To assist in identifying the presence of certain types of cancer, immunological disorders, and infections associated with the presence of cryoglobulins.

Patient Preparation
There are no food, fluid, activity, or medication restrictions unless by medical direction.

Normal Findings
(Method: Visual observation for changes in appearance) Negative.

Critical Findings and Potential Interventions


(Study type: Blood collected in a red-top tube; related body system: Immune system.) Cryoglobulins are abnormal proteins of three types (Type I, Type II, Type III), now known to be associated with immunological disorders, especially those of viral origin. Cryoglobulinemia occurs more frequently in women in than men; symptoms usually begin to appear in middle age. Cryoglobulins cause vascular problems evidenced in signs and symptoms, especially in cold weather, such as bluing, bruising, numbness, pain, paleness, rashes, and tingling of the skin. Raynaud disease, also known as Raynaud phenomenon, is an inflammatory reaction in the fingers and toes that occurs with exposure to cold. Because they can precipitate in the blood vessels, cryoglobulins may cause significant skin damage leading to ulcerations or gangrene. Precipitates can also cause inflammation, bleeding, and clotting in vessels of major organs such as the kidneys and liver.

The cryoglobulin test has two steps: the serum sample is first observed for precipitation at three intervals (24, 48, and 72 hr) after storage at 4°C. In the second step of the procedure, the sample is warmed. True cryoglobulins disappear on warming. The cryoglobulin test does not distinguish between the three types of cryoglobulins. Additional tests to identify underlying diseases associated with cryoglobulinemia include:

  • Antinuclear antibody testing (related to connective tissue diseases such as SLE and Sjögren syndrome)
  • Complement levels (related to hypocomplimentemia, especially low C4 levels)
  • CBC/RBC count (e.g., related to anemia of chronic disease)
  • CBC/WBC count (e.g., related to infection or leukemia)
  • Liver function tests followed by viral serology (e.g., related to Hepatitis C)
  • Rheumatoid factor (positive findings in 80%–90% of Type II and Type III associated cases)
  • Viral antigens or antibodies (e.g., related to viral hepatitis)


  • Assist in diagnosis of neoplastic diseases, acute and chronic infections, and collagen diseases.
  • Detect cryoglobulinemia in patients with symptoms indicating or mimicking Raynaud disease.
  • Monitor course of collagen and rheumatic disorders.

Interfering Factors

Factors that may alter the results of the study

  • Testing the sample prematurely (before total precipitation) may yield incorrect results.
  • Failure to maintain sample at normal body temperature before centrifugation can affect results.

Other Considerations:

  • A recent fatty meal can increase turbidity of the blood, decreasing visibility.

Potential Medical Diagnosis: Clinical Significance of Results

Increased In:

Cryoglobulins are present in varying degrees in associated conditions.

    Type I cryoglobulin (monoclonal cryoglobulinemia; most commonly IgM or IgG associated with a B cell lymphoproliferative disease)
  • Chronic lymphocytic leukemia
  • Lymphoma
  • Multiple myeloma
  • Type II cryoglobulin (mixed cryoglobulinemia of monoclonal IgM with rheumatoid factor reactivity and polyclonal IgG most commonly associated with a viral disease)
  • Epstein-Barr (infectious mononucleosis)
  • Hepatitis B
  • Hepatitis C (the most common cause for type II cryoglobulinemia)
  • HIV
  • Malaria
  • Membranoproliferative glomerulonephritis
  • Rheumatoid arthritis
  • Sjögren syndrome
  • Toxoplasmosis
  • Waldenström macroglobulinemia
  • Type III cryoglobulin (mixtures of polyclonal IgM with rheumatoid factor reactivity and polyclonal IgG associated with collagen vascular, infectious, or chronic inflammatory diseases similar to Type II cryoglobulinemia)
  • Acute poststreptococcal glomerulonephritis
  • Cirrhosis
  • Endocarditis
  • Epstein-Barr (infectious mononucleosis)
  • Hepatitis B
  • Hepatitis C
  • Infectious mononucleosis
  • Membranoproliferative glomerulonephritis
  • Polymyalgia rheumatica
  • Rheumatoid arthritis
  • Sarcoidosis
  • Systemic lupus erythematosus

Decreased In:

Nursing Implications

Before the Study: Planning and Implementation

Teaching the Patient What to Expect

  • Inform the patient this test can assist in assessing for immune system disorders.
  • Explain that a blood sample is needed for the test.

After the Study: Potential Nursing Actions

Followup Evaluation and Desired Outcomes

  • Acknowledges that additional testing may be performed in order to evaluate or monitor progression of the disease process and determine the need for a change in therapy.
  • Understands that a diagnosis associated with cryoglobulinemia will require lifestyle changes that include avoiding smoke, increasing exercise, recognize and control stressful situations, and avoid moving between rapidly changing temperatures (hot to cold or visa versa).

Cryoglobulinis the Nursing Central Word of the day!