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 study examines the effect of hemolysis on results of selected chemical assays. Hemolysis was simulated by adding hemolysate to serum to give hemoglobin concentrations of 90 to 2800 mg/liter and a rating by technologists of 0 to 4+ hemolyzed. The effect of hemolysis on values
for some serum constituents, particularly acid phosphatase and creatine kinase, was shown to be method dependent.

Not unexpectedly, hemolysis most affects results for lactate dehydrogenase.

Hemolysis is a common cause of unsatisfactory serum

samples obtained for chemical analysis. In vitro, hemolysis

can result from improper drawing and handling of specimens, or can occur during centrifugation and separation procedures. Even with proper use, an evacuated blood-collection tube can contain a specimen that is so slightly hemolyzed that hemolysis is visually undetectable from the color of the serum. Hemolysis can produce three sorts of effects: the release of erythrocytic constituents can result in some increased values for serum; there is some dilution, resulting in decreased values; and hemoglobin may interfere directly, e.g., in the colorimetric quantitation of constituents. Caraway (1) reported that erythrocytes contain about 160-fold as much lactate dehydrogenase, 67-fold as much acid phenyl phosphatase, 20-fold as much aspartate aminotransferase, and 23-fold as much potassium as does plasma. Dilution resulting from gross hemolysis might affect analyses for cholesterol esters, sodium, and calcium because the erythrocyte/plasma concentration ratio for these constituents is less than 0.11. Laessig et al. (2) examined the effect on serum chemical values of adding 0.1 and 1.0% intact or lysed erythrocytes. Nonhemolyzed cells were found to have little effect on test results. The current study correlates clinical chemical results with in vitro hemolysis as qualitatively evaluated by laboratory technologists and as measured by increasing hemoglobin concentration. This type of correlation results in more useful data than could be obtained from previous studies in which the change in values were related to the percentage lysed erythrocytes in serum (2), or to hemoglobin concentration in serum (3, 4). Almost all the methods studied are currently in wide use, and the results should be valuable in replacing data accumulated for methods that no longer are much used (4).

Materials and Methods

To study the effect of in vitro hemolysis

of whole blood, we

added lysed erythrocytes to pooled specimens of serum, preDepartments of Pathology and of Biochemistry and Biophysics, Loyola University Medical Center, Maywood, Ill. 60153. This paper is based on an exhibit, which won the Gold Medal at the ASCP-CAP meeting, Las Vegas, 1977. Direct correspondence to this author (Clinical Laboratories). Received Feb. 28, 1978; accepted Aug. 28, 1978. 1966 CLINICAL CHEMISTRY, Vol. 24, No. 11, 1978

pared from leftover parts of specimens received in the laboratory for analysis, which had been collected with use of evacuated blood-collection tubes (15-mi Vacutainer Tubes; Becton-Dickinson Rutherford, N.J. 07070; cat. no. M3218). The six serum pools so obtained were stored at -20 #{176}C until use, when they were thawed at room temperature and filtered through Whatman No. 1 paper, (W. R. Balston, Ltd.). Erythrocyte hemolysates were prepared from blood samples with disodium ethylenediaminetetraacetate as anticoagulant (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 de-ionized water and 2.0mg of sodium saponin per milliliter final volume. (In a control experiment, addition of saponin to serum was found not to affect the chemistry values obtained.) The hemolysates were examined microscopically to ensure that all erythrocytes had been lysed. Sufficient hemolysate was added to 20-ml portions of the pool (samples A-L) to equal the presence of 0, 0.125,0.25,0.50,0.75, 1.0,2.0, 3.0.4.0,5.0,6.25, and 7.5ml of erythrocytes per liter of serum. Aliquots of each sample were preserved with disodium citrate monohydrate (final concentration, 10 g/liter) and stored at -20 #{176}C until assayed for acid phosphatase activity (within 48 h). Except for acid phosphatase activities, samples were analyzed within 24 h as part of the normal laboratory routine. Each 20-ml portion of the six pools (i.e., 72 samples) was analyzed by all of the procedures detailed below. The appearance of the sample was first qualitatively ranked by experienced laboratory technologists from no visible hemolysis to 4+ hemolysis, and its hemoglobin concentration was determined by the benzidine method (5). Electrolyte (Na+, K+, C1, HCO3-) concentrations were determined with the Stat Ion (Technicon Instruments Corp., Tarrytown, N.Y. 10591) with use of ion-selective electrodes for sodium, potassium, and chloride, and a titrimetric procedure for carbon dioxide.2 Sodium and potassium concentrations were also determined with a flame photometer (IL 343; Instrumentation Laboratory, Inc., Lexington, Mass. 02173). Serum iron concentration was determined by two methods, that used with the Du Pont aca (Du Pont Co., Wilmington, Del. 19898) and that of Henry et al. (6), in which bathophenanthroline dye binds to ferrous ions to form a colored complex. In the former method, iron bound to transferrin is released under acidic conditions and reduced by hydroxylamine; in the method of Henry et al., hot trichloroacetic acid is used to precipitate the proteins and free the iron, with hydrazine sulfate acting as the reducing agent. Serum magnesium was determined by both atomic absorption spectrophotometry (IL 253) and by the method of Connerty et a!. (7) used with the Du Pont aca.

Aspartate aminotransferase
termined
2

by the method Publication

(EC 2.6.1.1) activity was deof Henry (8) with use of reagents
(1975).

Technicon

No. TK5-0301-00

Table 1. Results for Serum Electrolytes and Some Cationsa

HemoglobIn Hemoglobin, (qualitative) mg/liter 0 90 trace 320 2+ 1440
4+

2800

Change (0 U/liter

4+)

Stat Ion

Sodium, mmol/liter
Chloride, Potassium, mmol/liter mmol/liter

Bicarbonate, mmol/liter Flame photometer

Sodium, mmol/liter Potassium, mmol/llter

143 108 23.3

4.3
143

143 108 22.6

4.4

143 109 22.0

4.7

143 109 21.5

5.1

0 +1 -1.8
+0.8

0 +1 -8
+19

0 0.5 -2.2 10.9 -0.5 7.9 5.3 0 0 7.8

4.3 780
1.7

143 4.4 780

1.7

143 4.7 850

1.8

142 5.0 860

1.7

-1 +0.7 +80 0 0 +200

-1 +16 +10 0 0 +24

aca

Iron, sg/Ilter
Magnesium, mmol/liter
Atomic absorption

Magnesium, mmol/liter Manual-Henry

1.9 820

1.8 830

1.8 890

1.9 1020

Iron, igIliter
Mean value for six pools. b 95% confIdence lImits 1.81 for f-test.
a

Table 2. Enzyme Values a

Hemoglobin (qualitative) Hemoglobin, mg/liter 0 90 trace 320 2+ 1440 4+ 2800

Change (0 U/liter

4+)

Activity, U/liter

Aspartate aminotransferase Du Pont aca

Gilford 3500
(Dade Reagents)

31 32

34 32

47 41

57 54

+26 +22

+84 +69

8.5 4.6

Lactate dehydrogenase Du Pont aca

Gilford 3500 (Dade Reagents)

a-Hydroxybutyrate Du Pont aca Creatine kinase Du Pont aca dehydrogenase

184 170

207 194

320 301

448 434

+260 +264

+143 +155

14.9 15.0

267 57 57 0.18 0.41 0.19

309 66 57 0.18 0.41 0.24

481 98 62 0.19 0.43 0.41

677 131 77 0.22 0.47 0.79

+440 +74 +20 +0.04 +0.06 +0.6

+153 +130 +35 +22 +15 +315

14.9 6.8 2.7 0.5

-

Gilford 3500
(Worthington Reagents) Acid phosphatase Du Pont aca
Bodansky
a Mean
C

Bessey, Lowry, Brock

value ofsix pools in U/liter. b 95% confidence limits 1.81 for f-test. C Assayed In only two pools.

9.1

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 dehydrogenase (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 inhibitor 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 Bedansky (16)-thymolphthalein phosphate and iI-glycerophosphate, 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 phosCLINICAL CHEMISTRY, Vol. 24, No. 11, 1978

1967

QUALITATIVE

HEMOLYSIS
++ +++

TRACE 37 370

HEMOGLOBIN (mg/L) 570 990

197

3200

Fig. 1. Qualitative evaluationof hemolysis and quantitation of hemoglobin concentration these conditions. However, tartrate added to the buffer system selectively inhibits the prostatic isoenzyme.
phatases under Results were also obtained by continuous-flow (SMA 12/60; Technicon). The analytical methods cated in the legend to Figure 3. analysis are inditransferase values showed significant increases. There was also

a drop (22%) in apparent

total bilirubin

concentration.

Discussion
Our results agree with those found by previous investigators (1,2). Changes were minimal for these tests affected only by dilution, because the increase in volume for a grossly hemolyzed specimen was only 1.5%. The increase in hemoglobin. concentration at this concentration of added lysed erythrocytes (7.5mlfliter) was 2710 mg/liter. The expected increase would be 2550mg of hemoglobin per liter, based on an average concentration of 340 g of hemoglobin per liter in erythrocytes (1). The serum sample with this elevated hemoglobin concentration was bright red and clearly was grossly hemolyzed. Addition of 0.75 ml of lysed erythrocytes per liter of serum made it faint red, with a hemoglobin concentration of 320 mg/liter, the lowest concentration consistently categorized by the technologists as trace hemolysis. Although the color differences in the samples prepared for the study are subtle (Figure 1), most experienced technologists were able to categorize the samples as trace, 1+, 2+, 3+, 4+, or grossly hemolyzed. This description can be valuable in the interpretation of chemical results obtained on such samples (Tables

Results
The analyses for free hemoglobin in the aliquots of the six serum pools indicated mean values of 90 to 2800 mg of hemoglobin per liter for 0 to 7.5 ml of added lysed erythrocytes per liter of serum, a range evaluated by the technologists as 0 to 4+ hemolysis. Table 1 summarizes the serum electrolyte values. Potassium values were most affected, in direct proportion to the amount of hemolysate added, the average increase in potassium concentration being 0.75 mmolfliter for hemoglobin concentrations from 90 to 2800 mg/liter, or about 1.2-fold. There was also a 7.5% decrease in bicarbonate concentration. Included in Table 1 is serum iron, which increased in concentration by as much as 24%, depending on the methodology used. Table 2 summarizes the mean values for enzyme activities. By either procedure we used, lactate dehydrogenase appears to be most sensitive to hemolysis; hydroxybutyrate dehydrogenase (heart-associated fraction of lactate dehydrogenase) reflects the same sensitivity. The increase of 260 U of lactate dehydrogenase per liter resulted in a 2.5-fold higher enzyme activity at 2800 mg of hemoglobin per liter of serum than at 90 mg/liter A modest increase of 24 U/liter in aspartate aminotransferase activity was nevertheless a twofold increase in this enzymes activity in serum. Creatine kinase and acid phosphatase both demonstrate a definite methodological difference in results. For acid phosphatase measured with prostatic isoenzyme-specific substrates, there was a negligible increase in enzyme activity, whereas the increase in total acid phosphatase activity was fourfold. For creatine kinase, the increase in enzyme activity as measured with the Gilford 3500 (Worthington reagents) was 1.4-fold, whereas that on the Du Pont aca was 2.3-fold. Table 3 summarizes values obtained with the SMA 12/60. In most instances, little or no change was observed; however, as expected, lactate dehydrogenase and aspartate amino1968 CLINICAL CHEMISTRY, Vol. 24. No.

1-3).
In looking at the data presented in the tables, the reader should not attach undue importance to the percentage increase or decrease in concentration or activity. Concentration change is more important since it is relatively independent

of the baseline concentration of any constituent. There were major changes in potassium, bicarbonate, and iron concentrations. The average potassium increase (Table 1) of 0.75 mmolfliter is exactly what would be expected, based on a potassium concentration of 100 mmol/ liter in erythrocytes (1). This increase, perhaps less than one might intuitively expect with 5+ hemolysis, indicates that lesser degrees of hemolysis would probably be cause for concern only for values at the extremes of the normal range. Plasma samples behave similarly but, as expected, have a lower initial potassium concentration (18). The 8% decrease in bicarbonate
concentration measured with the colorimetric end-point of at 435 and 500 nm), because measured with a pH electrode the Stat Ion probably reflects the titration (ratio of readings the concentration of total CO2 is unaffected by hemolysis (19).

11, 1978

Table 3. Values Obtained on Continuous-Flow Analysis8

Hemoglobin Hemoglobin,
(qualitative)

mg/liter

0 90

trace 320

2+ 1440

4+

Change (0

4+)

2800

u/liter

1. Calcium, mg/liter
2. Inorganic phosphorus, mg/liter

93

93

94
39 1140

38
1130

39
1140

93 39

Glucose, mg/liter 4. Urea nitrogen, mg/liter 5. Uric acid, mg/liter

3.

182
55 39 60 2060

182
55 39 60 2090 71

182
56 39 60 2120

1140 182
56 39 60 2130 72
4.1

6. 7. 8. 9.

Albumin, g/liter Alkaline phosphatase, Cholesterol, mg/liter

Total protein, g/liter

U/liter

0 +1 +10 0 +1 0 0 +70
+2

0
+2

0
1.6

+1 0
+2

0.23 0
0.7

70
5.2
179 36

72
4.6

10. Totalbilirubin, mg/liter

11. Lactate dehydrogenase, U/liter 12. Aspartate aminotransferase, U/liter

a

4.8 201
38

-1.1
+245

0 0 +3 +3 -28
+137 +66

0 0 0.6 1.6
3.6 18.3

318
48

424

60

+24

9.7

Values are means for six pools. b 95% confIdence lImits 1.81 for t-test. 2. 3. 4. 5.
6. 7.
8.

1. CalcIum, Technicon MethodNo.SF4-0003FE5, cresophthalein complexone. Inorganic phosphorus, Technlcon Method No. SF4-0004FE5, phosphomolybdicacid.
Glucose Biodynamics/bmc, Indianapolis, IN 46250. Trinder method. Urea nitrogen. Technicon Method No. SF4-0001FF5,diacetyl monoxime. UrIc Acid, Technicon Method No. SF4-0013FJ5,phosphotungstate. Albumin, Technicon Method No. SF4-0030FE5, bromcresol green. Alkaline phosphatase, Technlcon Method No. SF4-0006FG5, Bessey, Lowry and Brock, automated by Morgenstern. Cholesterol, Blodynamics/bmc, Indianapolis, Ind. 46250, Trlnder method. Total protein, Technicon Method No. SF4-0014FJ5,bluret. Total bilirubin. Technicon Method No. SF4-0018FF5, Jendrassik and &of. automated by Gambino. Lactate dehydrogenase, Technicon Method No. SF4-0021FF5, 340 nm. Aspartate amlnotransferase. Technicon Method No. SF4-OO1OFJ5.340 nm.

9.

10.
11.

12.

Iron concentration as measured by the Du Pont aca and Henry (7) methods exhibited 10 and 24% increases, respectively, in grossly hemolyzed samples (Figure 2). In Henrys method the greater increase might be attributedto the use of hot trichloroacetic acid to release iron from transferrin, resulting also in the release of a small percentage (<2%) of the heme iron. The results obtained from measurement of the concentration of sodium (serum [Nai/erythrocyte [Na+] = 8.75; 1), calcium (serum [Ca2]/erythrocyte [Ca2J = 10; 1), magnesium (serum [Mg2]/erythrocyte [Mg2-i = 0.35; 18) and chloride (serum [Clj/erythrocyte [C1] = 2; 1) were unaffected by hemolysis, even at the 4+ level (2800 mg per liter) of hemoglobin. Of the enzymes studied, aspartate aminotransferase, lactate dehydrogenase, and hydroxybutyrate dehydrogenase gave uniform results with the methodologies tested. Lactate dehydrogenase best reflects the degree of hemolysis by its increased activity. Also, the increase in lactate dehydrogenase activity resulting from the addition of 7.5 ml of lysed erythrocytes per liter (2710 mg of hemoglobin per liter) is 264 UI liter, about 10-fold the increase of 23 U/liter found for the addition of 0.75 ml of lysed erythrocytes (230 mg of hemoglobin per liter). This approximate relationship was found in most values significantly affected by hemolysis. Differences attributable to methodology were found in the measurement of both acid phosphatase and creatine kinase. The method of Bessey et al., which measures both erythrocyte and prostatic acid phosphatase isoenzymes, exhibited a fourfold increase over the range of hemolysis examined, whereas those procedures in which substrates (thymophthalein phosphate and 3-glycerophosphate) with great specificity for prostatic isoenzyme (15) are used showed only modest increases. The percentage increase in total acid phosphatase activity was probably enhanced by the initial enzyme activity of the serum pools, which was at the low end of the normal range.

of erythrocytes

of creatine kinase, which is not a constituent (20), is interfered with because adenylate kinase is released from erythrocytes by hemolysis. As can be seen in Figure 3, the competitive inhibitor, adenosine monophosphate, used in the Worthington reagents is a more effective inhibitor of this interfering enzyme than is fluoride, a noncompetitive inhibitor used with the aca. Recent work has indicated that using adenosine monophosphate in combination with diadenosine pentaphosphate results in superior inhibition of adenylate kinase (14, 21). The apparent decrease in total bilirubin observed with the SMA 12/60 is artifactual. Hemoglobin can compete with nitrite for sulfanilic acid (22), and methemoglobin formation is known to affect the diazotization procedure (23). Another problem, not assessed in this study but which may
2600
2400 2200 2000 $00 600 I400 1200 .

Measurement

,apwr. ET

AL.

OACA

0
5

1000 80< 600 400 200 0 400 $00 200 1600 2000 2400

-a--.-

2600

MEMOG&.061N (MG/LI

t
TRACE
+

1
++

1
+4+

C
+4+4

QUALITATIVE

HEMOLYS1S

Fig. 2. Effectof increasingconcentration of hemolysate on

serum iron concentration
CLINICAL CHEMISTRY, Vol. 24, No. 11, 1978 1969

#{149} OI$O
O

2800

- 80RDU4G10N

ACA

I
1200 1600 2000 2400 2800

OGLOS1N

(MG/U

C
TRACE

C
+ QUAUWNE
+4

C
HEMOLYSS

Fig. 3. Methodological difference in serum creatine kinase activity with increasing concentration of added hemolysate lead to major alterations in chemistry values, relates to the length of time the serum remains exposed to the clot. To assess the magnitude of this type of problem, we drew two blood samples; the specimen in tube 1 was allowed to clot for 1 h before the serum was separated whereas that in tube 2 was allowed to lie on its side for 24 h before the serum was separated. The samples were analyzed with the SMA 12/60 and for potassium. Tube 2 (24 h) showed significant increases in inorganic phosphorus (232%), lactate dehydrogenase (23%), and potassium (67%), and a decrease in glucose (82%), as compared to the other sample (tube 1). Neither specimen was visibly hemolyzed, but tube 2 had a modestly increased hemoglobin concentration (to 200 mg/liter). This type of effect should not be overlooked when one is confronted with spuriously abnormal values. Our results indicate that the overall effect of hemolysis can be quite significant, causing large increases in certain clinical chemical values and in particular in enzyme activities. The ability of technologists to assessthe degree of hemolysis (trace to 4+) and therefore evaluate the degree of interference with specific tests can, if used properly, aid in the formulation of decisions as to whether to redraw a specimen. It should also be clear that care must be taken in assessing the effect of hemoglobin or hemolysis on laboratory results, because different methods for the same analyte can lead to a dramatic variation in results. This type of information is especially important in interpreting the chemistry values of timed samples, which obviously cannot be redrawn.
Supported

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). 3. Sclwartz, M., Interferences in diagnostic biochemical procedures. Adu. Clin. Chem. 16, 1(1973). 4. Brydon,W. G., and Roberts, L. B., The effect of haemolysis on the determination of 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 of serum iron and iron-binding capacity. Clin. Chirn. Acta 3, 523 (1958). 7. Connerty,H. V.,Lau, H. S.C.,and Briggs, A. R., Spectrophotometric determination of magnesium by use of methylthymol blue. Clin. Chem. 17,661 (1971). 8. Henry, R. J., Chiamari, N., Golub, 0. J., and Berkman, S., Revised spectrophotometric methods for the determination of glutamicoxalacetic transaminase, glutamic-pyruvic transaminase and lactic 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 and zinc concentrations in serum. N. EngI. J. Med. 255,449(1956). 10. Gay, R., McComb, R., and Bowers, G., Optimum reaction conditions for human lactate dehydrogenase isoenzymes as they affect total lactate dehydrogenase activity. GUn. Chem. 14,740(1968). 11. Rosalki, S. B., and Wilkinson, J. H., Serum hydroxybutyrate dehydrogenase in diagnosis. J. Am. Med. Assoc. 189,61 (1964). 12. Oliver, L T., A spectrophotometric method for the determination of creatine phosphokinase myokinase. Biochem. J. 61,116 (1955). 13. Rosalki, S. B., An improved procedure for serum creatine phosphokinase determination. J. Lab. Clin. Med. 69,696 (1967). 14. Szasz,G., Gerhardt, W., Gruber, W., and Bernt, E., Creatine kinasa in serum: 2. Interference of adenylate kinase with the assay. Clin. Chem. 22, 1806 (1976). 15. Roy, A. U., Brower, M. E., and Hayden, J. E., Sodium thymophthalein monophosphate: A new acid phosphatase substrate with greater specificity for the prostatic enzyme in serum. Clin. Chem. 17, 1093 (1971). 16. Henry, R. J., Clinical Chemistry: Principles and Technics, 1st. ed., Harper and Row, New York, N.Y., 1965, p 486. 17. Bessey, 0. A., Lowry, 0. H., and Brock, M. J., A method for the rapid determination of alkaline phosphatase with five cubic milliliters of serum. J. Biol. Chem. 164,321 (1946). 18. Tietz, N. W., Electrolytes. In Fundamentals of Clinical Chemistry, 2nd ed., N. Tietz, Ed.,W. B. Saunders, Philadelphia, Pa., 1976, p 873. 19. Hicks, J. M., Aldrich, F. T., and Iosefsohn, M., An evaluation of the Beckman Chloride/Carbon Dioxide Analyzer. Clin. Chem. 22, 1868 (1976). 20. Kachmar, J. F., and Moss, D. W., Enzymes. In Fundamentals of Clinical Chemistry, 2nd ed., N. Tietz, Ed., W. B. Saunders, Philadelphia, Pa., 1976, p 583.
21. Szasz, G., Gerhardt,

in part by NIH Research 5 TO! GM02112-04.

Training

Grant in Clinical

W., and

Gruber,

W., Creatine kinase in serum:

Chemistry

References
1. Caraway, T. W., Chemical and diagnostic specificity of laboratory Am. J. Clin. Pathol. 37, 445 (1962). 2. Laessig, R. H., Hassemer, D. J., Paskey, T. A., and Schwartz, T.
tests.

3. Further study of adenylate kinase inhibitors. Clin. Chem. 23,1888 (1977). 22. Caraway, W. T., and Kammeyer, C. W., Chemical interference by drugs and other substances with clinical laboratory test procedures. Clin. Chim. Acta 41, 395 (1972). 23. McGann, C. J., and Carter, R. E., The effect of hemolysis on the Van den Bergh reaction for serum bilirubin. J. Pediat. 57, 199
(1960).

1970

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