The use of recombinant factor VIIa in liver diseases

Franchini, Massimo; Montagnana, Martina; Targher, Giovanni; Zaffanello, Marco; Lippi, Giuseppe

doi:10.1097/mbc.0b013e32830496a7

Cited by 21 publications

(17 citation statements)

References 91 publications

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“…FVIIa is currently generating significant interest for trauma care and for uncontrolled haemorrhage and coagulopathy [51]. Other indications for FVIIa therapy include patients with bleeding tendencies from liver disease [52], thrombocytopenia [53], qualitative platelet dysfunction [54] and for patients with normal coagulation systems undergoing extensive surgery [55] or who have experienced major trauma and haemorrhage [56]. As mentioned above, development of antibody-based inhibitors is one of the most serious limitations of haemophilia A and B replacement therapy and renders conventional replacement therapy ineffective.…”

Section: Proteases Are Ubiquitous In Biologymentioning

confidence: 99%

Proteases as therapeutics

Craik

Page

Madison

2011

Biochemical Journal

204

151

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Proteases are an expanding class of drugs that hold great promise. The U.S. FDA (Food and Drug Administration) has approved 12 protease therapies, and a number of next generation or completely new proteases are in clinical development. Although they are a well-recognized class of targets for inhibitors, proteases themselves have not typically been considered as a drug class despite their application in the clinic over the last several decades; initially as plasma fractions and later as purified products. Although the predominant use of proteases has been in treating cardiovascular disease, they are also emerging as useful agents in the treatment of sepsis, digestive disorders, inflammation, cystic fibrosis, retinal disorders, psoriasis and other diseases. In the present review, we outline the history of proteases as therapeutics, provide an overview of their current clinical application, and describe several approaches to improve and expand their clinical application. Undoubtedly, our ability to harness proteolysis for disease treatment will increase with our understanding of protease biology and the molecular mechanisms responsible. New technologies for rationally engineering proteases, as well as improved delivery options, will expand greatly the potential applications of these enzymes. The recognition that proteases are, in fact, an established class of safe and efficacious drugs will stimulate investigation of additional therapeutic applications for these enzymes. Proteases therefore have a bright future as a distinct therapeutic class with diverse clinical applications.

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Section: Proteases Are Ubiquitous In Biologymentioning

confidence: 99%

Proteases as therapeutics

Craik

Page

Madison

2011

Biochemical Journal

204

151

View full text Add to dashboard Cite

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“…16 Bendtsen et al, conducted a meta-analysis (n=497) of acute variceal bleeding in patients with end stage liver disease receiving rFVIIa or placebo. 17 While factor administration did decrease the recurrence of bleeding within five days of administration it did not affect the five day or 40-day survival of patients.…”

Section: Discussionmentioning

confidence: 99%

Clinical Outcomes of a Pharmacy-Led Blood Factor Stewardship Program

Trueg

Lowe²,

Kiel³

2017

American Journal of Therapeutics

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To report the results of a pharmacist-directed blood factor stewardship program targeting off-label utilization designed to limit use to established organizational guidelines in high-risk populations. Prospective evaluation of recombinant factor VIIa and prothrombin complex concentrate orders beginning June 2013 through May 2014 and a matched retrospective cohort from June 2012 to May 2013. Matched cohorts were evaluated for 28-day mortality, change in international normalized ratio (INR), adverse events, concurrent blood product use, and cost savings. Forty-two orders for blood factor were ordered between June 2013 and May 2014, 70 orders in the year before (N = 112). Twenty eight–day mortality was not different between the cohorts: 53.9% versus 50% (P = 0.77). Blood factor use with underlying liver failure and active bleeding was strongly associated with 28-day mortality: odds ratio (95% confidence interval), 2.9 (1.5–7.14) and 2.91 (0.01–2.91), respectively. Blood products dispensed increased over the year with plasma products the most significant (1 vs. 4 P = 0.004). All other clinical outcomes were nonsignificant. An annual cost savings of $375,539 was achieved, primarily through a significant reduction in recombinant factor VIIa and avoidance in high-risk patients. Use of off-label blood factors can be controlled through a pharmacist-led stewardship program. Twenty eight–day mortality was not different between the 2 cohorts; however, identification of risk factors for death associated with blood factor use allows for restriction in high-risk populations, creates a discussion of futile care, and yields cost savings.

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“…Clinical trials are needed to better define the role of recombinant activated factor VII in the treatment of bleeding complications of liver disorder [21].…”

Section: Discussionmentioning

confidence: 99%