R E V I E W Treatment of hereditary angioedema with plasma-derived C1 inhibitor Michael J Prematta Tracy Prematta Timothy J Craig Section of Allergy and Immunology, Penn State University, Milton S. Hershey Medical Center, PA, USA Correspondence:Timothy J Craig Penn State University, Milton S. Hershey Medical Center, 500 University Drive, PA 17033, Hershey, USA Email tcraig@hmc.psu.edu Background: Plasma-derived C1 inhibitor (C1-INH) concentrate is a treatment option for acute hereditary angioedema (HAE) attacks and is considered the standard-of-care in many countries, although it is not yet available in the United States. Studies are still being conducted to establish its safety and efﬁcacy as required by the FDA. Objective: To review the medical literature to determine if C1-INH concentrate is a safe and effective treatment for acute HAE attacks. Methods: The following keywords were searched in PubMed and OVID: C1 esterase inhibitor, C1-inhibitor, C1 inhibitor, and hereditary angioedema treatment. English-language articles were searched from 1966 to the present to look for studies demonstrating the efﬁcacy and the safety of C1-INH concentrate. Results: The English-language literature search revealed several studies showing signiﬁcantly improved relief of HAE symptoms with the administration of C1-INH concentrate – many studies demonstrated some improvement of symptoms within 30 minutes. Side effects have been similar to placebo, and no proven cases of viral transmission have occurred in over 20 years. Conclusion: C1-INH concentrate appears to be a very safe and effective treatment option for HAE. Keywords: hereditary angioedema, c1 inhibitor, c1 esterase inhibitor, hereditary angioedema treatment Introduction Hereditary angioedema (HAE) is an autosomal dominant inherited condition caused by a quantitative or qualitative deﬁciency of C1-esterase inhibitor (C1-INH). C1-INH is the main regulator of the early steps of the classic complement pathway. Without C1-INH, uncontrolled activation of the classic pathway of the complement system can occur, along with the activation of other inﬂammatory mediators. In addition to the suppressive effect on the complement pathway, C1-INH also inhibits the kallikrein- kinin system, bradykinin activation, lectin pathway, plasmin, and factors 11a and 12a of the coagulation pathway. Presently, the unregulated activation of bradykinin is thought to cause the changes we call angioedema (Schneider et al 2007). Angioedema can either occur spontaneously or after a traumatic or stressful event, which leads to edema formation. The condition is characterized by acute attacks of sudden edema formation in the skin or in the walls of the upper respiratory tract or gastrointestinal tract. Cases of laryngeal edema can rapidly become life threatening. Cases of gastroin- testinal attacks have been misdiagnosed and have lead to unnecessary surgeries (Ohela et al 1973). The clinical course, triggers, and frequency of attacks can be difﬁcult to predict. The approach to treatment has two main goals: one is to prevent acute attacks of hereditary angioedema from developing, and the other is to rapidly terminate acute angioedema attacks if they do occur. Therapeutics and Clinical Risk Management 2008:4(5) 975–982 © 2008 Dove Medical Press Limited. All rights reserved 975