Answering your questions; Heparin drawing tubes.

Q What is the difference between sodium heparin and lithium heparin tubes when drawing for a digoxin? I have been taught to draw all drug levels in a plain top red tube with no gel separator. We have an Axsym, and it says to use serum or sodium heparin. We only have lithium heparin tubes.

A The use of anticoagulants allows for the analysis of whole-blood specimens or plasma constituents obtained by centrifugation and separation of plasma. Generally, lithium heparin is added in small quantities and has been found to have little, if any, effect on the determination of many different analytes, in contrast to calcium chelator anticoagulants, such as calcium citrate or calcium oxalate. Included in the extremely long list of analytes for which lithium heparin is recommended is digoxin. (1) The sodium salt of heparin may also be used in place of lithium heparin, with the exception of analysis of sodium itself. (1) Specifically, sodium heparin is not known to affect the determination of digoxin, nor are EDTA or citrate. (2) The actual volume of anticoagulant used in a collection tube may cause some degree of fluid shift from the cells in the blood to the plasma. This is, however, a negligible effect. (1) Since the two anticoagulants may be used interchangeably when determining digoxin levels, no specific literature exists as to which anticoagulant offers a more exact determination.

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Gel separators consist of silicone gel material that is integrated into the base of the tube. This material causes the isolation of serum from whole blood during the centrifugation process. (1) Centrifugation of the tube causes a temporary alteration in the gel's specific gravity so that it is intermediate to that of the red-blood cells and the serum. (1) As a result, when the gel hardens, it forms a barrier that separates serum from red-blood cells. Generally, gel separator tubes are discouraged when measuring therapeutic drug levels, since it is claimed that drugs will slowly adsorb onto the gel surface, especially when stored for a period of time prior to testing. (3) Digoxin levels in plain tubes (red tops) versus levels obtained in gel separator tubes were compared, showing no significant difference. (4), (5) A difference was seen, however, in the level of other therapeutic drugs, such as tricyclic antidepressants. (4)

In short, there is no body of evidence to suggest that sodium or lithium heparin tubes affect the determination of digoxin levels. Also, gel separator tubes may be used to collect blood for digoxin levels, but they are not suitable for all therapeutic-drug determinations.

--Frank Cruz, III, MD

Department of Pathology

Oregon Health and Science University

Portland, OR

References

(1.) Henry, JB, ed. Clinical Diagnosis and Management by Laboratory Methods, 20th ed. W.B. Saunders Company, Philadelphia, 2001.

(2.) Young, DS. Effects of Preanalytical Variables on Clinical Laboratory Tests. 2nd ed. Washington DC: American Association of Clinical Chemistry; 1997: 3-180-181.

(3.) Koch, TR, et al. Suitability of collection tubes with separator gels for therapeutic drug monitoring. Ther Drug Monit. Vol 12.(3), 1999:277-280.

(4.) Dasgupta, A., et al. Time-Dependent Absorption of Therapeutic Drugs by the Gel of the Greiner Vacuette Blood Collection Tube. Ther Drug Monit 2000; 22,(4):427-431.

(5.) Datta P. Stability of digoxin and digitoxin in specimens collected in blood collection tubes containing serum separator gels. Clin Biochem. 1998; 31:273-275.

Edited by Daniel M. Baer, MD

Daniel M. Baer, MD, is professor emeritus of laboratory medicine at Oregon Health and Science University in Portland, OR, and a member of MLO's editorial advisory board.

Daniel M. Baer, MD, is professor emeritus of laboratory medicine at Oregon Health and Science University in Portland, OR, and a member of MLO's editorial advisory board.