Abstract
Perhaps the most important lesson offered by this book is that we should not accept manufacturers’ claims about the extent of interference in analytical methods, or interference indices measured by our analysers, at face value. It is stated on the flysheet that this book is Volume 5 in a series on Patient Safety and we are reminded that interference in our laboratory methods can have a significant impact on patient safety if it goes unrecognized. In the preface and throughout the text, it is reinforced that we have a responsibility to patients to ensure that we know the extent to which every individual test we perform is affected by icterus and lipaemia. We are also advised that we should have a policy in place that states how we report results when we know that they have been affected by endogenous interferents.
The title indicates that interference in icteric, lipaemic and turbid samples is addressed; however, the term ‘turbidity’ is used interchangeably in the text with ‘lipaemia’, without apology for dismissing the effects of hypergammaglobulinaemia. Interference from haemolysis is not discussed, although the phenomenon of intravascular haemolysis would presumably bring interference from haemoglobin into the realm of significant endogenous interferents.
Chapters 1 to 5 discuss accuracy goals for laboratory tests, the nature of icteric and lipaemic interference (focusing on their impact on assays using spectrophotometric detection) and the ways interference can be detected. Within Chapter 2 there is a detailed description of spectrophotometry, in which Beer’s law is written, confusingly, ‘A = abC’, without mention of the term ‘extinction coefficient’. Later in the book, Beer’s law is written in the conventional format A = ɛlc, but it is incorrectly stated that ‘extinction coefficients are in units of per Mole/L for a path length of 1 cm’. There is much repetition in this chapter; I found it very badly structured and also poorly written, with many errors. For example, it is stated that ‘bilirubin is unique in that it absorbs light without the need for reaction’ – what about haemoglobin, or carotene, or porphyrins? How many endogenous chromophores can one name? It was with a wary and critical eye that I read the rest of the book.
Information given in kit inserts is scrutinized and the authors highlight the very valid point that interference studies performed by spiking specimens with ditaurobilirubin (a synthetic form of conjugated bilirubin) and with Intralipid (an emulsified fat preparation made from soybeans) may not accurately reflect interference caused by the complex mixture of conjugated, albumin-bound and free bilirubin in jaundiced patients’ samples or by the complex mixture of triglycerides, chylomicrons and lipoproteins in a lipaemic patient’s samples. They also point out that the lipaemia and icterus indices that automated analysers report are not standardized and are not commutable from one platform to another. Suggestions are made of ways in which laboratories can conduct their own investigation into interference in automated assays. Reference is made to Clinical and Laboratory Standards Institute (CLSI) guidelines for interference testing and there are some very rudimentary and confusing examples of protocols for using these guidelines; I could only conclude that I would rather consult the guidelines themselves.
Chapters 6 and 7 attempt to summarise the clinical origin of jaundice and describe the various forms of circulating bilirubin (conjugated, free unconjugated, unconjugated bilirubin non-covalently and covalently bound to albumin) and their spectral properties, as well as their potential for chemical interference from chemical reaction with assay intermediates. Chapters 8 and 9 aim to do the same for lipaemia; listing conditions associated with chylomicronaemia, hypertriglyceridaemia, etc. and describing the different light scattering properties of various lipids and lipoproteins. Unfortunately, I found these chapters incredibly difficult to read and peppered with errors, e.g. ‘The rise of bilirubin in infants results from … an increased absorbance of bilirubin by the intestines because infants lack the same bacteria as adults that degrade bilirubin … and haemolytic disease of the newborn … and an immature liver’ – there is no mention of a newborn’s relative polycythaemia and increased red cell turnover, despite those factors being described in the paper referred to by the authors.
Chapters 10 to 12 contain some very detailed statistical analyses of complex interference and illustrate that interference in an analytical method from icterus or lipaemia is not necessarily linear. Using the phenomenon of variable interference from bilirubin in several serum creatinine assays, a very useful and detailed description is given of the statistical methods for determining at what concentration of analyte, and what concentration of interferent, the degree of interference becomes statistically significant. Finally, the authors describe different strategies a laboratory may use to communicate the finding of interference in a laboratory test to the requesting clinician and patient, again emphasizing that accurate communication is key to patient safety.
I found this book to be a very frustrating read. It is a useful book, in that it presents a number of valid points and refers to an array of useful (and mostly historical) publications on the subject of interference in laboratory tests. However, I cannot recommend it in its current form to anyone preparing for FRCPath as I feel it contains too many errors. I found myself constantly searching on PubMed and Google for the original publications referenced by the authors in a bid to verify their information. It is also very difficult to read as it is badly structured and contains much repetition. This is really unfortunate, because the subject is an important one and one that is very relevant to laboratories working towards accreditation against ISO15189.