Lactate Dehydrogenase (LD) Isoenzymes
Lactate Dehydrogenase (LD) Isoenzymes | | | |
| Number | | 001842 |
CPT | | 83625; 83615 |
Synonyms | | Lactic Acid Dehydrogenase Isoenzymes ; LDH Isoenzymes ; LD
Isoenzymes |
Test Includes | | Total serum LD and relative percentage of isoenzymes
(LD1-5) |
| Specimen | | Serum |
| Volume | | 3 mL |
| Minimum Volume | | 1 mL |
| Container | | Red-top tube |
| Collection | | Separate serum from cells within 45 minutes of collection. |
Storage Instructions | | Maintain specimen at room temperature. Do not
refrigerate or freeze. LD5 is least stable with
13% lost at room temperature after 48 hours, 18% lost at
refrigerated temperatures. |
| Patient Preparation | | Cardiac enzymes and isoenzymes are best interpreted as a
sequential series. Typically, a series of 3: 1 at admission
(or initial event) and 2 more at 6- to 8-hour intervals. |
| Causes for Rejection | | Hemolysis; prolonged contact of serum with red cells;
specimen received frozen; specimen older than 48 hours
after collection at time of testing |
Reference Interval | | | Total: 100-250
IU/L; LD1:
16% to 35%; LD2: 24% to
41%; LD3: 16% to 27%;
LD4: 5% to 14%;
LD5: 5% to 24%. See
table. LD Isoenzyme
Interpretation
| Abbrev1 |
Total LDH |
LD1 |
LD2 |
LD3 |
LD4 |
LD5
| |
| Case 1 | H | H | H | - |
- | - |
| Case 2 | H | H | H | - |
- | - |
| Case 3 | H | H> | H | - |
- | - |
| Case 4 | H | H> | H | - |
- | H |
| Case 5 | H | H | H | - |
- | H |
| Case 6 | H | - | - | - |
H | H |
| Case 7 | H | - | H | H |
H | - |
| Case 8 | H | H | H | H |
H | H |
| Case 9 | H | - | - | - |
- | - |
| Case 10 | N | - | - | - |
- | - |
| Case 11 | H | - | - | - |
- | H |
| Case 12 |
Other patterns not
shown | |
1See following
interpretation of
abbreviations
H = high (increased)
- = within reference (normal) interval or decreased
N = within reference (normal) interval
Interpretations:
Case 1: Patient specimen was visibly
hemolyzed which may have produced the elevations of
LD1 and
LD2 on the LD isoenzyme
pattern.
Case 2: The LD isoenzyme pattern
demonstrates elevations of
LD1and
LD2. These increases
would be compatible with diagnostic considerations
involving myocardial infarction, megaloblastic anemia,
acute renal infarction, in vivo hemolytic process
(eg, hemolytic anemia), or in the later stages of muscular
dystrophy.
Case 3: The LD isoenzyme pattern
demonstrates LD1 greater
than LD2. In the
appropriate clinical setting, this pattern is most
compatible with postmyocardial infarction occurring at
least 8-12 hours prior to venipuncture.
Case 4: The LD isoenzyme pattern demonstrates
LD1greater
than LD2 and an increase
of LD5. This pattern
would be most compatible with passive hepatic congestion
following an acute myocardial infarction or right-sided
congestive heart failure associated with myocardial
infarction.
Case 5: The LD isoenzyme pattern demonstrates
elevations of LD1 and
LD2and an increase of
LD5. This pattern would
be compatible with diagnostic considerations involving
passive hepatic congestion or right-sided congestive heart
failure which may have followed acute myocardial
damage.
Case 6: The LD isoenzyme pattern demonstrates
elevations of LD4and
LD5. These increases
would be compatible with hepatic (cirrhosis, viral
hepatitis, toxic hepatitis) or skeletal muscle injury. This
pattern may also be associated with congestive heart
failure.
Case 7: The LD isoenzyme pattern
demonstrates elevations of
LD2,
LD3 and
LD4. Increases of these
isoenzyme fractions are nonspecific but have been
associated with septic shock, pulmonary emboli, and some
neoplastic processes.
Case 8: The LD isoenzyme pattern demonstrates
elevations of all isoenzymes without dominating fractions.
This pattern is nonspecific but has been associated with
septic shock, pulmonary emboli, and some neoplastic
processes.
Case 9: The LD isoenzyme pattern appears
normal despite elevation of the total LD.
Case 10: The LD isoenzyme pattern appears
normal with a normal total LD.
Case 11: The LD isoenzyme pattern
demonstrates an elevated
LD5 fraction which may be
associated with hepatic anoxia due to congestive heart
failure or the early stages of muscular dystrophy.
Case 12: The LD isoenzyme pattern is
nonspecific. Recommend correlation with the clinical
condition of the patient. |
Use | | Changes of LD isoenzymes periodically measured following
onset of chest pain, studying the relationships of the
anodic fractions, provide important information for the
differential diagnosis of acute infarct of myocardium. The
differential diagnosis of certain other diseases is
enhanced as well with use of LD isoenzymes.
Useful in the differential diagnosis of acute myocardial
infarction, megaloblastic anemia (folate deficiency,
pernicious anemia), hemolytic anemia, and very occasionally
renal infarct. These entities are characterized by
LD1 increases, often with
LD1:
LD2 inversion.
The isomorphic pattern (total LD significantly high with no
increase in percentage, of any fraction) is seen with
neoplasia, cardiorespiratory diseases, hypothyroidism,
infectious mononucleosis, and other inflammatory states,
uremia, and necrosis.
LD5 increases are seen
with striated muscle lesions (eg, trauma) and with liver
diseases (eg, hepatic congestion, congestive heart failure,
hepatitis, cirrhosis, alcoholism).
LD5 increase is probably
more significant when the
LD5:
LD4 ratio is increased.
Although a modicum of controversy exists regarding the most
suitable criteria for LD isoenzymes for the diagnosis of
acute myocardial infarction, almost all laboratories
recognize abnormality when
LD1 equals or is greater
than LD2. Alternatives to
LD1 greater than
LD2 have been
proposed. Using an electrophoretic method (Helena),
Rotenberg et al suggested the criterion of
LD1 >90
units/L.1 A 1988 study
examines application of
LD1:
LD4 and other
ratios and finds that the
LD1:
LD4 ratio optimizes
earlier and is the most powerful diagnostic ratio for acute
myocardial infarction.2
A few percent of normal individuals may have
LD1:
LD2 ratios
as high as 0.81. A ratio of 0.82-0.99 is suspicious of
myocardial injury. A ratio >1.0 is diagnostic of myocardial
injury, if other clinical criteria are met. In unstable
angina, an increase of the
LD1:
LD2 ratio is described
with normal total LD.3
However, progressively increasing
LD1:
LD2 ratio without
complete inversion may have diagnostic significance for
acute myocardial
infarct.4
Persistent LD1:
LD2 flip following acute
myocardial infarct may represent a marker for
reinfarction.5 Especially
when acute myocardial infarction is complicated by shock,
the isomorphic pattern may be
found.6
LD1:
LD2 inversion
commonly appears subsequent to the isomorphic pattern in
instances of acute myocardial
infarction.7
The appearance of a LD "flip" (when
LD1 is greater than
LD2) is extremely helpful
in diagnosis of MI. The presence of a LD "flip" a day
following or with the detection of CK-MB is essentially
diagnostic of MI, if baseline cardiac enzymes/isoenzymes
are normal and if rises and falls are as anticipated for
the diagnosis of acute MI. While CK-MB peaks 12-24 hours
after onset of infarction, LD isoenzymes usually become
diagnostic at about 36-55 hours after onset and return to
normal between 3 and 14 days after onset. |
Limitations | | Timing is important in diagnosis of acute myocardial
infarct (MI). In a small percentage of patients with acute
myocardial infarction, the expected flip (reversal) of
LD1:
LD2 does not occur; in
such patients, there is often simply an increase in
LD1. |
| Methodology | | Electrophoresis |
Additional Information | | Patterns of LD isoenzymes in acute pulmonary edema include
the isomorphic pattern and
LD5
increase.8 Serum LD
increases also in patients with bacterial pneumonia, in
whom LD isoenzyme patterns are
described.9
Macroenzymes, high molecular weight
complexes, occur with LD as well as with CK and other
enzymes. LD isoenzymes may complex to IgA or IgG. Such LD
macroenzymes are characterized by abnormal position of
isoenzyme bands, broadening or abnormal motility of a
band and otherwise unexplained increase of total serum LD.
Some of these patients have abnormal ANA results and
IgG complexes.10
Some have abnormalities of light
chains.11 Treatment with
streptokinase was found to produce a LD-streptokinase
complex which was seen as a band at the origin in
electrophoresis.12
An isoenzyme band cathodal to
LD5 has
been called LD6.
It is not an immunoglobulin complex. It has occurred in
subjects with liver disease and is said to indicate a grave
prognosis.10,13,14
The association between
LD1 and
testicular seminoma has been widely recognized. Its
relationship to nonseminomatous testicular tumors as well
are described.15 The
ovarian equivalent of seminoma is dysgerminoma,
which also may relate to
LD1
increases.16,17 A variety
of malignant tumors are characterized by total LD
increases, sometimes with isomorphic
patterns7 or with
LD5
increases.18
Increase LD5:
LD1 ratio is suggestive
of prostatic carcinoma or other
cancers.19 Increases in
LD1:
LD4 ratio was found
to be a good indicator of
MI.20
In a series of 220 patients with carcinoma of breast, LD was
the most common enzyme elevated. The nonspecificity of
single enzyme elevation was discussed, but enzymes provide
an inexpensive baseline for postoperative follow-up. Enzyme
elevation defines a subgroup of patients deserving further
evaluation.21 In
malignancy of various types, there is reported an abnormal
isoenzyme of LD migrating between albumin and
LD1 on agarose gel
electrophoresis.22
An inverted LD5:
LD4 ratio is not to be
confused with LD1:
LD2 ratio, used to
evaluate acute MI. There is evidence that when
LD5 sufficiently exceeds
LD4,
liver disease might exist. Such liver disease might be
primary or secondary (eg, congestive heart failure).
Additional tests which may be useful, if clinically
indicated, to work up such possible liver disease or
injury might include ALT (SGPT), GGT, serum protein
electrophoresis, and prothrombin time.
LD5 is the
striated muscle as well as the liver fraction. Although
striated muscle problems are usually clinically obvious,
occasionally the physician does not get a clinical history
of the postictal state or of various withdrawal syndromes.
In such situations, a CK may be helpful. |
Footnotes | | 1.
Rotenberg Z, Davidson E, Weinberger I, et al. The
efficiency of lactate dehydrogenase isoenzyme determination
for the diagnosis of acute myocardial infarction. Arch
Pathol Lab Med. 1988; 112(9):895-897.
2. Loughlin JF, Krijnen PM,
Jablonsky G, et al. Diagnostic efficiency of four lactate
dehydrogenase isoenzyme-1 ratios in serum after myocardial
infarction. Clin Chem. 1988;34:1960-1965.
3. Rotenberg Z, Weinberger
I, Sagle A, et al. Lactate dehydrogenase isoenzymes in
serum during unstable angina. Clin Chem.
1986; 32:1566-1567.
4. Jablonsky G, Leung FY,
Henderson AR. Changes in LD1/LD2 ratio during the first day
after myocardial infarction. Clin Chem. 1985;
31:1621-1624.
5. Rotenberg Z, Weinberger
I, Sagie A, et al. Lactate dehydrogenase isoenzymes in
serum during recent acute myocardial infarction.
Clin Chem. 1987; 33:1419-1420.
6. Rotenberg Z, Weinberger
I, Davidson E, et al. Atypical patterns of lactate
dehydrogenase isoenzymes in acute myocardial infarction.
Clin Chem. 1988; 349(6):1096-1098.
7. Jacobs DS, Robinson RA,
Clark GM, et al. Clinical significance of the isomorphic
pattern of the isoenzymes of serum lactate dehydrogenase.
Ann Clin Lab Sci. 1977;7:411-421.
8. Rotenberg Z, Weinberger
I, Davidson E, et al. Patterns of lactate dehydrogenase
isoenzymes in serum of patients with acute pulmonary edema.
Clin Chem. 1988; 34(8)1882-1884.
9. Rotenberg Z, Weinberger
I, Davidson E, et al.Significance of isolated increases in
total lactate dehydrogenase and its isoenzymes in serum of
patients with bacterial Pneumonia. Clin Chem.
1988; 34(7):1503-1505.
10. Gorus F, Aelbrecht W,
Van Camp B. Circulating IgG-complex, dissociable by
addition of NAD+. Clin Chem. 1982;28:236-239.
11. Pesce MA. The CK and LD
macroenzymes. Lab Management.1984; 22:29-41.
12. Podlasek SJ, Dufour DR,
McPherson RA. Alterations lactate dehydrogenase isoenzyme
patterns after therapy with streptokinase of streptococcal
infection. Clin Chem.1989; 35(8):1763-1766.
13. Vladutiu AO. Cathodic
lactate dehydrogenase (LDH 6): A sign of ominous prognosis?
Arch Pathol Lab Med. 1983;107:612-613.
14. Wolf PL. Lactate
dehydrogenase-6: A biochemical sign of serious hepatic
circulatory disturbance. Arch Intern Med.
1985; 145:1396-1397.
15. Von Eyben FE, Blaabjerg
O, Petersen PH, et al. Serum lactate dehydrogenase
isoenzyme 1 as a marker of testicular germ cell tumor. J
Urol. 1988; 140(5):989-990.
16. Schwartz PE, Morris JM.
Serum lactic dehydrogenase: A tumor marker for
dysgerminoma. Obstet Gynecol.
1988;72(3 Pt 2):511-515.
17. Yoshimura T, Takemori K,
Okazaki T, et al, Serum lactate dehydrogenase and its
isoenzymes in patients with ovarian dysgerminoma . Int
J Gynaecol Obstet. 1988, 27:459-465.
18. Rotenberg Z, Weinberger
I, Sagie A, et al, Total lactate dehydrogenase and its
isoenzymes in serum of patients with non-small-cell lung
cancer. Clin Chem. 1988,34:668-670.
19. Manzo V, Sun T, and Lien
YY. Misdiagnosis of acute myocardial infarction. Ann
Clin Lab Sci. 1980,20(5):324-328.
20. Galbraith LV, Leung FY,
Jablonsky G, et al. Time-related changes in the diagnostic
utility of total lactate dehydrogenase, lactate
dehydrogenase isoenzyme-1, and two lactate dehydrogenase
isoenzyme-1 ratios in serum after myocardial infarction.
Clin Chem. 1990,36(7):1317-1322.
21. Clark CP 3d, Foreman ML,
Peters GN, et al. Efficacy of preoperative liver function
tests and ultrasound in detecting hepatic metastasis in
carcinoma of the breast. Surg Gynecol Obstet.
1988,167(6):510-514.
22. Giannoulaki EE, Kalpaxis
DL, Tentas C, et al. Lactate dehydrogenase isoenzyme
pattern in sera of patients with malignant diseases.
Clin Chem. 1989,35(3):396-399. |
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