You’re sitting by the EMS radio when a call comes in: 56 y/o male with no reported PMHx presenting with facial swelling that started earlier this morning. His lips are so swollen that he’s having some trouble controlling his secretions. He received epinephrine and diphenhydramine en route without too much improvement.
He rolls in and is saturating 93% on room air. It’s angioedema! You’ve seen it enough times before. You decide to round out the allergic reaction cocktail with methylprednisolone - no improvement at all. So this is probably non-histaminergic angioedema - what’s next?
DEEP DIVE: TREATMENT OF BRADYKININ-MEDIATED ANGIOEDEMA
Tranexamic acid (TXA) or aminocaproic acid – functions by blocking conversion of plasminogen to plasmin, which otherwise augments kallikrein activation.
TXA dose: 1g IV slow push over 10 minutes.
Aminocaproic acid dose: 4-5g IV in the first hour > 1g/hour maintenance.
*Do NOT use in post-thrombolytic angioedema
A 2025 retrospective study in JEM demonstrated that patients treated with TXA did not necessarily have improved clinical outcomes – but it’s unclear if this is partially due to sicker patients receiving TXA.
C1- Esterase Concentrate – for those with known C1-inhibitor deficiency
Dose: Berinert is preferred – give 20u/kg.
*Extremely expensive and not as easily available – probably not a good first or second line for unclear etiology of angioedema.
Fresh Frozen Plasma (FFP) – contains both ACE and C1-inhibitor, thus useful in angioedema related to these deficiencies.
Dose: 2u initially, may re-dose 2 more units if needed.
This week’s Cheese is meant to bring caution to what is considered a standard of therapy for hereditary angioedema - While C1- inhibitor concentrate is the best option and typically most quickly effective, TXA and FFP have been a mainstay of stabilization as well.
It is important to note, however, that FFP should be used with caution!
The US Hereditary Angioedema Association no longer recommends the use of FFP for treatment of hereditary angioedema due to concern for increased risk of side effects including transfusion-related injury in addition to potential worsening of angioedema. FFP contains kallikrein and kininogen, which are crucial to the production of bradykinin - so this can on occasion add oil to the fire in bradykinin-mediated angioedema. A 2025 retrospective study examined treatment outcomes of 441 patients taken from the Nationwide Inpatient Database (2021 sample) to show that FFP use was associated with increased length of stay (LOS) in those with comorbidities including respiratory disease, CAD/HTN, urticaria, or in those who had severe presentations of hereditary angioedema. However, in those with seizures, SLE, or diabetes, patients given FFP were found to have a lower average LOS. Limitations of this study however include small sample sizes when subcategorized by comorbidity - for instance, the renal disease category only included 2 patients. There have also been sporadic case reports prior to this study that demonstrated acute decompensation in patients after administration of FFP. All to say, it may not have the safety profile that TXA does and should be given with caution. In a setting where C1 inhibitor concentrate or ICU access is limited, FFP may still be a good adjunct when trying to stabilize in the ED as it is readily available. Just know that it may be important to watch closely for worsening symptoms.
References:
https://www.emrap.org/corependium/chapter/recgmcfxPSDNkQRTU/Angioedema#h.ofz8g6uon9v1
https://onlinelibrary.wiley.com/action/showCitFormats?doi=10.1111%2Fjch.13097
https://www.sciencedirect.com/science/article/abs/pii/S0735675716303394?via%3Dihub
Authored by Nanditha Ravichandran MD and Eric Leser MD