and more effective treatment of attacks, reduced frequency of acute HAE attacks, and fewer hospitalizations. While C1-INH concentrate appears very effective from clinical trials, its safety is also very important. Since C1-INH concentrate is puriﬁed from human plasma, there is a theoretical risk of transmission of infectious agents such as hepatitis B, hepatitis C, HIV, and other viruses. The safety of C1-INH concentrate is ensured through multiple steps. The initial step is plasma donor selection. Individual donors are screened for risk factors for viral diseases along with elevated ALT. In 1986, the donor screening for HIV began and was added to hepatitis B serology screening. Serologic testing for hepatitis C began in 1993, and has since advanced to include screening for other viruses. In 1985, the safety of C1-INH concentrate improved after the introduction of a step in which the concentrate was heated for 10 hours at 60 °C to inactivate viruses (Cicardi et al 1995). Also, one company now uses a nanoﬁltration step in which a 15 nm ﬁlter is used to remove viruses and even prions (Terpstra et al 2007). None of the studies using either Lev’s or CSL Behring’s products have found any evidence of viral seroconversion with C1-INH concentrate infusions; however, earlier stud- ies before viral inactivation procedures demonstrated HCV transmission secondary to C1-INH from Immuno produced C1-INH (Cicardi et al 1995). One of the main C1-INH prod- ucts is Berinert P®, and the company that produces it claims that over 100 million units of Berinert P® have been admin- istered with no proven cases of viral transmission (Juers and Groner 2004). Thus, it appears to be a very safe treatment with few reported side effects compared with placebo and no proven viral infections in association with infusion since the introduction of the heat step. Similarly, Cinryze® has been used in Europe both in trials and clinical use and has no evidence of viral transmission (Lev, pers comm). Based on over 20 years of data, including recently completed double-blind, placebo-controlled trials, C1-INH concentrate appears to be very effective in the treatment of acute HAE attacks. The only other currently available treatment for acute attacks is FFP, which is a controversial treatment. C1-INH concentrate does not have the other sub- strates that FFP carries that give FFP the theoretical risk of worsening an attack. C1-INH also has the added beneﬁt of increased viral safety compared with FFP due to the puriﬁ- cation and pasteurization steps performed. No studies have compared C1-INH concentrate with any of the new emerging therapies. These alternative therapies may prove to be as effective for acute attacks, but will unlikely be utilized for prophylaxis secondary to their short half-lives. Therapeutics and Clinical Risk Management 2008:4(5) Plasma-derived C1 inhibitor for hereditary angioedema Conclusion C1-INH concentrate is considered standard of care in many countries for the treatment of HAE, and will likely soon be available in the US. Studies have shown it to be a very effective treatment with improvement of symptoms within 30 minutes to one hour. It appears very safe with no proven viral transmission since the introduction of the heat step. The side effect proﬁle in a recent study was very similar to placebo. In addition to treating acute HAE attacks, it may also be beneﬁcial as a chronic prophylactic agent, and may one day be approved for home infusion in properly selected patients with appropriate training. The present data on C1-INH concentrate appear very promising, and the avail- ability of C1-INH concentrate in more countries will improve quality of life and productivity, as well as reduce anxiety and disability for patients with HAE. 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