LDH as a Biomarker for Hemolysis
Yes, lactate dehydrogenase (LDH) is a well-established biomarker for hemolysis, though it lacks specificity and should be interpreted alongside other laboratory findings.
Role of LDH in Hemolysis Detection
LDH is released during the breakdown of red blood cells and serves as a key indicator of hemolytic processes. According to the American Society of Hematology guidelines, LDH is specifically mentioned as one of the diagnostic criteria for delayed hemolytic transfusion reactions (DHTR) in sickle cell disease 1. When evaluating for hemolysis, LDH elevation is typically accompanied by:
- Decreased hemoglobin levels
- Reduced haptoglobin
- Elevated bilirubin
- Presence of schistocytes in peripheral blood smear
- Negative direct and indirect Coombs tests (in non-immune hemolysis)
LDH Isoenzymes in Hemolysis
The specificity of LDH for hemolysis is enhanced by examining its isoenzyme pattern:
- LDH1 and LDH2 are the predominant isoforms in erythrocytes 2
- In true hemolytic conditions, these isoenzymes are disproportionately elevated
- Isoenzyme fractionation can confirm the erythrocyte origin of elevated LDH 2
Limitations of LDH as a Hemolysis Marker
Despite its utility, LDH has important limitations:
Lack of specificity: LDH is present in many tissues and can be elevated in various conditions including:
Normal LDH in hemolysis: Some cases of autoimmune hemolytic anemia (AIHA) present with normal LDH levels despite other evidence of hemolysis 4. Studies have shown that up to 25% of AIHA cases may have normal LDH levels.
Non-hemolytic sources in conditions with hemolysis: In thrombotic thrombocytopenic purpura (TTP), a condition associated with microangiopathic hemolysis, research has shown that LDH elevation may be predominantly from damaged tissues rather than from hemolyzed erythrocytes 5.
Clinical Application
When using LDH to evaluate for hemolysis:
Always interpret in context with other hemolytic markers:
- Decreased hemoglobin
- Reduced haptoglobin (more specific for hemolysis)
- Elevated indirect bilirubin
- Reticulocytosis
- Presence of schistocytes
Serial measurements are more valuable than single readings 6, 7
Consider LDH isoenzyme fractionation when the source of LDH elevation is unclear
Be aware of baseline elevation in certain conditions like sickle cell disease where chronic hemolysis may lead to persistently elevated LDH 2
Threshold Values
- LDH >2.5 times the upper limit of normal is often used as a threshold for significant hemolysis in various clinical contexts 7
- In mechanical circulatory support settings, an increase in plasma-free hemoglobin (>40 mg/dL) may be more specific for hemolysis than LDH changes 6
In summary, while LDH is a valuable biomarker for hemolysis, it should be interpreted as part of a comprehensive panel of hemolytic markers rather than in isolation due to its limited specificity.