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CAD K2EDTA Plasma Samples

by | Sep 16, 2023 | News Releases | 0 comments

Bay Biosciences provides high quality, clinical grade bio-specimens, cryogenically preserved K2EDTA plasma and peripheral blood mononuclear cells (PBMC) biofluid samples from patients diagnosed with Cold Agglutinin Disease (CAD).

The K2EDTA plasma and PBMC biofluid specimens are processed from patient’s peripheral whole-blood using customized collection and processing protocols.

The cold agglutinin disease (CAD) bio-specimens are collected from unique patients diagnosed with cold agglutinin disease (CAD) disease and are provided to a valued pharmaceutical customer for research, diagnostics, discovery and drug development.

Cold Agglutinin Disease (CAD) Overview

Cold agglutinin disease (CAD) is a rare acquired autoimmune disorder in which exposure to cold temperatures between 32 to 50 F (0 and 10 C) causes autoantibodies, also called cold agglutinins, to bind tightly to red blood cells (RBCs) and inducing their lysis (disintegration), resulting in anemia.

When the number of red blood cells in the body is too low, this can result in anemia. It’s estimated that more than 1.6 billion people in the world have anemia.

One kind of anemia is called hemolytic anemia, or anemia caused by the destruction of red blood cells. There are various kinds of hemolytic anemias, including cold agglutinin disease (CAD).

In cold agglutinin disease (CAD) autoantibodies bind to the erythrocyte membrane leading to premature erythrocyte destruction (hemolysis) characterize autoimmune hemolytic anemia. The presence of high concentrations of circulating cold sensitive antibodies, usually IgM and autoantibodies are active at temperatures below 30 °C (86 °F), directed against red blood cells, causing them to agglutinate and undergo lysis.

When cold agglutinin disease (CAD) patient’s blood is exposed to cold temperatures 32 °F (0 °C) to 50 °F (10 °C), certain proteins that normally attack bacteria (IgM antibodies) attach themselves to red blood cells and bind them together into clumps (agglutination).

This eventually causes red blood cells to be prematurely destroyed (hemolysis) leading to anemia and other associated signs and symptoms. 

Cold agglutinin disease can be primary (unknown cause) or secondary, due to an underlying condition such as an infection, another autoimmune disease, or certain cancers. Treatment depends on many factors including the severity of the condition, the signs and symptoms present in each person, and the underlying cause.

Types of Cold Agglutinin Disease (CAD)

There are two types of cold agglutinin disease (CAD):

  • Primary (CAD)
  • Secondary (CAD)

Primary CAD is when the triggering factor is unknown and there’s no other condition causing it. Secondary CAD is when it’s associated with an underlying disorder. This occurs in up to 70 percent of people living with CAD.

Underlying disorders associated with CAD include the following:


Causes of Cold Agglutinin Disease (CAD)

Cold agglutinin disease (CAD) is caused by autoantibodies called cold agglutinins, which cling to RBCs at low temperatures. This causes the RBCs to clump together and prompts the immune system to destroy them, leading to severe depletion of RBCs in the blood and resulting in anemia.

CAD, which commonly affects adults who are of middle age and older, may manifest as a primary disease, in which the underlying mechanism is not known, or as a secondary disease caused by other underlying medical issues such as:


Signs and Symptoms Cold Agglutinin Disease (CAD)

Symptoms of cold agglutinin disease (CAD) are often triggered or made worse by cold temperatures or a viral infection. Therefore, symptoms generally are worse during winter months.

Symptoms may arise suddenly leading to abrupt onset of severe anemia and hemoglobinuria or develop more gradually and insidiously in the background without patient’s realization.

Most CAD patients have symptoms of hemolytic anemia (destruction of red blood cells, causing low levels of red blood cells), the number of symptoms and severity of symptoms may depend on how severe the anemia is.

Following are the common signs and symptoms of  hemolytic anemia developed caused by Cold Agglutinin Disease (CAD):

Other symptoms of Cold Agglutinin Disease (CAD):
  • Acrocyanosis: dark purple to grayish discoloration in the fingertips, nose, toes, and ears.
  • Pain or discomfort swallowing cold foods and liquids
  • Livido reticularis: Patchy, reticulated (spider web-like) vascular pattern on the skin with a red-blue or purple color.
  • Raynaud’s Phenomenon: cold intolerance such as pain and a bluish color fingertips and toes.
  • Skin ulceration or necrosis (in severe cases)
  • Enlarged liver and spleen in some CAD cases
  • Heart problems such as an irregular heartbeat (arrhythmias), heart murmur, enlarged heart which can lead to heart failure. These may occur because the heart has to work harder to make sure the body gets enough healthy red blood cells.


Diagnosis of Cold Agglutinin Disease (CAD)

Cold agglutinin disease (CAD) is suspected when patients show signs and symptoms typical of the CAD disease during cold temperatures. CAD also is suspected when there are unexplained reasons for hemolytic anemia or the observation of red blood cells (RBC) clumping in a cooled blood collection tube or a blood smear.

Following are several diagnostic tests performed to confirm Cold agglutinin disease (CAD):
  • A blood smear that can reveal the abnormal clumping (agglutination) of the RBCs.
  • Blood tests such as a complete blood count (CBC) to detect anemia, the estimation of hemoglobin levels to analyze the extent of anemia, tests to identify and quantify reticulocytes, which are immature red blood cells that are normally not present in the blood, but are found in conditions of hemolytic anemia while the body tries to compensate for low RBC counts.
  • Biochemical tests on blood samples to identify the levels of the lactate dehydrogenase (LDH) enzyme, haptoglobin protein, and the liver metabolite, bilirubin, which is produced by the breakdown of hemoglobin.
  • A physical examination that can detect hepatosplenomegaly.
  • Direct Coombs test or antiglobulin that can detect the presence of autoantibodies immunoglobulin M (IgM) or cold agglutinins or the complement proteins that are attached to the surface of the RBCs.


Treatment of Cold Agglutinin Disease (CAD)

Cold agglutinin disease (CAD) patients whose disease symptoms are not severe, drug therapy is not required, and CAD can be resolved by avoiding exposure to cold, keeping warm, or moving to a warmer climate.

In more severe CAD cases, monotherapy with Rituximab, an antibody that selectively binds to and induces the destruction of immune cells called B-cells that produce the autoantibodies, can be used. This is effective in about 60% of cases. The response is generally observed within one to two months of treatment, and the effect of the treatment can last one to two years. However, Rituximab is now recommended as the first-line treatment of CAD.

Combined treatment with rituximab and fludarabine results in higher response rates (76% of cases) and longer periods of remissions (on average, 6.5 years). However, the combined treatment can have serious side effects. That is why it is recommended only when rituximab has not worked alone.

Rituximab combined with oral Cytoxan (cyclophosphamide), prednisone or other immunosuppressive medications may be used for cases of CAD that do not resolve with other treatments.

In more severe cases, plasma exchange or plasmapheresis may be performed to remove the IgM or cold agglutinin antibodies from the blood to reduce or alleviate disease symptoms. However, the effect of plasmapheresis is temporary because the B-cells that generate these antibodies are not removed by this procedure. It is useful to overcome acute hemolytic crisis and before surgery-requiring hypothermia.

Previously, corticosteroids treatment has been prescribed for CAD patients. However, patients usually require very high doses of corticosteroids to alleviate symptoms (at levels not considered safe). Hence, corticosteroid treatment is no longer recommended.

In extreme cases, a blood transfusion may be required. Care has to be taken to transfuse warm blood. Moreover, transfusion of blood products with high plasma content should be avoided because elevated levels of complement proteins can cause hemolysis, which exacerbates the condition.

Risk Factors of Cold Agglutinin Disease (CAD)

Risk factors can increase your chance of developing a disease. Having one or more risk factors does not mean you’ll definitely develop the disease. It means that you’re at a higher risk.

Risk factors for CAD can include:

  • Being female
  • Having an associated condition previously listed
  • Living in a colder climate

According to a 2020 report that categorized people as men and women, CAD is almost twice as common in women than men.

Outlook of Cold Agglutinin Disease (CAD)

The outlook for people with CAD can vary widely. It may depend on things like the severity of the disease and your symptoms, and whether you have an underlying condition.

If an infection or unknown condition causes CAD, your outlook is typically good to excellent. This is especially true if you avoid unnecessary exposure to cold temperatures.

But if HIV or certain types of cancers cause CAD, the outlook is typically less favorable. This is because of the characteristics of the underlying illnesses.

Bay Biosciences is a global leader in providing researchers with high quality, clinical grade, fully characterized human tissue samples, bio-specimens, and human bio-fluid collections.

Samples available include cancer (tumor) tissue, cancer serum, cancer plasma, cancer, peripheral blood mononuclear cells (PBMC). and human tissue samples from most other therapeutic areas and diseases.

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Our biobank procures and stores fully consented, deidentified and institutional review boards (IRB) approved human tissue samples and matched controls.

All our human tissue collections, human specimens and human bio-fluids are provided with detailed, samples associated patient’s clinical data.

This critical patient’s clinical data includes information relating to their past and current disease, treatment history, lifestyle choices, biomarkers, and genetic information.

Patient’s data is extremely valuable for researchers and is used to help identify new effective treatments (drug discovery & development) in oncology, and other therapeutic areas and diseases.

Bay Biosciences banks wide variety of human tissue samples and biological samples, including cryogenically preserved at – 80°C.

Including fresh frozen tissue samples, tumor tissue samples, formalin-fixed paraffin-embedded (FFPE), tissue slides, with matching human bio-fluids, whole blood and blood-derived products such as serum, plasma and PBMC.

Bay Biosciences is a global leader in collecting and providing human tissue samples according to the specified requirements and customized, tailor-made collection protocols.

Please contact us anytime to discuss your special research projects and customized human tissue sample requirements.

Types of Biospecimens

Bay Biosciences provides human tissue samples (human specimens) from diseased and normal healthy donors which includes:

We can also procure most human bio-specimens, special collections and requests for human samples that are difficult to find. All our human tissue samples are procured through IRB-approved clinical protocols and procedures.

In addition to the standard processing protocols, Bay Biosciences can also provide human plasma, serum, and PBMC bio-fluid samples using custom processing protocols; you buy donor-specific collections in higher volumes and specified sample aliquots from us.

Bay Biosciences also provides human samples from normal healthy donors; volunteers, for controls and clinical research, contact us Now.

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