NACB - Scientific Shorts
NACB - Scientific Shorts (formerly NACB Blog)
By Douglas F. Stickle, PhD
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 The American Chemical Society's Chemical & Engineering News recently had a cover story on use of filter paper bloodspots by big pharma, entitled "Drug development: dried blood spots could trump plasma" (1). The article followed two 2010 issues of the journal Bioanalysis that were devoted to the topic (2, 3). Incentives for bloodspot use in this context include efficient use of animals in preliminary ADME studies; additionally, there are potentially large cost savings in specimen management (collection, transport, storage) in conducting large population and clinical trials studies. The possibilities for use of this sample type are driven in part by the analytical capabilities of modern mass spectrometry techniques. For many analytes, it seems likely that aggregate data derived from bloodspots from among a large number of patients could provide a suitably accurate assessment of drug properties for drug development and approval studies. Use of this sample type in individual case management is another matter entirely, but the pharma studies may suggest new opportunities in this regard.

Bloodspots are known in lab medicine mostly because of their spectacularly successful use in newborn screening (some 4 million samples per year in the US), measuring scores of analytes via relatively simple procedures. Although procedures for bloodspot analysis have been reported for many analytes (e.g., those listed now years ago by Mei et al. (4)), there has been only limited implementation of bloodspots in routine practice in laboratory medicine outside of newborn screening. PKU monitoring is one common example; lead screening is more esoteric. Are there other examples in routine use? A recent Clin Chem paper describing %Hb A1c measurement in bloodspots might well find use in patient care (5).

A fundamental consideration regarding suitability of this sample type as applied to management of individual patients is whether the intention is for screening vs. quantitative analysis. Screening in infectious disease testing is essentially qualitative. Screening for metabolic disorders is based on quantitative assessment, but in a context in which abnormal findings for targeted disease states are in general expected to be pronounced. Quantitative analysis against cutoffs for concentrations among subjects that collectively present a stable, predictable continuum of observed concentrations (e.g., for therapeutic drug monitoring, for elevated blood lead levels) is a greater challenge when using bloodspots.
 
For quantitative analysis, there are multiple preanalytical factors affecting properties of bloodspots that cause an inherent degree of variability in the composition of punch samples relative to whole blood. The exact volume of blood per punch depends on patient-specific factors such as hematocrit; there is a certain amount of chromatographic separation of components on application of blood to filter paper; the exact means of collection (single drop vs. multiple drop) can affect punch properties. These are details for the clinical chemist to know about -- that a punch sample is not exactly a dried aliquot of whole blood. The preanalytical factors affecting the relation between bloodspot punches and whole blood aliquots may not be substantially important for certain analyses, but they may confound others. Hematocrit variation alone can be a substantial confounding factor for some analytes (6).
 
Given the known caveats, are there nonetheless additional applications of bloodspots that might be appropriate for lab medicine to pursue and provide? For instance, use of bloodspots for long-term monitoring of immunosuppressants would be desirable for some patients, especially for patients living in rural areas, if monitoring or pre-visit testing could occur without the patient having to visit a hospital or laboratory. This would appear to be a straightforward application of bloodspots. Technical aspects of the approach have been described by numerous papers and abstracts. Implementation is currently very limited, however.
 
Can additional development of testing by bloodspots as a routine sample type for certain analytes benefit patients or clinicians in service of patients? Could certain routine analyses by bloodspot benefit pediatric patients? Novel uses of filter paper specimens might apply to urine specimens as well (7). It is possible that the current pursuits of pharma to utilize bloodspots might eventually extend to new uses of bloodspots in general lab medicine.

 

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About the Author
Douglas F. Stickle, PhD
Douglas F. Stickle, PhD 
 

References

1. Chemical & Engineering News, 17 January 2011, pp. 13-17
2. Bioanalysis 2010;2(8):1343-4.
3. Bioanalysis 2010;2(11):1781.
4. Mei JV, Alexander JR, Adam BW, Hannon WH. Use of filter paper for the collection and analysis of human whole blood specimens. J Nutr 2001;131(5):1631S-6S.
5. Egier DA, Keys JL, Hall SK, McQueen MJ. Measurement of hemoglobin A1c from filter papers for population-based studies. Clin Chem 2011;57(4):577-85.
6. Deniff P, Spooner S. The effect of hematocrit on assay bias when using dried blood spots samples for the quantitative bioanalysis of drugs. European Bioanlysis Forum Workshop: Connecting Strategies on Dried Blood Spots, June 17-18, 2010, Brussels, Belgium

7. Meany DL, Clarke W. Opiate DAU screening using dried urine specimens. Clin Chim Acta. 2009;401(1-2):188-9.