‘Best match’ transfusions an option for CAD children, despite concerns
Donor blood incompatibility could give patient's self-reactive antibodies a target
Blood transfusions may be challenging in children with cold agglutinin disease (CAD), but should remain an option for those with severe disease, a small study in India suggests.
Most of the eight children with CAD in the study received a blood transfusion, but none were complete matches in terms of blood features. Only one child had an adverse reaction to the transfusion, however.
“Best match” blood can be transfused to these patients under close supervision without any serious side effects,” the researchers wrote in “Clinical and immunohematological characterization of autoimmune hemolytic anemia in children,” which was published in Transfusion and Apheresis Science.
CAD is a type of autoimmune hemolytic anemia (AIHA), a group of autoimmune conditions marked by the abnormal production of self-reactive antibodies that wrongly attack red blood cells, resulting in their destruction, or hemolysis.
This leads to too few red blood cells (anemia) and poor oxygen transport throughout the body, which can be life-threatening.
In CAD, these disease-driving antibodies, called cold agglutinins, bind to red blood cells at low temperatures. In other forms of AIHA, self-reactive antibodies are active at warm temperatures, or across a range of temperatures.
Blood transfusions challenging in AIHAs
CAD, and AIHA in general, is rare in adults and even rarer in children. Since “only few reports on childhood AIHA are available in the literature,” characterizing blood-related and clinical features in this patient population is “essential for correct diagnosis of the disease and its management,” wrote three researchers in India who described the clinical and blood features of 29 children newly diagnosed with AIHA from 2014-2020, eight of them with CAD.
Of the eight with CAD, five were girls and three were boys. Their ages ranged from 3 to 14 and all had the disease for a year or less. Most (75%) had secondary CAD, which means the disease resulted from an underlying condition, such as an infection. Most (83%) had a history of respiratory infection with germs such as the Epstein–Barr virus and mycoplasma pneumonia bacterium.
All the children with CAD showed symptoms related to anemia, such as weakness and fatigue, and pale skin. Five (62.5%) had irregular heartbeats and shortness of breath, and fever and jaundice were each reported in four children (50%). Jaundice is yellowing of the skin or eyes due to the buildup of bilirubin, a waste product of hemolysis.
Other findings included enlarged liver or spleen (37.5%), bluish discoloration and numbness of the extremities (37.5%), abdominal discomfort (25%), and abnormally high levels of red blood cells in their urine (25%).
The Coombs test, which checks for self-reactive antibodies bound to red blood cells, was positive. It also revealed that in most of the children with CAD (87.5%), their red blood cells were coated with a complement protein called C3. The complement system has a key role in helping the body fight infection, but contributes to hemolysis in CAD.
As expected, cold agglutinins bound to red blood cells at temperatures ranging from 4 C (39.2 F) to 22 C (71.6 F).
Six (75%) children received a blood transfusion, which is necessary when CAD is severe enough. A total of 11 blood units were transfused and each patient received an average of 1.8 blood units.
In five of them (83.3%), however, the donor’s blood type didn’t match the child’s. In all six transfused children, there was crossmatch incompatibility with the donor’s blood, meaning the donor’s red blood cells would likely be the target of the patient’s self-reactive antibodies.
“Transfusion management of these patients was problematic because of the presence of free autoantibodies in the [blood],” the researchers wrote.
Despite this, all the children received blood units that were the “best match” — those expected to be the least likely to become a target of the child’s cold agglutinins.
One of them (12.5%) had side effects after the blood transfusion, including a sudden spike in fever, known as febrile nonhemolytic transfusion reaction.
“Although blood transfusion in AIHA is a challenge … it should not be withheld in a critically ill patient even in the absence of compatible blood,” the researchers wrote.