title: Thrombotic events associated with C1 esterase inhibitor products in patients with hereditary angioedema: investigation from the United States Food and Drug Administration adverse event reporting system database.
abstract: OBJECTIVE
  To investigate reports of thrombotic events associated with the use of C1 esterase inhibitor products in patients with hereditary angioedema in the United States.
  
  
  METHODS
  Retrospective data mining analysis.
  
  
  METHODS
  The United States Food and Drug Administration (FDA) adverse event reporting system (AERS) database.
  
  
  RESULTS
  Case reports of C1 esterase inhibitor products, thrombotic events, and C1 esterase inhibitor product-associated thrombotic events (i.e., combination cases) were extracted from the AERS database, using the time frames of each respective product's FDA approval date through the second quarter of 2011. Bayesian statistical methodology within the neural network architecture was implemented to identify potential signals of a drug-associated adverse event. A potential signal is generated when the lower limit of the 95% 2-sided confidence interval of the information component, denoted by IC₀₂₅ , is greater than zero. This suggests that the particular drug-associated adverse event was reported to the database more often than statistically expected from reports available in the database. Ten combination cases of thrombotic events associated with the use of one C1 esterase inhibitor product (Cinryze) were identified in patients with hereditary angioedema. A potential signal demonstrated by an IC₀₂₅ value greater than zero (IC₀₂₅ = 2.91) was generated for these combination cases.
  
  
  CONCLUSIONS
  The extracted cases from the AERS indicate continuing reports of thrombotic events associated with the use of one C1 esterase inhibitor product among patients with hereditary angioedema. The AERS is incapable of establishing a causal link and detecting the true frequency of an adverse event associated with a drug; however, potential signals of C1 esterase inhibitor product-associated thrombotic events among patients with hereditary angioedema were identified in the extracted combination cases.
authors.affiliation: Department of Pharmacy Practice, School of Pharmacy, South College, Knoxville, Tennessee 37919, USA. pgandhi@southcollegetn.edu
authors.forename: Pranav K
authors.initials: PK
authors.lastname: Gandhi
authors.forename: William M
authors.initials: WM
authors.lastname: Gentry
authors.forename: Michael B
authors.initials: MB
authors.lastname: Bottorff
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D054179:Angioedemas, Hereditary / Q000188:drug therapy*; D001499:Bayes Theorem; D002648:Child; D003174:Complement C1 Inactivator Proteins / Q000009:adverse effects / Q000627:therapeutic use; D050718:Complement C1 Inhibitor Protein; D003173:Complement C1s / Q000037:antagonists & inhibitors*; D051056:Complement Inactivating Agents / Q000009:adverse effects* / Q000627:therapeutic use; D057225:Data Mining; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016571:Neural Networks, Computer; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D013927:Thrombosis / Q000139:chemically induced*; D014481:United States; D014486:United States Food and Drug Administration; D055815:Young Adult
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D051056:Complement Inactivating Agents; D010455:Peptides; C469952:SERPING1 protein, human; C511194:ecallantide; D003173:Complement C1s