An investigation of the pre-analytical variability in laboratory testing and its influence on result interpretation and patient management

Interpretation of laboratory tests in clinical practice is based on an understanding of the disease process within or between individuals. This is demonstrated by the variability of pathology results as compared to the previous result or against the reference range, made up from the intrinsic pathophysiological changes and also variation associated with the in vitro changes to the sample. My work is on identification and minimisation of the result variation in the pre-analytical phase, accounting for 60-70% of the errors associated with laboratory testing. The first project of my thesis is based on four studies that consider the in vitro stability of parathyroid hormone (PTH) and C-reactive protein (CRP), in which significant sample degradation is observed due to sample tube type, anticoagulant used and time to separation. The second project considers ethnic variation as a source of intra individual variation. Specifically considering intra individual ethnic variation in total cholesterol (TC) and high density lipoprotein cholesterol (HDLC), reporting significant differences were observed between Caucasian Indo-Asians in HDLC, in addition I investigated the relationship between low maternal vitamin B12 concentrations in Caucasian women and cord blood cholesterol. The third project considered the variation in laboratory results due to pre-existing conditions causing interference in common laboratory tests. I published on the effect of lipaemia on common laboratory tests, showing lipaemia does have a significant effect on laboratory tests. The following study found that the raised prolactin seen in rheumatoid arthritis is not artefactual but due to changes in cross reactivity due of prolactin subtypes. The final paper of this project shows, through a collection of case studies falsely elevated serum calcium levels in patients with paraproteinaemia