Importance of HAE Treatments

Hereditary angioedema attacks cause swelling, and these should be taken as seriously as anaphylaxis. They should *not* be treated as anaphylaxis though, as the biochemical changes that occur are different, so the medications that treat allergic reactions are generally not helpful for hereditary angioedema attacks. In some situations, epinephrine may buy a bit of time, but using it instead of an HAE specific medication means that HAE treatment is actually being delayed, so typically it should only be used if it's all that's available in the moment, and even then, it may not help.

It is known that with an attack the earlier it is treated the better the outcome ie. the severity will be reduced, the length of the attack will be reduced. It can also reduce the amount of medication overall needed, as the further an attack has progressed before being treated, the more likely it is that additional treatment doses will be needed.

HAE specific medications include:

C1 inhibitor - generally purified from human plasma, although there is also on produced via recombinant technology from rabbit milk. This is the protein that those with type 1 and 2 are lacking either in amount or proper functioning but it is also beneficial to many of those with normal C1 inhibitor HAE, as it still ultimately leads to a reduction of bradykinin. There are different concentrations and fairly new for on-label use is the ability to inject this subcutaneous, typically for newer more concentrated versions, although that's only for prevention. Some still inject it via IV for prevention. IV is the only route of administration that's approved for attacks, as this route leads to a faster response. This is the only HAE specific medication that comes in multiple brands.

Firazyr - a subcutaneous injection for attacks, and some will use it off-label for prevention as well. It prevents bradykinin from binding to a receptor.

*Update* - Now available as the generic icatibant

Kalbitor - a subcutaneous injection for attacks. I have not come across anyone who uses it off-label for prevention. It inhibits kallikrein, preventing the conversion of kininogen to bradykinin. Less countries have approved its use compared to the above 2, and in the US it is not intended for self-administration, a medical professional needs to do it. I've not heard of it being approved for self-administration, although it's possible this occurs in some countries.

Takhzyro - the most recent approved HAE specific medication. It's a subcutaneous injection for prevention and doses are typically 2 weeks to a month apart. whereas C1 inhibitor is often given multiple times a week when used for prevention. This is a monocolonal antibody to kallikrein, so like Kalbitor it prevent bradykinin from being formed.

*New* Orladeyo - A pill! Many people with HAE are thrilled to have an oral medication. It also inhibits plasma kallikrein. Typically used once/day to prevent attacks.

New drugs are also being studied.

Non-specific HAE medications that are actually useful for HAE:

Attenuated androgens - these are 'male' hormones although the masculizing effects have been minimized. When access to new medications is available, these are rarely used, as there can be serious side effects, especially when used long term and can also cause a deepening of the voice, acne and increased body hair growth.

Tranexamic acid - typically used to help control bleeding, it inhibits the formation of plasmin. It can be administered orally or injected via IV and can also be used as a mouthwash and is useful that way prior to dental treatments. The effectiveness in treating HAE is questionable. It is not very effective for treating attacks, and this use is discouraged by those who study HAE, but it is used that way by some when they have no access to HAE specific treatments. Some use it long term for prevention, and it can be used for short term prophylaxis alongside HAE medications.

Fresh frozen plasma - used mostly for attacks, it contains C1 inhibitor. As this is human plasma, it also contains proteins involved with bradykinin production. It has the potential to make attacks worse, but during life-threatening attacks, when no HAE specific medication is available this is the most effective option.

Sadly, many doctors are unaware of these medications. It's not unusual for those experiencing HAE attacks to be offered the medications for allergic reactions during an attack, and even if bringing their medication with them to a hospital, treatment is often delayed. There are published case studies of people being intubated for days during a laryngeal attack before being given appropriate medication. It's not unusual for someone with an attack to be afraid and having to argue with medical professionals to get their medication, to have a treatment plan written by a specialist followed. Patients experience pain beyond what they need to, preventable deaths occur. Needless surgeries are also performed, one of the most common being removal of the appendix (reported to 23% of those with hereditary angioedema) which as surgery & trauma itself is a trigger is actually quite harmful during an attack. Other surgeries include exploratory surgeries, removal of the gall bladder, and hysterectomies although these are not exhaustive. Often times, 1 injection of an appropriate medication would prevent so much pain and fear and can also save a life.