LDH-3 Test

When cells in your lungs, lymph nodes, or brain are injured, they leak a specific version of an enzyme called LDH-3 (lactate dehydrogenase isoenzyme 3) into your bloodstream. A standard metabolic panel might show total LDH is elevated, but it cannot tell you where the damage is coming from. LDH-3 narrows that question considerably, pointing toward a handful of tissues where this particular version of the enzyme is most concentrated.

That distinction matters because total LDH rises in dozens of conditions, from a hard workout to advanced cancer. When your doctor sees a high total LDH and shrugs, you are left without a next step. LDH-3, measured alongside its sister versions, can reveal whether the source is your lungs, your blood cells, or something else entirely.

What LDH-3 Is and Where It Comes From

LDH (lactate dehydrogenase) is an enzyme found in nearly every cell in your body. Its job is to help convert lactate and pyruvate (two small molecules cells use to generate energy) back and forth. Because LDH sits inside cells, it only appears in your blood in meaningful amounts when cells are damaged or dying.

Your body makes five versions of LDH, numbered 1 through 5, each built from a slightly different combination of two protein building blocks called the H (heart) and M (muscle) subunits. LDH-3 is built from two H subunits and two M subunits (2H2M), placing it in the middle of the spectrum. Each version is concentrated in different tissues, which is what makes the pattern useful for identifying the source of damage.

Because LDH-3 is especially abundant in lung cells (called pneumocytes) that line the air sacs and in lymphoid tissue, an elevated LDH-3 reading most commonly points to damage in one of those locations.

Blood Cancers and Lymphoma

LDH-3 has its strongest track record in blood cancers, where it serves as both a diagnostic clue and a prognostic signal. In non-Hodgkin lymphoma (NHL), about 64% of patients have high LDH-3 values at the time of diagnosis and 65% at relapse. Elevated LDH-3 in NHL is linked to more aggressive tumor types, more advanced disease stage, and shorter survival, even when total LDH is already known to be high.

In children with acute lymphoblastic leukemia (ALL), LDH-3 is the dominant version at diagnosis. High-risk children show a pattern where LDH-3 exceeds LDH-2, producing an LDH-3 to LDH-2 ratio greater than 1. This flipped ratio does not appear in standard-risk patients, making it a potentially useful marker for distinguishing severity early on.

In Burkitt lymphoma and multiple myeloma, LDH-3 elevation tracks with tumor burden and predicts poorer response to treatment. In chronic granulocytic leukemia (CGL, also known as chronic myeloid leukemia), LDH-3 is elevated in 92% of patients with active disease. As patients enter remission, LDH-3 falls, with only 40% still showing elevated levels in partial remission and just 13% in complete remission. This makes it a practical marker for monitoring whether treatment is working.

Lung Injury and Respiratory Disease

Because lung tissue is rich in LDH-3, severe lung damage is a logical trigger for elevated readings. In COVID-19, total LDH elevation was associated with roughly 6 times the risk of severe disease and 16 times the risk of death in a pooled analysis. One study of 111 COVID-19 patients found that LDH-3 levels specifically were an independent risk factor for clinical deterioration.

However, a separate small study found that elevated total LDH in COVID-19 patients was not always due to a specific spike in LDH-3, suggesting that multiple organs contribute to the LDH rise during severe infection. The takeaway: LDH-3 can flag lung-origin damage, but in a systemic illness, the picture may be mixed.

In patients with acute flare-ups of chronic obstructive pulmonary disease (COPD), LDH isoenzyme patterns differ from those seen in other types of lower respiratory infections. This suggests that the way your respiratory muscles and lung tissue adapt during a COPD flare leaves a distinct enzymatic fingerprint.

Heart Failure and Cardiac Injury

While LDH-1 is the classic cardiac version, total LDH (which includes LDH-3 and all other versions) has strong prognostic value after heart attacks. In a study of 685 elderly patients with acute heart attacks, higher baseline total LDH independently predicted later heart failure. A large trial of over 8,000 patients with heart failure and reduced pumping ability found that higher total LDH was independently tied to worse outcomes.

These findings use total LDH rather than LDH-3 specifically. If your LDH-3 is elevated in the context of cardiac symptoms, the more likely explanation is lung congestion (fluid backing up into the lungs from a failing heart) rather than direct heart muscle damage, which would typically raise LDH-1 instead.

Gynecologic Diagnosis

An unexpected but well-documented use of LDH-3 is in evaluating uterine masses. A study of over 2,200 women found that a scoring system combining LDH-3 and LDH-1 values (called the U.M.G. risk index) could distinguish between benign uterine growths and those suspicious for cancer with 100% sensitivity and 99.6% specificity. That is an exceptionally strong diagnostic performance for any blood-based test.

Reference Ranges

LDH-3 is typically reported as a percentage of total LDH activity, measured by separating the five versions using a technique called electrophoresis (which sorts proteins by their electrical charge). Results can also be reported as absolute activity in units per liter (U/L). Because different labs use different electrophoresis methods and instruments, the exact numbers that count as "normal" vary from one laboratory to another.

An analysis of over 3,500 healthy adults across multiple Asian countries found that LDH isoenzyme patterns are influenced by age, sex, body mass index (BMI), and even blood type. This means that a single universal cutpoint for "normal" LDH-3 does not exist. Your lab will report its own reference range based on its specific method and local population.

As a general orientation, most labs report LDH-3 as roughly 18% to 30% of total LDH activity. If your LDH-3 percentage is elevated above the lab's upper limit, or if the absolute LDH-3 value is high, the next step is to look at the pattern of all five versions together and correlate with your clinical picture. A high LDH-3 alongside normal LDH-1 and LDH-5 points toward lung or lymphoid tissue as the source.

When Results Can Be Misleading

The biggest source of misleading LDH-3 results is hemolysis, which is the destruction of red blood cells during or after the blood draw. If your sample is even slightly hemolyzed (the blood turns pinkish instead of clear yellow after spinning), the LDH released from broken red blood cells will inflate total LDH and distort the isoenzyme pattern, since red blood cells are rich in LDH-1 and LDH-2. This can make it harder to interpret LDH-3 accurately.

Intense physical exercise can temporarily raise total LDH by causing minor muscle cell damage. Because skeletal muscle contributes mainly LDH-4 and LDH-5, this usually does not raise LDH-3 specifically, but it can shift the overall ratios and complicate interpretation. Draw your blood on a rest day if you are looking for a clean baseline.

Any acute illness, surgery, or systemic infection can cause a transient rise in multiple LDH versions simultaneously, making it difficult to pinpoint a single organ as the source. If you are acutely ill when your blood is drawn, retest once you have recovered to get a more interpretable result.

Tracking Your Trend

A single LDH-3 reading is a snapshot, and snapshots can be misleading. The real value of this test comes from watching how LDH-3 changes over time. In chronic granulocytic leukemia, for example, the drop from 92% of patients having abnormal LDH-3 in active disease to just 13% in complete remission shows how powerfully trending this marker can track treatment response.

If you are monitoring a known condition, the cadence should match your treatment cycle. For someone tracking a blood cancer, that might mean testing at each treatment evaluation. For someone investigating an unexplained total LDH elevation, get a baseline isoenzyme profile, address any identified issue, then retest in 4 to 8 weeks to see whether the pattern has shifted.

Always compare results from the same laboratory. Different electrophoresis methods can give slightly different percentages, so switching labs mid-trend can introduce noise that looks like a real change.

What to Do With an Abnormal Result

If your LDH-3 comes back elevated, the first step is to look at the full isoenzyme profile. An isolated LDH-3 elevation with normal LDH-1 and LDH-5 points toward the lungs or lymphoid tissue. If LDH-3 is high alongside LDH-4 or LDH-5, the picture is more mixed and could involve multiple organs.

Next, rule out sample problems. Ask your lab whether there was any hemolysis in the sample. If there was, retest with a fresh, carefully handled draw before interpreting the result.

If the result is confirmed on a clean sample, the clinical context determines the next move. For someone with respiratory symptoms, a chest X-ray or CT scan and pulmonary function testing are logical companions. For someone with suspected or known blood cancer, a complete blood count (CBC) with differential, a peripheral blood smear, and possibly a hematology consultation are appropriate. If you have no obvious symptoms but your total LDH was incidentally high and the isoenzyme profile points to LDH-3, a follow-up with a pulmonologist or hematologist can help determine whether further imaging or bone marrow evaluation is warranted.