Elevated LDH Fraction 1 (LDH-1): Clinical Significance
An elevated LDH-1 fraction primarily indicates cardiac or red blood cell injury, as LDH-1 is the predominant isoenzyme in heart muscle and erythrocytes. 1
Tissue Distribution and Diagnostic Implications
LDH-1 (also called LDH-H or heart-type) is concentrated in specific tissues that determine its diagnostic significance:
- Cardiac muscle contains the highest concentrations of LDH-1, making elevation a marker of myocardial injury or infarction 1
- Red blood cells are rich in LDH-1 and LDH-2, so hemolysis (intravascular or in vitro) elevates these fractions 2, 1
- Renal cortex also contains significant LDH-1, though kidney injury more commonly elevates other markers 1
Critical Diagnostic Considerations
Hemolysis Must Be Excluded First
Before attributing elevated LDH-1 to pathology, you must rule out specimen hemolysis, which falsely elevates LDH-1 and LDH-2 through red blood cell breakdown during collection or processing. 3 If the sample appears hemolyzed (pink-tinged serum), repeat the test with careful phlebotomy technique 3.
Cardiac vs. Hemolytic Origin
The LDH-1/LDH-2 ratio helps distinguish these sources:
- LDH-1 > LDH-2 (ratio >1.0) suggests myocardial injury, as cardiac tissue releases predominantly LDH-1 1
- Both LDH-1 and LDH-2 elevated proportionally suggests hemolysis, since erythrocytes contain both isoenzymes 2, 1
Unexpected Finding: TTP and Tissue Ischemia
Contrary to traditional teaching, a prospective study of thrombotic thrombocytopenic purpura (TTP) patients found that LDH-1 and LDH-2 were NOT disproportionately elevated despite significant hemolysis; instead, LDH-5 (liver/muscle) was consistently elevated 1-2 fold above normal, suggesting the total LDH elevation resulted from widespread tissue ischemia rather than hemolysis alone 2. This challenges the assumption that hemolytic conditions automatically produce LDH-1 predominance.
Clinical Algorithm for Elevated LDH-1
Inspect the specimen: If hemolyzed, redraw and retest 3
Check cardiac markers: Order troponin, CK-MB, and ECG if myocardial injury is suspected 1
Assess for hemolysis:
Evaluate LDH isoenzyme pattern:
Common Pitfalls
Macro-LDH: Rarely, LDH complexes with immunoglobulin G create persistently elevated total LDH without true tissue injury; this typically affects total LDH rather than specific fractions but should be considered in otherwise healthy individuals with unexplained persistent elevation 4
Species variation: LDH isoenzyme patterns vary significantly between species, so veterinary reference ranges cannot be extrapolated to humans 1
Non-specific elevation: While LDH-1 elevation narrows the differential compared to total LDH, it remains less specific than troponin for cardiac injury or haptoglobin for hemolysis 1, 5