Test Code LAB4071 CRYOGLOBULIN
Specimen Type
10 mL Glass Red Top tube
Specimen Volume
30 mL
Minimum Volume
5 mL
Turnaround Time
7 days
Test Schedule
Daily
Sample Stability
Refrigerated: 7 Days
Method
Precipitation
Reference Ranges
Cryoglobulin Negative
Cryocrit < 0.1%
CPT Codes
82595
Test Components
Cryoglobulin.
Cryocrit.
Collection Instructions
Draw 3 × 10ml glass red top tubes. Keep Warm using activated heat pack and transport directly to the lab.
Once at the lab, place in 37°C degree heat block or submerge upright in 37°C waterbath as soon as possible to fully clot.
Specimens MUST be kept at 37°C during collection, tansporation and processing.
Specimen Processing
- Place 3 x10 mL red top serum tubes upright in the 37°C heat block or submerged upright in 37°C waterbath for at least 1 hour to allow the tubes tob fully clot.
- Place 3 conical centrifuge tubes in the heat block to warm to 37°C before use.
Note: We do not advise using disposable conical centrifuge tubes (the ones commonly used in urinalysis or body fluids) as they crack easily and often do not withstand the faster centrifugation process.
- After 1 hour, and without spinning the tubes, aliquot the unclotted supernatant from all serum tubes into one of the pre-warmed conical centrifuge tube.
Important: For the next step DO NOT use refrigerated centrifuge.
- Centrifuge the conical centrifuge tube for 5 minutes at 3000 rpm
- When centrifugation is complete, remove the other 2 empty conical tubes from water bath
- Place exactly 5 mL of serum in one of the empty, pre-warmed conical centrifuge tube
- Place the remaining serum in the second empty, pre-warmed conical centrifuge tube
- Label and cap the tubes and store at 2-8°C.
Result Interpretation
Results will be preliminarily determined as negative or positive on a daily basis. Results from 24 hours, 48 hours, 72 hours and 7 days will be reported in the LIS on day 7. Any positive results will require a crycrit calculation on the conical tube with 5mL and re-warming of the 2nd conical tube to verify if the specimen is a true postive.
Limitations
- Tests is not useful for general screening of a population without a clinical suspicion of cryoglobulinemia.
- Temperature control before and after serum separation is very important. Failure to keep specimen at 37°C during the processing of the sample can lead to false-negative results.
- Falsely low cryocrits will occur if the precipitated serum is not kept cold while determining the cryocrit.
Clinical Information
Cryoglobulins are proteins (either immunoglobulins (Ig) or a mixture of immunoglobulins and complement components) that precipitate at temperatures below 37°C and re-solubilize again upon warming. Cryoglobulinemia is a condition defined as the persistent presence of abnormal immunoglobulins in serum. The clinical manifestations of cryoglobulinemia usually include purpura, weakness, and arthralgia; however, the underlying disease may also contribute to other symptoms. Cryoglobulins have been classified into three types by correlating the immunochemical characteristic of cryoglobulinemia with clinical features of patients. Type I monoclonal cryoglobulinemia (or simple cryoglobulinemia) is characterized by a single monoclonal Ig, usually IgM or IgG. Type I cryoglobulins develop in the setting of a lymphoproliferative disease and malignancies such as multiple myeloma, chronic lymphocytic leukemia, and Waldenström macroglobulinemia. Type I cryoglobulins account for about 10% of cryoglobulins and usually precipitate within 24 hours at 4°C. In Type II cryoglobulins are composed of a mixture of a monoclonal immunoglobulin with rheumatoid factor (RF) activity and polyclonal Ig. Most common form combines monoclonal IgM and polyclonal IgG (or mixed cryoglobulinemia). Type II cryoglobulins are often associated with persistent viral infections, particularly hepatitis C virus (HCV) infection. Type III consists of a mixture of polyclonal IgG and polyclonal IgM, often secondary to autoimmune disorders. These mixed types (II and III) are usually associated with infectious diseases, notably chronic HCV infection; B cell malignancies; and autoimmune diseases such as Sjögren’s syndrome and systemic lupus erythematosus (SLE). Mixed cryoglobulinemia account for approximately 90% of cryoglobulins and because they are composed of immune complexes, can take up to a week to precipitate at 4°C.