What does it mean if Lactate Dehydrogenase (LDH) is elevated and plasma free hemoglobin is low?

High LDH with Low Plasma Free Hemoglobin: Diagnostic Implications

Elevated lactate dehydrogenase (LDH) with low plasma free hemoglobin most likely indicates tissue damage or malignancy rather than hemolysis, as hemolytic conditions typically show elevated levels of both markers. 1

Understanding the Pattern

When interpreting this laboratory pattern, consider the following:

Mechanism

• LDH is an intracellular enzyme released during tissue damage or cell death
• Plasma free hemoglobin increases specifically during hemolysis (red blood cell destruction)
• This pattern (high LDH, low free hemoglobin) suggests non-hemolytic causes of LDH elevation 1, 2

Primary Diagnostic Considerations

1. Malignancies:

   • Solid tumors with metastasis (particularly liver metastases)
   • Hematologic malignancies (lymphomas, multiple myeloma)
   • Advanced germ cell tumors 3, 1, 4

2. Tissue Damage/Ischemia:

   • Myocardial infarction
   • Pulmonary embolism
   • Tissue infarction 1

3. Infections:

   • Severe bacterial or viral infections
   • Sepsis 1, 4

4. Mechanical Circulatory Support Complications:

   • Pump thrombosis in patients with ventricular assist devices 3

Clinical Significance

• Very high isolated LDH (≥800 IU/L) without liver enzyme elevation is strongly associated with:

  • Cancer (27% vs. 4% in controls)
  • Liver metastases (14% vs. 3%)
  • Hematologic malignancies (5% vs. 0%)
  • Infections (57% vs. 28%) 4

• Prognostic implications:

  • Independent predictor of mortality
  • Associated with longer hospital stays (9.3 vs. 4.1 days)
  • Higher in-hospital complication rates
  • Higher mortality rate (26.6% vs. 4.3%) 4

Recommended Evaluation

Initial Assessment

• Complete blood count with differential
• Comprehensive metabolic panel
• Review of medication history (some medications can cause LDH elevation)
• Evaluation for occult infection 1

Additional Testing Based on Clinical Suspicion

• For suspected malignancy:

  • Tumor markers (AFP, hCG for germ cell tumors) 3
  • Imaging studies (CT, MRI)
  • Consider bone marrow examination for suspected hematologic malignancy 3, 1

• For suspected tissue damage:

  • Cardiac biomarkers (troponin)
  • Imaging appropriate to suspected site of damage 1

• For mechanical circulatory support patients:

  • Evaluate for pump thrombosis
  • Consider device-specific evaluations 3

Important Caveats

1. Sample Processing Considerations:

   • Serum is preferred over plasma for LDH testing
   • Plasma specimens can show falsely elevated LDH (average 22% higher) due to platelet lysis 5

2. Interpretation Challenges:

   • LDH lacks specificity and must be interpreted in clinical context
   • LDH isoenzymes may provide more specific information about the source of elevation 1

3. Monitoring Considerations:

   • Serial measurements are more valuable than single readings
   • Baseline levels should be established when monitoring treatment response 1

This laboratory pattern warrants thorough investigation for underlying serious conditions, particularly malignancies and severe infections, given its association with poor outcomes and high mortality rates.