Successful long-term prophylaxis with human plasma-derived C1 inhibitor in planning and carrying out pregnancy

Hereditary angioedema with C1 inhibitor deficiency (C1-INHHAE) is a rare autosomal dominant disorder characterized by recurrent attacks of edema in different locations, which may be peripheral or affect internal tissues, as the gastrointestinal tract causing abdominal pain or the upper airways, producing life-threatening asphyxia.1 The physiopathology of the disease involves several vasoactive peptides, such as bradykinin, which increase endothelial permeability and vascular leakage. The C1 inhibitor (C1-INH) quantitative or qualitative deficiency is the characteristic biomarker of the disease. The clinical manifestations reduce the physical and social functioning with a significant impact in the quality of life of patients.2 Frequent attack triggers are stress, trauma and infections. Direct and indirect costs of the disease have been estimated on 42 000 US$ a year per patient, but when attack severity and frequency are considered, costs rise up to 92 000 US$.3 Therapy is addressed by treating or preventing acute attacks and the regimen should always be individualized. Blocking bradykinin receptor agents, kallikrein synthesis inhibitors and C1-INH are used as treatment for acute attacks. Human plasma-derived C1INH (pdC1-INH) is used as treatment for acute attacks and can also be prophylactically administrated either before surgery and invasive procedures or continuously for long-term prophylaxis, when symptoms are frequent and/or severe.1 Treatment with attenuated androgens for long term prophylaxis has declined lately as their prolonged use have been related to various side effects.4,5 During pregnancy, C1-INH-HAE canworsen due to the increased estrogen levels, although most series describe an unpredictable course.6 Even in the same woman, different pregnancies show differences in frequency and severity of angioedema (AE) attacks.7 Treatment options during pregnancy are limited. The administration of pdC1-INH has been proven safe and effective in acute attacks, but also as short and long-term prophylaxis.8 Fresh frozen plasma can be an alternative for acute attacks, it is cost-effective and safe, as viral transmission is minimal due to effective screening of blood products. However, its content of complement factors has the potential to worsen HAE symptoms. Antifibrinolytic agents such as tranexamic and epsilon aminocaproic acids can be used as prophylaxis; however, potential risks and benefits must be considered, and there are few data on their use during pregnancy. Attenuated androgens such as danazol, are contraindicated during pregnancy, in fact they should be withdrawn at least one month