Lactate Dehydrogenase (LD) Isoenzymes

Overview:

Lactate dehydrogenase (LD) is an enzyme that is found in almost all of the body's cells, but only a small amount of it is usually detectable in the blood. LD is released from the cells into the bloodstream when cells are damaged or destroyed. Because of this, the LD test can be used as a general marker of injury to cells.

Although there is some overlap, each of the five LD isoenzymes tends to be concentrated in specific body tissues. In general, the isoenzyme locations are as follows:

- LD1: Heart, red blood cells, kidney

- LD2: Heart, red blood cells, kidney (lesser amounts than LD1)

- LD3: Lungs and other tissues

- LD4: White blood cells, lymph nodes, muscle, liver (lesser amounts than LD5)

- LD5: Liver, skeletal muscle

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 the 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 an 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 to 24 hours after onset of infarction, LD isoenzymes usually become diagnostic at about 36 to 55 hours after onset and return to normal between 3 and 14 days after onset.

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.

1. Rotenberg Z, Davidson E, Weinberger I, Fuchs J, Sperling O, Agmon J. The efficiency of lactate dehydrogenase isoenzyme determination for the diagnosis of acute myocardial infarction. Arch Pathol Lab Med. 1988; 112(9):895-897. PubMed 3415440

2. Loughlin JF, Krijnen PM, Jablonsky G, Leung FY, Henderson AR. Diagnostic efficiency of four lactate dehydrogenase isoenzyme-1 ratios in serum after myocardial infarction. Clin Chem. 1988 Oct; 34(2):1960-1965. PubMed 3168204

3. Rotenberg Z, Weinberger I, Sagie A, Fuchs J, Sperling O, Agmon J. Lactate dehydrogenase isoenzymes in serum during unstable angina. Clin Chem. 1986 Aug; 32(8):1566-1567. PubMed 3731454

4. Jablonsky G, Leung FY, Henderson AR. Changes in the ratio of lactate dehydrogenase isoenzymes 1 and 2 during the first day after acute myocardial infarction. Clin Chem. 1985 Oct; 31(10):1621-1624. PubMed 4042327

5. Rotenberg Z, Weinberger I, Sagie A, Fuchs J, Sperling O, Agmon J. Lactate dehydrogenase isoenzymes in serum during recent acute myocardial infarction. Clin Chem. 1987 Aug; 33(8):1419-1420. PubMed 3608159

6. Rotenberg Z, Weinberger I, Davidson E, Fuchs J, Sperling O, Agmon J. Atypical patterns of lactate dehydrogenase isoenzymes in acute myocardial infarction. Clin Chem. 1988 Jun, 34(6):1096-1098. PubMed 3378325

7. Jacobs DS, Robinson RA, Clark GM, Tucker JM. Clinical significance of the isomorphic pattern of the isoenzymes of serum lactate dehydrogenase. Ann Clin Lab Sci. 1977 Sep-Oct; 7(5):411-421. PubMed 900865

8. Rotenberg Z, Weinberger I, Davidson E, Fuchs J, Sperling O, Agmon J. Patterns of lactate dehydrogenase isoenzymes in serum of patients with acute pulmonary edema. Clin Chem. 1988 Sep; 34(9):1882-1884. PubMed 3416439

9. Rotenberg Z, Weinberger I, Davidson E, Fuchs J, Sperling O, Agmon J. Significance of isolated increases in total lactate dehydrogenase and its isoenzymes in serum of patients with bacterial pneumonia. Clin Chem. 1988 Jul; 34(7):1503-1505. PubMed 3390929

10. Gorus F, Aelbrecht W, Van Camp B. Circulating IgG-LD complex, dissociable by addition of NAD.+. Clin Chem. 1982 Jan; 28(1):236-239. PubMed 7055917

11. Pesce MA. The CK and LD macroenzymes. Lab Management. 1984 Nov 29; 22:29-41.

12. Podlasek SJ, Dufour DR, McPherson RA. Alterations in lactate dehydrogenase isoenzyme patterns after therapy with streptokinase or streptococcal infection. Clin Chem. 1989 Aug; 35(8):1763-1766. PubMed 2758647

13. Vladutiu AO. Cathodic lactate dehydrogenase (LDH 6): A sign of ominous prognosis? Arch Pathol Lab Med. 1983 Nov; 107(11):612-613. PubMed 6688723

14. Wolf PL. Lactate dehydrogenase-6: A biochemical sign of serious hepatic circulatory disturbance. Arch Intern Med. 1985 Aug; 145(8):1396-1397. PubMed 4026470

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 Nov; 140(5):986-990. PubMed 2845154

16. Schwartz PE, Morris JM. Serum lactic dehydrogenase: a tumor marker for dysgerminoma. Obstet Gynecol. 1988 Sep; 72(3 Pt 2):51