Biological Variation of Hemostasis Variables in Thrombosis and Bleeding: Consequences for Performance Specifications

Clin Chem. 2016 Dec;62(12):1639-1646. doi: 10.1373/clinchem.2016.261248. Epub 2016 Sep 27.

Abstract

Background: Levels of hemostasis factors vary between and within individuals as a result of genetic and environmental factors and analytical variation of the assays. The current state of the art for defining analytical precision requirements for analytical testing is based on this between- and within-individual (biological) variation. However, information on biological variation in hemostasis variables is still limited.The aim of this study was to determine the biological variation of coagulation variables involved in thrombosis and bleeding to provide a recommendation for performance specifications and to assess whether hemostasis assays fulfill the recommendation.

Methods: We performed a longitudinal study by repeated blood sampling (in total 13 times over a 1-year period) in 40 healthy individuals and measured prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, antithrombin, factor VIII, factor IX, von Willebrand factor (VWF), protein C, and protein S. We evaluated the effect of the biological variation on parameters of analytical variation and propose required performance specifications.

Results: Biological variation was highly different for various hemostasis variables: the within-subject variation ranged from 2.6% (PT) to 25.6% [VWF collagen binding (CB) activity], the between-subject variation varied from 4.1% (PT) to 31.2% (VWF:ristocetin cofactor acitivity), and the assay variation from 1.3% (PT) to 12.9% (VWF:CB).

Conclusions: With the reagents and analyzers used in this study, most of the hemostasis tests variables fulfill the current quality criteria for diagnosis and monitoring of routine hemostasis assays.

MeSH terms

  • Adult
  • Aged
  • Blood Coagulation
  • Female
  • Healthy Volunteers
  • Hemorrhage*
  • Hemostasis*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Thrombosis / blood*
  • Young Adult