Multiple myeloma causes a distinct pattern of lab abnormalities that typically shows up across several types of blood and urine tests. The hallmark findings fall under the acronym CRAB: high calcium, renal (kidney) problems, anemia, and bone lesions. But several other lab values shift as well, and understanding which ones matter can help you make sense of a diagnosis or follow disease activity over time.
The CRAB Criteria: Four Core Abnormalities
The International Myeloma Working Group introduced the CRAB acronym in 2003 to capture the four most common ways myeloma damages the body. Each letter points to a specific lab finding or imaging result that signals the disease has become active and needs treatment.
- Calcium (elevated): Serum calcium above 11.0 mg/dL. Myeloma breaks down bone tissue, releasing calcium into the bloodstream. Levels above 13 mg/dL at initial presentation strongly suggest a malignancy is driving the elevation. Symptoms include excessive thirst, frequent urination, constipation, and confusion.
- Renal impairment: Serum creatinine above 2 mg/dL or a creatinine clearance below 40 mL/min. Abnormal proteins produced by myeloma cells can clog and damage the tiny filtering units in the kidneys.
- Anemia: Hemoglobin below 10 g/dL. Myeloma crowds out healthy blood-producing cells in the bone marrow. About 70% of newly diagnosed patients are anemic, with a median hemoglobin around 11.0 g/dL. Roughly 5% present with hemoglobin below 8.0 g/dL, which is severe enough to cause pronounced fatigue and shortness of breath.
- Bone disease: One or more holes (osteolytic lesions) visible on imaging. This is identified through X-rays, CT scans, or PET scans rather than a blood draw, but it’s grouped with the lab findings because it’s part of the same diagnostic checklist.
Having even one of these CRAB findings, combined with evidence of abnormal plasma cells, is enough to classify the disease as active myeloma requiring treatment.
Monoclonal Protein on Electrophoresis
The most characteristic lab finding in myeloma is an abnormal spike on a test called serum protein electrophoresis (SPEP). This test separates your blood proteins by size and electrical charge. In myeloma, a single clone of plasma cells churns out large quantities of one identical protein, creating a sharp spike on the readout called an M-spike or M-protein.
The size of the M-spike helps distinguish myeloma from its precursor conditions. An M-spike under 3 g/dL with fewer than 10% plasma cells in the bone marrow and no organ damage points to MGUS, a common and usually harmless condition. An M-spike of 3 g/dL or higher without organ damage suggests smoldering myeloma, a precancerous stage. Active myeloma can produce an M-spike at any concentration, but it’s accompanied by organ damage or other markers of aggressive disease.
A similar test can be run on urine (called UPEP) to detect abnormal proteins the kidneys have filtered out. When these proteins are light chain fragments, they’re historically called Bence Jones proteins. The standard method uses a 24-hour urine collection, and results are reported in milligrams per 24 hours. About 3% of myeloma cases are “non-secretory,” meaning no M-protein shows up on either blood or urine electrophoresis, which makes diagnosis harder.
Serum Free Light Chains
Antibodies are made of two types of protein chains: heavy and light. In myeloma, the cancerous plasma cells often produce an excess of one type of light chain (either kappa or lambda), which circulates freely in the blood. A serum free light chain test measures both types and calculates their ratio.
The normal diagnostic ratio ranges from 0.26 to 1.65. A ratio outside this range suggests one light chain is being overproduced, which is a hallmark of plasma cell disorders. About two-thirds of myeloma patients overproduce kappa light chains, and one-third overproduce lambda. This test is especially valuable for detecting disease that doesn’t produce a visible M-spike on standard electrophoresis.
Bone Marrow Plasma Cell Percentage
A bone marrow biopsy isn’t a blood test, but it produces one of the most important numbers in myeloma diagnosis. Normally, plasma cells make up a small fraction of bone marrow cells. A finding of 10% or more clonal plasma cells is one of the key diagnostic criteria for myeloma. In many patients, the percentage is far higher, sometimes exceeding 60% or 90%, which correlates with more advanced disease.
LDH and Beta-2 Microglobulin: Gauging Severity
Two additional blood tests help doctors assess how aggressive the disease is and predict outcomes. Lactate dehydrogenase (LDH) is an enzyme released when cells are damaged or multiplying rapidly. Elevated LDH in myeloma signals a high tumor burden. Patients with LDH above 250 U/L in one study had a median survival of just 4 months compared to 20 months for those with lower levels. LDH is rarely elevated at diagnosis but tends to climb as the disease progresses or if myeloma develops outside the bone marrow.
Beta-2 microglobulin is a small protein shed by myeloma cells. It’s a cornerstone of the International Staging System, which groups patients into three risk categories based on beta-2 microglobulin and albumin levels. Higher beta-2 microglobulin generally means more myeloma cells are present in the body.
Complete Blood Count Changes
Beyond hemoglobin, a standard complete blood count (CBC) often reveals other abnormalities. White blood cell counts may be low because myeloma displaces normal immune cells in the marrow, leaving patients more vulnerable to infections. Platelet counts can also drop for the same reason, increasing bruising and bleeding risk. Both of these findings reflect the extent to which myeloma has overtaken normal bone marrow function. Low platelet count has been identified as an independent prognostic factor alongside staging systems and LDH.
Albumin and Total Protein
A basic metabolic panel or liver panel will often show low albumin in myeloma patients. Albumin is a protein made by the liver that reflects overall nutritional status and inflammation levels. Myeloma drives it down through chronic inflammation and poor nutrition. At the same time, total protein levels may be paradoxically high because the massive amount of M-protein produced by myeloma cells gets counted in the total. This combination of low albumin but high total protein is a classic red flag that prompts further testing.
How These Labs Fit Together
No single lab test confirms myeloma on its own. Diagnosis requires a combination: evidence of clonal plasma cells (from a bone marrow biopsy or M-protein detection) plus signs of organ damage (CRAB criteria) or biomarkers indicating the disease is likely to cause damage soon, such as a free light chain ratio of 100 or higher or bone marrow plasma cells above 60%. The full picture emerges from layering these results together, which is why an initial myeloma workup involves so many different blood draws, urine collections, and imaging studies at once.