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

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

In addition, patients diagnosed with CAD provide the cold agglutinin disease (CAD) bio-specimens. for research, diagnostics, discovery, and drug development.

Cold Agglutinin Disease (CAD) Overview

Cold agglutinin disease (CAD) is a rare acquired autoimmune disorder. In which, specifically, 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 induce their lysis (disintegration). Consequently, this results in anemia.

When the body has too few red blood cells, this can indeed result in anemia. Moreover, experts estimate that more than 1.6 billion people in the world have anemia.

One kind of anemia, in particular, is called hemolytic anemia, or anemia that results from the destruction of red blood cells. Furthermore, various kinds of hemolytic anemias exist, including cold agglutinin disease (CAD).

Additionally, cold agglutinin disease can be primary (unknown cause) or secondary, caused by an underlying condition such as an infection, another autoimmune disease, or certain cancers.

Thus, 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)

Two types of cold agglutinin disease (CAD) exist:

Firstly, Primary (CAD) and, secondly, Secondary (CAD). Doctors identify Primary CAD when the triggering factor is unknown, and, furthermore, there’s no other condition causing it.

In contrast, they identify Secondary CAD when an underlying disorder associates with it.

This, in fact, occurs in up to 70 percent of people living with CAD.

Moreover, researchers associate underlying disorders with CAD, including:

– Immuno-proliferative diseases, which occur when your immune system cells multiply too quickly, such as in non-Hodgkin’s lymphoma or chronic lymphocytic leukemia (CLL).
– Additionally, mumps.
– Also, cytomegalovirus.
– Lastly, connective tissue disorders like lupus or rheumatoid arthritis (RA).

Causes of Cold Agglutinin Disease (CAD)

Autoantibodies called cold agglutinins cause cold agglutinin disease (CAD), which, in turn, cling to RBCs at low temperatures. Consequently, this clumping causes the immune system to destroy the RBCs, leading to severe depletion of RBCs in the blood and, as a result, resulting in anemia.

Furthermore, middle-aged and older adults commonly experience CAD, which may manifest as either a primary disease, where the underlying mechanism is not known, or as a secondary disease caused by other underlying medical issues such as:

– Bacterial infections
– Viral infections
– Parasitic infections
– Other autoimmune diseases such as systemic lupus erythematous (SLE)
– Certain types of cancer.

Signs and Symptoms Cold Agglutinin Disease (CAD)

Cold temperatures or a viral infection often trigger or worsen symptoms of cold agglutinin disease (CAD). Therefore, as a result, symptoms generally worsen during winter months.

Furthermore, symptoms may arise suddenly, leading to an abrupt onset of severe anemia and hemoglobinuria; alternatively, they may develop more gradually and insidiously in the background without the patient realizing it.

Moreover, most CAD patients experience symptoms of hemolytic anemia (destruction of red blood cells, causing low levels of red blood cells). Consequently, the number of symptoms and their severity may depend on how severe the anemia is.

Common Symptoms

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 causes dark purple to grayish discoloration in the fingertips, nose, toes, and ears.
  • Swallowing cold foods and liquids causes pain or discomfort.
  • Livido reticularis presents as a patchy, reticulated (spider web-like) vascular pattern on the skin with a red-blue or purple color.
  • Raynaud’s Phenomenon results in cold intolerance, such as pain and a bluish color in the fingertips and toes.
  • Skin ulceration or necrosis occurs in severe cases.
  • Some CAD cases show an enlarged liver and spleen.
  • Heart problems such as an irregular heartbeat (arrhythmias), heart murmur, and enlarged heart can develop, which may lead to heart failure.These issues arise because the heart has to work harder to ensure the body receives 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. Researchers also suspect CAD when unexplained reasons for hemolytic anemia occur or when they observe red blood cells (RBC) clumping in a cooled blood collection tube or a blood smear.

Several diagnostic tests are performed to confirm Cold agglutinin disease(CAD). For example:

  • A blood smear can reveal the abnormal clumping (agglutination) of the RBCs.
  • Doctors perform blood tests such as a complete blood count (CBC) to detect anemia, estimate hemoglobin levels to analyze the extent of anemia, and identify and quantify reticulocytes, which are immature red blood cells that are normally not present in the blood but appear in conditions of hemolytic anemia while the body tries to compensate for low RBC counts.
  • Researchers conduct biochemical tests on blood samples to identify the levels of the lactate dehydrogenase (LDH) enzyme, haptoglobin protein, and the liver metabolite, bilirubin, which the body produces by breaking down hemoglobin.
  • A doctor can perform a physical examination that detects hepatosplenomegaly.
  • The Direct Coombs test or antiglobulin  detects the presence of autoantibodies immunoglobulin M (IgM) or cold agglutinins or the complement proteins that attach to the surface of the RBCs.

Treatment of Cold Agglutinin Disease (CAD)

Cold agglutinin disease (CAD) patients whose disease symptoms are not severe do not require drug therapy, and they can resolve CAD 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. 

Researchers generally observe the response within one to two months of treatment, and the treatment can have lasting effects for one to two years.However, doctors now recommend Rituximab 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.

Medications

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.

Biospecimens

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

Specifically, aamples 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.

Moreover, Bay Biosciences maintains and manages its own biorepository, the human tissue bank (biobank) consisting of thousands of diseased samples (specimens) and from normal healthy donors available in all formats and types.

In fact, our biobank procures and stores fully consented, de-identified and institutional review boards (IRB) approved human tissue samples and matched controls.

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

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

Moreover, 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.

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

For example 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.

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

Therefore, 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:

Customized Collections

Moreover, we can also procure most human bio-specimens, furthermore; we offer 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. Additionally you buy donor-specific collections in higher volumes and specified sample aliquots from us.

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

 

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