ALGORITHM —
INITIAL EVALUATION —
Lactate dehydrogenase (abbreviated LD or LDH) is a cytoplasmic enzyme present in tissues throughout the body. Heart, muscle, kidney, lung, and erythrocytes have the highest concentration. LDH is nonspecifically elevated in many disorders (table 1). Interpretation of an elevated level depends on the reason for the test, comprehensive history and physical examination, initial laboratory tests, and whether the patient is acutely ill. Review (or obtain, if not available) tests usually reported along with LDH:
●Complete blood count (CBC) with differential and platelet count
●Serum creatinine
●Liver biochemical tests, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (see "Overview of liver biochemical tests", section on 'Lactate dehydrogenase')
Further evaluation depends on the clinical assessment.
Acute illness — Marked elevations in serum LDH levels can be observed in acutely ill individuals due to cell injury (eg, ischemia). The hemodynamic insult is usually apparent clinically before evidence of cell injury appears. Identify and address findings that require urgent attention. As examples:
●Prolonged hypoxia and shock with multiorgan failure. (See "Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock".)
●Ischemic hepatitis – Early massive rise in LDH levels associated with a rapid rise in serum aminotransferase levels (>1000 international units/L or 50 times the upper limit of normal [ULN]). (See "Ischemic hepatitis, hepatic infarction, and ischemic cholangiopathy".)
●Drug-induced life-threatening clinical syndromes – Neuroleptic agents, serotonin syndrome, recreational drugs. (See "Serotonin syndrome (serotonin toxicity)", section on 'Diagnosis and diagnostic criteria' and "MDMA (ecstasy) intoxication", section on 'Clinical features' and "Neuroleptic malignant syndrome", section on 'Evaluation and diagnosis'.)
●Tumor lysis syndrome. (See "Tumor lysis syndrome: Pathogenesis, clinical manifestations, definition, etiology and risk factors".)
●Rapid intravascular hemolysis – Thrombotic microangiopathy, acute hemolytic transfusion reaction, rapid intravascular hemolysis. (See "Diagnosis of hemolytic anemia in adults", section on 'Immediate management issues before the cause is identified'.)
●Infections – Pneumocystis carinii (jirovecii) pneumonia (PCP), infectious mononucleosis, malaria, tuberculosis, and toxoplasmosis.
Chronic illness
Suspected hemolysis — Serum LDH is one of several tests used to confirm hemolysis in patients diagnosed with anemia, when hemolysis is suspected and other causes have been excluded. Signs of red blood cell (RBC) destruction include increased LDH, low haptoglobin, and increased indirect (unconjugated) bilirubin. (See "Low hemoglobin, hematocrit in adults".)
Review (or obtain, if not available):
●Serial CBCs with differential and platelet count to determine the pace and severity of hemolysis
●Corrected or absolute reticulocyte count, peripheral blood smear to assess bone marrow production and RBC morphology
●Haptoglobin
●Bilirubin
●Direct antiglobulin test (Coombs test) to identify immune-mediated RBC destruction
Assess for the underlying cause, including medications for possible drug-related hemolysis (table 2). (See "Drug-induced hemolytic anemia" and "Diagnosis of hemolytic anemia in adults", section on 'Post-diagnostic testing to determine the cause'.)
Prognostic metric in cancer — LDH elevations in malignancy are not useful in the diagnosis of cancer but may be of prognostic value in patients with advanced cancer. In metastatic melanoma, an elevation in serum LDH level may be the first indication of liver metastases. LDH is one of several tumor markers in the following cancers:
●Germ cell tumors of the ovary. (See "Ovarian germ cell tumors: Pathology, epidemiology, clinical manifestations, and diagnosis", section on 'Tumor markers'.)
●Testicular cancer. (See "Serum tumor markers in testicular germ cell tumors", section on 'Lactate dehydrogenase'.)
●Multiple myeloma. (See "Multiple myeloma: Staging and prognostic studies", section on 'Revised International Staging System (R-ISS)'.)
●Prostate cancer. (See "Overview of the treatment of castration-resistant prostate cancer (CRPC)", section on 'Clinical parameters'.)
●Non-Hodgkin lymphoma, both indolent and aggressive. (See "Prognosis of diffuse large B cell lymphoma", section on 'Overview'.)
●Cutaneous melanoma. (See "Tumor, node, metastasis (TNM) staging system and other prognostic factors in cutaneous melanoma", section on 'Distant metastases (M)'.)
Analysis of pleural effusion — An important initial step in the analysis of pleural fluid is to ascertain whether the fluid is a transudate or an exudate. The pleural fluid is an exudate if the pleural fluid to serum LDH ratio is >0.6 or if the pleural fluid LDH is greater than two-thirds of the ULN. (See "Pleural fluid analysis in adults with a pleural effusion", section on 'Lactate dehydrogenase'.)
Further evaluation is required to identify the cause (table 3).
Seemingly well — Moderate to slight elevations in LDH levels can be observed as an incidental finding in asymptomatic, healthy individuals who have an LDH measured as part of a biochemical profile. No further evaluation is usually necessary unless there are worrisome clinical features (table 1).
If the laboratory reports a hemolyzed specimen in a seemingly well individual, it may be due to traumatic venipuncture, transportation via pneumatic tube, or vigorous mixing, which can cause release of LDH from hemolyzed RBCs into serum. Obtain repeat LDH in this setting.
REFERENCE RANGE —
Interpretation of a specific abnormal result should be based upon the reference range reported for that result.
The normal reference range for LDH varies widely from laboratory to laboratory because the assay measures the enzymatic activity of LDH rather than the quantity of LDH. Serial LDH measurements should be performed using the same assay.
CITATIONS —
The supporting references for this content are accessible in the linked topics.