Cryoglobulinemia: Causes, Types, Associated Diseases, Effects, Symptoms, Diagnosis, Treatment and Complications

It is a disease caused by the increase of cryoglobulins in the blood.

Excessive amounts of cryoglobulins in the blood cause the blood to become thick and viscous at a lower body temperature.

An increase in the viscosity of the blood causes blockage of the blood vessels resulting in many serious complications.

Cryoglobulinemia in conclusion is a pathological condition in which there are excessive amounts of cryoglobulins in the blood, which tend to thicken at low temperatures.

It is also known that cryoglobulinemia associated with other diseases, such as multiple myeloma and hepatitis C .


  • Cryoglobulinemia is considered an autoimmune disorder, and its cause is not known with certainty. This disorder appears to be triggered by cold temperatures.
  • Cryoglobulinemia has been associated with many different diseases. It is commonly associated with chronic inflammatory diseases such as chronic liver disease.
  • Mixed cryoglobulinemia is rarely associated with lymphoproliferative disorders.
  • Cryoglobulins circulate in the blood and become thick and precipitate at low body temperature. The cause of the change in physical characteristics such as hyperviscosity, at low temperature is not known.
  • Cryoglobulins are proteins that work like antibodies.
  • Cryoglobulin increases in autoimmune disease. And in hepatitis C infections.

Types of cryoglobulinemia

Cryoglobulinemia is basically classified into three types: Type I, Type II, and Type III.

  1. Cryoglobulinemia Type I: It is caused by monoclonal antibodies. This type is usually related to cancerous conditions of the blood or immune system.
  2. Type II cryoglobulinemia : It is caused by the monoclonal antibodies Immunoglobulin M, Immunoglobulin G, and Immunoglobulin A. These types of cryoglobulinemia are most often found in people with chronic inflammatory diseases such as hepatitis C.
  3. Cryoglobulinemia type III: This disease is caused by polyclonal immunoglobulin, Immunoglobulin M, and Immunoglobulin G.

Associated diseases

The following diseases often have an increased level of Cryoglobulins in the blood:

Effects of cryoglobulinemia on organs

Ischemic changes

Serum cryoglobulin causes thick serum precipitation at low temperatures.

The increased viscosity of the blood eventually begins to slow the blood flow or block the smaller vessels.

Reduced blood supply to tissues and organs causes ischemia ( lack of blood supply ) and numerous complications, including kidney failure .

Tissue and organ damage

Cryoglobulinemia is a disease that damages secondary tissue. Blockage of blood supply to normal tissue and organ causes ischemia.

Symptoms of cryoglobulinemia

The prognosis of cryoglobulinemia depends on the presence or absence of underlying diseases. Kidney damage caused by vasculitis can be serious, and recent reports show that permanent kidney failure occurs in about 10% of patients.

Death can be the result of serious heart disease, infection, or brain hemorrhage.

Cryoglobulinemia mainly causes blood clots, stroke, and vasculitis (inflamed blood vessels). Vasculitis of the arteries can lead to blockage of the arteries, often causing damage to organs that receive blood from affected blood vessels, such as the skin or kidneys.

Because cryoglobulinemia increases the density of the blood, symptoms can appear throughout the body.

Common symptoms include weakness, arthralgia (joint pain), purpura (bleeding under the skin causing purple or red spots), Raynaud’s phenomenon, fever, weight loss, hypertension, numbness or tingling in the hands or eyes. feet, skin ulcers, gangrene and abdominal pain.

Mixed cryoglobulinemia involves more than one type of cryoglobulin. It is characterized by arthritis, splenomegaly (enlarged spleen), vasculitis of the skin, purpura (bleeding under the skin), as well as nerve and kidney diseases.

This can lead to recurring pain in the abdomen, heart attack, and bleeding in the lungs. There may also be weight loss and decreased appetite.

The patient may be asymptomatic with an abnormal blood test that suggests abnormal levels of cryoglobulin in the blood. The symptoms of cryoglobulinemia, nonspecific and systemic, depend on the target organ involved in the disease.

Other non-specific symptoms of cryoglobulinemia are:

  • Fatigue.
  • Weightloss.

The specific symptoms of cryoglobulinemia III are:

  • Skin: purple bruises, rash, and skin ulcer.
  • Skeletal system: joint pain, muscle pain, ankle swelling (swollen feet), and Raynaud’s phenomenon.
  • Nervous system: peripheral neuropathy, numbness and weakness.
  • Respiratory system: dyspnea or shortness of breath.
  • Kidney: Glomerulonephritis causes hematuria, proteinuria, and kidney failure.
  • Cardiovascular system: hypertension.
  • Gastrointestinal system: enlarged liver and spleen.


After checking the patient’s history and performing a physical exam, a blood or urine test may be done if cryoglobulinemia is suspected.

During these procedures, a sample of blood or urine is checked under a microscope for the presence of abnormal immunoglobulins.

A blood test may be done to check for cold sensitivity antibodies.

During the procedure, a 15-20 ml blood sample is taken. The serum (the liquid portion of the blood, where cryoglobulins are found) is removed and placed in a cooler at 1ºC for one to seven days.

If agglomeration occurs, cryoglobulins are present. The amount of cryoglobulins is determined by the amount of clumping that occurs.

A skin biopsy may be performed during diagnosis. A small amount of skin is removed and tested in a laboratory to determine if cryoglobulin deposits are present.

In the clinical examination, tests such as:

  • Hepatomegaly: enlargement of the liver.
  • Hypertension: increased blood pressure.
  • Splenomegaly: enlarged spleen.
  • Peripheral neuropathy and numbness.
  • Laboratory studies for cryoglobulinemia.
  • Blood test.

The red cell sedimentation rate is increased in cryoglobulinemia.

Cryoglobulin test to detect the presence of cryoglobulins

  • Liver function tests will generally be high in cryoglobulinemia.
  • It is positive in laboratory tests, the test for rheumatoid factor.
  • Skin biopsy: A test is done if the skin ulcer does not heal.

On urine examination, hematuria and proteinuria are seen if the patient is suffering from cryoglobulinemia-induced glomerulonephritis.

Treatment for cryoglobulinemia

  • General: Treatment depends on the type of cryoglobulin, the presence of an underlying disease, and the severity of symptoms. Cryoglobulinemia is usually treated with a combination of medications that reduce inflammation and suppress the immune system.
  • Antiviral therapy: If cryoglobulinemia is associated with the hepatitis C virus, the patient will be treated with antiviral medications such as ribavirin.
  • Corticosteroids: Corticosteroids such as prednisone have been used to treat the inflamed blood vessels associated with the various types of cryoglobulinemia.
  • Interferons: Some evidence suggests that interferon alpha may help treat patients who have the hepatitis C virus, especially if the disease is mild. Peginterferon alfa-2a has been used in combination with ribavirin to treat patients with chronic hepatitis C who have not received interferon-alfa before.
  • Immunosuppressants: Immunosuppressants such as cyclophosphamide (Cytoxan or Neosar) or azathioprine (Imuran) have been used to treat various types of cryoglobulinemia.
  • Nonsteroidal anti-inflammatory drugs: Nonsteroidal anti-inflammatory drugs such as ibuprofen (Motrin or Advil) have been used to reduce inflammation in blood vessels associated with the various types of cryoglobulinemia.
  • Plasmapheresis: Plasmapheresis has been used to relieve symptoms associated with the various types of cryoglobulinemia. During the procedure, whole blood is removed from the body and plasma (which contains antibodies) is separated from the cells.


Some of the complications are:

  • Rare cases of bleeding in the digestive tract.
  • Rare cases of heart disease.
  • Ulcer infection.
  • Renal insufficiency.
  • Liver failure.