Establishing reference intervals in the coagulation laboratory

Abstract

Introduction: Obtaining a reference interval (RI) is a challenge for any laboratory and becomes more complicated in the coagulation laboratory due to testing on samples with limited stability on reagents that are poorly standardized. Reference intervals are required to be able to evaluate results in relation to a patients' hemostatic disorder. This becomes one of the most important tasks conducted in the coagulation laboratory. However, many laboratories lack the time, finances and in many cases the expertise to conduct this study.

Methods: Many RI are obtained from package inserts, or from publications written by experts in lieu of laboratories conducting their own studies. An overview of validating reference intervals and options for verifying or transference of reference intervals is discussed.

Results: Based on the confidence interval and the acceptability of risk laboratories are willing to accept, coagulation laboratories have options to conduct robust studies for their RI. Data mining or global reference studies may help to provide data for age specific ranges.

Conclusions: Pre-analytical variables and selection of healthy subjects have the largest impact on coagulation testing outcomes and need to be well controlled during the establishment of reference intervals. Laboratories have options in lieu of conducting a full validation on how to verify RI based on smaller RI studies or transference of RI after determining compatibility of the original RI study.

Keywords: coagulation; reference interval; validation; verification.