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Blood Test Tracker

Cryoglobulin Screen

Checks whether proteins in your blood clump when cold and dissolve when warmed. A negative result means none were seen.

AI-verified against cited sources. Awaiting expert reviewLOINC 5117-7

What it is

Cryoglobulins are antibodies that clump or turn gel-like when blood cools below body temperature and dissolve again when it is warmed. This test checks whether any are present in your serum. The blood has to be drawn into a warm tube and kept warm until it clots. The serum is then kept cold and checked for a few days. Cryoglobulins are hard to measure, so the test should be done by a lab that is set up for it.

Why it matters

Cryoglobulins can block small blood vessels or cause inflammation in them, which can lead to skin spots or sores, joint pain, numbness or tingling, or kidney problems. A positive test is a clue that clinicians follow up with typing tests and checks for hepatitis C, autoimmune conditions and blood disorders. A negative result means none were seen, but a sample that cooled too early can miss them. Small amounts are also found in some people who are healthy.

If it’s high

A positive result means proteins that clump in the cold were seen in your serum. A positive test alone doesn't mean you have cryoglobulinemia, the disease, because small amounts can show up during infections and in some healthy people. Clinicians look at the type, the amount and your symptoms. Many other things can cause this, and your clinician can put it in context.

Common causes

  • Low levels in people who are otherwise healthy
  • Hepatitis C infection, which is the leading cause of mixed cryoglobulins
  • Other infections, such as hepatitis B, HIV or infectious mononucleosis
  • Autoimmune conditions, such as lupus or rheumatoid arthritis
  • Blood and lymph conditions, such as multiple myeloma, Waldenström macroglobulinemia, lymphoma or leukemia
  • No clear cause, in a smaller share of people

What can help

  • Ask whether typing the cryoglobulin and measuring its amount (cryocrit) would help
  • Ask whether hepatitis C and B tests, rheumatoid factor, C4 and kidney and urine tests are worth doing
  • If the test was negative but symptoms continue, ask whether it should be repeated with careful warm handling

What can affect your result

  • Warm handling: the sample must stay at 37 °C from the draw until the blood clots, or the result can be falsely negative
  • Tube and sample type: serum from a plain tube is needed, not plasma or gel-barrier tubes
  • Length of cold incubation: ARUP reads the result at 72 hours, while other labs look for up to 7 days
  • Heparin: a catheter with heparin or heparin treatment can create look-alike precipitates
  • Amount of cryoglobulin: very low levels can take longer to appear or be missed
  • Blood that cools before it clots can lose its cryoglobulins and give a false negative result. The tube should be warm when drawn and kept at body temperature (37 °C) until the blood has clotted (ARUP, MedlinePlus, 2017 review).
  • ARUP does not accept plasma or gel-barrier (serum separator) tubes for this test, and a draw from a catheter that holds heparin should be avoided (MedlinePlus).
  • Heparin or fibrinogen can form cold precipitates that look like cryoglobulins, so labs confirm that the precipitate dissolves again on warming (2017 review).
  • A small blood volume can miss low levels, and ARUP notes that less than 3 mL of serum may reduce sensitivity.
  • ARUP asks for fasting (overnight or at least 8 hours) and rejects grossly fatty (lipemic) or hemolyzed samples.

Weeks to months, depending on the cause. In treatment studies for hepatitis C summarized in a 2026 review, cryoglobulin levels fell in most people, but they disappeared completely in only about 30%.

When to talk to a clinician

Talk with your clinician about a positive result, especially with a purple or red rash on the legs, painful or color-changing fingers or toes in the cold, joint pain, numbness or tingling, foamy or dark urine, or swelling. Get prompt medical care for new skin sores, fingers or toes that turn blue or black, sudden weakness, chest pain or trouble breathing.

Questions you could ask

  • Was my sample kept warm correctly, and would repeating the test help if my symptoms continue?
  • What type of cryoglobulin is it, and should we measure the amount (cryocrit)?
  • Should we check for hepatitis C and other possible causes?
  • Do my kidney and urine tests need a closer look?

Questions people ask

Why does my blood have to stay warm for this test?

Cryoglobulins clump in the cold. If your blood cools before it clots, they can stick to the clot and be lost, so the result may read negative even when they are present. That is why the tube is warmed and the sample is kept at body temperature.

Does a positive result mean I'm sick?

Not by itself. Small amounts can appear during infections and in some healthy people. Clinicians look at the type, the amount and your symptoms. If you have symptoms, further tests may follow.

Why can results take several days?

After the blood clots, the serum is kept cold and checked over time. ARUP checks daily for three days, and other protocols look for up to seven days, because low levels take longer to appear.

Show the science and sources

For clinicians and researchers

Cryoglobulins are immunoglobulins that precipitate in serum below 37 °C and redissolve on rewarming. Brouet's classification has three types: type I is a single monoclonal immunoglobulin (IgM or IgG), linked to lymphoproliferative disease such as myeloma or Waldenström macroglobulinemia, and causes hyperviscosity and vessel blockage; type II is a monoclonal IgM with rheumatoid factor activity bound to polyclonal IgG; and type III is polyclonal IgM and IgG. Types II and III are called mixed cryoglobulinemia and cause immune-complex, complement-mediated small-vessel vasculitis, with HCV linked to about 80–90% of mixed cryoglobulinemia cases (2026 review). Mixed cryoglobulinemia typically shows high rheumatoid factor and low C4. Preanalytical steps are critical: blood is drawn in a pre-warmed plain tube without anticoagulant or gel, kept at 37 °C until clotted, and spun warm (2017 review). ARUP asks for about 7 mL of blood, separates serum within 1 hour and inspects daily over 3 days (negative at 72 hours), while other protocols hold serum at 4 °C in a Wintrobe tube for at least 7 days (2017 review). Thermoreversibility is confirmed by rewarming, because heparin-fibronectin or fibrinogen-fibrin complexes can mimic cryoglobulins. The cryocrit is a semi-quantitative measure of the precipitate; the precipitate can be washed and typed by immunofixation (2017 review). The presence of cryoglobulins or cold agglutinins may affect IgM measurement (Waldenström 2013 review). ARUP notes cryoglobulins can be found at low levels in apparently healthy people.

LOINC 5117-7 (primary), 12203-6, 12202-8, 12204-4, 12207-7, 2167-5. Specimen: serum.

Sources

  1. Cryoglobulin, Qualitative (test 0050185), ARUP Laboratories
  2. Cryoglobulins, MedlinePlus (National Library of Medicine) (2025)
  3. Cryoglobulin Test and Cryoglobulinemia Hepatitis C-Virus Related, Mediterranean Journal of Hematology and Infectious Diseases (2017)
  4. Cryoglobulinemia: An update on classification, pathophysiology, clinical presentation, and management, Journal of Internal Medicine (2026)
  5. How to manage Waldenstrom's macroglobulinemia, Leukemia (2013)
  6. LOINC code lookup (NLM Clinical Tables), National Library of Medicine

AI-verified against cited sources. Awaiting expert review. Last reviewed 2026-10-03. How we build and check these pages.

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