Physicians’ search for blood cancer reveals secondary CAD

Microscopic analysis reveals cold agglutinin disease secondary to B-cell lymphoma

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A scientist wearing safety goggles and gloves works with petri dishes and vials of blood in a laboratory.

A case of cold agglutinin disease (CAD) secondary to a type of blood cancer called B-cell lymphoma was confirmed after carefully examining blood samples under the microscope, a study reports.

The case study illustrates the “importance of microscopic observation in the exploration of undergoing causes of cold agglutination,” the researchers wrote in the study “A patient with the highly suspected B cell lymphoma accompanied by the erythrocytes cold agglutination: Case report,” published in the journal Medicine.

CAD is an autoimmune disorder characterized by self-reactive antibodies  called cold agglutinins that stick to red blood cells at low temperatures, causing them to clump together and marking them for destruction.

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The disease is classified as primary when it arises for an unknown reason, and secondary when it occurs as the result of an underlying condition, such as cancer or infections.

Here, physicians at the Zhejiang Provincial People’s Hospital, in China, described the case of a 67-year-old man who had CAD secondary to a B-cell lymphoma, a type of blood cancer marked by the excess growth of B-cells.

B-cells are the immune cells responsible for producing antibodies, including not only those that normally fight infections and cancer, but also those that drive autoimmune diseases such as CAD.

The man was admitted to the hospital after having chills and fever for 15 days. Upon examination, his fever was linked to an infection. He also had a severely low number of red blood cells (anemia) and thrombocytopenia, or low counts of platelets, which are the tiny blood fragments involved in blood clotting.

A CT scan revealed a blockage in the right adrenal gland located on top of the right kidney.

Despite receiving immediate treatment with an into-the-vein antibiotic, the man went into infectious shock and multiple organ failure. He was transferred to the intensive care unit for additional treatment.

Blood analysis reveals inconsistencies

Further blood analysis showed inconsistent results between the number of red blood cells and levels of hemoglobin, the protein in these cells that transports oxygen throughout the body. He also had higher-than-normal levels of markers of red blood cell destruction.

Besides anemia and thrombocytopenia, his blood showed signs of blood red cell clumping and some atypical lymphocytes, a group of immune cells that include B-cells.

When carefully examining his blood sample, the researchers found “the blood on the interior tube wall was sand-like,” the team wrote, indicating the occurrence of red blood cell aggregation. The clumping resolved after warming the blood sample to 37 C (98.6 F), supporting a CAD diagnosis.

Secondary cold agglutinin disease investigated

To search for potential causes of CAD, the researchers looked at the warmed blood sample under the microscope. While at a warm temperature, red blood cells looked normal and did not form clumps, lymphocytes showed some structural abnormalities.

Based on these abnormalities and the fact that the man also had high levels of lactate dehydrogenase activity, a marker of tissue damage, the researchers suspected lymphoma, a blood cancer characterized by excess growth of lymphocytes.

Analysis of the man’s blood marrow, where blood cells are formed, confirmed the presence of an unusually higher number of lymphocytes that subsequent analysis confirmed were B-cells. There also was a higher-than-normal proportion of abnormal B-cells in the man’s blood.

These findings strongly suggested the presence of a B-cell lymphoma. However, a confirmatory bone marrow biopsy was not conducted due to worsening of the patient’s health and the request of discharge by his relatives.

A test for the presence of cold agglutinins also was not performed.

Overall, this case suggests that “microscopic observation is proven a practical and useful approach in the exploration of undergoing causes of cold agglutination and relevant anemia, which can provide a rapid and reliable laboratory suggestion for clinical diagnosis and treatment,” the researchers concluded.