Cryoglobulins are abnormal proteins in the blood. If you have cryoglobulinemia (kry-o-glob-u-lih-NEE-me-uh), these proteins may clump together at temperatures below 98.6 F (37 C). These gelatinous protein clumps can impede your blood circulation, which can damage your skin, joints, nerves and organs — particularly your kidneys and liver.

Cryoglobulinemia care at Mayo Clinic


Symptoms usually come and go, and may include:

  • Skin lesions. Most people with cryoglobulinemia develop purplish skin lesions on their legs. In some people, leg ulcers also occur.
  • Joint pain. Symptoms resembling rheumatoid arthritis are common in cryoglobulinemia.
  • Peripheral neuropathy. Cryoglobulinemia can damage the nerves at the tips of your fingers and toes, causing numbness and other problems.


Cryoglobulinemia has been associated with:

  • Infections. Hepatitis C is the most common infection associated with cryoglobulinemia. Others include hepatitis B, HIV, Epstein-Barr, toxoplasmosis and malaria.
  • Certain cancers. Some cancers of the blood, such as multiple myeloma, Waldenstrom macroglobulinemia and chronic lymphocytic leukemia, can sometimes cause cryoglobulinemia.
  • Autoimmune disorders. Disease such as lupus, rheumatoid arthritis and Sjogren's syndrome increase the risk of developing cryoglobulinemia.

Risk factors

Risk factors of cryoglobulinemia may include:

  • Your sex. Cryoglobulinemia occurs more frequently in women than in men.
  • Age. Symptoms of cryoglobulinemia usually begin in middle age.
  • Other diseases. Cryoglobulinemia is associated with diseases such as hepatitis C, HIV, multiple myeloma, Waldenstrom macroglobulinemia, lupus and Sjogren's syndrome.

Cryoglobulinemia care at Mayo Clinic

Jan. 18, 2022

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  2. Ferri FF. Cryoglobulinemia. In: Ferri's Clinical Advisor 2020. Elsevier; 2020. https://www.clinicalkey.com. Accessed Nov. 13, 2019.
  3. AskMayoExpert. Cryoglobulinemia. Mayo Clinic. 2019.
  4. Desbois AC, et al. Cryoglobulinemia: An update in 2019. Joint Bone Spine. 2019; doi:10.1016/j.jbspin.2019.01.016.
  5. Therapeutic apheresis. Merck Manual Professional Version. https://www.merckmanuals.com/professional/hematology-and-oncology/transfusion-medicine/therapeutic-apheresis?query=plasmapheresis. Accessed Nov. 13, 2019.
  6. Muchtar E, et al. How I treat cryoglobulinemia. Blood. 2017; doi:10.1182/blood-2016-09-719773.
  7. Gertz MA (expert opinion). Mayo Clinic. Nov. 18, 2019.


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