/07/25/a-brief-overview-of-7-day-platelets/LABLOGATORY