Variability in Plasma Donors May Explain Different Clinical Outcomes for Angioedema Patients, Study Says

Angiotensin-converting enzyme (ACE) activity levels can vary among different donors of fresh frozen plasma (FFP) — commonly used for the treatment of non-allergic angioedema triggered by ACE inhibitors — which may partially explain why clinical outcomes differ among these patients, a study reports.

The study, “Possible donor-dependent differences in efficacy of fresh frozen plasma for treatment of ACE inhibitor–induced angioedema,” was published in The Journal of Allergy and Clinical Immunology: In Practice.

Angioedema is the medical term to describe tissue swelling, typically caused by a severe allergic reaction. The swelling is caused by the expansion of blood vessels in the deep layers of the skin or mucosa, leading to the accumulation of fluid (edema).

In patients with non-allergic angioedema, medications that are normally used to lower blood pressure and improve heart health, such as ACE inhibitors and renin-angiotensin-aldosterone-system blockers (RAE blockers), may induce tissue swelling.

Unlike other types of angioedema, non-allergic angioedema does not respond to allergy medications, such as antihistamines, corticosteroids, and epinephrine (e.g., EpiPen), or to non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen.

Previous case reports have shown that FFP may be effective at treating non-allergic angioedema triggered by ACE inhibitors. FFP is a readily available alternative treatment method in which patients receive from healthy donors plasma that contains the C1-inhibitor (C1-INH) protein they are lacking. This protein is important for blocking the activity of other proteins (plasma kallikrein and coagulation factor 12) that produce bradykinin, a substance that causes tissue swelling.

Unfortunately, the effectiveness of FFP for the treatment of non-allergic angioedema triggered by ACE inhibitors has been extremely variable.

“One possible explanation for this variability that has not been considered in the literature is the potential variation in ACE activity levels between FFP units from different blood donors — indeed, it is likely that a number of donors take ACE inhibitors,” the researchers wrote.

To test this hypothesis, a group of scientists from the Washington University School of Medicine and the Saint Louis School of Medicine measured the ACE activity levels in 330 samples from a group of blood donors from the American Red Cross Missouri/Illinois Blood Services.

Correlation analyses failed to identify a relationship between the sex of the donors and ACE activity levels. However, a mild inverse relationship was found between age of donors and activity levels of ACE in the plasma, meaning the older the donors, the lower the activity.

While the median ACE activity levels were 37.65 U/liter, 39 (11.8%) donors had ACE activity levels lower than 20 U/liter, suggesting the use of ACE inhibitors.

“This strongly suggests that the variability of the reported efficacy of FFP for treatment of ACE inhibitor-induced angioedema is at least in part due to a wide variation of ACE  activity levels between different units of FFP,” the investigators wrote.

“Although several case reports and case series have suggested that FFP is efficacious, randomized controlled trials to prove its benefit are imperative. Our findings indicate that these trials should utilize FFP that contains high levels of ACE activity,” they concluded.