Fresh frozen plasma for on-demand hereditary angioedema treatment in South Africa and Iran

BACKGROUND: International guideline-recommended on-demand treatments for hereditary angioedema (HAE) include: C1-esterase inhibitor (plasma-derived or recombinant), or bradykinin-receptor antagonists. In most low- and middle-income countries (LMIC) these products are not registered or are unaffordable. Solvent-detergent, fresh or freeze-dried plasma therapy is thus the only available on-demand treatment in these settings; but published data on efficacy and safety are limited. This study evaluated the efficacy and safety of on-demand plasma treatment of acute HAE in two LMICs. METHODS: A retrospective folder or patient registry review of acute swelling episodes necessitating emergency room attendance amongst known HAE patients was conducted at treatment centers in South Africa and Iran. Data collected included the site of angioedema, timing and amount of fresh frozen plasma (FFP) administered, time-to-resolution, hospital length of stay and adverse events. RESULTS: There were 176 acute swelling episodes amongst 43 HAE patients; 98 were treated with FFP. The face, upper airway, and abdomen were involved in 15.3% (15/98), 53.1% (52/98) and 29.6% (29/98) of episodes treated with FFP respectively. Median (interquartile range ([IQR]) of FFP administered was 400 (280–560) mLs. In all episodes except two, FFP led to resolution, with median (IQR) hours to resolution 4 (2–12). Five transfusion reactions occurred, with one case of anaphylaxis and no deaths; giving an adverse reaction rate of 5%. Differences between South Africa and Iran included: (1) proportion of HAE type II(2) median (IQR) hours to FFP administration and hospitalization, (3) number of intubations after FFP infusion. Healthcare cost for FFP treatment was USD369- 791 in South Africa and USD275-550 in Iran, largely influenced by hospital length of stay. CONCLUSIONS: Plasma (fresh-frozen) remains the only available effective on-demand treatment for acute HAE in many countries. FFP is effective and safe, but time-to-resolution is slower and adverse events are more frequent than published data on targeted therapies. Overall healthcare cost of FFP approaches that of targeted therapies – now available through global access programs – when hospitalization is prolonged.