RESUMO
BACKGROUND: Hereditary angioedema with C1 inhibitor deficiency (HAE-C1INH) is caused by dysfunctional C1-INH protein due to mutations in the SERPING1 gene encoding C1-INH. Marfan syndrome is a genetic connective tissue disease that affects the cardiovascular and ocular systems along with the skeletal system. In this case, we present the successful treatment of post-pericardiotomy syndrome unresponsive to classical therapy, which has not been described in the literature. The syndrome developed in a patient with hereditary angioedema (HAE) who underwent open heart surgery due to cardiac involvement in Marfan syndrome. CASE: A nine-year-old male HAE-C1INH patient underwent open heart surgery secondary to cardiac involvement caused by Marfan syndrome. To prevent HAE attacks, 1000 units of C1 inhibitor concentrate therapy were given 2 hours before and 24 hours after the operation. Post-pericardiotomy syndrome was diagnosed on the postoperative second day and ibuprofen 15 mg/kg/day (3 weeks) was started. Since there was no response to classical treatment on the 21st postoperative day, C1 inhibitor concentrate treatment was planned as 1000 units/ dose for 2 days a week considering a prolonged hereditary angioedema attack. In the second week of treatment, complete recovery was achieved for pericardial effusion with a total of 4 doses. CONCLUSIONS: We emphasize that in patients with hereditary angioedema undergoing this treatment, care should be taken in terms of complications that may be associated with the disease even if short-term prophylaxis is given before operations and that longer-term use of C1 inhibitor concentrate has a place in treatment.
Assuntos
Angioedemas Hereditários , Síndrome de Marfan , Masculino , Humanos , Criança , Proteína Inibidora do Complemento C1/uso terapêutico , Proteína Inibidora do Complemento C1/genética , Angioedemas Hereditários/complicações , Angioedemas Hereditários/tratamento farmacológico , Angioedemas Hereditários/prevenção & controle , Síndrome de Marfan/complicações , Síndrome de Marfan/tratamento farmacológico , Pericardiectomia , CoraçãoRESUMO
INTRODUCTION: For prophylaxis of hereditary angioedema (HAE) attacks, replacement therapy with human C1-inhibitor (C1-INH) treatment is approved and available as intravenous [C1-INH(IV)] (Cinryze®) and subcutaneous [C1-INH(SC)] HAEGARDA® preparations. In the absence of a head-to-head comparative study of the two treatment modalities, an indirect comparison of data from 2 independent but similar clinical trials was undertaken. METHODS: Two similar randomized, double-blind, placebo-controlled, crossover studies were identified which evaluated either C1-INH(SC) (COMPACT; NCT01912456; 16 weeks) or C1-INH(IV) (CHANGE; NCT01005888; 14 weeks) vs. placebo (on-demand treatment only) for routine prevention of HAE attacks. Individual patient data from each trial were used to conduct an indirect comparison of treatment effects. Attack reductions (absolute and percent of mean/median number of monthly HAE attacks reduction over placebo) were compared between the two C1-INH formulations at approved/recommended doses: C1-INH(SC) 60 IU/kg twice weekly (n = 45) and 1000 U of C1-INH(IV) twice weekly (n = 22). Point estimates were adjusted using mixed and quantile regression models that controlled for study design. RESULTS: The absolute mean monthly numbers of HAE attack reductions were 3.6 (95% CI 2.9, 4.2) for C1-INH(SC) 60 IU/kg vs. placebo and 2.3 (1.4, 3.3) for C1-INH(IV) vs. placebo; between-product difference, 1.3 (0.1, 2.4; P = 0.034). The mean percent reduction in monthly attack rate was significantly greater with C1-INH(SC) as compared with C1-INH(IV) (84% vs. 51%; P < 0.001). The percentages of subjects experiencing ≥ 50%, ≥ 70%, and ≥ 90% reductions in monthly HAE attack rates versus placebo were significantly higher with C1-INH(SC) 60 IU/kg as compared to C1-INH(IV) 1000 U (≥ 50% reduction: 91% vs. 50%, odds ratio [OR] = 10.33, P = 0.003; ≥ 70% reduction: 84% vs. 46%, OR = 6.19, P = 0.005; ≥ 90% reduction: 57% vs. 18%, OR = 6.04, P = 0.007). CONCLUSION: Within the limitations of an indirect study comparison, this analysis suggests greater attack reduction with twice-weekly C1-INH(SC) 60 IU/kg as compared to twice-weekly C1-INH(IV) 1000 U for the routine prevention of HAE attacks.