CRYOGLOBULINEMIA is somewhat similar to Cold Agglutinin Disease on the surface, but it is not the same.  It is only the same, in regard to being a temperature triggered blood hazard.    It also shares a common discoloration symptom similar to CAD.

The discoloration, in both CRYOGLOBULINEMIA and CAD, is often also confused with yet another disease called Raynaud’s which is caused not by any type of clumping, but by vascular constrictions.

The discoloration in general, of all of these diseases, is often referred to as “Raynaud’s Phenomenon“.  Not really Raynaud’s itself.  Which can lead to some confusion if someone isn’t paying attention. Or doesn’t know enough to ask for more specific information.

CRYOGLOBULINEMIA is abnormal proteins (cryoglobulins) that are found in the blood.   Specifically, Immunoglobulins, (i.e. IgG, IgM, IgA, or light chains).  Which are affected by temperature below below 98.6°F/37°C.  These proteins can clump together (Precipitate) within the blood vessels.  They dissolve when rewarmed. (This in not the same as Agglutination).

With Precipitate the clumping is not attacking/destroying Red Blood Cells (not causing Hemolysis), as Cold Agglutinin Disease does.

Note: Precipitate differs, from Agglutination that is associated with Cold Agglutinin Disease.

Other symptoms include paleness, cold extremities, bruising, rashes, pain, and weakness.  The relative quantity of Cryoglobulins in the blood impacts how reactive Precipitate/”Protein Clumping” may be.

Ignoring this clumping/Precipitate, and its symptoms.  Can lead to blood circulation issues that cause a variety of symptoms and problems.  Anything from temporary pain, to damage to skin, muscles, nerves, joints, and organs.  It can cause inflammation, bleeding, clotting, neuropathy, and necrosis.

Testing:  Cryoglobulinemia is diagnosed by a specific blood test that detects the relative quantity of cryoglobulins in the blood.

Mishandling the blood sample can result in inaccurate results.   There are specific requirements necessary to perform this test.  This test is not available at all labs.  Be sure to discuss this with your doctor and lab manager.

The cryoglobulins test is negative (no cryoglobulins found) in most healthy people and is not routinely ordered for those without symptoms.

Initial testing will not distinguish between various types of Cryoglobulins.  To determine which proteins are involved  “Protein Electrophoresis Testing” is necessary.

A blood sample must be collected in prewarmed tubes and kept at body temperature during test preparation.  The collected serum is then refrigerated for 72 hours and examined every day for precipitates.  If they are present, the quantity is estimated.  Then the sample is warmed to see if the precipitate dissolves.  If they do, then cryoglobulins are present.

Additional testing may be done to determine the specific type of Cryoglobulin.

A positive test for cryoglobulins may be seen in numerous conditions. Some examples include:

* Lyme Disease, Mono, Hepatitis C.  Also Hepatitis B, HIV, EB, Malaria, and toxoplasmosis.
* Kidney Disease
Autoimmune Diseases:
*Lupus erythematosus, rheumatoid arthritis, and Sjögren syndrome
*Increase in lymphocytes such as multiple myeloma, lymphoma and lymphoid leukemia

Treatments: Steroids, Plasmapheresis to remove cryoglobulins from the plasma.  If other conditions like Hepatitis C is found.  Anti-Viral therapy may be prescribed by a Hematologist.

If Myeloma or Lymphoma is detected, a Hematologist/Oncologist is recommended.

Many people who have cryoglobulinemia are chronically infected with hepatitis C virus (HCV), although not everyone with HCV, will develop cryoglobulinemia.

In addition to Protein Electrophoresis (See note 1 below) and, depending on the suspected underlying condition.  Other tests that may be performed including Hepatitis C, ANA, Mono test, and Rheumatoid factor, to name a few.

Note 1: Protein Electrophoresis is performed on serum (the fluid portion of blood), urine samples, or, in certain circumstances, cerebrospinal fluid (CSF).

Protein electrophoresis is used to identify and measure the presence of abnormal proteins, the absence of normal proteins, and/or to detect various protein electrophoresis patterns associated with certain conditions.

Protein electrophoresis tests give a doctor a rough estimate of how much of each of the protein fractions is present and whether any abnormal proteins or protein patterns are present.