CAD develops secondary to leukemia in man, 64: Case study
First documented instance illustrates diagnostic challenges
A 64-year-old man in Iran developed cold agglutinin disease (CAD) secondary to acute myeloid leukemia (AML), a type of blood cancer, a case study reports.
The blood cancer was detected only after the man started to experience CAD symptoms and a biopsy of the bone marrow, the spongy tissue in which blood cells are produced, was conducted. While the man initially responded to treatment for his underlying cancer and no longer showed signs of CAD, he eventually died of AML-related complications.
“This is the first documented case of [CAD] related to AML, contributing to the growing knowledge of the connection between autoimmune hemolytic anemia and [blood] cancers,” researchers wrote. Autoimmune hemolytic anemia is a group of rare autoimmune conditions, including CAD, that are marked by abnormal immune attacks against healthy red blood cells.
The case study, “Cold Agglutinin Syndrome as the Initial Presentation of Acute Myeloid Leukemia: A Case Report,” was published in Clinical Case Reports.
Acute myeloid leukemia identified as underlying cause of man’s CAD
CAD is caused by the production of self-reactive antibodies, called cold agglutinins, that bind to red blood cells at low temperatures, making them clump together and become marked for destruction, or hemolysis.
The disease may be primary if it develops without other underlying health problems, or secondary — also called cold agglutinin syndrome — if it develops as a complication of other health issues, including blood cancers.
In this study, researchers at the Babol University of Medical Sciences in Iran described the case of a man in which acute myeloid leukemia was the underlying cause of his CAD.
This type of blood cancer is marked by the uncontrolled growth of certain cells, called early myeloid cells, in the bone marrow. They ultimately prevent the production of healthy red blood cells, white blood cells, and platelets, the latter of which are involved in blood clotting.
The man was admitted to the emergency room due to weakness and jaundice, or yellowing of the skin and white parts of the eyes, along with a history of lack of appetite and a loss of 15 kg (about 33 lbs) in the previous six months. He also had a recent history of fever, blood in the urine, shortness of breath, and dizziness.
In addition, the man recalled a recent contact from the laboratory for blood resampling due to blood clotting, when his samples had to be kept at 37ºC until use.
Previous laboratory studies indicated elevated levels of white blood cells and low levels of red blood cells, platelets, and hemoglobin, the protein that carries oxygen in red blood cells.
Patient eventually died due to leukostasis, liver failure
On the first day of hospitalization, blood examination revealed the presence of red blood cell clumps. Blood work also showed low hemoglobin levels and high levels of lactate dehydrogenase and bilirubin, two markers of hemolysis. The man also tested positive for cold agglutinins. All these findings led to a diagnosis of CAD of unknown cause.
The man received two blood transfusions in warm conditions and a single dose of rituximab, a therapy commonly used off-label for CAD and sold as Rituxan, among others.
Several tests were then conducted to identify the underlying cause of CAD, including screens for bacterial and viral infections, imaging scans for solid tumors, and a bone marrow biopsy for blood cancer. The results of the biopsy were consistent with AML.
The man started standard treatment for the underlying blood cancer, including 5-azacytidine and Venclexta (venetoclax), which gradually eased his symptoms and resolved his jaundice. His lab test results improved, showing a stabilization of hemoglobin levels.
This is the first case in which acute myeloid leukemia was the underlying cause of [CAD] and emphasizes that hemolysis caused by cold agglutinin[s] requires a full workup, including bone marrow biopsy.
The man was discharged about a month after admission, while continuing daily Venclexta treatment.
About two weeks after discharge, he was admitted to the emergency department due to progressive weakness and an inability to stand. He had extremely elevated white blood cell counts, which were found to be related to his AML. The man eventually died due to leukostasis in liver blood vessels and liver failure.
Leukostasis is a medical emergency most commonly seen with AML that is caused by extremely high white blood cell counts that accumulate in blood vessels, which may block blood flow and cause tissue damage.
“This is the first case in which acute myeloid leukemia was the underlying cause of [CAD] and emphasizes that hemolysis caused by cold agglutinin[s] requires a full workup, including bone marrow biopsy,” the researchers wrote. “Furthermore, [this case] illustrates the challenges involved in diagnosing [CAD] linked with malignancies.”
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