CLIN. CHEM.

24/11, 1966-1970 (1978)

Effect of In Vitro Hemolysis on Chemical Values for Serum

Joseph J. Frank, Edward W. Bermes, Margaret J. Bickel, and Bruce F. Watkins

Hemolysis in serum specimens is commonplace. This pared from leftover parts of specimens received in the labo-
study examines the effect of hemolysis on results of se- ratory for analysis, which had been collected with use of
lected chemical assays. Hemolysis was simulated by evacuated blood-collection tubes (15-mi Vacutainer Tubes;
adding hemolysate to serum to give hemoglobin concen- Becton-Dickinson Rutherford, N.J. 07070; cat. no. M3218).
trations of 90 to 2800 mg/liter and a rating by technologists The six serum pools so obtained were stored at -20 #{176}C until
of 0 to 4+ hemolyzed. The effect of hemolysis on values use, when they were thawed at room temperature and filtered
for some serum constituents, particularly acid phosphatase through Whatman No. 1 paper, (W. R. Balston, Ltd.).
and creatine kinase, was shown to be method dependent. Erythrocyte hemolysates were prepared from blood samples
Not unexpectedly, hemolysis most affects results for with disodium ethylenediaminetetraacetate as anticoagulant
lactate dehydrogenase. (Vacutainer Tube, cat. no. M3204QS). The erythrocytes,
separated by centrifugation, were washed three times with
isotonic saline and then lysed by adding an equal volume of
Hemolysis is a common cause of unsatisfactory serum
de-ionized water and 2.0mg of sodium saponin per milliliter
samples obtained for chemical analysis. In vitro, hemolysis
final volume. (In a control experiment, addition of saponin
can result from improper drawing and handling of specimens,
to serum was found not to affect the chemistry values ob-
or can occur during centrifugation and separation procedures.
tained.) The hemolysates were examined microscopically to
Even with proper use, an evacuated blood-collection tube can
ensure that all erythrocytes had been lysed. Sufficient he-
contain a specimen that is so slightly hemolyzed that hemol-
molysate was added to 20-ml portions of the pool (samples
ysis is visually undetectable from the color of the serum.
A-L) to equal the presence of 0, 0.125,0.25,0.50,0.75, 1.0,2.0,
Hemolysis can produce three sorts of effects: the release of
3.0.4.0,5.0,6.25, and 7.5ml of erythrocytes per liter of serum.
erythrocytic constituents can result in some increased values Aliquots of each sample were preserved with disodium citrate
for serum; there is some dilution, resulting in decreased values; monohydrate (final concentration, 10 g/liter) and stored at
and hemoglobin may interfere directly, e.g., in the colorimetric
-20 #{176}Cuntil assayed for acid phosphatase activity (within 48
quantitation of constituents. Caraway (1) reported that
h). Except for acid phosphatase activities, samples were an-
erythrocytes contain about 160-fold as much lactate dehy-
alyzed within 24 h as part of the normal laboratory routine.
drogenase, 67-fold as much acid phenyl phosphatase, 20-fold
Each 20-ml portion of the six pools (i.e., 72 samples) was an-
as much aspartate aminotransferase, and 23-fold as much
alyzed by all of the procedures detailed below.
potassium as does plasma. Dilution resulting from gross he-
The appearance of the sample was first qualitatively ranked
molysis might affect analyses for cholesterol esters, sodium,
by experienced laboratory technologists from no visible he-
and calcium because the erythrocyte/plasma concentration
molysis to 4+ hemolysis, and its hemoglobin concentration
ratio for these constituents is less than 0.11. Laessig et al. (2)
was determined by the benzidine method (5).
examined the effect on serum chemical values of adding 0.1
Electrolyte (Na+, K+, C1, HCO3-) concentrations were
and 1.0% intact or lysed erythrocytes. Nonhemolyzed cells
determined with the Stat Ion (Technicon Instruments Corp.,
were found to have little effect on test results.
Tarrytown, N.Y. 10591) with use of ion-selective electrodes
The current study correlates clinical chemical results with
for sodium, potassium, and chloride, and a titrimetric proce-
in vitro hemolysis as qualitatively evaluated by laboratory
dure for carbon dioxide.2 Sodium and potassium concentra-
technologists and as measured by increasing hemoglobin
tions were also determined with a flame photometer (IL 343;
concentration. This type of correlation results in more useful
Instrumentation Laboratory, Inc., Lexington, Mass. 02173).
data than could be obtained from previous studies in which
Serum iron concentration was determined by two methods,
the change in values were related to the percentage lysed
that used with the Du Pont aca (Du Pont Co., Wilmington,
erythrocytes in serum (2), or to hemoglobin concentration in
Del. 19898) and that of Henry et al. (6), in which bathophen-
serum (3, 4). Almost all the methods studied are currently in
anthroline dye binds to ferrous ions to form a colored complex.
wide use, and the results should be valuable in replacing data
In the former method, iron bound to transferrin is released
accumulated for methods that no longer are much used (4). under acidic conditions and reduced by hydroxylamine; in the
method of Henry et al., hot trichloroacetic acid is used to
Materials and Methods precipitate the proteins and free the iron, with hydrazine
To study the effect of in vitro hemolysis of whole blood, we sulfate acting as the reducing agent. Serum magnesium was
determined by both atomic absorption spectrophotometry (IL
added lysed erythrocytes to pooled specimens of serum, pre-
253) and by the method of Connerty et a!. (7) used with the
Departments of Pathology and of Biochemistry and Biophysics, Du Pont aca.
Loyola University Medical Center, Maywood, Ill. 60153. Aspartate aminotransferase (EC 2.6.1.1) activity was de-
This paper is based on an exhibit, which won the Gold Medal at the termined by the method of Henry (8) with use of reagents
ASCP-CAP meeting, Las Vegas, 1977.
Direct correspondence to this author (Clinical Laboratories).
Received Feb. 28, 1978; accepted Aug. 28, 1978. 2 Technicon Publication No. TK5-0301-00 (1975).

1966 CLINICAL CHEMISTRY, Vol. 24, No. 11, 1978

 Table 1. Results for Serum Electrolytes and Some Cationsa
HemoglobIn (qualitative) Change (0
0 trace 2+ 4+ - 4+)
Hemoglobin, mg/liter 90 320 1440 2800 U/liter
Stat Ion
Sodium, mmol/liter 143 143 143 143 0 0 0
Chloride, mmol/liter 108 108 109 109 +1 +1 0.5
Bicarbonate, mmol/liter 23.3 22.6 22.0 21.5 -1.8 -8 -2.2
Potassium, mmol/liter 4.3 4.4 4.7 5.1 +0.8 +19 10.9
Flame photometer
Sodium, mmol/liter 143 143 143 142 -1 -1 -0.5
Potassium, mmol/llter 4.3 4.4 4.7 5.0 +0.7 +16 7.9
aca
Iron, sg/Ilter 780 780 850 860 +80 +10 5.3
Magnesium, mmol/liter 1.7 1.7 1.8 1.7 0 0 0
Atomic absorption
Magnesium, mmol/liter 1.9 1.8 1.8 1.9 0 0 0
Manual-Henry
Iron, igIliter 820 830 890 1020 +200 +24 7.8
a Mean valuefor six pools.
b 95% confIdence lImits 1.81 for f-test.

Table 2. Enzyme Values a

Hemoglobin (qualitative) 0 trace 2+ 4+ Change (0 - 4+)
Hemoglobin, mg/liter 90 320 1440 2800 U/liter %
U/liter
Activity,
Aspartateaminotransferase
Du Pont aca 31 34 47 57 +26 +84 8.5
Gilford 3500 32 32 41 54 +22 +69 4.6
(Dade Reagents)
Lactate dehydrogenase
Du Pont aca 184 207 320 448 +260 +143 14.9
Gilford 3500 170 194 301 434 +264 +155 15.0
(Dade Reagents)
a-Hydroxybutyrate dehydrogenase
Du Pont aca 267 309 481 677 +440 +153 14.9
Creatine kinase
Du Pont aca 57 66 98 131 +74 +130 6.8
Gilford 3500
(Worthington Reagents) 57 57 62 77 +20 +35 2.7
Acid phosphatase
Du Pont aca 0.18 0.18 0.19 0.22 +0.04 +22 0.5
Bodansky C 0.41 0.41 0.43 0.47 +0.06 +15 -
Bessey, Lowry, Brock 0.19 0.24 0.41 0.79 +0.6 +315 9.1
a Mean valueofsix pools in U/liter.
b 95% confidence limits 1.81 for f-test.
C Assayed In only two pools.

from two manufacturers, Du Pont (aca) and Dade (Miami,
Fla. 33152), with a Model 3500 Analyzer (Gilford Instruments,
Oberlin, Ohio 44074). Lactate dehydrogenase (EC 1.1.1.27)
activity was measured with the DuPont aca and the Gilford
3500 (Dade reagents) by the method of Wacker et al. (9) as
modified by Gay et al. (10). 3-Hydroxybutyrate dehydroge-
nase (EC 1.1.1.30) activity was measured with the DuPont aca
by an adaptation of the Rosalki and Wilkinson technique (11).
Creatine kinase (EC 2.7.3.2) activity was determined by
similar methods based on modifications of the procedures of
Oliver (12) and Rosalki (13). The two methods, Du Pont aca
and Statzyme CPK-n-1 (Worthington Diagnostics, Freehold,
N.J. 07728), used with a Gilford 3500, differed only in the in-
hibitor used to prevent increased apparent creatine kinase
activity caused by adenylate kinase (EC 2.7.4.3), a constituent
of erythrocytes (14).
Acid phosphatase (EC 3.1.3.2) activity was measured by
three different methods. In two of the procedures-that of
Roy eta!. (15), used with the Du Pont aca, and that of Bed-
ansky (16)-thymolphthalein phosphate and iI-glycerophos-
phate, respectively, are used as substrates. These compounds
are specific substrates for the prostatic isoenzyme. In the third
method, that of Bessey et al. (17), p-nitrophenyl phosphate
is used as substrate. This substrate is cleaved by other phos-

CLINICAL CHEMISTRY, Vol. 24, No. 11, 1978 1967

 QUALITATIVE HEMOLYSIS
TRACE + ++ +++
HEMOGLOBIN (mg/L)
37 370 570 990 197 3200
Fig. 1. Qualitative evaluationof hemolysis and quantitation
of hemoglobin concentration

transferase values showed significant increases. There was also

phatases these conditions. However, tartrate added to
under
the buffer system selectively inhibits the prostatic isoen- a drop (22%) in apparent total bilirubin concentration.
zyme.
Results were also obtained by continuous-flow analysis Discussion
(SMA 12/60; Technicon). The analytical methods are indi- Our results agree with those found by previous investigators
cated in the legend to Figure 3. (1,2). Changes were minimal for these tests affected only by
dilution, because the increase in volume for a grossly hemo-
lyzed specimen was only 1.5%. The increase in hemoglobin.
Results concentration at this concentration of added lysed erythro-
The analyses for free hemoglobin in the aliquots of the six cytes (7.5mlfliter) was 2710 mg/liter. The expected increase
serum pools indicated mean values of 90 to 2800 mg of he- would be 2550mg of hemoglobin per liter, based on an average
moglobin per liter for 0 to 7.5 ml of added lysed erythrocytes concentration of 340 g of hemoglobin per liter in erythrocytes
per liter of serum, a range evaluated by the technologists as (1). The serum sample with this elevated hemoglobin con-
0 to 4+ hemolysis. centration was bright red and clearly was grossly hemolyzed.
Table 1 summarizes the serum electrolyte values. Potassium Addition of 0.75 ml of lysed erythrocytes per liter of serum
values were most affected, in direct proportion to the amount made it faint red, with a hemoglobin concentration of 320
of hemolysate added, the average increase in potassium con- mg/liter, the lowest concentration consistently categorized
centration being 0.75 mmolfliter for hemoglobin concentra- by the technologists as trace hemolysis. Although the color
tions from 90 to 2800 mg/liter, or about 1.2-fold. There was differences in the samples prepared for the study are subtle
also a 7.5% decrease in bicarbonate concentration. Included (Figure 1), most experienced technologists were able to cate-
in Table 1 is serum iron, which increased in concentration by gorize the samples as trace, 1+, 2+, 3+, 4+, or grossly he-
as much as 24%, depending on the methodology used. molyzed. This description can be valuable in the interpreta-
Table 2 summarizes the mean values for enzyme activities. tion of chemical results obtained on such samples (Tables
By either procedure we used, lactate dehydrogenase appears 1-3).
to be most sensitive to hemolysis; hydroxybutyrate dehy- In looking at the data presented in the tables, the reader
drogenase (heart-associated fraction of lactate dehydrogenase) should not attach undue importance to the percentage in-
reflects the same sensitivity. The increase of 260 U of lactate crease or decrease in concentration or activity. Concentration
dehydrogenase per liter resulted in a 2.5-fold higher enzyme change is more important since it is relatively independent
activity at 2800 mg of hemoglobin per liter of serum than at of the baseline concentration of any constituent.
90 mg/liter A modest increase of 24 U/liter in aspartate ami- There were major changes in potassium, bicarbonate, and
notransferase activity was nevertheless a twofold increase in iron concentrations. The average potassium increase (Table
this enzymes activity in serum. Creatine kinase and acid 1) of 0.75 mmolfliter is exactly what would be expected, based
phosphatase both demonstrate a definite methodological on a potassium concentration of 100 mmol/ literin erythro-
difference in results. For acid phosphatase measured with cytes (1). This increase, perhaps less than one might intui-
prostatic isoenzyme-specific substrates, there was a negligible tively expect with 5+ hemolysis, indicates that lesser degrees
increase in enzyme activity, whereas the increase in total acid of hemolysis would probably be cause for concern only for
phosphatase activity was fourfold. For creatine kinase, the values at the extremes of the normal range. Plasma samples
increase in enzyme activity as measured with the Gilford 3500 behave similarly but, as expected, have a lower initial potas-
(Worthington reagents) was 1.4-fold, whereas that on the Du sium concentration (18). The 8% decrease in bicarbonate
Pont aca was 2.3-fold. concentration measured with the Stat Ion probably reflects
Table 3 summarizes values obtained with the SMA 12/60. the colorimetric end-point of the titration (ratio of readings
In most instances, little or no change was observed; however, at 435 and 500 nm), because the concentration of total CO2
as expected, lactate dehydrogenase and aspartate amino- measured with a pH electrode is unaffected by hemolysis (19).

1968 CLINICAL CHEMISTRY, Vol. 24. No. 11, 1978

 Table 3. Values Obtained on Continuous-Flow Analysis8
Hemoglobin (qualitative)
0 trace 2+ 4+ Change (0 - 4+)
Hemoglobin, mg/liter 90 320 1440 2800 u/liter
1. Calcium, mg/liter 93 93 94 93 0 0 0
2. Inorganic phosphorus, mg/liter 38 39 39 39 +1 +2 1.6
3. Glucose, mg/liter 1130 1140 1140 1140 +10 +1 0.23
4. Urea nitrogen, mg/liter 182 182 182 182 0 0 0
5. Uric acid, mg/liter 55 55 56 56 +1 +2 0.7
6. Albumin, g/liter 39 39 39 39 0 0 0
7. Alkaline phosphatase, U/liter 60 60 60 60 0 0 0
8. Cholesterol, mg/liter 2060 2090 2120 2130 +70 +3 0.6
9. Total protein, g/liter 70 71 72 72 +2 +3 1.6
10. Totalbilirubin,
mg/liter 5.2 4.8 4.6 4.1 -1.1 -28 3.6
11. Lactate dehydrogenase, U/liter 179 201 318 424 +245 +137 18.3
12. Aspartate aminotransferase, U/liter 36 38 48 60 +24 +66 9.7
a Values are means for six pools.
b 95% confIdence lImits 1.81 for t-test.

1. CalcIum, Technicon MethodNo.SF4-0003FE5, cresophthalein complexone.

2. Inorganicphosphorus,Technlcon Method No. SF4-0004FE5, phosphomolybdicacid.
3. Glucose Biodynamics/bmc, Indianapolis, IN 46250. Trinder method.
4. Urea nitrogen. Technicon Method No. SF4-0001FF5,diacetyl monoxime.
5. UrIc Acid, Technicon Method No. SF4-0013FJ5,phosphotungstate.
6. Albumin, Technicon Method No. SF4-0030FE5, bromcresol green.
7. Alkaline phosphatase, Technlcon Method No. SF4-0006FG5, Bessey, Lowry and Brock, automated by Morgenstern.
8. Cholesterol, Blodynamics/bmc, Indianapolis, Ind. 46250, Trlnder method.
9. Total protein, Technicon Method No. SF4-0014FJ5,bluret.
10. Total bilirubin. Technicon Method No. SF4-0018FF5, Jendrassik and &of. automated by Gambino.
11. Lactate dehydrogenase, Technicon Method No. SF4-0021FF5, 340 nm.
12. Aspartate amlnotransferase. Technicon Method No. SF4-OO1OFJ5.340 nm.

Iron concentration as measured by the Du Pont aca and Measurement of creatine kinase, which is not a constituent
Henry (7) methods exhibited 10 and 24% increases, respec- of erythrocytes (20), is interfered with because adenylate ki-
tively, in grossly hemolyzed samples (Figure 2). In Henrys nase is released from erythrocytes by hemolysis. As can be seen
method the greater increase might be attributedto the use of in Figure 3, the competitive inhibitor, adenosine monophos-
hot trichloroacetic acid to release iron from transferrin, re- phate, used in the Worthington reagents is a more effective
sulting also in the release of a small percentage (<2%) of the inhibitor of this interfering enzyme than is fluoride, a non-
heme iron. The results obtained from measurement of the competitive inhibitor used with the aca. Recent work has in-
concentration of sodium (serum [Nai/erythrocyte [Na+] = dicated that using adenosine monophosphate in combination
8.75; 1), calcium (serum [Ca2]/erythrocyte [Ca2J = 10; 1), with diadenosine pentaphosphate results in superior inhibi-
magnesium (serum [Mg2]/erythrocyte [Mg2-i = 0.35; 18) and tion of adenylate kinase (14, 21).
chloride (serum [Clj/erythrocyte [C1] = 2; 1) were unaf- The apparent decrease in total bilirubin observed with the
fected by hemolysis, even at the 4+ level (2800 mg per liter) SMA 12/60 is artifactual. Hemoglobin can compete with ni-
of hemoglobin. trite for sulfanilic acid (22), and methemoglobin formation
Of the enzymes studied, aspartate aminotransferase, lactate is known to affect the diazotization procedure (23).
dehydrogenase, and hydroxybutyrate dehydrogenase gave Another problem, not assessed in this study but which may
uniform results with the methodologies tested. Lactate de-
hydrogenase best reflects the degree of hemolysis by its in- 2600
creased activity. Also, the increase in lactate dehydrogenase 2400

activity resulting from the addition of 7.5 ml of lysed eryth- 2200 . ,apwr. ET AL.

rocytes per liter (2710 mg of hemoglobin per liter) is 264 UI 2000 OACA

liter, about 10-fold the increase of 23 U/liter found for the $00

addition of 0.75 ml of lysed erythrocytes (230 mg of hemo- 600

globin per liter). This approximate relationship was found in I400

most values significantly affected by hemolysis. 1200

1000 -a--.-
Differences attributable to methodology were found in the 0
5 80<
measurement of both acid phosphatase and creatine kinase.
600
The method of Bessey et al., which measures both erythrocyte
400
and prostatic acid phosphatase isoenzymes, exhibited a
200
fourfold increase over the range of hemolysis examined,
whereas those procedures in which substrates (thymo- 0 400 $00 200 1600 2000 2400 2600

phthalein phosphate and 3-glycerophosphate) with great MEMOG&.061N

(MG/LI
specificity for prostatic isoenzyme (15) are used showed only t 1 1 C C
modest increases. The percentage increase in total acid TRACE + ++ +4+ +4+4

QUALITATIVE HEMOLYS1S
phosphatase activity was probably enhanced by the initial
enzyme activity of the serum pools, which was at the low end Fig. 2. Effectof increasingconcentration of hemolysate on
of the normal range. serum iron concentration

CLINICAL CHEMISTRY, Vol. 24, No. 11, 1978 1969

 H., The effects of 0.1 and 1.0 per cent erythrocytes and heniolysia on
serum chemistry values. Am. J. Clin. Pathol. 66,639(1976).
#{149}
OI$O 2800 - 80RDU4G10N 3. Sclwartz, M., Interferences in diagnostic biochemical procedures.
O ACA
Adu. Clin. Chem. 16, 1(1973).
4. Brydon,W. G., and Roberts, L. B., The effect of haemolysis on the
determinationof plasma constituents. Clin. Chim. Acta 41, 435
(1972).
5. Crosby, W. H., and Furth, F. W., A modification of the benzidine
method formeasurement ofhemoglobininplasma and urine. Blood
11,380 (1956).
6. Henry, R. J., Sobs!, C., and Chiamori, N., On the determination
I of serum iron and iron-binding
(1958).
capacity.Clin. Chirn. Acta 3, 523

1200 1600 2000 2400 2800

7. Connerty,H. V.,Lau, H. S.C.,and Briggs, A. R., Spectrophoto-
OGLOS1N (MG/U metric determination of magnesium by use of methylthymol blue.
C C C C C Clin. Chem. 17,661(1971).
TRACE + +4 8. Henry, R. J., Chiamari, N., Golub, 0. J., and Berkman, S., Revised
QUAUWNE HEMOLYSS spectrophotometric methods for the determination of glutamic-
oxalacetic transaminase, glutamic-pyruvic transaminase and lactic
Fig. 3. Methodological difference in serum creatine kinase ac-
tivity with increasing concentration of added hemolysate acid dehydrogenase. Am. J. Clin. Pat hol. 34,381 (1960).
9. Wacker, W., Ulmer, D., and Vallee, B., Metalloenzymes and
myocardial infarction. II. Malic and lactic dehydrogenase activities
lead to major alterations in chemistry values, relates to the and zinc concentrations in serum. N. EngI. J. Med. 255,449(1956).
length of time the serum remains exposed to the clot. To assess 10. Gay, R., McComb, R., and Bowers, G., Optimum reaction con-
ditions for human lactate dehydrogenase isoenzymes as they affect
the magnitude of this type of problem, we drew two blood
total lactate dehydrogenase activity. GUn. Chem. 14,740(1968).
samples; the specimen in tube 1 was allowed to clot for 1 h
11. Rosalki, S. B., and Wilkinson, J. H., Serum hydroxybutyrate
before the serum was separated whereas that in tube 2 was dehydrogenase in diagnosis. J. Am. Med. Assoc. 189,61 (1964).
allowed to lie on its side for 24 h before the serum was sepa-
12. Oliver, L T., A spectrophotometric method for the determination
rated. The samples were analyzed with the SMA 12/60 and of creatine phosphokinase myokinase. Biochem. J. 61,116 (1955).
for potassium. Tube 2 (24 h) showed significant increases in 13. Rosalki, S. B., An improved procedure for serum creatine phos-
inorganic phosphorus (232%), lactate dehydrogenase (23%), phokinase determination. J. Lab. Clin. Med. 69,696 (1967).
and potassium (67%), and a decrease in glucose (82%), as 14. Szasz,G., Gerhardt,W., Gruber, W., and Bernt, E., Creatine ki-
compared to the other sample (tube 1). Neither specimen was nasa in serum: 2. Interference of adenylate kinase with the assay. Clin.
visibly hemolyzed, but tube 2 had a modestly increased he- Chem. 22, 1806 (1976).
moglobin concentration (to 200 mg/liter). This type of effect 15. Roy, A. U., Brower, M. E., and Hayden, J. E., Sodium thymo-
should not be overlooked when one is confronted with spu- phthalein monophosphate: A new acid phosphatase substratewith
riously abnormal values. greaterspecificity for the prostatic enzyme in serum. Clin. Chem. 17,
1093 (1971).
Our results indicate that the overall effect of hemolysis can
be quite significant, causing large increases in certain clinical 16. Henry, R. J., Clinical Chemistry: Principles and Technics, 1st.
ed., Harper and Row, New York, N.Y., 1965, p 486.
chemical values and in particular in enzyme activities. The
17. Bessey, 0. A., Lowry, 0. H., and Brock, M. J., A method for the
ability of technologists to assessthe degree of hemolysis (trace
rapid determination of alkaline phosphatase with five cubic milliliters
to 4+) and therefore evaluate the degree of interference with of serum. J. Biol. Chem. 164,321 (1946).
specific tests can, if used properly, aid in the formulation of 18. Tietz, N. W., Electrolytes. In Fundamentals of Clinical Chem-
decisions as to whether to redraw a specimen. It should also istry, 2nd ed., N. Tietz,Ed.,W. B. Saunders, Philadelphia, Pa., 1976,
be clear that care must be taken in assessing the effect of he- p 873.
moglobin or hemolysis on laboratory results, because different 19. Hicks, J. M., Aldrich, F. T., and Iosefsohn, M., An evaluation of
methods for the same analyte can lead to a dramatic variation the Beckman Chloride/Carbon Dioxide Analyzer. Clin. Chem. 22,
in results. This type of information is especially important in 1868 (1976).
interpreting the chemistry values of timed samples, which 20. Kachmar, J. F., and Moss, D. W., Enzymes. In Fundamentals of
obviously cannot be redrawn. Clinical Chemistry, 2nd ed., N. Tietz, Ed., W. B. Saunders, Phila-
delphia, Pa., 1976, p 583.
21. Szasz, G., Gerhardt, W., and Gruber, W., Creatine kinase in serum:
Supported in part by NIH Research Training Grant in Clinical 3. Further study of adenylate kinase inhibitors. Clin. Chem. 23,1888
(1977).
Chemistry 5 TO! GM02112-04.
22. Caraway, W. T., and Kammeyer, C. W., Chemical interference
References by drugs and other substances with clinical laboratory test procedures.
Clin. Chim. Acta 41, 395 (1972).
1. Caraway, T. W., Chemical and diagnostic specificity of laboratory 23. McGann, C. J., and Carter, R. E., The effect of hemolysis on the
tests.Am. J. Clin. Pathol. 37, 445 (1962). Van den Bergh reaction for serum bilirubin. J. Pediat. 57, 199
2. Laessig, R. H., Hassemer, D. J., Paskey, T. A., and Schwartz, T. (1960).

1970 CLINICAL CHEMISTRY, Vol. 24, No. 11, 1978