What is the significance of elevated Lactate Dehydrogenase (LDH)?

From the Guidelines

Elevated Lactate Dehydrogenase (LDH) is a significant clinical finding that indicates a poorer prognosis in various conditions, including cancers, and should prompt further diagnostic testing to determine the underlying cause. Elevated LDH is a non-specific marker for tissue damage or cell death, and can be seen in conditions such as myocardial infarction, pulmonary embolism, hemolysis, certain cancers (particularly lymphomas, leukemias, and metastatic cancers), liver disease, muscle damage, and severe infections 1. In cancer patients, elevated LDH often correlates with tumor burden and can indicate a poorer prognosis. For example, in osteosarcoma, elevated serum LDH level is associated with a worse prognosis, with 5-year disease-free survival rates of 39.5% for patients with high LDH levels and 60% for those with normal values 1. Similarly, in follicular lymphoma, elevated LDH is a risk factor for a poorer prognosis, as outlined in the Follicular Lymphoma-specific International Prognostic Index (FLIPI) risk factors 1. Some key points to consider when evaluating elevated LDH include:

• The degree of elevation, with massive elevations (5-10 times normal) typically seen in conditions like tumor lysis syndrome, severe hemolysis, or extensive tissue damage
• The clinical context, including the patient's symptoms and presentation
• The need for further diagnostic testing to determine the underlying cause of the elevated LDH
• The potential impact of elevated LDH on prognosis and treatment outcomes in cancer patients Normal LDH ranges typically fall between 140-280 U/L, though reference ranges may vary by laboratory. In summary, elevated LDH is a significant clinical finding that requires prompt evaluation and further diagnostic testing to determine the underlying cause and guide treatment decisions.

From the Research

Significance of Elevated Lactate Dehydrogenase (LDH)

Elevated LDH levels can be indicative of various conditions, including:

• Hemolysis, where red blood cells are broken down, releasing LDH into the bloodstream 2, 3
• Thrombotic thrombocytopenic purpura (TTP), a blood disorder characterized by the formation of blood clots in small blood vessels 2, 4, 3
• Hemolytic uremic syndrome (HUS), a condition characterized by the breakdown of red blood cells and kidney failure 4, 5
• Pump-induced thrombosis in patients with continuous-flow left ventricular assist devices (CF-LVADs) 6

LDH Isoenzymes

LDH exists as five isoenzymes, each with a unique tissue distribution:

• LDH-1 and LDH-2 are associated with erythrocytes and are elevated in conditions such as TTP and HUS 2, 6
• LDH-3 is not typically elevated in these conditions 2
• LDH-4 and LDH-5 are associated with skeletal muscle and liver, and are elevated in conditions such as TTP 2
• LDH-5 is also elevated in patients with CF-LVAD pump thrombosis 6

Clinical Implications

Elevated LDH levels can have significant clinical implications, including:

• Predicting response to plasma exchange in patients with TTP/HUS 4
• Diagnosing pump-induced thrombosis in patients with CF-LVADs 6
• Assessing the severity of microangiopathic changes in patients with TTP 3
• Identifying patients with athrombocytopenic thrombotic microangiopathy, a condition that may be overlooked based on current diagnostic criteria 5