In search of therapy for transfusion-related acute lung injury (TRALI)

A blood transfusion can sometimes cause serious side effects, such as transfusion-related acute lung injury (TRALI). Researchers are working to better understand this life-threatening reaction.

In the case of TRALI, fluid accumulates in the lungs within a few hours after a blood transfusion, causing breathing difficulties, which could potentially lead to death. The risk is particularly high in the intensive care unit (ICU), where seriously ill patients often receive transfusions. Currently, there is no effective treatment.

Rick Kapur, research group leader at the Experimental Immunohematology department of Sanquin, has been investigating the underlying mechanism of TRALI for many years. He explains that a combination of factors, including the patient's immunocompromised state as well as components in the transfusion product, can trigger an immunological reaction that damages the pulmonary vessels.

Male blood plasma

Alexander Vlaar, professor of translational intensive care medicine and head of the ICU at Amsterdam UMC, notes that female donor blood is a striking example. "Approximately 40 percent of women who have had multiple pregnancies develop antibodies in their blood. If you receive that blood as a patient and have a matching antigen, you have a higher risk of TRALI. Since 2007, only male donor plasma has been used for patient care in Western countries, resulting in a two-thirds reduction in side effects. Other strategies are being developed to still use female donor plasma safely."

Complement system

Kapur suspects that the patient's complement system plays a crucial role in TRALI. "This system is essential in the defense against microorganisms. We have discovered that when it becomes overactive due to antibodies, it can lead to damage, such as TRALI. Together with other Sanquin groups, we aim to inhibit this and mitigate TRALI. Additionally, we continue to explore other potential therapeutic targets. Once we develop a therapy, we can investigate its effectiveness in a multicenter clinical trial with Alexander's collaboration."

Reverse TRALI

Another phenomenon that Kapur and Vlaar focus on is the so-called Reverse TRALI. In this case, an interaction occurs between the patient's antibodies and antigens in the donor blood. The clinical picture is similar. The researchers are studying how this process works. Kapur: "Reverse TRALI is often underestimated, and there is currently no standardized diagnostic method. We aim to develop one together. Additionally, we are searching for targets to slow down this form of TRALI."

Translational research

Kapur and Vlaar are addressing TRALI from multiple angles. For example, they are examining the influence of storage quality and duration of blood products. Vlaar explains: "We want to determine whether the blood of a particular donor may deteriorate during storage due to excessive waste products by the cells. This could contribute to TRALI. Collaborating with Sanquin on translational research is incredibly rewarding. By gaining more insights, we hope to collectively gain full control over this harmful transfusion reaction."