LDH blood test: what lactate dehydrogenase is, the normal range and what a high LDH means

A high LDH means cells somewhere have been damaged or are turning over faster than usual, and the enzyme has leaked into your blood. On its own the result does not say which cells. The first check is whether the sample was hemolysed, since red cells are so rich in LDH that a rough draw can double the result; a repeat from a smooth venepuncture settles this. The next check is recent exercise: a hard run, a long hike or an unaccustomed workout raises LDH to 1.5 to 2 times normal for several days.

If the rise is real, the rest of the blood work points to the source. A low haptoglobin, high reticulocyte count and raised indirect bilirubin with a high LDH indicate hemolysis, whether from an autoimmune process, a mechanical heart valve, sickle cell disease or a microangiopathy such as TTP. A very high LDH with a high MCV and low B12 or folate means megaloblastic anemia, where red cell precursors die in the marrow. A high ALT and AST point to the liver, a high CK to muscle, a high troponin to the heart, and a high CRP with cough or fever to pneumonia. LDH is also raised in many infections, including mononucleosis, influenza and COVID-19, where it tracks severity.

Cancer is the cause people worry about most. Lymphoma, leukemia, germ cell tumors, melanoma and widespread metastatic disease of many types raise LDH through rapid cell turnover and tumor breakdown, and in those specific cancers the LDH level is used for staging and prognosis. However, LDH is not a cancer screening test: most raised values have a benign explanation, and a modestly high LDH in someone with no other findings is far more likely to be exercise, a hemolysed sample or a passing infection. Cancer enters the picture when LDH stays high with swollen lymph nodes, night sweats, unexplained weight loss, a mass or abnormal blood counts.

Common causes

1. 1.

   Hemolysed sample (artefact)

   The most common reason for an unexpectedly high LDH. A tight tourniquet, small needle, vigorous mixing or delayed separation breaks red cells in the tube; the lab usually adds a hemolysis flag. The potassium and AST are often raised in the same sample. Repeat before investigating.

2. 2.

   Hemolytic anemia

   Autoimmune hemolysis, hereditary spherocytosis, G6PD deficiency, sickle cell crisis, mechanical heart valves, thrombotic thrombocytopenic purpura and hemolytic uremic syndrome all release LDH, typically 2 to 10 times normal, with low haptoglobin, high reticulocytes and raised indirect bilirubin. In TTP, LDH is used to follow response to treatment.

3. 3.

   Vitamin B12 or folate deficiency (megaloblastic anemia)

   Red cell precursors die inside the marrow (ineffective erythropoiesis), producing some of the highest LDH values seen, often 1,000 to 5,000 U/L, with a high MCV and low haptoglobin. The LDH falls within days of starting replacement.

4. 4.

   Strenuous or unaccustomed exercise

   Marathon running raises LDH about 1.5 to 2 fold for 3 to 7 days, and heavy resistance training or eccentric exercise does the same, usually with a raised CK. The rise is from muscle and is harmless.

5. 5.

   Liver disease

   Viral hepatitis, alcoholic hepatitis, drug-induced liver injury, ischemic hepatitis and liver metastases raise LDH (mainly LDH-5) alongside ALT and AST. In ischemic hepatitis the ALT to LDH ratio is characteristically low.

6. 6.

   Heart attack and other tissue infarction

   LDH rises 24 to 72 hours after a myocardial infarction, peaks around day 3 to 4 and returns to normal in 1 to 2 weeks; troponin has replaced it for diagnosis. Kidney, lung, bowel and spleen infarction raise LDH similarly, which is why it is checked in suspected mesenteric ischemia.

7. 7.

   Muscle injury and rhabdomyolysis

   Crush injury, severe exertion, seizures, statin myopathy and inflammatory myositis release LDH from skeletal muscle together with CK, which is the more specific marker; in rhabdomyolysis both can reach several thousand.

8. 8.

   Lymphoma, leukemia, germ cell tumors, melanoma and metastatic cancer

   Rapid turnover and tumor necrosis raise LDH in proportion to tumor bulk. It is a formal prognostic factor in aggressive lymphoma (IPI), testicular cancer (S stage) and melanoma (AJCC M category), and it rises sharply in tumor lysis syndrome after chemotherapy. Other cancers raise it less consistently.

9. 9.

   Infections

   Pneumocystis pneumonia in immunocompromised people, bacterial pneumonia, mononucleosis, influenza, COVID-19, HIV, malaria (through hemolysis) and sepsis all raise LDH, often to 1.5 to 3 times normal, with higher values marking more severe illness.

10. 10.

    Hypothyroidism, pancreatitis, kidney disease and some medicines

    Untreated hypothyroidism raises LDH and CK modestly; acute pancreatitis, acute kidney injury, glomerulonephritis and shock with poor organ perfusion raise it; anesthetics, aspirin in high doses, some chemotherapy agents and interferon can raise it. Alcohol and anabolic steroids raise it through liver and muscle effects.

Symptoms that can go with it

• Often none: a mildly raised LDH from exercise or a hemolysed sample causes no symptoms
• Fatigue, breathlessness on exertion, pale or yellow-tinged skin and dark urine with hemolytic or megaloblastic anemia
• Muscle pain, weakness and tea-colored urine after extreme exertion, injury or with statin myopathy
• Fever, cough and breathlessness with pneumonia; sore throat, swollen glands and exhaustion with mononucleosis
• Chest pain or pressure with a heart attack, severe abdominal pain out of proportion to examination with bowel ischemia
• Painless swollen lymph nodes, drenching night sweats, unexplained weight loss or itching with lymphoma
• Fever, confusion, bruising and purple spots with a very high LDH and low platelets (possible TTP), which is an emergency

A low LDH is uncommon and almost never a problem. The reference range reflects normal cell turnover, and a value a little below it simply means little tissue is being damaged, which is good. Laboratories rarely act on it, and there is no condition in which a low LDH is itself harmful.

There are two genuine causes worth knowing. Large doses of vitamin C (ascorbic acid) and a few other substances interfere with the chemistry of some LDH assays and give a falsely low reading. And very rarely, an inherited deficiency of one LDH subunit (LDH-A or LDH-B deficiency) produces a very low result; LDH-A deficiency can cause muscle pain, cramps and dark urine with hard exercise, while LDH-B deficiency causes no symptoms at all.

Common causes

1. 1.

   Normal variation

   Healthy people at rest with low cell turnover can fall just below the printed range, particularly on assays with a high lower limit.

2. 2.

   High-dose vitamin C and assay interference

   Ascorbic acid at gram doses, and some other reducing substances, can lower the measured LDH on certain analyzers without changing the real level.

3. 3.

   Inherited LDH subunit deficiency

   LDH-A (M subunit) deficiency is a rare cause of exercise intolerance and exertional myoglobinuria; LDH-B (H subunit) deficiency is a harmless laboratory finding. Both give a very low total LDH.

4. 4.

   Sample or analytical error

   Rarely, a dilution problem or analyzer fault yields an implausibly low value; a repeat resolves it.

Symptoms that can go with it

• None in nearly all cases
• Exercise-induced muscle pain, cramps and dark urine in the rare LDH-A deficiency