title: "Hook-like effect" causes false-negative point-of-care urine pregnancy testing in emergency patients.
abstract: BACKGROUND
  Failure to detect pregnancy in the emergency department (ED) can have important consequences. Urine human chorionic gonadotropin (uhCG) point-of-care (POC) assays are valued for rapidly detecting early pregnancy with high sensitivity. However, under certain conditions, POC uhCG tests can fail to detect pregnancy.
  
  
  OBJECTIVE
  In investigating a series of late first-trimester false-negative pregnancy tests in our ED, a novel and distinct causative phenomenon was recently elucidated in our institution. We discuss uhCG POC tests, review our false-negative rate, and describe mechanisms for false negatives and potential remedies.
  
  
  CONCLUSIONS
  The false-negative POC uhCG rate is very low, but in the setting of a large volume of tests, the numbers are worth consideration. In positive uhCG POC tests, free and fixed antibodies bind hCG to form a "sandwich"; hCG is present in several variant forms that change in their concentrations at different stages of pregnancy. When in excess, intact hCG can saturate the antibodies, preventing sandwich formation (hook effect phenomenon). Some assays may include an antibody that does not recognize certain variants present in later stages of pregnancy. When this variant is in excess, it can bind one antibody avidly and the other not at all, resulting in a false-negative test (hook-like phenomenon). In both situations, dilution is key to an accurate test.
  
  
  CONCLUSIONS
  Manufacturers should consider that uhCG tests are routinely used at many stages of pregnancy. Characterizing uhCG variants recognized by their tests and eliminating lot-to-lot variability may help improve uhCG test performance. Clinicians need to be aware of and familiarize themselves with the limitations of the specific type of uhCG POC tests used in their practice, recognizing that under certain circumstances, false-negative tests can occur.
authors.affiliation: Division of Emergency Medicine, Washington University School of Medicine, St. Louis, Missouri 63110-1010, USA.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Griffey
authors.forename: Caleb J
authors.initials: CJ
authors.lastname: Trent
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Bavolek
authors.forename: Jacob B
authors.initials: JB
authors.lastname: Keeperman
authors.forename: Christopher
authors.initials: C
authors.lastname: Sampson
authors.forename: Robert F
authors.initials: RF
authors.lastname: Poirier
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000652:urine; D006063:Chorionic Gonadotropin / Q000652:urine*; D004636:Emergency Service, Hospital; D005188:False Negative Reactions; D005260:Female; D006801:Humans; D019095:Point-of-Care Systems; D011247:Pregnancy; D011258:Pregnancy Tests / Q000379:methods* / Q000592:standards; D011261:Pregnancy Trimester, First / Q000652:urine; D016216:Ultrasonography, Prenatal; D016482:Urinalysis / Q000379:methods; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006063:Chorionic Gonadotropin