Fresh frozen plasma for angioedema

Last updated March 5, 2024, by Margarida Maia, PhD
Fact-checked by Joana Carvalho, PhD

What is fresh frozen plasma for angioedema?

Plasma is the liquid component of blood, which makes up about 55% of the blood’s total volume in people. This clear, straw-colored liquid contains many proteins, including the clotting factors that help to control bleeding and the C1-esterase inhibitor protein that is missing or abnormal in certain forms of angioedema.

Fresh frozen plasma (FFP) is a plasma product that can be prepared from a donor’s whole blood, or collected by apheresis — a procedure that allows red blood cells, white blood cells, and platelets to be removed from whole blood.

Once plasma is collected, it can be frozen within eight hours at minus 18 C (minus 0.4 F) or colder and stored until transfusion, which is done via an intravenous (into-the-vein) administration after thawing.

Because FFP contains all clotting factors, it’s primarily used to temporarily supply missing or faulty clotting factors to patients with a clotting disorder or other blood problems. Its use is expected to help the blood to clot properly, thereby preventing or keeping bleeding under control.

FFP generally is indicated to:

• treat patients with a clotting disorder who are bleeding or at risk of bleeding, when specific treatment options like clotting factor concentrates are unavailable
• reverse the effects of warfarin, a blood thinner, in the event of major bleeding or to prepare for a surgical procedure
• replace plasma to treat some conditions marked by excessive red blood cell destruction and organ damage due to the formation of blood clots in small blood vessels.

The treatment also can be used in the context of angioedema, where it’s employed to provide proteins that aid in the management or prevention of acute swelling attacks.

Angioedema occurs when blood vessels leak fluid into the deeper layers of the skin or the mucous membranes lining internal organs and cavities in the body. This results in repeated attacks of swelling that can arise anywhere in the body and sometimes be accompanied by other symptoms like fatigue or abdominal pain.

The condition can become life-threatening if it causes swelling of the throat or voice box, known as laryngeal edema, which can result in airway obstruction.

For angioedema patients, FFP may be used in emergency settings to rapidly control life-threatening attacks that do not respond to other treatments, or when appropriate therapies are not readily available. It also may be used as a prophylactic treatment to prevent attacks in patients with hereditary angioedema (HAE) who are pregnant or undergoing surgery.

How does fresh frozen plasma work in angioedema?

HAE is a type of angioedema that mostly occurs due to genetic mutations that impair the production or function of a protein called C1-esterase inhibitor (C1-INH). This causes an enzyme called kallikrein to become overly active, driving the excessive production and release of bradykinin. High levels of bradykinin cause blood vessels to dilate, which allows fluid to leak into tissues and ultimately drives swelling.

Badykinin also is involved in another form of angioedema called nonallergic angioedema or drug-induced angioedema, where swelling occurs as a side effect of certain medications. This disease type is most commonly associated with angiotensin-converting enzyme inhibitors — a class of medications that are used to lower blood pressure, but also can increase the levels of bradykinin.

FFP can be used in these two forms of bradykinin-mediated angioedema to temporarily supply patients with C1-esterase inhibitor and angiotensin-converting enzyme.

By increasing the levels of C1-esterase inhibitor in circulation, the treatment is expected to bring swelling under control and ease symptoms of angioedema. Angiotensin-converting enzyme found within plasma also may help break down accumulated bradykinin, thereby easing swelling.

While acquired angioedema also is marked by C1-esterase inhibitor deficiency, either due to self-reactive antibodies that target the protein or due to higher consumption of C1-esterase inhibitor in certain conditions, there is not much data on the use of FFP in these patients. Two recent case reports have described the use of FFP in patients with this type of angioedema: in one, the therapy was used as a preventive treatment in preparation for surgery, while in the other, it was used along with other medications to bring swelling under control.

Benefits and risks of fresh frozen plasma

Unlike acute allergic angioedema, which occurs as a result of an allergic reaction, bradykinin-mediated angioedema may not respond to conventional medications, such as antihistamines, corticosteroids, or epinephrine (the EpiPen’s active ingredient)

While there are a number of medications approved to treat bradykinin-mediated angioedema, off-label use of FFP may still be recommended in certain situations. When a drug is used off-label, it’s given to a patient for a use that was not specifically approved by regulators.

Benefits of fresh frozen plasma

Treatment options for bradykinin-mediated angioedema range from a C1-esterase inhibitor concentrate (C1-INH), which contain a working version of the protein of the same name, to medications that block the action of kallikrein or bradykinin.

These medications, however, may not always be available in an emergency room for angioedema treatment. The use of FFP has been recommended for on-demand treatment of swelling attacks when no other treatment options are available or when access to those medications is limited by country policies or insurance coverage for reimbursement.

In emergency settings, FFP has been reported to control swelling, including in patients with laryngeal edema, when antihistamines, corticosteroids, and epinephrine had failed to do so. It also worked well in pregnant women and when given before surgery as a preventive treatment to reduce the risk of swelling.

Risks of fresh frozen plasma

While FFP is generally effective in treating swelling attacks, it also carries certain risks. In settings where other treatment options are available, FFP is not recommended due to its potential to:

• worsen symptoms of angioedema
• transmit infectious disease-causing agents
• cause an allergic reaction.

Transfusion-associated circulatory overload, a complication that may occur when a large volume of fluid is infused too rapidly into the body, is another one of the potential FFP risks for angioedema patients. Its symptoms include shortness of breath, low blood oxygen levels, swelling in the legs, high blood pressure, and a fast heartbeat.

Severe transfusion reactions also may occur if the FFP product is not appropriately matched with the person’s blood type. In these cases, antibodies found in the donor’s plasma may erroneously attack red blood cells in the patient’s blood, leading to symptoms such as fever, pain, flushing, and fainting.

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