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HelpTest ID LD_I Lactate Dehydrogenase (LDH) Isoenzymes, Serum
Reporting Name
Lactate Dehydrogenase Isoenzymes, SUseful For
Investigating a variety of diseases involving the heart, liver, muscle, kidney, lung, and blood
Differentiating heart-synthesized lactate dehydrogenase (LDH) from liver and other sources
Investigating unexplained causes of LDH elevations
Detection of macro-LDH
Profile Information
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| LD | Lactate Dehydrogenase (LD), S | Yes | Yes |
| LDI | LD Isoenzymes, S | No | Yes |
Specimen Type
SerumNecessary Information
Patient's age is required.
Specimen Required
Collection Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Submission Container/Tube: Plastic vial
Specimen Volume: 2 mL divided into 2 containers each containing 1 mL
Collection Instructions: Centrifuge and aliquot serum into 2 plastic vials, each containing 1 mL, within 2 hours of collection.
Specimen Minimum Volume
0.75 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum | Ambient (preferred) | 7 days | |
| Refrigerated | 48 hours |
Reference Values
LACTATE DEHYDROGENASE (LD)
1-30 days: 135-750 U/L
31 days-11 months: 180-435 U/L
1-3 years: 160-370 U/L
4-6 years: 145-345 U/L
7-9 years: 143-290 U/L
10-12 years: 120-293 U/L
13-15 years: 110-283 U/L
16-17 years: 105-233 U/L
≥18 years: 122-222 U/L
LD ISOENZYMES
I (fast band): 17.5-28.3%
II: 30.4-36.4%
III: 19.2-24.8%
IV: 9.6-15.6%
V (slow band): 5.5-12.7%
Day(s) Performed
Monday, Wednesday, Friday
Test Classification
This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.CPT Code Information
83615
83625
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| LD_I | Lactate Dehydrogenase Isoenzymes, S | 42929-0 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| LD | Lactate Dehydrogenase (LD), S | 14804-9 |
| 305 | LD Isoenzymes, S | 49279-3 |
| 3344 | Total LD Activity | 14804-9 |
| 2282 | I, Heart | 2536-1 |
| 2283 | II | 2539-5 |
| 2285 | III | 2542-9 |
| 2286 | IV | 2545-2 |
| 2287 | V, Liver | 2548-6 |
Clinical Information
Lactate dehydrogenase (LDH) is a tetrameric cytoplasmic enzyme present in all cells of the body with highest concentrations in heart, liver, muscle, kidney, lung, and erythrocytes. As with other proteins used as tissue-function markers, the appearance of LDH in the serum occurs only after prolonged hypoxia and is elevated in a number of clinical conditions, including cardiorespiratory diseases, malignancy, hemolysis, and disorders of the liver, kidneys, lung, and muscle.
. LDH exhibits 5 isomeric forms composed of H (heart) and M (muscle) subunits. The isoenzyme designation usually is LDH-I (H4), LDH-II (H3M), LDH-III (H2M2), LDH-IV (HM3), and LDH-V (M4). Each isoenzyme is differentially expressed in various tissues, which forms the basis of its importance as a diagnostic marker. For example, heart muscle cells preferentially synthesize H subunits, while liver cells synthesize M subunits nearly exclusively. Skeletal muscle synthesizes largely M subunits; therefore LDH-V is both a liver and skeletal muscle form of LDH. The LDH-I and LDH-V forms are most often used to indicate heart or liver pathology, respectively.
LDH-I appears elevated in the serum about 24 to 48 hours after a myocardial infarction (MI), though generally, it is not as useful as troponin for detection of MI, unless the MI occurred at least 24 hours prior to testing. Normally, LDH-II is greater than LDH-I; however, when an MI has occurred, there is a "flip" in the ratio of LDH-I/LDH-II from less than 1 to greater than 1 (or at least >0.9). Use of the ratio for evaluation of patients with possible cardiovascular injury has largely been replaced by troponin testing (TRPS / Troponin T, 5th Generation, Plasma).
The LDH-V form is pronounced in patients with either primary liver disease or liver hypoxia secondary to decreased perfusion, such as occurs following an MI. However, LDH-V is usually not as reliable as the transaminases (eg, aspartate aminotransferase, alanine aminotransferase) for evaluating liver function. LDH-V also may be elevated in muscular damage and diseases of the skin.
Although it does not appear to cause or be associated with any symptoms or particular diseases, the presence of macro-LDH (LDH combined with an immunoglobulin) can cause an idiosyncratic elevation of total LDH.
Interpretation
Marked elevations in lactate dehydrogenase (LDH) activity can be observed in megaloblastic anemia, untreated pernicious anemia, Hodgkin disease, abdominal and lung cancers, severe shock, and hypoxia.
Moderate-to-slight increases in LDH levels are seen in myocardial infarction (MI), pulmonary infarction, pulmonary embolism, leukemia, hemolytic anemia, infectious mononucleosis, progressive muscular dystrophy (especially in the early and middle stages of the disease), liver disease, and kidney disease.
In liver disease, elevations of LDH are not as great as the increases in aspartate aminotransferase and alanine aminotransferase.
Increased levels of the enzyme are found in about one-third of patients with kidney disease, especially those with tubular necrosis or pyelonephritis. However, these elevations do not correlate well with proteinuria or other parameters of kidney disease.
On occasion, a raised LDH level may be the only evidence to suggest the presence of a hidden pulmonary embolus.
LDH-II is found in myocardium. Following a severe MI, the diagnostic ratio of LDH-I divided by LDH-II will change from less than 0.9 to greater than 0.9. This is referred to as an LDH "flip".
LDH-I elevation not due to myocardial damage may indicate hemolytic disease or other forms of in vivo hemolysis.
Elevation of LDH-V (least mobile isoenzyme) usually denotes liver damage. It is rarely helpful in defining skeletal muscle disease.
Macro-LDH can occur, which results in an elevation of LDH for no clinical reason. Macro-LDH greatly affects the migration of LDH isoenzymes since the addition of an immunoglobulin molecule greatly retards the migration of the usual LDH isoenzymes. If macro-LDH is present, the electrophoretogram will show atypically migrating isoenzymes with LDH activity localized near the origin.
Cautions
A hemolyzed specimen is not acceptable as red blood cells contain much more lactate dehydrogenase (LDH) than serum. Causes of hemolysis can include transportation via pneumatic tube, vigorous mixing, or traumatic venipuncture. Tubes should be void of air bubbles to prevent minor hemolysis. LDH activity is one of the most sensitive indicators of in vitro hemolysis. Hemolysis causes anomalous elevation of LDH-I such that any ex vivo hemolysis must be strictly avoided.
Testing should be used with caution in patients with chronic hemolytic anemias such as sickle cell disease as LDH levels may be falsely elevated due to their clinical status.
Freezing or prolonged storage at 4° C (>12 hours) causes LDH-V to be lost.
Elevations of intermediate forms, LDH-II through LDH-IV, are rarely used to define a tissue of origin and such reports are largely anecdotal.
While increases in serum LDH also are seen following a myocardial infarction, the test has been replaced by the determination of troponin (TRPS / Troponin T, 5th Generation, Plasma).
Clinical Reference
1. Panteghini M, Bais R: Serum enzymes. In: Rifai N, Horvath AR, Wittwer CT, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier; 2018:407-431
2. Berridge BR, Herman E: In: Haschek and Rousseaux's Handbook of Toxicologic Pathology. 3rd ed. 2013
3. Farhana A, Lappin SL: Biochemistry, Lactate Dehydrogenase. In: StatPearls [Internet]. StatPearls Publishing; 2022. Updated May 8, 2022. Accessed September 7, 2022. Available at www.ncbi.nlm.nih.gov/books/NBK557536/
Method Description
Total Lactate Dehydrogenase:
Lactate and nicotinamide adenine dinucleotide (NAD[+]), in the presence of lactate dehydrogenase (LDH), are converted to pyruvate and NADH. The rate at which NADH is formed is determined by an increase in absorbance and is directly proportional to enzyme activity.(Package insert: LDH reagent. Roche Diagnostics; 08/2019)
Isoenzyme:
The 5 isoenzymes of LDH are separated by electrophoresis on agarose film. The serum samples are electrophoresed and separated LDH isoenzymes are visualized using a specific chromogenic substrate. The amount of resulting formazan precipitate is proportional to the LDH enzymatic activity. Densitometry is used to obtain relative quantification of each fraction. The fractions are numbered according to their electrophoretic mobility, LDH-I being the most mobile.(Tietz NW, ed. Clinical Guide to Laboratory Tests. 3rd ed. WB Saunders Company; 1995; package insert: Sebia Hydragel ISO-LDH. Sebia; 07/2019)
Report Available
3 to 6 daysReject Due To
| Gross hemolysis | Reject |
| Gross lipemia | OK |
Method Name
LDI: Electrophoresis Densitometry
LD: Photometric Rate Reaction