Elevated Lactate Dehydrogenase (LDH) - Differential Diagnosis Framework



LDH is a cytoplasmic enzyme present in tissues throughout the body.

 • Present in high concentrations in: RBCs, muscle, liver, and kidney

 • LDH assays can measure the amount of LDH present in the serum that has leaked from the tissues upon damage

 • Normal range of LDH is between 140 to 280 U/L

 • It can remain elevated for up to 7 days in the bloodstream



Hemolysis:

 • Hemolytic Anemias:

	- Spherocytosis, sickle cell disease, deficiency of red blood cell enzymes

	- Acquired: Microangiopathic hemolytic anemia, PNH, immune hemolysis

 • Ineffective Erythropoiesis:

	- Pernicious anemia, folic acid deficiency

	- Iron deficiency

	- Primary myelofibrosis

 • Hemolysis:

	- Prosthetic valves



Lung:

 • Pneumocystis pneumonia (late)

 • Tuberculosis

 • Legionnaires disease

 • Pulmonary infarction

 • COVID-19 Pneumonia

 • Other lung injuries



Hepatic Injury:

 • Early acute hepatitis

 • Ischemic hepatitis

 • Acute Hepatocellular Injury - Markedly elevated serum LDH level distinguishes ischemic hepatitis (ALT-to-LDH ratio < 1.5) from viral hepatitis (ALT-to-LDH ratio > 1.5) with a sensitivity and specificity of 94 and 84%



Renal:

 • Renal infarction



Muscle:

 • Rhabdomyolysis

 • Myopathies (inherited, acquired, drug)

 • Periodic paralyses



CNS Disorders:

 • Bacterial meningitis

 • Cerebral hemorrhage

 • Cerebral venous thrombosis



Cardiac:

 • Myocyte injury

 • Demand ischemia

 • Trauma, cardiovascular surgery

 • Toxins

 • Infection (myocarditis, rheumatic fever)

 • Drugs (alcohol, chemotherapy, cocaine, methysergide, carbon monoxide)



Malignancy:

 • Lymphomas

 • Leukemias

 • Serum biomarker used in metastatic melanoma

 • Solid tumors (testicular germ cell tumors)

 • Tumor lysis syndrome (large tumor burden)



Vasculitis:

 • Polyarteritis nodosa

 • Eosinophilic granulomatosis with polyangiitis

 • Granulomatosis with polyangiitis

 • Behçet's syndrome

 • Sarcoidosis



Idiosyncratic LDH Elevation:

 • The presence of macro-LDH (LDH combined with an immunoglobulin), not associated with any symptoms or particular disease



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