What is lactate dehydrogenase (LDH) used to test for?

What Lactate Dehydrogenase (LDH) Tests For

Lactate dehydrogenase is a nonspecific biomarker of tissue injury and cell death that is used clinically to detect cellular damage, differentiate pleural effusions, diagnose hemolysis, assess tumor burden in malignancies, and monitor tissue hypoperfusion in shock states. 1

Primary Clinical Applications

Tissue Damage and Cell Death Detection

• LDH is released into the bloodstream when cells are damaged or die, making it a sensitive marker for detecting tissue injury across multiple organ systems. 1, 2
• The enzyme is found in the cytoplasm of most cells throughout the body, with particularly high concentrations in the heart, liver, skeletal muscle, kidney, and red blood cells. 3
• When oxidative stress or cellular injury occurs, LDH leaks from damaged cells into the extracellular space and bloodstream, with levels correlating to the severity of tissue damage. 2

Pleural Effusion Differentiation

• The European Respiratory Society and British Thoracic Society recommend LDH as part of Light's criteria to distinguish exudative from transudative pleural effusions. 1
• A pleural fluid LDH greater than 0.67 (or 2/3) of the upper limit of normal serum LDH identifies exudates with 98% sensitivity and 72% specificity. 1
• A pleural fluid-to-serum LDH ratio greater than 0.6 also indicates an exudative effusion. 1

Hemolysis Diagnosis

• The combination of elevated LDH with decreased haptoglobin and elevated indirect bilirubin forms a diagnostic triad specific for hemolysis. 4
• LDH elevation reflects red blood cell destruction and release of intracellular enzymes into circulation. 4
• This must be interpreted alongside reticulocyte count, direct Coombs test, and peripheral blood smear to differentiate immune from non-immune hemolysis. 4
• A critical pitfall: LDH can also be elevated in liver disease, myocardial infarction, kidney disease, and muscle damage, so it cannot diagnose hemolysis in isolation. 4

Shock and Tissue Hypoperfusion Monitoring

• The European guideline on trauma management recommends blood lactate (not LDH itself, but related to lactate metabolism) as a sensitive test to estimate and monitor the extent of bleeding and tissue hypoperfusion. 5
• Serial LDH measurements provide objective evaluation of patient response to therapy in shock states. 5

Cancer Assessment

• Elevated LDH is associated with high tumor burden in hematologic malignancies like plasma cell leukemia and serves as a prognostic factor in Hodgkin's disease. 1
• Very high isolated LDH (≥800 IU/mL) is a distinguishing biomarker for metastatic cancer (27% of cases), liver metastases (14%), and hematologic malignancies (5%). 6
• LDH overexpression in cancers reflects anaerobic cellular metabolism and aggressive disease behavior. 7

Specific Disease Applications

Anemia Classification

• Normocytic anemia with elevated reticulocytes and elevated LDH indicates hemolytic anemia. 4
• Macrocytic anemia with normal/low reticulocytes and markedly elevated LDH (>3000 IU/L) suggests megaloblastic anemia from B12 or folate deficiency. 4
• Microcytic anemia with elevated reticulocytes suggests hemoglobinopathies like thalassemia. 4

Neonatal Cellular Damage

• The American Academy of Pediatrics recommends considering LDH testing when evaluating newborns with suspected cellular damage from hypoxic events. 8
• LDH serves as a marker for detecting tissue injury in various neonatal conditions. 8

Drug-Induced Hemolysis

• In daptomycin-induced immune hemolytic anemia, a rise in indirect bilirubin combined with elevated LDH indicates hemolysis rather than hepatic injury. 4
• Serial LDH monitoring is valuable for detecting worsening hemolysis or complications. 4

Prognostic Significance

Mortality Prediction

• Very high isolated LDH (≥800 IU/mL) is an independent predictor of mortality in admitted medical patients, associated with 26.6% mortality versus 4.3% in controls. 6
• Patients with very high LDH have significantly more in-hospital major complications and longer admission times (9.3 vs 4.1 days). 6

Infection Severity

• Very high isolated LDH is associated with severe infection in 57% of cases versus 28% in controls. 6

Important Limitations and Pitfalls

Because LDH is present in essentially all major organ systems, total serum LDH elevation is nonspecific and requires clinical context for interpretation. 1, 9

• LDH isoenzyme analysis can identify the tissue origin of elevation when needed, though this is ordered less frequently than total LDH. 1
• The upper limit of normal for LDH is highly laboratory-specific and depends on assay conditions. 1
• In trauma patients with alcohol consumption, lactate determination reliability may be lower. 5
• Haptoglobin can be decreased in patients with mechanical heart valves without clinically relevant hemolysis, potentially confounding hemolysis diagnosis. 4