title: Collection tubes containing citrate stabiliser over-estimate plasma glucose, when compared to other samples undergoing immediate plasma separation.
abstract: OBJECTIVE
  Blood collection tubes containing citrate lower pH, thereby inhibiting glycolysis. When compared to other additives, they introduce an over-estimation in measured glucose. This study explored this over-estimation across a range of glucose values. Blood samples collected into lithium-heparin tubes then cooled prior to immediate refrigerated plasma separation, were used as the primary comparator.
  
  
  METHODS
  Venous blood from individuals with and without diabetes was collected into tubes containing lithium-heparin, or fluoride, or fluoride-citrate (Terumo™ Venosafe). Plasma was separated at time intervals of zero, 2 and 24h. Preparation of the 'time zero' lithium-heparin and fluoride samples was optimised by processing these samples under cooled conditions. The remaining samples were prepared at room temperature. Plasma was analysed in the routine clinical laboratory using the hexokinase method.
  
  
  RESULTS
  Median plasma glucose for the 50 participants was 7.1mmol/L (range 3.1-21.5). At 'time zero', fluoride-citrate glucose was 0.37mmol/L (95% CI 0.26-0.48) higher than lithium-heparin glucose and 0.29mmol/L (95% CI 0.21-0.36) higher than glucose from fluoride tubes. Following delayed plasma separation at 24h, glucose loss from the lithium heparin tubes averaged 0.2mmol·L-1·hr-1. In contrast, the fluoride-citrate tubes showed minimal glucose loss over 24h.
  
  
  CONCLUSIONS
  Acid stabilises glycolysis but causes an over-estimation in glucose, across a range of plasma glucose values, when compared to blood collected into conventional tubes under cooled conditions. The magnitude of the over-estimation seen with the fluoride-citrate tubes is unlikely to be due solely to the differential glucose stabilisation rates of acid, compared to cooling.
authors.affiliation: School of Medicine, University of Otago Christchurch, Christchurch, New Zealand.
authors.forename: Rebekah
authors.initials: R
authors.lastname: Carey
authors.affiliation: Diabetes Centre, Christchurch Hospital, Christchurch, New Zealand; Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand. Electronic address: helen.lunt@cdhb.health.nz.
authors.forename: Helen
authors.initials: H
authors.lastname: Lunt
authors.affiliation: Diabetes Centre, Christchurch Hospital, Christchurch, New Zealand.
authors.forename: Helen F
authors.initials: HF
authors.lastname: Heenan
authors.affiliation: Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand.
authors.forename: Christopher M A
authors.initials: CM
authors.lastname: Frampton
authors.affiliation: Diabetes Centre, Christchurch Hospital, Christchurch, New Zealand; Canterbury Health Laboratories, Canterbury District Health Board, Christchurch, New Zealand.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Florkowski
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis*; D002951:Citrates / Q000737:chemistry*; D005260:Female; D006461:Hemolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D013048:Specimen Handling / Q000295:instrumentation*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002951:Citrates
keywords: Bias, systematic; Blood chemical analysis; Blood glucose; Citrate; Diabetes; Diagnosis, laboratory; Glycolysis; Plasma