Transfusions for anemia, clotting issues needed by most CAD patients
77% of patients require blood transfusions over course of their disease: US study
While cold agglutinin disease (CAD) may vary widely in severity and course, more than half of patients experience symptoms of anemia (too few red blood cells) and have slower blood clotting that may lead to excessive bleeding.
That’s according to a study in the U.S. that also found more than three-quarters of CAD patients continue to depend on blood transfusions over the course of their disease.
These findings highlight that, despite being a rare disease, “CAD poses considerable burden on patients and healthcare systems,” researchers wrote.
The study, “Clinical and laboratory characteristics of patients with cold agglutinin disease: A retrospective analysis at a tertiary medical center,” was published in the Asian Journal of Transfusion Science.
CAD occurs when self-reactive antibodies called cold agglutinins bind to red blood cells at cold temperatures, causing them to clump together and making them liable to destruction. As a result, patients develop anemia and symptoms such as fatigue and pain.
Due to its rarity, CAD has been mainly studied retrospectively in US
Due to its rarity, CAD and its features have been reported in the U.S. mainly in retrospective case series, and appropriately controlled clinical trials are difficult to conduct.
To know more about the clinical characteristics of the rare autoimmune disease, two researchers working at Henry Ford Hospital in Detroit, Michigan, reviewed data from 48 CAD patients who were followed at six centers from 2007 to 2018.
The study included 36 women and 12 men, ages 43 to 99, who were diagnosed with CAD. Most (38 patients or 79.2%) were white and 10 (20.8%) were African-Americans. Nearly one-third (31.1%) were found to have enlarged spleens on X-ray.
The most common clinical manifestation was symptoms of anemia, reported in 25 patients (52.1%). Jaundice (yellowish skin and eyes) and worsening of a known cancer were each reported in three patients (6.3%), while abdominal pain, sepsis (a life-threatening response to an infection), and acute liver failure were each reported in two patients (4.2%). Eight patients (16.7%) showed no symptoms.
The median level of hemoglobin — an oxygen-carrying protein used as a measure of anemia — was 8.6 grams per deciliter (g/dL), ranging from 3 to 12 g/dL (normal range typically starts at 12.1 g/dL for women and 13.8 g/dL for men). Anemia severity varied across patients, with more than half (54.2%) showing moderate anemia, 20 (41.7%) severe anemia, and two (4.2%) mild anemia.
“Anemia is common in patients with CAD and its severity varies over time with the disease course,” the researchers wrote, adding “most of our patients … presented with moderate-to-severe anemia.”
Red blood cells affected in most CAD patients
Blood work showed other signs of CAD in most patients. Specifically, three-quarters of patients (75%) had high numbers of immature red blood cells, and higher-than-normal levels of two markers of red blood cell destruction were detected in 68.2% to 85.1% of patients.
More than half (52.8%) also had coagulopathy, a bleeding problem where the blood takes too long to clot, and seven patients (14.6%) showed low numbers of clot-forming platelets.
Among the 26 patients tested for cold agglutinins, 20 (76.9%) were positive for the self-reactive antibodies.
“The study spans a long period with evolving understanding and management of CAD; this can explain the nonstandard diagnostic approach,” in which not all patients were tested for cold agglutinins, the researchers wrote.
At the time of diagnosis, 16 (33.3%) patients required a blood transfusion. During the course of their disease, 36 patients (75%) with severe anemia and 12 (25%) with moderate anemia received blood transfusions. Moreover, at the last follow-up, 37 (77.1%) required blood transfusions over the entire course of their disease, with a median of six units transfused over a median of 50.1 months (about four years).
Treatments varied for patients
Different treatments (not all standard) were given to patients: rituximab alone (33.4%), rituximab with steroids (12.5%), anti-cancer medication (12.5%), rituximab with bendamustine (10.4%), or steroids alone (8.3%). Supportive care alone was given to 11 patients (22.9%).
Four patients (8.3%) died within 30 days of their CAD diagnosis. The cause of death was acute liver failure in two patients, sepsis in one, and respiratory failure in another. Two patients developed a blood clot in a deep vein.
More than half of the patients (52.1%) were alive at the last follow-up, after a median of about four years (ranging from 10 days to about 13 years). The proportion of patients estimated to be alive five years after diagnosis was 58.2%; at 10 years, it was 30.8%.
“Patients vary widely in their disease severity and course, and the majority require CAD-related therapy during the course of their disease,” the researchers wrote, adding “most patients present with anemia and coagulopathy, and one-third of patients require blood transfusion on presentation.”
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